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Biomedical subjects

S Graham

Publications and source records attributed to S Graham.

At least 109 records · Page 6Linked to original sources
PubMed1995

Thrombocytopenia following autologous bone marrow transplantation: evidence for autoimmune aetiology and B cell clonal involvement.

Thrombocytopenia outlasting anaemia and neutropenia is a well recognised sequel of autologous bone marrow transplantation (BMT) but the pathogenesis remains unclear. Autoimmune destruction of platelets has been suggested as a possible mechanism. We studied 5 patients who had undergone autologous BMT and were found to have persistent thrombocytopenia (< 150 x 10(9)/l) 6 months from transplantation with a normal haemoglobin level and granulocyte count. Apart from a mild reduction in the megakaryocyte numbers in one case, no other quantitative or qualitative defects of the megakaryocyte lineage were present to explain the peripheral thrombocytopenia. Two cases had positive anti-platelet autoantibodies. Immunoglobulin heavy chain gene rearrangement studies of peripheral blood and bone marrow mononuclear cells using the polymerase chain reaction showed evidence of clonal rearrangement in one of the two cases with positive anti-platelet autoantibodies. Our results support the previous reports that anti-platelet antibody-mediated destruction of platelets may play a role in the pathogenesis of post-autologous BMT thrombocytopenia. Furthermore, the demonstration of a clonal B cell expansion in one of the cases with anti-platelet antibodies suggests an aetiological link between clonal B cells, autoantibody production and thrombocytopenia.

Adult↗
PubMed1994

Risk of premenopausal breast cancer and use of electric blankets.

Electric blanket use, estimated to significantly increase background exposure to 60-Hz electromagnetic fields, has been hypothesized to increase breast cancer risk. From 1986 to 1991 in western New York State, the authors investigated the use of electric blankets as a risk factor for breast cancer in a case-control study of premenopausal women. A total of 290 premenopausal breast cancer cases and 289 age-matched randomly selected community controls were queried in regard to their use of electric blankets in the previous 10 years, including frequency of use in season and mode of use. After adjusting for age, education, and other risk factors, the odds ratio for use of an electric blanket at any time in the previous 10 years (40% of cases and 37% of controls) was 1.18 (95% confidence interval (CI) 0.83-1.68). Estimates of risk did not differ in a dose-response fashion for number of years of electric blanket use. The risk associated with daily use in season relative to nonuse was 1.27 (95% CI 0.86-1.88). The risk of breast cancer among those who reported use of the blanket through the night was 1.43 (95% CI 0.94-2.17). However, the risk for those who reported daily use in season, continuously throughout the night for the previous 10 years was 1.10 (95% CI 0.59-2.05). These findings do not support the hypothesis that electric blanket use is associated with an increased risk for breast cancer. Studies with improved measures of more highly exposed individuals with quantification of total electromagnetic field exposure might clarify the uncertainties regarding risk of breast cancer associated with such exposure.

Adult↗
PubMed1994

CD8high (CD57+) T cells in normal, healthy individuals specifically suppress the generation of cytotoxic T lymphocytes to Epstein-Barr virus-transformed B cell lines.

