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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 163 records · Page 9Linked to original sources
PubMed1995

Interpreting self reported limiting long term illness.

OBJECTIVE: To examine the association between self reported limiting long term illness and other dimensions of self reported health. DESIGN: Stratified random sample of general population. SETTING: Lothian region, Scotland, in 1993. SUBJECTS: 6212 men and women aged 16 and over. MAIN OUTCOME MEASURES: Limiting long term illness was assessed by the same question as used in the 1991 United Kingdom census. The short form 36 health survey was used to assess other dimensions of health. RESULTS: Rates of limiting long term illness were much higher than reported in the census. Scores on general and physical health scales had strong associations with limiting long term illness, but after adjustment for these associations psychosocial health measures had little influence on limiting long term illness. Being at the lower rather than the upper quartile on the physical functioning scale more than doubled the odds of having limiting long term illness. Reported prevalence of many common illnesses was between two and three times higher among those with limiting long term illness. CONCLUSIONS: A positive response to the question used by the census to define limiting long term illness was strongly associated with physical limitations on activity and less strongly influenced by scores on scales of mental and social wellbeing. Socioeconomic effects on limiting long term illness seem largely mediated through measures of general health and physical limitations on health.

Activities of Daily Living↗
PubMed1995

Dethiobiotin synthetase: the carbonylation of 7,8-diaminonanoic acid proceeds regiospecifically via the N7-carbamate.

Dethiobiotin synthetase (DTBS) catalyzes the penultimate step in biotin biosynthesis, the formation of the ureido ring of dethiobiotin from (7R,8S)-7,8-diaminononanoic acid (7,8-diaminopelargonic acid, DAPA), CO2, and ATP. Solutions of DAPA at neutral pH readily formed a mixture of the N7- and N8-carbamates in the presence of CO2. However, four lines of evidence together indicated that only the N7-carbamate of DAPA was an intermediate in the reaction catalyzed by DTBS. (1) Addition of diazomethane to mixtures of DAPA and [14C]CO2 yielded a mixture of the N7- and N8-methyl carbamate esters, consistent with carbamate formation in free solution. In the presence of excess DTBS (over DAPA), the ratio of N7:N8-methyl carbamate esters recovered was roughly doubled, suggesting that the enzyme preferentially bound the N7-DAPA-carbamate. (2) Both N7- and N8-DAPA-carbamates were observed directly by 1H and 13C NMR in solutions containing DAPA and [13C]CO2. In the presence of excess DTBS (over DAPA) only one carbamate was observed, showing that carbamate binding to the enzyme was regiospecific. 13C NMR of mixtures containing enzyme, [7-15N]DAPA, and [13C]CO2 showed that the enzyme-bound carbamate was at N7 of DAPA. In addition, pulse-chase experiments showed that the binary complex of DTBS and N7-DAPA-carbamate became kinetically committed upon addition of MgATP. (3) The N7-DAPA-carbamate mimic, 3-(1-aminoethyl)nonanedioic acid, in which the carbamate nitrogen was replaced with a methylene group, cyclized to the corresponding lactam in the presence of DTBS and ATP; ADP and P(i) were also formed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Diamino↗
PubMed1995

The structure of U17 isolated from Streptomyces clavuligerus and its properties as an antioxidant thiol.

The predominant low-molecular-mass thiol produced by streptomycetes is a cysteine derivative previously designated as U17 [Newton, G. L., Fahey, R. C., Cohen, G. & Aharonowitz, Y. (1993) J. Bacteriol. 175, 2734-2742]. In this study we report the elucidation of the structure of the monobromobimane derivative of U17, which establishes the structure of U17 as 2-(N-acetylcysteinyl)amido-2-deoxy-alpha-D-glucopyranosyl-myo-inositol. The presence of the N-acetylcysteine moiety was indicated by formation of N-acetylcysteine-monobromobimane during acid hydrolysis of the monobromobimane derivative of U17. Complete hydrolysis released 1 mol glucosamine/mol cysteine as determined by carbohydrate and amino acid analysis. High-resolution mass spectral analysis gave a precise mass consistent with the molecular formula C27H40N4O14S. Analysis of 13C-NMR, one-dimensional 1H-NMR and two-dimensional NMR experiments identified the remaining C6H12O6 moiety as myo-inositol, confirmed the presence of N-acetylcysteine and glucosamine, and established the connectivity of the components. Two chemical properties of this novel thiol make it suitable as an intracellular storage form of cysteine and as an antioxidant thiol. First, it undergoes heavy-metal-ion catalyzed autoxidation at a rate dramatically lower than that for cysteine and markedly lower than that for glutathione or N-acetylcysteine. Secondly, the alpha-(1-->1) glycosidic link between glucosamine and myo-inositol is resistant to acid hydrolysis, hydrolysing at a rate comparable to that of the two amide bonds in the molecule.

