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151.
152.
While loss-of-function mutations in Gsalpha are invariably associated with the short stature and brachydactyly of Albright hereditary osteodystrophy (AHO), the association with hormone resistance (to parathyroid hormone and thyrotropin) typical of pseudohypoparathyroidism type Ia (PHP-Ia) is much more variable. Observational studies and DNA polymorphism analysis suggest that maternal transmission of the Gsalpha mutation may be required for full expression of clinical hormone resistance. To test this hypothesis, we studied transmission of a frameshift mutation in Gsalpha through three generations of a pedigree affected by AHO and PHP-Ia. While all family members carrying this loss-of-function mutation in one Gsalpha allele had AHO, neither the presence of the mutation nor the degree of reduction of erythrocyte Gsalpha bioactivity allowed prediction of phenotype (AHO alone versus AHO and PHP-Ia). Paternal transmission of the mutation (from the patriarch of the first generation to three members of the second generation) was not associated with concurrent PHP-Ia, but maternal transmission (from two women in the second generation to four children in the third generation) was invariably associated with PHP-Ia. No expansion of an upstream short CCG nucleotide repeat region was detected, nor was there evidence of uniparental disomy by polymorphism analysis. This report, the first to document the effects across three generations of both paternal and maternal transmission of a specific Gsalpha mutation, strongly supports the hypothesis that a maternal factor determines full expression of Gsalpha dysfunction as PHP-Ia. 相似文献
153.
Elicitins are 10-kDa proteins secreted by Phytophthora and Pythium fungi that elicit a hypersensitive-like necrotic reaction, leading to resistance against fungal and bacterial plant pathogens. Induction of necrosis and resistance were previously shown to be borne by different sites of the molecule. Furthermore, sequence comparison indicated several potential residues necessary for necrosis. The role of one of these residues was previously evidenced with site-directed mutagenesis. In order to locate other necrosis-determining sites and reveal the defense-eliciting sites, we synthesized a series of synthetic peptides. Tests were performed on two types of transgenic tobacco plants, both transformed with a construction containing the beta-glucuronidase reporter gene, in one case controlled by the promoter of the multiple stimulus response gene str 246C and in the other by the promoter of the pathogenesis-related gene PR1a. We report that only certain peptides were found to be active. Whereas PR1a induction was consistently correlated with induction of necrosis, four peptides were observed to induce only str 246C expression without necrosis, which led to differentiate the defense-eliciting sites from the necrotic sites. From the structure-function relationship thus obtained, two different defense pathways were inferred to be independently induced by elicitins. 相似文献
154.
SJ Ander LM Blomkvist JC M?lne KJ Johansson SP Smeds 《Canadian Metallurgical Quarterly》1997,20(11):640-647
The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands. 相似文献
155.
M Kanayama BW Cunningham JC Weis LM Parker K Kaneda PC McAfee 《Canadian Metallurgical Quarterly》1997,79(11):1710-1720
We investigated the temporal relationship among the biomechanical, radiographic, and histological properties of a posterolateral spinal fusion mass to elucidate the changes in load-sharing of the spinal instrumentation and that of the fusion mass throughout the healing process. Destabilization of the posterior spinal column and transpedicular screw fixation at the segments between the third and fourth and the fifth and sixth lumbar vertebrae was performed in twenty-four sheep. A posterolateral spinal arthrodesis with use of autologous corticocancellous bone graft was done randomly at one of the two segments; the other segment (without bone graft) served as the instrumented control. Six animals each were killed at four, eight, twelve, and sixteen weeks postoperatively. Biomechanical testing showed that the posterolateral fusion mass had increased mechanical stiffness after the fourth week. The strain on the hardware, measured with use of rods instrumented with strain-gauges, decreased significantly (p < 0.01) beginning at eight weeks. Radiographically, three independent observations of each of the six animals at each time-period showed that, although all of the fusion masses were considered solid unions at sixteen weeks, bridging of trabecular bone was noted during only ten of eighteen observations at twelve weeks, three of eighteen observations at eight weeks, and none of eighteen observations at four weeks. Computerized tomography and histomorphometric analyses demonstrated that mineralization in the fusion mass increased in a linear fashion even after eight weeks. Histologically, the fusion mass consisted predominantly of woven bone at eight weeks; thereafter, it was gradually trabeculated. CLINICAL RELEVANCE: We found a great discrepancy between biomechanical stability and histological maturation of the posterolateral fusion mass. The biomechanical properties of a stable spinal fusion preceded the radiographic appearance of a solid fusion by at least eight weeks, suggesting that immature woven bone provided substantial stiffness to the fusion mass. The spinal instrumentation was subjected predominantly to bending stress rather than to axial stress, and the load-sharing of the spinal instrumentation decreased concurrently with the development of the spinal fusion. 相似文献
156.
