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Frank A Middleton Marco G Trauzzi Antony E Shrimpton Karen L Gentile Christopher P Morley Helena Medeiros Michele T Pato Carlos N Pato 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(1):28-32
Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded. 相似文献
54.
Alex N. Bullock Julia Henckel Brian S. DeDecker Christopher M. Johnson Penka V. Nikolova Mark R. Proctor David P. Lane Alan R. Fersht 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(26):14338-14342
Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn2+ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions. 相似文献
55.
Hitoshi Ogino Nongchana Klangsuk Wu Jin Christopher T. Bowles Magdi H. Yacoub 《Artificial organs》1995,19(6):525-534
Abstract: The dependence of transient pressure characteristics of a ventricular assist device (VAD) on the compliance of its housing and cannulas was investigated in a mock circulation. The peak rate of change of pressure ( dP/dt max ) values was greater in the cannulas than other compartments and was associated with valve closure-induced pressure oscillations. When cannula compliance was increased from 0.0057 to 0.0129 cm3 /mm Hg, these values decreased by ˜20%, and outflow cannula pressure oscillation frequency decreased from 17.5 Hz by 35%. This trend was also apparent in the inflow. A VAD housing compliance increase from 0.0162 to 0.0483 cm3 /mm Hg caused a dP/dt max decrease of 30% in both the blood chamber and the outflow cannula. The effect of this change on the inflow was weaker implying that housing absorbs the energy associated with outflow deceleration more effectively than the inflow. These findings suggest that increasing VAD housing and cannulas compliance can improve hydrodynamic performance. 相似文献
56.
B. A. Johnson Donald R. Jasinski Gantt P. Galloway Henry Kranzler Robert Weinreib Raymond F. Anton Barbara J. Mason Michael J. Bohn Helen M. Pettinati Richard Rawson Christopher Clyde 《Psychopharmacology》1996,128(2):206-215
Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled
study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1
week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received
weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint,
there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in
drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a
beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference
between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively
high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ
significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related
prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects
can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important
role for ritanserin in the treatment of alcohol dependence.
Received: 30 April 1996/Final version: 3 July 1996 相似文献
57.
Firouzan Massoomi Pharm.D. John Savage Pharm.D. Christopher J. Destache Pharm.D. 《Pharmacotherapy》1993,13(1):46-59
Omeprazole is a member of a new class of substituted benzimidazoles. These agents inhibit the proton pump in the gastric parietal cell, blocking the final step in the gastric acid secretory pathway. Omeprazole has been investigated for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux, and various hypersecretory states. The prolonged inhibition of gastric acid secretion allows for once-daily dosing in patients with peptic ulcer disease and gastroesophageal reflux, and once- or twice-daily dosing in patients with Zollinger-Ellison syndrome. Compared with currently available therapies, omeprazole is well tolerated and demonstrates a more rapid ulcer healing rate. It is superior to conventional therapies in the treatment of Zollinger-Ellison syndrome. Side effects are infrequent when the drug is used for the short-term management of ulcers. 相似文献
58.
Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effectiveparalysis. © 1993 John Wiley & Sons, Inc. 相似文献
59.
60.
Barbara A. Bresnahan Christopher P. Johnson Matthew J. McIntosh Donald Stablein Sundaram Hariharan 《American journal of transplantation》2002,2(4):366-372
The optimal allocation of cadaveric kidneys for transplantation with reference to human leukocyte antigen (HLA) match and sharing these organs to a distant center remains controversial. The current analysis was performed using the United Network for Organ Sharing (UNOS) database for cadaveric kidney transplants (Tx) between 1988 and 1997. The graft survivals of zero-mismatch (matched) kidneys with the mate (mismatched) kidneys were compared. There were 2385 donors and 4770 Tx. Significant differences in recipient demographics between matched and mismatched Tx were: fewer African-American race (AA) in the matched group (9.0% vs. 21.9%), higher number of previous Tx (25.5% vs. 14.8%) and elevated mean cold ischemia time (24.0 vs. 22.2 h). Post-Tx dialysis requirements were similar (22.8% vs. 24.1%, p = 0.62) and matched kidneys had to travel more distance (920 vs. 232 miles). Using a Cox model, the matched group had a decreased relative hazard of graft failure of 23.0% (p = 0.0002) or 35% (p < 0.0001) with and without censoring for death. There was significantly better graft survival in the matched recipients in all pairs except AA (matched) and non-AA (mismatched). For older donors (> or = 50 years, n = 1508), the matched grafts survival was marginally significant (p =0.05). Matched kidneys have improved survival compared with the mismatched kidneys despite the longer distance traveled. The benefit of mismatched transplants was predominantly seen in non-AA. 相似文献