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Biomedical subjects

D E Barnes

Publications and source records attributed to D E Barnes.

53 records · Page 3Linked to original sources
PubMed1991

Gender influences subsite of origin of laryngeal carcinoma.

The relationship of gender to laryngeal cancer is not well understood. We analyzed 688 laryngeal cancers diagnosed in Kansas from 1980 through 1989 for sex differences in subsite distribution (glottis, supraglottis, subglottis, and laryngeal cartilage) as well as survival, histologic grade, and age at diagnosis. The ratio of glottic to supraglottic tumors was 22.12:1 in men and 0.56:1 in women, a highly significant difference. Survival in glottic tumors was significantly better than in supraglottic tumors, but survival was not significantly better for women than it was for men. Glottic tumors were significantly more likely than were supraglottic tumors to be of low-grade malignancy for all subjects and for male subjects alone, but not for female subjects alone. Women were younger at time of diagnosis than were men, but not significantly so. Gender is an important factor in the genesis of laryngeal cancer.

Aged↗
PubMed1991

Estimation of haloperidol concentrations in rat striatum after chronic treatment.

3H-Spiroperidol association and dissociation rate constants were determined in rat striatal homogenates in the presence of known concentrations of unlabelled haloperidol. The rate of 3H-spiroperidol association was progressively decreased in the presence of increasing concentrations of haloperidol and no changes were seen in 3H-spiroperidol dissociation rate constants. Measuring changes in 3H-spiroperidol association rate constants permitted detection of 0.1 pmol/ml unlabelled haloperidol in assay homogenates. Then, male Sprague-Dawley rats received daily injections of haloperidol (1.5 mg/kg) for 1-21 days. Twenty-four hours after the last injection, 3H-spiroperidol kinetic rate constants and Kd values were measured and found to be unchanged in all treatment groups. These findings suggest that, under these conditions of drug withdrawal and tissue preparation, which are widely employed in studies of chronic neuroleptic administration, residual haloperidol does not interfere with the estimation of 3H-spiroperidol binding parameters.

Animals↗
PubMed1990

Sensitization versus tolerance to the dopamine turnover-elevating effects of haloperidol: the effect of regular/intermittent dosing.

Recent clinical research suggests that particular patterns of changes in presynaptic dopamine (DA) turnover accompany the therapeutic response to neuroleptics. We sought to determine whether daily versus weekly dosing of haloperidol for 3 weeks produced distinct effects on DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) concentrations in multiple brain areas. Daily dosing favored the development of tolerance to the DA-turnover elevating effects of haloperidol in the striatum and nucleus accumbens. Weekly dosing favored the development of sensitization in the striatum, posterior olfactory tubercle, and ventral tegmental area. These results suggest that dosing schedules may determine, at least in part, the effects of chronic neuroleptic administration on presynaptic DA function.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Interrelationships between plasma homovanillic acid and indices of dopamine turnover in multiple brain areas during haloperidol and saline administration.

Haloperidol or saline was administered to rats daily for 1, 8, 15 or 22 days. During haloperidol, but not saline administration, changes in plasma homovanillic acid (HVA) concentrations were correlated with changes in nucleus accumbens HVA. Haloperidol administration also had a significant effect on the intercorrelation of dopamine (DA) concentrations and indices of DA turnover across multiple brain areas. In particular, intercorrelations of HVA concentrations among DA terminal brain areas (i.e. striatum, nucleus accumbens, and olfactory tubercle) occurred only during haloperidol treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Sensitization versus tolerance to haloperidol-induced catalepsy: multiple determinants.

The effects of dose, administration frequency, and behavioral testing conditions on the development of tolerance versus sensitization to haloperidol-induced catalepsy were tested in rats. Animals received daily or weekly injections of haloperidol (0.05-5.00 mg/kg SC) for up to 22 days. Catalepsy assessments were made either once or repeatedly using two tests: the horizontal bar and the inclined screen. Tolerance was found only in animals treated daily with haloperidol (1.5 mg/kg) and tested repeatedly on the horizontal bar. In contrast, sensitization was observed with various haloperidol doses, daily or weekly administration schedules (for most doses), either horizontal bar or inclined screen catalepsy tests, and repeated or single testing. Sensitization developed most strongly following weekly drug administration and repeated testing on the horizontal bar. No single experimental variable produced a definitive pattern of change in catalepsy over time. Dose, drug administration schedule, and behavioral test conditions all influenced the evolution of catalepsy during chronic haloperidol treatment.

Animals↗
PubMed1990

Human DNA ligase I cDNA: cloning and functional expression in Saccharomyces cerevisiae.