We have previously identified two subsets of CD8+, CD57+ lymphocytes in normal peripheral blood: i) T cells expressing high levels [CD8high(CD57+)] and ii) natural killer cells expressing low levels of surface CD8[CD8low(CD57+)]. We investigated the cytotoxic and suppressive function of CD8high(CD57+) T lymphocytes from normal, healthy individuals using standard chromium-release assays and limiting dilution analysis. In normal, healthy subjects, this cell subset suppressed the generation of cytotoxic T lymphocytes (CTL) to autologous, Epstein-Barr virus (EBV)-transformed B cell lines (BCL). Depletion of CD8high(CD57+) T lymphocytes from peripheral blood mononuclear cells (PBMC) resulted in a three- to sevenfold rise in CTL precursor frequency to autologous EBV-transformed BCL, but not allogeneic PBMC or BCL by LDA. Replacement of CD8high(CD57+) T lymphocytes in limiting dilution cultures led to the dose-dependent suppression of EBV-specific, but not allogeneic, CTL generation. Supernatant from CD8high(CD57+) T lymphocytes cultured with autologous BCL did not exhibit suppression, suggesting that soluble factors were not responsible. As CD8high(CD57+) T lymphocytes did not, themselves, exhibit cytotoxicity against autologous BCL, removal of BCL stimulator cells in co-culture was not the mechanism of suppression. Furthermore, while the CD8high(CD57+) T lymphocytes from healthy subjects suppressed the generation of CTL to autologous BCL, they did not suppress the cytotoxic activity of established mixed lymphocyte reactions or peptide-specific CTL clones, as has been reported in bone marrow transplant recipients and human immunodeficiency virus patients. This suggests that CD8high(CD57+) T lymphocytes from healthy subjects suppress the generation of, rather than killing by, CTL in a contact-dependent manner. To our knowledge, this is the first identification of a phenotypically distinct subset of human CD8+ T cells that can suppress generation of antigen-specific major histocompatibility complex class I-restricted CTL.

Adult↗
PubMed1994

Facilitated acquisition of a temporal discrimination following destruction of the ascending 5-hydroxytryptaminergic pathways.

This experiment examined the effect of destroying the 5-hydroxytryptaminergic (5HTergic) pathways on the acquisition and performance of discrimination between two brief time intervals. Rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats were trained in a series of discrete trials to press lever A following a 200-ms presentation of a light stimulus and lever B following an 800-ms presentation of the same stimulus. Both groups gradually acquired accurate performance, attaining 80%-85% accuracy by the end of 40 sessions. The lesioned group learnt the task significantly faster than the control group. When stable performance had been attained, "probe" trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) did not differ significantly between the two groups; however, the Weber fraction was significantly smaller in the lesioned group than in the control group. The levels of 5HT and 5-hydroxy-indole-acetic acid were markedly reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results indicate that destruction of the 5HTergic pathways facilitates acquisition of a temporal discrimination. The lack of an effect of the lesion on the bisection point contrasts with our previous finding using longer stimulus durations; it is suggested that different behavioural processes may underlie millisecond-range and second-range temporal discrimination, and that these may be differently affected by 5HT depletion.

5,7-Dihydroxytryptamine↗
PubMed1994

Abnormal insulin and glucose metabolism in the JCR:LA-corpulent rat.

The JCR:LA-corpulent rat, if homozygous for the cp gene, exhibits a syndrome characterized by obesity, hypertriglyceridemia, and hyperinsulinemia with impaired glucose tolerance. The insulin and glucose metabolism of lean and obese rats of this strain have been studied with the euglycemic insulin clamp technique in 3- and 9-month-old rats. Lean rats require a twofold greater glucose infusion rate than obese rats at high plasma insulin concentrations. Glucose turnover was measured using isotope dilution techniques and 1-3H-glucose. Glucose turnover in lean rats of both sexes increases by a factor of 2 to 3 at very high insulin levels. In contrast, obese male rats are unable to respond even to extreme insulin levels with an increase in basal glucose turnover, indicating a profound insulin resistance. The calculated hepatic glucose production is inhibited by high insulin levels in the obese male rats, while lean animals show no inhibition. Thus, the obese male rats have normal basal glucose turnover, but have a profound insulin insensitivity in peripheral tissues. These abnormalities are present at a much reduced level in the obese female rats. These results are consistent with the hypothesis that the hyperinsulinemia, which correlates strongly with cardiovascular disease in this strain of rat, is secondary to a marked peripheral insulin resistance.

Aging↗
PubMed1994

Diet diversity and risk of colon cancer in western New York.

