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991.
992.
An Epstein-Barr virus-associated superantigen 总被引:2,自引:0,他引:2
N Sutkowski T Palkama C Ciurli RP Sekaly DA Thorley-Lawson BT Huber 《Canadian Metallurgical Quarterly》1996,184(3):971-980
More than 90% of adults are latently infected with Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, a self-limiting lymphoproliferative disease characterized by extensive T cell activation. Reactivation of this herpesvirus during immunosuppression is often associated with oncogenesis. These considerations led us to analyze the early events that occur after exposure of the immune system to EBV. Strong major histocompatibility complex (MHC) class II-dependent but not MHC-restricted, T cell proliferation was observed in vitro in response to autologous, lytically infected EBV-transformed B cells. By measuring the appearance of the early activation marker CD69 on individual T cell V beta subsets, we could demonstrate selective activation of human V beta 13- T cells. This was confirmed with murine T cell hybridomas expressing various human BV genes. While EBV- Burkitt's lymphoma cells were nonstimulatory, they induced V beta-restricted T cell activation after EBV infection. EBV specific activation was also demonstrated in cord blood cells, excluding a recall-antigen response. Thus, all of the characteristics of a superantigen-stimulated response are seen, indicating that induction of the EBV lytic cycle is associated with the expression of a superantigen in B cells. A model is presented proposing a role for the superantigen in infection, latency, and oncogenesis. 相似文献
993.
Myasthenia gravis (MG) may occur in association with autoimmune thyroid diseases (AITD). The aim of this study was to evaluate the features of MG associated with AITD compared to those of MG without AITD. A total of 129 MG patients (34 men and 95 women; age range, 11-81 yr) were subdivided into: group A, 56 MG patients with AITD [25 with autoimmune thyroiditis and 31 with Graves' disease (GD)]; group B, 21 MG patients with nonautoimmune thyroid diseases; and group C, 52 MG patients without thyroid disease. The severity of MG was ranked according to the Osserman score. Laboratory evaluation included assays for antithyroid and antiacetylcholine receptor (AchRAb) antibodies. Ocular MG (Osserman's class 1) was more frequent in group A (41.0%) than in group B (14.2%; P < 0.03) or C (21.4%; P < 0.03). Severe generalized MG (classes > or = 2B) was more frequent in groups B (57.1%; P < 0.03) and C (51.9%; P < 0.02) than in group A (28.5%). GD patients with clinical evidence of ophthalmopathy had a higher frequency (P = 0.05) of ocular MG (57.8%) than GD patients without clinical ophthalmopathy (16.6%). Thymic disease was less frequent in group A (26.7%) than in group B (71.4%; P = 0.001) or C (59.7%; P = 0.001). The prevalence of thymic hyperplasia was 17.8%, 38.0%, and 40.3% in groups A, B, and C, respectively; the prevalence of thymoma was 8.9%, 33.4%, and 19.4%. When only patients with generalized MG were considered, thymic disease was less frequent (P < 0.02) in group A (40.6%) than in the remaining groups (69.4%). AchRAb was more frequent in groups B (57.1%) and C (57.6%; P < 0.03) than in group A (35.7%). In conclusion, MG associated with AITD has a mild clinical expression, with preferential ocular involvement and lower frequency of thymic disease and AchRAb. This supports the hypothesis that ocular and generalized MG are separate diseases with different spectra of associated diseases. Nonautoimmune thyroid diseases have no influence on the features of MG. The association of ocular MG and AITD might be due to a common autoimmune mechanism and/or a peculiar genetic background. 相似文献
994.
S Gründer D Firsov SS Chang NF Jaeger I Gautschi L Schild RP Lifton BC Rossier 《Canadian Metallurgical Quarterly》1997,16(5):899-907
Pseudohypoaldosteronism type 1 (PHA-1) is an inherited disease characterized by severe neonatal salt-wasting and caused by mutations in subunits of the amiloride-sensitive epithelial sodium channel (ENaC). A missense mutation (G37S) of the human ENaC beta subunit that causes loss of ENaC function and PHA-1 replaces a glycine that is conserved in the N-terminus of all members of the ENaC gene family. We now report an investigation of the mechanism of channel inactivation by this mutation. Homologous mutations, introduced into alpha, beta or gamma subunits, all significantly reduce macroscopic sodium channel currents recorded in Xenopus laevis oocytes. Quantitative determination of the number of channel molecules present at the cell surface showed no significant differences in surface expression of mutant compared with wild-type channels. Single channel conductances and ion selectivities of the mutant channels were identical to that of wild-type. These results suggest that the decrease in macroscopic Na currents is due to a decrease in channel open probability (P(o)), suggesting that mutations of a conserved glycine in the N-terminus of ENaC subunits change ENaC channel gating, which would explain the disease pathophysiology. Single channel recordings of channels containing the mutant alpha subunit (alphaG95S) directly demonstrate a striking reduction in P(o). We propose that this mutation favors a gating mode characterized by short-open and long-closed times. We suggest that determination of the gating mode of ENaC is a key regulator of channel activity. 相似文献
995.