Human cDNA clones encoding the major DNA ligase activity in proliferating cells, DNA ligase I, were isolated by two independent methods. In one approach, a human cDNA library was screened by hybridization with oligonucleotides deduced from partial amino acid sequence of purified bovine DNA ligase I. In an alternative approach, a human cDNA library was screened for functional expression of a polypeptide able to complement a cdc9 temperature-sensitive DNA ligase mutant of Saccharomyces cerevisiae. The sequence of an apparently full-length cDNA encodes a 102-kDa protein, indistinguishable in size from authentic human DNA ligase I. The deduced amino acid sequence of the human DNA ligase I cDNA is 40% homologous to the smaller DNA ligases of S. cerevisiae and Schizosaccharomyces pombe, homology being confined to the carboxyl-terminal regions of the respective proteins. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is transcribed from a single-copy gene on chromosome 19.

Amino Acid Sequence↗
PubMed1987

Neonatal mortality in Missouri home births, 1978-84.

A study was conducted of 4,054 Missouri home births occurring from 1978 through 1984. Of the 3,645 births whose planning status was identified, 3,067 (84 per cent) were planned to be at home. Neonatal mortality was elevated for both planned (17 observed deaths vs 8.59 expected deaths) and unplanned home births (45 observed vs 33.19 expected) compared with physician-attended hospital births. Nearly all of the mortality excess for planned home births occurred in association with lesser trained attendants (12 observed vs 4.42 expected), while for unplanned home births the excess was entirely among infants weighing 1500 grams or more (19 observed vs 3.50 expected). For planned home births attended by physicians, certified nurse-midwives, or Missouri Midwife Association recognized midwives, there was little difference between observed and expected deaths (5 observed vs 3.92 expected). There also was little difference in deaths for unplanned home births weighing less than 1500 grams (26 observed vs 29.69 expected) compared with hospital births. The study provides evidence of the importance of having skilled attendants present at planned home births.

Adolescent↗
PubMed1986

Behaviour of recombinant plasmids in Aspergillus nidulans: structure and stability.

A pyrG- Aspergillus strain was transformed with plasmid pDJB-1, derived from pBR325 by insertion of the Neurospora crassa pyr4 gene (orotidine 5'-phosphate carboxylase), giving mitotically unstable transformants. Aspergillus DNA which acted as an "autonomously replicating sequence" (ARS) in yeast was inserted into pDJB-1 and the resulting construct, pDJB12.1, gave mitotically stable transformants when introduced into Aspergillus. Transformants obtained with pDJB-1 and pDJB12.1 gave few pyr- progeny in crosses to a pyrG+ strain. Southern hybridisation analysis of pyr+ transformants obtained with pDJB-1 revealed restriction fragments expected for integrated plasmid but transformants obtained with pDJB12-1 showed only bands derived from free plasmid. pDJB-1 and derivatives of pDJB12.1 could be recovered from transformants. These derivatives could not be explained by straightforward excision of integrated pDJB12.1 sequences but could result from recombination between plasmid molecules. Hybridisation of undigested transformant DNAs showed that the transforming DNA was present in a high molecular weight form. These results suggest: (1) pDJB12.1 derivatives and possibly pDJB-1 can replicate autonomously in Aspergillus; (2) A. nidulans DNA acting as an ARS in yeast enhances replication and/or segregation of transforming plasmids in Aspergillus; and (3) recombinant plasmids may undergo rearrangements when introduced into Aspergillus.

Aspergillus nidulans↗
PubMed1986

Rapid glucose-dependent increases in phosphatidic acid and phosphoinositides in rat pancreatic islets.

Glucose effects on islet phospholipids were examined during direct incubation or after 3 days of 32P prelabeling in primary culture. In both cases, glucose increased the 32P content of phosphatidic acid (PA), phosphatidylinositol (PI), and polyphosphoinositides (PPI). Glucose-induced increases in PA, PI, and PPI in the culture-prelabeling experiments were evident within 1 min, dose related, and reflective of increases in phospholipid mass, which was confirmed in direct incubations by measurement of PI phosphorus. Thus, in addition to increasing PI-PPI hydrolysis, glucose increases de novo phospholipid synthesis in pancreatic islets. The latter may result from enhanced glycolysis and substrate availability for PA-PI-PPI synthesis, since glyceraldehyde and pyruvic acid also increased PI levels. Our findings raise the possibility that increases in PA, PI, and PPI synthesis could serve as a mechanism to enhance the generation of intracellular mediators, which are purported to regulate insulin secretion.

Animals↗
PubMed1985

The de novo phospholipid effect of insulin is associated with increases in diacylglycerol, but not inositol phosphates or cytosolic Ca2+.