The effect of diet diversity on colon cancer risk was examined among 205 male and 223 female cases with incident primary histologically confirmed colon cancer and age-, sex-, and neighborhood-matched controls. Diversity was defined as the number of food items on the food frequency interview reported eaten, more than monthly for total foods and for fruits, vegetables, grains, and meats. Adjusted risk of colon cancer associated with total diversity was increased for men in the highest quartile compared with those in the lowest [odds ratio (OR) 1.99, 95% confidence interval (CI) 0.95-4.15] but not for women. There was little association between risk and diversity within specific food groups for either sex, except risk of colon cancer was positively related to meat diversity in men (OR 6.78, 95% CI 2.80-16.45, highest quartile referent to lowest). We found that total diversity was positively related to colon cancer risk independent of other possible confounders. Diversity measures may capture additional diet-related disease risk elements, thus having implications for future recommendations regarding diet and disease.

Case-Control Studies↗
PubMed1994

Exposure to breastmilk in infancy and the risk of breast cancer.

Early childhood nutrition may affect the subsequent risk of breast cancer in adulthood. We examined the association of having been breastfed with risk of breast cancer in a case-control study of women age 40-85 years in western New York. Cases (N = 528) had newly diagnosed primary, pathologically confirmed breast cancer; controls (N = 602) were randomly selected from the same community and were frequency matched on age. Having been breastfed was associated with decreased risk. The multivariate adjusted odds ratio was 0.74, and the 95% confidence interval was 0.56-0.99. We found little difference in the association for pre- and postmenopausal women despite a much higher frequency of breastfeeding among the older women. These findings indicate that early nutriture in general and bottle feeding in particular may relate to breast cancer development in adulthood.

Adult↗
PubMed1994

The spelling for writing list.

Four different vocabulary lists based on the study of children's writing were used to generate a basic spelling list for students with learning disabilities and other poor spellers. For each vocabulary list, the smallest number of different words that accounted for 80% of the words children used in their writing were identified. Words that were common to only one or two of the lists or not normally used by children until fourth grade or later were eliminated. Each word was assigned a grade placement based on difficulty, pattern of occurrence in children's writing, and placement on current vocabulary lists and spelling materials. The resulting spelling list of 335 words is provided.

Child↗
PubMed1994

Cameroon: an African model for final stages of guinea worm eradication.

The Cameroon Guinea worm eradication program initiated case containment activities in 1991 in the Mayo-Sava Division, the only endemic region in the country. These activities differed from the Pakistan program, the only other operational model for dracunculiasis case containment, in two important ways. In Cameroon, next-level supervisors received reports of new cases from village health workers during routine weekly visits to endemic villages. The Pakistan program established a faster case reporting scheme that allowed higher level personnel (sector supervisors and regional managers) to confirm cases within one week of worm emergence. Second, in Cameroon case containment activities were extended only to villages reporting five or more cases the previous transmission season and villages with recent confirmed cases. In Pakistan, all villages reporting cases during the previous year were included in the program. A village-by-village case search one year after initiation of case containment in the Mayo-Sava indicated decreases of 60% in the number of cases and 51% in the number of villages reporting cases. Based on the apparent success of the efforts in Cameroon, we propose a two-stage scheme for implementation of case containment. Both stages are based on rapid detection and containment of cases, within 24 hr of worm emergence, by village-based health workers. In stage 1, cases are reported and confirmed during routine weekly visits to the endemic villages by next-level supervisors. Weekly reporting should be extended to all villages with recent confirmed cases and to as many villages reporting cases during the previous transmission season as logistically possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Cameroon↗
PubMed1993

Effect of castration on hyperlipidemic, insulin resistant JCR:LA-corpulent rats.