Postradiation sarcoma of bone is an uncommon but serious sequela of radiation therapy. Seventy-eight Mayo Clinic patients have been treated for sarcomas arising in irradiated bones. They received their initial radiotherapy for a wide variety of nonneoplastic and neoplastic conditions, both benign and malignant. Thirty-five sarcomas arose in bone that was normal at the time of radiotherapy, and 43 arose in irradiated preexisting osseous lesions. The latent period between radiotherapy and diagnosis of sarcoma averaged 14.3 years. Ninety percent of the postradiation sarcomas were either osteosarcomas or fibrosarcomas; chondrosarcoma, malignant (fibrous) histiocytoma, malignant lymphoma, Ewing's tumor, and metastasizing chondroblastoma also occurred. Prompt radical surgery, when feasible, is usually the treatment of choice for the sarcoma. About 30% of patients with sarcomas of the extremities or craniofacial bones survived 5 years without recurrence; there were no disease-free survivors among patients with tumors of the vertebral column, pelvis, or shoulder girdle. The low risk of sarcoma following radiotherapy for the treatment of cancer should not be a contraindication to its use in these patients; however, radiation therapy for benign bone tumors should be reserved for lesions that are not amenable to surgical treatment. An unusual case is also reported herein in which a fibrosarcoma was discovered in the humerus of a patient who had received radiotherapy 55 years previously for a verified osteosarcoma in the same site. 相似文献
996.
Abnormal calcification on skull films in the region of the sella turcica is not commonly found with chromophobe adenoma. A patient with such calcification in a verified chromophobe adenoma is presented. From the literature the incidence of calcification in these tumours is reviewed. The importance of considering a chromophobe adenoma in the differential diagnosis of parasellar calcification from the surgical point of view is mentioned. 相似文献
997.
998.
RP Forsberg 《Canadian Metallurgical Quarterly》1995,20(1):25-42
In an article titled, "Who Shall Live When Not All Can?", James Childress proposes a system for allocating scarce lifesaving medical resources based on random selection procedures. Childress writes of random selection procedures, [They] "cannot be dismissed as a 'non-rational' and 'non-human' ...without an inquiry into the reasons, including human values which might justify it." My thesis is that once we concentrate on determining the rationality of random selection procedures, we will see that Childress's claim that we cannot dismiss such procedures as 'non-rational' is open to question. My claim will be that while both random selection and social worth procedures are rationally defensible systems, random selection procedures easily lead to specific choices that are objectively irrational, apart from the limited perspective of the random selection process itself. 相似文献
999.
The functional anatomy of reaching and grasping simple objects was determined in nine healthy subjects with positron emission tomography imaging of regional cerebral blood flow (rCBF). In a prehension (grasping) task, subjects reached and grasped illuminated cylindrical objects with their right hand. In a pointing task, subjects reached and pointed over the same targets. In a control condition subjects looked at the targets. Both movement tasks increased activity in a distributed set of cortical and subcortical sites: contralateral motor, premotor, ventral supplementary motor area (SMA), cingulate, superior parietal, and dorsal occipital cortex. Cortical areas including cuneate and dorsal occipital cortex were more extensively activated than ventral occipital or temporal pathways. The left parietal operculum (putative SII) was recruited during grasping but not pointing. Blood flow changes were individually localized with respect to local cortical anatomy using sulcal landmarks. Consistent anatomic landmarks from MRI scans could be identified to locate sensorimotor, ventral SMA, and SII blood flow increases. The time required to complete individual movements and the amount of movement made during imaging correlated positively with the magnitude of rCBF increases during grasping in the contralateral inferior sensorimotor, cingulate, and ipsilateral inferior temporal cortex, and bilateral anterior cerebellum. This functional-anatomic study defines a cortical system for "pragmatic' manipulation of simple neutral objects. 相似文献
1000.