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J Downing

Publications and source records attributed to J Downing.

At least 19 recordsLinked to original sources
PubMed1998

Absence of DNA adduct formation by phenobarbital, polychlorinated biphenyls, and chlordane in mouse liver using the 32P-postlabeling assay.

Phenobarbital (PB), polychlorinated biphenyls (PCBs), and chlordane (CLD) increase liver tumor incidences in rodents, and all are tumor promoters. Most indirect tests for DNA reactivity, including mutagenicity and chromosomal damage, have been negative with these agents. Consequently, the modes of action for tumorigenesis by these compounds are not believed to involve direct DNA reactivity; however, only limited information from direct tests is available for the lack of DNA adduct formation. PB, PCBs, and CLD were tested for DNA adduct formation in the liver of male and female B6C3F1 mice after either single or 2-week dietary exposures. Single gavage dose levels were as follows: PB, 200 mg/kg; PCBs, 50 mg/kg; and CLD, 50 mg/kg. Dietary dose levels were as follows: PB, 1000 ppm; PCBs, 200 ppm and CLD, 200 ppm. Animals were killed 24 h following the end of test-substance administration. DNA was extracted from the liver, and DNA adduct concentrations were enriched using either 1-butanol extraction of adducted nucleotides or nuclease P1 digestion of unadducted nucleotides. Using this protocol, none of the three test compounds produced DNA adducts detected by 32P-postlabeling. Similar negative results were obtained for DNA from the livers of both male and female mice receiving either single or 2-week exposures. The two positive controls, benzidine for the 1-butanol extraction procedure and 2-acetylaminofluorene for the nuclease P1 procedure, showed the expected patterns of DNA adducts. These results support the conclusion that the carcinogenicity of PB, PCBs, and CLD in experimental animals is not the result of direct DNA reactivity, but involves epigenetic mechanisms.

2-Acetylaminofluorene↗
PubMed1998

Stimulation of ovarian oxytocin secretion and uterine prostaglandin release by exogenous progesterone early in the cycle of the ovarian auto-transplanted ewe.

The present study was undertaken to determine whether the administration of progesterone, early in the oestrous cycle, had an influence on ovarian oxytocin secretion and on peripheral concentrations of the prostaglandin F2 alpha metabolite 13,14-dihydro-15-keto PGF2 alpha (PGFM) in the ovarian auto-transplanted ewe. Twelve ewes with ovarian auto-transplants (n = 6 per group) were randomly assigned to receive an i.m. injection of progesterone (12.5 mg) or vehicle, twice a day, on days 1, 2 and 3 of the oestrous cycle. Beginning on day 7, blood samples were collected at intervals of 1 h from the ovarian and contralateral jugular veins for up to 70 h. Ovarian oxytocin secretion rate and jugular concentrations of PGFM and progesterone were determined by radioimmunoassay. The number of ewes that showed pulses of both ovarian oxytocin and PGFM was significantly (P < 0.05) greater in progesterone-treated ewes than in control ewes. In progesterone-treated ewes, the average number of ovarian oxytocin pulses per ewe was 9.66 +/- 5.5 (mean +/- SD) and the interval between pulses was 7.18 +/- 5.8 h. The mean amplitude and amount of oxytocin released, as calculated by the area under the curve of ovarian oxytocin pulses, were 6.27 +/- 1.98 ng min-1 and (10.05 +/- 8.91 ng min-1)tau, respectively (where tau is the number of hours between the last time point before and the first time point after a significant increase in hormone concentration was detected by the Pulsar program). The mean amplitude and area under the curve of PGFM pulses were 317.22 +/- 5.65 pg ml-1 and (383.36 +/- 1.77 pg ml-1)tau, respectively. The average number of pulses of plasma PGFM observed per ewe was 5.8 +/- 1.9 and interpulse interval for plasma PGFM pulses was 10.32 +/- 8.7 h between day 7 and day 9 after oestrus. These data indicate that administration of progesterone during the first 3 days of the oestrous cycle results in the premature release of ovarian oxytocin and uterine prostaglandin F2 alpha.

