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)

We examined T cell development and T cell repertoire in transgenic mice expressing a single T cell receptor (TCR) alpha chain derived from the H-2Db-lymphocytic choriomeningitis virus (LCMV)-specific cytolytic T lymphocyte (CTL) clone P14. To generate these alpha P14 mice, mice transgenic for the P14 TCR alpha chain were backcrossed to TCR alpha-deficient mice. Thymi from alpha P14 mice exhibited a marked decrease of mature CD4+8- and CD8+4- single-positive thymocytes comparable to thymi from TCR alpha-deficient mice. Correspondingly, the number of peripheral T cells was reduced in the CD4 (tenfold) and in the CD8 (twofold) subsets when compared to normal mice. T cells from alpha P14 mice generated a primary anti-LCMV CTL response when stimulated in vitro with LCMV in contrast to normal mice which require priming in vivo; elimination of LCMV in vivo was, however, not improved. Flow cytometric analysis of T cells with V beta-specific antibodies showed a diverse endogenous TCR V beta repertoire. Functional analysis of the T cell repertoire, however, revealed a strongly reduced (30-fold) allogeneic and the absence of a vesicular stomatitis virus-specific CTL response and an impaired ability to provide T cell help for antibody isotype switching. Thus, T cell selection in the thymus was impaired and the T cell repertoire was limited in mice expressing only one type of TCR alpha chain.
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PMID:T cell development and repertoire of mice expressing a single T cell receptor alpha chain. 758 40

Infectious disease specialists have proposed guidelines on diagnostic evaluation of HIV infected patients with diarrhea. They are based on using clues from a careful history, physical examination, and evaluation of known laboratory data. Early on, clinicians must differentiate between small and large bowel diarrhea to properly evaluate any patient with diarrhea. If available, they should use the patient's absolute CD4 count, duration of diarrhea, frequency and characteristics of stools, degree of weight loss, and exposure history (e.g., residence and water supply). When conducting the patient history, clinicians should ask about recent antibiotic or antiretroviral use, previous opportunistic infections, and other illnesses or hospitalizations. The physical exam should include height and weight, orthostatic blood pressure, and degree of wasting. Abnormalities of skin and mucous membrane may indicate nutrient deficiencies (e.g., vitamin B deficiency = stomatitis). The disease specialists provide us with an algorithm to the diagnostic evaluation of HIV infected patients with diarrhea using the CD4 cell count and the type of diarrhea (small or large bowel) as the defining factors. For example, clinicians should request stool cultures for Salmonella, Campylobacter, and Yersinia and examination with saline and iodine for the presence of ova and parasites for patients with CD4 counts greater than 200 cells x 1 million/l and small bowel diarrhea. If the patient also has a fever, blood cultures should be done to test for Salmonella. If all these tests are negative and the patient still has symptoms, modified acid-fast staining should be done to look for cryptosporidium oocysts. If this test is negative and symptoms continue, upper endoscopy with biopsy is warranted. This strategy should result in a less time-consuming and more directed diagnostic strategy that may improve quality of life.
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PMID:Diagnostic strategies in HIV-infected patients with diarrhea. 766 16

We have analyzed cytotoxic thymus-derived lymphocyte (CTL) responses to vesicular stomatitis virus (VSV) to determine whether VSV precursor CTL (pCTL) can be primed in vivo in the absence of CD4+ cells. Our studies demonstrated that secondary anti-VSV CTL responses in vitro were markedly reduced by CD4-depletion prior to priming in vivo with VSV. Limiting dilution analysis indicated that the vast majority (> 90%) of VSV pCTL failed to become primed when exposed to VSV in the absence of CD4+ cells. A second minor population (5-10%) of pCTL was identified that was reproducibly primed in CD4-deficient mice. In contrast to CD4-depleted mice infected with free, infectious virus, CD4-deficient mice primed with VSV-infected, activated B cells mounted normal secondary anti-VSV CTL responses in vitro. Precursor estimates indicated that virtually all VSV pCTL became primed using this cellular immunogen. CD4-independent priming could not be achieved using VSV-infected, activated T cells, another permissive cell type for VSV replication. Thus, most VSV pCTL require inductive signals from classical CD4+ helper T cells in order to become primed in vivo and this requirement may be regulated in vivo by the antigen presenting cell.
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PMID:Priming antiviral cytotoxic T lymphocytes: requirement for CD4+ cells is dependent on the antigen presenting cell in vivo. 791 64

