In vivo primary induction of virus-specific CTL by immunization with 9-mer synthetic peptides.

A primary cytotoxic T lymphocyte (CTL) response in vivo requires antigen presentation by cytosolic processing and can not in general be obtained by vaccination with soluble proteins. In the present work we have found that vaccination of mice with pre-processed synthetic peptides, corresponding to endogenous 9-mers produced in influenza A virus-infected cells, resulted in strong primary CTL responses. The generated CTL efficiently killed virus-infected target cells with preference for viral strains having the identical amino acid sequences to the peptides used for immunization. The optimal conditions for a primary in vivo CTL response was obtained with 100 micrograms peptide dissolved in incomplete Freund's adjuvant and injected s.c. at the base of tail. Spleen cells which had been primed 7-10 days earlier were restimulated for 5 days in vitro, using an optimal low peptide concentration (0.05 microM) and tested against virus-infected and peptide-treated target cells. The peptide-induced CTL were major histocompatibility complex class I restricted and CD8 positive.     

山东省潍坊东部地区精神分裂症1号染色体基因扫描研究

目的对精神分裂症患者及正常对照者的1号染色体进行扫描,查找精神分裂症的关联位点。方法在1号染色体上间隔10cM（厘摩）遗传距离,选择了31个微卫星遗传位点,用DNA混合池的方法对119例精神分裂症患者与119名正常对照者的DNA样本分别混合后进行基因组扫描。经卡方检验分析,对比患者组与对照组的等位基因峰型比率的差异。结果在D1S2878遗传位点患者组与对照组的等位基因频率差异有统计学意义,P〈0.01。结论山东省潍坊东部地区精神分裂症患者群体中存在与1号染色体的关联区域。     

Effects of mutagenized X chromosomes of Drosophila melanogaster on viability and fitness in males

Drosophila melanogaster males were treated with different doses of X-rays or ethyl methanesulfonate (EMS) and mated so that mutagenized X chromosomes could be recovered and tested for lethal mutations and for less drastic mutations affecting viability and other aspects of fitness. The lethals were detected in standard X-linked lethal tests. The less drastic mutations were detected in one generation tests for effects on viability and in multigeneration tests for effects on overall fitness. The Poisson-corrected frequencies of the lethal mutations increased linearly with dose for both X-rays and EMS. Based on the data, 1 Krad X-rays given acutely induces the same number of lethals as 0.55 mM EMS administered by feeding. For some of the X-ray and EMS doses, the mutagenized chromosomes that were nonlethal reduced the viability of their carriers by a small amount, but there was no discernable dose-effect relationship. However in every case where a viability effect was seen, the percentage reduction was less than the corresponding frequency of lethals. All the groups of mutagenized nonlethal chromosomes reduced overall fitness by a significant percentage. Wherever a meaningful comparison was possible, this reduction was 2-3 times the reduction in viability, but, as in the viability data, no dose-effect relationship was discernable.     

Specific absorbed fractions from the image-based VIP-Man body model and EGS4-VLSI Monte Carlo code: internal electron emitters

VIP-Man is a whole-body anatomical model newly developed at Rensselaer from the high-resolution colour images of the National Library of Medicine's Visible Human Project. This paper summarizes the use of VIP-Man and the Monte Carlo method to calculate specific absorbed fractions from internal electron emitters. A specially designed EGS4 user code, named EGS4-VLSI, was developed to use the extremely large number of image data contained in the VIP-Man. Monoenergetic and isotropic electron emitters with energies from 100 keV to 4 MeV are considered to be uniformly distributed in 26 organs. This paper presents, for the first time, results of internal electron exposures based on a realistic whole-body tomographic model. Because VIP-Man has many organs and tissues that were previously not well defined (or not available) in other models, the efforts at Rensselaer and elsewhere bring an unprecedented opportunity to significantly improve the internal dosimetry.     

