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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 1,189 records · Page 66Linked to original sources

Salvage chemotherapy of refractory non-Hodgkin's lymphoma with aclacinomycin, behenoyl ara-C, etoposide, and prednisolone.

A total of 40 patients with recurrent non-Hodgkin's lymphoma were treated with ABEP combination chemotherapy (aclarubicin, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, etoposide, and prednisolone). A complete remission (CR) was achieved in 37.5% of the patients and partial remission, in 15.0%. The ABEP regimen proved to be effective in T-cell as well as B-cell lymphoma. It appears that the ABEP regimen may be partially non-cross-resistant with front-line doxorubicin-containing combinations. Survival for 39 months was achieved in 42.0% of the CR responders compared with 6.7% of partial responders (PRs) and nonresponders (NRs) (P less than 0.01). Disease-free survival for 45 months was seen in 66% of the CR patients. The ABEP regimen was effective in the treatment of patients with recurrent or refractory lymphoma, enabling hope for long-term survival in the majority of CR cases.

Aclarubicin↗

Phospholipase C activity in human placental membrane.

Receptor-stimulated hydrolysis of polyphosphoinositides by action of phospholipase C appears to be an important mediator of cell activation through the generation of the second messengers, in particular inositol triphosphate (IP3). In order to understand placental function better, activity of IP3 production from membrane in cell-free system was examined. Incubation of membrane preparation from [3H]inositol-labelled human placenta with Ca2+ in the presence of 1 mM ATP and 1 mM GTP resulted in the rapid production of IP3 in a dose dependent manner; half-maximal effect occurred at 10 microM. On the other hand, little effect was observed in the case of membrane prepared from [3H]arachidonic acid-labelled placenta, suggesting higher requirement of Ca2+ for phospholipase A2 activation. These data suggest that placenta contains phospholipase C hydrolyzing polyphosphoinositide at physiological concentration of Ca2. This is the first report to provide direct evidence of transmembrane signalling mechanisms in the human placenta, and may provide a clue to the etiology of placental disorders.

Female↗

Constitutive production of interleukin 6/B cell stimulatory factor-2 from inflammatory synovium.

Interleukin 6 (IL-6) production from synovial tissues of various diseases was examined. Augmented IL-6 production was found in inflammatory synovium not only in RA but also in other kinds of synovitis, including psoriatic arthritis and Behçet's disease. Increased amounts of IL-6-mRNA were detected in rheumatoid synovium using a dot blot hydridization technique. Furthermore, there was a positive correlation between IL-6 production and accumulation of plasma cells in the synovium. These findings suggest that IL-6 plays an important role not only in immune response but also in active inflammation in various kinds of synovitis.

Adult↗

Mesodermal mixed tumor primary in the fallopian tube.

Mullerian mixed tumors, as a group, are uncommon. Only 27 cases of this tumor of the fallopian tube have been reported to date. We report the 28th case of mixed mesodermal tumor, originating in the fallopian tube. A 79-year-old woman had mistaken a bloody vaginal discharge for hematuria. Various examinations showed no evidence of malignancy. However, computerized tomography revealed an intrapelvic tumor. Laparotomy was performed, with a suspicion of tubal malignancy. The final pathologic diagnosis was mixed mesodermal tumor, originating in the fallopian tube. Postoperatively, the patient was placed on oral adjuvant chemotherapy for 34 months. At present, she is doing well. Though no definite conclusions regarding the best method of therapy can be reached, an aggressive mode of therapy is recommended. The primary therapy is surgery; however, surgery followed by chemotherapy may have a potential benefit.

Aged↗

Carbohydrate binding specificity of the basic lectin from winged bean (Psophocarpus tetragonolobus).

