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111.
T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T- cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common V alpha nor a common J alpha segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the beta chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common V alpha (V alpha 19.1). In contrast to this common V alpha usage, there was a marked diversity of the J alpha segments and N-region addition that were associated with the V alpha 19.1 segment. This pattern of common V alpha usage associated with different N and J alpha segments suggests an immune-mediated selection process affecting the TCR alpha chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR alpha chain and that this autoreactivity might be implicated in this patient's anemia. 相似文献
112.
Lipomatous polyposis of the colon with multiple lipomas of peritoneal folds and giant diverticulosis
A case of multiple lipomatosis exclusively located in the colon is reported in a young male (33 years). It is characterized by a great number of lipomas with polyposis growth appearance, multiple lipomas of peritoneal folds, and giant diverticulosis probably caused by weakened areas of colonic wall induced by the lipomas. 相似文献
113.
114.
Joseph S. Gimbel Alan J. Kivitz Candace Bramson Mary Anne Nemeth David S. Keller Mark T. Brown Christine R. West Kenneth M. Verburg 《Pain》2014
A noncontrolled, randomized, multicenter study (NCT00924664) evaluated long-term safety and effectiveness of tanezumab in patients with chronic low back pain following a randomized placebo- and active-controlled parent study that evaluated analgesic efficacy. Patients were randomized to tanezumab 10 mg (n = 321) or 20 mg (n = 527) administered at 8-week intervals via 3 intravenous injections followed by 4 subcutaneous injections. Effectiveness analyses included change from parent study baseline in Brief Pain Inventory Short Form, Roland Morris Disability Questionnaire, and Patient’s Global Assessment of low back pain. Safety assessments included adverse event documentation, physical/neurological examinations, and laboratory tests. Mean treatment duration during the extension study was 194 and 202 days with tanezumab 10 and 20 mg, respectively. Both tanezumab doses provided similar and sustained improvements in all effectiveness outcomes. The most frequently reported adverse events were arthralgia, paresthesia, and hypoesthesia. Adverse events initially described as osteonecrosis were reported in 6 patients (tanezumab 10 mg, n = 2; tanezumab 20 mg, n = 4); 9 additional patients (tanezumab 10 mg, n = 7; tanezumab 20 mg, n = 2) underwent total joint replacement (TJR). A blinded, independent adjudication committee reviewed all 6 patients with reported osteonecrosis and 4 of the 9 patients undergoing TJR. Adjudication outcomes were osteonecrosis (n = 0), worsening osteoarthritis (n = 5; 1 rapidly progressive), and another diagnosis or indeterminate (n = 5). Tanezumab 10 mg had better tolerability than tanezumab 20 mg, and may represent an effective long-term treatment for chronic low back pain. 相似文献
115.
Christina L. Nemeth
zgül Gk Sophia N. Tomlinson Anjali Sharma Ann B. Moser Sujatha Kannan Rangaramanujam M. Kannan Ali Fatemi 《Neurotherapeutics》2023,20(1):272
X-linked adrenoleukodystrophy (ALD) is a genetic disorder that presents neurologically as either a rapid and fatal cerebral demyelinating disease in childhood (childhood cerebral adrenoleukodystrophy; ccALD) or slow degeneration of the spinal cord in adulthood (adrenomyeloneuropathy; AMN). All forms of ALD result from mutations in the ATP Binding Cassette Subfamily D Member (ABCD) 1 gene, encoding a peroxisomal transporter responsible for the import of very long chain fatty acids (VLCFA) and results mechanistically in a complex array of dysfunction, including endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, and inflammation. Few therapeutic options exist for these patients; however, an additional peroxisomal transport protein (ABCD2) has been successfully targeted previously for compensation of dysfunctional ABCD1. 4-Phenylbutyrate (4PBA), a potent activator of the ABCD1 homolog ABCD2, is FDA approved, but use for ALD has been stymied by a short half-life and thus a need for unfeasibly high doses. We conjugated 4PBA to hydroxyl polyamidoamine (PAMAM) dendrimers (D-4PBA) to a create a long-lasting and intracellularly targeted approach which crosses the blood–brain barrier to upregulate Abcd2 and its downstream pathways. Across two studies, Abcd1 knockout mice administered D-4PBA long term showed neurobehavioral improvement and increased Abcd2 expression. Furthermore, when the conjugate was administered early, significant reduction of VLCFA and improved survival of spinal cord neurons was observed. Taken together, these data show improved efficacy of D-4PBA compared to previous studies of free 4PBA alone, and promise for D-4PBA in the treatment of complex and chronic neurodegenerative diseases using a dendrimer delivery platform that has shown successes in recent clinical trials. While recovery in our studies was partial, combined therapies on the dendrimer platform may offer a safe and complete strategy for treatment of ALD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01311-x. 相似文献
116.
