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Biomedical subjects

S Graham

Publications and source records attributed to S Graham.

At least 73 records · Page 4Linked to original sources

Dietary epidemiology of cancer of the colon in western New York.

The authors interviewed 428 pathologically confirmed cases of colon cancer and controls matched on age, sex, race, and neighborhood in the New York counties containing the cities of Buffalo, Niagara Falls, and Rochester. Risk of colon cancer in both males and females, studied separately, appeared to increase with the amount of total fats and total calories ingested. In addition, we found the risk to increase with increases in the Quetelet index of relative weight (weight (kg)/height (m)2). Dietary fiber was only equivocally associated with risk. Fats and Quetelet index were associated with increased risk in a regression analysis adjusting each factor for the other, as well as for fiber, age, and socioeconomic status. The same was true for calories and Quetelet index. Future efforts to clarify a possible protective role for fiber and to disentangle the effects of fats and calories need to be undertaken. The fact that calories ingested and obesity are each associated with increased risk suggests the importance of studying calorie expenditure.

Body Height

The oncogenicity of chlorambucil in rheumatoid arthritis.

Chlorambucil is useful in patients with rheumatoid arthritis (RA) refractory to other agents but there is concern about the risk of haematological malignancy with this agent. A retrospective survey was performed to assess the incidence of all types of malignancy in 39 patients treated with chlorambucil (mean daily dose 4.25 mg, mean duration of treatment 25 months). These patients were compared with 30 patients with RA who received contemporaneously, the purine analogues azathioprine or 6-mercaptopurine (mean dose 100 mg, mean duration of treatment 24 months). Eight patients treated with chlorambucil and one patient receiving purine analogues developed cutaneous malignancy (p = 0.03). In the chlorambucil-treated patients these were mostly multiple and recurrent. Three patients treated with chlorambucil developed myeloid leukaemia or a preleukaemic state, whilst no patient treated with purine analogues developed this complication. The use of chlorambucil in RA is associated with an increased risk of cutaneous as well as haematological oncogenesis.

Acute Disease

Effects of 10- to 12-day treatment with L-thyroxine in rats with myocardial infarction.

The effects of treatment with L-thyroxine (T4) for 10-12 days on left ventricular (LV) function and myosin isoenzyme content in rats with LV dysfunction after myocardial infarction were studied. Electrocardiogram (ECG) criteria were used to select animals with large myocardial infarctions. These animals were divided into six groups: control and five treatment groups that received daily subcutaneous injections of T4 (1.5, 3, 6, 10, or 15 micrograms/100 g body wt) for 10-12 days. Intravascular pressures were then measured with micromanometer-tipped catheters, and the hearts were analyzed for myosin isoenzyme distribution. The lowest dose of T4 (1.5 micrograms) produced no changes in heart rate, LV pressure or aortic pressure (AoP), myosin isoenzyme composition, or serum T4 levels. Larger doses of T4 (3, 6, 10, and 15 micrograms) produced increases in LV rate of pressure development (dP/dt), heart rate, and T4 levels but did not change LV pressure or AoP. Myosin isoenzyme composition in the control group showed increases in the proportion of the V3 form and decreases in the V1 form compared with the normal pattern. T4 administration produced dose-dependent increases in the V1 myosin isoform and corresponding decreases in the amount of the V2 and V3 forms. Heart rate increases observed with larger doses of T4 could be prevented by addition of propranolol (500 mg/l) to the drinking water. However, in rats treated with T4 and propranolol, LV pressure, AoP, LV dP/dt, and myosin isoenzyme composition were unchanged compared with T4-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The production of a macrophage-activating factor from rainbow trout Salmo gairdneri leucocytes.

Rainbow trout head kidney and blood leucocytes are shown to be capable of secreting a soluble macrophage-activating factor (MAF) after stimulation with concanavalin A (Con A). The presence of phorbol myristate acetate (PMA) as a co-stimulant increased the production of MAF. Both respiratory burst activity (nitroblue tetrazolium, NBT, reduction and H2O2 production) and bactericidal activity were enhanced after incubation of resident or elicited macrophages with the MAF-containing supernatants for 48-72 hr. The target culture period before the addition of MAF did not affect their responsiveness, but a continuous presence of MAF was necessary for maximal stimulation.

Aeromonas

A prospective randomized trial of alpha 2B-interferon/gamma-interferon or the combination in advanced metastatic renal cell carcinoma.

Eighty-nine patients with advanced measurable metastatic renal cell carcinoma were entered into a prospective randomized trial comparing alpha-interferon to gamma-interferon and to the combination. The trial was performed in order to confirm the activity of gamma-interferon and assess the potential clinical synergism. Response rates were 5, 10, and 5%, respectively. The low response rate may have been due to the inability to raise the doses of the interferons to higher levels. Clinical synergy at this dose, route, and schedule of administration in renal cell carcinoma does not exist.

Carcinoma, Renal Cell

In vivo effects of zinc deficiency on calmodulin concentrations in selected rat tissues.