We have previously reported that insulin increases the synthesis de novo of phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) in BC3H-1 myocytes and/or rat adipose tissue. Here we have further characterized these effects of insulin and examined whether there are concomitant changes in inositol phosphate generation and Ca2+ mobilization. We found that insulin provoked very rapid increases in PI content (20% within 15 s in myocytes) and, after a slight lag, PIP and PIP2 content in both BC3H-1 myocytes and rat fat pads (measured by increases in 32P or 3H content after prelabelling phospholipids to constant specific radioactivity by prior incubation with 32Pi or [3H]inositol). Insulin also increased 32Pi incorporation into these phospholipids when 32Pi was added either simultaneously with insulin or 1 h after insulin. Thus, the insulin-induced increase in phospholipid content appeared to be due to an increase in phospholipid synthesis, which was maintained for at least 2 h. Insulin increased DAG content in BC3H-1 myocytes and adipose tissue, but failed to increase the levels of inositol monophosphate (IP), inositol bisphosphate (IP2) or inositol trisphosphate (IP3). The failure to observe an increase in IP3 (a postulated 'second messenger' which mobilizes intracellular Ca2+) was paralleled by a failure to observe an insulin-induced increase in the cytosolic concentration of Ca2+ in BC3H-1 myocytes as measured by Quin 2 fluorescence. Like insulin, the phorbol diester 12-O-tetradecanoylphorbol 13-acetate (TPA) increased the transport of 2-deoxyglucose and aminoisobutyric acid in BC3H-1 myocytes. These effects of insulin and TPA appeared to be independent of extracellular Ca2+. We conclude that the phospholipid synthesis de novo effect of insulin is provoked very rapidly, and is attended by increases in DAG but not IP3 or Ca2+ mobilization. The insulin-induced increase in DAG does not appear to be a consequence of phospholipase C acting upon the expanded PI + PIP + PIP2 pool, but may be derived directly from PA. Our findings suggest the possibility that DAG (through protein kinase C activation) may function as an important intracellular 'messenger' for controlling metabolic processes during insulin action.

Adipose Tissue↗
PubMed1985

Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes.

We evaluated the possibility that diacylglycerol may function as a second messenger in insulin action. To this end, we employed 12-O-tetradecanoyl phorbol 13-acetate (TPA) to mimic diacylglycerol in BC3H-1 myocytes. Like insulin, TPA provoked rapid increases in 2-deoxyglucose transport and pyruvate dehydrogenase activity in mature insulin-responsive BC3H-1 cultured myocytes. TPA also stimulated amino acid uptake, as evidenced by uptake of alpha-methylaminoisobutyric acid; the relatively slow time course of this effect paralleled that of insulin. In contrast, the effects of TPA were not apparent in undifferentiated BC3H-1 myoblasts, which were also unresponsive to insulin. The insulin-like effects in the myocytes appeared to be specific for TPA, the biologically active phorbol diester which activates protein kinase C, as other tested phorbol derivatives were without effect. Effects of maximally effective concentrations of TPA and insulin were nonadditive. Two synthetic diacylglycerols, 1,2-diolien and 1-oleoyl-2-acetyl-sn-glycerol, also provoked insulin-like effects on 2-deoxyglucose transport. Since insulin rapidly increases diacylglycerol levels in these cells, and TPA mimics diacylglycerol biochemically, it is possible that insulin may control cellular processes through changes in diacylglycerol.

Amino Acids↗
PubMed1984

Effects of insulin and protein synthesis inhibitors on phospholipid metabolism, diacylglycerol levels, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes.

BC3H-1 myocytes were cultured with 32PO4 for 3 days to label phospholipids to constant specific activity. Subsequent treatment with physiological concentrations of insulin provoked 40-70% increases in 32PO4 levels (reflecting increases in mass) in phosphatidic acid, phosphatidylinositol, and polyphosphoinositides, and, lesser, 20-25% increases in phosphatidylserine and the combined chromatographic area containing phosphatidylethanolamine plus phosphatidylcholine plus phosphatidylcholine. Insulin-induced increases in phospholipids were significant within 5 min and near-maximal at 15-30 min. Comparable rapid insulin-induced increases in [3H]phosphatidylinositol were observed in myocytes prelabeled with [3H]inositol. These insulin effects (as per prolonged pulse-chase experiments) were due to increase phospholipid synthesis rather than decreased phospholipid degradation. Cycloheximide (and puromycin) pretreatment prevented insulin-induced increases in phospholipids and rapidly reversed ongoing insulin effects on phospholipids and pyruvate dehydrogenase activity. Insulin also rapidly increased diacylglycerol levels. These findings suggest that: (a) insulin provokes rapid increases in de novo synthesis of phosphatidic acid and its derivatives, e.g. phosphoinositides and diacylglycerol; (b) protein synthesis inhibitors diminish phospholipid levels in insulin-treated (but not control) tissues by increasing phospholipid degradation (?phospholipase(s) activation); and (c) changes in phospholipids and diacylglycerol may be important for changes in pyruvate dehydrogenase and other enzymatic activities during treatment with insulin and/or protein synthesis inhibitors.

