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Biomedical subjects

J K Howard

Publications and source records attributed to J K Howard.

At least 19 recordsLinked to original sources
PubMed2000

Starvation, leptin and epithelial cell proliferation in the gastrointestinal tract of the mouse.

BACKGROUND/AIMS: Leptin, the ob/ob gene product, is a recently discovered peptide hormone, secreted by adipocytes, which can act as a satiety factor to regulate food intake. Its levels thus will be related to the presence of food in the lumen of the gut, and food intake is one of the most potent stimuli for intestinal epithelial cell proliferation. Leptin has a variety of other actions and the aim of this study was to see if one of these was to stimulate mucosal growth. METHODS: Three groups of mice were fed ad libitum, starved for 48 h or starved for 48 h and given twice-daily intraperitoneal injections of recombinant leptin (1 microg/g). RESULTS: Starvation led to a 20% decrease in body weight and a similar decrease in the weights of the intestines. Starvation also markedly inhibited intestinal epithelial cell proliferation. Leptin had little effect on the small intestine and did not stimulate proliferation. However, in the hind gut it was associated with small but significant decreases in caecal weight, distal colon mitotic counts (p = 0.036) and in colonic crypt area (approximately 20%, p<0.001). CONCLUSION: Leptin did not stimulate intestinal cell proliferation, however it did have a paradoxical inhibitory action on the caecum and colon.

Animals↗
PubMed2000

Increased leptin levels in serum and peritoneal fluid of patients with pelvic endometriosis.

Pelvic endometriosis is an immune-related chronic inflammatory disease, characterized by ectopic implants of endometrium in the peritoneal cavity and associated with increased secretion of proinflammatory cytokines and neoangiogenesis. Leptin, the adipocyte-derived hormone, has been shown to have a role in food intake, basal metabolism, and reproductive function. Leptin levels are dynamically regulated, being elevated by inflammatory mediators and reduced by starvation. Leptin itself can influence the proinflammatory immune responses of CD4+ T lymphocytes, and reports have also shown this hormone to be an angiogenic factor in vitro and in vivo. We investigated whether leptin concentrations in serum and peritoneal fluid (PF) differed between 13 patients with different stages of endometriosis and 15 age- and body mass index-matched controls. We found a statistically significant (P < 0.05) increase in leptin levels in serum (30.3 +/- 14.8 ng/mL) and PF (35.9 +/- 17.4 ng/mL) of patients with endometriosis, compared with our control population (serum, 15.6 +/- 8.4; PF, 17.5 +/- 7.2 ng/mL). Regression equations, relating leptin to body mass index, were also significantly different in endometriosis patients, compared with controls. Higher levels of leptin were observed in the earlier stages of endometriosis than advanced-stage disease. These data suggest that the proinflammatory and neoangiogenic actions of leptin may contribute to the pathogenesis of endometriosis.

Adult↗
PubMed1999

Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice.

Thymic atrophy is a prominent feature of malnutrition. Forty-eight hours' starvation of normal mice reduced the total thymocyte count to 13% of that observed in freely fed controls, predominantly because of a diminution in the cortical CD4(+)CD8(+) thymocyte subpopulation. Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes. The ob/ob mouse, which is unable to produce functional leptin because of a mutation in the obese gene, has impaired cellular immunity together with a marked reduction in the size and cellularity of the thymus. We found that ob/ob mice had a high level of thymocyte apoptosis resulting in a ratio of CD4(+)CD8(+) (cortical) to CD4(-)CD8(-) (precursor) thymocytes that was 4-fold lower than that observed in wild-type mice. Peripheral administration of recombinant leptin to ob/ob mice reduced thymocyte apoptosis and substantially increased both thymic cellularity and the CD4(+)CD8(+)/CD4(-)CD8(-) ratio. In contrast, a comparable weight loss in pair-fed PBS-treated ob/ob mice had no impact on thymocyte number. In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy.

Animals↗
PubMed1998

Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression.

Nutritional deprivation suppresses immune function. The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight. Circulating levels of this adipocyte-derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators. The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob) or its receptor (db/db), has never been explained. Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases. We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells. Leptin increased Th1 and suppressed Th2 cytokine production. Administration of leptin to mice reversed the immunosuppressive effects of acute starvation. Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.

Adult↗
PubMed1997

Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents.

The adipose tissue hormone, leptin, and the neuropeptide glucagon-like peptide-1 (7-36) amide (GLP-1) both reduce food intake and body weight in rodents. Using dual in situ hybridization, long isoform leptin receptor (OB-Rb) was localized to GLP-1 neurons originating in the nucleus of the solitary tract. ICV injection of the specific GLP-1 receptor antagonist, exendin(9-39), at the onset of dark phase, did not affect feeding in saline pre-treated controls, but blocked the reduction in food intake and body weight of leptin pre-treated rats. These findings suggest that GLP-1 neurons are a potential target for leptin in its control of feeding.