Animals↗
PubMed1997

Comparative studies of chromaffin cell proliferation in the adrenal medulla of rats and mice.

Spontaneous and drug-induced pheochromocytomas are common in rats and rare in mice. The antihypertensive drug reserpine has been shown to both induce pheochromocytomas and stimulate chromaffin cell proliferation in rats, leading to the hypothesis that reserpine causes pheochromocytomas indirectly by providing a proliferative setting in which DNA damage may occur. The present investigation was undertaken to obtain baseline information on the relationship across species between chromaffin cell proliferation and pheochromocytomas. Basal chromaffin cell proliferation was compared in age-matched young adult mice and rats. In addition, mice were studied for adrenal medullary responses to reserpine, and mouse chromaffin cells in vitro were studied for responses to agents that are mitogenic for cultured rat chromaffin cells. Concurrently maintained F-344 rats and several strains of mice showed no significant difference in basal BrdU incorporation over a 1-week period. Mice also showed an adrenal medullary proliferative response to reserpine that was comparable to the response previously reported for rats. However, there was a marked disparity between rat and mouse chromaffin cells in vitro, and cultured mouse chromaffin cells did not respond to any mitogens. The in vivo data indicate that interspecies differences in basal- or reserpine-stimulated chromaffin cell proliferation sufficient to account for different frequencies of pheochromocytomas are not detectable at a single time point in young adult animals. However, the possibility that such differences might emerge with aging has not been ruled out. These data further suggest either that stimulation of chromaffin cell proliferation might be necessary but not sufficient for development of pheochromocytomas or that stimulated proliferation in mice might not be sustained. The inability of cultured mouse chromaffin cells to respond to mitogens raises the speculation of whether mechanisms that prevent proliferation of normal chromaffin cells in vitro might also help to protect mice from developing pheochromocytomas.

Adrenal Gland Neoplasms↗
PubMed1997

Effect of oestradiol on ovarian oxytocin secretion rate and luteolysis in the ewe after ovarian auto-transplantation.

The release of ovarian oxytocin and uterine prostaglandin (PG)F2alpha in response to an oestradiol stimulus was investigated. On Day 15 post-oestrus, ten ewes with ovarian auto-transplants (n=5 per group) received an intra-muscular injection of either oestradiol benzoate (50 microg) or vehicle. Blood samples were collected from the ovarian and jugular veins at 30 and 0 min before, and at 15-min intervals up to 540 min after, injection. The secretion rate of ovarian progesterone remained elevated in four of five treated ewes and in all control ewes, indicating the presence of a functional corpus luteum. Peripheral oestradiol concentrations were significantly (P < 0.001) higher in treated than in control ewes. The number of ewes that released pulses of ovarian oxytocin > or =240 min following oestradiol benzoate injection was significantly (P < 0 05) greater than that in control ewes. Mean amplitude and area under both ovarian-vein oxytocin and jugular-vein 15 keto-13,14 dihydro prostaglandin F2alpha (PGFM) pulses were significantly increased in the treated ewes. These findings demonstrate that the administration of exogenous oestrogen provides a positive stimulus for the release of ovarian oxytocin and uterine PGF2alpha in the ovarian auto-transplanted ewe.

Animals↗
PubMed1997

Nonimmune phagocytosis of liposomes by rat alveolar macrophages is enhanced by vitronectin and is vitronectin-receptor mediated.

