Keratinocyte-derived Cytokines and UVB-Induced Immunosuppression

Ultraviolet radiation (UVB) in sunlight is known to have multiple effects on the immune system. Evidence suggests that UVB-induced immunosuppression is mediated in part by immunosuppressive and immunoregulatory cytokines. Our studies have utilized gene-targeted mutant mice to determine key molecular requirements essential for the development of UVB-induced immunosuppression. Preliminary results from our laboratory suggest that TNF-α plays a regulatory role in contact hypersensitivity, but is not a crucial factor for UVB-induced immunosuppression, and that multiple factors are involved in the induction of UVB mediated immunosuppression.     

镉对小鼠免疫功能的影响

采用单只动物多项免疫功能检测法,观察了小鼠在免疫后,不同时间一次灌胃30mg/kg氯化镉(CdCl_2)及反复多次灌胃不同剂量的CdCl_2,对小鼠免疫器官重量,迟发型变态反应(DTH),抗体形成细胞(IgM-PFC)及抗体滴度的影响。结果表明:反复多次灌胃4.8 mg/kg CdCl_2对小鼠DTH有明显抑制作用,提示CdCl_2对动物免疫功能有一定影响。     

Metastatic Behavior and Tumorigenicity of a Human Melanoma Cell Line (MM-RU) after Injection into Nude Mice

The ability of the human amelanotic melanoma cell line MM-RU to produce experimental metastases and to grow tumors at subcutaneous inoculation sites in 4-week-old nude mice was examined. After i.v. inoculation of 10⁶ cells, all injected mice (n=21) developed consistent numbers of metastatic pulmonary colonies within 32 days. The coefficients of variation for the number of colonies were between 17%–23% in three independent experiments. Survival time after i.v. inoculation was 63 ± 7 days (mean ± SD) (n=20). Within 20 days, subcutaneous inoculation of 5 × 10⁶ cells resulted in tumor growths of 13 ± 3 mm (mean ± SD) at the inoculation sites in all nude mice (n=12). The MM-RU cell line seems to be a simple, fast vehicle for testing the effect of melanoma growth modulators on experimental pulmonary metastases as well as on subcutaneously growing melanoma.     

The human desmin gene: A specific regulatory programme in skeletal muscle both in vitro and in transgenic mice

Desmin synthesis is restricted to cardiac, skeletal and smooth muscles. In several familial myopathies involving fibre disorganization, filamentous aggregation of desmin has been characterized. During the development of the mouse embryo, desmin is one of the first muscle proteins detected in both the heart and the somites. To identify the DNA sequences involved in the regulation of desmin gene expression a 4.5 kb 5′-flanking region of the human desmin gene has been isolated. Different mutants were used to characterize specific enhancers in vitro and in vivo. The results obtained with transgenic mice provide evidence that the 1 kb cis-regulatory sequences, functional in skeletal muscle cells in vitro, confer specific developmental control for skeletal muscles. Furthermore, distinct programmes for cardiac and skeletal muscle-specific expression of the desmin gene are revealed.     

流行性出血热病毒特异性转移因子的研究

对流行性出血热病毒(EHFV)特异性转移因子(EHFV-TF)的制备、特性及在小鼠体内的活性作用进行了研究。其理化性状与普通 TF 非常相似,能激活淋巴细胞的 E 受体(激活率为65.54%),明显提高 Et-RFC 的形成率。E-HFV-TF 还具有特异性抗原依赖活性:①促进 BALB/C 小鼠和 NIH 裸鼠特异性抗体的产生;②促进 LACA 小鼠脾细胞对 EHFV 反应的特异性应答;③促进脾细胞在 EHVF 存在时对 PHA 诱导下的增殖反应(促时率为151.3%)。EHFV—TF可推迟动物感染 HEFV 后的发病期,延长病程和推迟死亡时间;减轻发病动物脑肺充血、出血、水肿现象和肝肾病理损害程度。结果表明 EHFV-TF 不仅具有提高细胞免疫的非特异活性,而且具有对 EHFV 抗原的依赖活性。本研究提示,E-HFV-TF 可用于 EHFV 感染病人的治疗。     

Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice

Summary The putative serotonin (5-HT) receptor antagonist metitepin (0.5 mg/ kg, intraperitoneally) produced hypoalgesia in the increasing temperature hot-plate test and hyperalgesia in the tail-flick test in mice. The effects of metitepin were not altered after depletion of 5-HT by the neurotoxin 5,7-dihydroxytryptamine (5, 7-DHT, 80 g free base, intracerebroventricularly) or the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA, 400 mg/kg for 10 consecutive days). After chronic administration (2 or 5 mg/kg for 18 consecutive days) tolerance to the effect of metitepin (0.5 mg/kg) and cross-tolerance to the antinociceptive effect of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg) was found in the hot-plate test but not in the tail-flick test. It is suggested that metitepin may block descending 5-HT transmission while more complex mechanisms of action are involved at supraspinal level. One possibility is that metitepin exhibits partial agonist properties or, alternatively, that the drug may block 5-HT subsystems which tonically enhance nociception.     

