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101.
102.
Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q 总被引:5,自引:0,他引:5
Elmslie FV; Rees M; Williamson MP; Kerr M; Kjeldsen MJ; Pang KA; Sundqvist A; Friis ML; Chadwick D; Richens A; Covanis A; Santos M; Arzimanoglou A; Panayiotopoulos CP; Curtis D; Whitehouse WP; Gardiner RM 《Human molecular genetics》1997,6(8):1329-1334
The epilepsies are a group of disorders characterised by recurrent seizures
caused by episodes of abnormal neuronal hyperexcitability involving the
brain. Up to 60 million people are affected worldwide and genetic factors
may contribute to the aetiology in up to 40% of patients. The most common
human genetic epilepsies display a complex pattern of inheritance. These
are categorised as idiopathic in the absence of detectable structural or
metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive
and common variety of familial idiopathic generalised epilepsy (IGE) with a
prevalence of 0.5- 1.0 per 1000 and a ratio of sibling risk to population
prevalence (lambda(s)) of 42. The molecular genetic basis of these familial
idiopathic epilepsies is entirely unknown, but a mutation in the gene
CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine
receptor (nAChR), was recently identified in a rare Mendelian variety of
idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR
subunits were therefore tested for linkage to the JME trait in 34
pedigrees. Significant evidence for linkage with heterogeneity was found to
polymorphic loci encompassing the region in which the gene encoding the
alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at
alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to
genetic susceptibility to JME in a majority of the families studied.
相似文献
103.
Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups 总被引:12,自引:1,他引:12
Marron MP; Raffel LJ; Garchon HJ; Jacob CO; Serrano-Rios M; Martinez Larrad MT; Teng WP; Park Y; Zhang ZX; Goldstein DR; Tao YW; Beaurain G; Bach JF; Huang HS; Luo DF; Zeidler A; Rotter JI; Yang MC; Modilevsky T; Maclaren NK; She JX 《Human molecular genetics》1997,6(8):1275-1282
Linkage disequilibrium (association) analysis was used to evaluate a
candidate region near the CTLA4/CD28 genes using a multi-ethnic collection
of families with one or more children affected by IDDM. In the data set
unique to this study (Spanish, French, Mexican-American, Chinese and
Korean), the transmission/disequilibrium test (TDT) revealed a highly
significant deviation for transmission of alleles at the (AT)n
microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G
polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall
evidence for transmission deviation of the CTLA4 A/G alleles is also highly
significant (P = 0.00005) in the combined data set (669 multiplex and 357
simplex families) from this study and a previous report on families from
USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed
in these data sets. The British, Sardinian and Chinese data sets did not
show any deviation for the A/G polymorphism, while the Caucasian-American
data set showed a weak transmission deviation. Strong deviation for
transmission was seen in the three Mediterranean-European populations
(Italian, Spanish and French) (P = 10(-5)), the Mexican-American population
(P = 0.002) and the Korean population (P = 0.03). These results suggest
that a true IDDM susceptibility locus (designated IDDM12) is located near
CTLA4.
相似文献
104.
Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury 总被引:10,自引:1,他引:9
Objective To analyze the effect and mechanism of hyperbaric oxygen (HBO) treatment for severe brain injury (SBI). Methods Fifty-five patients were divided into a treatment group of 35 patients and a control group of 20 patients. We observed the alterations of clinical, brain electric earth map (BEAM), endothelin (ET) and transcranial ultrasonic Doppler (TCD) findings before and after HBO treatment as well as outcome. Results In the treatment group, Glasgow coma scale, BEAM and outcome improved after HBO treatment; compared with that of the control group, it showed a significant difference. After one course of treatment, treatment group ET was reduced from 91.24±12.18?ng/L to 68.88±14.37?ng/L (P<0.01); in control group, ET was reduced from 90.78±15.71?ng/L to 83.12±12.22?ng/L, with a statistically significant difference (P<0.05). TCD records of MCA mean velocity (Vm) was reduced from 64.2±4.8?cm/s to 51.6±4.2?cm/s (P<0.01), and a decrease in MCA systolic velocity (Vs) and pulse index (PI) values was statistically significant (P<0.01). Conclusion HBO treatment can improve the clinical, BEAM and outcome of severely brain injured patients, by decreasing acute stage ET and improving the blood velocity of MCA and decreasing cerebral vascular resistance. HBO treatment can reduce cerebral vascular spasms, cerebral ischemia and hypoxia. One of the important mechanisms of HBO treatment for severe brain injury is the lowering of intracranial pressure. 相似文献
105.