Pulmonary alveolar macrophages (AMs) engulf diverse materials. The mechanisms allowing AMs to recognize, bind, and phagocytose these materials are poorly understood. To test the hypothesis that the adhesive glycoprotein vitronectin (Vn) acts as a nonimmune opsonin, we studied AM-Vn binding and AM phagocytosis of fluorescent liposomes under the following conditions: (1) pretreatment of AMs with Vn, followed by incubation of AMs with liposomes containing increased amounts of Vn; (2) inhibition of phagocytosis by gly-arg-gly-asp-ser (RGD) and gly-pen-gly-arg-gly-asp-ser-pro-cys-ala (GPen); and (3) antibody blockade of the alpha(v)beta3 vitronectin receptor (VnR). Pretreatment of AMs with 0.1, 1, and 2 microM Vn progressively enhanced AM-Vn binding from 23,622 +/- 3,328 cpm to 40,847 +/- 6,530 cpm, 57,149 +/- 2,789 cpm, and 124,852 +/- 42,930 cpm, respectively (P < 0.05). AM pretreatment also increased phagocytosis of Vn-enriched liposomes, but not empty liposomes (20.7 +/- 0.4 liposomes/cell versus 11.5 +/- 0.5 liposomes/cell, P < 0.05). Moreover, increased concentrations of Vn in liposomes progressively increased phagocytic activity (3.7 +/- 0.3, 6.5 +/- 0.2, 11.5 +/- 0.5, and 16.5 +/- 0.6 liposomes/cell with 0.01, 0.1, and 1 microM Vn, respectively, P < 0.05). RGD inhibited Vn-enhanced phagocytosis (8.1 +/- 0.4 liposomes/cell to 3.4 +/- 0.2, 2.4 +/- 0.4, and 2.2 +/- 0.2 liposomes/cell with 0.02, 0.2, and 2 mM RGD, respectively, P < 0.05), as did GPen (4.7 +/- 0.8 liposomes/cell versus control = 10.9 +/- 1.5 liposomes/cell, P < 0.05) and anti-VnR antibody (3.3 +/- 0.4 liposomes/cell versus control = 8.9 +/- 1.7 liposomes/cell, P < 0.05). We conclude that AMs employ Vn as a nonimmune opsonin to enhance the efficiency of phagocytosis.

Animals↗
PubMed1996

The relationship of cardiovascular and psychological impairments to the health status of patients enrolled in cardiac rehabilitation programs.

BACKGROUND AND PURPOSE: Understanding the causes of differences in disability among individuals is an important research focus for rehabilitation professionals. The purpose of this study was to examine the relationship between health status and the impairments commonly associated with cardiovascular pathophysiology. SUBJECTS: The subjects were patients (N=789) enrolled in 13 cardiac rehabilitation programs in Massachusetts. METHODS: Data were collected on psychological and physiological impairments, demographic characteristics, and health status. Multivariate analyses were used to determine which measures of impairment and patient characteristics were related to health status. RESULTS: Psychological impairment was related to all scales of the MOS 36-item Short-Form Health Survey (SF-36). Very few measures of physiological impairment and individual characteristics were related to SF-36 scores. The models accounted for 16% to 57% of the variability of the instrument's scales. CONCLUSION AND DISCUSSION: In patients entering cardiac rehabilitation, psychological distress is related to poor health in both the physical and psychological dimensions. Variability in health status is not well explained by traditional measures of impairment or demographic characteristics. Physical therapists working to address their patients' health needs must consider collecting data, setting goals, and devising interventions that address psychological impairment.

Adult↗
PubMed1996

Pharmacokinetics of caffeine in the oestrogen-implanted ovariectomized ewe.

The disposition kinetics of caffeine and its metabolites theophylline, theobromine and paraxanthine in the oestrogen-implanted ovariectomized ewe following single intravenous doses of 5, 10, 15 or 20 mg/kg caffeine are described in this paper. Blood was collected at 5, 30 and 60 min, and at 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192 and 240 h after dosing. Caffeine concentrations peaked within 30 min of administration but remained in a plateau phase for 3-6 h before declining over a prolonged period of time. For caffeine the mean elimination half-life was calculated to be 47 h. Detectable caffeine concentrations remained for 10 days after administration in all groups. The area under the plasma concentration-time curve (AUC) values were used to compare tissue caffeine exposure and were, approximately, linearly related to dose. Metabolite concentrations were maintained at peak and near peak concentrations for 6-24 h after caffeine administration followed by prolonged elimination. Because of significant species differences in drug elimination rates, it is concluded that the ewe is not a suitable animal model in the clinical context. However, the sheep may well provide insights into caffeine's mechanism of action of relevance to veterinary drug research.

