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Biomedical subjects

S Hogan

Publications and source records attributed to S Hogan.

36 records · Page 2Linked to original sources
PubMed1987

Dependence of ATP citrate lyase activity on cell density of isolated rat hepatocytes.

The activities of two enzymes involved in the lipogenic process, ATP citrate lyase and NADP-linked malic enzyme were evaluated as a function of cell density in isolated rat hepatocytes. The activity of ATP citrate lyase was profoundly affected by cell density with the activity/cell being higher at low cell densities than at high cell densities. Malic enzyme was not similarly affected, nor was cellular ATP content. The effect was observed regardless of dietary state but was most dramatic with hepatocytes from fasted-refed rats. Both an activator and an inhibitor of ATP citrate lyase have been isolated from conditioned medium from cells at low density and at high density, respectively. The activator fraction was heat stable while the inhibitor fraction was heat labile, and both factors had molecular weights in excess of 10,000 daltons.

ATP Citrate (pro-S)-Lyase↗
PubMed1987

Resistance to diet-induced obesity: food intake, pancreatic sympathetic tone, and insulin.

After 15 wk on a moderately high-calorie high-fat (CM) diet, 43% of 40 3-mo-old male Sprague-Dawley rats developed diet-induced obesity (DIO) (29% more weight gain), whereas 57% of diet-resistant (DR) rats gained no more weight than 20 chow-fed controls. When switched to chow for another 7 wk, DR rats ate 13% less, gained 55% less weight, and had 49% lower food efficiency, whereas DIO rats ate 4% less but had comparable weight gain and efficiency to controls. DIO rats had 29% more carcass lipid (percent of carcass weight). DIO rat retroperitoneal white adipose pads had 65% more cells that were the same size as those in chow-fed pads; DR rat cells were similar to controls. Both DR and DIO rats increased norepinephrine turnover in their interscapular brown adipose pads by greater than 90%. DIO rats also had 40% lower pancreatic turnover; their plasma insulin levels were 327% of controls after 15 wk on the CM diet and 188% after 7 wk on chow. DR levels were the same as controls at both times. Therefore, regulation of caloric intake, pancreatic sympathetic tone, and plasma insulin levels were three important differences between rats that resisted and those that developed DIO on high-energy diets.

Adipose Tissue, Brown↗
PubMed1987

Mucoid strains of Pseudomonas aeruginosa are devoid of mannuronan C-5 epimerase.

Mucoid strains of Azotobacter vinelandii, Pseudomonas aeruginosa and Pseudomonas syringae var glycinia synthesize alginate, an extracellular copolymer comprising D-mannuronosyl and L-guluronosyl moieties. Extracellular mannuronan C-5 epimerase, which converts polymannuronate to alginate, was demonstrated in supernatant fluid from cultures of A. vinelandii. However, the enzyme could not be demonstrated, using the same assay, in supernatant fluids of cultures of mucoid strains of P. aeruginosa or of P. syringae var glycinia, or in cell-free sonic extracts of P. aeruginosa. The results suggest that the pathways of alginate biosynthesis in A. vinelandii and Pseudomonas species may differ.

Alginates↗
PubMed1987

Studies on the antiobesity activity of tetrahydrolipstatin, a potent and selective inhibitor of pancreatic lipase.

In summary, THL is a potent inhibitor of pancreatic lipase, which is both selective and irreversible in its action in vitro. It is also likely that THL inhibits pancreatic lipase in vivo, since its acute administration to mice and squirrel monkeys suppresses absorption of dietary triglycerides, without an apparent alteration in the absorption of fatty acids. The marked loss in body weight and carcass fat of DIO rats with subchronic administration of THL strongly suggests that inhibition of pancreatic lipase is a feasible strategy for the treatment of obesity. Whether obese humans will overeat in response to a reduction in body energy stores is not known. However, it is probable that compliance to a therapy which maintains the present level of food intake while inducing excretion of dietary fat, will be greater than a reducing diet alone or conjunction with the currently available antiobesity drugs.

Animals↗
PubMed1986

Increased brown adipose tissue thermogenesis in obese (ob/ob) mice fed a palatable diet.

Feeding female genetically obese (ob/ob) mice a palatable "cafeteria" diet results in increased sympathetic nervous system activity in brown adipose tissue and hypertrophy and increased thermogenesis of this tissue. There is an associated increase in the capacity of the ob/ob mouse to respond thermogenically to noradrenaline, prolongation of its survival in the cold, and an increase in body temperature at all times of day. Thus the cafeteria diet overcomes the usual refractoriness of brown adipose tissue of the ob/ob mouse to noradrenaline and to sympathetic stimulation, increases the low capacity for a thermogenic response to noradrenaline, almost normalizes resistance to cold, and increases the "set point" at which the ob/ob mouse regulates its body temperature. It is concluded that the repetitive sympathetic nervous stimulation engendered by the high-fat cafeteria diet has a trophic action on brown adipose tissue that improves its atrophied functional state and that the low sympathetic nervous system activity usually seen in brown adipose tissue of ob/ob mice eating chow under animal house conditions results in secondary atrophy of the tissue. The results point to a central location for the defect in the ob/ob mouse, perhaps in the control of the sympathetic nervous system in relation to diet availability and composition and to environmental temperature.

