Decreased incidence of renal cell carcinoma in rats with one kidney ingesting N-4-(4'-fluorobiphenyl)acetamide.

Buffalo strain male rats, 12 weeks of age, ingesting 0.04% N-4-(4'-fluorobiphenyl)acetamide in a semisynthetic diet with both kidneys intact were more susceptible to the development of hyperplasia and carcinomas of the kidney than were rats with a uninephrectomy.     

Inbreeding considerations in a REM sleep model for rat swimming activity

Summary Over the past few years, our laboratory group has elaborated a repeated measures rat swimming test. It provides an animal base for showing that the REM sleep mechanism is important to both emotional responsiveness and environmental adaptations. All of that work has been done with Sprague-Dawley rats obtained from a local supplier. Work done with two European rat stocks (by researchers in France and The Netherlands) shows general agreement with our own. In this presentation, we directly compare rats derived from an English vendor's Sprague-Dawley stock with the U.S. based Sprague-Dawley stock which we have been using. We also make strain comparisons via the F344 and the Long Evans strains. Although the literature has numerous examples of swimming test differences between inbred and wild rat stocks, strain difference effects have not been reported. We report that there are significant differences attributable to inbred strain but not to vendor on this measure.Supported by NIH/MBRS Grant 08192. Student coworkers who received program support were: D. Gillham, E. Hannas, M. Ochoa, and J. Lopez. N. Phillips made the figure.     

Increased susceptibility of Trypanosoma lewisi infected, or decomplemented rats to Salmonella typhimurium.

Rats infected with Trypanosoma lewisi or decomplemented by injection of cobra venom factor or complement activating factor of trypanosomes were found to be more susceptible to infection with Salmonella typhimurium. Decomplemented rats subsequently infected with T. lewisi developed higher blood parasitemia than did normal T. lewisi infected rats.     

Acid excretion in young and adult Wistar Kyoto and spontaneously hypertensive rats.

Wistar Kyoto rats (WKy), the most widely accepted control for SH rats, show an inability to excrete acid appropriately when compared to another normotensive strain, SD. Coupled with the fact than KWy also develops 'sodium-sensitive' hypertension, this makes them a more complex control than realized. At very young ages (less than 10-week-old), neither SH nor WKy show any deficiency in acid excretion.     

Decreased incidence of renal cell carcinoma in rats with one kidney ingesting N-4-(4′-fluorobiphenyl) acetamide

Summary Buffalo strain male rats, 12 weeks of age, ingesting 0.04% N-4-(4-fluorobiphenyl)acetamide in a semisynthetic diet with both kidneys intact were more susceptible to the development of hyperplasia and carcinomas of the kidney than were rats with a uninephrectomy.     

D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 micrograms of D-ala2-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10(-3) M, 2 microliters), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.     

The special Sm core structure of the U7 snRNP: far-reaching significance of a small nuclear ribonucleoprotein

The polypeptide composition of the U7 small nuclear ribonucleoprotein (snRNP) involved in histone messenger RNA (mRNA) 3' end formation has recently been elucidated. In contrast to spliceosomal snRNPs, which contain a ring-shaped assembly of seven so-called Sm proteins, in the U7 snRNP the Sm proteins D1 and D2 are replaced by U7-specific Sm-like proteins, Lsm10 and Lsm11. This polypeptide composition and the unusual structure of Lsm11, which plays a role in histone RNA processing, represent new themes in the biology of Sm/Lsm proteins. Moreover this structure has important consequences for snRNP assembly that is mediated by two complexes containing the PRMT5 methyltransferase and the SMN (survival of motor neurons) protein, respectively. Finally, the ability to alter this polypeptide composition by a small mutation in U7 snRNA forms the basis for using modified U7 snRNA derivatives to alter specific pre-mRNA splicing events, thereby opening up a new way for antisense gene therapy.     

Forecasting the economic recession in the U.K. 1979-1982: A comparison of model-based ex ante Forecasts

This paper compares the forecasts of recession and recovery made by five non-government U.K. teams modelling the economy (Cambridge Econometrics, the London Business School, the National Institute of Economic and Social Research, the Cambridge Economic Policy Group and the Liverpool Research Group). The paper concentrates on annual ex ante projections as published over the period 1978-1982, i.e. forecasts made, before the event, of the onset, length, depth and character of the economic recession in the U.K. which began in 1979. The comparison is in terms of year by year changes in production, unemployment, prices and other variables. It concludes that no group was systematically better or worse than other groups (confirming U.S. experience) and that the groups tended to perform better in their chosen areas of specialization, e.g. medium-term groups did better at forecasting the medium-term outcome.     

