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Biomedical subjects

B D White

Publications and source records attributed to B D White.

At least 19 recordsLinked to original sources
PubMed1996

Interaction of type I and type II corticosteroid receptor stimulation on carcass energy and carcass water.

The effects of chronic type I and type II corticosteroid receptor stimulation were examined in adrenalectomized Sprague-Dawley rats to quantify the relative contribution of body energy and body water changes to changes in body weight. Adrenalectomy caused a decrease in both body energy and water. Aldosterone (type I agonist) treatment increased body weight gain and returned energy accretion to the level of sham-operated animals. However, most of the change in body weight (72%) was attributable to a change in body water. The aldosterone-induced increase in body weight gain and carcass water were attenuated by RU-28362 (type II receptor agonist) infusion, suggesting that type II receptor stimulation can antagonize the effect of type I receptor stimulation. Changes in carcass water were paralleled by changes in soluble carcass sodium. Despite alterations in soluble body sodium, no measurable differences in cumulative sodium retention were found. These findings confirm previous studies suggesting an effect of type I receptor stimulation on energy accretion. However, they also caution that changes in body weight cannot be equated with changes in body energy.

Adrenalectomy↗
PubMed1996

Transient immunosuppression permits successful repetitive intravenous administration of an adenovirus vector.

The in vivo administration of adenovirus vectors frequently elicits a neutralizing antibody response which eliminates or substantially reduces the efficacy of subsequent treatments. Methods to overcome this significant barrier to repeat delivery will be required for the application of adenovirus-based gene therapy in the treatment of chronic disease. We have evaluated the relationship between the initial vector dose and the effectiveness of a second vector administration. C57BL/6 mice injected intravenously with up to 10(7) p.f.u. of a lacZ adenovirus vector, Av1lacZ4, expressed significant levels of human factor IX when injected with 2 x 10(8) p.f.u. of the factor IX vector, Av1H9F, 5 weeks later. An initial dose of 10(8) p.f.u. of Av1lacZ4 completely prevented expression of factor IX following the second administration due to the generation of neutralizing antibody. However, transient immunosuppression with deoxyspergualin (DSG) or cyclophosphamide at the time of initial exposure to 10(8) p.f.u. of Av1lacZ4 prevented the formation of anti-adenovirus neutralizing antibody and permitted an effective second administration of a factor IX vector. Furthermore, transient immunosuppression with cyclophosphamide concomitant with delivery of the factor IX vector enabled an effective administration of a third vector encoding human factor VIII. This approach, together with strategies to prolong the persistence of adenoviral vector expression, should permit long-term therapy with adenovirus-based vectors.

Adenoviruses, Human↗
PubMed1995

ICV administration of anti-NPY antisense oligonucleotide: effects on feeding behavior, body weight, peptide content and peptide release.

Neuropeptide-Y (NPY) is a potent stimulator of feeding, and chronic administration of the peptide has been shown to increase body weight. This study determined the chronic effects of repeated daily injections of an antisense phosphorothioate oligonucleotide complementary to the rat mRNA for NPY (aNPY) on food intake, feeding behavior and body weight change in rats. Five micrograms of the aNPY oligonucleotide in ten microliters of vehicle or a missense control oligonucleotide were administered intracerebroventricularly (ICV) for seven consecutive days. Cumulative food intake, meal size and meal duration were significantly lowered in aNPY-treated animals. Body weight change of aNPY-injected animals was significantly lower than controls, and the effect was reversed after treatments ceased. A two-bottle taste aversion paradigm was employed to determine the behavioral specificity of the anorectic effect, and the phosphorothioate oligonucleotide was found not to be aversive at the dosage used. Following an additional five day injection period, animals were killed and paraventricular nuclei (PVN) were dissected. In vitro release and tissue content of NPY from this brain area were evaluated by heterologous radioimmunoassay. Content of NPY was unchanged in this brain area. Paradoxically, in vitro release of NPY was increased in aNPY-treated animals.

