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991.
T Watanabe M Bai CR Lane S Matsumoto K Minamitani M Minagawa H Niimi EM Brown T Yasuda 《Canadian Metallurgical Quarterly》1998,83(7):2497-2502
Activating mutations of the extracellular calcium (Ca2+e)-sensing receptor (CaR) gene, mostly in its extracellular domain, can cause both familial and sporadic hypoparathyroidism. We report a Japanese family with severe hypoparathyroidism with pretreatment serum calcium (Ca) levels of 4.9-5.9 mg/dL. The proband presented with a seizure at 6 days of age. Her older brother and mother, who had also experienced seizures and tetany, respectively, likewise had hypoparathyroidism. A heterozygous missense mutation substituting a cysteine for the phenylalanine normally present at codon 788 (F788C) was identified in the CaR's fifth transmembrane domain and was shown to cosegregate with the disease. The mutation was absent in DNA from 50 control subjects. Analysis of the functional properties of the mutant receptor was carried out in transiently transfected HEK293 cells loaded with fura-2 by assessing Ca2+e-evoked increases in the cytosolic calcium concentration (Ca2+i). There was a leftward shift in the concentration-response curve for the mutant receptor [EC50 (effective concentration of Ca2+e producing half of the maximal Ca2+i response, 2.7 +/- 0.1 vs. 4.1 +/- 0.1 mmol/L for the wild-type receptor]. HEK293 cells cotransfected with both the wild-type and mutant CaRs (to mimic the heterozygous state in affected family members) showed an EC50 (3.0 +/- 0.1 mmol/L) similar to that of the mutant CaR alone. Thus, we confirm that 1) a gain of function mutation in the fifth transmembrane domain of the CaR causes severe familial hypoparathyroidism by rendering the receptor more sensitive than normal to activation by Ca2+e; 2) some patients in the family do not experience seizures despite their severe hypocalcemia; and 3) this condition needs to be differentiated from other causes of hypoparathyroidism. 相似文献
992.
CC Brown ME Piccone PW Mason TS McKenna MJ Grubman 《Canadian Metallurgical Quarterly》1996,70(8):5638-5641
Four calves were experimentally infected via aerosol with foot-and-mouth disease virus. Two were infected with a wild-type virus derived from a full-length infectious clone (A12-IC), and two were infected with a clone-derived virus lacking the leader gene (A12-LLV2), with euthanasia and tissue collection at 24 and 72 h postexposure (hpe). Clinical disease was apparent only in the animal given A12-IC and euthanized at 72 hpe. In situ hybridization revealed that the animal infected with A12-IC and euthanized at 24 hpe had abundant viral nucleic acid in the lung, present in clusters of positive cells in the respiratory bronchiolar epithelium and associated subepithelial regions. At 72 hpe in the A12-IC-infected calf, viral nucleic acid in the lung was present in interstitial areas, and in addition, viral nucleic acid was detectable in epithelial tissues around histologically apparent vesicles. In animals infected with A12-LLV2, viral nucleic acid was detectable in the lung at both 24 and 72 hpe, but staining revealed a more localized distribution with less nucleic acid than was found in animals given A12-IC. Therefore, it appears that after aerosol exposure to A12-IC, early replication is in the region of the lung, with subsequent dissemination to distal sites. In comparison, the A12-LLV2 virus is much less widely disseminated in the lung at 24 hpe, with no lesions or virus detectable in secondary sites at 72 hpe. The greatly reduced pathogenicity of A12-LLV2 may make it an excellent candidate for a modified live viral vaccine. 相似文献
993.
R Wang Y Charoenvit TM Daly CA Long G Corradin SL Hoffman 《Canadian Metallurgical Quarterly》1996,53(2-3):83-93
Most malariologists believe that optimal malaria vaccines will induce protective immune responses against different stages of the parasite's life cycle. A multiple antigen peptide (MAP) vaccine based on the Plasmodium yoelii circumsporozoite protein (PyCSP) protects mice against sporozoite challenge by inducing antibodies that prevent sporozoites from invading hepatocytes. A purified recombinant protein vaccine based on the P. yoelii merozoite surface protein-1 (PyMSP-1) protects mice against challenge with infected erythrocytes, presumably by inducing antibodies against the erythrocytic stage of the parasite. We now report studies designed to determine if the PyMSP-1 vaccine protects against challenge with sporozoites, the stage encountered in the field, and if immunization with a combination of the PyCSP and PyMSP-1 vaccines provides additive or synergistic protection against sporozoite challenge. In two experiments, using TiterMax or Ribi R-700 as adjuvant, 3 of 19 mice immunized with the PyMSP-1 vaccine were completely protected against sporozoite challenge. The remaining mice had significantly delayed onset and lower levels of peak parasitemia than did control mice (11.1 +/- 2.8% vs. 36.7 +/- 1.6% in experiment #2, P < 0.01). Immunization with the combination vaccine reduced by approximately 50% the level of antibodies induced to PyCSP and PyMSP-1, as compared to that induced by the individual components. However, in two experiments, there was evidence of additive protection. Six of 19 (31.6%) immunized with the PyCSP vaccine, 3 of 19 (15.8%) immunized with the PyMSP-1 vaccine, and 10 of 19 (52.6%) immunized with the combination were completely protected against sporozoit challenge. This modest increase in protection in the combination group may be a reflection of additive anti-PyCSP and anti-PyMSP-1 immunity, since mice in the combination group had diminished levels of antibodies to each components. These studies indicate that considerable work may be required to optimize the construction, delivery, and assessment of multi-stage malaria vaccines. 相似文献
994.
