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Biomedical subjects

Y Hinuma

Publications and source records attributed to Y Hinuma.

At least 19 recordsLinked to original sources
PubMed2001

[A family of early childhood-onset Charcot-Marie-Tooth disease type 2].

We reported a man and his son with Charcot-Marie-Tooth disease (CMT) type 2. Their age at onset was about 5 years. Their clinical examinations revealed muscle atrophy and weakness of both distal lower limbs, foot-drop, a reduction of the reflex in both Achilles tendons and sensory impairment of the glove and stocking type. Nerve conduction studies revealed remarkably low amplitude of compound muscle action potential compared to conduction velocity. The nerve biopsy of their sural nerves revealed loss of large myelinated fiber. We presumed that the clinical features of their disease were compatible with CMT2A or 2B. DNA analysis of our family members performed with microsatellite markers linked to the candidate regions of CMT2A and 2B, did not show apparent positive results. We speculate that this family was a novel gene locus of CMT type 2.

Adult↗
PubMed1998

S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.

S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two-to three-drug combination therapy for HIV infection.

Animals↗
PubMed1997

Response of the extramedullary lung plasmacytoma with pleural effusion to chemotherapy.

An elderly patient with extramedullary lung plasmacytoma and subsequent pleural effusion is described. The presence of abnormal plasma cells in the pleural fluid led to diagnosis. Histologically similar conditions such as multiple myeloma and solitary myeloma of bone were ruled out by clinical evaluation. These neoplasms usually occur in the head and neck area and are not characterized by paraprotein accumulation. Few cases in the lung have been reported. We describe a case of extramedullary plasmacytoma of the lung with plasmacytoma-induced pleural effusion and the presence of monoclonal paraprotein in both the serum and urine. Chemotherapy with melphalan was effective in reducing the size of the plasmacytoma, and pleurodesis was used to manage the pleural effusion.

Aged↗
PubMed1995

Identification of a highly specific surface marker of T-cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily.

Five monoclonal antibodies detected a surface antigen expressed exclusively on T-cell acute lymphoblastic leukemia (T-ALL) in a panel of 45 human hematopoietic cell lines, including T-cell lines derived from adult T-cell leukemia and those established by immortalization with human T-cell leukemia virus type 1 or Herpesvirus saimiri. Peripheral blood mononuclear cells, including fresh and activated T cells, were also completely devoid of this antigen. We designated this antigen as TALLA-1 (from T-ALL-associated antigen 1). By expression cloning, a cDNA clone encoding TALLA-1 was isolated from T-ALL cell line Molt-4. TALLA-1 was found to be a member of the transmembrane 4 superfamily (TM4SF). The cDNA was also essentially identical to A15, which was isolated from another T-ALL cell line, HPB-ALL, by differential hybridization with normal peripheral blood lymphocytes, and to CCG-B7, which was isolated from a brain cDNA library using CCG repeat as a probe. The gene product was now characterized in detail at the protein level. Northern blot analysis showed that the gene was expressed most strongly in brain, skeletal muscle and spleen. In a panel of 52 non-hematopoietic human cell lines, the majority of neuroblastoma cell lines were found to be positive for TALLA-1. Like ME491, CO-029 and L6, TALLA-1 may be another TM4SF member behaving as a potential tumor-associated antigen.

Amino Acid Sequence↗
PubMed1994

Autoantigen Ku protein is involved in DNA binding proteins which recognize the U5 repressive element of human T-cell leukemia virus type I long terminal repeat.

We have identified and analyzed a 27-nucleotide sequence (U5 repressive element, designated as U5RE) at the U5 region of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) which is required for HTLV-I basal transcriptional repression. The basal promoter strength of constructs that contained deletions in the U5 region of the LTR was analyzed by chloramphenicol acetyltransferase (CAT) assays following transfection of HeLa cells or Jurkat T-cells in the presence or absence of viral transactivator tax protein. We consistently observed a 2- to 5-fold increase in basal promoter activity when sequences between +277 to +306 were deleted. In vivo competition experiments suggested that the U5 DNA fragment from +269 to +295 contains a functional repressive element (U5RE). Using gel mobility shift assays, we have purified a highly enriched fraction that could specifically bind U5RE. This DNA affinity column fraction contained three major detectable proteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining: 110-, 80- and 70-kDa proteins. The 110-kDa protein appeared to be a novel DNA-binding protein whose characteristics are still obscure, while the 70- and 80-kDa proteins were shown to be related to the human autoantigen Ku, the Ku (p70/p80) complex, as demonstrated by amino acid sequencing and immunological analyses. As Ku is known to be involved in transcriptional regulation, the specific interaction of Ku with U5RE raises intriguing possibilities for its function in HTLV-I basal transcriptional repression.