Animals↗
PubMed1994

Sexual functioning post-myocardial infarction: effects of beta-blockers, psychological status and safety information.

Impaired sexual functioning limits the quality of life of 34-75% of post-myocardial infarction (MI) patients. This study examined the effects of three factors: (a) beta-blocker intake, (b) psychological distress, and (c) information about safety of sexual activity, on post-MI decreased sexual functioning. Sixty-three male post-MI, post-cardiac rehabilitation patients and their spouses participated in the study. Analyses of partial variance were conducted to test for the effect of each factor on sexual functioning. Controlling for age, results revealed that patients' psychological distress explained uniquely 24% of the variance on decreased post-MI sexual activity (p < 0.002). Beta-blocker intake and message received with regard to sexual activity safety were not significant predictors of observed changes. Interdisciplinary assessments and interventions are recommended.

Adrenergic beta-Antagonists↗
PubMed1994

The development of a massage service for cancer patients.

Despite major technological advances in the treatment of cancer, many patients are dissatisfied with conventional biomedical interventions. This is largely because they fail to resolve long term intractable problems such as chronic pain or stress. More emphasis is now being placed on quality of life. This shift in attitude has opened the door for complementary therapies as adjuvants to traditional models of cancer care. Changes within the NHS have facilitated this transition, by the creation of the 'internal market' and the development of central funding to individual clinical directorates. To exploit these opportunities, complementary, therapists must develop new skills and be prepared to adopt NHS standards of assessment to evaluate the efficacy of their work. Standards are a component of 'Quality assurance'. They are observable, achievable and measurable, and contribute towards an acceptable evaluation process. Standards are used by health care purchasers to assess which therapies should be made available to patients within the NHS. This paper describes the development of a massage service that has been integrated into the Hammersmith Oncology Department. The massage standard is seen to be fundamental and essential to the continued development and evaluation of the project.

Ancillary Services, Hospital↗
PubMed1994

Health status of individuals entering a cardiac rehabilitation program as measured by the medical outcomes study 36-item short-form survey (SF-36).

BACKGROUND AND PURPOSE: The goal of health care for individuals with chronic disease is the improvement of function and well-being. Although the individual's perception of his or her quality of life may be the best indicator of achievement of this goal, measurement of self-perceived quality of life, or health status, is not a routine component of evaluation. The purposes of this article are to describe the health status of individuals upon entry into a cardiac rehabilitation program and to demonstrate the use of a comprehensive, generic health status measure in this group. SUBJECTS: The subjects of this study were 789 men and women enrolled in one of 13 cardiac rehabilitation programs in the state of Massachusetts. METHODS: As part of a large database, subjects completed a 36-item generic questionnaire, Short Form 36 (SF-36), that examines eight health concepts. Scores range from 0% to 100%; a higher score is consistent with better health status. Results. Mean uncontrolled scores ranged from 26.6 to 70.8. Mean scores adjusted for sex, age, and education ranged from 27.1 to 70.9. In light of previously published data using a similar 20-item scale, our results show that cardiac disease is associated with reductions in health-related quality of life. CONCLUSION AND DISCUSSION: Health status measurement provides information that can supplement the usual measures of impairment in patients with cardiovascular disease. The findings of this study contribute to the understanding of health status of individuals who enroll in cardiac rehabilitation programs. The health status instrument used in this study has potential as a useful, practical measurement tool for use in the clinical setting.

Activities of Daily Living↗
PubMed1994

Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large cell lymphoma-associated t(2;5) translocation in Hodgkin's disease.

