Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and pathological analysis were performed on 127 cases of deep mycoses diagnosed by autopsy during the 24 years between 1964 and 1987 in Juntendo University Hospital. The following findings were obtained. 1) There has been a tendency for the number of mycoses to increase each year, especially notable for candidiasis and aspergillosis. 2) Underlying diseases were, in order of incidence, various hematologic diseases, solid tumors, inflammatory diseases and collagen diseases; the most common were various types of leukemia. 3) Candidiasis was often observed in patients with gastrointestinal tract cancers. Aspergillosis was often observed in patients with collagen diseases. 4) Regarding the visceral distribution of mycoses, aspergillosis was observed in the lung, candidiasis was observed in the lung, kidney and intestinal tract in decreasing order, and cryptococcosis was also observed in the lung and central nervous system. 5) There was a probability of fungal infections occurring in cases of lymphopenia. 6) A fever was present at the time of hospitalization in many cases of aspergillosis, and the presence of an indwelling catheter was a common feature in cases of candidiasis. 7) Fungemia was frequently observed in candidiasis, but very rarely in cases of aspergillosis. 8) The large amounts of corticosteroid hormones and blood transfusions were suspected as causative factors of fungal infections.
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PMID:[Clinical and pathological analysis of deep mycoses]. 206 3

In mice, monoclonal antibody (mAb) to the alpha1 integrin abrogate gastro-intestinal damage during graft-versus-host-disease (GVHD), suggesting anti alpha1 mAb as candidates for treatment in humans as well. Our current data show that one such reagent, mAb 1B3.1, when immobilized to plastic wells via rabbit- anti murine (ram) immunoglobulin (Ig) induces a protein kinase-dependent spreading of activated human T cells. Furthermore, it significantly increases the proliferative response, and expression of interleukin-2 (IL-2) receptors (R) and CD69, of resting T cells, expressing minimal integrin on the cell surface, to sub-optimal stimulation by anti-CD3 mAb. We found, in addition, that mAb 1B3.1 a) immuno-precipitates alpha1beta1 integrins from cell-surface iodinated canine epithelial cells b) is highly reactive with canine T cells after their activation and c) inhibits adhesion of canine T cells to collagen IV. Despite the potential ability of the mAb to co-activate T cells in vitro, two dogs that received 4 injections of 0.5-0.3 mg/Kg of mAb 1B3.1 remained healthy, developing only marginal transient lymphopenia. Injection of 0.75mg/Kg in a third dog induced a more marked lymphopenia, and an additional dose of 1.0 mg/Kg 2 weeks later was followed by gastrointestinal hemorrhage. importantly, the lymphopenia was associated with a greater and more persistent decrease of CD8+ than of CD4+ T cells, leading to an increase in the CD4/CD8 ratio 24 hours after the injection. Thus, despite it's co-activating effects in vitro, administration of this mAb in vivo is feasible when appropriately dosed, and may have immuno-modulatory effects.
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PMID:Parenteral administration of an activating monoclonal antibody to the alpha1beta1 integrin in dogs. 1104 60

Ataxia-telangiectasia is a syndrome of progressive cerebellar ataxia and other neurological manifestations associated with conjunctival and cutaneous telangiectases and with recurrent sino-pulmonary infections. Immunological and endocrine abnormalities occur. Two girls with this disease are described. The first had only minor respiratory infections; her serum proteins and immunity responses appeared normal. The second had recurrent pulmonary infections and bronchiectasis; she also exhibited sclerodermatous changes, poor development of secondary sexual characteristics with low urinary excretion of 17-ketosteroids, and lymphopenia. Autopsy at 17 years showed bilateral ovarian dysgerminomata and excessive cutaneous collagen as well as atrophy, and perhaps hypoplasia, of adrenals, thymus, spleen and lymphoid tissue (after steroid therapy). The cerebellum exhibited cortical degeneration. Both lungs were fibrotic with old and recent bronchopneumonia and bronchiectasis. The left lung was studied by injection of a latex preparation; no arteriovenous aneurysms were found, but the smaller pulmonary vessels showed some unusual morphological characteristics.
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PMID:ATAXIA-TELANGIECTASIA. 1422 60

A 37-year-old woman with a personal history of appendicectomy, cholecystectomy, left oophorectomy secondary to an ovarian cyst complication, nephritic colic with repeated episodes of pyelonephritis, alcoholic hepatopathy, Raynaud's phenomenon and bilateral exophthalmos showed an increase in volume in the root of the upper limbs and in the base of the neck over a period of 4 years, painful to the touch and of a soft consistency. She presented with a pseudo-athletic appearance (Fig. 1) produced by an increase in the volume at the root of the upper limbs, upper back and the back of the neck (Fig. 2). The lesions produced a pulling sensation and were associated with paresthesia, hyperesthesia, and a moderate loss of strength in both arms. A biopsy taken from the upper third of the right arm showed a diffuse proliferation of the subcutaneous adipose tissue, which appeared normal, and extended between the collagen fibers, reaching in some cases into the most superficial zones of the reticular dermis (Fig. 3). Laboratory evaluation revealed a chronic anemia, leukopenia with moderate lymphopenia, increased erythrocyte sedimentation rate, elevation of enzymes of hepatic function, decrease in total proteins, and increase in ferritin, all in the context of hepatopathy. Antinuclear antibodies and the hormonal profile were normal. Abdominal and gynecologic echography revealed a right ovarian cyst of no clinical relevance. Cranial nuclear magnetic resonance (NMR) revealed an increase in the periorbital fat responsible for bilateral exophthalmos.
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PMID:Benign symmetric lipomatosis (Launois-Bensaude syndrome). 1580 34