Amino Acid Sequence↗
PubMed1994

The gene encoding a new mitogenic factor in a Streptococcus pyogenes strain is distributed only in group A streptococci.

We recently cloned a gene encoding a new mitogenic factor (MF) from Streptococcus pyogenes NY-5. In the present study, we determined the distribution of this MF gene (mf) by PCR based upon its sequence. Of 371 streptococcal group A strains isolated from clinical specimens, 370 (99.7%) were positive for mf. The strain that was negative for the MF gene was also negative for the streptolysin O gene (slo). Some streptococcal strains belonging to groups C and G were negative for mf but positive for slo. Group B strains were negative for both. Furthermore, we examined the presence of mf in 54 strains belonging to 28 families and found mf only in group A streptococci. These results indicate that mf is distributed specifically in group A streptococci and the presence of mf in clinical samples strongly suggests infection with group A streptococci.

Bacterial Proteins↗
PubMed1993

Cloning, characterization and overexpression of a Streptococcus pyogenes gene encoding a new type of mitogenic factor.

A new type of mitogenic factor, termed MF, has been found in the culture supernatant of Streptococcus pyogenes and its N-terminal amino acid sequence has been determined. On the basis of this sequence, an S. pyogenes gene encoding MF was cloned and its nucleotide sequence was determined. The MF gene includes a long, open reading frame with 813 nucleotides capable of encoding the MF precursor protein with 271 amino acids. Removal of the putative 43 residues as a signal peptide results in the mature MF protein with 228 amino acids. The molecular mass of the mature MF is calculated as 25,363 which is consistent with the previously determined value of 25,370 for MF secreted from S. pyogenes. Neither nucleotide nor amino acid sequence homology was found between the mature MF and other streptococcal pyrogenic exotoxins, such as SPE A, SPE B and SPE C. The mature MF was recombinantly overexpressed as a fusion protein with glutathione S-transferase in Escherichia coli. The recombinant protein showed mitogenic activity in rabbit peripheral blood lymphocytes and immunoreactivity with the rabbit antiserum raised against the secreted MF from S. pyogenes. These data indicate that a unique gene encoding MF was cloned from S. pyogenes.

Amino Acid Sequence↗
PubMed1993

HTLV-I among Northern Territory aborigines.

OBJECTIVE: To survey the Aboriginal community of the Northern Territory for antibodies to human T-lymphotropic virus type I (HTLV-I) and to describe the distribution of the virus. DESIGN: A sero-epidemiological study using the Serodia particle-agglutination assay, indirect immunofluorescence and western blot. Evidence of HTLV-I-related diseases was sought through clinicians, and by searching the cancer register and medical records. SERA: Samples from 1897 Aborigines, including 1569 sera received by the Royal Darwin Hospital Pathology Department for syphilis serology between March and July 1988. Most of the specimens were from public health surveys and antenatal screening. RESULTS: Ninety-four samples (5.0%) were positive by the particle-agglutination assay method but only 36 (1.9%) were positive by both particle-agglutination assay and indirect immunofluorescence. After confirmation by western blot, the seroprevalence of HTLV-I was 1.7% (95% confidence interval, 1.2-2.3%). Western blot positivity was higher in samples from the "Cattle Country" and Alice Springs regions (i.e., 4.7% and 13.9% respectively). CONCLUSION: HTLV-I is endemic among Aborigines in inland Australia. These serological findings are supported by the recognition of two cases of adult T-cell leukaemia/lymphoma in this population.

Age Factors↗
PubMed1993

Identification of novel singly spliced pX mRNA transcripts common to all human T-cell leukemia virus type 1-related retroviruses.

