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J Dark

Publications and source records attributed to J Dark.

At least 19 recordsLinked to original sources
PubMed2003

Noradrenaline-induced lipolysis in adipose tissue is suppressed at hibernation temperatures in ground squirrels.

Responsiveness of white adipose tissue (WAT) and brown adipose tissue (BAT) from hibernating and nonhibernating golden-mantled ground squirrels (Spermophilus lateralis) to the lipolytic action of the sympathetic neurotransmitter, noradrenaline, was tested in vitro at temperatures characteristic of deep torpor (5 degrees C) and euthermia (37 degrees C). Noradrenaline-stimulated lipolysis, as indicated by WAT glycerol release, of tissue from hibernating ground squirrels was six- to ten-fold greater at 37 degrees C than at 5 degrees C. Noradrenaline was ineffective in increasing lipolysis at 5 degrees C. Noradrenaline-stimulated lipolysis in BAT was similarly suppressed at 5 degrees C. Noradrenaline-stimulated lipolysis was little affected by temperature change below approximately 15 degrees C but strongly correlated with temperature above approximately 15 degrees C. Noradrenaline-induced lipolysis of WAT from nonhibernating and hibernating ground squirrels did not differ at an incubation temperature of 5 degrees C. We conclude that noradrenaline-stimulated WAT lipolytic activity is markedly suppressed at the low temperatures characteristic of deep torpor and that there is no 'hibernation-specific' adaptation of WAT to enhance its responsiveness to noradrenaline at low tissue temperatures. Temperature dependence of noradrenaline-stimulated lipolysis may in part account for the shift from lipid to carbohydrate metabolism during the earliest stage of arousal from deep torpor.

Adipose Tissue↗
PubMed2002

Photoperiodic control of oestrous cycles in Syrian hamsters: mediation by the mediobasal hypothalamus.

To assess whether the mediobasal hypothalamus (MBH) is necessary for photoperiodic control of oestrous cycles and prolactin secretion, we tested intact female Syrian hamsters (controls) and those that had sustained unilateral or bilateral lesions of the MBH. All hamsters displayed 4-day oestrous cycles postoperatively in the long-day photoperiod (14 h light/day); control females and those with unilateral MBH damage ceased to undergo oestrous cycles approximately 8 weeks after transfer to a short-day photocycle (10 h light/day), whereas 12 of 15 females with bilateral MBH lesions continued to generate 4-day oestrous cycles throughout 22 weeks in short days. Serum prolactin concentrations were either undetectable or low in all hamsters 8 or 14 weeks after the transfer to short-day lengths, but increased above long-day baseline values by week 22. We conclude that melatonin-binding sites in the MBH mediate suppression of oestrous cycles but not prolactin secretion by short-day lengths; recovery of prolactin secretion in females during prolonged exposure to short-day lengths reflects development of refractoriness to melatonin in a substrate distinct from the MBH. These findings suggest that separate neural pathways mediate photoperiodic control of gonadotropin and prolactin secretion in female hamsters.

Animals↗
PubMed2000

Role of area postrema in control of torpor in Siberian hamsters.

Siberian hamsters undergo torpor during the short days of winter and in response to glucoprivation or food restriction. We tested whether the area postrema and the adjacent nucleus of the solitary tract (hereafter the AP), which monitor metabolic fuel availability, also control the onset of torpor. Siberian hamsters that had manifested torpor spontaneously or had entered torpor in response to 2-deoxy-D-glucose (2-DG) treatment were subjected to area postrema ablations (APx). Hamsters continued to display torpor postoperatively; most features of torpor were unaffected by APx. The AP is not necessary for expression of torpor elicited by short day lengths or metabolic challenge. In contrast, decreases in food intake manifested by hamsters treated with 2-DG were counteracted by APx. In Siberian hamsters, the AP appears to mediate effects of 2-DG on food intake but not torpor.

Animals↗
PubMed1999

Photoperiod modulates torpor and food intake in Siberian hamsters challenged with metabolic inhibitors.

