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991.
SC Ghivizzani R Kang HI Georgescu ER Lechman D Jaffurs JM Engle SC Watkins MH Tindal MK Suchanek LR McKenzie CH Evans PD Robbins 《Canadian Metallurgical Quarterly》1997,159(7):3604-3612
To investigate the pathophysiologic effects of chronically elevated intra-articular levels of IL-1 beta, we used an ex vivo gene transfer method to deliver and express human IL-1 beta (hIL-1 beta) in the knee joints of rabbits. Expression of hIL-1 beta resulted in a severe, highly aggressive form of arthritis analogous to chronic rheumatoid arthritis in humans. Intra-articular manifestations included intense inflammation, leukocytosis, synovial hypertrophy and hyperplasia, and highly aggressive pannus formation with erosion of the articular cartilage and periarticular bone. Systemic effects were also observed, including diarrhea, fever, weight loss, and an increased erythrocyte sedimentation rate. In addition, the hIL-1 beta was found to induce elevated levels of both rabbit IL-1 beta and TNF-alpha in synovial fluid. Following the loss of hIL-1 beta transgene expression between 14 and 28 days post-transplantation, many of these changes began to normalize. These results suggest that chronically elevated intra-articular levels of IL-1 beta alone are sufficient to produce virtually all the pathologies found in rheumatoid arthritis, and furthermore, demonstrate that gene transfer can be used to investigate the roles of specific gene products in the pathogenesis of arthritis. 相似文献
992.
Lymphotoxin (LT) provides a critical signal for the genesis of lymph nodes (LN) in mice. Here we show that mice treated in utero with LT beta-R-Ig, which binds to the membrane LT alpha 1 beta 2 heterotrimer, lacked most LN, yet retained a set of mucosal surface draining LN. Since mice genetically deficient in LT alpha lack all LN, including the mucosal set, we hypothesize that a novel LT alpha-dependent pathway controls their genesis. This novel set of mucosal LN cannot be discriminated on the basis of addressin expression. The discovery of LN in mice treated with LT beta-R-Ig fusion protein in utero allowed us to compare the roles of membrane LT alpha beta or soluble LT alpha/tumor necrosis factor (TNF) in the development of cellular organization in LN and spleen. Our results indicate that both membrane LT alpha beta and soluble LT alpha/TNF mediate T-B cell segregation and the organization of B cell follicles in spleen and LN. Interestingly, while antagonism of membrane LT alpha beta or soluble LT alpha/TNF prevented germinal center (GC) formation in spleen, antagonism of soluble LT alpha/TNF had no effect on LN formation. The data suggest that multiple LT/TNF ligands control B cell follicle organization in the spleen and LN of adult mice, and that the requirements for LT/TNF ligands in GC formation are distinct in the different lymphoid organs. 相似文献
993.
994.
The influence of health-related quality of life and social characteristics on hospital use by patients with AIDS in the Boston Health Study 总被引:2,自引:0,他引:2
JS Weissman PD Cleary GR Seage C Gatsonis JS Haas S Chasan-Taber AM Epstein 《Canadian Metallurgical Quarterly》1996,34(10):1037-1056
OBJECTIVES: The authors examine whether health-related quality of life (HRQL) and social factors were independent predictors of future hospital use for persons with acquired immunodeficiency syndrome (AIDS). METHODS: A panel of 305 patients with AIDS treated at three provider settings in the Boston, Massachusetts area were enrolled during 1990 and 1991. Data were collected at baseline study enrollment and again 4 months later. Patient interviews, hospital bills, and medical charts were used to measure hospital use (admissions and days during the 4 months after enrollment), sociodemographic characteristics (age, gender, race, education, insurance, homelessness, alcohol use, and AIDS risk factors), disease burden (patient severity and a three-level opportunistic diseases and complications score), HRQL (patient-reported symptoms, activities of daily living, neuropsychological status, and global health assessment), system of care, and use of prophylactic drugs. Logistic regression was used to estimate the odds of admission. Total days of hospital care by patients with at least one admission were analyzed using multiple linear regression. Clinical models of hospital use were developed first from the variables measuring disease burden and system of care. Models estimating the associations between hospital use and all other predictor variables measured at baseline then were estimated using stepwise techniques, controlling for variables in the core model. RESULTS: Patients were more likely than their reference groups to be hospitalized if they had serious opportunistic diseases (adjusted odds ratio [OR] = 2.7), had poorer neuropsychological status (OR = 1.9), were non-white (OR = 2.0), or were homeless (OR = 3.3) (all P < or = 0.05). Activities of daily living were associated moderately (OR = 1.3; P = 0.07). Only system of care and neuropsychological status predicted total hospital days. CONCLUSIONS: The results indicate that future hospital use by persons with AIDS may be influenced by social and other health-related factors in addition to the more clinically related characteristics that are recorded in a medical chart. It therefore may be appropriate to assess these factors when considering options for intervention or when comparing patterns of use among patient groups or settings. 相似文献
995.
From June 1994 through September 1995, 17 patients with gynecologic cancer were entered into a feasibility study using elemental supplements (ES) during the course of pelvic radiotherapy. The level of compliance with the ES regimen was evaluated by assessing sachet counts and patients' weekly diaries. Diaries were also used to assess compliance with a modified diet program. Bowel function in 45 patients receiving radiotherapy outside this study was assessed concurrently. All patients were reviewed weekly to record bowel function, which was also recorded 1 year after radiotherapy. After treatment of all patients the grade, duration of enteritis, need for antidiarrheal agents, and the likelihood of resolution at 1 year after radiotherapy were analyzed. The study used compliance with the ES regimen as its primary endpoint. Compliance with the ES regimen was achieved in 76.5% of patients, and compliance with the modified diet was achieved regardless of whether the ES was tolerated. Patients not complying with the ES, or who did not receive ES, had higher grade diarrhea, which was longer in duration and was less likely to have resolved than patients in the compliant group. Elemental supplements are well tolerated when taken during a course of pelvic radiotherapy and cause a mild diarrhea, which resolves after treatment has been discontinued. The lack of enteritis 1 year later in patients who complied with ES suggests that reducing the grade of acute enteritis might influence the appearance of later bowel effects. 相似文献
996.