Effect of adrenalectomy on sound-induced seizure susceptibility and intensity in genetically susceptible rats

Summary Neither seizure susceptibility nor intensity was altered by sham-operation or by adrenalectomy in adult rats that are genetically susceptible to sound-induced seizures. Thus, sound-induced seizures in genetically susceptible rats are analogous to those in genetically susceptible mice to the extent that removal of the adrenal glands does not alter established seizure characteristics in either species.     

Increased susceptibility ofTrypanosoma lewisi infected,or decomplemented rats toSalmonella typhimurium

Summary Rats infected withTrypanosoma lewisi or decomplemented by injection of cobra venom factor or complement activating factor of trypanosomes were found to be more susceptible to infection withSalmonella typhimurium. Decomplemented rats subsequently infected withT. lewisi developed higher blood parasitemia than did normalT. lewisi infected rats.This project is supported by the National Research Council of Canada grant A 0068 and a grant from the International Development Research Center.     

解聚复肾宁对糖尿病肾病大鼠TNF—OL、MCP-1的影响

目的观察解聚复肾宁（Jiejufushenning,JJFSN）对糖尿病（Diabetes mellitus,DM）大鼠肾组织肿瘤坏死因子-α（Tumorneerosisfactor-alpha,TNF-α）、单核细胞趋化蛋白-1（Monocyte chemoattractant protein-1,MCP-1）和血清TNF-α的影响,探讨其肾保护作用机制。方法腹腔注射链脲佐菌素（Streptozotocin,STZ）建立SD大鼠DM模型,将成模DM大鼠随机分为3组：DM模型组（B组）、JJFSN组（C组）、厄贝沙坦（Irbesartan）组（D组）,另设正常对照组（A组）。采用相应干预措施处理12周。常规方法测定12周末各组大鼠空腹血糖（FBG）、血尿素氮（BUN）、血肌酐（Scr）、肾重／体重（KW／BW）、24h尿蛋白（24huFro）;放免法测血清TNF-α含量：免疫组织化学方法测肾组织TNF—Ot、MCP-1的表达;PAS染色评估细胞外基质;电镜观察肾组织超微结构改变。结果与A组相比．B组大鼠FBG、BUN、Scr、KW／BW、24huPro及血清TNF-α升高（P〈0．05）,肾组织TNF—Ot、MCP-1表达明显增高（P〈0．05）;肾组织超微结构明显异常;C组和D组上述指标显著改善（P〈0．05）,肾组织超微结构异常改善。结论竹FSN能延缓DM大鼠肾损害进程,其机制可能与抑制TNF-α、MCP-1上调有关。     

皮质发育障碍模型鼠与正常鼠致痫的性别特点

目的 探讨X射线诱导的皮质发育障碍(DCDs)模型鼠与正常对照鼠致痫的性别特点.方法 将8只SD孕鼠完全随机分为正常对照组和实验组,实验组于X线直线加速器照射制作皮质发育障碍模型,正常对照组不做任何处理,仔鼠成年后按性别分成4组.分别给正常对照组雄雌性及实验组雄雌性仔鼠腹腔注射氯化锂-匹洛卡品,观察产生癫痫的潜伏期、注射总剂量、癫痫发生率.结果 腹腔注射氯化锂-匹洛卡品后DCDs雄鼠较雌鼠发生癫痫潜伏期明显缩短(P＜0.01),注射总剂量显著减少(P＜0.01),癫痫发生率高(P＜0.05).正常组雄鼠较雌鼠发生癫痫潜伏期缩短(P＜0.05)、注射总剂量减少(P＜0.05),癫痫发生率未见明显差异.结论 DCDs及正常鼠中雄性鼠较雌性鼠易感性高,更适于造模.     

Acid excretion in young and adult Wistar Kyoto and spontaneously hypertensive rats

Summary Wistar Kyoto rats (WKy), the most widely accepted control for SH rats, show an inability to excrete acid appropriately when compared to another normotensive strain, SD. Coupled with the fact that KWy also develops sodium-sensitive hypertension, this makes them a more complex control than realized. At very young ages (<10-week-old), neither SH nor WKy show any deficiency in acid excretion.Acknowledgments. Supported by AHA grant 76 1019 and NIH grant AM 15458. The excellent secretarial help of Susan Dreux and Betty Mendelson is acknowledged.     

