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Biomedical subjects

D Reed

Publications and source records attributed to D Reed.

At least 19 recordsLinked to original sources

Nonsteroidal antiinflammatory drugs cause apoptosis and induce cyclooxygenases in chicken embryo fibroblasts.

Programmed cell death (apoptosis) is an intrinsic part of organismal development and aging. Here we report that many nonsteroidal antiinflammatory drugs (NSAIDs) cause apoptosis when applied to v-src-transformed chicken embryo fibroblasts (CEFs). Cell death was characterized by morphological changes, the induction of tissue transglutaminase, and autodigestion of DNA. Dexamethasone, a repressor of cyclooxygenase (COX) 2, neither induced apoptosis nor altered the NSAID effect. Prostaglandin E2, the primary eicosanoid made by CEFs, also failed to inhibit apoptosis. Expression of the protooncogene bcl-2 is very low in CEFs and is not altered by NSAID treatment. In contrast, p20, a protein that may protect against apoptosis when fibroblasts enter G0 phase, was strongly repressed. The NSAID concentrations used here transiently inhibit COXs. Nevertheless, COX-1 and COX-2 mRNAs and COX-2 protein were induced. In some cell types, then, chronic NSAID treatment may lead to increased, rather than decreased, COX activity and, thus, exacerbate prostaglandin-mediated inflammatory effects. The COX-2 transcript is a partially spliced and nonfunctional form previously described. Thus, these findings suggest that COXs and their products play key roles in preventing apoptosis in CEFs and perhaps other cell types.

Animals

Women's self-disclosure of HIV infection: rates, reasons, and reactions.

A survey of 65 ethnically diverse women at 2 outpatient HIV clinics revealed relatively low rates of disclosure of HIV-positive serostatus to extended family members, somewhat higher rates for immediate family members, and highest rates for lovers and friends. Spanish-speaking Latinas were less likely to disclose their serostatus or to discuss HIV-related worries with others than English-speaking Latinas, African Americans, and Anglo Americans. Reasons for disclosure and nondisclosure varied by target. In general, targets reacted positively to disclosure. Implications for clinicians treating women with HIV infection are discussed.

Adolescent

Information processing and social competence in chronic schizophrenia.

The relationship between social competence and information processing among individuals with chronic schizophrenia was investigated. Thirty-eight inpatients participated in a role play test of social competence and completed a battery of information-processing tasks. Information processing was found to be significantly related to social competence, even after controlling for patient demographics, chronicity, and symptomatology. Higher global social competence was related to more efficient early information processing on a continuous performance/span of apprehension task. Composite indices of specific social competence (i.e., paralinguistic and nonverbal skills) were related to other aspects of information processing (e.g., reaction time). Implications for behavioral assessment and cognitive rehabilitation are discussed.

Adult

A protein-tyrosine/serine phosphatase encoded by the genome of the cyanobacterium Nostoc commune UTEX 584.

Protein-tyrosine phosphorylation has long been regarded as an exclusively eukaryotic phenomenon. Although some non-eukaryotes, mainly viruses, possess genes encoding protein-tyrosine kinases or protein-tyrosine phosphatases, these were probably appropriated from the eukaryotic hosts that constitute the sites of action of these enzymes. Herein we identify a gene, iphP, from the chromosome of the cyanobacterium Nostoc commune UTEX 584 that contains the His-Cys-Xaa-Ala-Gly-Xaa-Xaa-Arg sequence characteristic of known protein-tyrosine phosphatases. The expressed gene product, IphP, displayed protein-tyrosine phosphatase activity toward phosphotyrosine residues on reduced, carboxyamidomethylated, and maleylated lysozyme with optimum activity at pH 5.0. In addition, IphP dephosphorylated the phosphoseryl groups on casein that had been phosphorylated by the cAMP-dependent protein kinase. Cell lysates of N. commune probed with antibodies to phosphotyrosine indicated the presence of a tyrosine-phosphorylated protein of M(r) approximately 85 kDa. This tyrosine-phosphorylated protein was detected in cells grown in the presence of combined nitrogen but not in nitrogen-deficient media that induces the formation of differentiated N2-fixing cells (heterocysts). Together, these data suggest a role for protein-tyrosine phosphorylation in regulating cellular functions in this cyanobacterium. IphP is the first protein-tyrosine phosphatase to be discovered that is encoded by the chromosomal DNA of any prokaryote. Given the free-living nature of N. commune and the phylogenetic antiquity of the cyanobacteria, these findings suggest for the first time the existence of a protein-tyrosine phosphatase of genuine, unambiguous prokaryotic ancestry, thus raising fundamental questions as to the origin and role of tyrosine phosphorylation.

Amino Acid Sequence

Adrenal gland enlargement in major depression. A computed tomographic study.