Adipose Tissue, Brown↗
PubMed1985

Lack of diet-induced thermogenesis in brown adipose tissue of obese medial hypothalamic-lesioned rats.

Radiofrequency heat lesions were made in the medial hypothalamus of 12-week old male and female Holtzman rats. Two to three days later rats were offered a palatable cafeteria diet in addition to chow or were fed chow alone for the next 3-4 weeks. Male lesioned rats were only slightly hyperphagic on the chow diet and gained little extra weight. When fed the cafeteria diet, energy intake of male lesioned rats almost doubled in comparison with chow-fed lesioned rats and a very rapid extra weight gain occurred. Despite the marked hyperphagia, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed lesioned rats, as indicated by low mitochondrial guanosine diphosphate (GDP) binding. In female rats, lesions induced much greater hyperphagia and body weight gain than in male rats, particularly when they ate the cafeteria diet. Again, thermogenesis in brown adipose tissue was suppressed in the cafeteria-fed female lesioned rats. The proportion of energy derived from carbohydrate was not altered by the cafeteria diet in either male or female rats, whether lesioned or not, but there was an increase in the proportion of energy derived from fat at the expense of protein. No sex differences in food selection were observed. The accumulation of body fat was always greater in female lesioned rats than in male lesioned rats for similar food intakes. It is concluded that medial hypothalamic lesions prevent the normal occurrence of diet-induced thermogenesis in brown adipose tissue despite extreme overeating by the rats of a palatable cafeteria diet.

Adipose Tissue, Brown↗
PubMed1985

Impaired diet-induced thermogenesis in brown adipose tissue from rats made obese with parasagittal hypothalamic knife-cuts.

Two experiments were performed to determine if bilateral parasagittal hypothalamic knife-cuts (KCs), which produce long-term overeating and obesity, after biochemical indices of brown adipose tissue (BAT) reactivity to thermogenic stimuli. In the first study, responses to environmental cold were tested. Four weeks after surgery, KC rats had gained 4-5 times more weight than controls and were obese (increased Lee Obesity Index and weight of gonadal white fat). Before being sacrificed, groups of KC and control rats were exposed to 4 degrees C for 21 hr or remained at 28 degrees C. Interscapular BAT weighed 300% more in KC rats, due largely to increased white fat content. Functional indices of BAT thermogenic capacity (protein content, DNA content, cytochrome oxidase activity and mitochondrial guanosine diphosphate (GDP) binding) were normal at 28 degrees C. Exposure to 4 degrees C produced greatly enhanced responses but these were equivalent for both groups. This suggested an intact capacity for non-shivering thermogenesis in obese KC rats. In the second study, the same BAT responses were examined in other rats fed a palatable "cafeteria" diet (CAFE). One week after surgery, KC and control rats were subdivided into groups that received chow alone or chow plus four different palatable foods daily. Before sacrificing 4-5 weeks later, KC rats had gained 3-4 times more weight than controls and were obese. Interscapular BAT weighed 200-300% more in KC rats. CAFE feeding produced larger increments in all variables for KC vs. control rats. Most importantly, GDP binding was reduced in both KC groups, and significantly more so after CAFE feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1983

Brown adipose tissue of mice with gold thioglucose-induced obesity: effect of cold and diet.

Gold thioglucose (GTG)-obese mice have a larger than normal amount of brown adipose tissue (BAT) with ultrastructurally normal mitochondria. The tissue grows normally when the mice adapt to cafeteria feeding or to cold (8 degrees C). Acute exposure to cold causes a fairly normal thermogenic activation of BAT mitochondria of GTG-obese mice, both in dynamic and static phases of their obesity. However, chow-fed GTG-obese mice have BAT mitochondria that are in a low state of thermogenic activation, and these mice fail to respond to eating a cafeteria diet for 3 wk by a normal thermogenic activation of their BAT mitochondria. More prolonged cafeteria feeding for 11-13 wk, into the static phase of obesity, is associated with thermogenic activation of BAT mitochondria of GTG-obese mice. The capacity of GTG-obese mice to respond to noradrenaline (norepinephrine) by an increase in metabolic rate is greater than that of lean mice and is further enhanced by cold acclimation. It is concluded that BAT of the GTG-obese mouse is inherently functional, as is control of its thermogenic function and growth during cold exposure and cold acclimation. Dietary influences on BAT thermogenic function are, however, defective in the GTG-obese mouse at least during the dynamic phase of its obesity. The resulting failure of diet-induced thermogenesis would be expected to contribute to the known high metabolic efficiency of the GTG-obese mouse and, together with the hyperphagia, to the obesity induced by GTG.

