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Biomedical subjects

B J Mullen

Publications and source records attributed to B J Mullen.

18 recordsLinked to original sources
PubMed1996

Physiological effects of CNTF-induced wasting.

The authors have shown previously that in addition to its survival effects on neurons and glia, ciliary neurotrophic factor (CNTF) induced potent cachectic effects and acute phase proteins when present in the peripheral circulation at concentrations of < or = 10 ng/ml. These effects did not depend upon the induction of other cytokine family members. Described here are the specific physiological effects which systemic administration of CNTF can induce in somatic tissue. Mice implanted with C6 glioma cells, genetically modified to secrete CNTF, exhibited rapid catabolism of adipose tissue and skeletal muscle, depressed steady-state levels of glucose and triglycerides, elevations in red blood cell content, gall bladder hypertrophy and thymic atrophy, with a disproportionate loss of CD4+/CD8+ T cells. This cachectic wasting resulted in death over a period of 7-10 days. Implantation of the parental C6 line, or C6 cells which express a non-secreted form of CNTF, did not result in overt effects over this time period. These findings have implications both for the biology of CNTF family members, and the therapeutic use of factors such as CNTF in vivo.

Adipose Tissue↗
PubMed1993

Hydrops-ectopic calcification-moth-eaten skeletal dysplasia (Greenberg dysplasia): prenatal diagnosis and further delineation of a rare genetic disorder.

An offspring of consanguineous parents of East-Indian origin was found prenatally to have hydrops fetalis, short limb dwarfism, polydactyly and chondro-osseous changes consistent with Greenberg hydrops-ectopic calcification-moth-eaten skeletal dysplasia (HEM) dysplasia. The radiological changes include platyspondyly with multiple extra ossification centers, extraneous calcification in the ribs, sternum, pelvis, and epiphysis, and moth-eaten long bones. The histopathological changes included chondrocytes with dilated rough endoplasmic reticulum and inclusion bodies with homogeneous material of intermediate electron density. These findings further delineate the spectrum of this rare autosomal recessive skeletal dysplasia.

Abnormalities, Multiple↗
PubMed1993

Acalculous cholecystitis associated with cytomegalovirus and sclerosing cholangitis in a patient with acquired immunodeficiency syndrome.

Intra- and extrahepatic bile-duct strictures, papillary stenosis and acalculous cholecystitis have all been described in ill patients with acquired immunodeficiency syndrome (AIDS). Acalculous cholecystitis associated with cytomegalovirus (CMV), Cryptosporidium or Campylobacter organisms has typically been described in critically ill or moribund patients. The authors report a case of acute acalculous CMV cholecystitis in a 28-year-old man who presented with abdominal pain. The patient was infected with the human immunodeficiency virus (HIV) but was ambulatory and had had no AIDS-defining illness. The patient did not have any well-recognized risk factors for acalculous cholecystitis, showing that this entity can occur in relatively healthy HIV-infected patients as well as in the terminal stages of AIDS. The diagnosis should be considered when such a patient presents with abdominal pain. Furthermore, this patient had sclerosing cholangitis of the intra- and extrahepatic bile ducts as well as papillary stenosis. The cause of the acalculous cholecystitis was presumed to be CMV, but the disease progressed despite therapy with foscarnet.

AIDS-Related Opportunistic Infections↗
PubMed1992

Effect of starvation or restriction on self-selection of macronutrients in rats.

Two models of food deprivation were used to study feeding behavior: starvation and dietary restriction. Rats starved for 3 days had decreased protein intake during the first 2 days of refeeding followed by increased carbohydrate consumption compared to controls. During refeeding, total intake was initially low compared to controls. In a second starvation study of similar design, brain tissues [raphe, ventromedial hypothalamus (VMH)] and sera were collected for analysis before refeeding and on day 2 of refeeding. Starved and starved-refed rats had increased serum beta-hydroxybutyrate versus controls. In rats restricted for 5 days (5 g/day), total food intake was increased immediately and was characterized primarily by carbohydrate intake. Serotonin levels in the raphe were decreased in restricted rats and 5-hydroxyindole acetic acid (5-HIAA) increased in restricted-refed rats. Restriction caused an increase in blood levels of beta-hydroxybutyrate and a decrease in insulin and glucose compared to controls. Fat selection remained low throughout all studies. The data suggest that starvation and food restriction elicit different patterns of macronutrient selection upon refeeding.

3-Hydroxybutyric Acid↗
PubMed1992

Novel approach to diet design for determining macronutrient preference.