Previously, we and others have demonstrated that CD4-deficient mice have a normal number of T cells and B cells with a significant population of CD4-8-TcR alpha beta+ T cells. Surprisingly, however, these mice lacking CD4 show in vivo immunoglobulin isotype class switching from IgM to IgG in response to sheep erythrocytes and vesicular stomatitis virus. In this study we have depleted various subpopulations of T cells in vivo and shown that the population of CD4-8-TcR alpha beta+ T cells is responsible for providing "help" in the antibody response of CD4-deficient mice to vesicular stomatitis virus infection. We have used antigen-specific proliferation assays and blocking studies with class I and II major histocompatibility complex (MHC)-specific purified antibodies to show that these cells are class II MHC-restricted in responses against the T cell-dependent antigen keyhole limpet hemocyanin (KLH). Finally, phenotypic analysis of the CD4-CD8- thymocytes in CD4-deficient mice shows that these cells have a more mature phenotype than the CD4-8- thymocytes in wild type mice. These results indicate that CD4 is not absolutely necessary for positive selection or effector function of class II MHC-restricted helper T cells.
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PMID:Class II major histocompatibility complex-restricted T cell function in CD4-deficient mice. 791 97

To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies. Human CD4+DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide. These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/- mice, fully and stably reconstituting this limb of the human immune system in mice. This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS).
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PMID:Human CD4-major histocompatibility complex class II (DQw6) transgenic mice in an endogenous CD4/CD8-deficient background: reconstitution of phenotype and human-restricted function. 796 66

The small membrane protein Vpu of human immunodeficiency virus type 1 stimulates rapid degradation of CD4 molecules that are retained in the endoplasmic reticulum. To analyze the domain(s) of CD4 involved in Vpu-stimulated degradation, we examined degradation of hybrid proteins made between the vesicular stomatitis virus glycoprotein (VSV G) and CD4. Vpu expression stimulated rapid degradation of a hybrid consisting of the extracellular domain of VSV G linked to the transmembrane and cytoplasmic domains of CD4. Analysis of additional hybrids showed that both the cytoplasmic and transmembrane domains of CD4 were required for this Vpu-stimulated degradation. This conclusion is in apparent conflict with a recent study showing that the cytoplasmic domain of CD4 alone is sufficient to cause Vpu-stimulated degradation of a CD8-CD4 hybrid protein. The apparent conflict may be explained by the presence of related sequences or structures in the transmembrane domains of CD4 and CD8 that are involved in binding Vpu directly or that interact with the Vpu-stimulated degradation system.
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PMID:Stimulation of heterologous protein degradation by the Vpu protein of HIV-1 requires the transmembrane and cytoplasmic domains of CD4. 809 84

To determine whether central neuropathogenesis associated with vesicular stomatitis virus (VSV) infection is regulated by T cells, we have examined the effects of intranasal infection of mice lacking T cells. The mice examined were of two kinds: (i) thymus-deficient BALB/c nu/nu nice and (ii) BALB/c mice experimentally depleted of T cells by systemic infusions of a monoclonal antibody to the CD4 or CD8 cell surface molecules. These mice were infected intranasally with a single dose of replication-competent VSV. Brain tissue homogenates were analyzed for the presence of infectious virus. For each population of mice, infection-related mortality was assessed. In histological sections of brain, the distribution of viral antigens (Ags) was examined by immunocytochemistry. We found that recovery of infectious virus from homogenates of tissues obtained from athymic nu/nu animals was more than 10 times greater than that from samples from their euthymic littermates. With a single exception in a BALB/c nu/nu mouse, virus was not isolated from the spleen when it was administered intranasally. In these experimental infections, athymic mice succumbed 1 to 2 days before their euthymic littermates. A dose of virus that resulted in half of the nu/+ survival rate was uniformly lethal to nu/nu mice. In experiments with BALB/c mice depleted of either CD4+ or CD8+ T cells by in vivo antibody treatment, histological analysis revealed an increase in viral Ag distribution in comparison with control (medium-infused) infected mice. Necrosis and inflammation paralleled the extent of viral Ag expression. Viral Ags were detected in discrete areas that usually remain uninfected in immunocompetent mice. These areas include the neocortex and caudate putamen nuclei, the piriform cortex, and the lateral olfactory tract. Neuronal loss and necrosis were consistently found in the olfactory bulb and the horizontal/vertical band of Broca. In some of the T-cell depleted mice, necrosis was also evident in the hippocampus, fimbria, mammillary bodies, and hypothalamic nuclei. In the brain stem, perivascular cuffing was evident, but with little necrosis. Collectively, these data suggest that CD4+ and CD8+ T cells make only a minor contribution to the development of histopathology but rather function together to limit viral replication and transsynaptic or ventricular spread of virus, thus promoting recovery. The primary effectors of histopathology appear to be related more to the cytopathologic nature of the virus infection and non-T-cell-mediated mechanisms.
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PMID:Central neuropathogenesis of vesicular stomatitis virus infection of immunodeficient mice. 810 6