Acclimatization↗
PubMed1982

Brown adipose tissue of rats with obesity-inducing ventromedial hypothalamic lesions.

Male and female Holtzman rats were made hyperphagic and obese with bilateral radiofrequency heat lesions of the ventromedial hypothalamic (VMH) area. When VMH rats were maintained at 28 degrees C, their brown adipose tissue (BAT) DNA, protein, and cytochrome oxidase contents were normal although more stored lipid was present, as judged from a threefold increase in wet weight. Thermogenic activity of BAT mitochondria was normal in male VMH rats, as judged from the unchanged level of guanosine diphosphate (GDP) binding (known to be a sensitive index of the functional activity of the thermogenic proton conductance pathway), and reduced in female VMH rats. When rats with VMH lesions were exposed to cold (4 degrees C for 24 h), the visible hyperemia of their BAT and normal large increase in mitochondrial GDP binding indicated normal thermogenic responsiveness. We conclude that the medial nuclei of the hypothalamus and associated afferent or efferent nerve tracts do not represent an essential central nervous system link for cold-induced, sympathetic-mediated activation of BAT thermogenesis. It is possible, however, that diet-induced, sympathetic-mediated activation of BAT function and growth might require an intact VMH region because no enhancement of BAT mitochondrial function normally associated with hyperphagia was detected in these hyperphagic VMH-lesioned animals.

Adipose Tissue, Brown↗
PubMed1981

Abnormal brown adipose tissue in genetically obese mice (ob/ob): effect of thyroxine.

Lean and genetically obese (ob/ob): mice were treated daily for 2 wk with thyroxine (T4), noradrenaline, or thyroxine plus noradrenaline. T4 treatment of obese mice increased the abnormally low binding of GDP to brown adipose tissue mitochondria and permitted a cold-induced increase to occur. It also brought about a return to a more normal ultrastructure of the mitochondria of the obese mice. T4 treatment did not alter the binding of GDP to brown adipose tissue mitochondria of lean mice. The binding of GDP to brown adipose tissue mitochondria is known to be to a 32,000-dalton polypeptide associated with the thermogenic proton conductance pathway. T4 treatment did not alter the proportion of this polypeptide in the mitochondrial membrane in either lean or obese mice. Treatment with noradrenaline did not alter the binding of GDP to brown adipose tissue mitochondria in either lean or obese mice. The effect of T4 is thought to be due to an improvement in the defective responsiveness of brown adipose tissue to endogenous noradrenaline in the obese mice, known to be related to their poor cold resistance and obesity. The improvement allows a more normal noradrenaline-induced unmasking of GDP binding sites, both in response to diet and in response to cold. Such treatment is known to improve cold resistance of the obese mice, and this appears to be correlated with an improvement in the functioning of their defective brown adipose tissue.

Adipose Tissue, Brown↗
PubMed1979

Immunosuppressive effects of sulfato-trans-(-)-1,2-diaminocyclohexaneplatinum(II).

Sulfato-trans-(-)-1,2-diaminocyclohexane platinum(II) is a new antitumor agent. Its effect on immune responses was investigated. This agent inhibited lymphocyte transformation in response to phytohemagglutinin, pokeweed mitogen, and concanavalin A. It inhibited antibody plaque-forming spleen cells in AKR/J mice at doses ranging from 2.5 to 7.5 mg/kg i.p. It also prolonged the survival of skin grafts against major histocompatibility barriers in C57BL/6J mice transplanted with tail skin from CBA/J mice. The effective dose ranged from 2.5 to 5 mg/kg. This compound inhibited graft-versus-host reaction in three-week-old AKR/J X DBA/2JF1 mice receiving spleen cells from AKR/J mice i.p. Significant inhibition of graft-versus-host reaction was seen with doses ranging from 1 to 7.5 mg/kg i.p. These results suggest that this drug is immunosuppressive.

Animals↗
PubMedDate not supplied

Uncensored open access gastroscopy--limited resources--unlimited demand.

