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Biomedical subjects

R Lake

Publications and source records attributed to R Lake.

16 recordsLinked to original sources

Arctic contaminants: sources, occurrence and pathways.

Potentially toxic organic compounds, acids, metals and radionuclides in the northern polar region are a matter of concern as it becomes evident that long-range transport of pollution on hemispheric to global scales is damaging this part of the world. In this review and assessment of sources, occurrence, history and pathways of these substances in the north, the state of knowledge of the transport media--the ocean and atmospheric circulation--is also examined. A five-compartment model of the northern region is developed with the intent of assessing the pathways of northern contaminants. It shows that we know most about pathways of acids, metals and radionuclides and least about those of complex synthetic organic compounds. Of the total annual inputs of anthropogenic acidic sulphur and the metals lead and cadmium to the Arctic via the atmosphere, an estimated 10-14% are deposited. A water mass budget for the surface layer of the Arctic Ocean, the most biologically active part of that sea, is constructed to examine the mass budget for one of the major persistent organochlorine compound groups found in remote regions, hexachlorocyclohexanes (HCH), one isomer of which is lindane. It is concluded that both the atmosphere and the ocean are important transport media. Even for the HCH substances which are relatively easily measured and simple in composition compared to other synthetic organics, we know little about the occurrence and environmental physical/chemical characteristics that determine pathways into the food chain. More environmental measurements, chemical characterization studies and environmental chemical transport modelling are needed, as is better knowledge of the circulation of the Arctic Ocean and the marine food web.

Acids

The effect of pancreatic polypeptide and peptide YY on pancreatic blood flow and pancreatic exocrine secretion in the anesthetized dog.

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.

Animals

Prenatal care in northwestern Wisconsin.

The purposes of this study were to identify the components of prenatal care given by family practice physicians and obstetricians in a rural area and determine whether they were in agreement with standards of care advanced by the American College of Obstetricians and Gynecologists (ACOG). We surveyed 76 physicians (family physicians with and without residency training and obstetricians) and identified 40 components of regular prenatal care; they were consistent with 94% of the ACOG recommendations. Few differences were found in prenatal care practices by type of family practice training. Although the number of obstetricians was small, these specialists appeared more likely to agree with ACOG guidelines. Risk assessment instruments were not routinely used by most physicians, and the services of public health nurses were not generally recommended as part of prenatal care. The findings have implications for continuing medical education programs.

Female

Comparison of gas clearance and radioactive microspheres for pancreatic blood flow measurement.

Measurement of pancreatic blood flow (PBF) is technically demanding. Although radiolabeled microspheres are considered the "gold standard" for PBF assessment, they have practical limitations. In the current study, H2 and xenon-133 gas clearance techniques were adapted to PBF measurement and compared to radiolabeled microsphere techniques. Simultaneous measurements of PBF were made using either hydrogen or xenon gas washout and radiolabeled microspheres. Measurements were made under basal, vasoconstricted (vasopressin 2U i.v. or nicotine 4 micrograms/kg/h) and stimulated (secretin 125 ng/kg/h or 2 U/kg i.v.) conditions (random order). Mean PBF was 26.9 +/- 5.3, 50.5 +/- 2.3 and 27.6 +/- 5.2 ml/min/100 g basally, 36.9 +/- 8.0, 90.1 +/- 18.9, and 81.7 +/- 14.5 ml/min/100 g in the stimulated state, and 24.2 +/- 7.8, 25.0 +/- 3.5, and 14.9 +/- 7.5 ml/min/100 g in the vasoconstricted state for hydrogen gas clearance, xenon gas clearance, and radiolabeled microspheres, respectively. The H2 clearance technique resulted in tissue trauma, was complicated by frequent electrode displacement, and correlated poorly (r2 = 0.36, p greater than 0.05) with microsphere values. In contrast, xenon clearance measurement had no apparent effect on the pancreas and correlated well (r2 = 0.83, p less than 0.01) with microsphere data. We conclude that xenon clearance offers an attractive, validated alternative to radiolabeled microspheres for measuring pancreatic blood flow.

Animals

The latent factor structure of the WAIS-R: a factor analysis of individual item responses.

Factor analytic examination of a 166 x 166 intercorrelational matrix that represents individual item scores from the 11 subtests of the WAIS-R provided evidence of five interpretable factors (N = 409). Two of these were identified as the Verbal and Performance factors previously encountered in traditional WAIS-R subtest-based factor analyses. The other three factors were characterized readily as involving (1) Advanced Vocabulary skills; (2) Basic Responsivity and (3) Advanced Computational ability. All three of these "new" factors accounted for at least 10% of the total variance, and comments are made with regard to the possible significance of their discovery to such topics as subtest variation and profile psychodiagnostics, theories that pertain to the nature and structure of human intellectual functioning, and subtest-based personality measurement theories.

Adult

Mouse N-ras genes: organization of the functional locus and of a truncated cDNA-like pseudogene.

The N-ras gene was first identified in both humans and mice as a mutationally activated oncogene found in tumors. The nucleotide sequence and intron/exon structure of the coding region of the mouse gene have been determined previously. We have now determined the sequence and intron/exon structure of the 5' and 3' untranslated regions of mouse N-ras. Like its human homolog, the 3' untranslated region of the gene is encoded by two exons, and the 5' region is encoded by one. In addition, we have isolated and sequenced a second mouse gene homologous to N-ras. This locus, which we have named N-ras-2ps, resides at a chromosomal site distinct from N-ras and appears to be a truncated cDNA-like pseudogene.