Experimental infection with the Mt. Airy isolate of feline immunodeficiency virus (FIVMA), a lentivirus isolated from a domestic cat exhibiting signs of an immunodeficiency-like syndrome, results in transient lymphadenopathy, fever, stomatitis, enteritis, neurologic abnormalities, and immunosuppression. The effects of FIVMA infection on neutrophil and natural killer cell (NK) function were examined in vitro. Suppression of neutrophil chemiluminescence (CL) responses, as well as reduction in NK-mediated cytotoxicity were demonstrated. Neutrophil CL was decreased by 50% in infected cats when compared to control values. This loss of CL was present through 6 months after infection. In addition, NK-mediated cytotoxicity was approximately 50% less in FIVMA infected cats than in controls. Loss of innate immunity was paralleled with inversion in feline CD4/CD8 lymphocyte ratios and decreases in lymphocyte mitogenesis seen as early as 5 weeks after infection. These results suggest that FIVMA infection induces an immunodeficiency disorder in infected cats similar to that seen in human immunodeficiency virus infections.
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PMID:Loss of neutrophil and natural killer cell function following feline immunodeficiency virus infection. 810 92

TCR engagement in the thymus results in both survival and elimination signals for developing thymocytes. To examine whether both signals can be provided by the same cell type, we investigated the ability of a thymic epithelial cell (TEC) line 427.1, previously shown to allow positive selection in the thymus, to induce clonal deletion of immature thymocytes. [H-2b/s-->H-2s] bone marrow chimeras are non-responsive to antigens in the context of H-2b. However, chimeras that underwent intrathymic injection of H-2b/s 427.1 cells expressing vesicular stomatitis virus (VSV) nucleocapsid antigen acquired the ability to raise influenza, but not VSV specific H-2b restricted cytotoxic T lymphocyte (CTL) responses. The ability of 427.1 cells to delete CD4+CD8+ thymocytes was determined using mice transgenic for the TCR specific for ovalbumin (OVA) in the context of H-2Kb. OVA transfected, but not mock transfected 427.1 TECs, induced in vitro deletion of CD4+CD8+ TCR transgenic thymocytes manifested as a down-modulation of CD4 and CD8 molecules, a shift in the side versus forward scatter characteristics of thymocytes, and appearance of thymocytes with subdiploid content of DNA indicated the ongoing process of DNA fragmentation. The finding that the same TEC line is capable of inducing both positive and negative selection in the thymus suggests that thymocytes bearing TCRs specific for self peptides expressed by positively selecting thymic epithelium can be deleted. Therefore the expression of a unique set of MHC associated peptides by TECs does not appear to be the basis for the positive outcome of the TCR ligation on immature thymocytes.
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PMID:A thymic epithelial cell line induces both positive and negative selection in the thymus. 815

Neither single-agent therapy nor any combination treatment has been satisfactory enough to be regarded as standard in systemic advanced Kaposi sarcoma. In an attempt to achieve high efficacy in combination with low toxicity, we used a new liposomal formulation of doxorubicin. Pharmacologic data had established a long plasma half-life, an increased accumulation in tumor tissue, and a decrease in uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open-label, dose-escalating trial 40 male AIDS patients with advanced Kaposi sarcoma were enrolled to receive intravenous "stealth" liposomal doxorubicin biweekly at doses of 10 mg/m2 (n = 10), 20 mg/m2 (n = 27), and 40 mg/m2 (n = 3). The median CD4 count at baseline was 25/microL. After six cycles (12 weeks), 39 patients were evaluable. Three patients (7.5%) showed a complete response, which was histologically confirmed. A partial response was documented in 33 patients (85%). Stable disease was observed in three patients (7.5%). During a median treatment duration of 25 weeks, four patients developed stomatitis (10%), and four patients (10%) experienced alopecia. The most frequent hematologic toxicity was neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 toxicity was seen in 30%. Toxicity was dose-dependent and more frequent in the 40 mg/m2 stratum. During a median observation period of 25 weeks, opportunistic infections occurred in 57.5% of the patient population. We conclude that liposomal doxorubicin at dose levels of 10 and 20 mg/m2 is safe and effective for treatment of advanced Kaposi sarcoma in AIDS. A controlled trial comparing liposomal doxorubicin to conventional combination therapy is underway.
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PMID:Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma. 815 40


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