Animals↗
PubMed1995

Rats treated with somatotropin select diets higher in protein.

It was previously shown that somatotropin (STH) increases growth rate, improves food efficiency and stimulates protein accretion. In rats, STH also increases food intake. This study examined the effect of exogenous STH on rats' selection of diets varying in protein content. It was hypothesized that the increase in food intake in response to STH is driven by an increased protein requirement. Rats were allowed to select between two diets varying in casein (5 and 30%) or given a diet of a single casein level (20%). In each diet group, rats were treated with 0 or 4 mg of porcine STH/d. Rats treated with STH showed greater food intake (20%) and protein accretion (125%), regardless of diet. However, the greater food intake in rats allowed to select was due to greater consumption of the high protein diet. Diet selecting, STH-treated rats consumed 75% more of the 30% casein diet than did the saline-treated controls, while consuming a similar amount of 5% casein diet. Total protein intake (g/d) was 22 and 53% greater in rats injected with STH consuming the 20% casein diet and selection diets, respectively. The results indicate that rats injected with somatotropin select a diet greater in protein when compared with those not receiving somatotropin. It is suggested that the STH-induced increase in protein accretion results in a greater demand for essential amino acids. The mechanism whereby animals are able to monitor this greater need is not clear.

Animals↗
PubMed1995

Glucocorticoid receptor binding in porcine preadipocytes during development.

Previous studies have shown that the responsiveness of porcine preadipocytes to glucocorticoids increases progressively with fetal age. In the current study, the development of fetal glucocorticoid receptors in porcine preadipocytes was examined in primary cultures derived from 50-, 75-, and 105-d fetal and 7-d postnatal porcine adipose tissue. Three dams were used for each fetal age group and three young pigs were used for the postnatal studies. Using [3H]dexamethasone as the radioligand, cytosolic glucocorticoid receptors were measured in preadipocytes. There was an age-related increase in the number of glucocorticoid receptors during fetal development. The number of glucocorticoid receptors was very low in 50-d fetal porcine preadipocytes (1.350 +/- .178 fmol/mg of protein) and increased progressively to a peak at 105 d (8.990 +/- .741 fmol/mg of protein). This represents an approximate sixfold increase in receptor number between these two ages (P < .05). After birth, the glucocorticoid receptor number significantly decreased compared with that of 105-d fetuses (2.766 +/- .218 fmol/mg of protein, P < .05). Furthermore, the dissociation constant (Kd) of the glucocorticoid receptor in 105-d fetal preadipocytes was numerically smaller than the Kd of receptors derived from other age groups, although only significantly lower than that of the 75-d group (P < .05). Insulin markedly increased the number and binding affinity of glucocorticoid receptors in preadipocytes, indicating its potential involvement in regulation of glucocorticoid receptors. The effect of glucocorticoids on differentiation in preadipocytes is, at least in part, mediated by the number of glucocorticoid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗
PubMed1995

Current ethical and legal issues in gastrointestinal endoscopy.

The ethical and legal aspects of gastroenterology practice have changed over the past 20 years just as remarkably as the technological features of care. Answers to questions like "May competent adult patients refuse medical treatment?" and "Is the medically-mediated delivery of nutrition and hydration a 'medical treatment'?" must be considered in light of the Cruzan case and new arguments about the benefits and burdens of feeding tubes.

Endoscopy, Gastrointestinal↗
PubMed1994

Immunological and virological changes associated with decline in CD4/CD8 ratios in lymphoid organs of SIV-infected macaques.