To determine whether the well-documented hyperactivity of the hypothalamic-pituitary-adrenal axis in depressed patients includes adrenal gland hypertrophy, adrenal gland size was evaluated by computed tomography. Assessments consisted of (1) global ratings by two radiologists ignorant of the diagnostic identity of the subjects and (2) calculation of adrenal volume. Of the 38 patients with major depression, 12 were rated as exhibiting adrenal hypertrophy. Adrenal volumes in the depressed patients were significantly increased when compared with those of normal controls. Adrenal gland size was not correlated with dexamethasone suppression test results, patient age, duration of the depressive episode, or depression severity. These results are concordant with the hypothesis that chronic corticotropin hypersecretion in depression results in adrenocortical hypertrophy. Adrenal gland enlargement may be a measure of cumulative lifetime depression.

Adrenal Glands

RU486 in depression.

RU486 is a synthetic glucocorticoid antagonist. The authors used RU486 to examine the hypothesis that the elevated plasma cortisol and ACTH in patients is due to suprahypophyseal stimulation of the anterior pituitary. Seven patients and matched controls were studied before and after the administration of RU486. RU486 produced an increase in HPA activity in depressed patients. Thus providing support for the hypothesis that there is increased suprahypophyseal stimulation of the anterior pituitary.

Adrenocorticotropic Hormone

Social support and depression in men during alcoholism treatment.

Psychiatric comorbidities have been shown to be important predictors of the outcome of alcoholism treatment. This study examines whether perceived lack of social support can be identified as an independent predictor of symptoms of depression experienced during alcoholism treatment over and above the effects of personality characteristics and the severity of alcohol and psychiatric history. We studied 189 alcoholic men in treatment at a rural midwestern Department of Veterans Affairs medical center. Multiple regression analyses found that reduced social support significantly predicted depression (measured by the Beck Depression Inventory) during treatment while controlling for personality characteristics and the alcoholism and psychiatric subscales of the Addiction Severity Index. Although self-esteem, neuroticism, and psychiatric severity also were significantly associated with depression in the hierarchical regression model, social support demonstrated the strongest unique contribution to depression of any of the predictors. These results suggest that social support has an independent association with depression and perhaps may play an important role in improving treatment compliance and the outcome of alcoholism treatment.

Adult

Do coronary heart disease risk factors measured in the elderly have the same predictive roles as in the middle aged. Comparisons of relative and attributable risks.

Risk factors for the 12-year incidence of definite coronary heart disease (CHD) among 3440 men who were middle-aged (51 to 59 years old) and 1419 men who were elderly (65 to 74 years old) at baseline examination were examined for differences in predictive values in terms of both relative risk and attributable (excess) risk of the highest versus the lowest quartile or appropriate categories. In multivariate models using Cox life-table regression procedures, serum cholesterol level, cigarette smoking, systolic blood pressure, and history of treatment for diabetes were significant predictors of incident CHD for both age groups. Alcohol consumption when modeled as drinker versus nondrinker showed a protective effect in both younger and older men. There was no dose relationship, however, among elderly drinkers. While the relative risks for the variables studied were similar between the two age groups, the excess risk was typically between 1.5 to 2.0 times higher for the older than the middle-aged men. In contrast, the detrimental effect of adiposity as measured by body mass index appeared to decline after age 65 for both measures of risk. This may partly be attributed to diminished adiposity overall in the older age group. The implications of these results are that serum cholesterol level, smoking, hypertension, diabetes, and possibly alcohol consumption continue to be important predictors for CHD when measured after age 65, and that the public health impact of these risk factors, in terms of excess risk, may be more important in the elderly.

Age Factors

Are aortic aneurysms caused by atherosclerosis?

BACKGROUND: The emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii. METHODS AND RESULTS: Analyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure. CONCLUSIONS: From the perspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort.

Age Factors

Report of the Conference on Low Blood Cholesterol: Mortality Associations.

BACKGROUND: A National Heart, Lung, and Blood Institute (NHLBI) Conference was held October 9-10, 1990, to review and discuss existing data on U-shaped relations found between mortality rates and blood total cholesterol levels (TC) in some but not other studies. Presentations were given from 19 cohort studies from the United States, Europe, Israel, and Japan. A representative of each study presented its findings and also submitted tables of proportional hazards regression coefficients for entry TC levels in regard to death, and these were incorporated into a formal statistical overview adjusted for age, diastolic blood pressure, cigarette smoking, body mass index, and alcohol intake, as available. METHODS AND RESULTS: The U-shape for total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers (e.g., lung but not colon), respiratory disease, digestive disease, trauma, and residual deaths. Risk for combined noncardiovascular, noncancer causes of death decreased steadily across the range of TC. The conference considered possible explanations for the statistical associations found between low TC levels or active TC lowering and certain causes of death. One is that TC is lowered by some disease conditions themselves, such as wasting in chronic pulmonary disease or reduced production and secretion of cholesterol-bearing lipoproteins with liver disease. In this sort of situation, the TC:mortality association found in observational studies may be due to preexisting disease. This was addressed by excluding early deaths from the analysis, which did not change the results. The conference considered as well the biological function of cholesterol, which, if seriously deranged, might hypothetically cause a wide variety of diseases and dysfunction. The conference also considered the biological functions that might provide plausible mechanisms for the associations found. CONCLUSIONS: Definitive interpretation of the associations observed was not possible, although most participants considered it likely that many of the statistical associations of low or lowered TC level are explainable by confounding in one form or another. The conference focused on the apparent existence and nature of these associations and on the need to understand their source rather than on any pertinence of the findings for public health policy. Further research is recommended to explain the observed associations of low TC levels (and TC lowering) with certain noncardiovascular diseases. This includes studies of the time course of TC change in disease, the relation of TC to morbidity, further studies of possible epidemiological confounding, monitoring of population trends in TC and mortality, further studies of the relations in women, auditing of noncardiovascular events in trials, studies of cell membrane, genetic and molecular links to cholesterol metabolism, TC level and disease, studies of disease manifestations in specific lipid disorders, and further study of the proposed causal mechanisms linking low TC and hemorrhagic stroke.

