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991.
The first issue of Human Molecular Genetics which came out inApril 1992 included papers on genetic mapping of monogenic diseaseloci, disease mutation reports and somatic cell hybrid mapping,very much the hot topics of the day. Today the work of the moleculargeneticist has moved into an age where the emphasis is muchmore on the functional studies of disease genes and 相似文献
992.
993.
C. Hooijer M. Dinkgreve C. Jonker J. Lindeboom D. W. K. Kay 《International journal of geriatric psychiatry》1992,7(8):559-571
The coexistence of many screening tests for senile dementia raises the question of their potential differences. In an elderly community sample (n = 358), four different tests were applied in parallel. All tests were able to identify similar samples of subjects regarding sample size, age, education or depression. We failed to prove one test to be superior in predicting CAMDEX or AGECAT diagnoses of dementia. Yet, the individuals identified by different tests, and especially the cases of minimal dementia, were only partly identical and partly unique for each of the tests. There is a clear need for greater consensus about the use of screening tests for dementia. 相似文献
994.
We performed cytogenetic analyses of peripheral blood lymphocytes from 82 Midwestern B-cell chronic lymphocytic leukemia (B-CLL) patients. The cells were cultured with mitogens for 3-4 days. At least 15 metaphase cells were analyzed in 79 (96%) cases. Fifty (63%) of the 79 patients had clonal chromosomal alterations. Structural modifications of the long arm of chromosome 13 at or near band 13q14 were the most frequent abnormalities, identified in 23 (46%) of the patients with clonal abnormalities. In several patients, the abnormality involving band 13q14 was the sole chromosomal alteration. There was a high incidence of complex karyotypes. Nine patients had multiple subclones that appeared to result from clonal evolution; seven patients had cytogenetically unrelated clones; three patients had both subclones and cytogenetically unrelated clones. Nonclonal abnormalities were also prominent. Our study confirms the high incidence of clonal abnormalities involving chromosome arm 13q and documents the clustering of abnormalities at band 13q14 in B-CLL. The evidence for clonal evolution and the presence of multiple unrelated clones in these patients suggest that B-CLL may not be a karyotypically stable disease. 相似文献
995.
Kay Mursch Svorad Trnovec Heinrich Ratz Detlef Hammer Regine Horré Albrecht Klinghammer Sybren de Hoog Julianne Behnke-Mursch 《Child's nervous system》2006,22(2):189-192
Rationale We report on a cerebral infection by Pseudallescheria boydii in a 21-month-old boy after a near-drowning episode. MRI revealed multiple (>60) intracerebral abscesses.Methods The surgical therapy included CSF drainage and microsurgical resection of one abscess for microbiological diagnosis. Antimycotic therapy included terbinafine and intraventricular caspofungin in addition to voriconazole.Results Systemic side effects of chemotherapy were not observed. After placement of a ventriculoperitoneal shunt, the boy was transferred to a rehabilitation clinic and improved neurologically. After 20 months, MRI documented a continuing remission of the disease.Conclusion Our case proves that an aggressive treatment should be undertaken and can be successful in CNS pseudallescheriasis. 相似文献
996.
J N Wasserheit J R Harris J Chakraborty B A Kay K J Mason 《Studies in family planning》1989,20(2):69-80
In contrast to social, religious, and economic determinants of acceptance and sustained use of family planning in developing countries, perceived side effects resulting from reproductive tract infections can usually be ameliorated easily and expeditiously. This population-based study examines the magnitude and nature of morbidity due to reproductive tract infections among users of various contraceptive methods and among nonusers in a rural community in Bangladesh. Overall, 22 percent of the 2,929 women surveyed reported symptoms of reproductive tract infection. Of the 472 symptomatic women examined, 68 percent had clinical or laboratory evidence of infection. Users of intrauterine devices and tubectomy were each approximately four times as likely to report symptoms and seven times as likely to have examination-confirmed infection as nonusers. The epidemiology of reproductive tract infections in this population is addressed, and the findings are discussed in terms of their potential programmatic impact. 相似文献
997.
