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21.
22.
Although calcium supplements are widely used in the treatment of osteoporosis, their beneficial effect is not conclusively established. We now report some effects of a calcium supplement (1 g/day) given for 6 to 12 weeks to 15 postmenopausal osteoporotic women. The mean fasting urinary hydroxyproline/creatinine ratio decreased from 0.021 +/- 0.002 to 0.015 +/- 0.001 (P less than 0.0025), indicating a significant reduction in bone resorption. The mean plasma alkaline phosphatase fell from 123 +/- 5 U/l to 104 +/- 3.1 U/l (P less than 0.01), probably representing some secondary reduction in bone formation following the inhibition of bone resorption. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis. 相似文献
23.
Fluorine-19 nuclear magnetic resonance study of codon-anticodon interaction in 5-fluorouracil-substituted E. coli transfer RNAs. 总被引:2,自引:2,他引:0
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Codon-anticodon interaction was investigated in fully active 5-fluorouracil-substituted E. coli tRNAVal1 (anticodon FAC) by 19F NMR spectroscopy. Binding of the codon GpUpA results in the upfield shift of a 19F resonance at 3.9 ppm in the central region of the 19F NMR spectrum, whereas trinucleotides not complementary to the anticodon have no effect. The same 19F resonance shifts upfield upon formation of an anticodon-anticodon dimer between the 19F-labeled tRNA and E. coli tRNATyr2 (anticodon QUA). These results permit assignment of the peak at 3.9 ppm to the 5-fluorouracil at position 34 in the anticodon of fluorouracil-substituted tRNAVal1. The methionine codon ApUpG also causes a sequence-specific upfield shift of a peak in the central part of the 19F NMR spectrum of fluorinated E. coli tRNAMetm. However, ApUpG has no effect on the 19F spectrum of 19F-labeled E. coli tRNAMetf, indicating possible conformational differences between the anticodon loop of initiator and chain-elongating methionine tRNAs. 19F NMR experiments detect no binding of CpGpApA to the complementary FpFpCpG (replaces Tp psi pCpG) in the T-loop of 5-fluorouracil-substituted tRNAVal1, in the presence or absence of codon, suggesting that the tertiary interactions between the T- and D-loops are not disrupted by codon-anticodon interactions. 相似文献
24.
Reassembly of lipid-protein complexes of pulmonary surfactant. Proposed mechanism of interaction 总被引:9,自引:0,他引:9
We studied the interaction at 37 degrees C between a major apolipoprotein of pulmonary surfactant and 11 mixtures of lipids. The experiments were carried out in the presence of either 3 mM Ca2+ or 10 mM EDTA. The amount of apolipoprotein associated with lipid was independent of Ca2+. However the binding was sensitive to the percentage of gel-state lipid in the vesicles, and the amount of apolipoprotein in the recombinant lipoprotein complex decreased as the percentage of fully saturated phospholipid was reduced. Maximum association of the apolipoprotein occurred with lipid vesicles containing 85% 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 15% 1,2-dipalmitoyl-sn-glycero-3-phospho-1-glycerol or 1,2-dipalmitoyl-sn-glycerol. Fluorescence measurements on the apolipoprotein indicated that the tryptophan side chains were in a relatively hydrophobic environment, and that the wavelength of maximum fluorescence emission was not changed upon the binding of lipid. The results suggest that the principal mode of interaction between the apolipoprotein and lipids of surfactant is hydrophobic bonding. The most extensive binding occurs with lamellar lipids in a gel that would be expected to have inhomogeneities in packing density due to the presence of acidic phospholipids or other glycerolipids. The role of Ca2+ in this interaction has not been fully determined. Although it is not needed to effect the binding of the lipids and the apolipoprotein, it does influence the physical state of the complex, and possibly the stoichiometry of lipid to protein. Some of the processes mediated by Ca2+ in this interaction may be analogous to those observed in membrane fusion. Thus, Ca2+ probably causes segregation of the lamellar phospholipids into domains, inducing vesicular disruption and fusion. This lipid aggregates about hydrophobic sites on the protein, thereby forming high molecular weight reassembly complexes. 相似文献
25.
26.
This investigation was undertaken to study heat stress and dehydration effects on 1) plasma lactic acid (LA) concentration and 2) plasma LA effect on plasma volume conservation during thermal dehydration. Experiments were performed on conscious nonacclimated and heat-acclimated laboratory rats subjected to various levels of heat stress and/or dehydration (37-42 degrees C with and without drinking water). During the exposures, rectal temperature (Tre), plasma LA pyruvic acids, and hematocrit were measured. From these data, excess LA, indicative of anaerobic metabolism, was calculated. In separate experiments, transvascular protein efflux (half time of Evans blue-labeled albumin) was measured before and after plasma LA elevation, either by LA infusion or thermal dehydration. The results show that elevation of plasma LA was associated with a rise in Tre, with accelerated elevation within a Tre range of 41-42 degrees C. LA concentrations were similar for the same Tre in all experimental groups. In nonacclimated rats, this rise was accompanied by a significant rise in excess LA. In acclimated rats, only a minor rise in excess LA was observed. A positive correlation was found between plasma LA elevation and the increase in plasma protein efflux. It is concluded that there is a temperature threshold for the rise in plasma LA. In nonacclimated rats, local hypoxia may contribute to this rise. The data also suggest that, in nonacclimated rats, lactacidemia accelerates plasma protein and fluid loss, leading to circulatory failure during acute thermal dehydration. 相似文献
27.
