Age-Dependent Accumulation of Hybrid Vasopressin-Oxytocin Gene Products but not Hybrid Oxytocin-Vasopressin Products in the Endoplasmic Reticulum of Brattleboro Rats

The age-dependence of the incidence of magnocellular neurosecretory neurons containing abnormal accumulations of peptide in the rough endoplasmic reticulum was examined in homozygous Brattleboro rats and in their wild-type Long Evans counterparts. Neurons in which the immunophenotype of the peptide aggregates indicate that somatic cross-over mutations involving the 5' end of the vasopressin gene and the 3' end of the oxytocin gene have occurred, increased with age in homozygous Brattleboro rats, reaching a maximum of 24 cells per hypothalamus (approximately 0.6% of the vasopressin neurons). The increase occurred in both male and female animals but was significantly greater in females. The average incidence of such cells was 6 times greater in the supraoptic than in the paraventricular nucleus. No such cells could be detected in either nucleus of Long Evans rats despite the evidence for hybrid mRNA in these animals. Moreover, no accumulation of peptide translated from the hybrid mRNAs derived from the 5' end of the oxytocin gene and the 3' end of the vasopressin gene could be detected in either Brattleboro or Long Evans animals. These results strongly suggest that the accumulation of peptide in the rough endoplasmic reticulum of vasopressin neurons in homozygous Brattleboro rats is due to an abnormality other than the somatic crossing-over mutation. A second type of abnormal magnocellular neuron with accumulations of peptide in the rough endoplasmic reticulum, in which the immunophenotype of the peptide reveals products derived only from the oxytocin precursor, was present in both Long Evans and Brattleboro rats, but did not increase with age in Brattleboro rats. The incidence of these cells was similar in the supraoptic and paraventricular nuclei.     

PCR检测角膜内单疱病毒DNA的实验及临床研究

为了探索单疱病毒性角膜炎的发病机制和快速诊断ＨＳＫ。方法应用多聚酶链反应对感染的ＨＳＫ的２０只纯新西兰白兔和６０例ＨＳＫ患者的角膜进行了单疱病毒－１－ＤＮＡ检测。结果急性感染期的５只兔角膜和１２只人角膜均阳性；用稳定期４５ｄ的兔角供体行部分穿透性角膜移植术，术后５０ｄ１０只兔角膜中７只阳性，稳定期６个月－６年的１８只人角膜片，１２只阳性；３０例临床可疑ＨＳＫ角膜刮取物，２６例阳性；５只未感染ＨＳＫ     

Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols.zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence,zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.     

Codon 178 mutation of the human prion protein gene in a German family (Backer family): sequencing data from 72-year-old celloidin-embedded brain tissue

Familial Creutzfeldt-Jakob disease was first described in a family from northern Germany in the 1920s (Backer family). PCR amplification of DNA extracted from brain tissue embedded in celloidin 72 years ago shows a GAC to AAC substitution at codon 178 of the prion protein gene. This mutation is associated with fatal familial insomnia and familial Creutzfeldt-Jakob disease in a number of families of diverse ethnic background.     

Segregation analysis of diastolic blood pressure in a large pedigree

Hypertension, a major risk factor for cardiovascular diseases, is thought to be inherited to some extent. However, the nature of its genetic component remains unresolved. In the present study, data from a single large kindred (the HGAR1 pedigree) were used to search for evidence of single gene and multifactorial effects on diastolic blood pressure. Commingling analyses found that a mixture of three distributions fit the data significantly better than a single normal distribution, suggesting a major effect influencing diastolic blood pressure levels. However, segregation analysis, using regressive models, indicated that the transmission probabilities were not consistent with Mendelian expectations. There was no evidence of either major gene or polygenic effects on diastolic blood pressure levels in this family. © 1993 Wiley-Liss, Inc.     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

A learned odor decreases the number of Fos-immunopositive granule cells in the olfactory bulb of young rats

Olfactory stimulation evokes a column of activity within the olfactory bulb extending from the glomerular layer to the granule cell layer that can be visualized with 2-deoxyglucose autoradiography, optical imaging, Fos protein immunohistochemistry and c-fos mRNA in situ hybridization. The Fos response to odors is typified by the activity of relatively few juxtaglomerular cells, which often occur in foci, and a large number of granule cells extending through much of the bulb. In this study, we characterized the granule cell response to an odor for which young rats had acquired a preference. Fos-like immunoreactive granule cells were quantified by image analysis, and densely stained cells were counted in a region previously shown to be responsive to peppermint odor. We found that odor-trained pups have about half the number of Fos-immunopositive superficial granule cells which respond to a learned odor than do control pups. We then determined whether there was a correlation between the juxtaglomerular cell response and the response of the superficial granule cells deep to those glomerular layer cells. We found a positive correlation between the number of juxtaglomerular cells and the number of granule cells demonstrating Fos immunoreactivity in both control and trained pups, a relationship that changed with early olfactory training.     

In vivo gene transfer: focus on the kidney

Renal gene transfer techniques are being developed as a novelexperimental approach to understand the pathogenesis of renaldisease and to potentially develop new therapeutic tools. Wereview the currently available technology to introduce foreigngenetic material into renal tissue, i.e., retroviral, adenoviral,and liposomal transfer systems with their respective advantagesand caveats. Today, the transfer efficiency of these methodsappears to be sufficiently high to study the effects of transducedgenes on renal function and morphology in rat kidney. This willallow (i) the elucidation of the function of genes on the courseof renal disease in experimental animal models and (ii) themodulation of local expression of endogenous genes which presumptivelycontribute to renal pathology in these models. One strategyto accomplish this aim is the use of recombinant DNA technologyto design antisense DNA constructs or oligonucleotides, whichinterfere with the renal expression of target genes. We willalso discuss some of the shortcomings of the currently usedtechniques with respect to potential therapeutic use of genetransfer systems and gene modulation.