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Biomedical subjects

L C Wang

Publications and source records attributed to L C Wang.

At least 163 records · Page 9Linked to original sources

Seasonal difference in thermoregulatory responses to opiates in a mammalian hibernator.

Accumulated evidence suggests that increased endogenous opioid activities may facilitate the onset of hibernation. The present study investigated the change in thermoregulatory responses following ICV infusion of morphine or [D-Ala2]-Met enkephalinamide (EK) in unanesthetized, unrestrained Columbian ground squirrels (Spermophilus columbianus) during its annual hibernation cycle. In the nonhibernating phase, low doses of either morphine (less than 160 micrograms) or EK (less than 400 micrograms) elicited a dose-related hyperthermia and an increase in heat production, whereas a higher dose of opiates caused hypothermia and a decrease in metabolic rate. Naloxone (5 mg/kg, SC) pretreatment reduced or reversed both the hyper- and hypothermic responses to opiates. Lower ambient temperature (5 degrees C) enhanced the hypothermic response and attenuated the hyperthermic response. In the hibernating phase, euthermic ground squirrels exhibited a reduced responsiveness to exogenous opiates: the hyperthermic response to low dose of morphine (10 micrograms) was significantly reduced and hyperthermia, rather than hypothermia was observed at the highest dose of morphine (160 micrograms). The reduced responsiveness to opiates observed during the hibernating phase seems to suggest a reduction in opiate receptor efficacy which is in agreement with the contention that an increase in endogenous opioid activities may be incumbent with the commencement of hibernation.

Animals↗

Enhancement of cold-stimulated thermogenesis in the corpulent rat (LA/N cp) by aminophylline.

Previous studies on obese strains of rats (e.g., Zucker and LA/N cp) have shown that they are deficient in nonshivering thermogenesis and poor in cold tolerance. Our earlier studies have established that aminophylline (AMPY; 85% theophylline-15% ethylenediamine) is effective in significantly improving cold tolerance in the lean Sprague-Dawley rat regardless of age or thermogenic capacity. The present study tested whether AMPY may be also effective in improving cold tolerance in both young (12-18 wk) and older (36-42 wk) lean and corpulent LA/N cp rats. Contrary to previous reports, however, the norepinephrine (NE)-stimulated nonshivering thermogenesis was not only present but also equal in magnitude in the corpulent rats to that of their lean controls. Further, no difference in cold tolerance was observed between the two groups regardless of age. Similarly, AMPY (18.7 mg/kg ip) significantly improved thermogenesis and cold tolerance in both lean and corpulent rats, again without any age-related difference in response. These results indicate that, despite the existence of obesity, no difference in thermogenic capacity to either NE or cold stimulation is evident in the LA/N cp rats. Thus the ontogeny of obesity in this strain may be caused by factors other than deficiency in NE- or cold-stimulated thermogenesis at the end-organ level.

Aminophylline↗

Metabolic and hormonal responses in theophylline-increased cold resistance in males.

The effects of theophylline (a phosphodiesterase inhibitor-adenosine receptor antagonist) and substrate feeding (Ensure, 250 kcal/235 ml) on cold resistance were studied in seminude males undertaking submaximal (50% maximum O2 consumption), intermittent (34% of total time) exercise in the cold (-5 to 15 degrees C, individually adjusted) for 3 h. Each subject (n = 7) served as his own control and was tested on a weekly schedule. Under control treatment, rectal temperature (Tre) decreased by 0.9 degrees C to approximately 36.2 degrees C after cold exposure, whereas under theophylline and Ensure, the decrease of Tre was only 0.4 degrees C, indicating a significant increase (P less than 0.05) in cold resistance (50% better than control). The plasma concentration of theophylline was 4.8-5.9 micrograms/ml and was positively correlated with plasma concentration of free fatty acids. Plasma norepinephrine (NE) increased significantly during cold exposure; the absolute concentration was significantly higher after theophylline pretreatment. The plasma concentrations of glucose, epinephrine, cortisol, and adenosine 3',5'-cyclic monophosphate did not change and the changes of free thyroxine and triiodothyronine were minor. Together, the effectiveness of theophylline + Ensure in acutely increasing cold resistance may be due to increased substrate availability for thermogenesis, part of which, through theophylline's potentiation of both sympathetic release of NE and NE-stimulated lipolysis and part of which, through supplementary feeding of Ensure.

Adult↗

A simple purification of calmodulin by reversed phase chromatography with hydrophobic polymer 3520.

A new adsorption chromatography procedure for the purification of calmodulin from bovine brain was developed using polymeric adsorbent 3520. Calmodulin was first isolated by DEAE-Cellulose column chromatography and further purified to apparent homogeneity following elution with 50% ethanol from the adsorbent column. Polyacrylamide gel electrophoresis showed one band either in the presence of Ca2+ or EGTA. The polymeric adsorbent 3520 is a non-polar polymer lacking exchangeable groups. The selective adsorption of calmodulin is based on hydrophobic interaction within the matrix, and is Ca2+ independent. Neither high salt (0.5 M NaC1) nor EGTA (5 mM) was able to elute the CaM from the adsorption column whereas ethanol (50%) eluted it completely. This method is simple to use and it provides highly purified calmodulin with high yield.

