Search PubMed⌕ Search

Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 469 records · Page 26Linked to original sources
PubMed1995

Benefits of Medroxyprogesterone Acetate (MPA) in Advanced or Recurrent Breast Cancer with Higher Serum Concertration.

The efficacy of medroxyprogesterone acetate (MPA) therapy in controlling progressive measurable metastatic breast cancer was assessed in 61 patients. In addition serum MPA concentrations were measured by high performance liquid chromatography (HPLC) and subjective effects of treatment were monitored. Overall 24 patients (39.3%) achieved an objective response(2 complete responses [ CR ] and 22 partial responses [ PR ]). There was no significant relationships between response to therapy and menopausal status, metastatic sites, previous therapy, histological type, or disease-free interval. Patients with estrogen (ER) and progesterone (PgR) receptor-positive tumors responded more frequently. Significant differences in serum MPA concentrations were seen between responders and non-responders, objective tumor shrinkage being seen in patients with serum levels in excess of 55 ng/ml. There were few cases responding to the therapy with serum MPA concentrations lower than 25 ng/ml. The serum MPA levels significantly correlated with an improvement in the performance status and survival. Patients with serum MPA concentrations lower than 25 ng/ml had significantly poorer survival. There was a significant relationship between MPA level and dose per area of boby surface (mg/ m(2)) in cases with CR or PR or no change (NC). However, the serum levels of patients with progressive disease despite therapy were lower than the expected levels based on the body surface area. This study demonstrated that serum MPA concentration is a determining factor for therapeutic benefit in advanced or recurrent breast cancer.

Journal Article↗
PubMed1995

Effect of staphylokinase concentration of plasminogen activation.

Activation of Glu- and Lys-plasminogen by various concentrations of recombinant staphylokinase (SAK) were studied by the generation of amidolytic activity from the chromogenic substrate S-2251(H-D-Val-Leu-Lys-pNA) and by SDS-PAGE analysis. Surprisingly, excess SAK decreased and fixed the rate of S-2251 hydrolysis in a mixture of Lys-plasminogen and SAK. Since the effect of SAK on S-2251 hydrolysis by plasma was similar, the hydrolysis kinetics by free plasmin and plasmin-SAK complex were studied. Hydrolysis by either enzyme form followed Michaelis-Menten kinetics with a Km of 0.38 mM for plasma and 3.74 mM for SAK-plasmin complex. The catalytic rate constant was 22.7 s-1 for plasmin and 21.0 s-1 for the SAK-plasmin complex. With excess SAK and vigorous removal of plasmin activity from plasminogen, the pre-activation lag period differed greatly between Glu- and Lys-plasminogen. Based on the different substrate specificity of plasmin and plasmin-SAK complex, we analyzed the Glu-plasminogen activation with either catalytic or excess SAK. With excess SAK, almost no Lys-plasminogen was detectable and whole Glu-plasminogen was converted directly to Glu-plasmin, then gradually to Lys-plasmin. In contrast, Lys-plaminogen appeared rapidly with catalytic amount of SAK. These results suggest that inhibition of Glu-plasminogen to Lys-plasminogen to Lys-plasminogen conversion in the plasminogen-SAK complex in the presence of excess SAK prolonged the initial lag phase of activation.

Dose-Response Relationship, Drug↗
PubMed1995

IL-10 converts mouse lymphoma cells to a CTL-resistant, NK-sensitive phenotype with low but peptide-inducible MHC class I expression.

IL-10 has a variety of effects including: inhibition of monocyte MHC class II-dependent Ag presentation, Th1 cytokine production, and inhibition of T cell proliferation. Recently we have shown that IL-10 inhibits Ag presentation to human tumor-specific and allospecific CTL. In the present study we showed that transfection of the mouse lymphoma RMA (H-2b) with the IL-10 gene induced conversion to a RMA-S-like phenotype. The changes included an inhibition of lysis by minor histocompatibility or tumor Ag-specific CTLs and, conversely, a dramatic increase in susceptibility to lysis by NK cells. The RMA-10 transfectants showed levels of H-2 expression as low or even lower than those found on RMA-S. The levels of tested adhesion molecules were unaltered. Treatment of RMA with rIL-10 gave a less pronounced change in phenotype. In addition, relative to untreated target cells, IL-10 pretreated cells or IL-10 transfectants were unaltered in their capacity to affect cytotoxicity by cold target inhibition, arguing against the possibility that the observed effect could be a direct effect of IL-10 on the CTL. The expression of H-2 was partially restored by coculturing RMA-10 transfectants with class I-binding peptides. Taken together, these results indicate that IL-10 exerts a post-transcriptional effect on H-2 expression, compatible with an induced decrease in the access of peptides to the MHC class I complex. IL-10 is the first cytokine reported to have this effect and also the first factor shown to induce NK sensitivity and reduced sensitivity to CTL, an effect that may be of physiologic relevance.