Previous studies indicate that rats fed a saturated vs. unsaturated fat consume more of a high-protein/low-carbohydrate and less of a low-protein/high-carbohydrate diet. Present studies were conducted to determine whether saturated-fat-fed rats are preferring protein or avoiding carbohydrate. Three combinations of diets were prepared in which one macronutrient was held constant and two covaried: 1) high protein/low carbohydrate and low protein/high carbohydrate, 2) high fat/low carbohydrate and low fat/high carbohydrate, and 3) high fat/low protein and low fat/high protein. Male Sprague-Dawley rats (75-99 g) were fed either 34% tallow (n = 30) or corn oil (n = 30) diets for 4 days. These diets were removed and one third of each group was given one of the diet combinations. Rats previously fed tallow consumed more high-protein/low-carbohydrate and low-carbohydrate/high-fat diets and less high-carbohydrate/low-fat diet than controls previously fed corn oil. These data suggest that tallow-fed animals are avoiding carbohydrate rather than preferring protein.

Animals↗
PubMed1992

Somatostatin and growth hormone-releasing factor release from Zucker rat hypothalamic tissue.

Plasma somatotropin (ST) levels are depressed in the genetically obese Zucker rat compared to those of their littermates. It is believed that this defect is associated with one or both of the hypothalamic neuropeptides that control ST release: growth hormone releasing factor (GRF) and somatostatin (SS). The mechanism by which SS and GRF neuropeptides are regulated remains uncertain. The objective of this study was to examine the effect of 2 deoxy-glucose (2DG), isoproterenol (ISO), tryptophan (TRP), and 5HT on SS and GRF release in hypothalamic tissue from lean and obese Zucker rats. An in vitro perifusion system was established to examine the release of SS and GRF from perifused hypothalami taken from 8- and 12-week-old Zucker rats under basal conditions and in response to 2DG, ISO, TRP, 5HT, and KCl administration. Hypothalami were perifused with Dulbecco's modified eagle's medium continuously at 37 degrees C for 5 h at a flow rate of 100 ml/min. ISO and 2DG significantly (p < 0.05) increased SS levels from the obese rat, but no effect was observed from the lean littermate. GRF was not affected by 2DG or ISO in either genotypes. TRP and 5HT failed to affect SS or GRF release in lean or obese Zucker rats. It is proposed that the obese Zucker rat is more sensitive to glucose deprivation and to beta-adrenergic stimulation of SS release than the lean littermate.

Aging↗
PubMed1992

The effect of dietary fat on diet selection may involve central serotonin.

Rats consuming a diet of 34% tallow select more protein and less carbohydrate than rats fed either 5% corn oil or tallow or 34% corn oil (25). To examine potential mechanism(s) of this phenomenon, we fed rats diets containing either tallow or corn oil at levels of 5 or 34% for 2 days. Sera were analyzed, and rats fed 34% tallow had higher serum insulin compared with those fed 34% corn oil. In a second experiment, rats were fed either 34% corn oil or tallow for 2 days. Brain tissues were analyzed, and rats fed 34% tallow had elevated serotonin in the raphe area compared with those fed 34% corn oil. In a third experiment, rats were fed either 34% corn oil or tallow for 2 days and then given dl-fenfluramine before diet selection. Fenfluramine depressed food intake to a greater degree in rats fed 34% tallow compared with those fed corn oil. These findings suggest that the diet selection behavior observed in tallow-fed rats may be mediated by a central serotonin system.

Animals↗
PubMed1990

Macronutrient selection in rats: effect of fat type and level.

The effect of type and level of dietary fat on subsequent diet selection was examined in young Sprague-Dawley rats. Isoenergetic, isonitrogenous diets composed of corn oil or tallow (commercial grade), each at 5 or 34%, were fed to rats for 2 wk, and their preference for diets covarying in carbohydrate and protein was subsequently tested. When compared to either of the corn oil groups or the 5% tallow group, rats previously fed the high tallow diet selected more protein and less carbohydrate. Subsequent experiments testing the effects of 5, 20 or 34% tallow indicated that this preference for protein was induced by exposure to the tallow diets for only 18 h. In addition, the 34% tallow group selected more protein than did rats fed 5 or 20% tallow. Tests of diet selection with 5 or 34% corn oil, tallow or hydrogenated coconut oil indicated that rats fed 34% tallow ate significantly more protein than the 34% corn oil group. Furthermore, animals fed a 34% pure, additive-free tallow diet exhibited a preference for protein. These studies suggest that the type and level of dietary fat interact to influence dietary selection.

Animals↗
PubMed1990

Recombinant tumor necrosis factor-alpha chronically administered in rats: lack of cachectic effect.

