Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increased incidence of high-grade malignant non-Hodgkin's lymphomas has been reported in homosexual men. This phenomenon appears to represent another facet of the acquired immunodeficiency syndrome (AIDS). Histologically, the majority of these lymphomas have been small noncleaved cell lymphomas or immunoblastic lymphomas, subtypes most commonly associated with a B-cell phenotype, but immunologic data supporting this have been limited. Using a plastic embedding technique, we have examined a series of 31 malignant lymphomas, including nine from the central nervous system (CNS), in patients with AIDS or at high risk for AIDS. All 31 of the lymphomas were positive with one or more of the following B-cell markers: HLA-DR/la, Pan B, Leu 12, Leu 14, and IgM. All 31 were negative for the pan-T reagent Leu 4 and myeloid-macrophage markers (Leu M1, nonspecific esterase). In addition, seven of the nine CNS lymphomas showed strong plasma membrane staining for adenosine triphosphatase, a B-associated marker. These findings provide strong immunologic evidence for a B-cell origin in the lymphomas of AIDS.
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PMID:Malignant lymphomas in the acquired immunodeficiency syndrome. Additional evidence for a B-cell origin. 245 89

Suramin, a drug intensively used in the chemotherapy of African trypanosomiasis and onchocerciasis, is currently being tested in clinical trials for AIDS treatment. Its effects on mitochondrial energy metabolism in mammals were studied. At low concentrations it inhibited ATP synthesis and ATPase activity in submitochondrial particles, as well as ADP-stimulated oxygen consumption and the uncoupler-stimulated ATPase activity in intact rat liver mitochondria. At higher concentrations it also inhibited uncoupled electron transport in both submitochondrial particles and intact mitochondria. From comparison of the kinetic patterns of those inhibitions, evidence suggesting that the adenine nucleotide translocase may be another target for the action of suramin was obtained. The relevance of these findings to the understanding of the biochemical basis of suramin toxicity is discussed.
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PMID:Inhibition by suramin of mitochondrial ATP synthesis. 296

We used a panel of monoclonal and polyclonal antibodies to analyze frozen and paraffin-embedded lymph node biopsy specimens from 25 intravenous drug abusers (IVDA) with acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy histologically characterized by follicular hyperplasia. Our aim was to obtain diagnostic clues to this commonly occurring pattern. Double-labelling immunohistological studies were also performed on selected frozen sections and 13 plastic-embedded specimens were tested by a number of enzyme reactions. Consistent features in IVDA included abnormally high numbers of intrafollicular T-cells, positive for acid phosphatase and beta-glucuronidase, most of which had Leu-2a-positive phenotype; a marked reduction or loss of mantle zone B-cells (positive for surface IgD-IgM and alkaline phosphatase); and disarray of the network of follicular dendritic reticulum cells (DRCs), as revealed with DRC-1 and anti-S-100 protein antibodies or with reaction for 5'-nucleotidase. When present, distinctive intrafollicular clusters of Leu-2a-positive T-cells and mantle zone B-cells were nearly always associated with areas lacking DRCs in some patients. The intrafollicular hypervascularity invariably found in IVDA proved to be of a true capillary nature, as demonstrated by alkaline phosphatase, 5'-nucleotidase, and ATPase reactions. In control tissues, all showing absence of Leu-2a-positive intrafollicular T-cells, most of the above individual changes could be detected, although they were occasional, mild, and never associated within the same follicle. By contrast, combined immunohistological and enzyme histochemical findings in IVDA indicated that in most follicles such changes were marked and very often associated within the same follicle in each case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzyme and immunohistochemistry of follicular hyperplasia in AIDS-related lymphadenopathy. 345 32

Twenty-one cases (25 biopsies including 9 frozen biopsies) of Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were examined immunohistochemically, lectin-histochemically, and enzyme histochemically to ascertain the histogenesis of the lesion. The Kaposi's sarcomas were histologically subtyped according to a modified Schmid's classification (granulation tissue-like-, angiosarcoma-like- and spindle cell type). In almost all lesions, many atypical vasoforming cells and at least some spindle cells without definite evidence of vasoformation by conventional microscopy were positive for factor VIII-related antigen, BMA 120 (a new monoclonal antibody to an endothelial cell-specific antigen), Ulex europaeus I (UEA-I), alkaline phosphatase and ATPase. Linear reaction products for BMA 120 and UEA-I, suggesting the luminal surface of immature vascular channels, were sometimes recognized in the positive spindle cells. Electron micrographs confirmed endothelial characteristics, such as irregular and fragmented but distinct basal lamina and numerous pinocytotic vesicles, in both the UEA-I- and ATPase-positive spindle cells. Among spindle cells negative for the endothelial markers, there were many macrophages as a stromal reaction to tumor tissue, identified by monoclonal antibodies to macrophages (KiM 6, 7, 8 and EBM 11), acid phosphatase and alpha-naphthyl acetate esterase. The results of the immuno- and enzyme histochemical investigations did not correlate with the different histologic types of Kaposi's sarcoma. However, our results strongly suggest that tumor cells of Kaposi's sarcoma are derived from vascular endothelial cells rather than lymphatic endothelium.
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PMID:Histogenesis of Kaposi's sarcoma associated with AIDS: a histologic, immunohistochemical and enzyme histochemical study. 368 78

