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Biomedical subjects

M Matsuoka

Publications and source records attributed to M Matsuoka.

At least 19 recordsLinked to original sources
PubMed1995

Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 Tax.

L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium. Upon cellular activation, expression of the L-selectin gene is downregulated at both the protein and mRNA levels. To understand the mechanism of leukemic cell infiltration into organs, we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral transcriptional transactivator. Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens. Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation. Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients. Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration. The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level. Chloramphenicol acetyltransferase (CAT) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax. The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively). These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax. The overexpression of L-selectin, as well as of inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach the vascular endothelium, leading to transmigration and organ infitration.

Adult↗
PubMed1995

Column-switching high-performance liquid chromatographic system with a laser-induced fluorimetric detector for direct, automated assay of salivary cortisol.

In order to measure human stress, an easy and rapid, fully automated method for the determination of cortisol in saliva has been developed, using column-switching high-performance liquid chromatography with laser-induced fluorescence detection, which involves post-column labeling with sulfuric acid. The developed system requires only 0.1 ml of saliva, and a simple pretreatment consisting of dilution and filtration is sufficient. The column-switching system consisted of a Polymer-Coated Mixed-Functional silica (PCMF) column for deproteinization, and a CN column for frontal concentration and separation. An ODS column in place of the CN provided a better separation, but required a post-column make-up of water for safe reaction. Detection limit of cortisol was 8 fmol (signal-to-noise ratio = 3), which is adequate for routine determination of normal levels of cortisol (1-20 pmol/ml). The analysis time was about 40 min and reproducibility was excellent with an R.S.D. of less than 5%.

Chromatography, High Pressure Liquid↗
PubMed1995

Lack of the expression of EBNA-2 and LMP-1 in T-cell neoplasms possessing Epstein-Barr virus.

We investigated 34 cases of T-cell neoplasm [15 cases of T-cell granular lymphocytic leukemia (T-GLL), 10 cases of T-cell non-Hodgkin's lymphoma (T-NHL), six cases of T-cell chronic lymphocytic leukemia (T-CLL), and three cases of cutaneous T-cell lymphoma] to study their association with Epstein-Barr virus (EBV). In 4 (three T-NHL and one T-GLL) of 34 cases, EBV genome was detected in a single episomal form, while polyclonal EBV-DNA was detected in one (T-NHL) of the remaining cases. All three cases of T-NHL having monoclonal EBV episome showed histologically diffuse large-cell lymphoma and developed leukemic conversion. Phenotypic analysis showed that two of these four cases were CD4+, CD8-, and the remaining two cases were CD4-, CD8+. The cells from all four cases were confirmed to be in T-cell lineage by detecting the rearrangement of T-cell receptor (TCR) beta or gamma chain gene. By reverse transcription-polymerase chain reaction (RT-PCR), EBNA-1 was detected at low levels, and neither EBNA-2 nor LMP-1 were found in any of the three cases examined. Lack of the expression of EBNA-2 and LMP-1 was also confirmed by immunocytochemical staining. The cells of these four cases did not show rearrangement or overexpression of c-myc and bcl-2 genes by Southern and Northern blots, and the mutation of p53 gene was detected in only one patient. These results suggest that other latent gene products of EBV or other cellular oncogenes are involved in the development of Japanese T-cell neoplasm after EBV infection.

Antigens, Viral↗
PubMed1995

Cadmium-induced expression of immediate early genes in LLC-PK1 cells.

