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Biomedical subjects

J Schwartz

Publications and source records attributed to J Schwartz.

At least 271 records · Page 15Linked to original sources

Oral cancer inhibition by micronutrients. The experimental basis for clinical trials.

Extensive research has been carried out in experimental animals to demonstrate the anticancer activity of retinoids, carotenoids and tocopherol on oral cancer and oral precancerous leukoplakia. The anticancer properties of these micronutrients have been studied in experiments dealing with inhibition of carcinogenesis, prevention of oral cancer development and regression of established oral carcinoma. Synergism has been demonstrated in the anticancer activity of beta carotene and alpha tocopherol. Synergism has also been demonstrated between beta carotene and anticancer alkylating agents such as melphalan and cyclophosphamide. Micronutrients such as beta carotene have been found to inhibit both major phases of carcinogenesis--initiation and promotion. Animal studies of oral cancer inhibition, prevention and regression have been substantiated by tissue culture studies, using animal and human derived oral cancer cell lines and normal epithelial cells. Mechanisms of the anticancer activity of the micronutrients on experimental oral cancer have been explored. They include stimulation of elements of the immune system to kill cancer cells, and enhanced expression of heat-shock proteins and repressor genes such as P 53.

Animals↗

p53 in the anticancer mechanism of vitamin E.

Immunohistochemical techniques were used to study the expression of "wild type" p53 and "mutant" p53 in experimental cancer inhibition by vitamin E. The cancer model used was the squamous cell carcinoma of hamster buccal pouch induced by the carcinogen 7,12 dimethylbenz(a)anthracene (DMBA). Cancer development was studied sequentially for 8-14 weeks and specimens prepared for histological and immunohistochemical interpretation. Primary antibodies used were monoclonal antibodies for "wild type" and "mutant" p53. Specificity of antibodies was confirmed by flow cytometry. Peroxidase-antiperoxidase staining was used on the tissue specimens. In those animals receiving vitamin E the buccal pouch tumour development was significantly inhibited and there was a notable expression of "wild type" p53. There was also a relative absence of "mutant" p53 in the buccal pouch lesions of animals receiving vitamin E. These observations suggest that vitamin E may inhibit cancer formation by stimulating the expression of a cancer suppressor gene.

Animals↗

Peripheral blood leukocyte count and respiratory symptoms.

The relationship of peripheral blood leukocyte count to respiratory symptoms was explored in data from the Second Annual National Health and Nutrition Survey (NHANES II). The study sample consisted of 9237 white and nonwhite US adults between the ages of 30 and 74 years. Three respiratory symptom outcomes were utilized: physician-diagnosed chronic cough and chronic bronchitis and self-reported frequent wheeze apart from colds or flu in the past 12 months. Peripheral blood leukocyte counts were performed using a Coulter counter, model FN. Logistic regression analysis was performed for each of the three respiratory symptom outcomes controlling for age, race, gender, and cigarette-years of smoke exposure. The peripheral blood leukocyte count was a significant predictor for each symptom. For a standard deviation increase in the log leukocyte count, the relative odds of wheezing was 1.93 (95% confidence level [CI], 1.47 to 2.52); for chronic cough, 2.29 (95% CI, 1.74 to 3.00); and for bronchitis, 2.44 (95% CI, 1.77 to 3.35). Analyses restricted to never smokers gave similar results. These data suggest that peripheral blood leukocyte count correlates with respiratory symptoms and are consistent with the hypothesis that the leukocyte count is a serum marker of inflammation.

Adult↗

Inhibition of oral carcinogenesis by glutathione.

Forty young adult Syrian hamsters (Mesocricetus auratus) were divided into four groups of 10 animals each. In Group 1 (tumor control), the right buccal pouches were painted three times per week with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in heavy mineral oil (USP) with a no. 4 sable brush. In Group 2 (experimental group), the right buccal pouches were painted with DMBA, as in Group 1. In addition, Group 2 received 1 mg of reduced glutathione in 0.5 ml of mineral oil three times per week on days alternate to the DMBA application. The glutathione was administered systemically by mouth with a pipette. Group 3 received only glutathione, and Group 4 was untreated (control groups). Animals were sacrificed after 14 weeks, and tumors were counted and measured. Both right and left pouches were photographed, excised, fixed in formalin, sectioned in paraffin, and studied histologically. The animals receiving glutathione demonstrated significantly fewer and smaller tumors. The mean tumor burden was 315 mm3 in the glutathione-treated group and 3,040 mm3 in the untreated group. The statistical significance by Student's t test was < or = 0.0001. Histological study also revealed significantly fewer areas of dysplastic leukoplakia in the group treated with glutathione. This study represents the first demonstration of the anticancer effect of systemically administered reduced glutathione.

9,10-Dimethyl-1,2-benzanthracene↗

The effectiveness of a mixture of beta-carotene, alpha-tocopherol, glutathione, and ascorbic acid for cancer prevention.