Animals↗
PubMed1997

Plasma immunoreactive leptin concentration in end-stage renal disease.

1. Leptin is thought to be an inhibitor of appetite. As the kidney helps clear several polypeptide hormones, plasma leptin may accumulate in end-stage renal disease. 2. Plasma immunoreactive leptin was measured in four groups of subjects: haemodialysis, continuous ambulatory peritoneal dialysis and renal transplant patients and a group of healthy controls. Leptin was also measured before and after a single dialysis session. 3. There was a strong correlation between plasma immunoreactive leptin and body mass index in all groups except female haemodialysis patients. Leptin was higher in females than in males in all groups when controlled for body mass index. Mean plasma leptin [mean (SD)] was significantly higher in all renal groups [haemodialysis, 15.1 (3.6) ng/ml; continuous ambulatory peritoneal dialysis, 25.4 (4.3) ng/ml; transplants, 11.6 (2.6) ng/ml] compared with controls [5.3 (2.3) ng/ml]. There was a significant difference in the regression equations relating leptin and body mass index (dialysis > transplants > controls), even when controlled for gender. Leptin correlated modestly with serum creatinine in non-dialysis subjects. Plasma leptin immunoreactivity was slightly reduced by haemodialysis, but post-dialysis leptin was still significantly higher than that found in controls. 4. Chromatographic characterization of the high level of leptin immunoreactivity found in haemodialysis subjects showed a single elution peak corresponding to that of the highly purified human leptin standard. 5. In conclusion, leptin is higher than expected for body mass index in end-stage renal disease. Hyperleptinaemia could contribute to the anorexia and poor nutritional status commonly seen in renal failure.

Adult↗
PubMed1997

Neuropeptide Y induced feeding in the rat is mediated by a novel receptor.

There are now six recognized neuropeptide Y (NPY) receptor subtypes (Y1-Y4 and two recently cloned distinct receptors labeled Y5), of which Y1 and one of the Y5's have been suggested could mediate the effect of NPY on feeding. The fragments NPY(2-36) and NPY(3-36), which bind Y1 only poorly, were injected intracerebroventricularly (icv) and found to have similar dose-response relationships to NPY in the stimulation of feeding. However NPY (13-36), which stimulates both Y2 and Y5, caused no increase in food intake, even at high doses. Maximal stimulation with the classical Y1 agonist [Pro34]-NPY produced only 50% of the maximum effect of NPY itself despite fully inhibiting adenylyl cyclase activity in vitro in a Y1 system. The novel fragment [Pro34]-NPY(3-36) is as effective at stimulating food intake as the classical Y1 analogue [Pro34]-NPY but bound to the Y1 receptor with only 1/20th of the affinity of NPY and failed to inhibit adenylyl cyclase through this receptor. [Pro34]-NPY(3-36) is therefore a relatively appetite-selective ligand. Coadministration of high dose NPY(13-36) and [Pro34]NPY did not enhance feeding compared with [Pro34]-NPY alone. In addition, the NPY Y1 receptor antagonist BIBP-3226, which does not bind Y2, Y4, or Y5 receptors, significantly reduced NPY induced feeding. These results indicate that the feeding effect of icv NPY involves a novel receptor and that it is functionally distinct from the recognized receptor subtypes.

Adenylyl Cyclases↗
PubMed1996

A cardiovascular risk reduction program for the classroom.

A quasi-experimental, longitudinal study was conducted to test the effectiveness over a 1-year period of a cardiovascular risk reduction program for school-age children. The effectiveness of the program was measured with the children's knowledge of physiology of the heart and cardiovascular risk factors, their health habits, and their physical measurements. Ninety-eight children between the ages of 9 and 12 years participated in the study. The experimental group received a series of five 40-minute sessions on physiology of the heart, smoking, hypertension, diet, and physical activity. Short-term effectiveness of the program was found for the children's knowledge of physiology of the heart and smoking. Long-term effectiveness was found for running activity.

Cardiovascular Diseases↗
PubMed1991

Cardiovascular risk factors in children: a Bloomsday research report.

