Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.
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PMID:Clinical effects and pharmacokinetics of different dosage schedules of adriamycin. 94 83

T cell hybridomas with specificity for VSV (vesicular stomatitis virus)-infected cells were generated in an attempt to better define the la-restricted helper T cell response to VSV. The hybridomas were created by fusing BALB/c (H-2d) anti-VSV immune spleen cells to the murine thymoma BW 5147. These hybridomas produce IL-2 when stimulated with VSV-infected spleen cells. They were found to recognize viral antigens in association with I-Ad and, in addition, could also be stimulated by VSV-infected A20 cells (an Ia-positive B cell lymphoma of H-2d origin). The purified viral membrane glycoprotein, G protein, and Gs (secreted G protein that lacks the hydrophobic and intracytoplasmic domains) both stimulated IL-2 production when added to cultures of A20 and the hybridomas. These hybridomas therefore recognize a viral antigenic determinant on G protein. Since chemically-fixed antigen-presenting cells fail to stimulate the hybridomas after exogenous addition of purified G protein we can conclude that these T cell hybridomas recognize a processed form of the G protein. Stimulator cells created by expression in A20 of a transfected cDNA encoding G protein were also recognized. Recognition in this case was I-Ad-restricted, as anti-I-Ad monoclonal antibodies blocked stimulation, and an Ia-negative cell (P815) expressing a transfected G protein gene failed to stimulate the hybridomas. Even after paraformaldehyde fixation, G gene-transfected, Ia-positive cells could stimulate the hybridomas, suggesting that processing of this endogenously-synthesized antigen has occurred.
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PMID:T cell hybridomas define the class II MHC-restricted response to vesicular stomatitis virus infection. 285 79

Cytotoxic T lymphocytes (CTL) recognize antigenic peptides bound to major histocompatibility complex class I antigens on the cell surface of virus-infected cells. It is believed that the majority of peptides originate from cytoplasmic degradation of proteins assumed to be mediated by the "20S" proteasome. Cytosolic peptides are then translocated, presumably by transporters associated with antigen processing (TAP-1 and -2), into the lumen of the endoplasmic reticulum (ER) where binding and formation of the ternary complex between heavy chain, beta2-microglobulin (beta 2m) and peptide occurs. In this study, we have analyzed and compared the phenotype of two mutant cell lines, the thymoma cell line RMA-S and a small lung carcinoma cell line CMT.64, in order to address the mechanism that underlies the antigen processing deficiency of CMT.64 cells. Unlike RMA-S cells, vesicular stomatitis virus (VSV)-infected CMT.64 cells are not recognized by specific CTL. Interferon gamma (IFN-gamma) treatment of CMT.64 cells restores the ability of these cells to process and present VSV in the context of Kb. We show that although CMT.64 cells express a low level of beta 2m, the recognition of VSV-specific CTL is not restored by increasing the amount of beta 2m synthesized in CMT.64 cells. In addition, we find that CMT.64 cells express moderate levels of Kb heavy chain molecules, but most of it is unstable and rapidly degraded in the absence of IFN-gamma treatment. We infer that the antigen processing deficiency does not lie at the level of beta 2m or Kb production. We find also that the mRNAs for both TAP-1 and -2 are present in RMA and RMA-S cells but are absent in uninduced CMT.64 cells. Upon IFN-gamma induction, both mRNAs are highly expressed in CMT-64 cells. In addition, we find that the low molecular mass polypeptides 2 and 7, and additional components of the proteasome are induced by IFN-gamma in CMT-64 cells. Finally, introduction of the rat TAP-1 gene in CMT.64 cells restores CTL recognition of VSV-infected cells. These results indicate that a TAP-1 homodimer may translocate peptides in the ER and explain partially the CMT.64 defect and the RMA-S phenotype. These findings link a dysfunction in the transport and/or generation of antigenic peptides to the capacity of tumor cells to evade immunosurveillance and provide a unique model system to dissect this phenomenon.
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PMID:Comparison of cell lines deficient in antigen presentation reveals a functional role for TAP-1 alone in antigen processing. 793 Oct 74

