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Biomedical subjects

A Roy

Publications and source records attributed to A Roy.

At least 19 recordsLinked to original sources

Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression.

Hypothalamic-pituitary-adrenal (HPA) axis function was examined in relation to suicidal behavior in depression. There were no significant differences between depressed patients who had or had not attempted suicide for either cerebrospinal fluid concentrations of corticotropin-releasing hormone, plasma cortisol levels predexamethasone or postdexamethasone, or for urinary-free cortisol outputs. However, depressed patients who had made a violent suicide attempt had significantly higher 4 PM and maximum postdexamethasone plasma cortisol levels, and significantly more of them were cortisol nonsuppressors than patients who had made nonviolent suicide attempts. A 5-year follow-up was carried out. There were no significant differences on indices of HPA function between depressed patients who did or did not reattempt suicide during the follow-up or who had never attempted suicide. These results suggest the possibility that dysregulation of the HPA axis may be a determinant of violent suicidal behavior in depression.

Adult

Nucleotide sequence of the URA1 gene of Saccharomyces cerevisiae.

The complete nucleotide sequence of the URA1 gene encoding dihydroorotic acid dehydrogenase (DHOdehase) is presented. This enzyme catalyses the conversion of DHO to orotic acid and plays a major role in the pyrimidine pathway, as DHO is the effector of the positive control of the transcription of at least four genes, URA1, URA3, URA4 and URA10. Comparisons between the amino acid sequence of the yeast DHOdehase and sequences of DHOdehases previously isolated from Dictyostellum discoïdum, Escherichia coli and Bacillus subtilis reveal no obvious homologies.

Amino Acid Sequence

Marked reduction in indexes of dopamine metabolism among patients with depression who attempt suicide.

Cerebrospinal fluid studies have reported that low concentrations of the dopamine metabolite homovanillic acid are associated with suicidal behavior in depression. Although only a small proportion of homovanillic acid in the urine derives from the brain, we decided to examine 24-hour urinary outputs of homovanillic acid in relation to suicidal behavior in depression. Patients with depression who had attempted suicide had significantly smaller urinary outputs of homovanillic acid, dihydroxyphenylacetic acid, and total body output of dopamine (sum dopamine) than did patients with depression who had not attempted suicide. Patients with depression who reattempted suicide during 5-year follow-up had significantly smaller urinary outputs of homovanillic acid and sum dopamine than did patients who did not reattempt suicide, patients who never attempted suicide, and normal control subjects, and had significantly smaller outputs of dihydroxyphenylacetic acid than patients who never attempted suicide or control subjects. These data suggest that urinary outputs of homovanillic acid may be peripheral correlates of suicidality in depression. These data add to data on the low levels of homovanillic acid in cerebrospinal fluid in suggesting that diminished dopaminergic neurotransmission may play a part in suicidal behavior in depression.

3,4-Dihydroxyphenylacetic Acid

The transformation-defective adenovirus 12 host range mutant CS-1 lacks the E1a-specific 9.5S mRNA and contains a second deletion in E1b.

We have further analyzed structure and expression of the E1 region of the transformation-defective adenovirus 12 (Ad12) host range mutant CS-1. Using cDNA polymerase chain reaction analysis, the E1a region was found to give raise to five transcripts analogous to the Ad12wt 13S, 12S, 11S, 10S species and the normal 9S mRNA. Due to loss of a splice acceptor site at position 852, the Ad12wt-specific 9.5S transcript cannot be synthesized by the mutant CS-1. The fact that the virus is, however, completely viable indicates that this mRNA is dispensable for lytic growth of Ad12. Besides the deletions in E1a described previously, a second deletion of 31 base pairs was found in the E1b gene. It affects the start site of the E1b-specific mRNAs and destroys or eliminates the AUG sequence for the E1b 19-kD protein. As shown earlier, normal E1b mRNA expression is found in mutant-infected cells, but no 19-kD E1b protein was immunoprecipitated by an E1-specific rat tumor serum.

Adenovirus Early Proteins

Culture of renal arteriolar smooth muscle cells. Mitogenic responses to angiotensin II.

