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991.
Ohno K; Quiram PA; Milone M; Wang HL; Harper MC; Pruitt JN nd; Brengman JM; Pao L; Fischbeck KH; Crawford TO; Sine SM; Engel AG 《Human molecular genetics》1997,6(5):753-766
We describe and functionally characterize six mutations of the
acetylcholine receptor (AChR) epsilon subunit gene in three congenital
myasthenic syndrome patients. Endplate studies demonstrated severe endplate
AChR deficiency, dispersed endplate regions and well preserved junctional
folds in all three patients. Electrophysiologic studies were consistent
with expression of the fetal gamma-AChR at the endplates in one patient,
prolongation of some channel events in another and gamma- AChR expression
as well as some shorter than normal channel events in still another.
Genetic analysis revealed two recessive and heteroallelic epsilon subunit
gene mutations in each patient. One mutation in each (epsilonC190T [epsilon
R64X], epsilon 127ins5 and epsilon 553del 7) generates a nonsense codon
that predicts truncation of the epsilon subunit in its N-terminal,
extracellular domain; and one mutation in each generates a missense codon
(epsilon R147L, epsilon P245L and epsilon R311W). None of the mutations was
detected in 100 controls. Expression studies in HEK cells indicate that the
three nonsense mutations are null mutations and that surface expression of
AChRs harboring the missense mutations is significantly reduced. Kinetic
analysis of AChRs harboring the missense mutations show that epsilon R147L
is kinetically benign, epsilon P245L prolongs burst open duration 2-fold by
slowing the rate of channel closing and epsilon R311W shortens burst
duration 2-fold by slowing the rate of channel opening and speeding the
rate of ACh dissociation. The modest changes in activation kinetics are
probably overshadowed by reduced expression of the missense mutations. The
consequences of the endplate AChR deficiency are mitigated by persistent
expression of gamma-AChR, changes in the release of transmitter quanta and
appearance of multiple endplate regions on the muscle fiber.
相似文献
992.
Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome 总被引:5,自引:3,他引:5
Dalton CF; Laird SM; Estdale SE; Saravelos HG; Li TC 《Human reproduction (Oxford, England)》1998,13(11):3197-3202
The concentrations of endometrial proteins PP14 and CA-125 were measured in
uterine flushings taken on days LH+10 and LH+12 (10 and 12 days after
luteinizing hormone surge) of the menstrual cycle from 15 normal, fertile
women and 49 women who suffered recurrent miscarriage. The concentration of
PP14 was significantly lower in the flushings from the recurrent
miscarriage patients than in those from fertile controls on both day LH+10
(median: 1300, range: 3-10 300 ng/ml versus median: 13 933, range: 2174-40
404 ng/ml; P < 0.01) and LH+12 (median: 1560, range: 820-12 100 ng/ml
versus median: 14 047, range 1402-62 108 ng/ml; P < 0.05). Similarly
concentrations of CA-125 were significantly lower in flushings from
recurrent miscarriage women compared to controls on both day LH + 10
(median: 1555, range: 47-6710 U/ml versus median: 6385.5, range 2884-27 731
U/ml, P < 0.01) and LH+12 (median: 2892, range: 956-9974 U/ml versus
median: 7127.5, range: 1591-21 343 U/ml; P < 0.05). In contrast there
was no significant difference in the concentration of PP14 in plasma
samples taken on the same days as the flushings from recurrent miscarriage
patients and fertile controls. The concentrations of PP14 in uterine
flushings obtained on day LH + 10 or LH + 12 from recurrent miscarriage
women during a pre-pregnancy investigative cycle were significantly lower
(P < 0.05) in patients who went on to miscarry (median: 1000, range:
9-2900 ng/ml) than those who went on to have a live birth (median: 1440,
range: 4-12 100 ng/ml) during a subsequent pregnancy. In contrast there was
no significant difference in uterine CA-125 or plasma PP14 concentrations
between these two groups of recurrent miscarriage patients. The results
suggest that measurements of uterine PP14 and CA-125 may be useful in the
assessment of endometrial development in recurrent miscarriage patients and
suggest the importance of PP14 in preparing the endometrium for embryo
implantation. In addition pre-pregnancy uterine PP14 measurements may be
useful in predicting subsequent pregnancy outcome.
