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51.
Canfield MC; Tamarappoo BK; Moses AM; Verkman AS; Holtzman EJ 《Human molecular genetics》1997,6(11):1865-1871
Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused
most often by mutations in the vasopressin V2 receptor (AVPR2). We studied
a family which included a female patient with NDI with symptoms dating from
infancy. The patient responded to large doses of desmopressin (dDAVP) which
decreased urine volume from 10 to 4 I/day. Neither the parents nor the
three sisters were polyuric. The patient was found to be a compound
heterozygote for two novel recessive point mutations in the aquaporin-2
(AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is
the site for inhibition of water permeation by mercurial compounds and is
located near to the NPA motif conserved in all aquaporins. Osmotic water
permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2
was not increased over water control, while expression of L22V cRNA
increased the Pf to approximately 60% of that for wild-type AQP2.
Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the
function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO
cells showed that the C181W mutant had an endoplasmic reticulum-like
intracellular distribution, whereas L22V and wild-type AQP2 showed endosome
and plasma membrane staining. Water permeability assays showed a high Pf in
cells expressing wild-type and L22V AQP2. This study indicates that AQP2
mutations can confer partially responsive NDI.
相似文献
52.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
53.
Maša Davidović Nadine Zielonke Iris Lansdorp-Vogelaar Nereo Segnan Harry J. de Koning Eveline AM. Heijnsdijk 《Value in health》2021,24(3):353-360
ObjectivesTo quantify the impact of mammography-based screening on the quality of life, disability-adjusted life years (DALYs) averted or quality-adjusted life years (QALYs) gained can be used. We aimed to assess whether the use of DALYs averted or QALYs gained will lead to different cost-effective screening strategies.MethodsUsing the microsimulation model MISCAN, we simulated different breast cancer screening strategies varying in starting age (starting at 45, 47, and 50 years), stopping age (stopping at 69, 72, and 74 years), and frequency (annual [A], biennial [B], combination of both [A + B], and triennial [T]). In total, we defined 24 different breast cancer screening strategies, including no screening as a reference strategy. We calculated incremental cost-effectiveness ratios (ICERs) and compared which strategies were on the efficiency frontiers for DALYs and QALYs.ResultsBreast cancer screening averted between 46.00 and 105.58 DALYs and gained between 28.69 and 64.50 QALYs per 1000 women. For DALYs there were 5 strategies on the efficiency frontier (T50-69, T50-74, T45-74, B45-74, and A45-74). The same strategies plus one (B45-72) were on the efficiency frontier for QALYs.ConclusionsUsing DALYs averted instead of QALYs gained to assess the effects on quality of life from breast cancer screening in the Dutch population yields differences in ICERs, but almost the same strategies were on the efficiency frontiers. Whether the choice in outcome measure leads to a difference in optimal policy depends on the cost-effectiveness threshold. 相似文献
54.
James N. Ingle MD Carl G. Kardinal Vera J. Suman James E. Krook Alan K. Hatfield 《Investigational new drugs》1996,14(2):235-237
Summary Octreotide is a synthetic somatostatin analogue which has shown inhibitory activity against human breast cancer cells in culture. Ten patients with metastatic breast cancer and no prior hormonal therapy exposure received octreotide at 150 g subcutaneously thrice daily. No objective responses were observed and the median time to treatment failure was short at 57 days. 相似文献
55.
SCHOLZ J.; ROEWER N.; RUM U.; SCHMITZ W.; SCHOLZ H.; SCHULTE AM ESCH J. 《British journal of anaesthesia》1991,66(6):692-696
-Adrenoceptor stimulation may induce malignant hyperthermia(MH) in vivo. Consequently, we have investigated the effectsof the -adrenoceptor agonist phenylephrine and, for comparison,the effects of the ß-adrenoceptor agonist isoproterenolon inositol-lipid metabolism of malignant hyperthermia susceptible(MHS) and healthy control (MHN) swine. The experiments wereperformed on electrically stimulated (frequency 0.2 Hz) trabeculaeisolated from the right ventricles of the hearts of MHS andMHN animals. After labelling with [3H] inositol for 6 h, differentinositol phosphates were measured by high pressure liquid chromatography,including inositol 1 - phosphate, inositol 1,4-bisphosphate,inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP3)and inositol 1,3,4,5 - tetrakisphosphate. After stimulationwith isoproterenol, the inositol phosphate content did not increaseor vary between muscle from MHS and MHN animals. In contrast,all inositol phosphates increased after stimulation with phenylephrinein both muscle types, the effects being greater in MHS thanin MHN, especially as regards 1,4,5-IP3 content. As 1,4,5-IP3,a presumed second messenger, has been shown to mobilize intracellularcalcium, it is concluded that an enhanced -adrenergic responseis involved in the development of MH.