The behavior of the homozygous and heterozygous sub-types of rats which are genetically-selected for diabetes insipidus: A comparison with Long Evans and Wistar stocks

Several aspects of spontaneous and conditioned behavior (food and water intake, locomotion and emotionality, passive and active avoidance acquisition and retention) of standard (albino and pigmented) rats, and rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus, are reviewed. As would be expected, HODI rats have been repeatedly found to consume far more fluid than either HEDI or control rats. Pigmented rats appear to be more active than albinos. HODI rats exhibit less marked emotional responses than do control rats, among which the pigmented ones exhibit the highest emotionality. Light aversion is more evident in albino than in pigmented rats. No differences are found among HEDI, HODI and normal Long Evans rats. It is quite difficult to provide a clear-cut statement concerning inter-strain differences in passive avoidance behavior, possibly because of the variety of techniques employed. In any case, HODI rats do not perform worse than normal controls do. In one-way active avoidance paradigms, pigmented rats perform better than albinos, and the performance of HODI rats does not differ from that of controls. In two-way avoidance paradigms, albinos appear to outperform pigmented rats. Once again, there are no obvious differences between HODI and control animals.In addition to indicating that HODI rats may actually be less emotional than the other groups of rats reviewed here, the studies described once again fail to confirm the previously alleged functions of vasopressin in memory consolidation.     

D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Summary Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 g of D-ala²-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10^–3 M, 2 l), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.supported by the European Training Program in Brain and Behavior Research.     

Sexual maturation in female rats: hereditary, developmental and environmental aspects

Two physiological components of sexual maturation, vaginal opening and first estrus, apparently evolve similarly in Wistar and Sprague-Dawley rats. However, a bimodal distribution in the frequency of the days of vaginal opening is observed within a given strain, which is less related to heredity than to the timing and type of experiment. In addition, when the modulators of sexual maturation are reviewed, it can be observed that sensitivity to external stimuli can vary even within a strain. For a defined set of breeding conditions, one group of rats can be more susceptible to changes in the lighting regimen and not be affected by controlled stressors, while another group responds more to stress and less to light. The reason for susceptibility to one rather than another environmental factor under similar breeding conditions is not understood. In that context, it is difficult to evaluate the role of heredity when we cannot understand the full impact of the environment, not to mention maternal influence in fetal and early life. Using two lines of psychogenetically selected rats, it was possible to show that they had differences in sexual maturation, which strongly suggested a genetic predisposition. Nevertheless, the question arises as to whether the genetic locus directly affects organs implicated in sexual maturation or whether it acts on some unknown factor which only secondarily modifies sexual maturation. In summary, there is more need to understand the role of the environment, including that of the mother early in fetal and neonatal life. It is suggested that the mechanisms underlying organ growth are set for a given species, while developmental and environmental factors fix the timing of vaginal opening and first ovulation. In the rat, there appear to be two times which are preferred for vaginal opening, given the laboratory conditions that have been used in the last 20 or so years: an early period, at 31-35 days, and a late period, at 36-40 days. An explanation for this dichotomy would be that a combination of parameters (not necessarily always the same) is needed for vaginal opening. These parameters oscillate during sexual maturation with different frequencies, which can achieve resonance to lead to vaginal opening and ovulation only during given periods.     

Sexual maturation in female rats: Hereditary,developmental and environmental aspects

Two physiological components of sexual maturation, vaginal opening and first estrus, apparently evolve similarly in Wistar and Sprague-Dawley rats. However, a bimodal distribution in the frequency of the days of vaginal opening is observed within a given strain, which is less related to heredity than to the timing and type of experiment. In addition, when the modulators of sexual maturation are reviewed, it can be observed that sensitivity to external stimuli can vary even within a strain. For a defined set of breeding conditions, one group of rats can be more susceptible to changes in the lighting regimen and not be affected by controlled stressors, while another group responds more to stress and less to light. The reason for susceptibility to one rather than another environmental factor under similar breeding conditions is not understood. In that context, it is difficult to evaluate the role of heredity when we cannot understand the full impact of the environment, not to mention maternal influence in fetal and early life. Using two lines of psychogenetically selected rats, it was possible to show that they had differences in sexual maturation, which strongly suggested a genetic predisposition. Nevertheless, the question arises as to whether the genetic locus directly affects organs implicated in sexual maturation or whether it acts on some unknown factor which only secondarily modifies sexual maturation. In summary, there is more need to understand the role of the environment, including that of the mother early in fetal and neonatal life. It is suggested that the mechanisms underlying organ growth are set for a given species, while developmental and environmental factors fix the timing of vaginal opening and first ovulation. In the rat, there appear to be two times which are preferred for vaginal opening, given the laboratory conditions that have been used in the last 20 or so years: an early period, at 31–35 days, and a late period, at 36–40 days. An explanation for this dichotomy would be that a combination of parameters (not necessarily always the same) is needed for vaginal opening. These parameters oscillate during sexual maturation with different frequencies, which can achieve resonance to lead to vaginal opening and ovulation only during given periods.     