Hodgkin's disease (HD) and Ki-1 positive anaplastic large cell lymphoma (Ki-1 ALCL) appear pathologically and immunohistochemically related, and a common histogenesis has been postulated in at least some cases. The breakpoints of the t(2;5) (p23;q35) [corrected] translocation, which is reported in about 40% of Ki-1 ALCL, have recently been cloned. They involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase polymerase chain reaction (RT-PCR) using NPM and ALK primers consistently detects a fusion product in Ki-1 ALCL cases with the translocation. To determine if this tumor-specific genetic alteration also occurs in HD, we performed NPM-ALK RT-PCR on RNA samples extracted from 40 lymph node biopsies of HD (25 nodular sclerosis, 11 mixed cellularity, 2 lymphocyte depleted, 2 lymphocyte predominant). Using control samples, the sensitivity of the NPM-ALK RT-PCR assay was shown to be at least 1:10(4). Amplifiable template was confirmed in all samples by RT-PCR using beta-actin primers. None of the 40 cases showed the expected 177-bp RT-PCR product indicative of the translocation. We conclude that the most common primary genetic alteration in Ki-1 ALCL, the t(2;5), is absent or very infrequent in typical cases of HD. These results further support the concept that HD and Ki-1 ALCL are pathogenetically distinct entities.

Base Sequence↗
PubMed1992

Effects of pinealectomy on wool growth and wool follicle density in merino sheep.

There is evidence to indicate that pinealectomy may enhance wool growth in the sheep. The aim of this study was to determine the effect of pinealectomy on wool growth and wool follicle density in Merino sheep. Castrated Merino rams (4 months old) were either pinealectomized (P), sham-pinealectomized (S) or not treated (C). Wool growth on mid-side patches was measured every 4 weeks and follicle density was monitored in skin biopsies collected before treatment and at regular intervals for 60 weeks. Venous blood samples were taken on each of these occasions for prolactin analysis. Melatonin concentrations were determined in venous blood collected pre- and posttreatment from samples taken over a 24-hr period during the winter solstice. Pre- and posttreatment plasma melatonin levels (mean +/- SEM) 65 +/- 17 and < 13 pg/ml for P, 86 +/- 21 and 69 +/- 20 pg/ml for S, and 94 +/- 41 and 122 +/- 37 pg/ml for C, respectively, indicated that the pineal glands had been successfully removed. Wool growth, total follicle density and liveweight (mean +/- SEM) did not differ between treatment groups. Measurements at week 60 were 3.9 +/- 0.3, 4.1 +/- 0.2, and 3.8 +/- 0.3 gm clean wool/100 cm2; 66 +/- 6, 69 +/- 7, and 64 +/- 3 follicles/mm2; and 50.4 +/- 1.3, 50.8 +/- 1.4, and 52.6 +/- 1.1 kg liveweight for groups P, S, and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

MKW, a novel hematopoietic antigen.

A novel hematopoietic antigen was identified using a murine monoclonal antibody raised against KG-1 cells. This antigen, termed MKW, was also detected on the surface of the monocytic cell line U937, but not on the K562, ML1, or HL-60 cell lines. On normal hematopoietic cells, the antigen is expressed on the surface of monocytic and myelocytic cells and on a subpopulation of B-cells. During normal hematopoiesis, the surface expression of MKW is greatest and occurs very early on monocytic cells. Alternatively, in myeloid cells, surface expression occurs later and cell maturation is correlated with increased surface expression. When U937 cells are induced to differentiate, surface expression is transiently up-regulated. Surface expression of MKW, however, does not appear to be an activation antigen since activation of purified T- or B-cells failed to increase MKW on the cell surface. Leukemic blasts from 22 of 80 children (27%) with acute myeloblastic leukemia and from 29 of 225 children (13%) with acute lymphoblastic leukemia expressed MKW on the cell surface. Although surface expression of MKW was absent on T-cell lines, peripheral T-cells, and most B-cells, the antigen was identified in the cytoplasm of some B-cells, T-cells, and cell lines. Immunoprecipitation studies showed that MKW is a 52-kDa protein whether expressed on the cell surface or in the cytoplasm, and it appears to be nonglycosylated. Furthermore, studies with phosphatidylinositol-phospholipase C suggested that MKW is not attached to a glycolipid anchor. The biochemical characterization of MKW and its pattern of expression are distinct from any of the previously identified CD groups or published antigens. Since this unique antigen has prognostic significance in leukemia and appears to be associated with cell differentiation, its exact role in hematopoiesis should be investigated.

