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C Abraham

Publications and source records attributed to C Abraham.

71 records · Page 4Linked to original sources
PubMed1982

Huntington's disease: changes in striatal proteins reflect astrocytic gliosis.

Huntington's disease is an autosomal dominant neuronal degeneration characterized by age-related neuronal loss principally affecting caudate and putamen and, to a lesser extent, cerebral cortex. In order to identify selective polypeptide alterations in HD brain, we analyzed unfractionated homogenates and purified neuronal perikarya from striatum and cortex of 12 control and 14 HD brains by gel electrophoresis and immunochemical techniques. SDS polyacrylamide gel electrophoresis (SDS-PAGE) revealed a 3- to 8-fold increase in a 50,000 MW (50K) protein in HD striatal homogenates. Neuronal fractions isolated from the same tissue almost never showed this change. In cortex, 50 K protein was either normal or minimally increased. The increase at 50 K in striatal homogenates was often associated with variable increases of proteins at 40 K and 43 K. No other consistent polypeptide changes in HD brain tissue were found by one-dimensional SDS-PAGE. The increased 40 K protein in HD striatum extracts showed a strong immunoprecipitant line with an antiserum to GFA. This antiserum also produced greater immunofluorescent staining of HD than control striatum. Direct immunostaining of polypeptides in gels demonstrated selective staining of the 50 K, 43 K and 40 K proteins in HD striatum. The pattern was highly similar to that reported by Dahl et al. 6 for glial filament preparations that underwent postmortem proteolysis. We conclude that these polypeptide changes are related to increased glial filaments in affected HD tissue, and that similar protein changes reported in other human neuronal degenerations also reflect secondary astrocytic gliosis rather than the primary gene product.

Adult↗
PubMed1982

Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers.

The accumulation in aged human neurons of insoluble, high molecular weight filamentous polymers apparently linked by nondisulfide covalent bonds led us to examine human brain for the presence of transglutaminase (EC 2.3.2.13) and endogenous protein substrates for this crosslinking enzyme. We demonstrate the presence in brain of a transamidating enzyme that can covalently crosslink brain proteins into insoluble polymers in vitro by forming gamma-glutamyl-epsilon-lysine intermolecular bridges. Brain transglutaminase is Ca2+ dependent, has an electrophoretic mobility similar to that of erythrocyte transglutaminase, and is active in human postmortem brain from aged normal individuals and patients with Alzheimer disease (senile dementia). Brain neurofilament fractions incubated in the presence of transglutaminase, Ca2+, and the fluorescent amine dansylcadaverine form a fluorescent, nondisulfide-bonded insoluble polymer; this process is associated with a decrease in the amount of soluble neurofilament polypeptides in the preparation. Electron microscopy of the polymeric material reveals an extensive network of connecting filaments, which can be immunostained with various neurofilament antisera. Cystamine, an inhibitor of transglutaminase, prevents the neurofilament crosslinking. Glial filaments and myelin basic protein can also serve as substrates of brain transglutaminase in vitro. Although Alzheimer disease-type paired helical filaments are not formed under the specific in vitro conditions employed, the data suggest one possible mechanism for the covalent crosslinking of filaments into insoluble polymers during human neuronal aging.

Acyltransferases↗
PubMed1981

Vitrectomy.

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Adolescent↗
PubMed1979

T-cell division and aging.

The age-dependent drop in mixed lymphocyte reactivity and responsiveness to concanavalin A of lymph node and spleen cells of C57Bl/6J female mice were studied. The relative decrease in mixed lymphocyte reactivity was shown to be the same whether mounted against H-2 or Mls incompatibile stimulator cells. The time of peak response in vitro as well as the sensitivity to stimulator cell concentration are not altered with age. Cell cycle studies demonstrate that those cells which respond in vitro to alloantigens or to concanavalin A do so with a cell cycle which does not change with the age of the lymphocyte donor. In addition, regardless of the age of the donor, those cells which divide in vitro demonstrate identical capacities to redivide. These experiments suggest that the decline in observed T-cell proliferation in mixed lymphocyte and mitogen reactivity of senescent mice is not to a decreased cell generation time or to a reduced capacity to divide and redivide but rather to a smaller population of reactive cells.

Aging↗
PubMed1977

Reduced in vitro response to concanavalin A and lipopolysaccharide in senescent mice: a function of reduced number of responding cells.

The proliferative capacity of spleen cells from C57BL/6J female mice of various ages (3-28 months) to the polyclonal mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) was examined. It was found that both the T and B cell population of the spleen demonstrate an age-related decrease in their capacity to respond in vitro. Peak responses to both mitogens occurs at about 1 year of age. This age-related reduction in response is expressed in the degree of incorporation of [3H]thymidine into DNA, the total number of cells generated in vitro, the number of labeled cells per culture and the number of blast cells per culture. The day of peak response in vitro does not change with age. Studies of the cell cycle of cells responding to Con A and to LPS from 12 and 28-month-old mice demonstrate that the generation time of individual proliferating cells does not alter with age. Nor does it differ for the B cells responding to LPS or the T cells responding to Con A. These studies also demonstrate that the proliferating cells from senescent mice are equally capable of repeated cell divisions as are the cells from the 1-year-old adult mouse. It is concluded that the defect in senescent mice which leads to a reduced in vitro response to the polyclonal mitogens LPS and Con A is a reduction in the number of responding cells and not an alteration in the capacity of those cells which do respond to divide.

