Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 39-year-old man who had AIDS and who presented with an unusual cutaneous vascular lesion, which was clinically thought to be Kaposi's sarcoma. Histologically, the lesion was characterized by capillary proliferation and a mixed inflammatory infiltrate that included numerous histiocytes. The lesion was found to contain slender intracellular acid-fast bacilli, as well as plump extracellular Warthin-Starry-positive bacilli. The acid-fast bacilli were confirmed to be Mycobacterium avium-intracellulare by subsequent positive blood cultures for this organism. To further investigate the lesion, polymerase chain reaction DNA amplification and sequencing was performed, and the lesion was found to contain DNA sequences identical to those previously established for the agent of bacillary angiomatosis. The lesion is thought to represent a lesion of bacillary angiomatosis with secondary involvement by M. avium-intracellulare.
Diagn Mol Pathol 1992 Sep
PMID:Localization of Mycobacterium avium-intracellulare within a skin lesion of bacillary angiomatosis in a patient with AIDS. 128 77

Recent evidence suggests that the human immunodeficiency virus type 1 (HIV) trans-activator gene (tat) has transforming properties and may be a causative factor in the development of certain types of cancers, in particular Kaposi's sarcoma (i.e., Vogel J. et al. Nature 335:606-611, 1988). To help elucidate the potential role or roles of the HIV tat gene in neoplastic transformation, cell lines were constructed that constitutively express a functional tat gene product. HeLa cells were coelectroporated with two plasmids, one containing the HIV tat gene in an expression cassette and another containing the dominant selectable marker gene xanthine guanine phosphoribosyltransferase (XGPRT). After XGPRT selection, single-cell clones that expressed a functional tat protein were identified by measuring chloramphenicol acetyltransferase (CAT) activity after electroporating a plasmid containing the CAT gene transcriptionally controlled by HIV trans-activation-responsive region (tar). Phenotypic alterations resulting from the expression of tat were then determined. Control cells and tat-expressing cells grew at similar rates in culture. However, when grown as tumors in nude mice, tat-expressing cells produced a lower percentage of tumors, and the tumors that were produced either regressed, stopped growing, or grew at a very reduced rate compared with cells not expressing tat. These differences may have resulted from a tat-associated reduction in neovascularization in the tumors. A comparison of total cellular proteins by two-dimensional polyacrylamide gel electrophoresis indicated only one reproducible alteration in a polypeptide of approximately 44 kDa and pl of approximately 6.2 associated with tat expression. These cells may be very useful in future in vitro and in vivo studies designed to examine the effects of HIV tat on endothelial and vascular smooth-muscle cells and the role of tat in the etiology of Kaposi's sarcoma.
Mol Carcinog 1992
PMID:Alterations in tumor angiogenesis associated with stable expression of the HIV tat gene. 137 15

Kaposi's sarcoma (KS) has become a source of interest in recent years primarily for its strong association with the acquired immune deficiency syndrome (AIDS). Endothelial cells (EC) are central to inflammation and can regulate coagulation and leucocyte emigration and may be central to the development of the disease. As they are also capable of being infected by HIV in vivo, this infection may contribute to the immunosuppressive effects of HIV seen in AIDS. Recent work has shed new light on the mechanisms involved in EC proliferation. The aim of this article is to review such evidence implicating EC in the development of KS. Additionally, hypotheses will be put forward to explain the mechanism of the vascular proliferation in KS and the possible role of EC in HIV infection. There is therefore enormous potential for the therapeutic targeting of endothelium to control these diseases.
Mol Aspects Med 1991
PMID:Vascular endothelium: a potential role in HIV infection and the pathogenesis of Kaposi's sarcoma: observations and speculations. 172 17