Animals↗
PubMed1995

Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease.

T cells from mice bearing an experimental colon carcinoma, and from patients with colorectal and renal carcinomas, have atypical T-cell receptors (TCR). In the present study, further characterization of modulations in CD3- and CD16-associated zeta chain in peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from colorectal carcinomas was performed. Relative to PBL, the percentage of natural killer (NK) cells among fresh TIL was reduced, while a higher proportion of T cells expressing HLA-DR was found. As previously reported, we found significantly reduced levels of the CD3- and CD16-associated zeta chain in TIL and, to a lesser extent, also in patients' PBL. Levels of zeta chain in T and NK cells from non-cancerous colorectal tissue from patients were lower than in PBL but higher than in TIL, with a direct relationship between levels of this signal-transducing molecule and the distance from the tumor. In addition, zeta levels correlated with the Dukes' stage of the disease, since PBL from patients with lymph-node involvement or distant organ metastases (Dukes' stages C and D) had significantly less CD3 zeta than patients with localized disease (stages A and B). Patients' T cells also had decreased levels of cell-surface and cytoplasmic CD3 epsilon. We also observed reduced levels of the TCR accessory molecules CD4 and CD8, mainly on TIL but to a lesser extent also on patients' PBL. Biochemical analysis of anti-CD3 epsilon-immunoprecipitated TCR complexes demonstrated that the CD3 complex was not associated with the zeta chain, either on TIL or on PBL or on lymphocytes from non-cancerous colon tissue, suggesting a defect in the assembly of the TCR complex. Following several days of in vitro culture with recombinant interleukin-2 and phytohemagglutinin, anti-CD3 or anti-CD2 monoclonal antibodies (MAbs), levels of CD3 zeta chain as well as of cell surface CD3 epsilon were normalized. Our findings suggest an abnormal expression as well as assembly of several different signal-transducing molecules of T cells and NK cells, which correlate with the stage of the disease in patients with colorectal carcinomas.

Adult↗
PubMed1995

Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase I.

A number of studies have suggested that topoisomerase I (topo I) activity may be important in human immunodeficiency virus type 1 (HIV-1) replication. Specifically it has been reported that purified virus particles have topo I activity and that inhibitors of this enzyme can inhibit virus replication in vitro. We have investigated a possible association of HIV-1 gag proteins with topo I activity. We found that whereas the gag-encoded proteins by themselves do not have activity, the nucleocapsid protein p15 can interact with and enhance the activity of cellular topo I. Furthermore it could be demonstrated that topo I markedly enhanced HIV-1 reverse transcriptase activity in vitro and that this could be inhibited by the topo I-specific inhibitor camptothecin. The findings suggest that cellular topo I plays an important role in the reverse transcription of HIV-1 RNA and that the recruitment of this enzyme may be an important step in virus replication.

Base Sequence↗
PubMed1995

Responses of median preoptic neurons projecting to the hypothalamic paraventricular nucleus to osmotic stimulation in Wistar-Kyoto and spontaneously hypertensive rats.

Twenty-one median preoptic nucleus (MnPO) neurons in normotensive Wistar-Kyoto rats (WKY) and 18 MnPO neurons in spontaneously hypertensive rats (SHR) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) under urethane anesthesia. No significant differences in the latency, conduction velocity, or threshold of antidromic activation were observed between WKY and SHR. The spontaneous discharge rate was significantly higher in SHR than in WKY. The activity of these identified MnPO units was examined for response to intracarotid injections of isotonic (0.15 M NaCl solution, 0.05 ml) or hypertonic (0.3 M NaCl solution, 0.05 ml) saline. All the units did not change their activity to the injections of isotonic saline. Of these units, 14 units in WKY and 12 units in SHR displayed and 3 units in WKY and 4 units in SHR exhibited a reduction in neuronal activity following the injections of hypertonic saline, while the remaining 4 units in WKY and 2 units in SHR were unresponsive. The duration and frequency of excitatory response, but not the inhibitory response, caused by the osmotic stimulation was much greater in SHR than in WKY. These results show that MnPO neurons projecting to the PVN may carry the information from osmosensitive elements and that there is a difference between WKY and SHR in the responsivity of these MnPO neurons to the osmotic stimulation.

Animals↗
PubMed1995

An Evaluation of DNA Polymerase alpha as a Prognostic Predictor in Early Breast Cancers Smaller than 2 cm.