相似文献
993.
An association study was performed to elucidate the role of the serotonin
transporter (5-HTT) gene as a susceptibility factor for autism as treatment
of patients with antidepressant drugs which selectively target 5-HTT
reduced autistic or concomitant symptoms, such as repetitive behavior and
aggression, and ameliorate language use. Using the
transmission/disequilibrium test (TDT) an analysis was done for a common
polymorphism in the upstream regulatory region (5-HTTLPR), a VNTR in intron
2 of the gene and a haplotype of both loci in 52 trios fulfilling stringent
criteria for autism and an extended group of 65 trios including patients
showing no language delay in their first 3 years of life. A higher
frequency and preferential transmission of the long allele of the 5-HTTLPR
was observed, but the TDT gave a statistically significant value ( P = 0.
032) only for the extended patient group. This result is in contrast to a
recent study by a US group presenting preliminary evidence for preferential
transmission of the short allele of 5-HTTLPR in 86 trios. Both studies
failed to reveal significant linkage disequilibrium between the VNTR in
intron 2 of the gene and autism. In our study haplotype analysis of the
5-HTTLPR and the VNTR in intron 2 supplied evidence for an association of
5-HTT and autism in the stringent ( P = 0.069) and extended patient group (
P = 0.049). Overall, we were not able to replicate the findings of the
first study on 5-HTT and autism and instead observed a tendency for
association of the opposite genetic variant of the gene with the disorder.
The implications for genetic variants of the serotonin transporter in the
etiology of autism and possible subgroups of patients, therefore, needs
clarification in further studies with other and larger patient samples.
相似文献
994.
AD Harries SM Graham MM Weismuller NJM Claessens S Meijnen NJ Hargreaves C Mwansambo PN Kazembe FM Salaniponi 《Malawi medical journal : the journal of Medical Association of Malawi》2005,17(4):119-124
There were 22,982 cases of TB registered in Malawi in 1998, of which 2739 (11.9%) were children. Children accounted for 11.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extrapulmonary TB (EPTB). A significantly higher proportion of TB cases were diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. In 2001, all 44 non-private hospitals in Malawi that register and treat children with tuberculosis (TB) were surveyed to determine actual diagnostic practice. This cross sectional study identified 150 children aged 14 years or below in hospital receiving anti-TB treatment, 98 with pulmonary TB (PTB) and 52 with extrapulmonary TB (EPTB). Median duration of illness was 8 weeks. Most patients had fever, no response to anti-malarial treatment and antibiotics, and 40% had a positive family history of TB. Nearly 45% had weight for age < 60%. Diagnosis was mainly based on clinical features and radiography, with less than 10% having tuberculin skin tests or HIV serology, and very few having other sophisticated investigations. Diagnostic difficulties make it difficult to accurately define the actual burden of childhood TB in Malawi. Diagnostic practices are poor and treatment outcomes unsatisfactory. 相似文献
995.
Atrial fibrillation is the most commonly encountered arrythmia in clinical practice and is associated with significant morbidity
and mortality. Pharmacologic therapy, although useful for rate control, has proven much less effective in the long term maintenance
of sinus rhythm. The utility of implantable atrial defibrillators or pacing to prevent atrial fibrillation remains largely
untested. This article describes four catheter-based therapies for atrial fibrillation: His ablation, atrioventricular nodal
modification, the Maze procedure, and the ablation of pulmonary vein foci which initiate the arrhythmia. Whereas the first
two procedures are largely palliative and recommended for patients with symptomatic, drug-refractory atrial fibrillation,
the latter two offer the potential for a curative intervention. 相似文献
996.