Induction of immunity to a viral protein that had been transfected into a tumor cell line was studied. The nucleoprotein (NP) of vesicular stomatitis virus (VSV) was used as a model tumor-associated Ag after transfection into EL-4, and H-2b thymoma originating from C57BL/6 mice. The NP-transfected cell line (EL-4NP) was lysed by NP-specific CTL and was found to restimulate NP-specific CTL in vitro as efficiently as did VSV-infected macrophages. Despite both of these in vitro characteristics, C57BL/6 mice inoculated with EL-4NP did not mount a measurable NP-specific CTL response and developed a lethal tumor as rapidly as did mice given control EL-4. This lack of immunogenicity could not be explained by down-regulation of MHC class I molecules or by loss of NP; even EL-4NP cells metastasizing to the spleen kept their high restimulatory capacity and excellent target characteristics. However, once mice were immunized with VSV or with a vaccinia-VSV-NP recombinant virus they were protected against tumor growth of EL-4NP by CD8+ CTL but not by CD4+ T cells. Taken together, the failure of the tumor-associated Ag to induce a protective T cell response in vivo despite its excellent capacity to restimulate CTL in vitro may encourage adjuvant immunotherapy in cancer; even the effects of weakly immunizing tumor vaccines, e.g., recombinant viruses, may be efficiently amplified by tumor cells.
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PMID:Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells. 809 55

A vesiculobullous disease termed paraneoplastic pemphigus with distinct autoantibodies was newly described in 1990. All reported cases have occurred in patients with a history of neoplasia, including lymphoma, chronic lymphocytic leukemia, poorly differentiated sarcoma, and benign thymoma. As in pemphigus vulgaris, intraepithelial clefts with acantholysis are noted histopathologically, and intercellular binding of immunoreactants is seen with direct immunofluorescence studies of mucous membrane and skin biopsies. However, immunoreactants may also be found along the basement membrane zone in paraneoplastic pemphigus. Indirect immunofluorescence using rat bladder epithelium as substrate shows an intercellular pattern that appears to be highly specific for paraneoplastic pemphigus. We report a patient with non-Hodgkins lymphoma of 8 years duration who developed severe erosive stomatitis and lichenoid dermatitis after receiving chemotherapy for a relapse of lymphoma. Her case illustrates the typical features of the disorder described as paraneoplastic pemphigus. Neoplasia-associated pemphigus may be a more precise term for this disorder because the course of the blistering eruption does not always parallel the course of the underlying cancer. The clinical features, histopathologic findings, and immunofluorescence findings of this unique syndrome are reviewed.
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PMID:Paraneoplastic pemphigus. A distinct autoimmune vesiculobullous disorder associated with neoplasia. 842 20

A 76-year-old woman, with a history of thymoma, presented with a painful extensive stomatitis, painful paronychia, lichenoid papules on the hands and superficial erosions on the neck and the trunk. Histological examination showed lichenoid changes, acantholytic blister formation and apoptotic keratinocytes. Direct immunofluorescence was positive for IgG both in the epidermal intercellular spaces and along the basement membrane zone. Indirect immunofluorescence was similarly positive in a pemphigus vulgaris pattern. There was only a partial response to intravenous corticoids. These findings allowed the diagnosis of paraneoplastic pemphigus. The diagnostic characteristics, histopathology and the differential diagnosis of this disease are discussed.
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PMID:Paraneoplastic pemphigus in a patient with a thymoma. 1130 45