Animals↗

Substrate preference in aminophylline-stimulated thermogenesis.

The present study investigated the suitability of different substrates on aminophylline (AMPY)-induced thermogenesis in rats during cold exposure. Feeding of distilled water 60 min prior to cold exposure in two-day fasted rats resulted in the lowest total heat production and final body temperature in both saline- and AMPY-treated groups. Feeding of 5 ml Intralipid (2 Kcal/ml), a triglyceride mixture, did not improve thermogenesis beyond the control levels. However, feeding of isocaloric substitutes of sucrose elevated significantly the total thermogenesis by 7.9% and 7.4% and final body temperature by 2.23 and 1.61 degrees C, respectively, in saline- and AMPY-treated groups. The increase in thermogenesis by sucrose is not due to its thermic effect. It is concluded that sucrose, in combination with AMPY, may be of value in improving resistance to cold.

Aminophylline↗

Improving cold tolerance in elderly rats by aminophylline.

During severe cold exposure, old rats (23-26 months) were less capable in maintaining normal body temperature as compared to young rats (6-9 months) due to lower rate of heat production (HP). Single injection of optimal doses of aminophylline (AMPY; 10 and 18.7 mg/kg, i.p.), a phosphodiesterase inhibitor which enhances the intracellular cyclic AMP concentration, significantly increased the rate of HP in old rats to levels beyond the control values observed in young rats. Consequently, cold tolerance of the old rats was significantly improved. This AMPY-improved cold tolerance is apparently not due to increased non-shivering thermogenesis (NST) since AMPY failed to enhance norepinephrine-stimulated NST in the old rats. It is likely that AMPY increased substrate mobilization and/or conversion, thereby circumventing the limiting role of substrate availability for shivering thermogenesis. Thus, the age-dependent decrease in cold tolerance may be due to a reduced capacity for substrate mobilization when challenged by cold.

Aging↗

Structure and expression of two porcine genomic clones encoding class I MHC antigens.

Two nonallelic porcine class I MHC (SLA) genes have been isolated and characterized. Both genes are expressed in mouse L cells, directing the synthesis of class I SLA molecules that carry common monomorphic determinants but are serologically distinct. The corresponding DNA sequences have been determined. The organization of both of these genes is similar to that of other class I genes: a leader exon, three exons encoding extracellular domains, a transmembrane exon, and three intracytoplasmic exons. The two genes are highly homologous in both exon and intron segments, with average homologies of 88% and 80%, respectively. Nucleotide changes in exon 2 are clustered, whereas those in the other exons are dispersed throughout. Comparison of the swine DNA sequences with class I genes from other species reveals a generally high conservation of exons 2, 3, 4, and 6 with lower homology in the remaining protein-encoding domains. Introns are markedly less well conserved, although moderate homology is found between swine and human class I MHC genes in both introns and 3' flanking regions. Taken together with comparisons of the deduced protein sequences, these data indicate an order of swine greater than human greater than rabbit greater than mouse in the relationship of class I genes.

Amino Acid Sequence↗

Effects of fasting and aminophylline on norepinephrine-stimulated non-shivering thermogenesis.

In an attempt to further elucidate the mechanisms of fasting-depressed maximum thermogenesis and cold tolerance, norepinephrine (NE)-stimulated non-shivering thermogenesis (NST) in cold-acclimated rats was used as a functional index of possible alterations in adrenergic efficacy after fasting. Fasting decreased the magnitude of maximum NE-Stimulated NST by 18.2% [6.87 +/- 0.47 Kcal (Kg X 75 X min)-1 well-fed vs. 5.81 +/- 0.39 Kcal (Kg X 75 X min)-1 fasted], but the apparent adrenergic binding affinity was not affected [Ke = 0.43 micrograms NE min-1 well-fed vs. 0.55 micrograms NE min-1 fasted]. Pretreatment with aminophylline [15 mg Kg-1, i.p.], a phosphodiesterase inhibitor, restored the fasting-depressed NE-stimulated NST to the fed level. The results suggest that the depression of maximum thermogenesis after fasting is not due to changes in adrenergic binding characteristics but to alteration in cAMP production/degradation, resulting in decreased substrate mobilization for thermogenesis.

Aminophylline↗

Noncovalently bonded subunits of 22 and 28 kd are rapidly internalized by T cells reacted with anti-Leu-4 antibody.