We cultured smooth muscle cells from rat renal preglomerular arterioles by injecting a suspension of iron oxide into the left ventricle, separating the arterioles magnetically, and growing cells from explants. In passaged cultures we ascertained vascular smooth muscle purity of > 98% by morphology; contraction to norepinephrine and angiotensin; positive immunofluorescence staining through the sixth passage with monoclonal antibodies to smooth muscle-specific alpha- and gamma-isoactins, myosin, and desmin; and the absence of von Willebrand factor. Angiotensin II (10(-12)-10(-5) M) induced dose-dependent DNA synthesis and proliferation of subcultured (three times) arteriolar smooth muscle cells from a growth-arrested state (p < 0.01). Angiotensin II (10(-5) M) also induced the cells to express c-fos mRNA. We find no previous report of culture of smooth muscle cells from renal preglomerular arterioles. Our findings also provide evidence that angiotensin II is mitogenic to arteriolar muscle cells and thus may be involved in their hyperplasia accompanying hypertension.

Angiotensin II

Beta-glucosidase of a white-rot fungus Trametes gibbosa.

Extracellular beta-glucosidase was purified from a white-rot fungus, Trametes gibbosa by 50% ammonium sulphate saturation and Sephadex G-100 column chromatography. It showed maximum activity towards p-nitrophenyl- beta-D- glucopyranoside (pNpG). The pH optimum was 3.5. Temperature optimum was 40 degrees C but shifted to 50 degrees C on preincubation with pNpG. Hg2+, Fe3+ and Cu2+ strongly inhibited the activity. The enzyme was competitively inhibited by glucose with a Ki of 5.2 mM. The apparent molecular mass as determined by gel filtration chromatography was 640 kDa.

Ammonium Sulfate

Expression and secretion of an assembled tetrameric CH2-deleted antibody in E. coli.

We have expressed in E. coli a functional assembled antibody variant that is secreted into the media. The antibody variant is a CH2-deleted chimeric antibody 14.18, which was previously shown to be a potentially useful reagent for radioimmunodetection of human tumors. The bacterial expression vector contains a dicistronic unit comprised of a L-chain cDNA and a CH2-deleted H-chain cDNA. For translocation across the bacterial membranes, we have replaced the natural signal peptides of the H and L chains with the signal peptide of the bacterial protein pectate lyase B. When expressed in the JM105 host under the control of the trp-lac promoter, the products were secreted into the M9 growth media to about 350 micrograms/L. The secreted antibody, which can be readily purified from the media without any denaturation or renaturation steps, retains antigen-binding activity. SDS-PAGE and nondenaturing size exclusion high-pressure liquid chromatography showed that it is a mixture of assembled HL and fully assembled H2L2. In H2L2, inter-H chain disulfide bonds are not formed, and the two HL half-molecules are likely held together by the trans interaction between the two CH3 domains.

Antigens

[Extracorporeal circulation in acute ischemia of the lower limb with late detection].

The authors report a case of acute limb ischemia in a 19 years old patient seen at 9 hours of the injury. They describe a technique of "washing-reperfusion" by a cardio-pulmonary limb bypass (CPLB). Blood pH and kaliema measurements during CPLB were noted. The good clinical result except on the initial nerves deficit, should lead to think that this technique could take a place in the treatment of acute limb ischemia seen lately.

Acute Disease

Induction of tumour necrosis factor alpha in experimental animals treated with hepatotoxicants.

Administrations of hepatotoxicants namely carbon tetrachloride (CCl4:0.4 ml in 1.2 ml of liquid paraffin) and ANIT (1 ml of 1.5% solution in liquid paraffin) in Charles foster rats (force fed) and D-galactosamine (8 mg in water per swiss albino mouse, ip) induce the release of TNF-alpha in case of CCl4 and D-galactosamine. High TNF-alpha level was observed up to 48 hr in CCl4 and up to 24 hr in D-galactosamine treated animals. Elevated levels of biochemical like ALP and SGPT are also recorded. TNF-alpha level can be measured of tissue damage and prognosis in case of hepatitis.