Recombinant human tumor necrosis factor-alpha (rHuTNF) was injected into rats to test its reported cachectic effects. Rats were subcutaneously injected daily at 1730 hr with either saline or rHuTNF (0.25 mg/kg body wt) for either 5 or 14 days. Daily food intakes were significantly depressed only for the first day and first two days of rHuTNF injection in animals treated for 5 days and 14 days, respectively. There were no significant differences in daily body weights among the groups. Analysis of carcass composition revealed no significant differences in percentage of lipid or protein. Liver and inguinal pad weights were not significantly different. In vitro determination of lipogenesis showed it was enhanced in the inguinal pad and depressed in the liver only after 14 days of treatment. These results demonstrate that although in vivo rHuTNF may specifically alter tissue metabolism, it does not, by itself, result in a sustained cachectic effect.

Adipose Tissue↗
PubMed1987

Controlled evaluation of nabumetone in the treatment of active adult rheumatoid arthritis. Nabumetone versus naproxen double-blind parallel study.

Nabumetone is a new nonsteroidal anti-inflammatory agent. Therapy with nabumetone 1,000 mg given at bedtime was compared with naproxen 250 mg given twice daily in a prospective double-blind study of patients with rheumatoid arthritis. Both drugs were found to be efficacious in a comparable fashion. Both drugs were well tolerated in terms of patient withdrawal rates, which were 5 and 8 percent, respectively. Gastrointestinal side effects were the most commonly encountered problem. Nabumetone holds promise as an important new therapeutic approach in arthritis.

Adolescent↗
PubMed1987

Results of a six-month study comparing the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis.

The safety and efficacy of nabumetone (1,000 mg at bedtime) were compared with those of aspirin (900 mg four times daily) in the treatment of osteoarthritis in adult patients in a private practice setting as part of a six-month, double-blind, controlled, randomized, parallel group study. At screening, baseline, and Days 7, 14, 28, 56, 112, and 168, efficacy was evaluated according to independent assessments by the patients and the physician of overall osteoarthritic activity and pain and by the physician's assessment with respect to a defined activity. Of the 40 patients enrolled, 37 were evaluable for efficacy (19 in the nabumetone group and 18 in the aspirin group). Demographic parameters and diagnostic criteria for osteoarthritis were comparable between the groups, although there was a preponderance of women in the nabumetone group. Significant improvement from baseline in all five efficacy parameters was observed in both groups. Safety was evaluated for all 20 enrolled patients in each group. The percentage of aspirin-treated patients who withdrew from the study due to adverse experiences was greater (60 percent versus 20 percent), as was the number with at least one treatment-related adverse experience (19, or 95 percent, versus 11, or 55 percent). Treatment-related adverse experiences described as moderate or severe were reported by 70 percent of the aspirin-treated patients and by 35 percent of the nabumetone-treated patients. In this study, nabumetone 1,000 mg at bedtime had an acceptable safety profile and was as effective as aspirin 900 mg four times daily in the treatment of osteoarthritis.

Adult↗
PubMed1987

Comparison of the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis in adults.

A six-month, multicenter, double-blind study compared the efficacy and safety of two therapeutic regimens in 332 patients with osteoarthritis. The patients received either 1,000 mg of nabumetone as a single bedtime dose or 900 mg of aspirin in four divided doses. At the end of the study, patients in both treatment groups showed significant improvement from baseline for all five parameters; no statistically or clinically significant differences were observed between the groups. The safety data did reveal clinically and statistically significant differences between the groups. Aspirin-treated patients experienced a greater frequency of withdrawal from the study because of adverse experiences (34 percent versus 13 percent), a greater incidence of having at least one treatment-related adverse experience (73 percent versus 52 percent), a greater percentage of patients with at least one moderate or severe treatment-related adverse experience (47 percent versus 22 percent), and a greater percentage of patients with treatment-related adverse experiences affecting the gastrointestinal system (43 percent versus 32 percent) or the inner ear (32 percent versus 10 percent). The results of this study demonstrated that nabumetone, 1,000 mg at bedtime, is as efficacious as aspirin, 900 mg four times daily, produces fewer adverse effects, and is indicated in the treatment of osteoarthritis.

Adult↗
PubMed1986

Activities of cerebral dihydropteridine reductase and tyrosine hydroxylase in chronic uremia in rats.

The effect of chronic uremia on activities of cerebral dihydropteridine reductase (DHPR) and tyrosine hydroxylase (TH) and content of norepinephrine and dopamine was investigated in the male Sprague-Dawley rats. The uremic animals were fed diets containing either 8% or 18% casein ad libitum, and sham-operated pair-fed and ad libitum fed animals were used as controls. There were no significant differences in TH activity between the groups fed the two levels of protein. Uremic rats had lower activity of TH than pair-fed controls, and pair-fed controls had lower activity than ad libitum-fed animals. DHPR activity and norepinephrine and dopamine content did not differ among the groups. Our study suggests that the chronic uremic condition or restricted feeding causes a decrease in brain TH activity which is not mediated by decreased DHPR activity. Further, this decreased enzyme activity does not result in depressed catecholamine content, indicating the presence of a highly regulated mechanism controlling catecholamine levels.

