Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 631-bp region of the long terminal repeat (LTR) of a variant of human T-cell lymphoma/leukemia virus type I (HTLV-I), isolated from a healthy member of a remote, recently contacted group (Hagahai) in Papua New Guinea, was sequenced and compared to LTR sequences of other members of the primate T-cell lymphoma virus group (PTLV), including HTLV-I, simian T-cell lymphoma virus (STLV-I) and HTLV-II. Sequence analysis of the LTR of this New Guinean isolate, designated as HTLV-I(PNG-1), indicated a sequence divergence of 8.4% to 10.4% from prototype Japanese HTLV-I(ATK) and other HTLV-I and STLV-I isolates and 48.6% diversity from HTLV-II. Few mutations were found in the core elements of the transcriptional enhancer regions, the TATA box promoter, and the polyadenylation signal and site. Further, the observed changes did not significantly alter the inferred stability of the Rex response element, a stem loop structure critical for polyadenylation and Rex protein binding. Dendograms based on LTR sequences indicated that the strain of virus that evolved into HTLV-I(PNG-1) diverged from the other PTLV in the distant past, just after the progenitors of STLV-I from Asia, but before the ancestors of STLV-I from Africa. By contrast, other HTLV-I isolates were found to represent strains of virus that have diverged more recently and clustered primarily according to their geographical origin. These data confirm that HTLV-I(PNG-1) is a new and distinct variant of the PTLV group. Also, our analyses suggest that both HTLV-I and STLV-I may have originated in the Indo-Malay region and eventually spread to Africa and then to the New World and Japan with horizontal transmission between man and nonhuman primates possibly occurring over thousands of years.
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PMID:LTR sequence and phylogenetic analyses of a newly discovered variant of HTLV-I isolated from the Hagahai of Papua New Guinea. 160 4

OK-432, a streptococcal preparation, is known to have strong BRM functions and is expected to produce clinical improvement and prolongation of survival in treated cancer patients. In order to clarify the immunopharmacological mechanisms involved with its clinical effectiveness, intrapleural injection of OK-432 was attempted in patients with malignant pleural effusion due to metastasis from lung cancer. About 70-80% of patients thus treated showed clinical improvements with reduction or disappearance of effusion and effusion tumor cells within a week after the therapy. The clinical response was accompanied by an abrogation or reduction of suppressor macrophages and a stimulatory increase of effective cytotoxic cells resulting in an increase of NK and ATK activity. These in vivo effects observed in the OK-432-treated patients were reproducible in vitro by incubating normal or effusion lymphocytes with tumor-associated macrophages. OK-432 was also shown to reduce the locomotor inhibitory activity of macrophages toward LGL, and to augment the production of various sorts of cytokines, such as IL-1 and MCF by macrophages and IL-2 and NKCF by lymphocytes, all of them being exerted upon activation of the anti-tumor immunological mechanism.
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PMID:[Effective mechanisms of BRM, with special reference to induction of autologous tumor cell-killing (ATK) activity by OK-432]. 348 24

A study of simian T-cell leukemia virus type 1 (STLV-1) infection in a captive colony of 23 Macaca tonkeana macaques indicated that 17 animals had high human T-cell leukemia virus type 1 (HTLV-1) antibody titers. Genealogical analysis suggested mainly a mother-to-offspring transmission of this STLV-1. Three long-term T-cell lines, established from peripheral blood mononuclear cell cultures from three STLV-1-seropositive monkeys, produced HTLV-1 Gag and Env antigens and retroviral particles. The first complete nucleotide sequence of an STLV-1 (9,025 bp), obtained for one of these isolates, indicated an overall genetic organization similar to that of HTLV-1 but with a nucleotide variability for the structural genes ranging from 7.8 to 13.1% compared with the HTLV-1 ATK and STLV-1 PTM3 Asian prototypes. The Tax and Rex regulatory proteins were well conserved, while the pX region, known to encode new proteins in HTLV-1 (open reading frames I and II), was more divergent than that in the ATK strain. Furthermore, a fragment of 522 bp of the gp21 env gene from uncultured peripheral blood mononuclear cell DNAs from five of the STLV-1-infected monkeys was sequenced. Phylogenetic trees constructed with the long terminal repeat and env (gp46 and gp21) regions demonstrated that this new STLV-1 occupies a unique position within the Asian STLV-1 and HTLV-1 isolates, being, by most analyses, related more to the Australo-Melanesian HTLV-1 topotype than to any other Asian STLV-1. These data raise new hypotheses on the possible interspecies viral transmission between monkeys carrying STLV-1 and early Australoid settlers, ancestors of the present day Australo-Melanesian inhabitants, during their migrations from the Southeast Asian land mass to the greater Australian continent.
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PMID:Isolation and characterization of a new simian T-cell leukemia virus type 1 from naturally infected celebes macaques (Macaca tonkeana): complete nucleotide sequence and phylogenetic relationship with the Australo-Melanesian human T-cell leukemia virus type 1. 747 17