To identify molecular mechanisms underlying renal cell damage by cadmium, the effect of this heavy metal on the level of immediate early genes (IEGs) transcripts in LLC-PK1 cells was studied. Cadmium chloride (CdCl2) induced the expression of four IEGs examined, but with differing time courses. The level of c-fos mRNA peaked at 30 minutes, and then decreased. The levels of c-jun and c-myc transcripts reached a maximum at one hour, and remained elevated up to four hours. Egr-1 mRNA level peaked at one hour, and returned to the control level by three hours. Experiments with cycloheximide and actinomycin D showed, respectively, that induction of IEGs by cadmium occurred in a protein synthesis-independent and transcriptional activation-dependent manner. Cadmium induction of c-fos mRNA was reduced markedly by the intracellular calcium chelator, bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)-ester (BAPTA/AM), and was decreased partially by a protein kinase C (PKC) inhibitor, 1-(5-isoquinolinylsulfonyl)-2- methylpiperazine (H-7). These data indicate that IEG induction by cadmium requires intracellular calcium mobilization and occurs in part by a PKC-dependent pathway. Exposure of LLC-PK1 cells to CdCl2 (20 microM for 1 to 24 hr) resulted loss of cell viability and DNA fragmentation, which was indicative of apoptosis.

Animals↗
PubMed1995

Alternative RNA products from a rice homeobox gene.

Three cDNA clones were isolated from rice, OSH42, OSH44 and OSH45, which encode homeodomain sequences in the C-terminal region. The sequences of these cDNAs differ in the N- and C-termini, but they share an identical homeodomain and an acidic amino acid-rich region. The transcripts corresponding to these cDNAs are encoded by a single gene on rice chromosome 8. Differential transcription initiation results in a large transcript comprised of exons 1 and 3-7 and a smaller transcript comprised of exons 2-7. The larger transcript is constitutively expressed in all tissues tested, while the smaller transcript is expressed in leaves, stems and rachis but not in roots, flowers, or suspension callus cells. Alternative splicing also occurs at three different acceptor sites in intron 6 in all tissues tested. The GAL4 DNA-binding domain of yeast was used to study the function of various protein domains. The acidic amino acid-rich region activates the expression of a reporter gene controlled by the GAL4 target sequence, indicating that it functions as a transactivation domain. The larger transcript encodes a unique alanine and glycine-rich region on the N-terminal side of the acidic region, which is not encoded by the smaller transcript. This region completely suppresses the transactivation activity of the acidic region. This suggests that the product of the larger transcript fails to activate the expression of the target gene(s) while the product of the smaller transcript activates the expression of its target gene(s).

Alternative Splicing↗
PubMed1995

Studies on pyridonecarboxylic acids. IV. Synthesis and antibacterial activity evaluation of S-(-)- and R-(+)-6-fluoro-1-methyl-4-oxo-7- (1-piperazinyl)-4H-[1,3] thiazeto[3,2-a]quinoline-3-carboxylic acids.

Optically active isomers of 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H- [1,3] thiazeto [3,2-alpha] quinoline-3- carboxylic acid (NM394, 3) were prepared through optical resolution of their racemic intermediate ( +/- )-1 by high-performance liquid chromatography (HPLC). The absolute configuration at the C-1 position in the thiazeto-quinolone ring of ( - )-3 was confirmed by X-ray analysis ( - )-4 to be S. The in vitro antibacterial activity of ( - )-3 was 2--8 times that of (+)-3.

Anti-Infective Agents↗
PubMed1995

Seasonal variation in 24-h blood pressure pattern of young normotensive women.

To investigate the seasonal variations in ambulatory blood pressure patterns, 24-h blood pressure was measured every 15 minutes noninvasively in ten young normotensive women. Urine was collected every 4 hours. The examinations were repeated in spring, summer, autumn, and winter in a standardized living environment. The 24-h average systolic and diastolic blood pressures did not differ significantly among the seasons. Similarly, there were no significant differences in the average values of either daytime or nighttime blood pressure. In contrast, the average pulse rate during nighttime was significantly higher in winter than in summer (64 +/- 2 beats/min vs. 59 +/- 2 beats/min, p < 0.05). The variabilities of either blood pressure or pulse rate did not change significantly among the seasons. The mesors and acrophases of both systolic and diastolic blood pressures, determined by a single cosinor method, were not significantly different among the seasons. On the other hand, the acrophase of pulse rate appeared significantly later in winter (16:19) compared with those in spring (14:54), summer (14:42), and autumn (14:21). Urine volume and urinary excretion of norepinephrine were significantly greater in winter than in summer. These results indicate that the 24-h pattern of blood pressure is reproducible and shows no seasonal difference in young normotensive women.