Animals↗
PubMed1984

The genome structure of cowpox virus white pock variants.

A previous report described restriction endonuclease analysis of white pock variants of red cowpox virus and their characterization as deletion mutants lacking certain sequences including the repetition from one specific terminus of the wild-type genome. Further analysis has confirmed the terminal deletion but demonstrated that this is compensated at the site of deletion by the presence of an inverted duplication of a variable amount of sequence from the opposite terminus, with the effect of restoring a terminal repetition and the covalent, terminal crosslink. Nine of 11 white pock variants showed a similar deletion of about 21 Mdal mapping contiguously from the right-hand terminus and extending into a 2.4 Mdal restriction fragment. Two white variants showed larger deletions of about 24 and 27 Mdal respectively. These deletions were compensated by a copy of sequences from the opposite terminus which ranged in size from 3 to 27 Mdal. No terminal deletions smaller than 21 Mdal were observed in cowpox white variants or in clones retaining the red phenotype. In contrast with other orthopoxviruses, no deletions involving the left-hand terminus were found. Some independent white isolates had similar sizes of sequence copied from the opposite terminus, but some sibling clones from a single, pock-purified white isolate with the same size of deletion had different sizes of duplicated sequence. Other siblings isolated from an independent, three times pock-purified white clone, itself derived from a single parental red pock, differed from each other in the size of both the deletion and the duplicated sequence. These observations suggest preference for deletion in a particular region, conjunction of the genome termini during DNA replication and a requirement for the preservation of symmetrical termini in orthopoxvirus genome function.

Base Sequence↗
PubMed1981

Prenatal ethanol exposure permanently reduces the number of pyramidal neurons in rat hippocampus.

The effect of prenatal ethanol exposure in the rat on the development of dorsal hippocampal pyramidal and dentate gyrus granule cells was examined. Ethanol was administered in a nutritionally adequate liquid diet to pregnant rats during days 10--21 of gestation. Control groups were either pair-fed the same liquid diet, except for equicaloric substitution of sucrose for ethanol, or received free access to pelleted laboratory food. The brains of 60-day-old offspring exposed to ethanol during gestation were found to have 20% fewer dorsal hippocampal pyramidal cells than did those of controls. Prenatal ethanol exposure, however, did not affect the number of dentate gyrus granule cells. Prenatal exposure to ethanol permanently reduced the number of prenatally formed hippocampal neurons without altering physical growth, which suggested that the developing nervous system is particularly sensitive to the toxic effects of ethanol.

Alcohol Drinking↗
PubMed1980

Neuronal loss in hippocampus induced by prolonged ethanol consumption in rats.

Quantitative neurohistological techniques were used to examine the hippocampal complex of laboratory rats maintained on ethanol-containing or control diets for 5 months followed by a 2-month alcohol-free period. Chronic ethanol consumption resulted in a significant loss of hippocampal pyramidal and dentate gyrus granule cells. This study provides direct evidence that long-term ethanol consumption, in the absence of malnutrition, produces neuronal loss in the central nervous system.

Animals↗
PubMedDate not supplied

Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice.

DNA ligase IV is the most recently identified member of a family of enzymes joining DNA strand breaks in mammalian cell nuclei [1] [2]. The enzyme occurs in a complex with the XRCC4 gene product [3], an interaction mediated via its unique carboxyl terminus [4] [5]. Cells lacking XRCC4 are hypersensitive to ionising radiation and defective in V(D)J recombination [3] [6], implicating DNA ligase IV in the pathway of nonhomologous end-joining (NHEJ) of DNA double-strand breaks mediated by XRCC4, the Ku70/80 heterodimer and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in mammalian cells (reviewed in [7]). The phenotype of a null mutant of the Saccharomyces cerevisiae DNA ligase IV homologue indicates that the enzyme is non-essential and functions in yeast NHEJ [8] [9] [10]. Unlike other mammalian DNA ligases for which cDNAs have been characterised, DNA ligase IV is encoded by an intronless gene (LIG4). Here, we show that targeted disruption of LIG4 in the mouse leads to lethality associated with extensive apoptotic cell death in the embryonic central nervous system. Thus, unlike Ku70/80 and DNA-PKcs [11] [12] [13] [14], DNA ligase IV has an essential function in early mammalian development.

Animals↗