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

Saperconazole (R 66905) is a broad-spectrum antifungal triazole with potent in vitro activity against Aspergillus spp. A total of 279 strains were tested in brain heart infusion broth. Development of the Aspergillus spp. was completely inhibited at 0.1 and 1 microgram of saperconazole per ml for 80.3 and 99.6% of the strains, respectively. Normal and immunocompromised guinea pigs were infected intravenously with Aspergillus fumigatus and treated orally, intravenously, or intraperitoneally with saperconazole or intraperitoneally with amphotericin B. Leukopenia, neutropenia, lymphocytosis, and monocytosis were obtained with mechlorethamine hydrochloride; leukopenia, neutrophilia, and lymphopenia were obtained with cyclophosphamide. Saperconazole was dissolved for oral treatment in polyethylene glycol and for parenteral treatment in cyclodextrins. Amphotericin B was given parenterally as Fungizone (E.R. Squibb & Sons). Treatment was given once daily for 14 days. An early starting treatment was efficacious, but the activity of saperconazole was maintained even when the onset of the treatment was delayed to the moribund state. The activity of saperconazole was not altered in immunocompromised animals. Saperconazole was clearly superior to amphotericin B and free of side effects. The oral and parenteral formulations of saperconazole were equipotent. The systemic activity of saperconazole in guinea pigs was confirmed in invasive aspergillosis in pigeons.
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PMID:Oral and parenteral therapy with saperconazole (R 66905) of invasive aspergillosis in normal and immunocompromised animals. 261 73

We report a 5-year-old girl with adenosine deaminase (ADA) deficiency who was asymptomatic during the first years of life. At 3 years of age, she developed chronic and recurrent sinopulmonary infections, and at 4 1/2 years of age she had one major infection with Streptococcus pneumoniae (bacteremia and septic arthritis of the hip). Immunologic evaluation at 5 years of age revealed persistent lymphopenia, decreased helper-suppressor T cell ratios, and low proliferative responses to mitogens. The IgG, IgM, and IgA levels were normal; the IgG2 level was low normal or below normal. The patient had specific antibodies against toxoids and viral antigens but failed to produce antibodies against Haemophilus influenzae type b and pneumococcal polysaccharides. Although no symptoms of allergy were present, she had persistent eosinophilia and elevated IgE levels. The patient had 0.6% of normal ADA activity in erythrocytes and approximately 1% of normal ADA activity in peripheral blood mononuclear cells. Beginning at 6 years of age, she was treated with weekly injections of polyethylene glycol-modified bovine ADA. This treatment was well tolerated and effectively reversed the biochemical consequence of ADA deficiency. Concomitantly, she improved clinically and her T lymphocyte numbers and blastogenic responses to mitogens in vitro became normal. The late onset of clinical symptoms and relatively benign clinical course in this patient emphasize the need to consider ADA deficiency in a broad spectrum of immunodeficient children.
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PMID:Adenosine deaminase deficiency with late onset of recurrent infections: response to treatment with polyethylene glycol-modified adenosine deaminase. 326 Sep 44

Diethylene glycol monomethyl ether (DEGME) has been selected as a replacement anti-icing additive for ethylene glycol monomethyl ether (EGME) in Navy jet aircraft fuel. This experiment was performed to determine whether DEGME produced similar toxicity to EGME following dermal exposure. Male guinea pigs were dermally exposed to 1.00, 0.20, 0.04, or 0 (control) g/kg/day DEGME for 13 weeks, 5 days/week, 6 hr/day. Another group of animals was similarly exposed to 1.00 g/kg/day EGME. Body weights as well as testicular and splenic weights were reduced as a result of exposure to EGME, DEGME-exposed animals exhibited decreased splenic weight in the high- and medium-dose (1.00 and 0.20 g/kg/day) exposure groups only. Hematologic changes in EGME-exposed animals included mild anemia with increased erythrocytic mean corpuscular volumes and a lymphopenia with increased neutrophils. Similar hematological changes were not observed in any animals exposed to DEGME. Serum creatine kinase activity was increased in animals exposed to EGME, and serum lactate dehydrogenase activity was increased in EGME and 1.00 g/kg/day DEGME-exposed animals. In general, DEGME produced minimal toxicological changes following dermal exposure, whereas the toxicological changes observed following similar exposure to EGME were much more profound.
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PMID:A subchronic dermal exposure study of diethylene glycol monomethyl ether and ethylene glycol monomethyl ether in the male guinea pig. 369 23

Clinicopathologic findings were retrospectively evaluated in 26 cats and 24 dogs with ethylene glycol intoxication. Common clinical signs were ataxia, depression, vomiting, and hypothermia. Characteristic alterations in the hemogram and serum chemical profile included neutrophilia, lymphopenia, azotemia, hyperphosphatemia, hypocalcemia, hyperglycemia, and decreased whole blood bicarbonate. Common urinalysis findings included isosthenuria, proteinuria, glucosuria, hematuria, calcium oxalate and hippurate crystalluria, and the presence of renal epithelial cells, white blood cells, and granular and cellular casts in the urine sediment. The high death rate (78%) was attributed to delays in presentation, diagnosis, and therapy.
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PMID:Clinicopathologic findings in dogs and cats with ethylene glycol intoxication. 669 34