Cardiovascular risk factors identified in major studies of children include a family history of heart disease, smoking, blood pressure, dietary factors, exercise or fitness level, and stress. The purpose of this descriptive study was to identify differences in children's physical measurements with regard to six cardiovascular risk factors. A descriptive design using three questionnaires and physical measurements was used. The questionnaires included the Bloomsday Cardiovascular Fitness Questionnaire, the Coronary Risk Profile, and the Diet Habit Survey. Physical measurements included blood pressure readings, weight, total serum cholesterol, and high-density lipoprotein levels. A convenience sample of 78, predominantly Caucasian children between the ages of 7 and 18 years (M = 13.13, SD = 2.79) participated. Results indicated that differences in physical measurements were significantly for children with respect to the cardiovascular risk factors, including dietary factors, blood pressure, exercise, and stress. Nursing implications for thorough assessment and intervention through education are discussed.

Adolescent↗
PubMed1987

Time trends and occupational differences in cancer of the testis in New Zealand.

The findings are reported from a New Zealand Cancer Registry-based case-control study involving 427 male patients with testicular cancer registered during the period 1979-1983 and aged 20 years or more at time of registration. Controls were also males chosen from the Cancer Registry with two controls per case, matched on age and year of registration. It was found that, as in other countries, persons in the upper social class groupings were at increased risk of testicular cancer. Persons in professional occupations were also at increased risk, but the odds ratio of 1.09 was much smaller than found in other studies. The previously reported excess risks for farmers, food and beverage workers, forestry workers, and pulp and paper workers were not supported by the New Zealand data. On the other hand, the previously reported excess risk for sales and service workers including members of the armed forces was supported, to some extent, by the New Zealand data with odds ratios of 1.38 (95% confidence limits 0.98-1.93) and 2.15 (95% confidence limits 0.80-5.79), respectively. Other groups with elevated risk include: physicians (odds ratio = 6.50, 95% confidence limits 1.29-32.6); production supervisors (odds ratio = 2.85,95% confidence limits 1.00-8.13); and motor vehicle mechanics (odds ratio = 2.02, 95% confidence limits 0.93-4.42). However, the New Zealand data generally does not suggest that occupational factors (or lifestyle factors associated with occupation) are of major direct importance in the etiology of testicular cancer. The incidence of testicular cancer has a bimodal age distribution in New Zealand and has risen markedly during the period 1948-1979. The New Zealand data differed from patterns observed in other countries in that the relative increase was approximately uniform across age groups rather than being stronger in the younger age groups.

Age Factors↗
PubMed1986

Secular trends in anencephalus prevalence in New Zealand.

Although the aetiology of anencephalus is unknown, changes in prevalence over time are thought to provide strong evidence of the effect of environmental factors in causation. In a number of countries the rate of this neural tube defect is declining. The rate in New Zealand has also fallen significantly (p less than 0.001) from 1.17/1000 total births in 1968 to 0.39/1000 in 1983, with the greatest decrease occurring in the female rate (approximately 4.16% per year). The aetiological implications of these findings and their consequences for programmes of prenatal diagnostic testing and maternal screening are discussed.

Abortion, Therapeutic↗
PubMed1986

Risk factors in the prevalence of anencephalus and spina bifida in New Zealand.

This paper presents results from an epidemiological study on the 51 anencephalus and 53 spina bifida cases in the 1978 New Zealand birth cohort. Multiple sources were used in the ascertainment, and the prevalence rates were 0.98 and 1.02 per 1,000 total births, respectively. No association was found with the traditional indicators of the effect of environmental factors: maternal age, social class, nuptiality, month of birth, or estimated month of conception. Males comprised 41% of anencephalus and 36% of spina bifida cases; the prevalence was higher in the non-Maori than in the Maori population. New Zealand-born mothers appear to have a much lower risk of spina bifida, but not anencephaly, than those born in England/Scotland. The rate for the latter population was within the range of a number of UK-based studies. As the bloodstock of New Zealand whites has been predominantly derived from the UK population, and as New Zealand is a low prevalence area, this suggests that the higher risk for these women is likely to be attributable to factors present in their birthplace but absent in New Zealand. These findings provide further evidence that the epidemiologic patterns of anencephalus and spina bifida in low-prevalence areas are at variance with those in high-prevalence areas, such as the United Kingdom. They also support the hypothesis that the contrast in rates between high- and low-prevalence areas is a reflection of the impact of environmental factors in high-prevalence areas on the "background" or baseline frequency of anencephalus and spina bifida found in low-prevalence areas.

Adult↗
PubMed1986

Case-control study of multiple myeloma and farming.