The JCR:LA-cp rat exhibits an obese, insulin resistant, hyperlipidemic syndrome. Obese male rats, only, develop atherosclerosis and ischemic myocardial lesions. The obese males have a greater hyperinsulinemia, but the obese females have a much greater hypertriglyceridemia due to hypersecretion of very low density lipoprotein (VLDL). Obese rats of both sexes were surgically castrated at 6 weeks of age to study the influence of testosterone and estrogen secretion on the sexual dimorphism of metabolism and disease in this strain. Castration had no effect on body weight or food consumption up to 16 weeks of age. Castrated male rats had significantly improved glucose tolerance, but a doubled serum triglyceride concentration. Castrated female rats showed approximately halved triglyceride levels. The distribution of the triglyceride molecular species was altered in the castrated male rats to resemble that of the females in which there was no change with castration. The effects suggest that testosterone may inhibit hepatic triglyceride secretion and promotes insulin insensitivity. Estrogen appears to exacerbate hepatic hypersecretion of VLDL. Castration had no effect on myocardial lesion frequency in 9-month-old rats of either sex. This implies that estrogen does not exert a direct protective effect against cardiovascular disease in this animal model.

Animals↗
PubMed1993

Coffee, cigarette smoking, and bladder cancer in western New York.

The association between consumption of coffee and bladder cancer and the effect modification of cigarette smoking was investigated as part of a comprehensive case-control study. The study population consisted of 351 case patients with histologically confirmed transitional cell carcinomas of the bladder among white males and 855 white male control subjects selected from Erie, Niagara, and Monroe counties in New York from 1979 to 1985. Usual diet, coffee consumption, and cigarette use were estimated by comprehensive interviews using a detailed food frequency questionnaire. After adjustment for age, education, and dietary risk factors by multiple logistic regression, risk was found to increase with increasing pack-years of cigarette use with an odds ratio in the highest quartile of 2.7 (95% confidence interval, 1.8 to 4.0) when compared to the lowest quartile. Coffee consumption was associated with an increased risk for bladder cancer among the heaviest coffee drinkers after adjustment for cigarette smoking and other dietary risk factors (odds ratio, 2.1; 95% confidence interval, 1.3 to 3.2). The effect was more pronounced among nonsmokers, especially among those 65 years and older. These findings support the contention that coffee is a weak carcinogen.

Adult↗
PubMed1993

Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV): use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3.

The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenicity of the NS-4 protein was investigated by epitope mapping and by enzyme-linked immunosorbent assay with branched oligopeptides. Epitope mapping of the region between amino acid residues 1679 and 1768 in the HCV polyprotein revealed two major antigenic regions (1961 to 1708 and 1710 to 1728) that were recognized by antibody elicited upon natural infection of HCV. The antigenic regions were highly variable between variants of HCV, with only 50 to 60% amino acid sequence similarity between types 1, 2, and 3. Although limited serological cross-reactivity between HCV types was detected between peptides, particularly in the first antigenic region of NS-4, type-specific reactivity formed the principal component of the natural humoral immune response to NS-4. Type-specific antibody to particular HCV types was detected in 89% of the samples from anti-HCV-positive blood donors and correlated almost exactly with genotypic analysis of HCV sequences amplified from the samples by polymerase chain reaction. Whereas almost all blood donors appeared to be infected with a single virus type (97%), a higher proportion of samples (40%) from hemophiliacs infected from transfusion of non-heat-inactivated clotting factor contained antibody to two or even all three HCV types, providing evidence that long-term exposure may lead to multiple infection with different variants of HCV.

Amino Acid Sequence↗
PubMed1993

Analysis of the human T-cell response to picornaviruses: identification of T-cell epitopes close to B-cell epitopes in poliovirus.

