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Biomedical subjects

M Jain

Publications and source records attributed to M Jain.

At least 163 records · Page 9Linked to original sources

Dietary factors and risk of prostate cancer: a case-control study in Ontario, Canada.

The relationship between risk of prostate cancer and dietary intake of energy, fat, vitamin A, and other nutrients was investigated in a case-control study conducted in Ontario, Canada. Cases were men with a recent, histologically confirmed diagnosis of adenocarcinoma of the prostate notified to the Ontario Cancer Registry between April 1990 and April 1992. Controls were selected randomly from assessment lists maintained by the Ontario Ministry of Revenue, and were frequency-matched to the cases on age. The study included 207 cases (51.4 percent of those eligible) and 207 controls (39.4 percent of those eligible), and information on dietary intake was collected from them by means of a quantitative diet history. There was a positive association between energy intake and risk of prostate cancer, such that men at the uppermost quartile level of energy intake had a 75 percent increase in risk. In contrast, there was no clear association between the non-energy effects of total fat and monounsaturated fat intake and prostate cancer risk. There was some evidence for an inverse association with saturated fat intake, although the dose-response pattern was irregular. There was a weak (statistically nonsignificant) positive association between polyunsaturated fat intake and risk of prostate cancer. Relatively high levels of retinol intake were associated with reduced risk, but there was essentially no association between dietary beta-carotene intake and risk. There was no alteration in risk in association with dietary fiber, cholesterol, and vitamins C and E. Although these patterns were evident both overall and within age-strata, and persisted after adjustment for a number of potential confounding factors, they could reflect (in particular) the effect of nonrespondent bias.

Adenocarcinoma↗

A note on scoring clones given a probe ordering.

We present an efficient algorithm for scoring clones given an ordering of probes under a schema proposed by Alizadeh et al. (1994) in the context of physical mapping with unique probes. The algorithm runs in time linear in the number of blocks of ones in the underlying sparse incidence matrix. A sparse and efficient algorithm for this task is important as it appears to be a central task in most algorithms for physical mapping.

Algorithms↗

Role of MAP kinase activation in bovine tracheal smooth muscle mitogenesis.

Abnormal growth of airway smooth muscle may play an important role in the pathogenesis of human airway diseases. Little is known about the proliferative responses of cultured airway smooth muscle cells, nor of the precise pathways responsible for mitogenesis in these cells. We assessed DNA synthesis, cell proliferation, and mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes after exposure to four potential mitogens: platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and 5-hydroxytryptamine (5-HT). Stimulation with either PDGF or IGF-1 induced substantial increases in DNA synthesis and cell number, as reflected by [3H]thymidine incorporation, flow cytometry, and methylene blue staining. Treatment with EGF or 5-HT, on the other hand, induced only modest DNA synthesis and no increase in cell number. Immunoblots and kinase renaturation assays of cell extracts demonstrated activation of both the 42- and 44-kDa MAP kinases within minutes of either PDGF, IGF-1, EGF, or 5-HT exposure. However, relative to EGF and 5-HT stimulation, late-phase MAP kinase activation was significantly greater after treatment with the mitogens PDGF and IGF-1. We conclude that in cultured bovine tracheal myocytes 1) PDGF and IGF-1 are potent mitogens; 2) MAP kinase may be activated subsequent to stimulation of either receptor tyrosine kinases (PDGF, EGF, IGF-1) or G protein-linked receptors lacking in known tyrosine kinase activity (5-HT); and 3) unsustained MAP kinase activation is insufficient for mitogenesis. Finally, the finding that mitogenicity correlates with the late phase of MAP kinase activation is consistent with the notion that sustained MAP kinase activation is important for bovine tracheal myocyte proliferation.

Animals↗

Extracellular processing of phospholipids is required for permeability barrier homeostasis.

Three key lipid types, cholesterol, ceramides (CER), and free fatty acids (FA), form the stratum corneum (SC) lamellar bilayers that mediate barrier function. Prior studies have shown that barrier requirements regulate CER generation from glucosylCER, and that this catabolic step takes place within the SC interstices. Here, we addressed whether extracellular processing of phospholipids (PL), the FA precursor delivered to the SC interstices with glucosylCER and cholesterol during exocytosis of lamellar body contents, is also required for barrier homeostasis. We applied two chemically unrelated inhibitors of phospholipase A2 (PLA2-I), BPB (irreversible) and MJ33 (reversible), topically to hairless mice after barrier perturbation with acetone. Both inhibitors delayed barrier recovery at non-cytotoxic doses, while MJ45, an analogue known to inhibit PLA2-II but not PLA2-I, had no effect. Moreover, the delays in barrier recovery induced by BPB and MJ33 could be overridden by co-applications of palmitic acid, but not linoleic acid or lysolecithin. Furthermore, inhibitor-treatment resulted in accumulation of PL and depletion of FA in the SC by 4 h, as well as the persistence of "immature" lamellar body-derived membrane structures in the SC interstices. Finally, these changes in membrane structure were reversed when inhibitor-treated SC was incubated in vitro with palmitic acid. These studies show that: 1) inhibition of PLA2 results in abnormalities in lipid composition and SC structure that alter barrier homeostasis; and 2) the functional defect can be attributed to a deficiency of nonessential FA within the SC. Thus, extracellular processing of PL into FA is required for normal barrier function.