Siberian hamsters, Phodopus sungorus, exposed to a short photoperiod (SP) were challenged with 2-deoxy-D-glucose (2DG), which disrupts glycolysis and induces torpor in animals maintained in long photoperiods (LP), or mercaptoacetate (MA), which disrupts fatty acid oxidation. SP decreased rather than facilitated the induction of torpor by 2DG; decreased torpor in response to 2DG coincided with onset of spontaneous torpor in SP hamsters. In contrast, MA induced hypothermia in hamsters kept in SP but not LP, but did not induce full torpor. We conclude that short day lengths do not induce spontaneous torpor by increasing responsiveness to glucose availability; instead, responsiveness to glucoprivation is, if anything, blunted in SP. The occurrence of spontaneous torpor may be unrelated to concurrent metabolic fuel availability. Although 2DG and MA had different effects on thermoregulation in short vs. long day lengths, each treatment decreased 24-h food intake in hamsters in both photoperiods.

Animals↗
PubMed1999

Hypoglycemia and torpor in Siberian hamsters.

We tested whether reduced blood glucose concentrations are necessary and sufficient for initiation of torpor in Siberian hamsters. During spontaneous torpor bouts, body temperature (Tb) decreases from the euthermic value of 37 to <31 degrees C. Among hamsters that displayed torpor during maintenance in a short-day length (10 h light/day) at an air temperature of 15 degrees C, blood glucose concentrations decreased significantly by 28% as Tb fell from 37 to <31 degrees C and increased during rewarming so that by the time Tb first was >36 degrees C, glucose concentrations had returned to the value preceding torpor. Hamsters did not display torpor when maintained in a long-day length (16 h light/day) and injected with a range of insulin doses (1-50 U/kg body mass), some of which resulted in sustained, pronounced hypoglycemia. We conclude that changes in blood glucose concentrations may be a consequence rather than a cause of the torpid state and question whether induction of torpor by 2-deoxy-D-glucose is due to its general glucoprivic actions.

Animals↗
PubMed1999

Ventromedial hypothalamic mediation of photoperiodic gonadal responses in male Syrian hamsters.

Short day lengths induce testicular regression in seasonally breeding Syrian hamsters. To test whether the ventromedial hypothalamus is necessary to maintain reproductive quiescence once testicular regression has been achieved, photoregressed male hamsters were subjected to lesions of the ventromedial hypothalamus (VMHx), pinealectomy (Pinx), or sham operation (Sham). VMHx hamsters underwent accelerated gonadal recrudescence compared to Pinx and Sham hamsters. Recovery of prolactin concentrations (PRL) to values characteristic of long-day hamsters was hastened in the VMHx animals compared to Sham hamsters. Concentrations of follicle stimulating hormone (FSH) increased prematurely in both the VMHx and Pinx animals, beginning a few weeks after surgery. By the time the gonads had undergone recrudescence and the hamsters were refractory to melatonin, PRL and FSH concentrations had returned to baseline long-day values in all groups; there was no evidence of hypersecretion of either hormone in any of the animals with lesions. Melatonin concentrations of VMHx hamsters did not differ from those of sham-operated animals, but because only a single determination was made, it remains possible that VMH damage altered the duration of nightly melatonin secretion. An intact VMH appears to be essential for the continued maintenance of reproductive suppression induced by exposure to short day lengths; these and earlier findings suggest that the VMH-dorsomedial hypothalamic complex mediates regression of the reproductive apparatus during decreasing day lengths of late summer and early autumn and also is necessary to sustain regression during the winter months.

Animals↗
PubMed1998

Effect of immunosuppression after cardiac transplantation in early childhood on antibody response to polysaccharide antigen.