Silvia Ravera Susana P Monteiro Johan Jacob de Gier Trudy van der Linden Trinidad Gómez-Talegón F Javier álvarez the DRUID Project WP Partners? 《British journal of clinical pharmacology》2012,74(6):920-931
AIMS
To illustrate (i) the criteria and the development of the DRUID categorization system, (ii) the number of medicines that have currently been categorized, (iii) the added value of the DRUID categorization system and (iv) the next steps in the implementation of the DRUID system.METHODS
The development of the DRUID categorization system was based on several criteria. The following steps were considered: (i) conditions of use of the medicine, (ii) pharmacodynamic and pharmacokinetic data, (iii) pharmacovigilance data, including prevalence of undesirable effects, (iv) experimental and epidemiological data, (v) additional data derived from the patient information leaflet, existing categorization systems and (vi) final categorization. DRUID proposed four tiered categories for medicines and driving.RESULTS
In total, 3054 medicines were reviewed and over 1541 medicines were categorized (the rest were no longer on the EU market). Nearly half of the 1541 medicines were categorized 0 (no or negligible influence on fitness to drive), about 26% were placed in category I (minor influence on fitness to drive) and 17% were categorized as II or III (moderate or severe influence on fitness to drive).CONCLUSIONS
The current DRUID categorization system established and defined standardized and harmonized criteria to categorize commonly used medications, based on their influence on fitness to drive. Further efforts are needed to implement the DRUID categorization system at a European level and further activities should be undertaken in order to reinforce the awareness of health care professionals and patients on the effects of medicines on fitness to drive. 相似文献106.
E. Mayatepek M. Schröder D. Kohlmüller WP Bieger W. Nützenadel 《Acta paediatrica (Oslo, Norway : 1992)》1997,86(10):1138-1140
The effects on isoelectrofocusing patterns of serum glycoproteins were studied in a patient with CDG syndrome type I and phosphomannomutase deficiency during 3 weeks of continuous intravenous mannose infusion. Doses of 5. 7 g/kg/day led to stable serum mannose levels up to 2. 0 mmol/1 and were well tolerated without signs of liver or renal toxicity. While most of the pathological glycoprotein patterns, including α1 -antitrypsin, typical for CDG syndrome type I remained unchanged, mannose infusion led to a unique change of the isoelectrofocusing pattern of serum sialotransferrins with appearance of two extra bands after 3 weeks of treatment. 相似文献
107.
短链脂肪酸在溃疡性结肠炎病因及治疗中的作用 总被引:5,自引:4,他引:1
溃疡性结肠炎(ulcerative colitis,UC)的病因仍不是十分清楚.关于该疾病的假说主要集中在粘膜损伤的启动及持续机制上.病因学假说有短链脂肪酸(short chain fally acid,SCFA)的代谢障碍[1],细菌的化学趋向性多肽导致表皮屏障功能的丧失[2]、细菌内毒素[3]、细菌产生的硫化物[1]及免疫网络的失调和肠腔粘膜免疫活性的增强[4]等.有许多证据支持上述假说,但也有一些不尽完善之处.现就SCFA在UC病因及治疗上的研究成果作一综述. 相似文献
108.
Peter Widschwendter Thomas WP Friedl Lukas Schwentner Nikolaus DeGregorio Bernadette Jaeger Amelie Schramm Inga Bekes Miriam Deniz Krisztian Lato Tobias Weissenbacher Bernd Kost Ulrich Andergassen Julia Jueckstock Julia Neugebauer Elisabeth Trapp Peter A. Fasching Matthias W. Beckmann Andreas Schneeweiss Ines Schrader Brigitte Rack Wolfgang Janni Christoph Scholz 《Breast cancer research : BCR》2015,17(1)
Introduction
Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear.Methods
This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors.Results
Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes.Conclusions
Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors.Trial registration
Clinicaltrials.gov . Registered September 2005. NCT02181101相似文献109.
