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71.
BACKGROUND: The AVPR2 gene encodes the type 2 vasopressin receptor, a member of the vasopressin/oxytocin receptor subfamily of G protein-coupled receptors. Disruption of AVPR2 causes X-linked congenital nephrogenic diabetes insipidus (NDI), yet the functional significance of most gene sequence variations found in association with NDI has not been proven. The large number of naturally occurring AVPR2 mutations constitutes a model system for studying the structure-function relationship of G protein-coupled receptors. This analysis can be aided by examining amino acid sequence variation and conservation among evolutionarily disparate members of the subfamily. METHODS: Twenty-five new NDI patients were evaluated by DNA sequencing for mutations in AVPR2. Receptors encoded by eighteen NDI alleles were tested for physiologic signaling activity in response to varying concentrations of arginine vasopressin (AVP) in a sensitive cell culture assay. Seventeen amino acid sequences from the vasopressin/oxytocin receptor subfamily were aligned and conserved residues were identified and correlated with the locations of NDI associated variations. RESULTS: Twenty-four variant alleles were found among the 25 new patients. Thirteen had no prior family history of expressed NDI. All 18 of the NDI-associated AVPR2 alleles tested for function demonstrated diminished response to stimulation with AVP. Twelve failed to respond at all, whereas six signaled only at high AVP concentrations. Evolutionarily conserved residues clustered in the transmembrane domains and in the first and second extracellular loops, and NDI-associated missense mutations appeared mostly in the conserved domains. CONCLUSIONS: Sporadic cases are frequent and they usually represent the X-linked rather than the autosomal form of NDI. Genetic and functional testing can confirm this in individual cases. Mutations in this study affecting ligand binding domains tend to retain partial signaling in vitro, whereas those that introduce a charged residue in a transmembrane domain are inactive. The minimal partial signaling observed in cultured cells is unlikely to correlate with clinically significant urine concentrating ability. Other AVPR2 mutations with milder effects on receptor function probably exist, but may not be expressed clinically as typical NDI. 相似文献
72.
In Escherichia coli, chi is a recombination hotspot that stimulates RecBCD-dependent exchange at and to one side of itself. chi activity is highest at chi and decreases with distance from chi. The decrease in chi activity may be a simple property of the physical distance over which chi can stimulate recombination. Alternatively, the decay in chi activity with distance may reflect the high likelihood that chi-stimulated recombination occurs in a single chi-proximal act, to the exclusion of additional chi-stimulated exchanges more distal to chi. To test the models, we determined if chi activity decreases as a function of physical distance (i.e., DNA base pairs) or genetic distance (homologous DNA base pairs). Our results indicate that chi activity decays as a function of genetic distance. In addition, we found that the sbcB gene product (exonuclease I, a 3'-->5' ssDNA exonuclease) modulates the distance over which chi can act. In contrast, the recJ gene product (a 5'-->3' ssDNA exonuclease) does not alter the decay of chi activity. 相似文献
73.
RS Veazey DW Horohov JL Krahenbuhl HW Taylor JL Oliver TG Snider 《Canadian Metallurgical Quarterly》1995,47(1-2):79-87
Susceptibility of C57BL/6 (Bcgs) and C3H/HeN (Bcgr) mice to an intraperitoneal infection with Mycobacterium paratuberculosis strain 19698 was compared (by histopathology and the number of mycobacteria isolated from the spleen). Mycobacterial counts from the spleen of Bcgr mice progressively decreased over the course of infection but remained unchanged in Bcgs mice. Granulomatous lesions and acid-fast bacteria were consistently present in the liver and lymph nodes of Bcgs mice, whereas lesions were transient or absent in Bcgr mice. These results indicate that Bcgr mice are inherently resistant to M. paratuberculosis, whereas Bcgs mice are inherently susceptible. These differences may prove useful in elucidating the mechanisms of resistance and susceptibility to paratuberculosis and other mycobacterial infections. 相似文献
74.
75.
RS Wu 《Canadian Metallurgical Quarterly》1998,36(3):111-112
Metastases is an uncommon cause of tumors in the sinonasal region. We report a patient with hepatocellular carcinoma which metastasized to the nasal cavity. 相似文献
76.
77.
A series of experiments was conducted under controlled soil moisture and temperature conditions in a growth chamber to examine the effect of a range of nutrient seed coatings on the emergence to wheat (Triticum aestivum L. cv. Kite) and oats (Avena sativa L. cv. Blackbutt) sown in a coarse sandy loam soil. Final emergence of oats was not reduced by a coating containing 10 kg P ha–1 (as monocalcium phosphate [MCP]) whereas the same coating reduced wheat emergence by 15%. The emergence of both wheat and oats was severely reduced by urea coatings (supplying 10 kg N ha–1) to 33 and 13% respectively; this injury was lessened markedly by the inclusion of phenyl phosphorodiamidate (PPD) in the urea coatings at 1% (w/w) (emergence increased to 66 and 56% respectively).Low soil moisture (67% of field capacity [FC]) resulted in almost no emergence of wheat coated with urea (± bentonites of different pH). In soil at FC, the addition of bentonite of pH 5 (B5) to urea coatings permitted greater emergence (54%) than when bentonite of pH 9 (B9) was added (32%) which, in turn, permitted greater emergence than urea coating alone (10%). When PPD and bentonite (B5 or B9) were combined either singly or together with urea in seed coatings, PPD was more effective than either of the bentonites in reducing injury and masked the slight positive effect of B5.Coatings containing various combinations of N and P sources (at 3.6 and at 8 kg ha–1 respectively) all reduced the emergence of wheat compared to raw seed (91% emergence). When applied alone, MCP was least damaging (74%); the combination of MCP with ammonium sulfate (AS) caused somewhat more injury (68%) whilst combination with calcium nitrate (CN) caused most injury (29%). In contrast, CN alone caused relatively little damage (73%) whilst AS alone was more damaging (50%). There was no significant regression found between percentage emergence and either the calculated partial salt index or the pH of the nutrient coatings. Further work is needed to examine the mechanisms of injury due to nutrient seed coatings so that safe but effective formulations can be developed. 相似文献
78.
79.
RS Hamas 《Canadian Metallurgical Quarterly》1995,19(1):21-25
A prospective study concerning colorectal polyps in symptomatic patients was held at Lima, Perú, an area considered of low incidence for colorectal neoplasia. In 137 patients, 272 polyps were resected by colonoscopic polypectomy or surgery. 55.9% were adenomas, 40.4% non neoplastic polyps and 3.7% polypoid carcinomas. The distribution of polyps, and the incidence of dysplasia and malignant changes in the adenomas, were similar of that reported in areas with high incidence of colorectal cancer. A high proportion of patients with adenomas (21.4% had a synchronous advanced carcinoma, specially if there were multiple adenomas. The figure was lower in patients with only non neoplastic polyps (7.5%). There were no cases of "de novo" carcinoma. This evidence suggest that adenomas play an essential role in colorectal cancer histogenesis, even in areas of low incidence of this neoplasia. 相似文献
80.
MD Dake DC Miller RS Mitchell CP Semba KA Moore T Sakai 《Canadian Metallurgical Quarterly》1998,116(5):689-703; discussion 703-4
OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future. 相似文献