BACKGROUND: Three children who had cardiac transplantation before age 4 years later presented with recurrent sinopulmonary infection caused by organisms including Streptococcus pneumoniae, in which capsular polysaccharide plays an important part, one developed bronchiectasis. We therefore studied responses to polysaccharide antigen after immunosuppression started in early childhood. METHODS: Antibodies against pneumococcal and haemophilus polysaccharides, and total IgG, IgG1, IgG2, and IgA concentrations were measured in 33 cardiac-transplant recipients transplanted before the age 4 years (group 1) and after that age (group 2). Patients with low pneumococcal and haemophilus antibody concentrations were immunised with 23 polyvalent pneumococcal and tetanus-haemophilus conjugate vaccines and antibody responses were measured. FINDINGS: Five patients from group 1 and seven from group 2 were transplanted for congenital heart disease and ten patients in each group had heart transplants because of cardiomyopathy; none were asplenic. Group 1 (16 patients) were aged 2-10 years when investigated, group 2 (17 patients), were 6-16 years. Four of 16 patients in group 1 responded to pneumococcal polysaccharide vaccine compared with 14 of 17 in group 2 (p=0.0016). This difference remained when those in group 1, aged less than 4 years at investigation, were excluded (p=0.0060). Response to haemophilus-conjugate vaccine was similar in both groups (14 of 16 vs 14 of 17, p=1.0). Significantly more patients who failed to respond to pneumococcal vaccine had low IgG2 concentrations (p=0.0269). INTERPRETATION: Children who had a transplantation and immunosuppression in early childhood before they had developed antibody responses to pneumococcal polysaccharide, still failed to show a response when older-ie, when such responses are the norm. Ongoing immunosuppression prevents the maturation of antipolysaccharide responses leaving children susceptible to severe and recurrent damaging infection.

Aging↗
PubMed1998

Suprachiasmatic nucleus: role in circannual body mass and hibernation rhythms of ground squirrels.

Female golden-mantled ground squirrels that sustained complete ablation of the suprachiasmatic nucleus (SCNx) were housed pre- and post-operatively at 23 degrees C and then at 6.5 degrees C for 5-7 yr. SCNx and control animals held at the higher temperature manifested circannual rhythms (CARs) in body mass. In contrast, body mass CARs were not expressed in 50% of SCNx squirrels during cold exposure; rhythm amplitude was reduced to 25-40% of pre-operative values and the interval between successive peaks in body mass fell outside the circannual range. Unlike normal squirrels that hibernate for about 6 months during each circannual cycle, these SCNx squirrels expressed bouts of torpor nearly continuously throughout 2.5 yr of cold exposure. Body mass increases were often observed during hibernation--a phenomenon never observed in control animals. The remaining SCNx squirrels that did not hibernate continuously displayed CARs in body mass within the normal range. The effects of SCN ablation on body mass rhythms presumably are related to disrupted patterns of hibernation, food intake, and metabolism. The SCN, which sustains neural and metabolic activity at low tissue temperatures, may exert greater influence on thermoregulation and metabolism during the hibernation season than at other times of year, thereby accounting for the greater effect of SCN ablation in squirrels maintained at low ambient temperatures.

Animals↗
PubMed1998

Role of orthotopic heart transplantation in the management of patients with recurrent ventricular tachyarrhythmias following myocardial infarction.

OBJECTIVE: To report the outcome of an intention to treat by heart transplantation strategy in two groups of patients after infarction, one with both left ventricular failure (LVF) and ventricular tachyarrhythmias (VTA) (group A) and the other with progressive LVF following antiarrhythmic surgery for VTA (group B). PATIENTS AND METHODS: Group A comprised 17 consecutive patients for whom transplantation was considered the best primary non-pharmacological treatment; group B comprised five consecutive patients assessed and planned for transplantation after antiarrhythmic surgery. RESULTS: In group A, eight patients underwent transplantation and all survived the first 30 day period. At median follow up of 55 months (range 11 to 109) seven of this subgroup were still alive. Five patients died of recurrent VTA before transplantation, despite circulatory support. In the face of uncontrollable VTA, four of these underwent "high risk" antiarrhythmic surgery while awaiting transplantation: three died of LVF within 30 days and one was saved by heart transplantation two days after arrhythmia surgery. Mortality for the transplantation strategy in group A patients was 47% by intention to treat analysis. Quality of life in the eight actually transplanted, however, was good and only one died during median follow up of 56 months. The five patients in group B were accepted for transplantation for progressive LVF at a median of 21 months (range 12 to 28) after antiarrhythmic surgery. One died of LVF before transplantation, 22 months after initial surgery; another died of high output LVF three days after transplantation. Thus mortality of the intended strategy was 40%. The three transplanted patients are alive and well at 8-86 months. CONCLUSIONS: Although the short and medium term outcome in category A or B patients who undergo transplantation is good, the overall success of the transplantation strategy in category A patients is limited by lack of donors in the short time frame in which they are required.