We investigated the possible role of a defect in antigen-presenting cells in the acquired immunodeficiency syndrome (AIDS), by enumeration of Langerhans' cells, the epidermal antigen-presenting cells. These cells were stained for the characteristic markers, surface Ia antigen and surface ATPase activity. A significant reduction was observed in the number of stained cells per square millimeter of body-surface area in 24 patients with AIDS and either opportunistic infections (Ia, 258 +/- 34, and ATPase, 274 +/- 46) or Kaposi's sarcoma (Ia, 378 +/- 100, and ATPase, 530 +/- 26), as compared with 38 appropriate controls (Ia, 721 +/- 13, and ATPase, 693 +/- 12). Examination of six patients with an "AIDS-related complex" revealed significantly reduced numbers of Langerhans' cells per square millimeter; this reduction was more pronounced in staining for Ia antigen (306 +/- 69) than in staining for ATPase activity (517 +/- 101). Given the known role of Ia expression in antigen presentation, we suggest that functional alterations in Langerhans' cells, and perhaps also in antigen-presenting cells in tissues other than skin, may be involved in the pathogenesis of AIDS.
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PMID:Reduced Langerhans' cell Ia antigen and ATPase activity in patients with the acquired immunodeficiency syndrome. 623 58

Diffuse intense lung uptake of TI-201 chloride without abnormal Ga-67 citrate in a case of cytomegalovirus pneumonitis in a patient with AIDS is presented. An autopsy performed within 4 days of imaging revealed no pulmonary pathology other than diffuse cytomegalovirus infection with abundant histiocytes and inclusion bodies and pulmonary congestive heart failure. Among the various mechanisms of TI-201 accumulation, active transport through Na-K ATPase appears to be predominant in this case, as suggested by innumerable histiocytes. It is the authors' experience that positive TI-201 uptake without abnormal Ga-67 accumulation is highly specific for pulmonary Kaposi sarcoma. The presence of such discrepancy between TI-201 and Ga-67 uptake in AIDS patients decreases the specificity of a TI-201 positive/Ga-67 negative lesion for pulmonary Kaposi sarcoma, especially with the rising incidence of both cytomegalovirus and Kaposi sarcoma in AIDS patients.
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PMID:Diffuse bilateral lung uptake of TI-201 chloride in CMV pneumonitis. Case presentation with histopathologic correlation. 764 42

Pneumocystis carinii is an opportunistic fungus which causes interstitial pneumonia in patients with acquired immunodeficiency syndrome (AIDS). Cytoplasmic pH (pHi) regulation in short-term-cultured P. carinii trophozoites was studied using the fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(-6)-carboxyfluorescein. With an extracellular pH of 7.4, the mean baseline pHi of P. carinii trophozoites was 7.40 +/- 0.10 (n = 8). This steady-state pHi was not significantly affected in the absence of extracellular Na+ or K+. Moreover, steady-state pHi was maintained in the nominal absence of HCO3- and was not affected by the Cl-/HCO(3-)-exchanger inhibitor 4, 4'-di-isothiocyanato-dihydrostilbene-2, 2'-disulphonic acid (100 microM), or the Na+/H(+)-exchanger inhibitor N-ethyl-N-isopropylamiloride (100 microM). In contrast, the general inhibitors of ATPases, N-ethylmaleimide (1 mM), and dicyclohexylcarbodi-imide (100 microM), and the inhibitor of yeast H(+)-ATPase, diethylstilbestrol (12.5-100 microM), decreased pHi, while the K+/H(+)-ATPase inhibitor omeprazole (50-400 microM), and the vacuolar-type H(+)-ATPase inhibitor bafilomycin A1 (1-5 microM) only produced a dose-dependent acidification of the cells when used at high concentrations. In addition, steady-state pHi depended on the availability of cellular ATP, since it was decreased by the ATP synthase inhibitors oligomycin (1 microgram/ml) and sodium azide (1 mM), and by the uncoupler of oxidative phosphorylation carbonyl cyanide p-trifluorophenylhydrazone (1 microM), agents that were able to deplete significantly the intracellular ATP levels. Taken together, these results are consistent with an important role of an H(+)-ATPase similar to those found in other fungi in the regulation of pHi homoeostasis in P. carinii trophozoites.
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PMID:An H(+)-ATPase regulates cytoplasmic pH in Pneumocystis carinii trophozoites. 868 17