Animals↗
PubMed1986

Surgical treatment of lung cancer: promise and problems of early diagnosis.

Recent studies have shown that the survival of patients with lung cancer is improved if the tumour is resected before it becomes larger than 3 cm in diameter and before it spreads to lymph nodes. While this suggests a positive benefit from early detection, recent mass-screening studies have claimed that the benefit obtained from this procedure is illusory because it relates to a lead-time bias. This study reports the results of surgical resection of 143 primary lung cancers. The data confirmed that the predicted 5-year survival was greatest (74%) following resection of lesions that were less than 3 cm in diameter without node involvement. Analysis showed that the age of these patients was 63 +/- 8 years, the same as in patients with larger tumours and more extensive node involvement. This suggests that tumours progress rapidly from a stage at which resection is beneficial to stages at which it is not. Although it is desirable that tests predict the presence of small tumours, the high requirements for sensitivity and specificity at current prevalence rates for lung cancer make this goal impractical.

Adenocarcinoma↗
PubMed1984

Validity of a food frequency questionnaire for the determination of individual food intake.

The validity of a food frequency questionnaire for dietary assessment was tested with 31 college students living and dining in a dormitory. A food frequency questionnaire was mailed to participants requesting them to estimate their usual intake of specific food items. Actual food consumption was determined at each meal with self-report forms. These forms required participants to indicate foods chosen at that meal. To test the validity of the frequency questionnaire, regression equations were calculated for each individual using the frequency questionnaire data as the independent variable (X) and actual intake data as the dependent variable (Y). Eighty-four percent of the r values were greater than 0.50 and 55% were greater than 0.71. All were significant at the 0.002 level or below. As an alternative test of validity, the percentage of over- and underestimation of each food group was also assessed. Foods which are often major components of a meal (eg, flesh foods) were estimated with greater accuracy than those foods which could be considered accessory (eg, nuts or seeds). While it appears that a large percentage of individuals could accurately estimate their intake with this technique, some individuals were unsuccessful in doing so. Further research is needed to identify individual characteristics which may predict success with this technique.

Diet Surveys↗
PubMed1982

Validity of telephoned diet recalls and records for assessment of individual food intake.

Six methods of assessing individual food intake reported by telephone were compared for accuracy. A sample of 107 students eating in a dormitory dining hall was used. Two 7-day and four 3-day diet records were reported by telephone to either an interviewer or an answering device; and fourteen 6-h recalls and seven 24-h recalls were obtained by an interviewer over the telephone. To examine validity, the investigators observed respondents' intake for 28 days. Food item agreement scores comparing observed and reported data were calculated. Seven-day records were most accurate (87% food item agreement); 3-day records and 6-h recalls were equivalent (75%); and 24-h recalls were least accurate (69%). There were no significant difference in accuracy of reporting records to an interviewer versus a recording device, but respondents preferred the interviewer. Results of telephoned reporting compare favorably with personal interview techniques used by other investigators, indicating that telephoned methods should be further explored in community settings.

Adolescent↗
PubMed1977

Activation of complement components C3 and factor B in synovial fluids.

Synovial fluids from 106 patients with various types of arthritis were examined for the presence of conversion products of C3 by means of crossed antigen-antibody electrophoresis and for products of factor B by immunoelectrophoresis. C3 conversion was found in all 15 fluids from patients with seropositive rheumatoid arthritis, in 11 of 15 with seronegative rheumatoid arthritis, in the majority with probable and possible rheumatoid arthritis, juvenile rheumatoid arthritis, SLE, pseudogout, gout, Reiter's syndrome, and frequently in other arthritides studied, but in only one of 15 with degenerative arthritis. In 53 synovial fluids a single C3 conversion peak was seen in addition to the native protein and in 18 others two conversion peaks were present. In many synovial fluids showing conversion whole-complement titers and C3 protein concentrations were normal. In both rheumatoid arthritis and crystal synovitis the per cent of C3 conversion, as estimated by planimetry, correlated with synovial fluid leukocyte counts, Factor B conversion was found in 31 fluids and usually occurred in fluids also showing C3 conversion. The findings indicate that in vivo activation of components of the classical and alternative considered mediated by immune complexes. Activation is also commonly present in a wide variety of other inflammatory arthritides and ofter would not be recognized by measuring only concentrations of hemolytic whole complement or C3 by immunodiffusion. The positive association between C3 conversion and synovial fluid polymorphonuclear leukocytes suggests that chemotactic factors generated from complement may be responsible for the attraction of leukocytes into the synovial space in these diseases.

Arthritis↗