Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model

Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts.To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17±4 g hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8±2.3 to 45.1±3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7±89.8 to 2,181±135.4 mmHg/s in the contraction rate, and 713±60.2 to 1,364±137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure.     

Genetic mapping of genes regulating the thymus size in back-cross rats between the laboratory BUF/Mna strain and the MITE strain derived from the wild rat, Rattus norvegicus

The thymoma prone BUF/Mna (B) rat is a useful model for Studying the genes responsible for thymus enlargement during the stage of young growth. Among the strains of rats, B rats have the largest thymuses at al stages of life. A locus, Ten-1 , which contributes to thymus enlargement in back-cross (BC) rats between the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the precise location of the bus, (B×(B×MITE)F1) BC rats were generated by crossing the B strain with the Inbred MITE (M) strain, which was established from captured, Japanese wild rats, and were examined by linkage study using polymerase chain reaction with 67 microsatellite markers. Linkages with thymus enlargements were found In genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11 , and D1Mit6 , by X^2-test and Student's t -test, which confirmed the presence of the genetic locus associated with thymus enlargement, Ten-1 , in this region. Paradoxically, a suppressive locus, Tsu-1 , to thymus enlargement was also found on chromosome 3, showing linkages of phenotype of the small thymus with genotypes of SCN2A, CAT D3Mit16 , and D3Mit13 . By analyses of mapmaker/exp and mapmaker/qtl, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1 and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively.     

Latent inhibition of conditioned odor potentiation of startle: a developmental analysis

We conducted a two-part study of age and latent inhibition in the rat. In the first part of the study, rats given odor-shock pairings at 23 or 75 days of age exhibited a potentiated startle response in the presence of the odor the following day. This effect did not occur in rats trained at 16 or 20 days of age. Odor pre-exposure on the day prior to conditioning markedly reduced the odor potentiation of startle effect in 23- and 75-day-old rats but had no effect in 16 and 20-day-olds. In the second part of the study, rats were pre-exposed to the odor at 16 or 20 days of age and then conditioned at 23 days of age. When tested the day after conditioning, these pre-exposed rats exhibited a disruption in the odor potentiation of startle effect. We compare our results with other studies of latent inhibition, and with recent studies on whether conditioned responses are appropriate to the animal's age at training or their age at test.     

银杏叶提取物联合盐酸文拉法辛对抑郁大鼠海马nNOS蛋白表达及NO水平的影响

目的 :探讨抑郁症脑损伤的机制 ,研究银杏叶提取物 (EGb)及合成抗抑郁药盐酸文拉法辛(Venlafaxine)对抑郁大鼠的抗脑损伤及神经元保护作用。方法 :慢性应激建立大鼠抑郁模型。将 84只雄性大鼠分为正常对照组、抑郁模型组和不同治疗组。快速断头法处死 ,取海马后一侧进行免疫组化反应 ,观察海马CA3区nNOS蛋白的表达 ;另一侧检测NO含量 ;同时测定血清中NO含量。结果 :抑郁模型组海马nNOS表达增加 ,海马及血清中NO含量增加 ,P <0 0 1;联合用药组海马nNOS表达下降 ,海马及血清中NO含量减少 ,P <0 0 1。结论 :慢性应激增加海马nNOS表达 ;EGb有减轻神经元损伤 ,保护神经元的作用 ,其与Venlafaxine合用可能会达到对抑郁进行多靶点、多层次的治疗 ,弥补单一用药的不足。     

Effect of adenosine and β-endorphin on contractions of the vas deferens of rats differing in predisposition to ethanol

Laboratory for the Search for and Study of Agents for Prevention and Treatment of Drug Addictions, Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 12, pp. 700–702, December, 1989.     

Analysis of depressed cell-mediated immunity in asbestos workers

To explore the mechanisms of asbestos-related perturbations of the immune system, we evaluated the in vitro cell-mediated immunity of five asymptomatic asbestos workers with hypergammaglobulinemia and decreased T-cell numbers. These results were compared with those in 10 matched controls. Analysis of T-lymphocyte populations revealed decreased absolute numbers of OKT4+ (helper/inducer) T cells in the peripheral blood and phytohemagglutinin (PHA)-stimulated mononuclear cell cultures of the workers. When chrysotile asbestos was added to PHA cultures, expansion of OKT4+ cell populations was disproportionately inhibited in workers' cultures. Furthermore, control proliferative responses to PHA became indistinguishable from initial worker responses. These effects were incompletely explained by the cytotoxic effects of asbestos on cultured lymphocytes. We conclude that both in vivo and in vitro exposure of mononuclear cell populations to asbestos may lead to a diminution of helper-inducer T-cell numbers. In asbestos-exposed individuals, this latter lymphocyte subpopulation appears to be especially sensitive to in vitro asbestos exposure. Although the clinical implications of these findings are unclear, we hypothesize that many of the immunologic abnormalities that occur in asbestos workers could be explained by direct asbestos effects on the OKT4+ immunoregulatory population.     