罗格列酮和二甲双胍对初诊2型糖尿病胰岛素抵抗的影响 总被引:1,自引:0,他引:1
目的:观察罗格列酮和二甲双胍对初诊2型糖尿病患者胰岛素抵抗(IR)的影响. 方法:初诊2型糖尿病48例,在饮食和运动治疗基础上随机给予罗格列酮片4 mg 1次/d,即罗格列酮组;给予二甲双胍片500 mg 2次/d,即二甲双胍组,疗程12 wk. 结果:在两组患者取得相当降糖疗效基础上,二甲双胍组和罗格列酮在治疗后空腹和馒头餐后C肽水平均较用药前有明显降低、IR亦有降低、β细胞功能明显改善. 罗格列酮在降低餐后胰岛素、改善IR方面优于二甲双胍,两药物治疗前后血游离脂肪酸水平未见显著差异. 结论:二甲双胍和罗格列酮都可降低IR和改善β细胞功能,在降低IR方面,罗格列酮优于二甲双胍. 相似文献
997.
A potential danger of bedclothes covering the face 总被引:1,自引:0,他引:1
AJ Campbell DPG Bolton SM Williams BJ Taylor 《Acta paediatrica (Oslo, Norway : 1992)》1996,85(3):281-284
Investigations of infants dying unexpectedly have reported up to 28% being found completely under bedding. No detailed physiological studies looking at the possibilities of asphyxia in this situation are available. The aim was to determine the potential for asphyxia under different types and thicknesses of bedding. A mechanical model of a 3-month-old infant's respiratory system was used. Bedding was positioned over the head in a supine position, and inspired carbon dioxide recorded. With a fixed respiratory rate and tidal volume, carbon dioxide accumulation increased with increasing layers of blankets. Up to 8.3% inspired carbon dioxide was recorded with more than four layers of blankets. A cotton sheet between the face and blankets reduced the accumulation by half. An infant found dead under bedding may have been exposed to an asphyxial stress. Suffocation from rebreathing trapped, expired gases can be a cause of death in this situation. 相似文献
998.
D Mahalanabis ASG Faruque SS Hoque SM Faruque 《Acta paediatrica (Oslo, Norway : 1992)》1995,84(3):289-293
In a controlled trial, a hypotonic oral rehydration solution (ORS) (Na+ 67, K+ 20, CP66, citrate 7, glucose 89mmol/1 osmolality 249 mosmol/kg) was compared with a standard WHO-ORS (Na+ 90, K+ 20, Cl- 80, citrate 10, glucose lllmmol/1, osmolality 311 mosmol/kg) in 60 children aged 5-24 months with acute watery diarrhoea. In the hypotonic ORS group, stool frequency, proportion of children who vomited, ORS requirements and purging rate over 24-48 h were reduced by 33% ( p = 0.01), 30% ( p = 0.02), 21% ( p = 0.067) and 21% ( p = 0.03), respectively. The proportion of children who vomited and the purging rate over 48 h were reduced by 23% ( p = 0.03) and 10% ( p = 0.097), respectively. Serum electrolytes after 48 h were comparable. The beneficial effect of hypotonic ORS was most marked in, and largely contributed by, the subgroup negative for rotavirus. 相似文献
999.
SM Pueschel 《Acta paediatrica (Oslo, Norway : 1992)》1995,84(7):823-827
1000.
Objective: To describe the reasons why it is difficult to decide whether to attribute some infant deaths to accidents or to SIDS.
Methodology To extract from infant deaths data in South Australia those where the cause of death is debatable.
Results The risks associated with rocking cradles, bed sharing, bedclothes, couch sleeping, unsafe cots or beds and the prone position are presented.
Conclusions : Uniform worldwide death scene investigations for all infant deaths should help identify unsafe sleeping conditions for infants. 相似文献
Methodology To extract from infant deaths data in South Australia those where the cause of death is debatable.
Results The risks associated with rocking cradles, bed sharing, bedclothes, couch sleeping, unsafe cots or beds and the prone position are presented.
Conclusions : Uniform worldwide death scene investigations for all infant deaths should help identify unsafe sleeping conditions for infants. 相似文献