Grey collie dogs have cyclic fluctuations in their blood cell counts caused by a regulatory defect of hematopoietic stem cells. To examine the role of stem cell factor (SCF) or its receptor in this disorder, we investigated the stimulatory effects of recombinant canine SCF (rc-SCF) on in vitro marrow cultures, cloned and sequenced the grey collie SCF gene, and treated three grey collies with rc-SCF, either alone or in combination with recombinant canine granulocyte colony-stimulating factor (rcG-CSF). Colony-forming unit granulocyte-macrophage formation from grey collie or normal dog marrow showed similar dose-response curves for rc-SCF. Cloning and sequencing the SCF gene for two grey collies showed no evidence of mutations in the coding region of the SCF gene. Treatment with rc-SCF (10 to 100 micrograms/kg/d) did not induce neutrophilia except at the highest dose (100 micrograms/kg/d), but daily rc-SCF abrogated the neutropenic periods in doses of 20 micrograms/kg/d or greater. Combination of rc-G-CSF (0.5 to 1.0 microgram/kg/d) with rc-SCF treatment (20 to 50 micrograms/kg/d) suggested a synergistic effect, ie, the neutrophil levels on combined therapy were higher than the sum of the levels when these two cytokines were given separately. Long-term treatment of these dogs with rc-SCF in doses of 10 to 30 micrograms/kg/d was generally well tolerated, suggesting that SCF may be useful as a therapy for some chronic hypoproliferative disorders of hematopoiesis. 相似文献
110.
Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia 总被引:6,自引:2,他引:6
Look AT; Roberson PK; Williams DL; Rivera G; Bowman WP; Pui CH; Ochs J; Abromowitch M; Kalwinsky D; Dahl GV 《Blood》1985,65(5):1079-1086
Using flow cytometric techniques, we determined the pretreatment distribution of DNA content in propidium iodide-stained leukemic blasts from 205 children with "standard-risk" acute lymphoblastic leukemia (ALL). Risk assignment was based on an initial WBC count less than 100 X 10(9)/L, no thymic mass, no meningeal leukemia, and lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. A single aneuploid leukemic line was detected in 74 cases (36.1%): 70 hyperdiploid and four hypodiploid. For hyperdiploid cases, the DNA index (DI, or ratio of the DNA content of leukemic v normal G0/G1 cells) ranged from 1.06 to 2.0 (median, 1.20). A secondary leukemic line with hyperdiploid cellular DNA content was identified in 21 cases with diploid primary lines. Children whose primary leukemic line showed a DI greater than or equal to 1.16 (n = 57) had significantly better responses to treatment than did those with either a diploid DI (n = 130; P = .002) or values in the range of 1.01 to 1.15 (n = 14; P = .001). The relative risk of failure for hyperdiploid cases with DI greater than or equal to 1.16, corresponding to greater than or equal to 53 chromosomes, was one-third that of the other two groups. Treatment responses of patients with both diploid and hyperdiploid lines were identical to those associated with single diploid lines, but significantly worse than those associated with single hyperdiploid lines with DI greater than or equal to 1.16 (P = .016). The most favorable prognostic variables selected by a Cox proportional hazards model were: DI greater than or equal to 1.16 (P = .001), white race (P = .022), WBC less than or equal to 25 X 10(9)/L (P = .032), age between 2 and 9 years (P = .075), and hemoglobin less than 7.0 g/dL (P = .094). DNA index greater than or equal to 1.16 retained its significant prognostic impact even after adjustment for other variables (P = .001). With the combination of DI greater than or equal to 1.16 and WBC less than or equal to 25 X 10(9)/L, one can identify a group of children with ALL who have a low probability of relapse when treated with current therapy. If they remain disease-free after longer follow-up, it may be advisable to treat them with less intensive, hence less toxic, chemotherapy than patients with higher WBC counts or lower DI values. 相似文献