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排序方式: 共有191条查询结果,搜索用时 15 毫秒
1.
E Paul A Manheimer-Lory A Livneh A Solomon C Aranow C Ghossein R Shefner D Offen M Pillinger B Diamond 《International reviews of immunology》1990,5(3-4):295-313
We have adopted an idiotypic approach to study the double stranded DNA (dsDNA) binding antibodies of systemic lupus erythematosus (SLE). Three anti-idiotypic reagents, 8.12, 3I, and F4, identify cross reactive idiotypes that are each expressed on anti-dsDNA antibodies in the sera of many patients with SLE. These idiotypic antibodies are implicated in the pathogenesis of SLE as they are present in immune complex deposits in the kidneys of patients with SLE glomerulonephritis. The autoantibody associated idiotypes are also expressed on antibodies that do not bind DNA. We are investigating the origin of the pathogenic anti-dsDNA antibodies of SLE by comparing the autoantibodies, the antibodies to foreign antigens, and the myeloma proteins that express each SLE associated idiotype. In conjunction with serological analysis of these idiotypic systems, molecular genetic studies indicate that both the 8.12 and the 3I autoantibody associated idiotypes may be germline encoded, while the F4 idiotype is generated by somatic mutation. The data further suggest that the antigenic specificity of the pathogenic anti-DNA antibodies of SLE is acquired through somatic mutation of germline immunoglobulin genes. By studying the regulation of genes capable of encoding pathogenic autoantibodies, in both SLE patients and non-autoimmune individuals, we may be able to elucidate the pathogenesis of autoimmune disease and begin to design more effective therapeutic interventions. 相似文献
2.
Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis. 总被引:8,自引:0,他引:8
Alexander Stojadinovic Murray F Brennan Axel Hoos Atilla Omeroglu Denis H Y Leung Maria E Dudas Aviram Nissan Carlos Cordon-Cardo Ronald A Ghossein 《Modern pathology》2003,16(8):742-751
We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins. 相似文献
3.
Marie Hudson Cybele Ghossein Virginia Steen 《Presse medicale (Paris, France : 1983)》2021,50(1):104063
Scleroderma renal crisis (SRC) is a rare but life-threatening complication of systemic sclerosis (SSc) characterized by malignant hypertension and acute kidney injury. Historically, SRC was the leading cause of death in SSc. However, with the advent of angiotensin converting enzyme (ACE) inhibitors, mortality rates have decreased significantly. Nevertheless, one-year outcomes remain poor, with over 30% mortality and 25% of patients remaining dialysis-dependent. There is an urgent need to improve early recognition and treatment, and to identify novel treatments to improve outcomes of SRC. In this chapter, the clinical features, classification, pathophysiology, differential diagnosis, management and outcomes of SRC are presented. Specific issues relating to pregnancy, prophylactic ACE inhibition and management of essential hypertension are also discussed. 相似文献
4.
Richard J Wong Mei-Ki Chan Zhenkun Yu Ronald A Ghossein Ivan Ngai Prasad S Adusumilli Brendon M Stiles Jatin P Shah Bhuvanesh Singh Yuman Fong 《Clinical cancer research》2004,10(13):4509-4516
PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application. 相似文献
5.
Cybele Blood 《Death Studies》2014,38(4):224-233
Postmortem photography is a widespread practice in perinatal bereavement care, yet few studies have explored how it affects bereaved parents, or how it might be received by parents of older children. This study is an examination of the meaning, utility, and social context of postmortem photography in a sample of 181 bereaved parents. Data were subjected to both quantitative and qualitative analysis. Photographs were positively regarded by most parents after perinatal death and several parents of older children. Other parents rejected postmortem photography for aesthetic, personal, or cultural reasons. Brief recommendations are offered for healthcare providers. 相似文献
6.
Robbins RJ Srivastava S Shaha A Ghossein R Larson SM Fleisher M Tuttle RM 《The Journal of clinical endocrinology and metabolism》2004,89(12):6010-6016
The serum thyroglobulin (Tg) level is the most sensitive marker for detecting residual thyroid carcinoma. We hypothesized that the basal and TSH-stimulated Tg levels in patients with metastatic thyroid carcinoma would reflect tumor volume, histological subtype, and location of metastatic lesions. A retrospective review of 417 thyroid cancer survivors undergoing evaluation for residual disease with the assistance of recombinant human TSH (rhTSH) was performed. In 169 patients with metastatic disease, we found that the basal Tg level directly correlated with the number of lesions, and that it was highest in patients with follicular and lowest in those with papillary thyroid carcinoma. The basal Tg level was highest in patients with bone metastases and lowest in those with cervical metastases. The fold increase in the serum Tg after rhTSH treatment was highest in papillary thyroid carcinoma and lowest in Hurthle cell carcinoma. The fold increase in Tg was not influenced by tumor volume or by the site of metastatic lesions. Multivariate analysis showed multiple interactions between factors, but did not identify one factor that significantly influenced basal Tg or fold increase. We conclude that the location and volume of metastases influence basal Tg, but not its responsiveness to rhTSH, whereas the histological type of carcinoma influences both basal Tg and responsiveness to rhTSH. 相似文献
7.
8.
Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression 总被引:1,自引:0,他引:1
BACKGROUND: Genetic screening studies suggest that genetic changes underlie progression from well differentiated to anaplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression. METHODS: Tissue microarrarys (TMAs) were constructed from well-differentiated papillary thyroid carcinoma (WDPTC; n = 41), poorly differentiated thyroid carcinoma (PDTC; n = 43), and anaplastic thyroid carcinoma (ATC; n = 22). TMAs were immunostained for 7 different cell cycle/apoptosis-related genes (p53, Ki-67, bcl-2, mdm-2, cyclin D1, p21, and p27). RESULTS: p53 (0%, 12%, 32%) and Ki-67 (5%, 49%, 82%) were expressed with increasing frequency, and bcl-2 (68%, 42%, 0%) and p21 (40%, 7%, 0%) with decreasing frequency in WDPTC to PDTC and ATC, respectively (P < .001). Interestingly, mdm-2 (54%, 5%, 0%) showed decreased expression along the progression axis (P < .001). p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression from WDPTC to PDTC to ATC. CONCLUSIONS: These data confirm the presence of increasing genetic complexity with progressive dedifferentiation in thyroid cancer, with aberrant tumor suppressor activity and increased proliferative activity being most prevalent in ATC. The data also confirm the intermediate position of PDTC in the classification scheme of thyroid carcinomas. 相似文献
9.
10.
Jesse Rijks MD Mohammed A. Ghossein MD Philippe C. Wouters MD PhD Muhammet Dural MD Alexander H. Maass MD PhD Mathias Meine MD PhD Mariëlle Kloosterman MD PhD Justin Luermans MD PhD Frits W. Prinzen MD PhD Kevin Vernooy MD PhD Antonius M. W. van Stipdonk MD PhD 《Journal of cardiovascular electrophysiology》2023,34(4):1006-1014