995.
For all teens, the process of moving from childhood to adulthood is challenging. For young people with disabilities, transitioning to independence presents even more challenges. Barriers to successful transition for young people with disabilities include low expectations by parents and other significant people in the community, lack of knowledge of existing career and vocational education services, and lack of self-advocacy skills. This article provides an overview of issues related to transitioning to adult independence and offers suggestions for assessment, planning, and intervention that can help nurses be effective partners with families and other caregivers in transition efforts. Nurses caring for children with disabilities can help families see strengths in their children and develop realistic, developmentally-appropriate expectations for skill development, attitudes, and behaviors that will promote self-sufficiency in adulthood. Nurses can help families think about possibilities for independence and refer families to community resources that can help young people with disabilities pursue postsecondary education, obtain and maintain jobs, and live independently. 相似文献
996.
We assessed the importance of flow regime to the success of native and non‐native fish species by analysing winter/spring seining data collected from 1987 to 1997 on the resident fish communities of the lower Tuolumne River, California. The data were analysed using regression models to predict the percentage of non‐native fish at a site. The regression models included various combinations of the variables longitudinal location of the site, mean April/May stream discharge in the year of sampling, and mean April/May stream discharge in the previous year. Comparison of the models indicated that the best model included longitudinal location and stream discharge in the previous year. This model is consistent with the hypothesis that flow in the previous year differentially affects reproductive success of native and non‐native species and thus the resulting community sampled in the following winter/spring. A detrended correspondence analysis of percentage abundance species data identified a co‐occurring group of native species and a co‐occurring group of non‐native species with the non‐native red shiner (Cyprinella lutrensis) grouping separately. The differing reproductive strategies of the species were consistent with the hypothesis concerning spawning success. Our results indicate that flow regime is an important determinant of the reproductive success of native and non‐native fish species in regulated rivers. Manipulations of flow regime are a potentially powerful tool for managing native fish species, but should be considered in combination with other restoration efforts and in the context of ecosystem restoration. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
997.
998.
IE Ehrmann PS Ellis S Mazeyrat S Duthie N Brockdorff MG Mattei MA Gavin NA Affara GM Brown E Simpson MJ Mitchell DM Scott 《Canadian Metallurgical Quarterly》1998,7(11):1725-1737
The Delta Sxrb interval of the mouse Y chromosome is critical for spermatogenesis and expression of the male-specific minor transplantation antigen H-Y. Several genes have been mapped to this interval and each has a homologue on the X chromosome. Four, Zfy1 , Zfy2 , Ube1y and Dffry , are expressed specifically in the testis and their X homologues are not transcribed from the inactive X chromosome. A further two, Smcy and Uty , are ubiquitously expressed and their X homologues escape X-inactivation. Here we report the identification of another gene from this region of the mouse Y chromosome. It encodes the highly conserved eukaryotic translation initiation factor eIF-2gamma. In the mouse this gene is ubiquitously expressed, has an X chromosome homologue which maps close to Dmd and escapes X-inactivation. The coding regions of the X and Y genes show 86% nucleotide identity and encode putative products with 98% amino acid identity. In humans, the eIF-2gamma structural gene is located on the X chromosome at Xp21 and this also escapes X-inactivation. However, there is no evidence of a Y copy of this gene in humans. We have identified autosomal retroposons of eIF-2gamma in both humans and mice and an additional retroposon on the X chromosome in some mouse strains. Ark blot analysis of eutherian and metatherian genomic DNA indicates that X-Y homologues are present in all species tested except simian primates and kangaroo and that retroposons are common to a wide range of mammals. These results shed light on the evolution of X-Y homologous genes. 相似文献
999.
We present a computationally efficient algorithm for highlighting long linear features in images. The algorithm is based on the recursive binary decomposition of the image into subimages that have been line enhanced along different directions. After a number of successive decompositions, the subimages are recombined to yield a line enhanced image. The performance of the algorithm is similar to that of rotating-kernel-type enhancement routines. However, the new algorithm can be executed much faster, making it ideal for use on large noisy images such as those provided by synthetic aperature radar. 相似文献
1000.
VM Hirsch ME Sharkey CR Brown B Brichacek S Goldstein J Wakefield R Byrum WR Elkins BH Hahn JD Lifson M Stevenson 《Canadian Metallurgical Quarterly》1998,4(12):1401-1408
The viral accessory protein Vpx is required for productive in vitro infection of macrophages by simian immunodeficiency virus from sooty mangabey monkeys (SIV(SM)). To evaluate the roles of Vpx and macrophage infection in vivo, we inoculated pigtailed macaques intravenously or intrarectally with the molecularly cloned, macrophage tropic, acutely pathogenic virus SIV(SM) PBj 6.6, or accessory gene deletion mutants (deltaVpr or deltaVpx) of this virus. Both wild-type and SIV(SM) PBj deltaVpx viruses were readily transmitted across the rectal mucosa. A subsequent 'stepwise' process of local amplification of infection and dissemination was observed for wild-type virus, but not for SIV(SM) PBj deltaVpx, which also showed considerable impairment of the overall kinetics and extent of its replication. In animals co-inoculated with equivalent amounts of wild-type and SIV(SM) Pbj deltaVpx intravenously or intrarectally, the deltaVpx mutant was at a strong competitive disadvantage. Vpx-dependent viral amplification at local sites of initial infection, perhaps through a macrophage-dependent mechanism, may be a prerequisite for efficient dissemination of infection and pathogenic consequences after exposure through either mucosal or intravenous routes. 相似文献