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991.
DW Benson CA MacRae MR Vesely EP Walsh JG Seidman CE Seidman CA Satler 《Canadian Metallurgical Quarterly》1996,93(10):1791-1795
BACKGROUND: Long QT syndrome (LQT) is an inherited cardiac disorder that results in syncope, seizures, and sudden death. In a family with LQT, we identified a novel mutation in human ether-a-go-go-related gene (HERG), a voltage-gated potassium channel. METHODS AND RESULTS: We used DNA sequence analysis, restriction enzyme digestion analysis, and allele-specific oligonucleotide hybridization to identify the HERG mutation. A single nucleotide substitution of thymidine to guanine (T1961G) changed the coding sense of HERG from isoleucine to arginine (Ile593Arg) in the channel pore region. The mutation was present in all affected family members; the mutation was not present in unaffected family members or in 100 normal, unrelated individuals. CONCLUSIONS: We conclude that the Ile593Arg missense mutation in HERG is the cause of LQT in this family because it segregates with disease, its presence was confirmed in three ways, and it is not found in normal individuals. The Ile593Arg mutation may result in a change in potassium selectivity and permeability leading to a loss of HERG function, thereby resulting in LQT. 相似文献
992.
CL Halbert TA Standaert ML Aitken IE Alexander DW Russell AD Miller 《Canadian Metallurgical Quarterly》1997,71(8):5932-5941
The ability of recombinant adeno-associated virus (AAV) vectors to integrate into the host genome and to transduce nondividing cells makes them attractive as vehicles for gene delivery. In this study, we assessed the ability of several AAV vectors to transduce airway cells in rabbits by measuring marker gene expression. AAV vectors that transferred either a beta-galactosidase (beta-gal) or a human placental alkaline phosphatase (AP) gene were delivered to one lobe of the rabbit lung by use of a balloon catheter placed under fluoroscopic guidance. We observed vector-encoded beta-gal or AP staining almost exclusively in the epithelial and smooth muscle cells in the bronchus at the region of balloon placement. The overall efficiency of transduction in the balloon-treated bronchial epithelium was low but reached 20% in some areas. The majority of the staining was in ciliated cells but was also observed in basal cells and airway smooth muscle cells. We observed an 80-fold decrease in marker-positive epithelial cells during the 60-day period after vector infusion, whereas the number of marker-positive smooth muscle cells stayed constant. Although treatment with the topoisomerase inhibitor etoposide dramatically enhanced AAV transduction in primary airway epithelial cells in culture, treatment of rabbits did not improve transduction rates in the airway. Vector readministration failed to produce additional transduction events, which correlated with the appearance of neutralizing antibodies. These results indicate that both readministration and immune modulation will be required in the use of AAV vectors for gene therapy to the airway epithelium. 相似文献
993.
We characterized apneas by a quantitative method (esophageal pressure measurements) and by a qualitative method (strain gauges) at the same time in 22 patients with sleep-related breathing disorders. Detection of respiratory effort by strain gauges significantly overestimated the total number of central apneas in each patient. Despite this overestimation, none of the patients was wrongly diagnosed as having pure central sleep apnea syndrome. Strain gauges are sufficiently reliable for the characterization of apneas in most patients. When strain gauges reveal that most apneas are central in origin, verification by esophageal pressure measurements is recommended. 相似文献
994.