The phagocytic activity of polymorphonuclears from peripheral blood (PMN) and the qualitative characteristic of lymphocyte populations and circulating immune complexes (CIC) were studied dynamically in 35 infants with salmonellosis. The phagocytic activity of PMNs was evaluated by phagocytic index, phagocytic number, the absolute phagocytic index and the nitroblue tetrazolium test. Lymphocyte populations were determined by immunofluoroscent assay with monoclonal antibodies, and CIC by precipitation with polyethylene glycol. Decreased level of the PMNs phagocytic activity was found in the acute phase of salmonellosis. Both B- and T-lymphopenia with subset dysbalance associated with greater decrease of T4 lymphocytes were identified. During the convalescent period the immunological parameters of the bacteriologically healthy infants were close to normal whereas the Salmonella bacteria carriers demonstrated deviations which persisted in the acute phase of the disease. The immunological parameters studied can be used as additional diagnostic and prognostic criteria in infants with salmonellosis.
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PMID:A study on some immunological parameters in infants with salmonellosis. 957 45

Adenosine deaminase (ADA) is an enzyme involved in purine metabolism and has a major role in the development and function of lymphoid cells. Congenital deficiency of ADA results in severe immunodeficiency. Patients with congenital ADA deficiency treated with polyethylene glycol-conjugated bovine ADA develop antibodies to ADA. This leads us to investigate the role of anti-ADA antibodies in patients with systemic rheumatic diseases. Commercially available ADA was used in ELISA and immunoblots for detection of anti-ADA antibodies. Four out of 100 patients examined were positive for anti-ADA antibodies. Two of them had peripheral blood lymphopenia but the antibody levels did not appear to correlate with the lymphocyte counts. Immunoblotting revealed that the antibodies recognized a 40 kDa peptide of ADA, corresponding to ADA1, the major component of ADA. Affinity-purified antibodies were used to locate the distribution of ADA on Hep-2 cells and lymphocytes by indirect immunofluorescence. Anti-ADA antibodies gave a distinct nuclear speckled pattern on acetone-fixed cells. With viable cell immunofluorescence, anti-ADA antibodies also stained the cell surface of HEp-2 cells and lymphocytes, indicating surface expression of ADA. The anti-ADA antibodies failed to gain access into the cytoplasm or nuclei when added to the cultures of HEp-2 cells. In summary, this is the first report of detection of anti-ADA1 autoantibody which is a new type of ANA with discrete, speckled nuclear staining, but which may not be associated with lymphopenia.
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PMID:Anti-adenosine deaminase antibodies in lupus erythematosus. 1199 81

We describe the effects of polyethylene glycol-conjugated adenosine deaminase (ADA) replacement therapy on lymphocyte counts, activation, apoptosis, proliferation, and cytokine secretion in a 14-month-old girl with "delayed-onset" ADA deficiency and marked immunodysregulation. Pretreatment lymphopenia affected T cells (CD4, 150/microl; CD8, 459/microl), B cells (16/microl), and NK cells (55/microl). T cells were uniformly activated and largely apoptotic (CD4, 59%; CD8, 82%); and T-cell-dependent cytokine levels in plasma were elevated, including the levels of interleukin 2 (IL-2; 26 pg/ml), IL-4 (81 pg/ml), IL-5 (46 pg/ml), gamma interferon (1,430 pg/ml), tumor necrosis factor alpha (210 pg/ml), and IL-10 (168 pg/ml). Mitogen-stimulated peripheral blood mononuclear cells show reduced IL-2 secretion and proliferation. During the first 5 months of therapy there was clinical improvement and partial immune reconstitution, with nearly normal lymphocyte subset numbers, reduced T-cell activation and CD4-cell apoptosis, and decreased plasma cytokine levels. In parallel, IL-2 secretion and the lymphocyte mitogenic response improved. Between 4 and 7 months, immunoglobulin G antibodies to bovine ADA developed and resulted in the complete reversal of immune recovery.
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PMID:polyethylene glycol-conjugated adenosine deaminase (ADA) therapy provides temporary immune reconstitution to a child with delayed-onset ADA deficiency. 1652 90

Adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) comprises approximately 10% to 15% of all cases of SCID. The clinical effects of ADA deficiency are manifest most dramatically in the immune system, where it leads to severe lymphopenia. Although hematopoietic stem cell transplantation remains the mainstay of treatment for ADA-deficient SCID, 2 other treatment options are available, namely enzyme replacement therapy with PEG-ADA and autologous hematopoietic stem cell gene therapy. In this article the author reviews the available data on treatment by these different options, and offers an overview on when each of the different treatment options should be used.
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PMID:Bone marrow transplantation and alternatives for adenosine deaminase deficiency. 2049 98

Scant information exists about pegylated interferons (PEG-IFNs) use for treating hypereosinophilic syndrome (HES). We describe 6 patients with HES-1 patient with a newly identified chromosomal abnormality-who received PEG-IFNs. PEG-IFN alpha-2b replaced interferon (IFN) alpha-2b for 4 patients and was initial treatment of 2 patients. PEG-IFN alpha-2a was substituted when PEG-IFN alpha-2b became unavailable. PEG-IFNs were well tolerated and controlled eosinophilia. The dose of PEG-IFNs often could be tapered and the interval between doses lengthened beyond 7 days. Adverse effects included dose-related increases in liver enzyme levels, hair loss, mild lymphopenia, and neutropenia. PEG-IFNs are effective treatment of HES.
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PMID:Use of pegylated interferon in hypereosinophilic syndrome. 2211 11

Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive, and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene therapy (HSC-GT). Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties.
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PMID:Autoimmune dysregulation and purine metabolism in adenosine deaminase deficiency. 2296 65


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