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991.
992.
Y. Z. Ziylan J. M. Lefauconnier G. Bernard J. M. Bourre 《Journal of neurochemistry》1989,52(3):684-689
The effect of dexamethasone administration and withdrawal was studied with respect to blood-brain barrier function. The tracers alpha-[3H]aminoisobutyric acid (AIB) (MW 104) and [14C]sucrose (MW 342), which have a low permeability across the intact endothelium, were simultaneously injected intravenously in rats treated with dexamethasone and placebo-treated control animals or in rats in which dexamethasone treatment was discontinued 3 days before the experiment. Unidirectional transfer constants (Ki) were determined in discrete brain regions. Steroid administration reduced the rate of influx of AIB and sucrose, whereas discontinuation of drug resulted in an increased permeability. These findings suggest that when exposure to glucocorticoids is prolonged, the efficiency of medical treatment of CNS diseases may decrease due to reduction of drug delivery to CNS. Thus, these experimental findings may have particular importance in the clinical setting of drug administration when considering the combination of steroids with other drugs, and may aid in understanding better the pathogenesis of some types of brain edema seen in patients from whom corticosteroid therapy has been withdrawn. 相似文献
993.
M. N. Collinson Andrew M. Fisher Jean Walker Jane Currie Lisa Williams Paul Roberts 《Human genetics》1997,101(2):175-180
We present 33 families in which a pericentric inversion of chromosome 10 is segregating. In addition, we summarise the data
on 32 families in which an apparently identical inv(10) has been reported in the literature. Ascertainment was through prenatal
diagnosis or with a normal phenotype in 21/33 families. In the other 12 families, probands were ascertained through a wide
variety of referral reasons but in all but one case (a stillbirth), studies of the family showed that the reason for referral
was unrelated to the chromosome abnormality. There has been, to our knowledge, no recorded instance of a recombinant chromosome
10 arising from this inversion and no excess of infertility or spontaneous abortion among carriers of either sex. We propose
that inv(10)(p11.2q21.2) can be regarded as a variant analogous to the pericentric inversion of chromosome 2(p11q13). We conclude
that prenatal chromosome analysis is not justified for inv(10) carriers. In addition, family investigation of carrier status
is not warranted in view of the unnecessary concern this may cause parents and other family members.
Received: 7 July 1997 / Accepted: 4 August 1997 相似文献
994.
Shigeaki Nonoyama Mitsunobu Shimadzu Hano Toru Kuniaki Seyama Hiroyuki Nunoi Michael Neubauer Jun-ichi Yata Hans D. Ochs 《Human genetics》1997,99(5):624-627
X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency caused by a defective CD40 ligand. We identified mutations
of the CD40 ligand gene in 13 unrelated Japanese XHIM patients. Of the four patients with missense mutations, one had a mutation
within the transmembrane domain, and the three others had mutations affecting the TNF homology region of the extracellular
domain. Two of the missense mutations resulted in the substitution of amino acids that are highly conserved in TNF family
proteins. Three patients had nonsense mutations, all of which resulted in the truncation of the TNF homology domain of the
CD40 ligand. Three patients had genomic DNA deletions of 2, 3 or 4 nucleotides, respectively. All of the deletions were flanked
by direct repeat sequences, suggesting that these deletions were caused by slipped mispairing. Three patients had mutations
within introns resulting in altered splicing, and multiple splicing products were found in one patient. Thus, each of the
13 Japanese patients had different mutations, 9 of them being novel mutations. These results indicate that mutations in XHIM
are highly heterogeneous, although codon 140 seems to be a hot spot of the CD40 ligand gene since two additional point mutations
were located at Trp 140, bringing the total numbers of mutations affecting codon 140 to six. In one XHIM family with a missense
mutation, prenatal diagnosis was performed by single-strand conformation polymorphism analysis of genomic DNA of a male fetus.
Received: 20 August 1996 相似文献
995.
The Huntington’s disease mutation has been identified as a CAG/polyglutamine repeat expansion in a large gene of unknown
function. In order to develop the transgenic systems necessary to uncover the molecular pathology of this disorder, it is
necessary to be able to manipulate highly expanded CAG repeats in a cloned form. We have identified a patient with an expanded
allele of greater than 170 repeat units and have cloned the mutant allele in the lambda zap vector. The recovery of highly
expanded repeats after clone propagation was more efficient when repeats were maintained as lambda phage clones rather than
as the plasmid counterparts. Manipulation of the repeats as phage clones has enabled us to generate Huntington’s disease transgenic
mice that contain highly expanded (CAG)115–(CAG)150 repeats and that develop a progressive neurological phenotype.
Received: 7 October 1996 / Revised: 5 December 1996 相似文献
996.