Adult↗
PubMed1995

Protection of the brain by carnitine.

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.

Ammonia↗
PubMed1995

Visible light-sensitized oxidation of arachidonic acid in the presence of inperatorin.

To understand the mechanism of the phototoxic effects of inperatorin, a psoralen derivative used as a pigmentation agent, we have investigated the photosensitized oxidation of arachidonic acid (ARA) by irradiation with visible light (> 400 nm) in the presence of inperatorin. HPLC and GC/MS analyses of the products showed the formation of many hydroperoxyeicosatetraenoic acids (HPETEs) including the products of lipoxygenase-catalyzed reactions such as 5- and 15-HPETEs, which are the precursors of chemical mediators such as leukotrienes and lipoxins, during the reaction. Active oxygen scavening agents such as D-mannitol, superoxide dismutase, and beta-carotene inhibited the formation of the oxidation products, indicating that the oxidation reaction was mediated by various active oxygen species. These results suggest that the phototoxic effects of inperatorin could also be induced by visible light and could be explained at least partially in terms of inflammation initiated by the biologically active HPETEs arising from photosensitized oxygenation reactions of ARA with the drug.

Arachidonic Acid↗
PubMed1995

[Endoscopic lithotomy using sublingual nitroglycerin].

After medical sphincter dilation using sud-lingual nitroglycerin, endoscopic removal of common bile duct stones in 15 patients was carried out. Complete stone removal was obtained in 14 of 15 patients. Only 0.3 mg to 0.6 mg nitroglycerin was needed to give an enough dilation of the orifice for cannulating the basket catheter into the bile duct. Mechanical lithotriptor was smoothly cannulated in one patient because of possible impaction. Blood pressure was dropped transiently in one patient by nitroglycerin, however, the general condition of the patient was stable. This procedure is safe, easy and effective in preserving sphincter function. Acute cholecystitis, a common complication of persistent gallbladder stone after endoscopic sphincterotomy, may be avoided by employing this method. More clinical studies, on long term and in a large scale of patients, are necessary to reduce complications that usually occur after sphincterotomy.

Female↗
PubMed1995

Adult T cell leukemia following HTLV-I-associated myelopathy/tropical spastic paraparesis: case reports and implication to the natural course of ATL.

Adult T cell leukemia (ATL) is the T cell malignancy caused by human T lymphotropic virus type I (HTLV-I), and HTLV-I is also the causative agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although HTLV-I causes both diseases, concomitant occurrence is reported to be rare. This paper describes two cases of HAM/TSP that developed into lymphoma-type ATL after the onset of HAM/TSP. In one case, the same HTLV-I infected clone could be detected by polymerase chain reaction in peripheral blood obtained when the patient was diagnosed as HAM/TSP. This finding showed that the HTLV-I clone already existed at the stage of HAM/TSP. Since frequent detection of clonal proliferation of HTLV-I infected cells has been reported previously in patients with HAM/TSP, careful follow-up is needed for patients with HAM/TSP.

Base Sequence↗
PubMed1995

[Inhibitory effects of menogaril to the proliferation of HTLV-I infected T-cell lines and fresh tumor cells from adult T-cell leukemia patients].

Anti-cancer effect of anthracyclines are well established. In vitro inhibitory effects of a new anthracyclin-derivative drug, menogaril (TUT-7) which is developed for oral administration, on three human T-cell leukemia virus type-I (HTLV-I) infected T-cell lines, a HTLV-I non-infected T cell line, and fresh tumor cells from four adult T-cell leukemia (ATL) cases are evaluated and compared to those of doxorubicin. The inhibitory effects of TUT-7 is almost as much as those of doxorubicin. Both TUT-7 and doxorubicin induced apoptosis to a HTLV-I infected cell line and inhibited proliferation of fresh tumor cells from ATL of chronic, acute and lymphoma type in a dose dependent manner. We have already reported that skin eruption of ATL patient improved by oral administration of TUT-7. This new anthracyclin-derivative would be useful in treating ATL patients even in out-patients clinic keeping a good quality of life.