Bruton tyrosine kinase (EC 2.7.1.112) [Btk, encoded by Btk in mice and BTK in humans (formerly known as atk, BPK, or emb)], which is variously mutated in chromosome X-linked agammaglobulinemia patients and X-linked immunodeficient (xid) mice, has the pleckstrin homology (PH) domain at its amino terminus. The PH domain of Btk expressed as a bacterial fusion protein directly interacts with protein kinase C in mast cell lysates. Evidence was obtained that Btk is physically associated with protein kinase C in intact murine mast cells as well. Both Ca(2+)-dependent (alpha, beta I, and beta II) and Ca(2+)-independent protein kinase C isoforms (epsilon and zeta) in mast cells interact with the PH domain of Btk in vitro, and protein kinase C beta I is associated with Btk in vivo. Btk served as a substrate of protein kinase C, and its enzymatic activity was down-regulated by protein kinase C-mediated phosphorylation. Furthermore, depletion or inhibition of protein kinase C with pharmacological agents resulted in an enhancement of the tyrosine phosphorylation of Btk induced by mast cell activation.
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PMID:The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C. 752 30

Twenty-one patients with malignant peritoneal or pleural effusions of gastric carcinomas were treated with intracavitary injection of lentinan (LNT). LNT was injected at a dosage of 4 mg/week for 4 weeks. In total, fifteen (71%) of twenty-one patients demonstrated clinical responses. Toxicity caused a high fever in only one case. LAK and ATK activities induced from peritoneal exudate cells (PEC) after culture with autologous tumor and interleukin-2 were examined before and after LNT injection. ATK activity was augmented, but LAK activity was reduced after LNT injection. These results indicate that intracavitary injection of LNT is a useful treatment for malignant effusions, and that LNT augments the induction of cytotoxic T-lymphocytes.
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PMID:[Clinical effects and immunological analysis of intraabdominal and intrapleural injection of lentinan for malignant ascites and pleural effusion of gastric carcinoma]. 757 68

Human T-cell-leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). The different disease outcome may be attributable to subtle mutations leading to modification of viral tropism or infectivity. Initial attempts found a very high level of sequence conservation among all HTLV-I strains. However, only one complete proviral DNA sequence is reported from a TSP/HAM patient, with a provirus derived from immortalized lymphocytes, which might be expected to be a leukemogenic variant rather than a neurotropic one. We cloned and sequenced a complete HTLV-I provirus (HTLV-IBoi) derived from the uncultured lymphocytes of a sub-acute post-transfusional TSP/HAM patient with clonal integration of HTLV-I. HTLV-IBoi proviral genome is 9033 bp long, and its overall genetic organization is similar to that of the prototype HTLV-I(ATK), without major deletions or insertions. No premature termination codon was found in the 4 open reading frames of the pX region. Divergence at the nucleotide level of HTLV-IBoi from the reported full-length HTLV-I varies from 1 to 9.4%, and indicates that it corresponds to a cosmopolitan genotype. This study did not identify specific sequences associated with neurotropic strains.
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PMID:Human T-cell-leukemia virus type I in post-transfusional spastic paraparesis: complete proviral sequence from uncultured blood cells. 759 Dec 56