The behavior of the homozygous and heterozygous sub-types of rats which are genetically-selected for diabetes insipidus: a comparison with Long Evans and Wistar stocks

Several aspects of spontaneous and conditioned behavior (food and water intake, locomotion and emotionality, passive and active avoidance acquisition and retention) of standard (albino and pigmented) rats, and rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus, are reviewed. As would be expected, HODI rats have been repeatedly found to consume far more fluid than either HEDI or control rats. Pigmented rats appear to be more active than albinos. HODI rats exhibit less marked emotional responses than do control rats, among which the pigmented ones exhibit the highest emotionality. Light aversion is more evident in albino than in pigmented rats. No differences are found among HEDI, HODI and normal Long Evans rats. It is quite difficult to provide a clear-cut statement concerning inter-strain differences in passive avoidance behavior, possibly because of the variety of techniques employed. In any case, HODI rats do not perform worse than normal controls do. In one-way active avoidance paradigms, pigmented rats perform better than albinos, and the performance of HODI rats does not differ from that of controls. In two-way avoidance paradigms, albinos appear to outperform pigmented rats. Once again, there are no obvious differences between HODI and control animals. In addition to indicating that HODI rats may actually be less emotional than the other groups of rats reviewed here, the studies described once again fail to confirm the previously alleged functions of vasopressin in memory consolidation.     

Metallothionein expression in the central nervous system of multiple sclerosis patients

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show here that, as in EAE, MT-I+II proteins were expressed in brain lesions of MS patients. Cells expressing MT-I+II were mainly astrocytes and activated monocytes/macrophages. Interestingly, the levels of MT-I+II were slightly increased in the inactive MS lesions in comparison with the active lesions, suggesting that MTs may be important in disease remission.     

外源性干细胞因子对糖尿病胃轻瘫大鼠胃动力的影响

目的 探讨外源性干细胞子(Stem cell factor,SCF)对糖尿病胃轻瘫大鼠(diabetic gastroparesis,DGP)胃电及胃阻抗的影响.方法 30只SD雄性大鼠随机分为实验组和对照组,实验组采用一次性腹腔注射链脲佐菌素(streptozotocin,STZ) 50 mg/kg并高糖高脂饲料喂食建立DGP模型;成模后随机分为糖尿病组(DM组,n=8)、糖尿病+外源性干细胞因子治疗组(DM+ SCF组,n=8);DM+ SCF组腹腔注射SCF 0.4 ug/(kg·d),共15天,对照组和DM组每天腹腔注射等量的磷酸盐缓冲液(pH=7.4).阻抗式胃动力系统检测大鼠胃动力和同步胃电,透射电镜观察胃窦平滑肌细胞超微结构的变化.结果 DM组大鼠胃电节律紊乱,胃电主功率百分比较对照组显著降低(P＜0.01);DM组大鼠阻抗主功率百分比明显降低(P＜0.01),阻抗胃动过缓功率百分比明显升高(P＜0.01);DM大鼠予SCF干预后,胃电、胃阻抗主功率百分比均有所改善(p ＜0.01;P＜0.05);DM组大鼠胃窦平滑肌细胞胞核肿胀、肌浆网、内质网扩张,部分细胞胞质内细胞器溶解、消失;DM组大鼠予SCF干预后胃窦平滑肌细胞超微结构改善,电镜下仅见平滑肌细胞胞核轻度肿胀,密斑、密体、肌丝稍减少,余细胞器未见明显异常改变.结论 外源性SCF能显著改善DGP大鼠的胃电,并能部分改善其胃蠕动,其机制与胃窦平滑肌结构的改善有关.