We report the sequence of the entire human gene encoding beta-glucocerebrosidase and that of the associated pseudogene. The gene contains 11 exons extending from base pair 355 to base pair 7232 in the overall sequence. The gene promoter contains TATA- and CAT-like boxes upstream of the major 5' end of the glucocerebrosidase RNA. The two TATA boxes lie between nucleotides (-23)-(-27) and (-33)-(-39) and the two possible CAT boxes reside between nucleotides (-90)-(-94) and (-96)-(-99) in relation to the major 5' end of the mRNA. The functionality of the promoter region was monitored by coupling it to the bacterial gene coding for chloramphenicol acetyltransferase (CAT) and assaying the expression of the enzyme in cells transfected with this vector. The glucocerebrosidase promoter not only directs synthesis of the bacterial enzyme but also exhibits the same pattern of tissue-specific expression as that of the endogenous gene. An apparently tightly linked pseudogene is approximately 96% homologous to the functional gene. However, introns 2, 4, 6, and 7 have large "deletions" consisting of Alu sequences 313, 626, 320, and 277 bp in length, respectively. It is entirely possible that the ancestral gene lacks these sequences and that they have been inserted into the introns of the functioning gene. There is also a 55-bp deletion from a part of exon 9 flanked by a short inverted repeat. The sequence data should facilitate development of methods for diagnosis of Gaucher disease at the molecular level. 相似文献
28.
Sera from approximately 30% of patients with systemic lupus erythematosus (SLE) contain high titers of autoantibodies that bind to the 52-kDa Ro/SSA protein. We previously detected polymorphisms in the 52-kDa Ro/SSA gene (SSA1) with restriction enzymes, one of which is strongly associated with the presence of SLE (P < 0.0005) in African Americans. A higher disease frequency and more severe forms of the disease are commonly noted among these female patients. To determine the location and nature of this polymorphism, we obtained two clones that span 8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six exons were identified, and their nucleotide sequences plus adjacent noncoding regions were determined. No differences were found between these exons and the coding region of one of the reported cDNAs. The disease-associated polymorphic site suggested by a restriction enzyme map and confirmed by DNA amplification and nucleotide sequencing was present upstream of exon 1. This polymorphism may be a genetic marker for a disease-related variation in the coding region for the protein or in the upstream regulatory region of this gene. Although this RFLP is present in Japanese, it is not associated with lupus in this race. 相似文献
29.
Prevalence of nine mutations among Jewish and non-Jewish Gaucher disease patients. 总被引:5,自引:1,他引:4
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M Horowitz G Tzuri N Eyal A Berebi E H Kolodny R O Brady N W Barton A Abrahamov A Zimran 《American journal of human genetics》1993,53(4):921-930
The frequency of nine different mutated alleles known to occur in the glucocerebrosidase gene was determined in 247 Gaucher patients, of whom 176 were of Jewish extraction, 2 were Jewish with one converted parent, and 69 were of non-Jewish origin. DNA was prepared from peripheral blood, active glucocerebrosidase sequences were amplified by using the PCR technique, and the mutations were identified by using the allele-specific oligonucleotide hybridization method. The N37OS mutation appeared in 69.77% of the mutated alleles in Jewish patients and in 22.86% of the mutated alleles in non-Jews. The 84GG mutation, which has not been found so far among non-Jewish patients, existed in 10.17% of the disease alleles among Jewish patients. The IVS + 1 mutation constituted 2.26% of the disease alleles among Jewish patients and 1.43% among the non-Jewish patients. RecTL, a complex allele containing four single-base-pair changes, occurred in 2.26% of the alleles in Jewish patients and was found in two (1.43%) of the patients of non-Jewish extraction. Another complex allele, designated "RecNciI" and containing three single-point mutations, appeared in 7.8% of alleles of non-Jewish patients and in only two (0.56%) of the Jewish families. The prevalence of the L444P mutation among non-Jewish Gaucher patients was 31.43%, while its prevalence among Jewish patients was only 4.24%. The prevalence of two other point mutations--D409H and R463C--was 5.00% and 3.57%, respectively, among non-Jewish patients and was not found among the Jewish Gaucher patient population. The prevalence of the R496H mutation, found so far only among Jewish patients, was 1.13%. The results presented demonstrate that seven mutations identify 90.40% of the mutations among Jewish patients and that these seven mutations allow diagnosis of only 73.52% of the non-Jewish patients. Identification of additional mutant alleles will enhance the accuracy of carrier detection. 相似文献
30.