In the first 3 yr of an uncensored open access gastroscopy service in a County Hospital, 891 patients attended for first gastroscopy. The data on these patients is presented and compared with a randomly selected group who attended for gastroscopy in the yr prior to the establishment of the service having come to the normal Consultant clinics. In the open access group the gastroscopy examination was normal in 29 per cent (32 per cent comparator group), 31 per cent had major abnormalities (33 per cent comparator group) and 40 per cent had minor abnormalities (35 per cent comparator group). Delay time from referral to endoscopy was 37 days for open access patients (45 days comparator group). Only 6 per cent of open access patients were brought back to O.P.D. (47 per cent comparator group) and 72 per cent of open access patients returned directly to their family doctor (28 per cent comparator group). A comparison of the Clonmel findings with British centres reporting their results shows a broadly similar picture. It is concluded that almost 1,300 unnecessary clinic visits were avoided by the provision of the open access service, some reduction in delay time to gastroscopy was achieved, the family doctor maintained control of patient management in the great majority of patients, the pattern of referral was not inappropriate and compared very well with the comparator group. Over the 3 yr there was a large increase in the number of gastroscopies performed which caused resource difficulties. It is recommended that adequate planning of these requirements should be carried out before an open access service is started. At least 1 additional dedicated gastroscopy only endoscopy service per week would be required.

Gastroscopy↗
PubMedDate not supplied

Methylene blue but not indigo carmine is toxic to human luteal cells in vitro.

Methylene blue (MB) is reported to be teratogenic when injected intra-amniotically. Indigo carmine (IC) appears to be a safe alternative. To determine if MB has potential detrimental effects on ovarian tissue, we compared the effect of MB and IC on human granulosa luteal cell (GC) function in vitro. Human oocyte-cumulus complexes were obtained during in vitro fertilization cycles and one to three were placed in an organ culture dish. After insemination with sperm, oocytes were removed the day after retrieval and the attached GC were washed daily for 3 more days by changing 2 mL of culture medium. All the dishes were treated with human chorionic gonadotropin (hCG) for the next 24 h and progesterone (P) production during this interval was taken as baseline. Test chemicals were added with hCG for the next 48 h with daily media changes. The P production during the last 24 h of chemical treatment was expressed as a percentage of the baseline. MB significantly reduced P production whereas IC did not appear to have any effect. Moreover, under inverted microscopy more than 90% of the GC cells contained several small bluish intracellular granules when exposed to 0.01% MB but not 0.01% IC. These results indicate that MB may be taken up and processed by GC cells and inhibits P production. This finding adds to previous reports on the use of in vitro GC assay to identify potential reproductive toxicants. The clinical significance of this preliminary study needs further investigation.

Cells, Cultured↗
PubMedDate not supplied

The impact of variation in trauma care times: urban versus rural.

STUDY OBJECTIVES: To document the existence and nature of variation in times to trauma care between urban and rural locations; to assess the impact of identified variations on outcome. DESIGN: Retrospective case review. SETTING: Washington state, 1986. PARTICIPANTS: Motor-vehicle-collision fatalities. METHODS: Previously unreported definitions of urban and rural location and possibly preventable death were used to conduct a comparative analysis of urban and rural fatalities. Trauma care times in the prehospital and the emergency department (ED) phases of care were abstracted. Their relationships to corresponding crude death rates and possibly preventable death rates also were examined. RESULTS: Prehospital times averaged two times longer in rural locations than in urban areas. Fist-physician contact in the ED averaged six times longer in rural locations than in urban settings. Concomitantly, the crude death rate in rural settings was three times that of the urban areas. The overall possibly preventable death rate was double the urban rates in rural incidents. When stratified by phase of care, rate of possibly preventable death showed no urban/rural variation for the prehospital phase, but was three times greater for the ED phase in rural areas than in urban ones. CONCLUSIONS: Trauma care times and adverse outcome appear to be associated. Allocation of resources to decrease length of and geographic variation in time to definitive care, particularly in the ED phase, seems appropriate.

Accidents, Traffic↗
PubMedDate not supplied

A cyproheptadine fatality.

A 28-year-old man was found dead by his girlfriend. No anatomic cause of death was identified at autopsy. The heart-blood ethanol concentration was 0.09 g/dL. Comprehensive testing for abused and therapeutic drugs in the blood and urine identified cyproheptadine, a serotonin and histamine antagonist. This was one of the medications prescribed for the girlfriend, who admitted that several tablets were missing from the vial. The heart blood contained 0.46 mg/L of cyproheptadine. A review of the literature indicated that only trace amounts of parent drug are identified in the blood following therapeutic use of cyproheptadine. Therefore, the medical examiner concluded that the cause of death in this case was ethanol and cyproheptadine intoxication.

Adult↗
PubMedDate not supplied

Red foxes (Vulpes vulpes) in Ireland as hosts for parasites of potential zoonotic and veterinary significance.

Intestinal washes, faecal flotations and serological examinations for antibodies to Toxoplasma gondii and Neospora caninum were used to assess the prevalence of parasites in carcases of foxes killed on roads or shot in the Dublin area and surrounding counties. The ascarids Uncinaria stenocephala and Toxocara canis were prevalent, as was the trematode Alaria alata. Taenia species, eggs of Capillaria species and sporocysts of Sarcocystis species were also found. Only one fox out of 70 examined was seropositive for N. caninum, whereas 24 of 51 were seropositive for T. gondii.

Ancylostomatoidea↗