The decline in CD4/CD8 ratios in lymph nodes (LNs) of SIV macaques and HIV-infected individuals occurs later than that in blood. In a previous study, long-term SIV-infected macaques were delineated into two groups: (1) those whose LNs had normal CD4/CD8 ratios and (2) those whose LNs had low CD4/CD8 ratios. In the present investigation, LNs, spleens, and blood from these groups have been further analyzed to ascertain the cellular and virological events, particularly those involving CD8+ cells, that occur concomitantly with LN CD4% decline. An increase in the percent of CD69-, IL-2R(p75)-, CD45RA1o CD8+ cells was the most constant event observed in lymphoid tissue from mid- to late-stage SIV-infected monkeys. Such cells were sometimes observed in LNs prior to any other immunological or morphological changes. However, decline in LN CD4/CD8 ratios and the associated degeneration of follicular dendritic cells (FDCs) in the germinal centers (GCs) of these nodes were observed only when both CD8+ cell infiltration of GCs and accumulation of viral antigens within the FDC network could be demonstrated. These dramatic changes were also associated with significantly reduced responsiveness to mitogens throughout the lymphoid compartment. In terms of viral burden, immunological and structural collapse of LNs was not always associated with increased viral DNA levels. Despite the CD4+ cell decline in blood during HIV and SIV infections, the immunological and architectural collapse of the lymphoid compartment, which comprises the bulk of the lymphocytes in the body, appears to be a critical event leading to the onset of AIDS. The present findings suggest that increased CD8+ cell activity as well as decrease in CD4+ cell function both contribute to this process.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Vagotomy and mercaptoacetate influence the effect of dietary fat on macronutrient selection by rats.

We have previously shown that rats fed saturated fat prefer a high protein, low carbohydrate diet, whereas animals fed unsaturated fat prefer a low protein, high carbohydrate diet. The purpose of the present study was to determine whether this "saturated fat effect" requires 1) the oxidation of the dietary fat and 2) an intact hepatic vagus nerve. Male Sprague-Dawley rats were vagotomized (hepatic branch) or sham-operated and injected with either mercaptoacetate (fatty acid oxidation inhibitor) or saline. Next, half of each group was given saturated fat (beef tallow) or unsaturated fat (corn oil) by gastric tube. All animals were given a choice between two mixed diets that differed in protein and carbohydrate. Sham-operated rats fed saturated fat ate more of the protein diet than did rats fed unsaturated fat. Vagotomy attenuated the intake of the protein diet in animals fed saturated fat. Mercaptoacetate or vagotomy had no effect on diet selection in rats fed unsaturated fat. These data indicate that the effect of saturated fat on diet selection requires an intact hepatic vagus and may be modulated by fatty acid oxidation. Furthermore, the mechanism for altering diet selection can be induced after a single meal.

3-Hydroxybutyric Acid↗
PubMed1994

Low protein diets increase neuropeptide Y gene expression in the basomedial hypothalamus of rats.

Food deprivation elevates both neuropeptide Y (NPY) gene expression in the basomedial hypothalamus and NPY levels in the paraventricular nucleus (PVN). To gain a better understanding of the dietary control of NPY, we systematically examined the effects of macronutrient restriction on the gene expression of NPY in the basomedial hypothalamus and NPY content in the PVN. Rats were fed one of eight different diets for 12 d. The control group was fed a modified AIN-76 diet. One group was fed the modified AIN-76 diet but was restricted in energy by 50%. Six isocaloric (to the control diet) test diets were prepared, each with an individual macronutrient reduced by 50%. Neuropeptide Y gene expression was elevated in protein-restricted animals as well as in energy-restricted animals. Carbohydrate or fat restriction seemed to have no effect on NPY gene expression. Though the NPY content in the PVN was not different between any groups, two findings were consistent with greater NPY release in protein-restricted animals. Animals fed a low protein diet were hyperphagic and had a greater amount of body fat. This study suggests that low levels of dietary protein may have a role in the regulation of NPY gene expression.

Animals↗
PubMed1994

Anterior spinal hernia: an increasingly recognised cause of thoracic cord dysfunction.