Little is known about the nature and specificity of T-cell-mediated responses to picornaviruses in humans. In this study, the nature of the T-cell response to seven picornaviruses, including polioviruses, coxsackieviruses B3 and B4, human rhinovirus 14, and encephalomyocarditis virus, was determined. Twenty-nine individuals responded to poliovirus type 3, coxsackievirus B3, and encephalomyocarditis virus by proliferation of T cells, and from such cultures, 130 virus-specific T-cell lines were established. T-cell lines generated in response to encephalomyocarditis virus were exclusively strain specific. However, the majority of T-cell lines established in response to viruses, other than encephalomyocarditis virus, were cross-reactive to each other. Their cross-reactivity was confirmed in 2 of the 30 picornavirus-specific clonally derived T-cell lines from two subjects, but the majority of these lines were serotype specific. T-cell epitopes adjacent to each of the B-cell antigenic sites in VP1 of poliovirus type 3 were identified. The response to the region adjacent to B-cell antigenic site 1 (residues 97 to 114) was dominant between individuals. The localization of this major CD4 T-cell epitope may permit the construction of chimeric viruses utilizing the natural picornavirus T-cell response to augment production of antibody specific for inserted sequences.

Amino Acid Sequence↗
PubMed1993

Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120.

A number of linear and conformation-dependent neutralizing monoclonal antibodies (MAbs) have been mapped to the first and second variable (V1 and V2) domains of human immunodeficiency virus type 1 (HIV-1) gp120. The majority of these MAbs are as effective at neutralizing HIV-1 infectivity as MAbs to the V3 domain and the CD4 binding site. The linear MAbs bind to amino acid residues 162 to 171, and changes at residues 183/184 (PI/SG) and 191/192/193 (YSL/GSS) within the V2 domain abrogate the binding of the two conformation-dependent MAbs, 11/68b and CRA-4, respectively. Surprisingly, a change at residue 435 (Y/H or Y/S), in a region of gp120 near the CD4 binding site (M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W. C. Goh, E. Terwilliger, A. Dayton, C. Rosen, W. Haseltine, and J. Sodroski, Science 237:1351-1355, 1987; L. A. Lasky, G. M. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. Capon, Cell 50:975-985, 1987; and U. Olshevsky, E. Helseth, C. Furman, J. Li, W. Haseltine, and J. Sodroski, J. Virol. 64:5701-5707, 1990), abrogated gp120 recognition by both of the conformation-dependent MAbs. However, both MAbs 11/68b and CRA-4 were able to bind to HIV-1 V1V2 chimeric fusion proteins expressing the V1V2 domains in the absence of C4, suggesting that residues in C4 are not components of the epitopes but that amino acid changes in C4 may affect the structure of the V1V2 domains. This is consistent with the ability of soluble CD4 to block 11/68b and CRA-4 binding to both native cell surface-expressed gp120 and recombinant gp120 and suggests that the binding of the neutralizing MAbs to the virus occurs prior to receptor interaction. Since the reciprocal inhibition, i.e., antibody inhibition of CD4-gp120 binding, was not observed, the mechanism of neutralization is probably not a blockade of virus-receptor interaction. Finally, we demonstrate that linear sequences from the V2 region are immunogenic in HIV-1-infected individuals, suggesting that the primary neutralizing response may be directed to both V2 and V3 epitopes.

Amino Acid Sequence↗
PubMed1993

Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon.

Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.

Aged↗
PubMed1993

Knowledge of writing and the composing process, attitude toward writing, and self-efficacy for students with and without learning disabilities.

Twenty-nine seventh- and eighth-grade (21 males and 8 females) and 10 fourth- and fifth-grade (7 males and 3 females) students with learning disabilities, as well as 18 seventh- and eighth-grade (14 males and 4 females) and 11 fourth- and fifth-grade (7 males and 4 females) normally achieving students, were administered an interview designed to assess their knowledge of writing and the composing process, attitude toward writing, and self-efficacy as a writer. Students with learning disabilities were found to have less mature conceptualizations of writing than their normally achieving counterparts. Furthermore, while students with learning disabilities were generally positive about writing, they viewed it less favorably than their regular classmates. Finally, there were no differences between the two groups of students in their evaluations of their competence in either writing or carrying out the processes underlying effective composing.

Adolescent↗