Antibodies, Monoclonal↗
PubMed1992

Functional versus standardized assessment procedures: implications for educational programming.

Teacher perceptions of the educational value of two distinct assessment procedures for assessing an 8-year-old student with severe to profound multiple disabilities were compared. Direct service providers (N = 38) from a public school system, randomly distributed into three groups, were asked to use an 8-item Likert-type survey to rate one of three assessment packages: standardized, functional-ecological, and a combined package. Results for four of the eight items were statistically significant. The functional-ecological approach was perceived to be most beneficial for educational intervention. Implications for greater emphasis on a functional-ecological assessment procedure versus standardized procedures were discussed.

Activities of Daily Living↗
PubMed1991

White-black differences in cardiovascular malformations in infancy and socioeconomic factors. The Baltimore-Washington Infant Study Group.

Cardiovascular malformations were examined for white/black variation in the Baltimore-Washington Infant Study. In this population-based case-control study, cases (n = 2,087) were live births with cardiovascular malformations ascertained through pediatric cardiology centers and 53 hospitals in Maryland, the District of Columbia, and northern Virginia between 1981 and 1987. Controls (n = 2,721) were a random sample of infants from the live-birth cohort that gave rise to the cases. The proportion of infants that were white was similar for all cases as a group and controls (0.68 and 0.67, respectively). Subgroup analysis, however, revealed an excess of white infants among cases with Ebstein's anomaly (odds ratio (OR) = 3.7, 95% confidence interval (Cl) 1.1-12.5), aortic stenosis (OR = 3.6, 95% Cl 1.7-7.6), pulmonary atresia (OR = 2.5, 95% Cl 1.0-6.1), coarctation of the aorta (OR = 2.2, 95% Cl 1.4-3.5), and D-transposition of the great arteries (OR = 1.6, 95% Cl 1.1-2.5), and a deficit of white infants among cases with pulmonary stenosis (OR = 0.6, 95% Cl 0.4-0.8) and heterotaxia (OR = 0.4, 95% Cl 0.3-0.8). These associations remained when cases were stratified by infant's age or by method of diagnosis. Controlling for socioeconomic factors attenuated the white excess for Ebstein's anomaly (OR = 3.0, 95% Cl 0.9-10.5), disclosed a white excess among cases of L-transposition of the great arteries (OR = 2.8, 95% Cl 1.0-8.0), and revealed that the white excess for aortic stenosis was limited to low and middle socioeconomic strata. These results highlight racial variations in cardiovascular malformations, suggest that socioeconomic factors account for some of this variation, and identify malformation subgroups for which further evaluation of sociocultural, environmental, and familial factors is needed.

Black or African American↗
PubMed1991

Neurogenic signals regulate chromaffin cell proliferation and mediate the mitogenic effect of reserpine in the adult rat adrenal medulla.

The adrenal medulla is innervated by nerve fibers from several sources, which synapse on chromaffin cells and stimulate the secretion of catecholamines. The antihypertensive agent reserpine is known to reflexively increase this neurogenic stimulation by depleting catecholamine stores, and long-term administration of reserpine is associated with adrenal medullary hyperplasia and neoplasia. To determine the role of neurogenic signals in regulating normal and reserpine-stimulated proliferation of chromaffin cells, the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating nuclei was assessed in the adrenal medulla of adult rats. Unilateral adrenal denervation caused a 4-5 fold decrease in chromaffin cell labeling by 5-bromo-2'-deoxyuridine during a 2-week labeling period. Denervation also prevented stimulation of labeling in animals receiving reserpine in their diet. These findings suggest that neurogenic control of cell proliferation may play an important role in the pathogenesis of adrenal medullary hyperplasia and neoplasia, and in the normal development of the peripheral and central nervous systems.

Adrenal Medulla↗