M. Hakoda Naoyuki Kamatani Sakura Kurumada Yuko Hirai Kimitaka Sakamoto Hisashi Yamanaka Chihiro Terai Sadao Kashiwazaki 《Human genetics》1997,99(2):164-170
Both germline and somatic mutations are known to affect phenotypes of human cells in vivo. In previous studies, we cloned
mutant peripheral blood T cells from germline heterozygous humans for adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7)
deficiency and found that approximately 1.3 × 10–4 peripheral T cells had undergone in vivo somatic mutations. Loss of heterozygosity (LOH) was the major cause of the mutations
at the APRT locus since approximately 80% of the mutant T cell clones exhibited loss of normal alleles. In the present study,
we identified three heterozygous individuals for APRT deficiency (representing two separate families), in whom none of the
somatic mutant cells exhibited LOH at the APRT locus. The germline mutant APRT alleles of these heterozygotes from two unrelated
families had the same gross DNA abnormalities detectable by Southern blotting. None of the germline mutant APRT alleles so
far reported had such gross DNA abnormalities. The data suggest that the germline mutation unique to these heterozygous individuals
is associated with the abrogation of LOH in somatic cells. The absence of LOH at a different locus has already been reported
in vitro in an established cell line but the present study describes the first such event in vivo in human individuals.
Received: 10 May 1996 相似文献
997.
A. Falconi D. Lorenzo S. Curti F. R. Morales M. Borde 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1997,181(2):143-151
The present study was designed to examine the synaptic events in neurons of the pacemaker nucleus of Gymnotus carapo during the increase in rate of the electric organ discharge following activation of Mauthner cells. Pacemaker and relay cells
were investigated using intracellular recordings which were performed under two different conditions: (1) with the pacemaker
nucleus spontaneously discharging and (2) after its activity was abolished by anesthesia. Mauthner axon activation induced
an increase in the rate of pacemaker cell discharges. This response was accompanied by an increase in the slope of the pacemaker
potential (up to 110%) and a depolarization of these cells. The discharges of relay cells followed one to one those of pacemaker
cells. In contrast to that observed in pacemaker cells, only brief depolarizing antidromic effects could be evoked in relay
cells after Mauthner axon activation. In quiescent pacemaker cells, Mauthner cell activation induced a prolonged (up to 500 ms)
depolarizing potential with an average amplitude of 1.92 ± 0.82 mV; its latency was 4.43 ± 1.14 ms. Our data indicate that,
within the pacemaker nucleus, the population of pacemaker cells is the only target for Mauthner cell-evoked, short-latency
excitatory synaptic actions.
Accepted: 1 March 1997 相似文献
998.
999.
Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats 总被引:3,自引:0,他引:3
L J Porrino M C Ritz N L Goodman L G Sharpe M J Kuhar S R Goldberg 《Life sciences》1989,45(17):1529-1535
The effects of the administration of serotonergic drugs on infusion rates of rats self-administering cocaine and amphetamine on an FR-10 schedule of reinforcement in daily 4 hour sessions were compared. Pretreatment with fluoxetine (2.5, 5, and 10 mg/kg), an inhibitor of serotonin reuptake, significantly decreased rates of responding maintained by amphetamine, but had no effect on responding maintained by cocaine at any of the doses tested. Pretreatment with cinanserin (3, 10, and 17.5 mg/kg), a serotonergic receptor antagonist, decreased rates of amphetamine self-administration at the highest dose tested, and also had no effect on cocaine self-administration. These data suggest a differential sensitivity of cocaine and amphetamine self-administration to pharmacological manipulation of central serotonin systems. They are consistent with biochemical data which demonstrates a negative correlation between the reinforcing potency of amphetamine-like drugs, but not cocaine-like drugs and their potency at serotonin binding sites. 相似文献
1000.
A human gene similar to Drosophila melanogaster peanut maps to the DiGeorge syndrome region of 22q11
Judith M. McKie Helen F. Sutherland Emma Harvey Ung-Jin Kim P. J. Scambler 《Human genetics》1997,101(1):6-12
A Drosophila-related expressed sequence tag (DRES) with sequence similarity to the peanut gene has previously been localized to human chromosome 22q11. We have isolated the cDNA corresponding to this DRES and show that it is a novel member of the family of septin genes, which encode proteins with GTPase activity thought to interact during cytokinesis. The predicted protein has P-loop nucleotide binding and GTPase motifs. The gene, which we call PNUTL1, maps to the region of 22q11.2 frequently deleted in DiGeorge and velo-cardio-facial syndromes and is particularly highly expressed in the brain. The mouse homologue, Pnutl1, maps to MMU16 adding to the growing number of genes from the DiGeorge syndrome region that map to this chromosome. 相似文献