1-Naphthylisothiocyanate

Suicide in twins.

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.

Adult

Mental disorders among alcoholics. Relationship to age of onset and cerebrospinal fluid neuropeptides.

Eighty-one percent of 339 alcoholics participating in a research program were found to have associated mental disorders. Alcoholics with onset of heavy drinking before 20 years of age had significantly more antisocial personality traits, drug abuse, bipolar disorder, panic disorder, suicide attempts, and paternal alcoholism than alcoholics with onset after age 20 years. Alcoholics with onset before and after 20 years of age also differed significantly from each other for cerebrospinal fluid concentrations of diazepam-binding inhibitor and somatostatin. These results support the notion that age of onset may delineate subgroups of alcoholics with significant clinical and neurochemical differences.

Adult

Depression among alcoholics. Relationship to clinical and cerebrospinal fluid variables.

Although depression is common among alcoholics, its determinants are poorly understood. Among 339 alcoholics, 111 (33%) had a history of major depression. Depressed, compared with never-depressed alcoholics, had a higher daily alcohol intake, more lifetime diagnoses of other anxiety and affective disorders and drug abuse, more had attempted suicide, and more reported alcoholism in both parents. Depressed alcoholics also had significantly lower cerebrospinal fluid levels of the dopamine metabolite homovanillic acid and of gamma-aminobutyric acid. Among subgroups of depressed alcoholics, secondary compared with primary depressives were more often divorced, of lower social status, with an earlier onset of alcoholism, and higher Michigan Alcohol Screening Test scores. Secondary depressives also had significantly lower cerebrospinal fluid concentrations of homovanillic acid than never depressed alcoholics. These results suggest that certain psychosocial variables, alcohol consumption, and neurochemical variables may be specifically associated with depression in alcoholics.

Adult

Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls.

Alcoholics as a group have been consistently reported to show differences from controls on various personality inventories. Moreover, neurobiologic substrates have been postulated to underlie personality dimensions. Therefore, we compared alcoholics with controls on measures of personality and investigated relationships between measures of personality and cerebrospinal fluid monoamine metabolite concentrations. The alcoholics were significantly different from controls on many personality measurements. There were significant, negative correlations between interview-derived lifetime aggression scores and cerebrospinal fluid concentrations of both the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid. However, there were no significant correlations between any cerebrospinal fluid monoamine metabolite concentrations and scores on personality inventories.

3,4-Dihydroxyphenylacetic Acid

Descriptive epidemiology of intravenous heroin users--a new risk group for transmission of HIV in India.

India is considered to have a low incidence of HIV infection so far. Nevertheless, an epidemic of HIV infection has been reported recently among intra-venous drug users (IVDUs) in Manipur, a north-eastern state of India, bordering Myanmar (Burma). This report describes the epidemiology of intravenous drug abuse in the state of Manipur. Four hundred and fifty IVDUs were interviewed. Their age (median 24 years) and sex patterns (95% male) differ from those reported from western countries. It is estimated that there may be approximately 15,000 such addicts in a population of 1.8 million and 50% of them could be positive for HIV. Knowledge of AIDS and its transmission is significantly higher among the addicts than non-addict controls. Free availability of heroin was found to be the major factor responsible for the high rate of addiction. It is presumed that two other neighbouring States which are well-connected to Manipur and also have a common border with Myanmar (part of the 'Golden Triangle') may have a similar problem with HIV infection.

Acquired Immunodeficiency Syndrome

Cerebrospinal fluid diazepam binding inhibitor in depressed patients and normal controls.

Diazepam binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Levels of DBI in cerebrospinal fluid (CSF) were found to be elevated in depressed patients, when compared to age- and sex-matched normal controls. Levels of the peptide, corticotropin-releasing hormone (CRH), in CSF have been found to be elevated in depressed patients. Significant positive correlations between levels of DBI and CRH in the CSF of depressed patients and normal controls were found. These data suggest the possibility that DBI may have a role in coordinating responses to stress in humans, in addition to its possible role in the pathophysiology of depression.

Adult