Animals↗

A randomized controlled trial of vitamin A supplementation in acute diarrhea.

Effect of vitamin A supplementation on duration of diarrhea was evaluated in 108 cases between 6 months to 5 years of age suffering from acute diarrhea of less than 3 days duration and results were compared with equal number of age and sex matched controls having comparable feeding pattern, nutritional and socio-economic status and clinical profile who did not receive vitamin A supplementation. There was no significant difference in the mean duration of diarrhea in cases who received vitamin A and the controls. However, on subgroup analysis of the study and control groups a significant (p = 0.009) beneficial effect of vitamin A supplementation was noticed in cases who had a pre-existing vitamin A deficiency with CIC stage 3/5 and above. Even though vitamin A supplementation in malnourished children did not significantly alter the duration of diarrhea, a beneficial effect was observed in children who had CIC state 3 and above in association with malnutrition (p = 0.025). Our results indicate that vitamin A supplementation does not significantly reduce the duration of a diarrheal episode. However, in children with pre-existing vitamin A deficiency particularly those who have associated malnutrition it may have a beneficial effect.

Child↗

Assessment of thyroid functions and its role in body growth in thalassemia major.

The present study was done to establish the role of thyroid gland in causing growth retardation in regularly transfused thalassemic children. Growth, skeletal maturation and thyroid functions were assessed in 25 patients of thalassemia major in the age range of 5-17 years (mean age 10.3 +/ 3.6 years). Thirteen patients were migrants from Pakistan and 12 were of Indian origin. Twenty-five age and sex matched children who were not anemic served as controls. Thalassemic children received multiple blood transfusions ranging from 36-350 units with a mean of 168.4 +/ 98.9 (+/ 1 SD). The mean pretransfusion hemoglobin was 8.7 +/ 1.6 g/dl. Twenty eight per cent patients were below the 5th percentile for height and another 24% between 5th and 10th percentiles. The height age retardation was more pronounced than bone age retardation. The mean serum total T3 and T4 levels were significantly lower (p < 0.001) and the mean serum TSH levels were significantly higher (p < 0.005) in patients with thalassemia major as compared to the controls. Eight patients had high TSH levels; of these 5 had compensated primary subclinical hypothyroidism (elevated TSH with normal T3 and T4) and 3 had uncompensated primary sub-clinical hypothyroidism (elevated TSH, low T4 and normal T3). Two patients had low T4 with normal T3 and TSH levels. Thyroid dysfunction was not related to age, sex, hemoglobin levels and country of origin but transfused iron load (units/kg, units/year) was significantly higher in patients with hypothyroid function compared to those with euthyroid function (p < 0.005). Height age, weight age and bone age retardations were more pronounced in patients with hypothyroid function; however, the difference was not statistically significant. It is concluded that hypothyroidism is unlikely to be the sole cause of growth retardation; however, it may have a potentiating or permissive role. The strong association of high transfused iron load and decreased thyroid function stresses the need for intensive chelation therapy.

Adolescent↗

Endoscopic management of large bile duct stones by mechanical lithotripsy.

OBJECTIVE: Our experience in treating large common bile duct stones using Olympus basket mechanical lithotripter (BML 2Q) and Soehendra lithotripter is reported. METHODS: Between July 1990 and December 1993, twenty two patients with common bile duct stones too large to be extracted by Dormia basket or balloon were treated with BML lithotripter or Soehendra lithotripter. RESULTS: The stone diameters ranged from 1.5 to 2.8 cm. Fourteen patients required one session of lithotripsy, four patients two sessions each, and two patients three sessions each. BML lithotripter was used in 14 patients. In the remaining eight patients the stones were fragmented with Soehendra lithotripter when the basket got impacted while attempting extraction. Mechanical lithotripsy was successful in 20 patients (91%). Indwelling stent was used in one patient; one patient underwent surgery. CONCLUSION: Mechanical lithotripsy is safe for the treatment of large common bile duct stones, with a success rate above ninety percent.

Adult↗

Pre-morbid body size and the prognosis of women with breast cancer.