Human T-cell leukemia virus type 1 (HTLV-1) and its related viruses, that is, human T-cell leukemia virus type 2 (HTLV-2), simian T-cell leukemia virus (STLV), and bovine leukemia virus (BLV), encode a doubly spliced pX mRNA transcript in addition to the singly spliced env and unspliced gag-pol mRNAs common to the prototypic simple retroviruses, such as murine and avian leukemia viruses. In HTLV-1-infected cells, we recently identified the novel singly spliced pX mRNA responsible for expressing the smaller rex gene product, p21X. In the present study we demonstrate that the novel singly spliced pX mRNA is also expressed in cells infected with HTLV-2, STLV, and BLV, respectively. This finding indicates that all members of the HTLV-1-related virus group have the common ability to express the singly spliced pX mRNA. This novel mRNA in the HTLV-1-related virus group may be analogous to the two-exon nef specific mRNA in human immunodeficiency virus type 1.

Animals↗
PubMed1992

C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1-induced syncytium formation is a member of a new family of transmembrane proteins including CD9, CD37, CD53, and CD63.

C33 Ag was originally identified by mAb inhibitory to syncytium formation induced by human T cell leukemia virus type 1. The Ag was shown to be a highly heterogeneous glycoprotein consisting of a 28-kDa protein and N-linked oligosaccharides ranging from 10 to 50 kDa. In the present study, cDNA clones were isolated from a human T cell cDNA expression library in Escherichia coli by using mAb C33. The identity of cDNA was verified by immunostaining and immunoprecipitation of transfected NIH3T3 cells with mAb. The cDNA contained an open reading frame of a 267-amino acid sequence which was a type III integral membrane protein of 29.6 kDa with four putative transmembrane domains and three putative N-glycosylation sites. The C33 gene was found to belong to a newly defined family of genes for membrane proteins, such as CD9, CD37, CD53, CD63, and TAPA-1, and was identical to R2, a cDNA recently isolated because of its strong up-regulation after T cell activation. Availability of mAb for C33 Ag enabled us to define its distribution in human leukocytes. C33 Ag was expressed in CD4+ T cells, CD19+ B cells, CD14+ monocytes, and CD16+ granulocytes. Its expression was low in CD8+ T cells and mostly negative in CD16+ NK cells. PHA stimulation enhanced the expression of C33 Ag in CD4+ T cells by about 5-fold and in CD8+ T cells by about 20-fold. PHA stimulation also induced the dramatic size changes in the N-linked sugars previously shown to accompany human T cell leukemia virus type 1-induced transformation of CD4+ T cells.

Amino Acid Sequence↗
PubMed1992

Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines.

Sixteen human T-cell lines were studied for the expression of a cell-adhesion molecule ICAM-1 and its counter-receptor LFA-1. The cell lines included 3 human T-cell-leukemia-virus-type-I (HTLV-1)-negative cell lines derived from acute lymphoblastic leukemia (ALL) and 13 HTLV-1-positive cell lines, 7 of them established from cord- or peripheral-blood T cells by in vitro transformation with HTLV-1, 2 derived from HTLV-1 carriers, and 4 derived from patients with adult T-cell leukemia (ATL). In sharp contrast to a basal level of ICAM-1 in 3 HTLV-1-negative ALL cell lines, strong induction of ICAM-1 was seen in all HTLV-1-positive T-cell lines except for MT-1, one of the 4 ATL cell lines used in the present study. On the other hand, the expression of LFA-1 (CD11a and CD18) was more or less similar among the cell lines with and without HTLV-1. Interestingly, however, 3 out of 4 ATL cell lines (TL-Om1, H582, HUT102) revealed striking depression of LFA-1 expression. Several lines of evidence strongly argued against direct involvement of the viral transactivator p40tax or some autocrine cytokines in the induction of ICAM-1 in HTLV-1-positive T-cell lines. It was also found that ICAM-1 and LFA-1 were involved in syncytium formation induced in the co-culture of HTLV-1-positive and HTLV-1-negative human T-cell lines. Implications of constitutive expression of ICAM-1 for certain clinical manifestations of ATL and of depression of either ICAM-1 or LFA-1 during progression of ATL are discussed.

Animals↗
PubMed1992

A new type of mitogenic factor produced by Streptococcus pyogenes.