Using immunofluorescence analysis in a FACS or cytofluorograph, we monitored the density of four different human T cell surface molecules (Leu-1/OKT1, Leu-2/OKT5,8, Leu-3/OKT4, and Leu-4/OKT3) at different intervals of incubation at 37 degrees C with monoclonal antibodies that react with these structures. Leu-1 and Leu-2 are probable human homologues of the murine Lyt-1 and Lyt-2,3 antigens, respectively. Leu-3 is a 55 kd antigen that is restricted to Leu-2- (helper) T cells. Leu-4 is expressed by all peripheral T cells and has at least two components of 22 and 28 kd that have an undefined structural relationship. The ultimate degree of modulation of each antigen varied considerably. Modulation of Leu-4 was particularly striking, because this antigen disappeared completely from the cell membrane within 7 hr of culture with saturating concentrations of alpha Leu-4. After modulation of surface 125I-labeled T cells, Leu-4 was found in the detergent-solubilized cell lysate, but not in the cellfree supernatant, indicating that it was internalized. Our results also indicated that the internalized antigen-antibody complex existed in at least two forms: a) as an antigen-antibody complex having only the lower m.w. (22 kd) component bound to antibody, or b) as free antigen having the 28 kd chain in noncovalent association with the 22 kd moiety. These studies indicate that the Leu-4 structure is composed of at least two distinct chains that are noncovalently associated. The rapid modulation and structural properties of the Leu-4 complex are discussed in the context of its possible functions in T cell immunity.

Antibodies, Monoclonal↗

Elicitation of supramaximal thermogenesis by aminophylline in the rat.

Previous studies in rats indicate that maximal thermogenesis during severe cold exposure is suppressed by overnight fasting. Since fasting depresses sympathetic activity and the activity of adrenergic receptors, both of which affect substrate mobilization in cold, the present study attempted to restore maximal thermogenesis in fasted rats by exogenous sympathomimetics and a hypoxanthine (aminophylline). In overnight-fasted rats, exogenous sympathomimetics had no effect in further enhancing maximal thermogenesis induced by exposure to severe cold (in He-O2 at -10 degrees C), indicating maximization of endogenous sympathetic discharge and saturation of adrenergic receptor binding during severe cold exposure. In contrast, aminophylline (1.25-37.5 mg/kg ip) elicited "supramaximal thermogenesis" beyond control maximums in both fasted (+19.4%) and fed +14.4%) conditions in a dose-dependent manner, resulting in improved cold tolerance and prevention of hypothermia. Since aminophylline acts distally to adrenergic receptors to increase intracellular adenosine 3',5'-cyclic monophosphate concentration, it is possible that such increases could enhance substrate mobilization to support supramaximal thermogenesis in severe cold.

Aminophylline↗

Studies on the regulation of pineal melatonin production in the Richardson's ground squirrel (Spermophilus richardsonii).

The acute exposure of wild-captured Richardson's ground squirrels to fluorescent light (intensity = 370-400 ftc) at 2400h, 4 hours after the onset of darkness, was followed by a slight depression in the activity of pineal N-acetyltransferase (NAT); during the same 60 min period, pineal melatonin levels were not inhibited. Conversely, when laboratory-raised squirrels were either exposed to light at night or kept in their normal period of darkness, pineal NAT activity and melatonin levels differed greatly between the two groups. In darkness both NAT and melatonin rose sharply and remained elevated during most of the night. When animals were exposed to light at night the NAT rhythm was completely suppressed and the rise in melatonin was severely dampened. Finally, the administration of isoproterenol (6 mg/kg) increased otherwise low daytime levels of both NAT activity and melatonin levels in the pineal gland of the ground squirrel.

Animals↗

Modulation of maximum thermogenesis by feeding in the white rat.

The present study investigated the availability of substrates as a limiting factor in acute cold exposure. By use of a self-control experimental design, thermogenesis was measured in rats at -10 degrees C under 21% O2-79% He following different feeding regimes. Overnight fasting resulted in the lowest total heat production (9,949 +/- 189 cal/120 min, mean +/- SE, n = 11), maximum rate of thermogenesis (1,320 +/- 23 cal/15 min), and final body temperature (31.0 +/- 0.3 degrees C). The values were significantly lower than those found after overnight rationing (10,630 +/- 231, 1,386 +/- 29, and 32.8 +/- 0.5, respectively) or ad libitum feeding (10,821 +/- 224, 1,395 +/- 27, and 33.5 +/- 0.3). Rats fasted overnight but fed intragastrically a 5-ml substrate mixture (3 kcal/ml) 60 min prior to cold exposure resulted in the highest values for all parameters (11,553 +/- 207, 1,488 +/- 23, and 33.7 +/- 0.4). The increases were not due to the specific dynamic action of food. Since the levels of maximum thermogenesis and cold tolerance can be modulated by feeding, it is evident that substrate availability limits thermogenesis in severe cold independent of respiratory-cardiovascular functions and cellular oxidative capabilities.

Animals↗