We studied the transduction of primary human B lymphocytes and myeloma cells with lentiviral vectors. In peripheral blood B cells that had been activated with helper T cells (murine thymoma EL-4 B5) and cytokines, multiply attenuated HIV-1-derived vectors pseudotyped with vesicular stomatitis virus (VSV) G-envelope protein achieved the expression of green fluorescence protein (GFP) in 27% +/- 12% (mean +/- 1 SD; median, 27%) of B cells in different experiments. When compared in parallel cultures, the transducibility of B cells from different donors exhibited little variation. The human cytomegalovirus (CMV) promoter gave 4- to 6-fold higher GFP expression than did the human elongation factor-1alpha promoter. A murine retroviral vector pseudotyped with VSV G protein proved inefficient even in mitotically active primary B cells. B cells freshly stimulated with Epstein-Barr virus were also transducible by HIV vectors (24% +/- 9%), but B cells activated with CD40 ligand and cytokines resisted transduction. Thus, different culture systems gave different results. Freshly isolated, nondividing myeloma cells were efficiently transduced by HIV vectors; for 6 myelomas the range was 14% to 77% (median, 28%) GFP(+) cells. HIV vectors with a mutant integrase led to no significant GFP signal in primary B or myeloma cells, suggesting that vector integration was required for high transduction. In conclusion, HIV vectors are promising tools for studies of gene functions in primary human B cells and myeloma cells for the purposes of research and the development of gene therapies.
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PMID:Efficient transduction of primary human B lymphocytes and nondividing myeloma B cells with HIV-1-derived lentiviral vectors. 1240 92

Elderly individuals are susceptible to autoimmune bullous dermatoses (ABDs), which may be associated with high morbidity and mortality. ABDs result from an autoimmune response to components of the basement membrane zone at the dermal-epidermal junction or desmosomes. Bullous pemphigoid results from autoimmunity to hemidesmosomal proteins present in the basement membrane of stratified squamous epithelia. Patients present with tense blisters in flexural areas of the skin. Mild disease may be treated with potent topical corticosteroids, while extensive disease usually requires systemic corticosteroids or systemic immunosuppressive agents such as azathioprine. Mucosal pemphigoid affects one or more mucous membranes that are lined by stratified squamous epithelia. The two most commonly involved sites are the eye and the oral cavity. Lesions frequently result in scar formation that may cause blindness. Patients with severe disease or ocular involvement require aggressive therapy with corticosteroids and cyclophosphamide. Epidermolysis bullosa acquisita results from autoimmunity to type VII collagen in the anchoring fibrils of the basement membrane. Lesions may either arise on an inflammatory base or be non-inflammatory and result primarily from trauma. Treatment options include corticosteroids, dapsone, ciclosporin, methotrexate and plasmapheresis/immunoapheresis. Paraneoplastic pemphigus results from autoimmunity to multiple desmosomal antigens. The disorder is associated with neoplasms, especially leukaemia, lymphoma and thymoma. Patients present with stomatitis and polymorphous skin eruption. The disease may respond to successful treatment of the underlying neoplasm or may require immunosuppressive therapy.
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PMID:Autoimmune bullous dermatoses in the elderly: an update on pathophysiology, diagnosis and management. 2003 Apr 29

We herein firstly reported that a patient with thymoma-associated pemphigus (TAP) underwent a robotic-assisted trans-subxiphoid thoracoscopic extended thymectomy and then achieved stable resolution. The patient, a 47-year-old male, was first admitted to our hospital owing to stomatitis and bullae of the trunk after four months' prednisone treatment. On admission, chest computed tomography (CT) revealed an anterior-mediastinal mass and it was initially diagnosed as a thymoma. He was positive for anti-BP (bullous pemphigoid)-180 antibody and anti-desmoglein 3 antibody. Then, a robotic-assisted thymectomy was performed, following which, the anti-BP-180 and anti-desmoglein 3 antibody titres have declined. The patient's mucocutaneous lesions improved, and the steroid dose was gradually decreased from 60 to 40 mg/day. According to previous reports, and the experience of the presented case, we therefore believe that early extended thymectomy is an effective therapeutic intervention for TAP.
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PMID:Robotic trans-subxiphoid extended thymectomy in a patient with thymoma-associated pemphigus. 2874 Jun 98