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Biomedical subjects

S B Harris

Publications and source records attributed to S B Harris.

At least 91 records · Page 5Linked to original sources
PubMed1996

Genetic variation of intestinal fatty acid-binding protein associated with variation in body mass in aboriginal Canadians.

We hypothesized that genomic variation affecting the primary amino acid sequence of the intestinal fatty acid-binding protein would be related to variation in body mass index and associated clinical phenotypes in aboriginal Canadians. We studied 507 adult native Canadians from an isolated community in Northern Ontario. We found that the frequency of the T54 variant of the intestinal fatty acid-binding protein gene was 0.14 in this sample. The presence of this variant was associated with significant increases in body mass index, percent body fat, and fasting plasma triglyceride concentration (P = 0.012, 0.019, and 0.012, respectively). However, the variant was not associated with the presence of diabetes mellitus. These findings suggest that the T54 variant of the intestinal fatty acid-binding protein is associated with differences in fat metabolism in this aboriginal population.

Adult↗
PubMed1996

Non-insulin-dependent diabetes mellitus among First Nations children. New entity among First Nations people of north western Ontario.

OBJECTIVE: To describe the emergence of a new clinical form of non-insulin-dependent diabetes mellitus (NIDDM) among First Nations children. DESIGN: Case series developed through retrospective review of a computerized diabetes registry and of records from a hospital and clinic. SETTING: Sioux Lookout Zone Hospital, a secondary care referral hospital for 28 remote First Nations communities in northwestern Ontario, affiliated with the University of Toronto's Sioux Lookout Program. PARTICIPANTS: Eighteen First Nations youths younger than 16 years identified via the Sioux Lookout Diabetes Program registry and via hospital discharge records from 1978 to 1994. Three of the 18 subjects were excluded because data essential to the study were missing from their records. MAIN OUTCOME MEASURES: Prevalence of NIDDM in this population, clinical presentation at diagnosis, and associated risk factors (including family history, obesity, and clinical management). RESULTS: Age-adjusted prevalence was 2.5/1000 in this population, the highest yet reported for NIDDM in this age group. Ratio of female to male subjects was 6:1. Typical patients were asymptomatic, obese adolescents who were not prone to ketosis and whose families had a strong history of NIDDM. CONCLUSIONS: Non-insulin-dependent diabetes mellitus can occur during childhood, particularly among First Nations people.

Adolescent↗
PubMed1994

Serum glucose, glucose tolerance, corticosterone and free fatty acids during aging in energy restricted mice.

Energy restriction, the only method known to increase maximum life span in laboratory animals, was used as a tool to test hypotheses regarding possible mechanisms of aging. Serum glucose and corticosterone (CS) concentrations in mice of a long-lived hybrid mouse strain, aged 7, 17, and 29 months, and on 50%, 80%, and 100% of ad libitum intake, were measured. Serum glucose and CS concentrations were also measured in response to intraperitoneal (i.p.) glucose challenge in mice at ages 7 and 29 months. Serum glucose and CS concentrations were also measured at several time points over 36 h, to assess their diurnal variation. There were no differences in single fasting glucose concentrations in 7- and 29-month-old mice at the same degree of energy restriction, but energy restriction decreased glucose concentrations. Serum CS concentrations were generally increased restricted animals with respect to fully fed ones. Average serum glucose concentrations were found to be significantly decreased by dietary restriction. Glucose tolerance curves were unchanged by age in ad libitum fed or 50% restricted animals, but in 80% ad libitum groups, older animals showed evidence of decreased glucose tolerance with respect to young animals. For each age, peak serum glucose concentrations after i.p. glucose loading varied with degree of energy restriction, with more severely restricted animals showing less glucose tolerance. Average serum CS concentrations were elevated at 7 months by restriction, especially at night and long after feeding, but we found no differences with age or diet in average CS concentrations. Our serum glucose results support the hypothesis that nonenzymatic glycation is mechanistically involved in normal aging. Our serum CS results do not support the hypothesis that CS contributes significantly to the pathophysiology of normal aging in mice.

Aging↗
PubMed1994

The rupture rate of acute flexor tendon repairs mobilized by the controlled active motion regimen.