Previous studies have shown that beta-carotene and alpha-tocopherol can act synergistically to inhibit the growth of experimentally induced oral cancer. The initial studies on the synergistic anticancer activity of antioxidants have been extended to include reduced glutathione and ascorbic acid. Sixty male hamsters (4-5 wks old) were divided into six equal groups. Groups 1-6 were treated with 7,12-dimethylbenz[a]anthracene (DMBA) (0.5% solution). Group 2 received a mixture containing equal amounts of beta-carotene, dl-alpha-tocopherol (vitamin E), glutathione, and l-ascorbic acid (vitamin C) (12.5 micrograms) delivered orally by pipette. Groups 3-6 were treated with beta-carotene alone (50 micrograms), vitamin E alone (50 micrograms), glutathione (50 micrograms) alone, and vitamin C alone (50 micrograms). Animals were euthanized at 12 and 14 weeks. Tumors were counted and measured, and tumor burden was calculated for each experimental group. The mixture of antioxidants significantly reduced tumor burden, whereas the beta-carotene, vitamin E, and reduced glutathione treatments also reduced tumor burden. beta-Carotene and glutathione provided greater levels of chemoprevention than vitamin E as single agents. In contrast, vitamin C treatment produced no antitumor effect but increased tumor burden by Week 14. This mixture of antioxidants produced a significant synergistic chemoprevention of oral cancer.

9,10-Dimethyl-1,2-benzanthracene↗

Head-up tilt testing with and without isoproterenol infusion in healthy subjects of different ages.

Passive head-up tilt testing with or without infusion of isoproterenol is used in the investigation and management of patients with syncope. Twenty-five healthy asymptomatic volunteers prospectively grouped according to age (young [28 +/- 1.7 years]: n = 9; middle [51 +/- 3.3 years]: n = 11; elderly [81 +/- 2.4 years]: n = 5; mean +/- SE) were studied during: (1) supine carotid sinus massage; (2) 60 degrees head-up tilt alone; and (3) infusion of isoproterenol to raise the heart rate 20% above supine baseline, prior to 10-minute repeat tilt. Symptoms occurred in three subjects (12%) and only occurred with passive tilting alone. Two young subjects had syncope with sinus pauses greater than 10 seconds. One elderly subject developed atrial flutter. No subject had symptoms or hypotension during tilt plus isoproterenol or a pause greater than 3 seconds with carotid sinus massage. With passive tilt, mean heart rate increased by 16 +/- 6 beats/min and 18 +/- 7.8 beats/min in the young and middle aged subjects (P < 0.05), but only by 6 +/- 5 beats/min in the elderly (P = NS, supine vs 60 degrees in each group). With head-up tilt plus isoproterenol infusion, the mean heart rate elevation in response to tilt was 17 +/- 9 beats/min, 8 +/- 3 beats/min, and 12 +/- 4 beats/min for the young, middle, and elderly subjects, respectively (P < 0.05, supine vs 60 degrees in each group).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Baroreflex buffering of pressor response to vasopressin is mediated by V1, not V2, receptors in conscious rats.

Arginine vasopressin (AVP) enhances reflex buffering of its own pressor response, thus attenuating its vasoconstrictor potential in vivo. To investigate the extent to which this effect of AVP is mediated by V1 or V2 receptors, mean arterial pressure (MAP) and heart rate (HR) changes were examined in response to graded injections of AVP or [Phe2,Orn8]oxytocin, a potent, selective V1-receptor agonist, in the absence and presence of infusion of [Val4,D-Arg8]VP, a selective V2-receptor agonist. Responses were compared in intact and autonomically blocked conscious rats. During autonomic blockade with methscopolamine and hexamethonium, the pressor sensitivities to AVP and [Phe2,Orn8]oxytocin were similarly increased. Infusion of the V2-receptor agonist had no effect by itself on MAP or HR in conscious intact rats. It also did not alter the pressor responses to the V1 agonist, in either intact or autonomically blocked rats. In the presence of the V2 agonist, the decrease in heart rate induced by the V1 agonist was enhanced. These results indicate that reflex buffering of the pressor response to AVP in the conscious rat is mediated by V1 and not V2 receptors. However, V2 receptors may be involved in modulating the heart rate response to AVP.

Animals↗

Particulate air pollution and hospital emergency room visits for asthma in Seattle.

Recent studies have associated short-term exposure to respirable particulate matter (PM10) exposure with peak flow decrements, increased symptoms of respiratory irritation, increased use of asthma medications, and increased hospitalization for asthma. Increased mortality from chronic respiratory disease has also been reported. To help confirm whether PM10 exposure is a risk factor for the exacerbation of asthma, we compiled daily records of asthma emergency room visits from eight hospitals in the Seattle area. In Poisson regressions controlling for weather, season, time trends, age, hospital, and day of the week, the daily counts of emergency room visits for persons under age 65 were significantly associated with PM10 exposure on the previous day. The mean of the previous 4 days' PM10 was a better predictor (p < 0.005). The relative risk for a 30 micrograms/m3 increase in PM10 was 1.12 (95% confidence interval 1.20 to 1.04). Daily PM10 concentrations never exceeded 70% of the current ambient air quality standards during the period. The consistency of investigations of the health effects of PM10 suggest that increased attention should be given to the control of particulate matter air pollution.