Decreased accumulation of endogenous brain-derived neurotrophic factor against constricting sciatic nerve ligatures in streptozotocin-diabetic and galactose-fed rats

Anterograde and retrograde trafficking of brain-derived neurotrophic factor (BDNF) was examined in streptozotocin-diabetic and galactose-fed rats by measuring accumulation of endogenous neurotrophin proximal and distal to two constricting sciatic nerve ligatures and by direct injection of radiolabeled neurotrophin into the sciatic nerve. Compared to controls, accumulation of endogenous BDNF proximal and distal to the ligatures as well as basal levels in non-ligated nerve segments were decreased in streptozotocin-diabetic and galactose-fed rats. Neither streptozotocin diabetes nor galactose intoxication affected the amount of 125I-labeled BDNF retrogradely transported to the DRG after injection into the sciatic nerve. These results suggest that reduced anterograde and retrograde accumulations of BDNF in experimental diabetes are not a result of impaired capacity for receptor-mediated transport.     

Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo

We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise. Weak theta-patterned stimulation, which did not produce LTP in control subjects, produced a robust and long-lasting LTP in Runners. LTP induction in both groups was dependent upon the activation of N-methyl-D-aspartate (NMDA) receptors, and could be blocked by the competitive antagonist [+/-]-3-[2-carboxypiperazin-4-yl] propanephosphonic acid. Consistent with these findings, we found that mRNA levels for NR2B subtype of NMDA receptor were increased specifically in the DG of Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF) and glutamate receptor 5 mRNA levels were also significantly elevated in the DG of Runners, but not in other areas of the hippocampus. Thus, alterations in the expression of BDNF, and specific glutamate receptor subtypes, may underlie the ability of exercise to enhance neurogenesis and reduce the threshold for LTP in the DG.     

Behavioral characteristics of a mouse model of cancer pain

Pain is a major symptom in cancer patients, and most cancer patients with advanced or terminal cancers suffer from chronic pain related to treatment failure and/or tumor progression. In the present study, we examined the development of cancer pain in mice. Murine hepatocarcinoma cells, HCa-1, were inoculated unilaterally into the thigh or the dorsum of the foot of male C3H/HeJ mice. Four weeks after inoculation, behavioral signs were observed for mechanical allodynia, cold allodynia, and hyperalgesia using a von Frey filament, acetone, and radiant heat, respectively. Bone invasion by the tumor commenced from 7 days after inoculation of tumor cells and was evident from 14 days after inoculation. Cold allodynia but neither mechanical allodynia nor hyperalgesia was observed in mice that received an inoculation into the thigh. On the contrary, mechanical allodynia and cold allodynia, but not hyperalgesia, were developed in mice with an inoculation into the foot. Sometimes, mirror-image pain was developed in these animals. These results suggest that carcinoma cells injected into the foot of mice may develop severe chronic pain related to cancer. This animal model of pain would be useful to elucidate the mechanisms of cancer pain in humans.     

胃肠道肿瘤中纤维粘连蛋白的分布及其与肿瘤生物学特性的关系

Through immunohistochemical technique, distribution of FN in normal mucosa, benign and malignant tumors of human gastrointestinal tract were studied. In normal and adenoma tissues, FN was found in both basement membrane (BN) and interstitial tissue. While in cancer tissue, there was a consistent decrease of BM FN content around the tumor nests particularly more apparently in cases of invading carcinoma. Statistical analysis showed that the reduction of BM FN was correlated with the degree of tumor dedifferentiation but not with the incidence of regional metastases. No association was noticed between the stroma FN and tumor behaviors. Since small blood vessels were usually delineated clearly by the staining for FN, FN might be considered as a marker in identifying the invasion of blood vessel wall by tumor cells. It is suggested that lack of BM FN in tumor tissues might be mainly due to decrease of FN synthesis by the tumor cells.     

Seroprevalence studies using a recombinant norwalk virus protein enzyme immunoassay

A recombinant Norwalk virus (NV) protein enzyme immunoassay was used to study the age of acquisition of NV IgG in various populations. In London, England, there was little evidence of infection during the first 2 years of life. However, the prevalence of NV IgG rose steadily throughout the period that children attend school, reaching a peak of 70% in the group aged 11–16 years. High levels of maternal antibody were detected in infants aged <3 months. Comparison of the acquisition of antibodies to three strains of human calicivirus in Japanese children in northern Japan indicated that although the majority had experienced infection with strains Japan and UK1 by the age of 12 years, only 22% possessed antibodies to NV. In Australian aborigines NV infection occurs early in life; by the age of 6 years over 90% of children were seropositive. © 1994 Wiley-Liss, Inc.