Alcohol Drinking

Predictors of arteriographically defined coronary stenosis in the Honolulu Heart Program. Comparisons of cohort and arteriography series analyses.

The purpose of this study was to determine if the major risk factors for clinical myocardial infarction also predicted coronary artery stenosis as defined by arteriography. Of a cohort of 7,591 men who were free of cardiovascular disease at entry, 357 had arteriographic studies during a 20-year follow-up period. Risk factor levels were therefore known prior to the onset of clinical symptoms and arteriographic studies. Men with arteriograms were divided into groups with and without prior clinical myocardial infarction. High blood pressure, serum cholesterol, obesity, and low alcohol intake predicted both severe coronary stenosis and incident myocardial infarction, thus indicating that these variables were associated with clinical events through the underlying process of atherosclerosis. Dietary intake of cholesterol and serum glucose also had similar but not always statistically significant patterns of association with both coronary stenosis and myocardial infarction. In contrast, serum triglyceride and cigarette smoking predicted clinical myocardial infarction, but not severe coronary stenosis. This suggests that these variables play a stronger role in the precipitation of acute clinical events than in the underlying process of atherosclerosis. The findings were quite different for several risk factors when analyzed in a case-control format using the arteriography series from this same data set. Examination of possible explanations for the differences raises questions concerning the use of arteriography series for etiologic studies of coronary atherosclerosis.

Aged

Tumor-associated macrophages share in vitro growth characteristics with resident but not elicited macrophages.

Recent studies have shown that tissue macrophages are capable of proliferation and that this capability is enhanced by various cytokines, including macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Tumor-associated macrophages (TAM) have been demonstrated to proliferate in vitro, but no information is currently available on the ability of M-CSF and GM-CSF to enhance this response. To address this problem, limiting dilution analysis was utilized to examine the proliferative ability of macrophages isolated from two murine tumors of distinct origin following growth in secondary hosts. As a means of comparison, resident peritoneal macrophages (RPM) and thioglycolate-elicited macrophages (TEM) were also analyzed. Results indicate that a rare subset of TAM and RPM is capable of proliferation and that M-CSF and GM-CSF enhance the frequency of TAM and RPM which proliferate, but do not enhance the growth of TEM.

Animals

Low activity sn-glycerol-3-phosphate dehydrogenase variants in natural populations of Drosophila melanogaster.

Eleven Australian natural populations of Drosophila melanogaster were screened by electrophoresis for evidence of null and/or low activity variants at the Gdph locus. Of 5018 alleles investigated, 57 had markedly lower GDPH activity, as judged by their heterozygous phenotypes, than control alleles. GPDH assays of 13 of these variant alleles showed that whilst they were heterogeneous in their properties and included electrophoretic variants and two categories of low-activity variant, there were no true null alleles. The most common low-activity variants exhibited dominance for GPDH activity in heterozygotes with normal alleles, and were shown to share this property with an allele previously isolated from a London (UK) population (Langley et al., 1981).

Alleles

Anterior spine fusion using Zielke instrumentation for adult thoracolumbar and lumbar scoliosis.

Analysis of adult patients undergoing anterior spine fusions with Zielke instrumentation between January 1983 and November 1986 was performed. Objectives were to review results of surgical treatment and identify factors affecting results. Charts, 3 foot standing anteroposterior and lateral and supine maximal side bending radiographs were reviewed. Subjective data were obtained by telephone. There were 26 patients, average age 41 years. Average radiographic follow-up was 48 months. Indications were pain and curve progression. Average correction was 63% of the instrumented curve. Average change of lordosis was 8 degrees and kyphosis was 6 degrees. Apical vertebral rotation corrected an average of 37%. Complications were: eight hardware failures, one deep infection, and two psychiatric events. The high-risk groups: curves greater than 60 degrees, patients older than 50 years of age, and rigid curves.

Adult