Gregory P Walcott G Neal Kay Vance J Plumb William M Smith Jack M Rogers Andrew E Epstein Raymond E Ideker 《Journal of the American College of Cardiology》2002,39(1):109-115
OBJECTIVES: This study was designed to characterize the organization of ventricular fibrillation (VF) on the endocardium of humans. BACKGROUND: Most proposed mechanisms for the maintenance of VF postulate the propagation of a number of activation wave fronts that reenter to maintain the arrhythmia. We tested the hypothesis that, in patients undergoing internal cardioverter-defibrillator implantation, VF consists primarily of a few large wave fronts on the endocardium. METHODS: Electrograms were recorded from a 36-electrode catheter in the left ventricle of 16 patients during VF. Activation times were chosen for a 2-s epoch for each fibrillation episode, and a two-dimensional Kolmogorov-Smirnov test was performed to determine if activation occurred randomly along the catheter over that time interval. The maximum cross-correlation was found for all possible pairs of electrodes on the catheter, and these values were plotted relative to the distance between the two electrodes. An exponential curve was then fit to the data, and a length constant was determined. Activation times were grouped into wave fronts along the catheter, and the lengths of the wave fronts were estimated. RESULTS: The Kolmogorov-Smirnov test showed that activation was not random along the catheter in any of the patients studied. The correlation length determined was 9 +/- 2 cm. The number of wave fronts recorded by the catheter was 9.2 +/- 2.9 wave fronts/s. The length of the pathway of each wave front along the catheter was 6.5 +/- 4.5 cm. CONCLUSIONS: Ventricular fibrillation is well organized on the endocardial surface of humans, consisting primarily of a few large wave fronts on the order of 6 to 9 cm. 相似文献
998.
Mark A. Kay 《International journal of hematology》2002,76(1):147-147
The goal of our work has been to establish an experimental basis for gene transfer as a method of treating hemophilia, an inherited bleeding disorder that results from the absence of functional Factor VIII or Factor IX. We have carried out pre-clinical and clinical studies of AAV-mediated gene transfer of the Factor IX gene in animal models and in human subjects with severe hemophilia B. Target tissues in humans have included both skeletal muscle (via direct intramuscular injection) and liver (via hepatic artery infusion). Our preclinical efficacy studies have demonstrated a life-long correction of the bleeding diathesis in hemophilia B in mice, and long-term therapeutic reconstitution of canine factor IX in deficient dogs after AAV-mediated gene transfer into the liver. To date, hemophilia B dogs have been followed for over 4 years and still maintain their initial levels of factor IX following the administration of AAV-2. As a result, a number of preclinical studies of AAV into the liver of various species were performed to generate the appropriate safety data to support a Phase I liver-based clinical trial. The comparative results from the two clinical trials, the correlative results of the preclinical studies from the animal models, and the potential advantages/disadvantages of the two approaches will be discussed. Hepatitis C Virus (HCV) infection is a major health problem world-wide. We have recently evaluated different gene transfer approaches for targeted disruption of the viral life cycle. RNA interference (RNAi) is a recently discovered RNA surveillance mechanism used in lower animals and plants to silence specific genes. We have recently demonstrated that RNAi can function in adult mammals. By adapting this to a gene transfer strategy, we have established selective suppression of a HCV-reporter chimeric gene in mouse liver. RNAi has potential for use as a gene therapeutic to treat HCV infection as well as a large number of other acquired and genetic disorders. 相似文献
999.