Obesity has been associated with poor prognosis of breast cancer, but studies investigating indicators of adiposity, independent of height, such as skinfold thickness and weight/height ratio, have been limited. From a cohort of 89,835 women in the National Breast Screening Study, data on histologically confirmed, incident cases of invasive carcinoma of breast, diagnosed between January 1981 to June 1992, were analyzed. Body measurements were taken at enrollment and other risk-factor information from a self-administered questionnaire completed prior to diagnosis of the breast cancer. Mortality data were obtained by linkage to Statistics Canada, provincial cancer registries, and annual follow-up of cases through physicians. Of the 5 measures of body size studied among cases, poor prognosis was associated with higher triceps skinfold thickness only. With every 5 mm increase in skinfold, the risk of dying increased approximately 12% (relative risk, 1.12; 95% confidence intervals, 1.01 to 1.24) in the 1033 cases examined and adjusted for age at diagnosis, number of positive axillary nodes involved, and body weight. Compared with women in the lowest quartile of skinfold thickness, women in the fourth quartile had a relative risk (RR) of 1.64 (95% CI, 0.99 to 2.73). None of the other measures--weight, height, body mass index or weight/height ratio--reached any statistical significance. Since the reliability and validity of skinfold measures used in our study were never established, and no data were available for changes in body size after diagnosis, the results of this study on skinfold thickness should be used only as indicative of a need for further studies.

Adult↗

Premorbid diet and the prognosis of women with breast cancer.

BACKGROUND: Consumption of a high-fat diet has been associated with poor survival in breast cancer patients. However, studies examining this association are limited and have not used adjustment of energy in their estimates. PURPOSE: The effect of usual diet before diagnosis of breast cancer on the risk of dying of breast cancer was examined in a cohort of women with breast cancer from the National Breast Screening Study (NBSS) in Canada. METHODS: From a cohort of 89,835 women in the NBSS, a total of 1270 histologically confirmed cases of invasive carcinoma of the breast were identified by active follow-up, supplemented by passive follow-up involving record linkage to provincial cancer registries. Of these, 678 case patients who had completed a diet history and were diagnosed from January 1982 up to June 1992 formed the cohort for this investigation. Diet was ascertained from a self-administered diet-history questionnaire. Mortality data were obtained by linkage to the Canadian Mortality Data Base of Statistics Canada, provincial cancer registries, and annual follow-up of cases through physicians. Risk of dying and survival probabilities were estimated by the Cox proportional hazards method and the actuarial life-table method. RESULTS: There were 83 deaths in this study cohort of 678 women; 76 deaths were due to breast cancer, and the remaining seven resulted from other causes. The 5-year survival rate was 90%. For every 5% increase in energy from saturated fat, the risk of dying of breast cancer increased by 50% (hazard ratio = 1.50; 95% confidence interval [CI]: 1.08-2.08). No significant increase in risk was seen with total fat intake (hazard ratio = 1.21; 95% CI = 0.91-1.61) or oleic acid intake (hazard ratio = 1.25; 95% CI = 0.90-1.74). There was a lower risk of dying of breast cancer in the highest quartiles of beta carotene intake (hazard ratio = 0.48; 95% CI = 0.23-0.99) and vitamin C intake (hazard ratio = 0.43; 95% CI: 0.21-0.86); both vitamins showed a significant dose-response relationship (P for trend, < or = .05). These effects varied with menopausal status at diagnosis and tumor characteristics. CONCLUSIONS: These results suggest an increased risk of dying of breast cancer with higher intakes of saturated fat before diagnosis and slightly reduced risk with higher intakes of beta carotene and vitamin C. IMPLICATIONS: More attention should be paid to premorbid dietary habits in relation to breast cancer prognosis. Further studies, however, need to be done with full ascertainment of dietary changes prior to and subsequent to diagnosis.

Adult↗

Dietary fat intake and risk of epithelial ovarian cancer.