When the AIDS epidemic was in its earliest stages, and prior to identification of HIV as the etiological factor, the use of volatile nitrites by the male homosexual community to enhance sexual activities appeared to have a significant role in this disease. Preliminary observations indicated that the portion of the male homosexual community which developed Kaposi's sarcoma were also heavy nitrite users. These nitrites had been demonstrated to be mutagenic in bacteria and thus it was postulated that they could be responsible for the appearance of the sarcoma. To evaluate further the genotoxic activity of these chemicals, six nitrites, including those most commonly used by homosexuals for sexual gratification, were selected for testing in the mouse lymphoma TK+/- and Salmonella typhimurium mutagenicity assays. One chemical, n-amyl nitrite, was negative in the mouse lymphoma assay, while the other five chemicals, n-butyl, isobutyl, iso-amyl, sec-butyl, and n-propyl nitrite, were positive. All six compounds were positive in the Salmonella assay. The mutagenic and known toxic effects of these chemicals remain a concern because a large population of teenagers and young adults continue to abuse these substances.
Environ Mol Mutagen 1989
PMID:Mutagenicity of some alkyl nitrites used as recreational drugs. 256 72

The presence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) was investigated using hybridization in 15 lymph nodes and one Kaposi's sarcoma skin lesion obtained from HIV-positive patients. Cryostat tissue sections were hybridized with chemically modified DNA probes for HBV and HIV. HIV genome was mainly observed in the cytoplasm of cells present in 7/15 lymph nodes and in the Kaposi's sarcoma skin lesion, thus indicating the expression of HIV replication. Control samples hybridized with an HTLV I probe were negative. HBV genome was found in the cytoplasm of lymphoid mononuclear cells in 2/7 lymph nodes, obtained from HIV+ patients without serum markers of ongoing HBV infection. Lymph node positivity for HBV DNA also confirms that lymphoid cells may be a target for HBV. Since HBV infection seems to precede HIV infection in nearly all patients, it is possible that it may represent a factor facilitating the development of the HIV-related disease.
Mol Cell Probes 1989 Jun
PMID:HBV and HIV expression in lymph nodes of HIV positive LAS patients: histology and in situ hybridization. 277 Jul 52

We recently reported that the protein encoded in a novel human oncogene isolated from Kaposi sarcoma DNA was a growth factor with significant homology to basic and acidic fibroblast growth factors (FGFs). To study the properties of this growth factor (referred to as K-FGF) and the mechanism by which the K-fgf oncogene transforms cells, we have studied the production and processing of K-FGF in COS-1 cells transfected with a plasmid encoding the K-fgf cDNA. The results show that, unlike basic and acidic FGFs, the K-FGF protein is cleaved after a signal peptide, glycosylated, and efficiently secreted as a mature protein of 176 or 175 amino acids. Inhibition of glycosylation impaired secretion, and the stability of the secreted K-FGF was greatly enhanced by the presence of heparin in the cultured medium. We have used the conditioned medium from transfected COS-1 cells to test K-FGF biological activity. Similar to basic FGF, the K-FGF protein was mitogenic for fibroblasts and endothelial cells and induced the growth of NIH 3T3 mouse cells in serum-free medium. Accordingly, K-fgf-transformed NIH 3T3 cells grew in serum-free medium, consistent with an autocrine mechanism of growth. We have also expressed the protein encoded in the K-fgf protooncogene in COS-1 cells, and it was indistinguishable in its molecular weight, glycosylation, secretion, and biological activity from K-FGF. Taken together, these results suggest that the mechanism of activation of this oncogene is due to overexpression rather than to mutations in the coding sequences.
Mol Cell Biol 1988 Jul
PMID:Processing, secretion, and biological properties of a novel growth factor of the fibroblast growth factor family with oncogenic potential. 304 99