JC López Pacios L Parra Muntaner MC Pi?eiro Fernández SC Gómez Cisneros E Sánchez Sánchez JA Rivas Escudero FJ Madrid García J García Alonso 《Canadian Metallurgical Quarterly》1998,51(4):331-333
The occurrence of secondary hypogonadism is a common finding in males who seek help with erectile dysfunction, although the relationship to diminished testosterone is unclear. Two possibilities exist regarding both the genesis and maintenance of the hypogonadotropic hypogonadal state. First, a defect in hypothalamic function, resulting in downregulation as well as in alterations of anterior pituitary function; second, estradiol inhibition of gonadotropin release, both of which result in decreased testosterone production. As testosterone levels decrease and estradiol levels increase, the ratio of free testosterone to estradiol reaches a critical point and the estrogenic gonadotropin suppressive effects predominate. This ratio may signal the biological point of no return and could become one of the criteria for defining the separation of the transitional hypogonadal state from the final 'end stage' hypogonadotropic hypogonadal state. As the aging process continues, there is a relative accumulation of fatty tissue, and aromatization accelerates the conversion of testosterone to estradiol. This additional secondary estradiol inhibition results in the maintenance of the testosterone deficient state, and the aging process continues uncontested. 相似文献
157.
Four women aged 30, 29, 52 and 43 years presented with what appeared to be subacute thyroiditis (De Quervain's thyroiditis). This disease is characterized by fatigue, a painful thyroid gland and thyrotoxic manifestations. The diagnosis is further based on a high erythrocyte sedimentation rate and low tracer uptake during thyroid scintigraphy. Only the first patient showed a typical course. In the second and third ones the painful thyroid was associated with nodular enlargement. Fine needle aspiration cytology was at first consistent with subacute thyroiditis but a repeated aspiration showed papillary carcinoma in the second and anaplastic carcinoma in the third patient. In the fourth one, subacute thyroiditis was accompanied by normochromic anaemia, a low serum albumin concentration and liver function disorders. She made a full recovery without treatment. Thyroid malignancies can mimic subacute thyroiditis. Persistent nodular enlargement of the thyroid is suspicious and requires careful investigation. 相似文献
158.
JC Clouse M Rogers RC Reba JL Littlefield PB Schneider M Pollycove 《Canadian Metallurgical Quarterly》1998,39(7):11N-13N, 27N, 30N
159.
Until recently the accepted treatment of choice for severe type-II fibular hemimelia has been Syme's or Boyd's amputation. The alternative of distraction lengthening using the Ilizarov technique is now available. We report three patients (four limbs) with type-II fibular hemimelia who were treated by the Ilizarov technique and followed up for two to six years. Severe progressive procurvatum and valgus deformity of the tibia and valgus deformity and lateral subluxation of the ankle were found in all four limbs. Multiple additional soft-tissue and bony surgery was necessary. In view of these problems we feel that reappraisal of the indications for lengthening in type-II fibular hemimelia is necessary. 相似文献
160.
SA Whitmore C Settasatian J Crawford KM Lower B McCallum R Seshadri CJ Cornelisse EW Moerland AM Cleton-Jansen AJ Tipping CG Mathew M Savnio A Savoia P Verlander AD Auerbach C Van Berkel JC Pronk NA Doggett DF Callen 《Canadian Metallurgical Quarterly》1998,52(3):325-331
BACKGROUND: Both fibroblast-mediated cytokine gene therapy and bone marrow transplantation (BMT) have proven to be efficient protocols for the recovery of bone marrow depression. In this report, the effects of fibroblast-mediated interleukin (IL)-6 gene therapy, in combination with BMT, on the recovery of irradiation-induced bone marrow depression were investigated. METHODS: NIH3T3 fibroblast cells engineered to secrete IL-6 (NIH3T3-IL-6) or NIH3T3 cells transduced with the neomycin gene (NIH3T3-Neo), in combination with 10(7), 10(6), or 10(5) syngeneic bone marrow cells, were implanted into irradiated mice. RESULTS: The platelets and white blood cells in the peripheral blood of the irradiated mice increased greatly 12 days after implantation of NIH3T3-IL-6 cells and BMT, the white blood cell counts were restored to a normal level 32 days after the combined therapy, and the platelet number was obviously higher than that in mice implanted with NIH3T3-Neo and BMT. Twenty and 25 days after the combined therapy, the mice showed accelerated recovery of colony-forming unit (CFU)-granulocyte/macrophages and CFU-megakaryocytes when compared with the mice implanted with NIH3T3-Neo cells and BMT. Ten days after lethal irradiation with gamma rays, the spleens formed more CFU-spleen in mice implanted with NIH3T3-IL-6 cells and BMT than in mice injected with phosphate-buffered saline or NIH3T3-Neo cells. Combined therapy with NIH3T3-IL-6 cell implantation and BMT delayed the survival period of the hematopoietic-depressed mice significantly when compared with therapy with NIH3T3-Neo cell implantation and BMT. CONCLUSIONS: These data demonstrated that the combined therapy of fibroblast-mediated IL-6 gene therapy and BMT could significantly promote the recovery of irradiation-induced hematopoietic depression. 相似文献