松花粉和松针提取物在亲脂性体外模型系统中抗氧化能力和机制的研究 总被引:3,自引:0,他引:3
目的:对松花粉和松针提取物在亲脂性抗氧化模型系统中的抗氧化能力和机制进行研究。方法:采用铜诱导的LDL氧化反应模型和Rose Bengal反应模型分别进行评价。结果:松花粉乙醇提取液具有较好的自由基链式反应阻断剂的作用,有效地推迟人血浆中低密度脂蛋白(LDL)氧化生成共轭二烯。松针乙醇提取液对LDL的保护作用优于松花粉。在Rose Bengal系统中,松花粉以清除自由基和螯合铜的两种机制抑制脂质过氧化反应的发生,而松针主要作为自由基清除剂发挥抗氧化作用。结论:松花粉和松针在两个亲脂性体外模型中均发挥很好的抗氧化能力,而抗氧化机制不尽相同。 相似文献
117.
Nikoletta Nagy Katalin Farkas Ágnes Kinyo Istvan B. Nemeth Erika Kis János Varga Zsuzsanna Bata‐Csorgo Lajos Kemeny Márta Szell 《Experimental dermatology》2012,21(12):967-969
Brooke–Spiegler syndrome (BSS; OMIM 605041) is an autosomal dominant disease characterized by skin appendage tumors due to mutations in the cylindromatosis gene (CYLD). We investigated a Hungarian BSS pedigree with two affected members, father and daughter. Direct sequencing demonstrated a novel missense mutation (c.2613C>G; p.His871Gln) in exon 19 within the ubiquitin‐specific protease domain of the encoded protein. We performed preliminary analysis to reveal the functional role of this novel mutation. Our data suggest that this novel CYLD mutation leads to increased ubiquitination of NEMO through influencing deubiquitinating activity of the CYLD protein and thus may result in enhanced NF‐κB signalling. 相似文献
118.
Robert A. Ersek M.D. F.A.C.S. Jose Alberto Navarro Dora Zsofia Nemeth George Sas M.D. 《Aesthetic plastic surgery》1993,17(3):225-228
Breast implants have evolved from the original saline-filled, smooth-surfaced silicone rubber bag to silicone gel-filled smooth-walled sacs to a combination of a silicone gel-filled bag within a saline-filled sac, and, most recently, a reversed, double-lumen implant with a saline bag inside of a gel-filled bag. Texture-surfaced implants were first used in 1970 when the standard silicone gelfilled implant was covered with a polyurethane foam. Because of concerns about the degradation products of this foam, they were removed from the market in 1991. In 1975 double-lumen silicone textured implants were developed, followed by silicone gel-filled textured implants. In 1990 a new radiolucent, biocompatible gel was produced that reduced the problem of radioopacity of silicone implants. Because of the gel's sufficiently low coefficient of friction, leakage caused by fold flaw freacture may also be decreased. We present a case where this new biocompatible gel implant was repositioned after four months. The resulting scar capsule in this soft breast was thin [<0.002 cm (0.008 in.)] and evenly textured as a mirror image of the textured silicone surface. Scanning electron microscopy and x-ray defraction spectrophotometry revealed no silicone bleed. 相似文献
119.
Ambulatory sclerotherapy for malignant pleural effusions 总被引:12,自引:0,他引:12
120.
EMG activity from eight shoulder muscles in parallel was recorded from 4 patients with generalized joint laxity. During external rotation of the humerus in 45° abduction, humeroscapular dislocation occurred in 2 patients and subluxation in the 2 others. The activity level in the subscapularis was low, and the activation speed was slow. The low muscle activity and delay in activation of the subscapularis muscle may contribute to the instability. 相似文献