A series of 233 patients with complete divisions of flexor tendons in zones 1 and 2 underwent operation following emergency admission over a period of 3.5 years. These included 203 patients with 317 divided tendons in 224 fingers injuries in zones 1 and 2 and 30 patients with 30 complete divisions of the flexor pollicis longus tendon in zones 1 and 2. All of these patients were mobilized post-operatively in a controlled active motion regimen. 13 (5.8%) fingers and five (16.6%) thumbs suffered tendon rupture during the post-operative period. Patients treated during the last year of the study were followed prospectively for a minimum period of 3 months; ten of the 16 (62.5%) fingers with zone 1 repairs, 50 of the 63 (79.4%) fingers with zone 2 repairs, all three (100%) FPL divisions in zone 1 and three of four (75%) FPL divisions in zone 2 had good and excellent results on assessment by the original Strickland criteria (Strickland and Glogovac, 1980). These results confirm the safety of this regimen as an alternative to other regimens of post-operative flexor tendon repair mobilization in zone 1 and 2 finger injuries. However, in the unmodified form used in this series, this regimen has too high a rupture rate for FPL mobilization.

Acute Disease↗
PubMed1994

Risk of clinical diabetes in a northern Native Canadian cohort.

A cohort of 630 non-diabetic adult Cree and Ojibwa Indians aged 20-64 from 6 remote communities in northern Manitoba and Ontario were followed for 46-63 months. During this period, 22 new cases of clinical diabetes were registered, an incidence density of 8.0/1000 person-years (95% confidence interval 5.8-10.3). Compared to the few published incidence studies, the rate in this population is slightly higher than the "general" North American population but still far below that of the extremely high risk groups such as Pima Indians and Nauruans. On multivariate analyses, fasting plasma glucose (FPG) level and body mass index (BMI) at baseline were significant independent predictors in a multiple logistic regression model that also contained age, sex, total cholesterol, HDL-cholesterol, triglycerides, hypertensive status, waist/hip ratio and subscapular/triceps skin-fold ratio. These associations are in accordance with current knowledge of the pathogenesis of non-insulin-dependent diabetes. This study indicates that a longitudinal follow-up study of a cohort of non-diabetic Native Canadians in remote communities is feasible. Useful data on the etiologic role of various risk factors can be generated which may be used in the planning of intervention programs in the control of this emerging health problem.

Adult↗
PubMed1992

The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans.

Biosphere 2 is a 3.15-acre space containing an ecosystem that is energetically open (sunlight, electric power, and heat) but materially closed, with air, water, and organic material being recycled. Since September 1991, eight subjects (four women and four men) have been sealed inside, living on food crops grown within. Their diet, low in calories (average, 1780 kcal/day; 1 kcal = 4.184 kJ), low in fat (10% of calories), and nutrient-dense, conforms to that which in numerous animal experiments has promoted health, retarded aging, and extended maximum life span. We report here medical data on the eight subjects, comparing preclosure data with data through 6 months of closure. Significant changes included: (i) weight, 74 to 62 kg (men) and 61 to 54 kg (women); (ii) mean systolic/diastolic blood pressure (eight subjects), 109/74 to 89/58 mmHg (1 mmHg = 133 Pa); (iii) total serum cholesterol, from 191 +/- 11 to 123 +/- 9 mg/dl (mean +/- SD; 36% mean reduction), and high density lipoprotein, from 62 +/- 8 to 38 +/- 5 (risk ratio unchanged); (iv) triglyceride, 139 to 96 mg/dl (men) and 78 to 114 mg/dl (women); (v) fasting glucose, 92 to 74 mg/dl; (vi) leukocyte count, 6.7 to 4.7 x 10(9) cells per liter. We conclude that drastic reductions in cholesterol and blood pressure may be instituted in normal individuals in Western countries by application of a carefully chosen diet and that a low-calorie nutrient-dense regime shows physiologic features in humans similar to those in other animal species.

Adult↗
PubMed1991

Lack of effect of age and dietary restriction on DNA single-stranded breaks in brain, liver, and kidney of (C3H x C57BL/10)F1 mice.

Single-stranded DNA breaks in brain, liver, and kidney of (C3H x C57BL/10)F1 mice 6 and 25 months of age on two dietary regimens (isonutrient diets at 85 and 50 kcal/week) were investigated by means of fluorometric analysis of DNA unwinding in alkaline solutions. No age-dependent alterations were found for either control or dietary restricted groups. Except for possible differences for liver in the young age groups, there were no significant differences in the amount of single-stranded DNA breaks between control and dietary restricted mice. These results suggest that the antiaging effects of dietary restriction in rodents are not mediated by a change in the number of accumulated nuclear DNA stranded breaks in internal organs.

Aging↗
PubMed1990

Dietary restriction alone and in combination with oral ethoxyquin/2-mercaptoethylamine in mice.