Adolescent↗

Dissociative disorders in psychiatric inpatients.

OBJECTIVE: This study attempted to determine 1) the prevalence of dissociative disorders in psychiatric inpatients, 2) the degree of reported childhood trauma in patients with dissociative disorders, and 3) the degree to which dissociative experiences are recognized in psychiatric patients. METHOD: A total of 110 patients consecutively admitted to a state psychiatric hospital were given the Dissociative Experiences Scale. Patients who scored above 25 were matched for age and gender with a group of patients who scored below 5 on the scale. All patients in the two groups were then interviewed in a blind manner, and the Dissociative Disorders Interview Schedule, the Traumatic Antecedent Questionnaire, and the posttraumatic stress disorder (PTSD) module of the Structured Clinical Interview for DSM-III-R, Nonpatient Version, were administered. Chart reviews were also conducted on all patients. RESULTS: Fifteen percent of the psychiatric patients scored above 25 on the Dissociative Experiences Scale; 100% of these patients met DSM-III criteria for a dissociative disorder. These patients had significantly higher rates of major depression, PTSD, substance abuse, and borderline personality than did the comparison patients, and they also reported significantly higher rates of childhood trauma. Chart review data revealed that dissociative symptoms were largely unrecognized. CONCLUSIONS: A high proportion of psychiatric inpatients have significant dissociative pathology, and these symptoms are underrecognized by clinicians. The proper diagnosis of these patients has important implications for their clinical course.

Adolescent↗

Isolated tuberculous pericarditis still exists: a case history.

A fifty-four-year-old woman from a high socioeconomic class developed acute isolated tuberculous pericarditis, three years after her sister had recovered from such disease. She was treated successfully by a triple drug regimen including isoniazid, rifampin, and ethambutol.

Drug Therapy, Combination↗

A variant of Noonan's syndrome: a case history.

The authors describe a variant of Noonan's syndrome hitherto undescribed. The special findings in this case were anomalous origin of the aortic arch vessels and focal glomerulonephritis.

Acute Kidney Injury↗

Bioactivity of human growth hormone in serum: validation of an in vitro bioassay.

GH, in clinical practice, is determined by RIA, but RIA estimates may not accurately reflect serum GH bioactivity. The available measures of GH bioactivity lack either sensitivity, specificity, or a physiologically relevant end point. The objective of this research was to develop a physiologically relevant GH bioassay which would not only measure the bioactivity of purified GH preparations, but would also have sufficient sensitivity to measure GH bioactivity in human serum. The method consisted of incubating murine 3T3-F442A adipocytes in serum-free medium containing BSA, 14C-glucose, and increasing concentrations of GH or test materials for 24 h, followed by measurement of conversion of glucose to lipid. Interference by nonspecific serum factors was reduced by the addition of 10 micrograms/liter insulin, 25 nM dexamethasone, and 37 nM estradiol to the medium. In the presence of 10 micrograms/liter insulin, 50 micrograms/liter insulin-like growth factor-1 did not alter the ability of GH to suppress lipid accumulation. Epinephrine and glucagon could suppress lipid accumulation but only at concentrations greatly in excess of the physiological range in serum. Twenty two thousand dalton hGH produced dose-dependent suppression of lipid accumulation which was linear between 0.625 and 10 micrograms/liter (r = 0.926; P = 0.0001) with a half-maximal response of 3.0 +/- 0.2 micrograms/liter (n = six experiments). The intra- and interassay coefficients of variation were 7% and 19%, respectively. The assay was specific for GH since addition of human PRL produced suppression of lipid accumulation only at concentrations where contamination of the preparation by GH became a significant factor. ACTH also suppressed lipid accumulation but only at doses of 1000 micrograms/liter or greater. Human placental lactogen and hLH, hFSH, and hTSH did not cross-react with GH in this assay. Addition of human serum did not alter the slope of ED50 of the GH dose-response curve. Pools of serum from prepubertal and pubertal boys and girls, subjects treated with arginine or insulin, a diabetic girl, and a boy with gigantism who had a serum GH content of 80 micrograms/liter by RIA and 40 micrograms/liter by bioassay, produced dose response curves parallel to that of the GH standard curve. Serum from patients with hypopituitarism did not produce significant suppression of lipid accumulation in any assay. Recovery of 5 micrograms/liter GH added to human serum was 94%. Twenty thousand dalton GH also suppressed lipid accumulation in this assay, but was 2-fold less potent than 22,000 dalton GH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