Phase II trial of interferon gamma and monoclonal antibody 17-1A in pancreatic cancer: biologic and clinical effects 总被引:1,自引:0,他引:1
M A Tempero C Sivinski Z Steplewski E Harvey L Klassen H D Kay 《Journal of clinical oncology》1990,8(12):2019-2026
Thirty patients with advanced measurable pancreatic adenocarcinoma were entered onto a phase II trial with recombinant interferon gamma (Biogen, Cambridge, MA; 10(6) U/m2 daily for 4 days) and monoclonal antibody (Mab) 17-1A (Centocor, Malvern, PA; 150 mg in autologous leukocytes on days 2, 3, and 4 following interferon infusion). The effect of a single interferon gamma treatment on natural and antibody-dependent cellular cytotoxicity (ADCC), Fc receptor occupancy by antibody, and human leukocyte antigen-DR (HLA-DR) expression on monocytes and lymphocytes was also studied. Toxicity was modest and generally limited to grade I to II fever, nausea and vomiting, and hepatotoxicity. Five patients were considered to be nonassessable for response. Of the 25 assessable patients, one objective response (complete remission for a duration of 4 months) was observed. Stable disease for 2 months or greater was noted in nine patients. The median survival for the group was 5 months. Analysis of cytotoxicity data obtained prior to treatment showed reduced natural cytotoxic activity in these patients compared with normal volunteers. A significant improvement in natural cytotoxic activity to normal levels occurred within 24 hours following the interferon gamma infusion. This was also associated with augmented antibody-dependent cellular cytotoxicity. Although HLA-DR expression was not increased on either monocytes or lymphocytes, an increased capacity of both lymphocytes and monocytes to bind Mab 17-1A was observed. In all in vitro assays of ADCC, the presence of antibody excess was associated with improved cytolytic activity. In spite of the favorable modulation of cytolytic activity and improved ability of effector cells to bind Mab, we failed to demonstrated adequate clinical efficacy in the treatment of patients with pancreatic adenocarcinoma using this dose and schedule of interferon gamma and Mab 17-1A. Future trials will focus on alternate schedules of Mab 17-1A with the hope of improving tumor antigen saturation and circulating levels of infused antibody. 相似文献
1000.
Female age, the length of involuntary infertility prior to investigation and fertility outcome 总被引:2,自引:1,他引:1
Dunphy B. C.; Kay R.; Barratt C.L.R.; Cooke I.D. 《Human reproduction (Oxford, England)》1989,4(5):527-530
The objectives of this study were two-fold: firstly to determinewhether female age exerts an influence on the fertility outcomeof couples attending an infertility clinic, independent of demographicand clinical details; and secondly to examine the relationshipbetween the length of involuntary infertility prior to investigationand the subsequent chance of conception. Seven-hundred-and-thirty-onesubjects whose partner did not have azoospermia were recruitedto the study. Female age ranged from 20 to 46 (mean = 31.1).Therange of involuntary infertility prior to investigation was12216 (mean = 62) months. One-hundred-and-twenty-fourwomen conceived. The following variables achieved the 5% levelof significance when a stepwise analysis was performed on allcases; the concentration of spermatozoa exhibiting slow or sluggishlinear or non-linear motility (x21= 17.57, P < 0.0001, RR= 1.67 per 50 x 106), female age x21= 12.44, P = 0.0004, RR= 0.92 per annum), tubal status (X2 = 12.22, P = 0.0005, RR= 2.15), length of infertility before investigation (X2 = 11.22,P = 0.0008, RR = 0.87 per annum) and past paternity (X2 = 8.43,P = 0.0037, RR = 1.81). Female age was found to be positivelycorrelated with the incidence and severity of ovulatory dysfunction,tubal occlusive disease, pelvic adhesions and endometriosis.Where the female partner was normal on investigation,all conceptions were independent of treatment to either partner.The following variable achieved the 5% level of significancewhen a stepwise analysis was performed on the latter group (n= 310): the concentration of spermatozoa that which exhibitedslow or sluggish linear or non-linear motility (X2 = 113.38,P = 0.0003, RR = 1.73 per 50x 106). 相似文献