BACKGROUND: Evidence exists that dietary fat may be a contributory factor in the development of hormone-related cancers such as ovarian cancer. Previous studies have demonstrated significantly higher circulating-estrogen levels among nonvegetarian women than among vegetarian women; the increase correlated directly with consumption of saturated fat. However, the contribution that dietary fat plays in the development of hormone-related cancers remains unresolved. PURPOSE: Our purpose was to evaluate whether saturated fat intake increases the risk of ovarian cancer development. METHODS: Population-based sampling was used to acquire cases and controls over a 3-year period from the study area, which included the highly populated region surrounding the western end of Lake Ontario, Canada. From the Ontario Cancer Registry, all histologically confirmed, primary malignant or borderline malignant epithelial ovarian tumors first diagnosed from November 1989 through October 1992 among study-area residents aged 35-79 years were determined. In total, 631 eligible case subjects were identified, of whom 450 (71.3%) were interviewed concerning reproduction and diet; 564 randomly selected population control subjects were similarly interviewed. From the quantitative diet-history information, average daily intakes of macronutrients and micronutrients were calculated. Unconditional continuous logistic regression methods were used for analysis, with adjustment for age at interview, number of full-term pregnancies, years of oral contraceptive use, and total daily caloric intake. RESULTS: Saturated fat consumption was associated with increasing risk of ovarian cancer (odds ratio [OR] = 1.20 for each 10 g/day of intake; 95% confidence interval [CI] = 1.03-1.40; one-sided P = .0082). No relationship was seen with intake of unsaturated fats. Egg consumption also appeared related to increased risk (OR = 1.42 for each 100 mg of egg cholesterol per day; 95% CI = 1.18-1.72; two-sided P = .0002), though this association may have resulted from disease-related changes in the dietary practices of case subjects prior to diagnosis. Consumption of vegetable fiber (but not fruit or cereal fiber) was associated with decreased risk (OR = 0.63 for each 10 g/day; 95% CI = 0.49-0.80; two-sided P = .0001). All three nutrients (saturated fat, egg cholesterol, and vegetable fiber) remained statistically significant when included in the same regression model. CONCLUSION: Diet may contribute to risk of ovarian cancer development. IMPLICATION: If confirmed in further studies, this association may allow women to appreciably lower their risk of ovarian cancer through dietary modifications: reducing the intake of saturated fats and eating more vegetables.

Adult↗

The genome reconstruction manager: a software environment for supporting high-throughput DNA sequencing.

A new software system designed for use in high-throughput DNA sequencing laboratories is described. The Genome Reconstruction Manager (GRM) was developed from requirements derived from ongoing large-scale DNA sequencing projects. Object-oriented principles were followed in designing the system, and tools supporting object-oriented system development were employed for its implementation. GRM provides several advances in software support for high-throughput DNA sequencing: support for random, directed, and mixed sequencing strategies; a novel system for fragment assembly; a commercial object data-base management system for data storage; a client/server architecture for using network computational servers; and an underlying data model that can evolve to support fully automatic sequence reconstruction. GRM is currently being deployed for production use in high-throughput DNA sequencing projects.

Algorithms↗

Orbital-tuberculosis.

Three cases of orbital tuberculosis are presented, two as cold abscess in the orbit and one as a chronic indolent sinus. A simple clinical test like Fine Needle Aspiration Cytology (FNAC) can demonstrate some or all of the characteristic pathological features like caseating necrosis, epitheloid cells and Langhan's giant cells. Important corroborative evidence can be obtained from the Tuberculin test and a positive therapeutic trial. While there are many other causes or orbital swelling and abscess, tuberculosis should be considered an important differential diagnosis in endemic areas. Simple tests like the tuberculin reaction and Fine Needle Aspiration Cytology should be considered among the routine diagnostic investigations for orbital swellings.

Abscess↗

Dietary lactose intake, lactose intolerance, and the risk of epithelial ovarian cancer in southern Ontario (Canada).

A case-control study of dietary factors and cancer of the ovary was conducted during 1989-92 in metropolitan Toronto and surrounding areas of southern Ontario, Canada. Four hundred and fifty women aged 35-79 years, with newly diagnosed, histologically verified, primary epithelial ovarian-cancer were interviewed concerning reproduction and diet. Over the same period, 564 randomly-selected population controls, frequency-matched to the cases within three 15-year age groups, also were interviewed. From information obtained by quantitative diet history, average daily macro- and micronutrient intake values were calculated through use of the United States Department of Agriculture Food Composition Databank, which was extended and modified for Canadian items and recipes. Analysis was performed with continuous, unconditional logistic-regression methods, adjusting for age at interview, number of full-term pregnancies, total duration of oral contraceptive use, and total daily caloric intake. Neither reported history of lactose intolerance, nor average daily consumption of lactose or free galactose, were found to be associated with risk of ovarian cancer. Lactose intake or intolerance did not appear to modify the protective effects of parity and oral contraceptive use. Nevertheless, other studies suggest that ovarian galactose metabolism still may have a relationship with risk of ovarian cancer, though more evidence is needed.

Adult↗

Growth factors and hematopoietic recovery.

Availability of hematopoietic growth factors (GC-SF, GM-CSF, erythropoietin, etc.) has started a new arena of dose-intensification. The use of such growth factors has resulted in faster hematopoietic recovery of cancer patients and now offers several new treatment modifications. These include: (1)dose-intensification without hematopoietic stem cell support, (2) speedier hematopoietic recovery after hematoablative therapy and stem cell transplantation (allogeneic or autologous); (3) use of combination of growth factors, and (4) improvement in the delivery of anti-microbial drugs which are toxic towards hematopoietic cells (Gancyclovir, Bactrim, etc.). The above treatment strategies are under active clinical trials and can provide improved, cost-effective methods of treating patients with cancer.

Bone Marrow Transplantation↗