A new type of mitogenic factor (protein) was purified from the culture supernatant of a strain of Streptococcus pyogenes by SP-Sephadex C-25 column chromatography, preparative isoelectric focusing and reversed-phase high-performance liquid chromatography. The purified factor, showing marked mitogenic activity in rabbit peripheral blood lymphocytes, gave a single-band staining for protein on SDS-PAGE. The molecular weight of the purified mitogenic factor was determined to be 25,370, which was different from those calculated from reported amino acid sequences deduced from 4 different nucleotide sequences of 3 kinds of streptococcal pyrogenic exotoxins (two SPEAs, SPEB and SPEC). The amino acid sequence of the N-terminal region of the purified mitogenic factor was determined to be Gln-Thr-Gln-Val-Ser-Asn-Asp-Val-Val-Leu-Asn-Asp-Gly-Ala-Ser-Lys-Tyr-Leu- Asn-Glu - Ala-, which was also different from the reported N-terminal sequences deduced from the 4 different nucleotide sequences. These data indicate that this mitogenic factor is distinct from the already described streptococcal pyrogenic exotoxins.

Amino Acid Sequence↗
PubMed1992

Herbal medicine use, Epstein-Barr virus, and risk of nasopharyngeal carcinoma.

Herbal medicine use is thought to be linked to nasopharyngeal carcinoma (NPC) either through its ability to reactivate the Epstein-Barr virus (EBV) or through a direct promoting effect on EBV-transformed cells. To investigate this, 104 histologically confirmed NPC cases and 205 matched controls were studied in The Philippines. Blood was collected to assess antibody titers against EBV, and an interview was administered which elicited information concerning herbal medicine use and other risk factors for NPC. Subjects strongly positive for anti-EBV antibodies (Epstein-Barr nuclear antigen [EBNA]) (titers greater than or equal to 1:80) were at a 21-fold excess risk of disease (95% confidence interval, 8.4, 51.8). Herbal medicine use was also associated with NPC (relative risk, 2.5; 95% confidence interval, 1.4, 4.5). Associations persisted after adjustment for education, smoking, Chinese ancestry, and consumption of salted fish. Exposure to herbal medicines among subjects testing negative/weakly positive for anti-EBNA antibodies was not associated with an elevation in risk (relative risk, 0.6), strong positivity to anti-EBNA antibodies in the absence of herbal medicine use was associated with a significant 16-fold excess risk of disease, and exposure to herbal medicines among subjects testing strongly positive for anti-EBNA antibodies was associated with a significant 49-fold excess risk of NPC when cases were compared to controls. Similar results were obtained when other serological measures of EBV exposure were used. Anti-EBV antibody titers were elevated in herbal medicine users compared to nonusers among cases but not among control subjects. This suggests that, if herbal medicines interact with EBV in the development of NPC, they do not do so by reactivating EBV infection but rather through a direct proliferative effect on EBV-transformed cells. Although the interaction between EBV and herbal medicines is biologically plausible, larger, more detailed studies need to be conducted to validate this preliminary finding.

Antibodies, Viral↗
PubMed1992

Induction of strong homotypic adhesion in human T cell lines positive with human T-cell leukemia virus type 1 by monoclonal antibodies to MHC class I and beta 2-microglobulin.

To identify the cellular receptors and other cell surface molecules playing essential roles in the transmission of human T-cell leukemia virus type 1 (HTLV-1), we have been isolating monoclonal antibodies (mAbs) that are capable of inhibiting HTLV-1-induced syncytium formation. In the present study, we isolated two mAbs, H11 (IgM) and H14 (IgG1), inhibitory to syncytium formation in the coculture of TOM-1 or C91/PL (both HTLV-1-positive human T-cell lines) and MOLT-4/8 (HTLV-1-negative human T-cell line) by immunizing the membrane fraction of human osteosarcoma line HOS. By immunoprecipitation and immunoblotting, H11 and H14 were found to be specific for MHC class I heavy chain and beta 2-microglobulin (beta 2 M), respectively. Among the four commercially obtained mAbs, two mAbs for MHC class I antigen and two mAbs to beta 2 M, one mAb to MHC class I antigen and one mAb to beta 2 M were also found to be inhibitory to the syncytium formation. The functional comparison of these mAbs revealed that the syncytium-inhibitory mAbs induced strong homotypic cell adhesion particularly in the HTLV-1-positive T-cell lines. This cell adhesion was dependent on temperature, energy metabolism, and microfilament function but not on the activity of protein kinase C or divalent cations. These results suggest a novel type of LFA-1-independent cell adhesion induced by signal transduction via MHC class I antigen.

Antibodies, Monoclonal↗