Animals

Preclinical safety evaluation of the benzodiazepine quazepam.

7-Chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4- benzodiazepine-2-thione (quazepam, Sch 16134, Dormalin) was evaluated for evidence of systemic toxicity, carcinogenicity and reproductive toxicity in several laboratory animal species including the hamster. Mutagenic potential was also assessed in one in vivo and three in vitro assays. In some studies, diazepam was used as a comparative control. Oral LD50 values were greater than 5000 mg/kg in the mouse and rat while i.p. LD50 values were approximately 900 and 2900 mg/kg in the mouse and rat, respectively. Studies in hamsters for 4 weeks at doses up to 500 mg/kg/d and for 51 weeks at doses up to 120 mg/kg/d demonstrated that the liver was the principal target organ in this species with the effects upon the liver related to dose and duration of dosing. Studies in the squirrel monkey for 13 and 52 weeks at doses up to 50 mg/kg/d demonstrated a transient ataxia, hypoactivity and somnolence during the initial two weeks of dosing. No unusual necropsy or microscopic observations were noted in the 13-week study. Male reproductive organs of quazepam-dosed monkeys were reduced in weight after 52 weeks. Moderate to marked impairment of spermatogenesis and higher liver weights with moderate to marked fatty change in both sexes were observed in groups given diazepam. Abrupt withdrawal of quazepam or diazepam after 52 weeks of dosing was associated at all dose levels with excitability, hyperactivity and convulsions. Two quazepam- and all diazepam-dosed monkeys died.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Oncogene activation and surface markers in mouse lymphomas induced by radiation and nitrosomethylurea.

Thymic lymphomas have been induced by gamma-radiation and treatment with the chemical nitrosomethylurea in different mice strains. As indicated by the NIH 3T3 focus forming assay, a significant percentage of the tumors contain activated oncogenes of the ras family (K or N). Cloning and sequencing has enabled us to identify single base mutations as the only significant alteration present in the activated oncogenes. These alterations result in the substitution of amino-acid 12 or 61 of the p21 product of the ras genes. With the use of synthetic oligonucleotides it has been found that the tumors do not all contain the same mutation and in one case so far the normal allele is absent.

Animals

Diagnosis of Alzheimer's disease and multiple infarct dementia by tomographic imaging of iodine-123 IMP.

Tomographic imaging of the brain was performed using a rotating slant hole collimator and [123I]N-isopropyl p-iodoamphetamine (IMP) in normal subjects (n = 6) and patients with either Alzheimer's disease (n = 5) or multiple infarct dementia (n = 3). Four blinded observers were asked to make a diagnosis from the images. Normal subjects and patients with multiple infarct dementia were correctly identified. Alzheimer's disease was diagnosed in three of the five patients with this disease. One patient with early Alzheimer's disease was classified as normal by two of the four observers. Another patient with Alzheimer's disease had an asymmetric distribution of IMP and was incorrectly diagnosed as multiple infarct dementia by all four observers. Limited angle tomography of the cerebral distribution of 123I appears to be a useful technique for the evaluation of demented patients.

Alzheimer Disease

Abnormalities in CNS monoamine metabolism in anorexia nervosa.

Patients with anorexia nervosa have disturbances of mood, appetite, and neuroendocrine function. Central nervous system monoamine pathways modulate these systems, and alterations in function of these systems may occur in anorexia nervosa. Because monoamine metabolism can be influenced by nutritional intake, we studied anorectics before and at intervals after correction of weight loss. Underweight anorectics had a 30% decrease in CSF homovanillic acid level and a 20% decrease in CSF 5-hydroxyindoleacetic acid concentration; these values returned to normal shortly after weight recovery. The CSF level of norepinephrine (NE) in underweight anorectics and in these patients a few weeks after weight restoration was similar to that in normal subjects. Long-term weight-recovered (20 +/- 7 months) anorectics, however, had a 50% decrease in CSF NE level compared with that of controls. Underweight anorectics have state-associated disturbances in dopamine and serotonin metabolism. Changes in NE metabolism are more complex and state independent. These abnormalities in neurotransmitter metabolism are part of the neurobiological syndrome of anorexia nervosa and may contribute to the characteristic changes in mood, behavior, and neuroendocrine function.

Adolescent

Norepinephrine and 3-methoxy-4-hydroxyphenyl glycol gradients in human cerebrospinal fluid.

The presence of abnormal levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG) in the cerebrospinal fluid (CSF) of some patients with affective disorders may indicate abnormal norepinephrine metabolism in these patients. The authors evaluated the relationship between norepinephrine and MHPG in CSF and found that both are present in increasing levels as more CSF is removed from the lumbar puncture needle. Norepinephrine and MHPG are closely related, although norepinephrine levels are more variable within and between subjects. Both norepinephrine and MHPG levels in CSF should provide important information about norepinephrine metabolism in affective disorders.

Affective Symptoms

Gilles de la Tourette's syndrome: clinical, genetic, psychologic, and biochemical aspects in 21 selected families.

Eighty-one patients and relatives with Tourette's syndrome, members of 21 selected families, participated in a 1-day clinic. In 12 of the 13 Jewish families and six of the eight non-Jewish families, there were multiple members with motor and vocal tics by observation or history. Males predominated among those with persistent symptoms, but among those with spontaneous clearing, females predominated. Twelve propositi had troublesome sexual and aggressive impulses, differing only quantitatively from normal. No evidence of abnormality was found in plasma dopamine beta hydroxylase, or norepinephrine levels.

Adolescent