The acquired immunodeficiency syndrome (AIDS) is a new disease characterized by severe dysfunction of both the T cell and B cell systems, occurring in previously healthy individuals. Affected individuals may have recurrent and chronic opportunistic infections and/or Kaposi's sarcoma or other malignancy. Analysis of the cellular and subcellular components of immunity demonstrates a profound depression in the number and function of helper/inducer T cells bearing the OKT4 (Leu 3) differentiation antigen and a concomitant defect in the synthesis of the immuno-enhancing soluble growth factor, interleukin 2 (IL-2). Hypotheses to explain the etiology of the immunological dysfunction and implications for future therapy of AIDS are discussed.
Mol Cell Biochem 1984 Aug
PMID:Characterization of the acquired immune deficiency syndrome at the cellular and molecular level. 609 6

The emergence of Kaposi's sarcoma (KS) among patients with HIV infection has raised a number of unsolved questions. The particular epidemiology and the etiology of KS remain unclear while both inflammatory cytokines and HIV-derived proteins appear to be involved in its pathogenesis as shown with the aid of in vitro KS-like cell cultures of animal models. Since KS rarely occurs among HIV-positive Caucasian females, sexual hormones, especially beta Human Chorionic Gonadotropin, have recently been reported as providing theoretically some protection against KS both in vitro and in vivo. All these aspects will be detailed as well as the therapeutic approaches which still remain unsatisfactory. So far, there is no curative treatment for KS and drug-induced toxicity is the limiting factor for the prolonged use of the current approaches. Perspectives for therapy will be discussed.
Cell Mol Biol (Noisy-le-grand) 1995 May
PMID:Kaposi's sarcoma in patients infected with human virus (HIV): an overview. 758 Aug 28

Nine patients with Kaposi's sarcoma and five suffering from T-cell lymphoma have been examined. Antibodies to HTLV-1 were not found in these patients. The primary cellular cultures were isolated from blood and lymph nodes of the patients. Viral particles (type C) were found in the culture obtained from the patient with lymphoma of T-cell origin. DNAs from the primary cellular cultures from patients with lymphoma or sarcoma contained the sequences homologous to gag-gene of HTLV-1. The data suppose the patients with T-cell lymphoma and Kaposi's sarcoma to carry HTLV-1 virus.
Mol Gen Mikrobiol Virusol
PMID:[Detection of markers of the human T-cell leukemia virus in patients with T-cell lymphoma and Kaposi's sarcoma]. 789 27

We examined the mutagenicity of iso-butyl nitrite (IBN) vapor and aqueous IBN solution in the Ames test to help evaluate the hazard of sniffing this vapor, a habit which might play a role in the induction of Kaposi's sarcoma associated with acquired immune deficiency syndrome. Chemical analysis showed that the saturated vapor contained 190 micrograms IBN/ml at 25 degrees C, and saturated aqueous solution, 2.6 mg IBN/ml at 21-23 degrees C. When agar plates containing Salmonella typhimurium TA-1535 and rat liver S-9 were exposed to IBN vapor, the number of mutants reached a maximum after 40 min. A mean of 307 mutants/plate (22 x background) was observed when the plates were exposed to IBN vapor for 30 min. Addition of 0.2 ml saturated IBN solution in water to similar plates gave a mean of 179 mutants/plate (7.9 x background) in the absence of S-9, confirming published results. The S-9 did not affect the results. Based on the IBN level in medium exposed to IBN vapor, the vapor was apparently 11 times more mutagenic than IBN solution. This was attributed to continuous replenishment of unstable IBN in the medium by the vapor. The half-life of IBN at 21-23 degrees C was > 1 hr for solutions in water and < 3 min for solutions in the assay medium. This instability was traced to a reaction with phosphate, presumably hydrolysis to nitrite and iso-butanol. IBN in solution was 2.8 times more mutagenic than sodium nitrite, suggesting that IBN was not mutagenic because of its conversion to nitrite. Iso-butanol was not mutagenic. The results demonstrate the potential hazard of sniffing IBN vapor.
Environ Mol Mutagen 1993
PMID:Mutagenicity of iso-butyl nitrite vapor in the Ames test and some relevant chemical properties, including the reaction of iso-butyl nitrite with phosphate. 846 28


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