Two cases of anterior spinal hernia are presented. The medical literature is reviewed, the syndrome characterised, and its cause and treatment discussed. The patient is typically middle aged with a history of stepwise slowly progressive mid-thoracic anterior hemicord syndrome manifesting as hemianalgesia below the affected segment, followed by contralateral lower limb spasticity that develops into an asymmetric paraparesis with sparing of dorsal column sensation. Radiological investigation demonstrates an enlarged dorsal arachnoid space in association with an apparently focally narrowed thoracic cord, kinked towards the anterior dura. At operation the cord is found to be prolapsed into an anterolateral dural diverticulum. The most likely cause of this syndrome is anterior spinal artery segmental branch ischaemia, in a cord chronically incarcerated in a congenital anterior meningocele. This readily treatable condition should be considered in all cases of thoracic cord dysfunction and surgical repair effected early to prevent stepwise progression to paraplegia.

Adult↗
PubMed1994

Type II corticosteroid receptor stimulation increases NPY gene expression in basomedial hypothalamus of rats.

Evidence has suggested that glucocorticoids may increase neuropeptide Y (NPY) activity and gene expression. In the present study, we sought to determine the corticosteroid receptor subtype through which glucocorticoids increase NPY gene expression in the basomedial hypothalamus. This was accomplished by continuous administration of selective type I and II corticosteroid agonists in adrenalectomized Sprague-Dawley rats. Dot-blot analysis was performed, and the amount of NPY mRNA was determined. Additionally, serum insulin and glucose concentrations were determined. Type II receptor stimulation increased NPY mRNA levels in the basomedial hypothalamus above that of sham animals. This implies that type II receptor stimulation by high physiological concentrations of serum corticosterone may also increase NPY gene expression in the basomedial hypothalamus. The type II receptor agonist-induced increase in NPY gene expression did not appear to be mediated by a decrease in serum insulin concentrations. The present results may have relevance to the increased gene expression of NPY observed in the basomedial hypothalamus of obese Zucker rats and in food-deprived animals.

Adrenalectomy↗
PubMed1993

Affinity of hepatic glucocorticoid receptors is influenced by energy/feeding status.

Genetically obese animals have been shown to have a reduced number and affinity of glucocorticoid receptors. The relationship between the alterations in receptor binding and the regulation of energy balance is not known. We sought to determine the role of body energy/feeding status on the binding characteristics of glucocorticoid receptors. To accomplish this, we examined the effect of long-term food restriction on the number and affinity of hepatic glucocorticoid receptors from Sprague-Dawley rats. After 3 weeks of food restriction (40% of ad lib), animals were bilaterally adrenalectomized. Livers were removed, a crude cytosolic glucocorticoid receptor fraction was isolated, and radioreceptor assays were performed. Glucocorticoid receptors from food-restricted rats showed a significant reduction in the dissociation constant (Kd) as compared to receptors derived from free-feeding controls. No difference in receptor number was observed. These results suggest that energy or feeding status of the animal may influence the affinity of hepatic glucocorticoid receptors, while receptor number may be independent of this status.

Adrenalectomy↗
PubMed1993

An account of the usefulness of a pilot clinical ethics program at a community hospital.

This article describes the development and implementation of a six-month pilot clinical ethics program at Saint Thomas Hospital (Nashville, Tenn). To assess the impact of this program, baseline data were gathered from a self-selected sample of critical and special care unit nurses and physicians about the "most troublesome" ethical dilemmas in their practices. Nurses and physicians reported facing similar dilemmas in practice. Nurses believed that chaplains and peers were most "beneficial" in resolving their "most troublesome" cases; physicians did not deem one particular individual or service to be of any greater benefit than any other in dilemma resolution. Nurses and physicians indicated that in many cases patients and families did not appear involved in the process. In a posttest survey following the pilot program, nurses rated the beneficial role of chaplains somewhat lower and agreed that the clinical ethics service was beneficial. As with the pretest sample, the posttest nurses evaluated the role of the attending physician as "detrimental" to resolving their ethical conflicts. In the posttest, physicians ranked the role of the clinical ethicist as comparable to that of chaplains and social workers.