*Address for correspondence: Abteilung für Anästhesiologie,Universitäts-Krankenhaus Eppendorf, Martinistrasse52, D-2000Hamburg 20, Germany.
Presented in part at the 1989 Meeting of the European Academyof Anaesthesiology in Bonn. 相似文献
56.
A study undertaken in a randomly selected village with a population of 695, a majority of whom were agriculturalists or laborers living in huts or mud houses. All couples in the reproductive age group (125) were interviewed in their homes, husbands and wives separately. Couples belonged to Hindu, Muslim, and Scheduled Caste groups. Of the 250 respondents, 120 were literate. About 96% were aware that births could be prevented, with vasectomy and tubectomy the best known methods. Nearly all the respondents gave friends and relatives as the source of their information; family planning workers and posters were given as the source by less than 1/2. 86% of thoce aware of contraceptive methods found family planning acceptable, most expressing the idea that a small family was easier to raise. All of the 14% opposed to family planning were Muslims whose opposiition stemmed from their religious beliefs. 44 of the couples had adopted family planning -- 24 husbands having had vasectomies and 20 of the wives tubectomies. The reasons most often given for not accepting family planning were desire for more chidlren and fear of complications. Of the sterilized respondents, a large number of the men complained of side effects, and 5 of the women complained of excessive bleeding. All of those who expressed complaints said they would not recommend the operation. It is concluded that while awareness of family planning is at an acceptable level, the problem is to make family planning itself acceptable. 1 recommendation is that sterilized couples should receive special medical attention to make their experiences more positive. 相似文献
57.
58.
SK Roy AM Tomkins SM Akramuzzaman RH Behrens R Haider D Mahalanabis G Fuchs 《Archives of disease in childhood》1997,77(3):196-200
OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished. 相似文献
59.
This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background. 相似文献
60.
Michael Crump Carol A. Sawka Gerrit DeBoer Roger B. Buchanan James N. Ingle John Forbes J. William Meakin Wendy Shelley Kathleen I. Pritchard 《Breast cancer research and treatment》1997,43(3):201-210
Increased dietary fat intake and rate of breastepithelial cell proliferation have each been associated withthe development of breast cancer. The goal ofthis study was to measure the effect ofa low fat, high carbohydrate diet on therate of breast epithelial cell proliferation in womenat high risk for breast cancer. Women wererecruited from the intervention and control groups ofa randomized low fat dietary intervention trial, breastepithelial cells were obtained by fine needle aspiration,and cell proliferation was assessed in these samplesusing immunofluorescent detection of Ki-67 and PCNA. Theeffects of needle size and study group oncell yield and cytologic features of the cellswere also examined. Fifty three women (20 inthe intervention group and 33 in the controlgroup) underwent the biopsy procedure. Slides from 38subjects were stained for Ki-67 and from 14subjects for PCNA. No cell proliferation (fluorescence) wasdetected for either Ki-67 or PCNA in anyof the slides. Epithelial cell yield and numberof stromal fragments were greater with a largerneedle size. Numbers of stromal fragments and bipolarnaked nuclei were greater in the low fatas compared to the control group but nodifferences in epithelial cell yield were observed betweenthe two groups. This study confirms that fineneedle aspiration biopsy is a feasible method ofobtaining epithelial cells from women without discrete breastmasses, but suggests that cell proliferation cannot beassessed using Ki-67 and PCNA in such samples. 相似文献