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41.
JE Joseph S Donohoe P Harrison IJ Mackie SJ Machin 《Canadian Metallurgical Quarterly》1998,7(5):333-340
Recent advances in glaucoma genetics hold potential for dramatically changing the clinical care of glaucoma patients. To date, 5 primary open-angle glaucoma genes and 2 congenital glaucoma genes have been mapped. As more glaucoma genes are identified, earlier diagnosis for glaucoma should become more readily available. Progress in molecular genetics holds considerable promise for both current and future therapy of glaucoma. Glaucoma classification will be tailored to each individual based upon that person's family history, i.e. family glaucoma genotype. In the future, the optimum treatment for a specific glaucoma patient might rely on the knowledge of the phenotype of that person's causal gene, without having to resort to 'trial and error'. At this time, glaucoma treatment is restricted to lowering intraocular pressure. In the near future, with the knowledge of the pathophysiology caused by the defective glaucoma gene, more traditional drug treatments may be used to bypass the gene defect. Ultimately, gene therapy would replace the mutant gene with a normal one before visual loss has occurred as has been done with a model for retinitis pigmentosa, the retinal degeneration mouse. 相似文献
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The effects of glyceryl nonivamide (GLNVA) on ionic currents were compared and examined in rat pituitary GH3 cells. Hyperpolarization-activated K+ currents in GH3 cells bathed in high-K+ Ca2+-free external solution were studied to assess effects of GLNVA on the an inwardly rectifying K+ current (I(K(IR))). GLNVA is very potent in blocking I(K(IR)) in a concentration-dependent manner, with a half maximal concentrations of 0.1 microM. The complete block of I(K(IR)) achieved with concentrations > or = 1 microM revealed the presence of a non-inactivating current. We also found that GLNVA at a concentration above 30 microM inhibited L-type voltage-dependent Ca2+ current and two components of K+ outward currents, while GLNVA (< or = 3 microM) did not have any effect on them. This study shows that GLNVA, in addition to retaining the capability of eliciting peptidergic neurons, is a selective block of I(K(IR)) in GH3 cells and will provide a useful tool for characterizing I(K(IR)) and understanding its physiological function. In addition, the carefulness should be taken about the interpretation of GLNVA-mediated responses in vivo or in vitro. 相似文献
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KR Gale DJ Waltisbuhl JM Bowden WK Jorgensen J Matheson IJ East H Zakrzewski G Leatch 《Canadian Metallurgical Quarterly》1998,20(9):441-445
The expression of synaptosomal-associated protein (SNAP-25), neural growth-associated protein (GAP-43) and neural cell adhesion molecule (NCAM) were studied in mouse olfactory cells and axons for 2 weeks following unilateral bulbectomy. The olfactory cells and axons in the control olfactory epithelium were positive for SNAP-25 but levels decreased in the atrophic olfactory epithelium 3 days after bulbectomy. There was no expression of SNAP-25 in the olfactory epithelium on the bulbectomy side 7 days after bulbectomy, indicating that this protein may be a good marker for the degeneration of olfactory cells. The expression of NCAM was still found in the atrophic olfactory epithelium at 7 days after bulbectomy, while the expression of NCAM in the olfactory epithelium of the bulbectomy side was stronger than that on the control side at 14 days after bulbectomy. The expression of GAP-43 in the olfactory axonal bundles of the bulbectomy side at 3 and 4 days after bulbectomy was stronger than that on the control side. These results suggest that upregulation of NCAM may be related to the regeneration of the olfactory cells, with upregulation of GAP-43 probably playing a role in axonal regeneration after bulbectomy. 相似文献
46.