Attitude of Health Personnel↗
PubMed1993

Decline in the CD4+ lymphocyte population in the blood of SIV-infected macaques is not reflected in lymph nodes.

Although loss of CD4+ lymphocytes in peripheral blood is a standard criterion for evaluating the course of HIV disease, little is known about changes within lymphoid organs, which contain the bulk (> 50%) of the body's lymphocytes. Because such studies are feasible only by using non-human primates, we have examined lymph nodes (LNs), spleen, and blood from monkeys infected with two isolates of simian immunodeficiency virus (SIV). During both the acute and chronic phases of these infections, characteristic reductions in the blood CD4+ cell levels are not reflected in LN, where the CD4+ pool remains within normal levels. However, when circulating CD4/CD8 ratios have consistently fallen to approximately 0.5, striking decreases in the percentage of CD4 cells (CD4%) and CD4/CD8 ratios in LN occur concomitantly with dramatic increases in viral antigen expression on follicular dendritic cells within LN germinal centers (GCs). The data suggest that loss from the total T cell pool in minimal until the final stages of SIV and HIV disease and that the immunological deterioration of LN is the event that precipitates the increased susceptibility to infections and progression to AIDS.

Acute Disease↗
PubMed1993

Activity of the hypothalamic-pituitary-adrenal axis is elevated in rats with activity-based anorexia.

Activity-based anorexia is characterized by suppressed food intake and excessive physical activity. These behaviors are typical of persons with anorexia nervosa. Activity of the hypothalamic-pituitary-adrenal axis is known to be elevated in anorexia nervosa. We investigated the status of this axis in activity-based anorexia. Meal fed-control (MFC) and meal fed-wheel running (MFWR) rats were given access to food for 90 min daily; MFWR animals were allowed access to an activity wheel the remainder of the day. The experiment terminated when MFWR animals reached 75% of preexperimental body weight (males 3.9 +/- 0.3 d; females 4.2 +/- 0.2 d). Male and female MFWR rats consumed less food than MFC animals, while maintaining a high level of wheel running. Corticosterone concentrations were significantly elevated in MFWR animals. Corticotropin-releasing hormone mRNA concentrations in the paraventricular nucleus were not different. Relative adrenal gland weights were greater and thymus gland weights were lower in MFWR animals. Changes in food intake could not be explained by differences in insulin, glucose, beta-hydroxybutyrate or norepinephrine concentrations. Our results suggest increased activity of the hypothalamic-pituitary-adrenal axis in activity-based anorexia.

Animals↗
PubMed1993

Continuing problems with patient self-determination.

Cruzan v. Director, Missouri Department of Health, the first "right to do die" case to be decided by the United States Supreme Court, constitutionalizes the principle of patient self-determination. The case encourages competent patients to reflect thoughtfully about the possibility that one day they may be incapacitated just as Nancy Beth Cruzan was and to prepare for that possibility by completing an advance directive. Furthermore, the recently enacted Patient Self-Determination Act requires hospitals to ask adult patients upon admission whether they have advance directives. However, a number of practical concerns arise for physicians about operationalizing these patient self-determination principles within their states and their scopes of practice. Will physicians be prosecuted for "assisting suicides" if they withdraw feeding tubes or forgo other life-sustaining treatments? Will physicians be liable in medical malpractice for "undertreatment" or "overtreatment" in such cases? Will physicians be asked to violate their own moral codes in treating patients? Will others intrude into the traditional physician-patient relationship and decision-making process? Will physicians be caught in the middle of troublesome family, staff, and institutional disputes? How will physicians learn of patients' advance directives? Will physicians be asked to continue care in futile cases? Will Cruzan's self-determination doctrine be improperly extended? Successful implementation of patient self-determination principles will require consideration and discussion of these practical physician concerns.

Attitude of Health Personnel↗