To investigate effects of dietary caloric restriction (DR) combined with antioxidant feeding, long-lived hybrid mice were divided into four dietary groups at weaning, and followed until natural death. Groups "C" and "R" received control (97 kcal/wk) and restricted (56 kcal/wk) diets respectively. Groups "C+ alpha ox" and "R+ alpha ox" received C or R diets supplemented with an antioxidant mixture (2-mercaptoethylamine plus ethoxyquin). R mice (mean life span 41 months) significantly outlived the other three groups (mean life span 30-34 months). Hepatic degeneration and increased hepatoma in the R+ alpha ox group suggested unusual hepatotoxicity of this regimen. Antioxidants had little effect on splenic cell mitogen response in similarly fed mice sacrificed at 12-15 months. Gompertz analysis suggests that the beneficial effect of DR may be due to reductions in initial vulnerability or rate-of-aging parameters, or both, and that the relative influence of each factor may vary with animal strain and DR protocol used.

Animals↗
PubMed1989

Inhalation developmental toxicity study of propylene oxide in Fischer 344 rats.

The developmental toxicity potential of propylene oxide (PO) was evaluated in Fischer 344 rats following inhalation exposure. Four groups of 25 mated female rats were exposed to 0, 100, 300, and 500 ppm of PO for 6 hr per day on Gestation Days 6 through 15, inclusive. Cesarean sections were performed on all females on Gestation Day 20 and the fetuses removed for morphological evaluation. Exposure to propylene oxide did not adversely affect survival, appearance, or behavior at any of the exposure levels tested. Maternal body weight gain and food consumption were reduced significantly among the females at the 500 ppm level during the exposure period. No exposure-related effects were noted with respect to maternal water consumption, organ weights, cesarean section, or fetal morphological observations with the sole exception of increased frequency of seventh cervical ribs in fetuses at the maternally toxic exposure level of 500 ppm. In summation, the no-observable-adverse-effect level (NOAEL) of propylene oxide, when administered to Fischer 344 rats via whole-body inhalation exposure, was considered to be 300 ppm.

Administration, Inhalation↗
PubMed1989

Fetal effects of inhalation exposure to cyclohexanone vapor in pregnant rats.

Cyclohexanone (CH), a solvent and thinner that has extensive use in industry, was investigated for developmental effects using pregnant Sprague-Dawley rats exposed to 100, 250 or 500 ppm concentrations in an inhalation chamber for seven hours per day from days 5 through 20 of pregnancy. Controls were exposed to room air. Maternal weight gain at 250 and 500 ppm CH was only slightly lower than in the control dams, and a grey mottling of the lungs was seen in a few of the CH-exposed dams. There were no significant differences between the CH and control groups in fetal weight, resorption sites, fetal death or sex ratio. External and soft tissue examinations revealed no significant incidence of malformations or variations in CH-exposed animals. A slight increase in the mean percent of rudimentary ribs per litter was observed in the 250 and 500 ppm CH-exposed groups. However, no significant numbers of skeletal malformations were noticed in either the CH or room air control groups. It was concluded that respiratory exposure of rats to as much as 500 ppm CH during organogenesis was unlikely to be developmentally toxic.

Administration, Inhalation↗
PubMed1987

Dietary restriction and aging: historical phases, mechanisms and current directions.

Energy intake restriction (ER) without essential nutrient deficiency retards aging and extends life span in all species tested so far, and across wide phylogenetic differences. Historical phases of this model system for studying aging have included modulation of the survival curve, effects on disease susceptibility and effects on physiological indices of aging; the current phase focuses upon possible mechanisms whereby ER influences such widely diverse phenomena. Mechanistic possibilities include effects on the immune system, on basal state and proliferation potential, metabolic rate, DNA repair, levels of free radical scavengers, chromatin structure and protein synthesis and turnover. The ER model may also be useful in analyzing unifactorial versus multifactorial theories of aging, and in clarifying the possible significance of physiological markers that correlate with differences in maximum life spans between species.

Aging↗
PubMed1986

Reproductive and teratogenic effects of nitrous oxide, halothane, isoflurane, and enflurane in Sprague-Dawley rats.