JJ Lee HJ Kim H Kook IJ Chung JS Seo KS Seo TJ Hwang 《Canadian Metallurgical Quarterly》1998,13(4):434-436
Nineteen patients with spina bifida and bilateral dislocation of the hips were studied with a minimal follow-up of 10 years. The average age at review was 21 years (range, 10-31). Ten patients had an upper neurologic level (thoracic to L3), and nine had a low lesion (L4 to sacrum). Three patients had no hip surgery. A closed or open reduction was performed in 12 hips, supplemented by one or more surgical procedures. Of these, 10 remained enlocated, and two had redislocated. In all other hips, several surgical procedures were performed, aimed at improvement of hip-flexion deformity or stability. At follow-up, one patient had occasional pain in one hip, which was dysplastic. Of the 10 patients with a high lesion, only two were walkers, but both had bilateral dislocation of the hips at follow-up. In contrast, all nine patients were walkers, but four of these had bilateral dislocation at follow-up. We found that a level pelvis and good range of motion of the hips are more important for ambulation than is reduction of bilateral hip dislocation. 相似文献
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EH Birnbaum L Stamm JF Rafferty RD Fry IJ Kodner JW Fleshman 《Canadian Metallurgical Quarterly》1996,39(11):1215-1221
PURPOSE: This study was undertaken to document the effect of pudendal nerve function on anal incontinence after repair of rectal prolapse. METHODS: Patients with full rectal prolapse (n = 24) were prospectively evaluated by anal manometry and pudendal nerve terminal motor latency (PNTML) before and after surgical correction of rectal prolapse (low anterior resection (LAR; n = 13) and retrorectal sacral fixation (RSF; n = 11)). RESULTS: Prolapse was corrected in all patients; there were no recurrences during a mean 25-month follow-up. Postoperative PNTML was prolonged bilaterally (> 2.2 ms) in six patients (3 LAR; 3 RSF); five patients were incontinent (83 percent). PNTML was prolonged unilaterally in eight patients (4 LAR; 4 RSF); three patients were incontinent (38 percent). PNTML was normal in five patients (3 LAR; 2 RSF); one was incontinent (20 percent). Postoperative squeeze pressures were significantly higher for patients with normal PNTML than for those with bilateral abnormal PNTML (145 vs. 66.5 mmHg; P = 0.0151). Patients with unilateral abnormal PNTML had higher postoperative squeeze pressures than those with bilateral abnormal PNTML, but the difference was not significant (94.8 vs. 66.5 mmHg; P = 0.3182). The surgical procedure did not affect postoperative sphincter function or PNTML. CONCLUSION: Injury to the pudendal nerve contributes to postoperative incontinence after repair of rectal prolapse. Status of anal continence after surgical correction of rectal prolapse can be predicted by postoperative measurement of PNTML. 相似文献
49.
JD Cogan W Wu JA Phillips IJ Arnhold A Agapito OV Fofanova MG Osorio I Bircan A Moreno BB Mendonca 《Canadian Metallurgical Quarterly》1998,83(9):3346-3349
Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation. 相似文献
50.
DR Bielenberg CD Bucana R Sanchez CK Donawho ML Kripke IJ Fidler 《Canadian Metallurgical Quarterly》1998,111(5):864-872
We determined whether cutaneous angiogenesis induced by exposure of mice to ultraviolet-B (UVB) radiation is associated with an imbalance between positive and negative angiogenesis-regulating molecules. Unshaved C3H/HeN mice were exposed to a single dose (15 kJ per m2) of UVB. At various times, the mice were killed, and their external ears were processed for routine histology and immunohistochemistry. Antibodies against proliferating cell nuclear antigen and bromodeoxyuridine identified dividing cells. Antibodies against CD31/ PECAM-1 identified endothelial cells, and antibodies against basic fibroblast growth factor (bFGF), vascular endothelial growth factor/vascular permeability factor, and interferon-beta (IFN-beta) identified angiogenesis-regulating molecules. Epidermal hyperplasia was documented by 48 h and reached a maximum on day 7 after exposure to UVB. The expression of bFGF increased by 24 h, whereas the expression of IFN-beta decreased by 72 h after exposure to UVB. The expression of vascular endothelial growth factor/vascular permeability factor increased slightly after irradiation. The altered balance between bFGF and IFN-beta was associated with increased endothelial cell proliferation (bromodeoxyuridine + CD31 + cells) within existing blood vessels, leading to telangiectasia and new blood vessels. UV-induced epidermal hyperplasia and cutaneous angiogenesis were highest in IFN-alpha/beta receptor knockout mice. These results demonstrate that in response to UVB radiation, dividing keratinocytes produce a positive angiogenic molecule (bFGF) but not a negative angiogenic molecule (IFN-beta), and that this altered balance is associated with enhanced cutaneous angiogenesis. 相似文献