Aging↗
PubMedDate not supplied

Religiosity and adolescents' premarital sexual attitudes and behaviour: an empirical study of conceptual issues.

A review of the literature concerning the relationship between religiosity and premarital sexual attitudes and behavior revealed inconsistencies in research findings and problems with methodology and operationalization of variables. A postal questionnaire to 527 16-18 year olds examined the associations between 6 models of religiosity (religious upbringing, denominational affiliation, ritual/behavioral, self-attitude/self-schema, and salience of religious identity) and personal sexual standards, attitudes towards sexually active others, virginal status, anticipation of sexual intercourse, and frequency of both coitus and noncoital sexual experiences over the previous year. A negative relationship between religiosity and a number of sexual attitudes and behaviors was observed, though nonsignificant relationships in the case of sexual experiences without intercourse suggested the maintenance of a technical virginity to accord with religious precepts. There was also some evidence that Catholic adolescents were more likely to be sexually active than non-Catholics when current religiosity was controlled for. The results lent strongest support to models which implicated self-conception either in terms of self-attitudes/self-schemas or the salience of religious identity. Implications of the study and suggestions for future research are outlined.

Adolescent↗
PubMedDate not supplied

Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins.

During ageing of the human brain, and particularly in senile dementia of the Alzheimer type (AD), many neurones progressively accumulate abnormal cytoplasmic fibres, called paired helical filaments (PHF). Each such fibre consists of a pair of intermediate (10 nm) filaments twisted into a double helix with a periodicity of 160 nm. PHF accumulate in large perikaryal masses, called neurofibrillary tangles, and are also found in degenerating cortical neurites that form neurite plaques. The density of PHF-containing neurites and cell bodies correlates with the degree of dementia and the extent of loss of cholinergic neurotransmitter function in AD. Recently, we demonstrated that PHF from human cerebral cortex are large, rigid polymers with unusual molecular properties, including insolubility in SDS, urea and other denaturing solvents and apparent resistance to protease digestion. These properties have so far prevented complete purification and analysis of the constituents of PHF. Based on their insolubility, we have developed a new method of preparing highly enriched PHF fractions and have raised an antiserum that is highly specific for PHF. We report here that this antiserum specifically labels PHF, free of any associated normal fibrous proteins and, unexpectedly, it reacts with neither neurofilaments nor any other normal cytoskeletal protein in brain sections or on immunoblotted gels. These anti-PHF antibodies have been used for the specific detection of Alzheimer-type PHF and in the search for cross-reacting antigens in various tissues, and are suitable for immunoaffinity purification of PHF. Our results indicate that PHF contain determinants that are not shared with normal neuronal fibrous proteins.

Aged↗
PubMedDate not supplied

Managing awareness: negotiating and coping with a terminal prognosis.

This study examined the way in which a terminal cancer prognosis was negotiated by patients and their lay carers, and the complexities involved in managing a context of awareness. Individual semi-structured interviews were undertaken with 16 patients and 14 lay carers. These were transcribed verbatim and analysed using a grounded theory approach. The process started with being given bad news, when the concept of life was no longer open-ended. The need to maintain hope influenced the amount of information sought by patients and their families and was an important strategy in helping patients cope with the knowledge of their disease. Levels of awareness appeared to be influenced less by setting, than by the way the prognosis was managed within individual families. Difficulties facing patients and carers in knowing how to communicate with each other within a context of open awareness suggest that they need help in learning how to do this. Achieving an environment to enable this requires private space and staff skilled in enabling and facilitating the complexities of communication between patients and their carers.

Adaptation, Psychological↗
PubMedDate not supplied

CD4 counts of normal and HIV-infected south Indian adults: do we need a new staging system?

BACKGROUND: The normal range of CD4 lymphocyte count varies among different ethnic groups. In populations with CD4 counts inherently lower than in the West, the Centers for Disease Control and Prevention (CDC) classification system of HIV-infected individuals may not be appropriate. No such criterion is currently available for ethnic south Indian HIV-infected individuals. We undertook this study to assess the applicability of the western case definition to south Indian HIV patients. METHODS: The CD4 counts of 104 normal and 79 HIV-infected south Indian adults were estimated by flowcytometry. The mean CD4 counts were estimated and compared between CDC groups A, B and C and controls. Receiver operator characteristics curves were generated to determine the cut-off that correlated best with clinical staging for this population. RESULTS: The mean CD4 and CD8 cell counts/microl and the CD4/CD8 ratio of the control group were 799.0, 919.6 and 0.94, respectively. For CDC groups A, B and C, the mean CD4 counts/microl were 454.4, 254.4 and 168; mean CD8 counts/microl were 1156, 1070.9 and 1191.3; and mean CD4/CD8 ratios were 0.44, 0.25 and 0.15, respectively. CONCLUSION: The mean CD4 count among normal south Indians is significantly lower than that in the western population and parallels that of the Chinese. When categorized based on the CDC classification system, the mean CD4 count of HIV-infected individuals was lower. Categories of CD4 counts > 300, 81-300 and < or =80 cells/microl and CD4% > 14, 7-14 and < or = 6 correlate better with disease progression among HIV-infected individuals. A longitudinal study is required before guidelines for the Indian population can be devised.

Adolescent↗