Galectin-3 (gal-3), a beta-galactoside-binding animal lectin, plays a role in cell-cell and cell-extracellular matrix interactions. Extracellular gal-3 modulates cell migration and adhesion in several physiological and pathological processes. Gal-3 is highly expressed in activated macrophages. Schistosoma mansoni eggs display a large amount of gal-3 ligands on their surface and elicit a well-characterized, macrophage-dependent, granulomatous, inflammatory reaction. Here, we have investigated the acute and chronic phases of S. mansoni infection in wild-type and gal-3(-/-) mice. In the absence of gal-3, chronic-phase granulomas were smaller in diameter, displaying thinner collagen fibers with a loose orientation. Schistosoma-infected gal-3(-/-) mice had remarkable changes in the monocyte/macrophage, eosinophil, and B lymphocyte subpopulations as compared with the infected wild-type mice. We observed a reduction of macrophage number, an increase in eosinophil absolute number, and a decrease in B lymphocyte subpopulation (B220(+/high) cells) in the periphery during the evolution of the disease in gal-3(-/-) mice. B lymphopenia was followed by an increase of plasma cell number in bone marrow, spleen, and mesenteric lymph nodes of the infected gal-3(-/-) mice. The plasma IgG and IgE levels also increased in these mice. Gal-3 plays a role in the organization, collagen distribution, and mobilization of inflammatory cells to chronic-phase granulomas, niches for extramedullary myelopoiesis, besides interfering with monocyte-to-macrophage and B cell-to-plasma cell differentiation.
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PMID:Kinetics of mobilization and differentiation of lymphohematopoietic cells during experimental murine schistosomiasis in galectin-3 -/- mice. 1745

Targeting angiogenesis in glioblastoma (GBM) may improve patient outcome by normalizing tumor vasculature and improving delivery of chemotherapeutics and oxygen. Consequently, concomitant administration of small molecule inhibitors of the VEGF pathway will likely have a positive impact on chemoradiation treatment outcome. We conducted a Phase I study of vatalanib, a small molecule inhibitor of VEGFR, PDGFR, and c-kit in patients with newly diagnosed GBM receiving radiation, temozolomide, and an enzyme-inducing anti-epileptic drug in order to determine the MTD of vatalanib in this patient population. We incorporated circulating biomarker and SNP analyses and pharmacokinetic studies. Nineteen patients were enrolled and the MTD was not reached at the time of study termination. Vatalanib was well tolerated with only 2 DLTs (thrombocytopenia and elevated transaminases). Other grade 3/4 toxicities included leukopenia, lymphopenia, neutropenia, and hand-foot syndrome. There were no wound-healing complications. Of the 13 patients evaluable for a radiographic response, 2 had a partial response and 9 had stable disease. Vatalanib significantly increased PlGF and sVEGFR1 in plasma circulation and decreased sVEGFR2 and sTie2. Plasma collagen IV increased significantly by day 50 of treatment. Vatalanib was well tolerated and this study demonstrates the safety of oral small molecule inhibitors in newly diagnosed GBM patients. Blood biomarkers may be useful as pharmacodynamic markers of response to anti-angiogenic therapies.
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PMID:Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide. 2082 42

Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking through the type 1 sphingosine 1-phosphate receptor (S1P(1)) and participates in many pathological conditions, including autoimmune diseases. We developed a novel S1P(1)-selective antagonist, TASP0277308, which is structurally unrelated to S1P. This antagonist competitively inhibited S1P-induced cellular responses, such as chemotaxis and receptor internalization. Furthermore, differing from previously reported S1P(1) antagonists, TASP0277308 demonstrated in vivo activities to induce lymphopenia, a block in T cell egress from the thymus, displacement of marginal zone B cells, and upregulation of CD69 expression on both T and B cells, all of which recapitulate phenotypes of S1P(1)-deficient lymphocytes. In a mouse collagen-induced arthritis model, TASP0277308 significantly suppressed the development of arthritis, even after the onset of disease. These findings provide the first chemical evidence to our knowledge that S1P(1) antagonism is responsible for immunosuppression in the treatment of autoimmune diseases and also resolve the discrepancies between genetic and chemical studies on the functions of S1P(1) in lymphocytes.
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PMID:Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatory activities. 2213 29

Sphingosine 1-phosphate (S1P) is a pleiotropic bioactive sphingolipid metabolite that regulates numerous processes important for immune responses. S1P is made within cells and must be transported out of cells to exert its effects through activation of 5 specific cell surface GPCRs in an autocrine or paracrine fashion. Spinster 2 (Spns2) transports S1P out of cells, and its deletion in mice reduces circulating levels of S1P, alters immune cell trafficking, and induces lymphopenia. Here we examined the effects of Spns2 deletion on adaptive immune responses and in autoimmune disease models. Airway inflammation and hypersensitivity as well as delayed-type contact hypersensitivity were attenuated in Spns2(-/-) mice. Similarly, Spns2 deletion reduced dextran sodium sulfate- and oxazolone-induced colitis. Intriguingly, Spns2(-/-) mice were protected from the development of experimental autoimmune encephalopathy, a model of the autoimmune disease multiple sclerosis. Deletion of Spns2 also strongly alleviated disease development in collagen-induced arthritis. These results point to a broad role for Spns2-mediated S1P transport in the initiation and development of adaptive immune related disorders.
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PMID:Spinster 2, a sphingosine-1-phosphate transporter, plays a critical role in inflammatory and autoimmune diseases. 2632 48