I Anderson CR Bartley RA Lerch WG Gray PD Friesen J Gorski 《Canadian Metallurgical Quarterly》1998,37(49):17287-17298
Estrogen receptor (ER) alpha is commonly thought to bind to a consensus estrogen response element (ERE) as a homodimer, but previous experiments have not ruled out the presence of other proteins in the ERalpha/ERE complex. To characterize this interaction in more detail, we overexpressed mouse (m) ERalpha in a baculovirus system, using the selective advantage of the apoptosis inhibitor p35. Recombinant mERalpha possesses the predicted molecular weight and binds 17beta-estradiol and an oligonucleotide containing a consensus vitellogenin ERE with high affinity. Over a wide concentration range of mERalpha protein (0.1-50 nM), only one complex was detected between mERalpha and vitellogenin ERE in gel shift assays. The ratio of E2:vitellogenin ERE bound by mERalpha was close to 2:1, and each complex contained only one ERE. The molecular weight of the complex was determined to be 160 000, very close to that predicted for two mERalpha proteins and one ERE oligonucleotide, therefore providing strong evidence that no other proteins were present. Recombinant mERalpha was purified such that it was the only protein observable by silver stain. Purified mERalpha and mERalpha in a nuclear extract behaved identically in Ferguson analysis, providing more evidence that only mERalpha was binding to the ERE. Purified mERalpha bound vitellogenin ERE with high affinity (Kd = 0. 92 +/- 0.20 nM), indicating that no other proteins are necessary for high-affinity mERalpha interaction with a consensus ERE. To determine whether ERalpha in an estrogen-responsive mammalian tissue behaves the same as the overexpressed mERalpha, we tested rat uterine cytosol by Ferguson analysis. ERalpha in rat uterine cytosol behaved identically to overexpressed mERalpha, suggesting that ERalpha in the uterine extract also binds to DNA predominantly as a homodimer with no additional proteins. 相似文献
997.
Brome mosaic bromovirus (BMV), a positive-stranded RNA virus, supports both homologous and nonhomologous RNA recombinations. Two BMV (temperature-sensitive) mutants with alterations in the 2a protein, the putative RNA polymerase component of the viral replicase, were tested for their ability to support both types of recombination. Here we report that one of these mutants with the Leu-486 substituted by Phe did not support nonhomologous recombination. Effect on homologous recombination was mainly on the location and precision of crossover events. The other 2a mutant with Asn-458 substituted by Asp did not negatively affect either type of recombination. Apparently, BMV RNA polymerase participates differently in the two types of recombination events. 相似文献
998.
Clinically, stress fractures appear to be a common overuse injury among athletes and in military recruits undertaking basic training; however, there is a lack of sound epidemiologic studies describing stress fracture occurrence in athletes. Few have directly compared stress fracture rates between sports to establish which poses the greatest risk for this injury. Furthermore, incidence rates, expressed in terms of exposure, have rarely been reported for stress fractures in athletes. Nevertheless, available data suggest that runners and ballet dancers are at relatively high risk for stress fractures. Although a gender difference in rates is clearly evident in military populations, this is less apparent in athletes. Other participant characteristics, such as age and race, may also influence stress fracture risk. The most common site of stress fracture in athletes is the tibia, although the site reflects the nature of the load applied to the skeleton. Stress fracture morbidity, expressed as the time until return to sport or activity, varies depending on the site. Generally, a period of 6 to 8 weeks is needed for healing; however, stress fractures at certain sites, such as the navicular and anterior tibial cortex, are often associated with protracted recovery and, in some cases, termination of sporting pursuits. 相似文献
999.
Two cases of an unusual finding of capsular pseudoinvasion in follicular thyroid adenomas after fine-needle aspiration (FNA) procedures are reported. These capsular breaches were noted along the hemorrhagic needle track, which traversed the normal peripheral thyroid parenchyma into the lesions. A reparative reaction was seen at some points along one of the tracks. Histologic examination also showed extrusion of the tumor parenchyma through the capsular interruption in one case. Surgical pathologists should be aware of this rare complication of FNA of thyroid follicular adenomas as a differential diagnosis of minimally invasive (encapsulated) follicular carcinoma. 相似文献
1000.
Recent evidence suggests that approximately 90% of retinal ganglion cells (RGCs) die by the process of apoptosis within 14 days of optic nerve transection. RGCs begin to disappear from the retina between 5 and 7 days postaxotomy when the highest percentage of RGCs show characteristics typical of apoptosis. A single intraocular injection of glial cell-line derived neurotrophic factor (GDNF) given at the time of axotomy resulted in a delay in the initiation of RGC death and increased the densities of surviving RGCs at 7, 10 and 14 days postaxotomy. The mean RGC densities in GDNF treated retinas at 7 (2381 +/- 144), 10 (1561 +/- 117) and 14 (1123 +/- 116) days postaxotomy were significantly higher than that of controls (1835 +/- 82, 835 +/- 272 and 485 +/- 39, respectively). The loss of RGCs was paralleled by increases in TUNEL positive staining in control retinas and a lower percentage of TUNEL positive cells in GDNF treated retinas at 5, 7 and 10 days postaxotomy. These results suggest that GDNF is capable of promoting RGC survival following injury, possibly by interfering with an essential step in apoptosis. 相似文献