Two groups of male Sprague-Dawley rats, one fed zinc-deficient diet, ad libitum, the other, pair-fed with the same diet, but given supplemental zinc in the drinking water (8 mg Zn++/ml) were studied. After ten weeks of diet, rats were exsanguinated and zinc and calmodulin concentrations in brain and testis were measured. Mean zinc concentration in testis was significantly decreased in rats fed zinc-deficient diet without supplemental Zn++, but mean zinc concentration in brain was not different. Similarly, mean calmodulin concentration in testis was decreased in rats fed zinc-deficient diet without supplemental Zn++ whereas mean calmodulin concentration in brain was not different. Distribution studies of zinc and calmodulin showed that both zinc and calmodulin were released more freely into soluble fractions of testis in rats fed zinc-deficient diet without supplemental Zn++. These results indicate, for the first time in in vivo studies, that zinc influences the calmodulin content of testis.

Animals

Detection of propionic acid vapor by rats with lesions of olfactory bulb areas associated with high 2-DG uptake.

This study tested the functional significance of recent 2-deoxyglucose (2-DG) results demonstrating a discrete focus of activity in the olfactory bulb of rats exposed to the vapor of propionic acid. Rats with lesions that destroyed this area of the olfactory bulb performed as well as did sham operated and lesioned controls in detection of amyl acetate, butanol, geraniol, propionic acid, and on a test for propionic acid threshold. Our results demonstrate that an area of the olfactory bulb containing a major focus of metabolic activity induced by exposure to an odor can be removed without producing a deficit in the detection of that odor.

Animals

Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model.

Human malignant mesothelioma of the pleura was successfully transplanted s.c. into athymic nude mice and grew as a solid neoplastic mass. Tumor growth resulted in death of the animals between 98 and 161 days after implantation. Minced samples of the growing tumor were propagated as a malignant peritoneal effusion. Animals with malignant ascites died predictably at 32 to 33 days. Light and electron microscopy, and immunocytochemistry demonstrated a similarity of the transplanted solid and fluid malignancies with the human primary mesothelioma. Cytogenetic analysis demonstrated a predominance of cells with a triploid number of identifiable but abnormal human chromosomes. This model, which mimics the clinical behavior of malignant mesothelioma in the human, may be of value in animal trials of chemotherapy and immunotherapy.

Animals

Diet and lung cancer risk: findings from the Western New York Diet Study.

This study compares the diets of 450 lung cancer cases (296 males, 154 females) with those of 902 controls (587 males, 315 females). Cases were lung cancer patients diagnosed between August 1980 and July 1984 in three western New York counties, while controls were selected from the general population of these same counties. Usual diet was estimated by detailed interviews using a modified food frequency method. Case-control comparisons were made for dietary fat, protein, fiber, calories, cholesterol, and vitamins A, C, and E according to quartiles of intake, adjusting for age and pack-years of cigarettes by multiple logistic regression. Risk was lower for males in the lowest quartile of total dietary fat intake compared with those in the highest quartile (relative risk = 0.5), although the overall trend in the association with dietary fat was not statistically significant (p = 0.12). Likewise, there was a weak, but not statistically significant, direct association between dietary cholesterol and lung cancer in men (p = 0.17). The intake of vitamin A from fruits and vegetables (carotene) was much more strongly associated with reduced cancer risk. For males, the relative risks by quartiles (lowest intake to highest intake) were 1.8, 1.8, 1.0, 1.0 (p for trend = 0.001). For females, this relation was considerably weaker, and was not statistically significant. These findings are generally in agreement with those of several previous studies. The risk reduction associated with vitamin A from fruits and vegetables (carotene) was most evident for males, for those with squamous cell cancers, for light or ex-smokers, and for those over 60 years of age.

Adult

Immunoaffinity purification of a 72K early antigen of human cytomegalovirus: analysis of humoral and cell-mediated immunity to the purified polypeptide.

An early antigen of human cytomegalovirus (HCMV) was purified from infected cells as a 72K polypeptide by immunoaffinity chromatography using a monoclonal antibody. It was located in both nucleus and cytoplasm, and was non-glycosylated and undetectable on the surface of infected cells. Known seropositive subjects had antibody against the purified protein and it elicited proliferative T cell responses in 10 of 16 subjects. Five of 14 T cell lines established in response to the purified protein were predominantly CD8+ and of these two showed major histocompatibility complex-restricted cytotoxicity against HCMV-infected cells. This provides further evidence that antigens expressed at early times may be targets for the immune response during persistent HCMV infection.

Antibody Formation

Hypotheses regarding caloric intake in cancer development.

The epidemiologic evidence on fats as related to cancer has until recently been equivocal. Some studies showed an inhibitory effect, some showed no effect, and a few showed a reduction in risk. More recently, however, epidemiologic inquiries have suggested that fats may be associated with increased risk of cancer of the breast, prostate, cervix, colon, rectum, larynx, and lung. The relationship is not a simple one. There is evidence that a high level of total calories ingested, regardless of whether the source is fats, carbohydrates, or proteins, increases risk. Still other studies suggest that calorie expenditure may be the important fact. Thus, obesity, derived from whatever source, may be etiologically related to some cancers. Fats being a potentially important contributor to obesity over the long term, may in this way increase risk.

Diet Surveys