The carbohydrate binding specificity of the basic lectin from winged bean (Psophocarpus tetragonolobus) was investigated by quantitative precipitin analysis using blood group A, B, H, Le and I substances and by precipitation inhibition with various mono- and oligosaccharides. The lectin precipitated best with A1 substances and moderately with B and A2 substances, but not with H or Le substances. Inhibition assays of lectin-blood group A1 precipitation demonstration that A substance-derived oligosaccharides having the common structure: D-GalNAc alpha(1----3)D-Gal-(beta 1----3/4) to a D-Glc, were the best inhibitors and about 8 and 4 times more active than D-GalNAc and D-GalNAc alpha(1----3)D-Gal, respectively. A difucosyl A-specific oligosaccharide (A-penta), a monofucosyl (A-tetra) and a non-fucosyl containing (A5II) oligosaccharide, D-GalNAc alpha(1----3)D-Gal beta(1----3)D-GlcNAc, had almost the same reactivity, suggesting that the fucose linked to the sub-terminal D-Gal or to the third sugar. D-GlcNAc, from the non-reducing end made no contribution to the carbohydrate binding. Although a terminal non-reducing D-GalNAc or D-Gal residue was indispensible for binding, the lectin bound not only to these terminal non-reducing galactopyranosyl residues, but also showed increased binding to oligosaccharides in which it was bonded to a sub-terminal D-Gal joined to a D-GlcNAc residue, as in blood group A or B substances. This defines the site, thus far, as complementary to a disaccharide plus the beta linkage to the third sugar (D-Glc or D-GlcNAc) from the non-reducing end. The role of the beta(1----3) or beta(1----4) linkage of the sub-terminal non-reducing D-Gal to the D-GlcNAc requires further study.

Binding Sites↗

Difference in thiamine metabolism between extensor digitorum longus and soleus muscles.

1. Thiamine diphosphate level was higher in soleus muscle than in extensor digitorum longus muscle in various animals, whereas thiamine triphosphate level was less in the former muscle than in the latter except for mouse. 2. 2-Oxoglutarate dehydrogenase, transketolase and thiamine pyrophosphokinase activities were higher in soleus muscle than in extensor digitorum longus in rat and guinea pig. 3. The differences between rat two muscle phenotypes in thiamine diphosphate, but not thiamine triphosphate, level and the thiamine-related enzyme activities disappeared after denervation. 4. Tenotomy had little effect on thiamine phosphate levels and the thiamine-related enzyme activities in rat skeletal muscles.

Animals↗

Tissue difference in cellular localization of thiamine phosphate esters.

1. Thiamine phosphate levels were determined in the soluble and particulate fractions of various rat tissues. 2. There was marked tissue difference in the cellular localization of thiamine phosphates. 3. Brain thiamine triphosphate was localized only in the particulate fraction, whereas skeletal muscle thiamine triphosphate was in the soluble fraction as a protein-unbound form.

Animals↗

Inhibition by taurine of Na(+)-Ca2+ exchange in sarcolemmal membrane vesicles from bovine and guinea pig hearts.

1. Taurine, but not GABA, beta-alanine and glycine, inhibited Na(+)-dependent Ca2+ uptake in bovine cardiac sarcolemmal membrane vesicles in a dose-dependent manner. 2. The inhibition of Na(+)-dependent Ca2+ uptake was noncompetitive with respect to Ca2+ concentration. 3. The inhibitory effect of taurine on the exchange was also observed in cardiac sarcolemmal vesicles prepared from guinea pig, but not from rat. 4. Taurine did not affect Na(+)-dependent Ca2+ efflux nor ATP-dependent Ca2+ uptake in the bovine cardiac membranes.

Adenosine Triphosphate↗

IgG1 plasmacytosis in interleukin 6 transgenic mice.

Interleukin 6 (IL-6) has been suggested to be involved in the pathogenesis of polyclonal and monoclonal plasma cell abnormalities. To address this possibility, transgenic mice carrying the human IL-6 genomic gene fused with a human immunoglobulin heavy chain enhancer were generated. High concentrations of human IL-6 and polyclonal increase in IgG1 (120- to 400-fold) in sera of all transgenic mice were observed. A massive plasmacytosis in thymus, lymph node, and spleen and an infiltration of plasma cells in lung, liver, and kidney were observed. However, the plasma cells were not transplantable to syngeneic mice and were found not to contain chromosomal aberrations including c-myc gene rearrangements. The evidence indicates that deregulated gene expression of IL-6 can trigger polyclonal plasmacytosis but cannot induce plasmacytoma. It is suggested that additional genetic changes may be required for the generation of plasma cell neoplasia. Other interesting findings in these transgenic mice were the development of mesangio-proliferative glomerulonephritis and an increase in megakaryocytes in bone marrow.

Animals↗

Chemical deglycosylation of hen ovomucoid: protective effect of carbohydrate moiety on tryptic hydrolysis and heat denaturation.

Hen ovomucoid was chemically deglycosylated by treatment with trifluoromethanesulfonic acid at 0 degrees C for 60 min. About 75 mol% of the carbohydrate moiety was removed from the glycoprotein without changing its amino acid composition, and its trypsin inhibitory activity and immunoreactivity with specific antibodies remained unchanged. The deglycosylated ovomucoid was inactivated and degraded easily by an excess amount of trypsin, whereas the native glycoprotein was not. Furthermore, the biological and immunological activities of the deglycosylated ovomucoid were lowered by heat treatment more easily than those of the native ovomucoid. These results suggest that the carbohydrate moiety of ovomucoid contributes to the stability of the ovomucoid molecule against tryptic hydrolysis and heat denaturation.

