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61.
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
62.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
63.
Rearrangement of Valproate Glucuronide in a Patient with Drug-Associated Hepatobiliary and Renal Dysfunction 总被引:1,自引:1,他引:0
Ronald G. Dickinson Ruth M. Kluck Wayne D. Hooper Marc Patterson John B. Chalk Mervyn J. Eadie 《Epilepsia》1985,26(6):589-593
Formation of beta-glucuronidase-resistant "glucuronides" of valproic acid (VPA) by intramolecular rearrangement of biosynthetic valproate glucuronide in vivo was investigated in a patient diagnosed with VPA-associated hepatobiliary and renal dysfunction. Plasma elimination half-life of VPA following cessation of the drug was 13.9 h. At the time of the toxicity, the concentration of conjugated VPA in plasma was very high (36-54% of nonconjugated VPA levels) relative to that in normal patients (2.9%). The fraction of conjugated VPA resistant to beta-glucuronidase hydrolysis was 0.28-0.47 in plasma and 0.15-0.42 in urine. The corresponding fraction in urine from normal patients receiving VPA therapy was 0.044. The evidence was consistent with retarded elimination of biosynthetic VPA glucuronide caused by renal and hepatobiliary dysfunction. Consequent prolongation of circulation of VPA glucuronide at the slightly alkaline pH of blood would permit extensive intramolecular rearrangement which is known to be pH-, temperature-, and time-dependent. The biological consequences of the presence of such beta-glucuronidase-resistant conjugated VPA in vivo are largely unknown. 相似文献
64.
The complications of extracorporeal shockwave lithotripsy: management and prevention 总被引:1,自引:0,他引:1
M J Coptcoat D R Webb M J Kellett M S Fletcher T A McNicholas I K Dickinson H N Whitfield J E Wickham 《British journal of urology》1986,58(6):578-580
Extracorporeal shockwave lithotripsy has been shown to be a safe and effective method of treating most upper urinary tract stones. Major complications, although few, include haemorrhage, septicaemia, "Steinstrasse" formation and cardiac arrhythmias. The experience from 600 consecutive cases is reviewed and methods of prevention are discussed. 相似文献
65.
S Jenkins C J Dickinson M A Heasman B W Ellis 《British medical journal (Clinical research ed.)》1986,292(6515):254-256
Four physicians comment on an issue paper from the Department of Health and Social Security about provisions of the Data Protection Act that would permit patient access to computerized health records in 1987 unless the Secretary of State rules otherwise. S. Jenkins, a general practitioner, fears that patient access would refocus the record on the doctor's best interests rather than the patient's. C.J. Dickinson, a medical professor, welcomes access as fostering trust. M.A. Heasman, a health administrator, opposes unrestricted access but urges physicians to reveal more to patients. B.W. Ellis, a consultant surgeon, holds that patients have a right to see their records, subject to physician discretion in disclosing information to the patient's general practitioner or other third party. An interprofessional working group's "Statement on subject access to personal health information" rejects unrestricted access lest it inhibit health professionals from recording sensitive data. 相似文献
66.
Improving health care for disabled people in COVID-19 and beyond: Lessons from Australia and England
Anne Kavanagh Helen Dickinson Gemma Carey Gwynnyth Llewellyn Eric Emerson George Disney Chris Hatton 《Disability and health journal》2021,14(2):101050
COVID-19 has exacerbated pre-existing difficulties children and adults with disability face accessing quality health care. Some people with disability are at greater risk of contracting COVID-19 because they require support for personal care and are unable to physically distance, e.g. those living in congregate settings. Additionally, some people with disability have health conditions that put them at higher risk of poor outcomes if they become infected. Despite this, governments have been slow to recognise, and respond to, the unique and diverse health care needs of people with disability during COVID-19. While some countries, including Australia, have improved access to high-quality health care for people with disability others, like England, have failed to support their citizens with disability. In this Commentary we describe the health care responses of England and Australia and make recommendations for rapidly improving health care for people with disability in the pandemic and beyond. 相似文献
67.
68.
Results are presented for the latent heat of ablation of bone using an erbium-YAG laser operating at 2.9m, and a holmium-YAG laser operating at 2.1m. The values are 8.2±1.0 kJ cm–3 and 18±2.0 kJ cm–3, respectively. Secondary damage to surrounding tissue is found to extend approximately 5m with the erbium laser and is greatly increased to 80m with significant charring in the case of holmium. These secondary damage zones are much smaller than those produced by the CO2 laser. 相似文献
69.
Development of sun compensation by honeybees: how partially experienced bees estimate the sun's course
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Dyer FC Dickinson JA 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(10):4471-4474
Honeybees and some other insects, in learning the sun's course, behave as if they can estimate the sun's position at times of day when they have never seen it, but there are competing ideas about the computational mechanisms underlying this ability. In an approach to this problem, we provided incubator-reared bees with opportunities to fly and see the sun only during the late afternoon. Then, on a cloudy day, we allowed bees to fly for the first time during the morning and early afternoon, and we observed how they oriented their waggle dances to indicate their direction of flight relative to the sun's position. The clouds denied the bees a direct view of celestial orientation cues and thus forced them to estimate the sun's position on the basis of their experience on previous evenings. During the test days, experience-restricted bees behaved during the entire morning as if they expected the sun to be in an approximately stationary position about 180 degrees from the average solar azimuth that they had experienced on previous evenings; then from about local noon onward they used the evening azimuth. This pattern suggests that honeybees are innately informed of the general pattern of solar movement, such that they can generate an internal representation that incorporates spatial and temporal features of the sun's course that they have never directly seen. 相似文献
70.
Measuring handicap: the London Handicap Scale, a new outcome measure for chronic disease. 总被引:5,自引:0,他引:5
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OBJECTIVE--To develop a handicap measurement scale in a self completion questionnaire format, with scale weights allowing quantification of handicap at an interval level of measurement. DESIGN--Adaptation of the International Classification of Impairments, Disabilities and handicaps into a practical questionnaire incorporating the dimensions of handicap mobility, occupation, physical independence, social integration, orientation, and economic self sufficiency and scale weights derived from interviews with a general population sample, with the technique of conjoint analysis. SETTING--Two general practices in different areas of London. SUBJECTS--240 adults aged 55-74 years randomly selected from the practices, 101 (42%) of whom agreed to be interviewed, and 79 (78%) of whom completed the exercise. MAIN MEASURES--Rating of severity of handicap associated with 30 hypothetical health scenarios on a visual analogue scale, from which was derived a matrix of scale weights ("part utilities") relating to different levels of disadvantage on each dimension, with a formula for combining them into an overall handicap score. Severity scores measured directly for five scenarios not used to derive the scale weights were compared with those calculated from the formula to validate the model. RESULTS--The part utilities obtained conformed with the expected hierarchy for each dimension, confirming the validity of the method. The measured severities and those calculated from the formula for the five scenarios used to validate the model agreed closely (Pearson's r = 0.98, p = 0.0009; Kendall's tau = 1.00, p = 0.007). CONCLUSIONS--This interval level handicap measurement scale will be useful in assessing both specific therapies and health services, in clinical trials, in analyses of cost effectiveness, and in assessments of quality assurance. 相似文献