Apoptosis↗
PubMed1995

ATL cells recognize self class II HLA antigens: implication to leukemogenesis.

Adult T cell leukemia (ATL) cells show the decreased expression of T cell receptor (TCR)/CD3 complex on their surfaces in vivo. It is well known that excess amounts of antigen modulate TCR/CD3 complex on antigen-specific T lymphocytes. We hypothesized that antigen receptor of ATL cells was down-regulated with some antigenic stimulation in vivo, which might play an important role in leukemogenesis. In order to test this possibility, we studied whether the fresh ATL cells from three cases would respond to autologous and allogeneic lymphoid cell lines. In two of three cases, ATL cells could proliferate in the presence of autologous cell lines. In one case, this proliferation could be completely inhibited by anti-CD3 and anti-human leukocyte antigen (HLA)-DQ monoclonal antibodies, indicating that ATL cells recognized self HLA-DQ. In another case, the proliferation was suppressed by anti-CD3 and HLA-DR antibodies. These findings showed that ATL cells of some cases were derived from autoreactive T lymphocytes and such stimulation via TCR/CD3 complex plays an important role in the leukemogenesis of ATL in vivo.

Autoantigens↗
PubMed1993

Deregulated c-fos modulates B cell responses to switch mediators.

We examined effects of deregulated c-fos on the proliferation and differentiation of B cells in vitro, using splenic B cells from H2-c-fos transgenic mice. When these cells were cultured with lipopolysaccharide (LPS) plus recombinant interleukin 4 (rIL-4) (10(4) U/ml), the proliferative response of the B cells was augmented with any dose of LPS used. This augmented proliferation resulted in an increase in IgG1 production in the culture, at the lower concentrations of LPS (< 2.5 micrograms/ml). However, H2-c-fos B cells did not produce IgG1 in the culture at higher concentrations of LPS (> 5 micrograms/ml) probably due to the perturbation of B cell differentiation to antibody-forming cells. These results suggest that the deregulated expression of c-fos modulates the proliferation and differentiation of B cells stimulated with LPS plus rIL-4.

Animals↗
PubMed1993

Acute myeloid leukemia possibly producing thrombopoietic factor(s).

A 75-year-old man developed a cluster of differentiation (CD)4-positive but human T-cell lymphotropic virus type I (HTLV-I)-negative T lymphoid neoplasm with overwhelming cutaneous involvement and mild thrombocytosis. Twelve courses tetrahydropyranyl adriamycin, cyclophosphamide, vincristine and prednisone (THP-COP) combination chemotherapy led him to complete remission. After four months of complete remission, however, atypical immature cells (blasts) appeared in peripheral blood and bone marrow. Surface marker analysis revealed the blasts to be CD2-, CD3-, CD4-, CD5-, CD7+, CD8-, CD10, CD13 +/-, CD19-, CD20-, CD25-, CD33+ and human leukocyte antigen-DR (HLA-DR+). Staining for myeloperoxidase, esterases, PAS and platelet peroxidase were all negative. The patient was diagnosed as having both CD7 and CD33 positive acute myeloid leukemia (AML). The relation between the T cell lymphoid neoplasm and AML was not clear. Thrombocytosis became more marked after acute leukemia occurred and the platelet count varied in parallel with the blast cell count in peripheral blood. When the leukemic cell count was high, thrombopoietic activity could be detected in the serum. In addition, conditioned medium obtained from primarily-cultured blasts had detectable thrombopoietic activity, which implied the blasts directly to produce a thrombopoietic factor(s). Analysis of the serum concentration for cytokines with associated thrombopoietic activity indicated that the blasts possibly produced a thrombopoietic factor(s) distinct from interleukin (IL)6, IL3, leukemia inhibitory factor (LIF), erythropoietin and granulocyte macrophage-colony stimulating factor. To our knowledge, this is the first reported case of an acute myeloid leukemia with marked thrombopoiesis (more than 2000 x 10(3)/microliter of maximum platelet count in peripheral blood.

Acetylcholinesterase↗