A total of 305 timed-pregnant Sprague-Dawley rats were exposed for 6 h a day on each of three consecutive days in one of three periods, i.e., pregnancy days 14-16, 11-13, or 8-10, either to 0.55 times the minimum alveolar concentration (MAC) of nitrous oxide (75%) or to 0.75 MAC of halothane (0.8%), isoflurane (1.05%) or enflurane (1.65%); an additional 232 positive-control (retinoic acid) and air control rats were studied. Reproductive indices were determined, and the 5178 offspring delivered at cesarean section were examined for external, internal, and skeletal abnormalities. There were no major or minor teratologic effects in anesthetic treated groups, although several developmental variants were observed in halothane- and enflurane-treated groups. Nitrous oxide exposure on days 14-16 resulted in a three-fold increase in fetal resorptions. The results suggest that the volatile anesthetics are not teratogenic and confirm that nitrous oxide may be associated with increased reproductive loss.

Abnormalities, Drug-Induced↗
PubMed1978

Preclinical safety evaluation of 15[S]15-methyl prostaglandin F2alpha : reproduction and teratology.

The abortifacient 15[S]15-methyl prostaglandin F2alpha, designated PGF2alpha (M), was tested in pregnant rats and rabbits for purposes of preclinical safety evaluation. The material tested was the tromethamine salt of PGF2alpha with the generic name, carboprost tromethamine. Doses of 0.25, 0.50, and 1 mg/kg given by subcutaneous injection to male and female rats for 3 or 6 consecutive days before mating did not have an adverse effect on reproduction. The principal finding in rat and rabbit teratology studies was that PGF2alpha (M) had a high order of embryolethality regardless of when it was administered. Rabbits were more sensitive than were rats and PGF2alpha (M) interfered with nidation or early embryonic development when given during the second week of gestation. The largest dose of PGF2alpha (M) that allowed some fetuses to survive was 0.25 mg/kg for rats and 0.005 mg/kg for rabbits when given by subcutaneous injection for 3 consecutive days at some point during organogenesis. Fetuses from rabbits given the doses of 0.0025 and 0.005 mg/kg were normal. There were a variety of skeletal anomalies (mostly of ribs and thoracic vertebrae) in fetuses from rats given, by subcutaneous injection, doses of PGF2alpha (M) ranging from 0.25 to 0.05 mg/kg for 3 consecutive days at some point during organogenesis. Although there were few gross or visceral anomaliies in either rats or rabbits, the incidence of osseous anomalies in rats was of both statistical and biologic significance. Rats given PGF2alpha (M) by subcutaneous injection beginning on the 15th day of gestation in a perinatal-postnatal study were most sensitive to the abortifacient. In that study the no-effect level was 0.0001 mg/kg. At larger doses ranging from 0.25 to 0.003 mg/kg, treatment was associated with abortion, poor viability, and impaired lactation.

Abnormalities, Drug-Induced↗
PubMed1977

Correlation of cytotoxicity and mitotic spindle dissolution by vinblastine in mammalian cells.

In two hamster cell lines that differed 100-fold in their vinblastine sensitivity, dissolution of the mitotic spindle by vinblastine in living cells correlated with cytotoxicity from vinblastine expressed as suppression of colony formation. The effect on the spindle apparatus occurred in 30 sec or less and thus provides a rapid assay for determining the cytotoxic effects of the Vinca alkaloids, as well as the potential for quantitative assay of solutions of Vinca derivatives.

Cell Line↗
PubMed1976

Teratology and percutaneous toxicity studies on hair dyes.

Twelve hair dye formulations were tested for systemic toxicity by topical application twice weekly for 13 wk to groups of 12 New Zealand white rabbits and for teratologic effects following applications to groups of 20 pregnant Charles River CD rats on days 1, 4, 7, 10, 13, 16, and 19 of gestation. The three semipermanent formulations were applied as is, and the nine oxidation dyes were mixed 1:1 with 6% hydrogen peroxide just prior to application, as in normal use. The formulations induced a broad spectrum of dyes and dye intermediates used or considered useful in oxidative and semipermanent hair color products. In the teratology study no biologically significant soft tissue or skeletal changes were noted. Similarly, the mean numbers of corpora lutea, implantation sites, live fetuses, and resorptions per pregnancy, as well as numbers of litters with resporptions, were not significantly affected by the dye treatment. In the percutaneous toxicity study there was no evidence of compound-induced systemic effects. Microscopic examination of 25 tissues from each animal gave no indication of histomorphologic evidence of toxicity. No dye discoloration of urine was seen at any time during the test or at necropsy. Some of the dye groups showed epidermal hyperplasia, which was probably a reflection of slight irritation due to the frequency of application of the oxidation formulations.

Abnormalities, Drug-Induced↗