PJ Lin CH Chang JP Chang DW Liu JJ Chu KT Tsai CL Kao MJ Hsieh 《Canadian Metallurgical Quarterly》1994,93(8):681-685
The surgical treatment of acute type A aortic dissection remains a great challenge to all cardiac surgeons. From January 1991 to June 1993, 21 consecutive patients (13 men and eight women, aged 34 to 74 years) underwent emergency operations to repair acute type A aortic dissection, with the aid of hypothermic circulatory arrest. The intima tear was located in the ascending aorta in 13 patients, in the aortic arch in five patients, and in the descending aorta in three patients. The dissected ascending aorta was replaced with sutureless, intraluminal vascular grafts in all 21 patients. The intima tears in the aortic arch of five patients were primarily repaired. Modified Cabrol's shunts were created in seven patients for hemostasis, and Dacron grafts were used to wrap the ascending aorta in 18 patients. Retrograde cerebral perfusion during circulatory arrest was performed on 15 patients. The circulatory arrest time was 37 +/- 10 minutes (mean +/- SD). All patients survived the operation and regained consciousness in the early postoperative period without neurologic deficit. Post-treatment follow-ups (mean, 18.2 months) were completed in all patients except one, who died 12 months after the operation as a result of a traffic accident. All of the surviving patients are doing well without any further aortic operations. Our experience suggests that surgical repair of the acute type A aortic dissection can be a simple and safe procedure if sutureless intraluminal grafts are used and hypothermic circulatory arrest and retrograde cerebral perfusion are utilized. 相似文献
995.
BJ Giantonio RK Alpaugh J Schultz C McAleer DW Newton B Shannon Y Guedez M Kotb L Vitek R Persson PO Gunnarsson T Kalland M Dohlsten B Persson LM Weiner 《Canadian Metallurgical Quarterly》1997,15(5):1994-2007
PURPOSE: To establish the maximum-tolerated dose (MTD) and define the toxicities of a single-dose infusion of PNU-214565, a recombinant Escherichia coli-derived fusion protein of Staphylococcal enterotoxin A (SEA) and the Fab-fragment of the C242 monoclonal antibody in patients with advanced colorectal and pancreatic carcinomas. To investigate the capability of PNU-214565 to induce a superantigen (SAg) response resulting in cytokine production and tumor regression. PATIENTS AND METHODS: Twenty-one patients (age range, 39 to 76 years; median, 64; 12 men, nine women; 18 colorectal, three pancreatic cancers) were treated with a single 3-hour infusion of PNU-214565, with doses ranging from 0.01 to 1.5 ng/kg. All patients had prior chemotherapy and a good performance status Eastern Cooperative Oncology Group [ECOG] performance status [PS] = 0 [n = 10]; PS = 1 [n = 11]), 10 had prior radiation, and 18 had prior surgery. RESULTS: Fever and hypotension were the most common toxicities. Fever of any grade occurred in 16 of 21 patients (76%): four of 21 (19%) with grade 2 and two of 21 (9.5%) with grade 3. Hypotension of any grade occurred in 13 of 21 (62%): four of 21 with grade 2 and one of 21 (5%) with grade 3. Interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF alpha) induction correlated with toxicity. In the two patients with grade 3 fever, peak IL-2 and TNF alpha levels were 2.9 IU/mL and 165 pg/mL, and 8.3 IU/mL and 245 pg/mL, respectively. Transient, > or = 50% decreases in circulating monocytes were observed in 17 of 21 patients as early as 0.5 hours (median time, 2 hours) from the start of infusion. Decreases (mean 33%) in circulating lymphocytes were observed in seven of 21 patients. All three patients with grade 3 toxicity were treated at the 0.5-ng/kg dose. The significance of baseline anti-SEA, human antimouse antibody (HAMA), CA242-soluble antigen levels, and T-cell receptor variable beta region (TCR V beta) subsets and histocompatibility leukocyte antigen-DR (HLA-DR) genotypes was assessed as possible predictors of toxicity. All toxicities were transient and easily managed. No grade 3 toxicity occurred at the higher dose levels. CONCLUSION: PNU-214565, a SAg-based tumor targeted therapy, is safe when given as a single 3-hour infusion at doses up to 1.5 ng/kg. The MTD for a single dose was not determined. The safety of a repeated dose schedule is currently under investigation, beginning with doses determined to be safe in this trial. 相似文献
996.