Adult↗
PubMed1998

Torpor in lactating Siberian hamsters subjected to glucoprivation.

Daily torpor has never been reported for any rodent species during lactation. To test whether torpor and lactation are incompatible processes, we administered 2-deoxy-D-glucose (2-DG), a glucose analog that interferes with cellular glycolysis, to Siberian hamsters during the 2nd wk postpartum. 2-DG (2,500 mg/kg of body mass) induced torpor in lactating as well as nonlactating females. Although depth of torpor did not differ between groups, duration of torpor tended to be shorter in lactating animals. Evidence of new milk bands suggests that pups were able to obtain milk from torpid dams. By contrast, dams subjected either to a combination of brief food deprivation and subsequent food restriction or just food restriction failed to display torpor, but instead cannibalized one or more pups. We conclude that torpor is possible during lactation; whether lactating dams in nature become torpid in response to energy shortages or cannibalize or abandon one or more of their offspring remains unknown.

Animals↗
PubMed1997

Metabolic fuel privation in hibernating and awake ground squirrels.

The nature of metabolic fuel utilization during hibernation and periodic arousal is not completely understood. 2-Deoxy-D-glucose (2DG) and mercaptoacetate (MA) were administered to hibernating ground squirrels. These drugs disrupt glucose and fatty acid oxidation, respectively. Telemetrically recorded body temperature (Tb) was analyzed to determine rate of rewarming from hibernation, duration of euthermia during periodic arousal, and proportion of animals arousing after treatments. 2DG given during hibernation significantly increased latency to regain euthermia, especially during the initial phase of rewarming (from first Tb > 10 degrees C to first Tb > 15 degrees C), without affecting the duration or other features of the ensuing euthermic period; MA did not affect rate of rewarming. MA treatment during hibernation affected thermoregulation after the animals aroused, including an increased duration of euthermia and maintenance of erratic patterns of Tb. The percentage of animals that aroused from hibernation was increased in a dose-dependent fashion by each drug. 2DG and MA treatments had little or no impact on nonhibernating ground squirrels in the cold. We suggest that glucose oxidation is important for rewarming from deep torpor; limited glucose availability cannot, however, support normal levels of euthermia when fatty acid oxidation is compromised. On the other hand, fatty acid oxidation may be less necessary for normal arousal from torpor, but critical for the maintenance of euthermia during the arousal phase.

Animals↗
PubMed1997

Metabolic fuel availability influences thermoregulation in deer mice (Peromyscus maniculatus).

Body temperature (Tb) was monitored telemetrically in adult deer mice kept in an environmental chamber at low ambient temperature (Ta = 15 degrees C). Mice were challenged with various doses of 2-deoxy-D-glucose (2DG, a glycolysis inhibitor) or mercaptoacetate (MA, a fatty acid oxidation inhibitor) or a combination of the two drugs. A preliminary study suggested that higher doses of 2DG and MA, either individually or together, tended to produce a transient decrease in Tb. In the main experiment, either 2DG or MA or the two drugs together was sufficient to induce a significant, temporary hypothermia. In neither experiment, however, did any treatment affect 24-h food intake or induce daily torpor. The latter outcome contrasts with Siberian hamsters, in which torpor is readily triggered by similar 2DG treatments. Apparently, glucoprivation and lipoprivation resulting from 2DG and MA treatments, respectively, sufficient to produce significant hypothermia, are inadequate to instigate torpor in Peromyscus.

Animals↗
PubMed1997

Alpha interferon gene deletions in post-transplant lymphoma.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplant and has been associated with high mortality using conventional chemotherapy. We have investigated 11 cases of PTLD for alterations to the interferon alpha (IFNA) and p16 genes on chromosome 9p using archival material. 4/9 (44%) cases had deletions of the IFNA genes, in contrast to 1/59 (1.7%) cases of intermediate/high-grade de novo NHL drawn from the same geographical region. PTLD may therefore represent a distinct NHL subgroup exhibiting distinct gene pathology.

Chromosomes, Human, Pair 9↗