A previous case-control study which utilised the occupational information available on the New Zealand Cancer Registry found an increased risk of multiple myeloma in agricultural workers consistent with previous findings in the United States. The findings are now presented for the second phase of the study which involved interviewing 76 cases of multiple myeloma (who had been included in the previous study) together with 315 controls with other types of cancer. The previous finding on an excess of farmers in the case group was confirmed by the interview data (odds ratio = 1.7, 95% confidence limits 1.0-2.9, P = 0.04). There were no significant differences between cases and controls regarding potential exposure to phenoxy herbicides or chlorophenols. There were also no significant differences regarding activities involving potential exposure to other agricultural chemicals, although the odds ratio for fencing work, which may involve exposure to arsenic and sodium pentachlorophenate, was 1.6 (95% confidence limits 0.9-2.7, P = 0.11). The odds ratios were significantly elevated for sheep farming (odds ratio = 1.9, 95% confidence limits 1.0-3.6, P = 0.04) and exposure to beef cattle (odds ratio = 1.7, 95% confidence limits 1.0-2.9, P = 0.05). The odds ratio was also elevated for persons reporting a history of hay fever (odds ratio = 1.9, 95% confidence limits 1.0-3.5, P = 0.05). Overall, these findings suggest that the search for the causes of elevated mortality in farmers from multiple myeloma should be directed to potential causes other than pesticide exposure.

Aged↗
PubMed1986

Occupation, social class and male cancer mortality in New Zealand, 1974-78.

Occupational and social class differences in cancer mortality among New Zealand males aged 15-64 are examined for the period 1974-78. Age-standardized cancer mortality rates are presented for the Registrar General's social classes as well as for each of six occupational orders and 79 occupational groups. The rates for specific cancer sites are also presented for each social class and for those occupational groups with significantly elevated relative risks. The findings of the social class analyses were generally consistent with those of recent British studies with mortality from cancer of the liver, larynx, lung, buccal cavity and stomach being particularly high in the lower social classes and mortality from multiple myeloma, malignant melanoma and lymphatic leukaemia being particularly high in the upper social classes. The findings of the occupational group analyses were also generally in line with those of recent British studies and those associations which have been found in British studies and were also present in the New Zealand data are discussed. It is concluded that there are a number of associations which warrant further investigation including: large bowel cancer in woodworkers and printers; bladder cancer in hairdressers and beauticians; and malignant lymphoma in farmers.

Adult↗
PubMed1986

Leukemia among New Zealand agricultural workers. A cancer registry-based study.

Mortality studies have indicated that workers in agriculture and forestry may be at increased risk of leukemia. Findings are reported from a New Zealand Cancer Registry-based case-control study involving 546 male leukemia patients registered during 1979-1983 and aged 20 years or more at time of registration. Controls were also males chosen from the Cancer Registry with four controls per case, matched on age and year of registration. The case group contained an excess of the occupational category involving agriculture and forestry (odds ratio (OR) = 1.24, 95% confidence interval (CI) = 0.95-1.61) with the greatest relative risk being for livestock farmers (OR = 3.00, 95% CI = 1.23-7.32). There was also an excess of electrical workers (OR = 1.72, 95% CI = 0.92-3.20). The agricultural excess was greatest in patients aged 65 years or more at time of registration (OR = 1.29, 95% CI = 0.94-1.78), particularly in patients with acute myeloid leukemia (OR = 1.55, 95% CI = 0.90-2.67) or acute monocytic leukemia OR = 10.38, 95% CI = 1.99-54.29), although the latter excess only involved five cases. Acute myeloid leukemia was also elevated in meat workers (OR = 2.51, 95% CI = 1.19-5.30).

Adult↗
PubMed1986

Non-Hodgkin's lymphoma and exposure to phenoxyherbicides, chlorophenols, fencing work, and meat works employment: a case-control study.

A previous case-control study which used the occupational information available on the New Zealand Cancer Registry found that agricultural workers were at increased risk of developing non-Hodgkin's lymphoma. The findings are now presented for the second phase of the study which entailed interviewing 83 cases of non-Hodgkin's lymphoma registered under code 202 of the International Classification of Diseases together with 168 controls with other types of cancer and 228 general population controls. The findings for the two control groups were similar, and there were no significant differences between cases and controls regarding potential exposure to phenoxy-herbicides (odds ratio = 1.4, 90% confidence limits 0.7-2.5, p = 0.26) or chlorophenols (odds ratio = 1.3, 90% confidence limits 0.6-2.7, p = 0.39). The odds ratio for fencing work, necessitating exposure to several potential risk factors including arsenic and sodium pentachlorophenate was 2.0 (90% confidence limits 1.3-3.0, p = 0.01). The odds ratio for employment in a meat works, necessitating potential exposure to 2, 4, 6-trichlorophenol and zoonotic viruses, was 1.8 (90% confidence limits 1.1-3.1, p = 0.04). There was a significant statistical interaction between the risks associated with these two activities, the odds ratio for involvement in both activities compared with involvement in neither being 5.7 (90% confidence limits 2.3-14.3, p = 0.03).

2,4,5-Trichlorophenoxyacetic Acid↗