Eukaryotic P-type ATPases use energy to drive the transport of cations across membranes. A complete P-ATPase gene (CpATPase1) has been isolated from Cryptosporidium parvum, one of the opportunistic pathogens in AIDS patients. The complete gene encodes 1528 amino acids, predicting a protein of 169 kDa. A hydropathy profile of the protein suggested there are eight transmembrane domains (TM). Expression of the gene was confirmed both by Northern blot analysis and RT-PCR. A fragment of the gene has been expressed as a 49 kDa GST-fusion protein. This protein was used to produce rabbit antiserum and fluorescent labeling has localized the protein to the sporozoite apical and perinuclear regions. SDS-PAGE and Western blot analysis show a 160 kDa major protein, close to the predicted size. The protein shares greatest overall identity and similarity to a putative organellar Ca2+ P-ATPase described for Plasmodium falciparum. Unlike P. falciparum, but consistent with all genes so far isolated from C. parvum, the gene contains no introns. The Ca2+ P-ATPases from these two Apicomplexa are large and do not have motifs predicting calmodulin-binding.
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PMID:Molecular analysis of a P-type ATPase from Cryptosporidium parvum. 949 52

The development of pharmacological approaches for preventing the loss of muscle proteins would be extremely valuable for cachectic patients. For example, severe wasting in cancer patients correlates with a reduced efficacy of chemotherapy and radiotherapy. Pentoxifylline (PTX) is a very inexpensive xanthine derivative, which is widely used in humans as a haemorheological agent, and inhibits tumor necrosis factor transcription. We have shown here that a daily administration of PTX prevents muscle atrophy and suppresses increased protein breakdown in Yoshida sarcoma-bearing rats by inhibiting the activation of a nonlysosomal, Ca(2+)-independent proteolytic pathway. PTX blocked the ubiquitin pathway, apparently by suppressing the enhanced expression of ubiquitin, the 14-kDa ubiquitin conjugating enzyme E2, and the C2 20S proteasome subunit in muscle from cancer rats. The 19S complex and 11S regulator associate with the 20S proteasome and regulate its peptidase activities. The mRNA levels for the ATPase subunit MSS1 of the 19S complex increased in cancer cachexia, in contrast with mRNAs of other regulatory subunits. This adaptation was suppressed by PTX, suggesting that the drug inhibited the activation of the 26S proteasome. This is the first demonstration of a pharmacological manipulation of the ubiquitin-proteasome pathway in cachexia with a drug which is well tolerated in humans. Overall, the data suggest that PTX can prevent muscle wasting in situations where tumor necrosis factor production rises, including cancer, sepsis, AIDS and trauma.
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PMID:Manipulation of the ubiquitin-proteasome pathway in cachexia: pentoxifylline suppresses the activation of 20S and 26S proteasomes in muscles from tumor-bearing rats. 1036 54

The human multidrug resistance P-glycoprotein (P-gp) contributes to the phenomenon of multidrug resistance during cancer and AIDS chemotherapy. A potential novel strategy to circumvent the effects of P-gp during chemotherapy is to prevent maturation of P-gp during biosynthesis so that the transporter does not reach the cell surface. Here we report that immature, core-glycosylated P-gp that is prevented from reaching the cell surface by processing mutations or by proteasome inhibitors such as lactacystin or MG-132 exhibited no detectable drug-stimulated ATPase activity. Disulfide cross-linking analysis also showed that the immature P-gp did not exhibit ATP-induced conformational changes as found in the mature enzyme. In addition, the immature P-gp was more sensitive to trypsin than the mature enzyme. These results suggest that P-gp is unlikely to be functional immediately after synthesis. These differences in the structural and enzymatic properties of the mature and core-glycosylated, immature P-gp could potentially be used during chemotherapy, and should result in the search for compounds that can specifically inhibit the maturation of P-gp.
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PMID:The human multidrug resistance P-glycoprotein is inactive when its maturation is inhibited: potential for a role in cancer chemotherapy. 1050 75


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