Adoptive Transfer of Suppression of Autoimmune Response to Rat Male Accessory Glands With Spleen Mononuclear Cells From Antigen-Pretreated Rats

ABSTRACT: The injection of the spleen mononuclear (SpM) cells, obtained from rats rendered unresponsive to autoantigen of rat male accessory glands (RAG) by pretreatment with low doses of purified fraction of RAG (containing the autoantigen), into normal syngeneic recipients markedly prevented the development of delayed type hypersensitivity (DTH) reaction to the autoantigen (suppression of the induction) (p < 0.001). The humoral response was not altered. The control animals were rat receptors of spleen mononuclear cells from donor rats pretreated with rat lung saline extract or 0.15 M NaCl. In contrast, the transference of SpM cells from donor rats pretreated with low doses of autoantigen prior to the immunization to rats previously immunized, did not modify the expression of the immune response against the autoantigen when compared with control rats. The suppression of the induction of DTH response was also obtained when prior to the immunization, the recipients received T-cell-enriched SpM cell population from unresponsive animals (p < 0.001), but not when they were injected with B-cell-enriched SpM cells. These results suggest that suppressor T cells capable of controlling induction of the autoimmune response against RAG autoantigen might be one of the immunoregulatory mechanisms that are activated when soluble autoantigen of RAG enter into circulation.     

Effect of chronic elevation of plasma calcium concentration by PTH or vitamin D3 on blood pressure and hypotensive activity of nifedipine in rats

The influence of a chronically elevated total plasma calcium concentration on blood pressure and heart rate was investigated in conscious normotensive rats. The plasma calcium concentration was elevated by continuous subcutaneous infusion with parathormone (PTH) after parathyreoidectomy, and by oral treatment with vitamin D₃. In both groups an elevated blood pressure was observed at the 1st day of treatment only. Blood pressure was returned to pretreatment values from the second day of treatments onaards. No significant changes in heart rate, due to hypercalcaemia, were observed. In hypercalcaemic rats, the calcium entry inhibitor nifedipine proved more potent in reducing blood pressure than in normocalcaemic control animals. Hydralazine was equipotent in reducing blood pressure in both groups. It is suggested, that the vasoconstrictor effects of a chronically elevated total plasma calcium concentration in conscious rats does not obviously result in a chronically elevated blood pressure, but rather in an enhanced sensitivity of the blood pressure towards calcium entry blockade.     

Uterotrophic effect of a saturated fatty acid 17-ester of estradiol-17beta administered orally to juvenile rats

In comparison to estradiol-17beta, the naturally synthesized estradiol-17beta-17-fatty acid esters are potent estrogens when administered subcutaneously. A lipophilic character of estradiol-17-esters could partially protect them from metabolic inactivation. In order to compare their relative estrogenic potency when administered orally, the uterotrophic response to different dosages (0, 2.5, 25, 250 and 2500 nmol/kg BW/day) of estradiol-17beta and estradiol-17beta-17-stearate was assessed in juvenile Sprague-Dawley female rats. Estrogens were administered by oral gavage once a day for 6 days. On the 7th day uterus and vagina were dissected, weighed, and examined microscopically. At 2.5 and 25 nmol/kg BW/day, no difference was detected in the uterus weight compared to control animals which received the vehicle alone (corn oil). At 250 nmol/kg BW/day, the uterotrophic response was maximal in estradiol-17beta-17-stearate-treated animals (x2.40-2.70), whereas it was moderate in estradiol-17beta-treated rats (x1.86) at the same dosage. This differential weight gain effect of estradiol-17beta-17-stearate was correlated with typical microscopic changes in uterus and vagina. The results are in favour of a stronger estrogenic effect of orally given lipoidal estrogens compared to estradiol-17beta. This could be explained by a slower but sustained absorption of estradiol-17beta released from estradiol-17beta-17-stearate by esterases and/or by a facilitated transfer of esters in the lymphatic circulation.     

Respiratory chemoreflexes and effects of cortical activation state in urethane anesthetized rats

Urethane anesthetized (< 1 .3 g/kg), Sprague-Dawley (SD) rats spontaneously cycled between a cortically desynchronized state (State I) and a cortically synchronized state (State III), which were very similar to awake and slow wave sleep (SWS) states in unanesthetized animals, based on EEG criteria. These low levels of urethane anaesthesia did not cause significant respiratory depression or reductions in sensitivity to hypoxia (10% O2 in nitrogen) or hypercapnia (5% CO2 in air) in rats in either State I or State III. Thus, breathing frequency (fR), tidal volume (VT) and total ventilation (VTOT) all increased on cortical activation in urethane-anaesthetized rats whether breathing air, the hypoxic or the hypercapnic gas mixture, in a manner that was very similar to that observed in unanaesthetized animals. The relative sensitivity to hypoxia was greater in State III than State I, the relative sensitivity to CO2, overall, was equal in both states, State III occurred less often during hypoxia and hypercapnia, and hypoxic, urethane-anaesthetized rats sighed frequently, particularly in State I. This is also similar to the situation seen in unanesthetized rats. Given the similarities seen between urethane anesthetized rats in the present study and literature values for unanesthetized rats, the data suggest that urethane-anaesthetized rats provide a good model system for studying respiratory patterns and chemoreflexes as a function of cortical activation state.