The Health Care Financing Administration has reported influenza immunization rates since 1994. The Department of Health and Human Services has set a minimum national target rate for the annual immunization of the elderly population at 60 percent, as published in Healthy People 2000. The Oklahoma Foundation for Medical Quality analyzed the Medicare claims data for Oklahoma for the 1995, 1996, and 1997 influenza seasons. Additionally, we reviewed the Behavioral Risk Factor Surveillance System influenza immunization data for 1995. Claims data for the 1997 influenza season show the immunization rate for the Medicare population of Oklahoma is 41.4 percent. The immunization rate for the African-American Medicare population was 22.3 percent for 1997, compared with 42.2 percent for the Caucasian population. The ten most populous counties in the state had a 9-percent higher rate of immunization than the other 67 counties. The Medicare population in Oklahoma is not receiving the influenza vaccination at the target rate. Especially underserved are the African-American and non-urban populations. There appear to be opportunities for improvement in the provision of the influenza vaccination for the Medicare population of Oklahoma. 相似文献
997.
GH Loneragan DH Gould RJ Callan CJ Sigurdson DW Hamar 《Canadian Metallurgical Quarterly》1998,213(11):1599-604, 1571
During a 2-week period, 16 of 150 recently weaned calves developed signs of polioencephalomalacia (PEM). One calf was examined and treated at our veterinary teaching hospital and a necropsy was performed on a calf that died. During the peak of the outbreak, clinicians visited the ranch. Ruminal hydrogen sulfide (H2S) and blood thiamine concentrations were measured in 10 clinically normal penmates of PEM-affected calves. Ruminal H2S concentrations were high (> 0.695 mg/L [> 500 ppm]) in all cattle (mean, 12.19 mg/L [8,770 ppm]). All blood thiamine values were within the reference range. Within 12 hours after measurement of blood thiamine concentrations, 2 of the calves from which samples were obtained developed clinical signs of PEM. Dietary analysis revealed an estimated sulfur intake of 0.9% per calf on a dry-matter basis. Hay contributed most of this sulfur. In the investigation reported here, an outbreak of PEM was associated with high ruminal H2S concentrations and excess sulfur intake without evidence of thiamine deficiency. 相似文献
998.
The cytoplasm of animal cells is structured by a scaffolding composed of actin microfilaments, microtubules, and intermediate filaments. Intermediate filaments, so named because their 10-nanometer diameter is intermediate between that of microfilaments (6 nanometers) and microtubules (23 nanometers), assemble into an anastomosed network within the cytoplasm. In combination with a recently identified class of cross-linking proteins that mediate interactions between intermediate filaments and the other cytoskeletal networks, evidence is reviewed here that intermediate filaments provide a flexible intracellular scaffolding whose function is to structure cytoplasm and to resist stresses externally applied to the cell. Mutations that weaken this structural framework increase the risk of cell rupture and cause a variety of human disorders. 相似文献
999.
J Seybold R Newton L Wright PA Finney N Suttorp PJ Barnes IM Adcock MA Giembycz 《Canadian Metallurgical Quarterly》1998,273(32):20575-20588
1000.
RATIONALE AND OBJECTIVES: The authors investigated the feasibility of using a low-field open-magnet magnetic resonance (MR) scanner to acquire functional flexion-extension images for range of motion (ROM) measurements on the lumbar spine. METHODS: Seventeen healthy subjects with no symptoms of back pain (age range, 22-59 years) were scanned in a low-field open-magnet MR scanner in the flexed, neutral, and extended positions. Each image was downloaded to a computer workstation for subsequent flexion-extension, lordosis, and ROM measurement. RESULTS: Data from two subjects were not analyzed because their images did not show all the lumbar vertebrae. For the remaining 15, there was a large variation in the magnitude of the ROM values (range, 9 degrees-70 degrees; mean 36.4 degrees, SD 16.5 degrees). However, there was a significant correlation between age and ROM (r = -0.63; P < 0.05). CONCLUSIONS: The low-field open-magnet MR scanner provides a method for noninvasive imaging of the lumbar spine, allowing the subject freedom of movement in the horizontal plane. This enables functional flexion-extension images of the lumbar spine to be acquired. 相似文献