We describe nucleotide sequences of human T-lymphotropic virus type I (HTLV-I) proviruses from three symptomatic family members with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) from Tumaco, Colombia. Polymerase chain reaction was used to clone the U3 region, envelope and tax/rex genes of these HTLV-I proviruses from fresh peripheral blood lymphocytes. Sequences in U3, env and tax/rex showed 96.9-99.5% conservation when compared with sequences from HTLV-I clone ATK, and 96.6-100% when compared with each other. The range of sequence divergence within the family was similar to that described between unrelated TSP/HAM patients of the same geographical origin. Certain mutations were present in all three family members, supporting a geographic and/or familial segregation of mutations.
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PMID:Nucleotide sequences of human T-lymphotropic virus type I (HTLV-I) from a family cluster with tropical spastic paraparesis/HTLV-I-associated myelopathy. 763 41

Human T cell lymphotropic virus type 1 (HTLV-1) is endemic in South America and the Caribbean basin. To clarify the genetic and phylogenetic relationship between an HTLV-1 strain isolated from a Brazilian woman with adult T cell leukemia and viral isolates from elsewhere in South America and from other geographic regions, selected regions of the gag, pol, env, and pX genes were amplified and directly sequenced. The overall sequence similarities between the Brazil-R-1 strain and the Japanese prototype ATK strain were 98.7% based on 1,295 nucleotides and 99.1% based on 429 amino acids. Phylogenetic analysis indicated that strain Brazil-R-1 clustered with other Brazilian and South American HTLV-1 isolates and was more closely related to Caribbean isolates from Martinique and Guadeloupe than to virus strains from other geographic regions. These data suggest a common source of HTLV-1 infection in the Caribbean basin and South America.
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PMID:Sequence and phylogenetic analyses of human T cell lymphotropic virus type 1 from a Brazilian woman with adult T cell leukemia: comparison with virus strains from South America and the Caribbean basin. 785 18

Human T-cell leukemia virus type 1 (HTLV-1) is etiologically associated with adult T-cell leukemia/lymphoma (ATL). The prototypic HTLV-1, ATK, is the only full-length provirus cloned from uncultured leukemic cells and completely sequenced prior to this study. We have determined the complete nucleotide sequence of another full-length HTLV-1 provirus cloned directly from leukemic cells. A premature termination codon was found in the second open reading frame (orf II) of the pX region. Our finding indicates that open reading frame II of the HTLV-1 pX region is not required for outgrowth of ATL leukemic clones in vivo.
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PMID:Nucleotide sequence analysis of a full-length human T-cell leukemia virus type I from adult T-cell leukemia cells: a prematurely terminated PX open reading frame II. 786 Jan 46

In order to better understand the genomic diversity and molecular phylogeny of the human retroviruses, the plasmas from 250 Zairean patients collected in 1969 were tested for antibodies to human T-cell lymphoma and human immunodeficiency viruses (HTLV or HIV) using ELISA and confirmatory Western blots and for viral nucleic acids by reverse transcriptase-directed PCR (RT-PCR). Interestingly, none of the patients was confirmed positive for HIV, even though this region is now endemic for HIV-1. However, 74 (30%) and 3 (1%) of the samples were positive for antibodies to HTLV-I and II, respectively. Forty-four of 74 (59%) Western blot-positive Zairean samples were RT-PCR positive for HTLV-I, while 1 of 3 (33%) of HTLV-II-seropositive samples was RT-PCR positive. On the contrary, none of the Western blot-negative or indeterminate samples were RT-PCR positive for either HTLV-I or HTLV-II. We have cloned and sequenced 140 bp of the pol gene flanked by SK110/SK111 from 8 HTLV-I- and 1 HTLV-II-positive archival samples from Zaire. The HTLV-I isolates from Zaire cluster together as a phylogenetic group, diverging from the prototype Japanese HTLV-I (ATK) by a range of 1.4 to 3.6%. Their close homology to some African STLV-I isolates suggests relatively recent interspecies transmission. The Zairean HTLV-II isolate is closely grouped with the HTLV-II substrain of isolates found in Paleo-Amerindians of the New World, making it unlikely that it represents an endemic African strain.
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PMID:Serological and nucleic acid analyses for HIV and HTLV infection on archival human plasma samples from Zaire. 791 21


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