Animals↗

Decrease in alpha 1-adrenoceptor reserve in mesenteric arteries isolated from spontaneously hypertensive rats.

The characterization of alpha-adrenoceptor-mediated contractile responses and the effects of the calcium channel blocker nifedipine on these responses were investigated in mesenteric arterial strips from 13-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Contractile responses to the alpha-adrenoceptor agonists phenylephrine and clonidine were mediated through the activation of alpha 1-adrenoceptors. The dose producing a half-maximum response (ED50) for the agonists was higher in SHR than in WKY. Affinities of alpha 1-adrenoceptors were similar between the two strains. When arterial strips from both strains were treated with the same concentration of phenoxybenzamine, the maximum response to each agonist was weaker in SHR. The alpha 1-adrenoceptor occupancy-response relationship for phenylephrine was hyperbolic and less steep in SHR, while the relationship for clonidine was linear in SHR but not in WKY. Alpha 1-adrenoceptor occupancy at a half-maximum response to each agonist was greater in SHR. Nifedipine inhibited the maximum responses to the agonists more profoundly in SHR than in WKY. This inhibition was greater in the response to clonidine than in the response to phenylephrine in both strains. When the maximum response to phenylephrine was reduced to the same extent in both strains by treatment with different concentrations of phenoxybenzamine, the responses to phenylephrine were more susceptible to inhibition by nifedipine. Under these conditions, the effects of nifedipine were similar between SHR and WKY. These results suggest that alpha 1-adrenoceptor reserve is reduced in SHR mesenteric artery compared with WKY, which may be responsible for the greater inhibition by nifedipine of the alpha 1-adrenoceptor-mediated contractions in SHR.

Adrenergic alpha-Agonists↗

The relationship between the percentage of circulating B cells, corticosteroid levels, and other immunologic parameters in thermally injured patients.

Thermal injury is known to induce alterations in the immune system, but the precise mechanisms have yet to be elucidated. We investigated the temporal relationship between serum and urine corticosteroid levels, the number of circulating B cells, serum immunoglobulin levels, and delayed hypersensitivity reactions in the postburn period. Fifteen adult patients (mean age, 44 years) admitted with thermal burns greater than 20% body surface area (BSA) (mean, 50%) were evaluated during four postburn periods. Using a bacterial adherence assay in blood smears, we observed an increased percentage of B lymphocytes (20.3%) in the early postburn period compared to normal controls obtained during the same time period (13.1%). The percentage of B cells gradually decreased during the subsequent 4 weeks and was not influenced by the eventual clinical outcome. The changes in B-cell percentage were paralleled by changes in the level of urine 17-hydroxysteroids. Serum IgG concentrations were low during the initial postburn period in survivors and nonsurvivors and returned to normal and above-normal levels in the late postburn period in both groups. The delayed hypersensitivity skin test reactions were also depressed in the immediate postburn period and returned to normal only in the surviving group at the end of the second postburn week. We speculate that the increased endogenous secretion of stress hormones results in an increase in circulating B cells secondary to their release from lymphoid organs and that the normalization of hormone levels as wound healing ensued was associated with the return of B cells to the lymphoid organs. This lymphocyte redistribution may result in polyclonal cellular interactions, with subsequent B-cell activation, and increased IgG production.

Adrenal Cortex Hormones↗

Results of a multicenter outpatient burn study on the safety and efficacy of Dimac-SSD, a new delivery system for silver sulfadiazine.

Dimac with silver sulfadiazine (Dimac-SSD), a new silver sulfadiazine delivery system, was evaluated prospectively in a multicenter study for the treatment of outpatient burn injuries. The goal of this study was to evaluate the effect of Dimac-SSD on the microbiology of the burn wounds and to quantitate its clinical safety and efficacy. A total of 197 patients were evaluated. Eight (4%) of these patients did not complete the study. Six patients withdrew because of local discomfort caused by the Dimac-SSD and two patients were terminated because of technical problems. The mean +/- SD duration of treatment with Dimac-SSD was 12 +/- 8.5 days, during which time the mean number of dressing changes was 2.9 per patient. During treatment with Dimac-SSD, the burn wound bacterial flora remained stable and overgrowth with Pseudomonas species or Gram-negative bacilli did not occur. Only four (2%) patients developed clinical infections; thus the Dimac-SSD appeared to have good antimicrobial effectiveness. This dressing was not associated with any organ system or metabolic side-effects and patient discomfort during application and removal was minimal. Thus this new delivery system for silver sulfadiazine was associated with excellent wound healing, a low incidence of wound infections, reduced frequency for dressing changes, and excellent patient compliance.