Antioxidants↗
PubMed1995

Structure of an antibody-lysozyme complex unexpected effect of conservative mutation.

The structure of the complex between the Fab HyHEL-5 and chicken lysozyme revealed a large interface region containing 23 lysozyme and 28 Fab residues. Arg68 of the lysozyme is centrally placed in this interface and theoretical studies together with binding assays of this Fab to different avian lysozymes have previously shown that this arginine residue is an important contributor to the binding. The Arg68-->Lys mutant binds 10(3) times less well to the HyHEL-5 Fab. We have examined the refined crystal structure of the complex of this mutant lysozyme with the Fab. No global changes occur, but there is an introduction of a new water molecule into the interface that mediates the hydrogen bonding interactions between the lysine and residues on the Fab. These data are compared with the effects of similar changes on the inhibition of serine proteases such as trypsin where the energetic effects of this substitution are small.

Animals↗
PubMed1995

Nucleocytoplasmic transport of the Rev protein of human immunodeficiency virus type 1 is dependent on the activation domain of the protein.

The human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev, which is required for the cytoplasmic expression of unspliced and incompletely spliced viral mRNAs, is located predominantly in the nucleolus. In this study, we show that Rev translocates from the nucleolus to the cytoplasm in HeLa and COS cells transfected with Rev under conditions where rRNA synthesis is inhibited (e.g., with actinomycin D). Dominant-negative mutants with mutations in the activation domain of Rev, which are known to inhibit wild-type Rev function in trans, are unable to leave the nucleus upon actinomycin D treatment. More importantly, when present in excess, these mutants inhibit the translocation of wild-type Rev. This correlation of inhibitory activities suggests that Rev function depends on its transport to and presence (at least transient) in the cytoplasm. In this context, we discuss the possibility that Rev is actively involved in the transport of HIV-1-specific mRNAs containing the Rev response element (a highly structured RNA sequence, which is specifically recognized by the Rev trans-activator). We also discuss the potential of nucleocytoplasmic export of Rev as a target for anti-HIV chemotherapy.

Amino Acid Sequence↗
PubMed1995

Lipid peroxidation in brain: interactions of L-DOPA/dopamine with ascorbate and iron.

Recent reports have stressed an accumulation of iron and enhanced levels of lipid peroxides in the substantia nigra as essential factors in the pathogenesis of Parkinson's disease. Many investigators believe that tissue antioxidants, such as ascorbate, play a protective role. On the other hand, L-DOPA, which is used extensively to treat Parkinson's disease, undergoes autoxidation (as does dopamine), thus generating reactive oxygen species. We studied lipid peroxidation (LPO) in mouse brain homogenates and evaluated the effects of iron (5 microM ferric-ADP), L-DOPA, dopamine and ascorbic acid, added either alone or in mixtures. Ascorbic acid was used at levels of 0.5 mM or 2.0 mM, approximating those present normally in brain. LPO in brain homogenates was stimulated by the addition of either ascorbic acid or iron, as well as by a combination of the two, in agreement with other reports. The effects of L-DOPA were complex: L-DOPA strongly suppressed LPO both with and without added iron-ADP. In sharp contrast, however, when ascorbic acid was also added, L-DOPA no longer suppressed LPO; indeed, L-DOPA stimulated LPO in the presence of added iron and ascorbic acid. Dopamine behaved similarly to L-DOPA. When ascorbic acid was studied over a concentration range, LPO was stimulated at 0.5, 1, 2 or 3 mM, with or without added iron and/or dopamine; 5 and 10 mM ascorbic acid were either not as effective or suppressed LPO below control levels. Deferoxamine, a powerful iron chelator, greatly suppressed LPO under all conditions, as did diethylenetriaminepentaacetate (DTPA). Added superoxide dismutase had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Human transplacental transfer of carbidopa/levodopa.

A paucity of information is available concerning the use of levodopa and carbidopa during pregnancy. Particularly lacking is whether these agents cross the placenta and whether levodopa undergoes metabolism in the fetus. The present study carried out in aborted fetal tissues demonstrates that levodopa crosses the placental barrier and suggests that it may be metabolized in fetal tissues, including the brain and spinal cord. The possibility exists that early exposure to levodopa or dopamine may alter the normal neuronal development in the fetus, and caution in the use of levodopa during pregnancy should be observed.

Antiparkinson Agents↗
PubMed1995

Indocyanine green angiography in Stargardt's flavimaculatus.