Comparison of genomic damage caused by 5-nitrofurantoin in young and adult mice using the in vivo micronucleus assay

The antibiotic 5-nitrofurantoin (5-NF) has been used widely for the treatment of urosepsis in children during the last 20 years. Recent experimentation suggests the need for reevaluating its genotoxic potential. Because of possible differences in the metabolism and clearance of 5-NF in young and adult animals, we conducted a study to determine whether micronuclei caused by 5-NF were age-related. The in vivo micronucleus (MN) assay was performed on 3- and 8-week-old mice given single intraperitoneal injections of 5, 10, and 50 mg/kg 5-NF. Blood samples from the tail vein were taken before injection (baseline) and at 48, 96, 168, and 336 hr (2 weeks) after the treatment. One thousand reticulocytes were analyzed for micronuclei from each animal. Compared to similar baseline values for young and adult mice, 5-NF caused a significant increase in MN frequency in both age groups. The mean MN frequency in the young animals was higher than in the adult animals for each dose and sampling time. MN frequencies remained significantly elevated in young animals even 2 weeks after exposure to 5-NF. The results of the study confirm the genotoxic potential of 5-NF in young and adult animals, and indicate that young animals are more sensitive to the genotoxic effects of 5-NF than adult mice and that the response in young mice persists for a significantly longer time. These findings may be related to poorly developed mechanisms of xenobiotic detoxification and renal elimination in young animals.     

Increased Hepatic Cholesterol Accumulation in Transgenic Mice Overexpressing Human Secretory Phospholipase A2 Group IIA

It has been demonstrated in transgenic mice that the overexpression of human phospholipase A2 group IIA (sPLA2), an acute-phase reactant, is associated with depressed plasma cholesterol levels, altered lipoprotein compositions, and increased lipid depositions in aortic walls. It was the aim of the present study to investigate whether the reduced plasma cholesterol levels in sPLA2-transgenic mice may be due to an increased transfer of lipids from sPLA2-modified lipoproteins to the liver and/or other nonvascular tissues. Ten sPLA2-transgenic mice and an equal number of nontransgenic littermates were fed a cholesterol-enriched (1%) diet for 13 weeks. After autopsy, cholesterol and triglyceride concentrations were measured in homogenates of liver, spleen, kidney, and myocardial tissues. Compared to the nontransgenic controls, the sPLA2-transgenic mice exhibited significantly lower plasma cholesterol levels, which was due to a reduction in both HDL and beta-lipoprotein (LDL + beta-VLDL) cholesterol. Liver tissues from the transgenic mice were found to contain significantly increased concentrations of free and esterified cholesterol, which was not associated with increased triglyceride concentrations. Spleen, kidney, and heart tissues of the two animal groups showed no significant differences in cholesterol or triglyceride concentrations. The findings suggest that the overexpression of human secretory phospholipase A2 group IIA leads to an enhanced delivery of cholesterol from phospholipolysed lipoproteins to the liver. This mechanism is likely to contribute to the development of hypocholesterolemia observed in patients with inflammatory diseases.     

Maternal effects in infant and adult phenotypes of 5HT1A and 5HT1B receptor knockout mice

The influence of the pre- and postweaning maternal environment on the offspring's phenotype was examined in 5-HT1A and 5-HT1B receptor knockout mice (KO1A and KO1B, respectively). We have previously shown that, when born to and raised by homozygous dams of the same genotype, adult KO1A are more anxious than wild-type (WT) mice, and adult KO1B are hyperactive and slightly less anxious than WT mice. We extend our studies here to the behavioral results of the offspring's own genotype, when the dam's genotype is constant, and the effects of the dam's genotype when the offspring's genotype is constant. In Experiments 1 and 2, KO1A-/- pups produced less ultrasonic vocalizations (USV) than controls in an isolation test on postnatal Day 7 when born to and reared by KO1A dams, either -/- or +/-. Heterozygous F1 pups reared by KO1A-/- dams produced more USV and were less anxious in the plus-maze at 2 to 3 months of age than F1 pups born to and reared by WT dams (Experiment 3). F1 pups reared by KO1B-/- dams produced less USV and were more anxious in the plus-maze than F1 pups reared by WT dams (Experiment 4). The results support a role for maternal effects that may comprise direct effects such as the dam's behavior and nutritional care of the pup, and possibly more complex indirect effects through the establishment of idiosyncratic dam-pup dyadic interactions. We recommend that breeding techniques that rely on same genotype (mutant-mutant or WT-WT) breeding pairs not be used to generate offspring when the focus of research is the study of gene function, but rather when familial effects need to be studied.