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11.
FV Elmslie M Rees MP Williamson M Kerr MJ Kjeldsen KA Pang A Sundqvist ML Friis D Chadwick A Richens A Covanis M Santos A Arzimanoglou CP Panayiotopoulos D Curtis WP Whitehouse RM Gardiner 《Canadian Metallurgical Quarterly》1997,6(8):1329-1334
The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied. 相似文献
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Advances in genetic engineering and expression systems have led to a rapid progress in the development of immunoglobulins fused to other proteins. These 'antibody fusion proteins' have novel properties and include antibodies fused to the cytokine interleukin-2. In the present review we describe strategies for construction of these antibody-interleukin-2 fusion proteins and discuss their in vitro and in vivo properties. Antibody-interleukin-2 fusion proteins retain both antibody associated functions such as antigen binding, complement activation and Fc gamma receptor binding as well as interleukin-2 associated functions such as the stimulation of proliferation of CTLL2 cells. In vivo, they produce strong potentiation of the host immune response against any associated antigen. In addition, these novel molecules are able to target tumor cells and produce a specific and effective T cell response capable of eliminating the tumor. These properties suggest that antibody-interleukin-2 fusion proteins will be useful in the diagnosis and/or treatment of human cancer as well as in the potentiation of human response against any associated antigen. 相似文献
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Minimum onset latency (Lmin) of single- and multiple-unit responses were mapped in the primary auditory cortex (AI) of barbiturate-anesthetized cats. Contralateral Lmin for multiple units was non-homogeneously distributed along the dorso-ventral/isofrequency axis of the AI. Responses with shorter latencies were more often located in the central, more sharply tuned region while longer latencies were more frequently encountered in the dorsal and ventral portions of the AI. For single units, a large scatter of Lmin values was found throughout the extent of the AI including cortical depth. The relationship between Lmin and previously reported spectral, intensity and temporal parameters was analyzed and revealed statistically significant correlations between minimum onset latency and the following response properties in some but not all studied animals: sharpness of tuning of a frequency response area 10 dB above threshold, broadband transient response, strongest response level, monotonicity of rate/level functions, dynamic range, and preferred frequency modulation sweep direction. This analysis suggests that Lmin is determined by several independent factors and that the prediction of Lmin based on relationships with other spectral and temporal response properties is inherently weak. The spatial distribution and the functional relationship between these response parameters may provide an important aspect of the time-based cortical representation of specific features in the animal's natural environment. 相似文献
15.
JA Koutcher AA Alfieri RL Stolfi ML Devitt JR Colofiore LD Nord DS Martin 《Canadian Metallurgical Quarterly》1993,53(15):3518-3523
The combination of N-(phosphonacetyl)-L-aspartate, 6-methylmercaptopurine, and 6-aminonicotinamide has been shown to be an effective antineoplastic regimen and also to enhance the effects of other chemotherapeutic agents. The mechanism of action of this combination of drugs is not known definitively, but one possible mechanism is biochemical modulation of energy metabolism and inhibition of production of tumor ATP. Tumor-bearing mice were treated with N-(phosphonacetyl)-L-aspartate, followed 17 h later by 6-methylmercaptopurine and 6-aminonicotinamide. 31P nuclear magnetic resonance spectroscopic studies demonstrated a significant depletion of high energy phosphates at 10 h post-6-methylmercaptopurine and 6-aminonicotinamide. The addition of radiation at this time was shown to induce a significantly longer tumor growth delay and a greater number of regressions (including durable complete regressions) than either chemotherapy or radiation alone. The combination of chemotherapy and radiation was found to be supra-additive compared to the antineoplastic effects of either modality administered separately, without a measurable increase in host toxicity. 相似文献
16.
J Karjalainen A Kanervo ML V?is?nen B Forsblom E Sarkiala H Jousimies-Somer 《Canadian Metallurgical Quarterly》1993,6(2-3):207-212
A total of 259 Gram-negative Porphyromonas-like rods isolated from subgingival plaque samples of 16 family-owned dogs with naturally occurring periodontitis were characterized phenotypically by biochemical reactions, metabolic end products and enzymatic activities (API-ZYMTM, RoscoTM). Four distinct groups were found. Group A isolates (63) were asaccharolytic, lipase negative, trypsin positive and produced phenylacetic acid (PAA) from peptone-yeast extract glucose broth. Unlike P. gingivalis strains they were catalase positive. Group B isolates (42) differed from those of group A by a positive lipase reaction and from those of group D by failing to ferment sugars. Group C isolates (88) were asaccharolytic and did not produce PAA. They were alpha-fucosidase, N-acetyl-beta-glucosaminidase (beta-NAG) and trypsin negative, resembling P. endodontalis, but unlike human isolates, they were catalase positive. Subgroup C.1 isolates (6) differed from those of parent group C by producing minor amounts of PAA, and subgroup C.2 isolates (12) were beta-NAG positive. Group D isolates (46) were weakly fermentative, lipase, catalase and trypsin positive, and produced PAA. They resembled the B (P.) salivosus type strain which, in our hands, fermented weakly glucose, lactose and mannose. Two isolates could not be assigned to any of the previous groups. 相似文献
17.
With increasing life span of patients with CF, more women with CF are becoming pregnant and others are seeking information about the risks involved during pregnancy and delivery. A striking limitation of the available information is the lack of large prospective studies of pregnant patients with CF matched for age and disease severity compared with their non-pregnant cohorts. A study investigating the effect of pregnancy on morbidity and mortality is being completed by the Cystic Fibrosis Foundation. We recommend that all women with CF be offered contraceptive measures and counseling on the maternal and fetal risks of pregnancy, including the genetic risks for the child. The issue of who will raise the child in the event of subsequent morbidity or maternal mortality should ideally be prospectively discussed. 相似文献
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V Robert F De Giorgi ML Massimino M Cantini T Pozzan 《Canadian Metallurgical Quarterly》1998,273(46):30372-30378
Direct monitoring of the free Ca2+ concentration in the sarcoplasmic reticulum (SR) was carried out in rat skeletal myotubes transfected with a specifically targeted aequorin chimera (srAEQ). Myotubes were also transfected with a chimeric aequorin (erAEQ) that we have demonstrated previously is retained in the endoplasmic reticulum (ER). Immunolocalization analysis showed that although both recombinant proteins are distributed in an endomembrane network identifiable with immature SR, the erAEQ protein was retained also in the perinuclear membrane. The difficulty of measuring [Ca2+] in 100-1000 microM range was overcome with the use of the synthetic coelenterazine analogue, coelenterazine n. We demonstrate that the steady state levels of [Ca2+] measured with srAEQ is around 300 microM, whereas that measured with erAEQ is significantly lower, i.e. around 200 microM. The effects of caffeine, high KCl, and nicotinic receptor stimulation, in the presence or absence of external calcium or after blockade of the Ca-ATPase, were investigated with both chimeras. The kinetics of [Ca2+] changes revealed by the erAEQ were similar, but not identical, neither quantitatively nor qualitatively, to those monitored with the srAEQ, indicating that at this stage of muscle development, differences exist between SR and ER in their mechanisms of Ca2+ handling. The functional implications of these findings are discussed. 相似文献