PURPOSE: We studied the indocyanine green videoangiographic characteristics of eyes in patients with Stargardt's flavimaculatus and fluorescein angiographic evidence of a dark choroid. METHODS: Affected individuals underwent ophthalmic examination and fluorescein angiographic examination. Indocyanine green videoangiography was performed on eight patients with classic Stargardt's flavimaculatus. Two additional asymptomatic patients with mild manifestations of Stargardt's flavimaculatus, both of whom were related to one patient with the classic phenotype, were also examined with indocyanine green videoangiography. RESULTS: Choroidal detail was evident in all patients examined with indocyanine green videoangiography, and varying degrees of choroidal vascular closure were documented in the maculas of eight patients. Retinal pigment epithelial flecks were found to block indocyanine green videoangiographic fluoresence progressively. Late indocyanine green videoangiographic imaes frequently showed retinal pigment epithelial involvement in areas of retina thought to be uninvolved clinically and by fluorescein angiography. Peripapillary crescents of hypofluorescence, which in some patients were not noted clinically or by fluorescein angiography, were observed in all ten patients examined with indocyanine green videoangiography. In one asymptomatic patient, retinal pigment epithelial flecks could be identified only with indocyanine green videoangiography. CONCLUSIONS: Indocyanine green videoangiography in conjunction with fluorescein angiography can be a valuable tool in the recognition and further understanding of Stargardt's flavimaculatus.

Adolescent↗
PubMed1995

Sarin-induced neuropathology in rats.

Sarin, a highly toxic cholinesterase (ChE) inhibitor, administered at near 1 LD50 dose causes severe signs of toxic cholinergic hyperactivity in both the peripheral and central nervous systems (CNS). The present study evaluated acute and long-term neuropathology following exposure to a single LD50 dose of sarin and compared it to lesions caused by equipotent doses of soman described previously. Rats surviving 1 LD50 dose of sarin (95 micrograms/kg; IM), were sacrificed at different time intervals post exposure (4 h-90 days) and their brains were taken for histological and morphometric study. Lesions of varying degrees of severity were found in about 70% of the animals, mainly in the hippocampus, piriform cortex, and thalamus. The damage was exacerbated with time and at three months post exposure, it extended to regions which were not initially affected. Morphometric analysis revealed a significant decline in the area of CA1 and CA3 hippocampal cells as well as in the number of CA1 cells. The neuropathological findings, although generally similar to those described following 1 LD50 soman, differed in some features, unique to each compound, for example, frontal cortex damage was specific to soman poisoning. It is concluded that sarin has a potent acute and long-term central neurotoxicity, which must be considered in the design of therapeutic regimes.

Animals↗
PubMed1995

Effect of immunoglobulin light chains from hemodialysis and continuous ambulatory peritoneal dialysis patients on polymorphonuclear leukocyte functions.

Circulating plasma factors accumulating in the serum of uremic patients have the potential to inhibit essential functions of polymorphonuclear leukocytes (PMNL). As a consequence, these factors can contribute to the increased risk for bacterial infections generally found in uremic patients. Free immunoglobulin light chains that are present in the serum of healthy adults at low levels appear in the serum of uremic patients at significantly higher levels. Therefore, kappa and lambda light chains in their monomeric and dimeric forms were isolated from hemodialysis and continuous ambulatory peritoneal dialysis patients and their potential to inhibit essential PMNL functions in in vitro assays was tested. It was found that all isolates tested were able to inhibit deoxyglucose uptake, a measure for the state of activation of PMNL, as well as chemotaxis. In contrast, free immunoglobulin light chains had no influence on the phagocytotic functions of PMNL. It was concluded that free immunoglobulin light chains are able to act as uremic toxins by interfering with essential PMNL functions and that their serum levels and fate during the treatment of uremic patients should be taken into consideration.

Chemotaxis↗
PubMed1995

The effects of trauma on young children: a case of 2-year-old twins.

Trauma and its effects on early intrapsychic development are issues that need to be better understood as young children are exposed to ever increasing levels of violence. In this paper, we have considered trauma from the perspective of its effects on young children in the context of chronic community and family violence. Characteristic features of adults with post traumatic stress disorder have been identified in children under 4 years old who have been exposed to extreme trauma. In understanding trauma and its effects on children, it is important to consider how external events may impact on intrapsychic structure and the development of the self. A case is presented of identical 2 year, 11 month old twin boys who were referred after having witnessed the shooting death of their mother by their father seven months earlier. The course of psychoanalytically informed play psychotherapy is discussed with a major goal of the therapy being to help the children work through the trauma and return to a healthy developmental course. While the twins responded well to treatment and were able to work through traumatic material, systematic follow-up is needed to determine the later developmental course.

Child, Preschool↗
PubMed1994

Impaired oxidation of pyruvate in human embryonic fibroblasts after exposure to L-dopa.

The effect of 3,4-dihydroxyphenylalanine (L-dopa) treatment on the ability of intact human cells to metabolize substrates for mitochondrial oxidative phosphorylation was studied in embryonic fibroblasts. Treatment with L-dopa (100-400 microM) for 48 h significantly reduced the oxidation of pyruvate but had no effect on succinate oxidation. The effect was dose-dependent and was still present 2 days after removal of L-dopa. Ascorbic acid (200 microM) protected the cells from the effects of L-dopa; ascorbate alone enhanced pyruvate but not succinate oxidation.

Ascorbic Acid↗