Acrylates↗

Acquired von Willebrand's syndrome with lupus-like serology.

We describe a 12-year-old boy with acquired von Willebrand's syndrome, who also had various autoantibodies. He presented with recent hemorrhagic symptoms and a prolonged bleeding time. Hemostatic studies revealed severely reduced levels of factor VIII procoagulant activity (VIII:C), von Willebrand's factor (vWF) antigen (vWF:Ag), and ristocetin cofactor activity (RCoF). An inhibitor that could be detected in the patient's plasma moderately decreased the levels of vWF:Ag in normal plasma, but did not interfere with the measurement of VIII:C or RCoF. Following the infusion of cryoprecipitate, half-lives of VIII:C, vWF:Ag, and RCoF were markedly reduced. 1-Deamino-8-D-arginine vasopressin infusion induced normalization of the prolonged bleeding time and caused a marked increase in VIII:C, vWF:Ag, and RCoF. Prior to treatment, there was a uniform reduction of all the multimers of plasma vWF in sodium dodecyl sulfate agarose gel electrophoresis. Following prednisone therapy, clinical and hemostatic findings were improved, and the multimeric patterns of vWF were normalized. These findings suggest that the low levels of all three parameters of factor VIII and all the multimers of plasma vWF in the patient are caused by rapid elimination of factor VIII complex from the circulation.

Child↗

Postnatal development of thiamine metabolism in rat brain.

The activities of thiamine diphosphatase (TDPase), thiamine triphosphatase (TTPase), and thiamine pyrophosphokinase and the contents of thiamine and its phosphate esters were determined in rat brain cortex, cerebellum, and liver from birth to adulthood. Microsomal TTPase activity in the cerebral cortex and cerebellum increased from birth to 3 weeks, whereas that in the liver did not change during postnatal development. Microsomal TDPase activity in the cerebral cortex showed a transient increase at 1-2 weeks, but that in the cerebellum did not change during development. In contrast to the activity of the brain enzyme, that of liver microsomal TDPase increased stepwise after birth. Thiamine pyrophosphokinase activity in the cerebellum increased from birth to 3 weeks and then decreased, whereas that in the cerebral cortex and liver showed less change during development. TDP and thiamine monophosphate (TMP) levels increased after birth and plateaued at 3 weeks whereas TTP and thiamine levels showed little change during development in the cerebral cortex and cerebellum. The contents of thiamine and its phosphate esters in the liver showed more complicated changes during development. It is concluded that thiamine metabolism in the brain changes during postnatal development in a different way from that in the liver and that the development of thiamine metabolism differs among brain regions.

Acid Anhydride Hydrolases↗

Decreased arterial responsiveness to multiple cyclic AMP-generating receptor agonists in spontaneously hypertensive rats.

1. Arterial relaxant responses via beta-adrenoceptors are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). Recent studies from this laboratory proposed that a reduced function of stimulatory guanosine 5'-triphosphate (GTP)-binding protein (Gs) is responsible for the decreased beta-adrenoceptor responsiveness in the SHR femoral artery. Since the Gs is common to all tissues, as opposed to receptors, which are tissue specific, the reduced function of Gs should lead to resistance to multiple receptors that act by activating adenylate cyclase (AC). To test this hypothesis, relaxant responses via beta-adrenoceptors, A2-adenosine, H2-histamine and D1-dopamine receptors were compared between arterial strips from 13 week-old WKY and age-matched SHR. 2. The relaxant responses to noradrenaline (NA) via beta-adrenoceptors in femoral, mesenteric, renal and carotid arteries were significantly decreased in the SHR, when compared with the respective arteries from WKY. 3. However, under the same conditions arterial relaxant responses to forskolin, an activator of AC, were not significantly different between the WKY and SHR. 4. The relaxant responses due to activation of A2-adenosine. H2-histamine and D1-dopamine receptors were significantly decreased in the SHR arteries. 5. Nitroprusside and nifedipine, agents which are independent of the Gs.AC system, produced similar arterial relaxations in the WKY and SHR. 6. These results support the hypothesis that a reduced function of Gs in the SHR is responsible for the decreased arterial responsiveness to a variety of receptor agonists whose mechanism of action involves AC activation.

Animals↗