We examined the relationship between proliferative activity determined by DNA polymerase alpha and clinicopathologic variables in breast cancer patients, and evaluated the usefulness of DNA polymerase alpha as a prognostic predictor in 337 early breast cancers with tumors smaller than 2 cm, which had favorable outcomes. About 60% of tumors had lower proliferative activity. A significant correlationwas found between DNA polymerase alpha and ER, PgR, histological type, or the degree of infiltration into lymphatic vessels which reflect the prognosis. Cancers with higher DNA polymerase alpha activity were associated with shorter disease-free and overall survival times. In a multivariate analysis the DNA polymerase alpha was found to be an independent and significant factor in early breast cancer.

Journal Article↗
PubMed1995

Chondroitin sulphate proteoglycans in the rat brain: candidates for axon barriers of sensory neurons and the possible modification by laminin of their actions.

The addition of chondroitin sulphate proteoglycans (CSPGs), purified from the rat brain, to the culture medium of PC12D cells inhibited their proliferation and neurite outgrowth. Therefore, we investigated the effects of several extracellular components on the inhibitory actions of CSPGs on PC12D cells, as well as their immunocytochemical distribution in the rat embryo to determine whether the findings in vitro could be reproduced in vivo. Coating of the substratum with polylysine was necessary for the appearance of the inhibitory effects of brain CSPGs on PC12D cells. The additional pretreatment of polylysine-coated dishes with laminin or fibronectin promoted the outgrowth of neurites from PC12D cells. Laminin and fibronectin, but not collagen (types I and IV) and CELL-TAK (cell adhesion molecules), prevented the inhibitory effects of brain CSPGs in a concentration-dependent manner. Doses producing 50% reduction by laminin (or fibronectin) of the CSPG effects were 1.5 (or 25) micrograms/ml for neurite outgrowth and 2.2 (or 28) micrograms/ml for proliferation. The ratio of dish-attached CSPGs to laminin necessary for 50% reduction was about approximately 50:1 (wt/wt). Laminin from any source had the same effect. Brain CSPGs also obviously impeded the growth of fibres from dorsal root ganglion explants and primary cultured dorsal root ganglion neurons. Neurocan (a major CSPG in the brain)-like immunoreactivity was detected in the boundary caps and roof plate in the rat embryo at 13.5 days of gestation, when DRG neurons were extending their axons to the neural tube. The distributions of laminin and tenascin appeared, respectively, to be slightly and considerably different from that of neurocan.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Progression and regression of coronary artery disease--linkage of clinical, pathologic, and angiographic findings.

Progression and regression of coronary artery disease are analyzed with respect to clinical, pathologic, and angiographic findings. Clinically, progression of coronary artery disease is highly unpredictable process. The pattern of progression is not linear in time but sometimes is rapid and other times is slow. The atherosclerotic lesion is not pathologically homogeneous. Regression therapies, therefore, might be effective depending on the composition of the lesion and the phase of atherosclerotic evolution. True clinical regression should be concordant with the clinical improvement of symptoms as well as prognosis. Further studies are required to establish the effectiveness of therapy for the prevention of progressive coronary artery disease.

Animals↗
PubMed1995

Differences in electrophysiological properties of angiotensinergic pathways from the subfornical organ to the median preoptic nucleus between normotensive Wistar-Kyoto and spontaneously hypertensive rats.

Electrophysiological properties of angiotensinergic pathways from the subfornical organ (SFO) to the median preoptic nucleus (MnPO) were investigated in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) under urethane anesthesia. The activity of SFO neurons that were antidromically activated by electrical stimulation of the MnPO was compared between WKY (n = 28) and SHR (n = 27). No significant differences were observed between WKY and SHR in the latency, conduction velocity, or threshold of antidromic activation. The firing rate was significantly shorter in SHR. The activity of MnPO neurons was tested for a response to microiontophoretic application of angiotensin II (ANG II) and electrical stimulation of the SFO. Sixteen of 46 MnPO neurons tested in WKY and 15 of 47 MnPO neurons tested in SHR were excited by both ANG II applied iontophoretically and SFO stimulation, and the excitatory responses were prevented by iontophoretically applied saralasin, a specific ANG II antagonist. In these MnPO neurons that demonstrated the excitation to both SFO stimulation and ANG II, the firing rate was significantly higher and the threshold current required to evoke the SFO stimulus-induced excitation was significantly lower in SHR. The sensitivity to SFO stimulation was much greater in SHR than in WKY. These results provide evidence that there are marked alterations in the physiological properties of the angiotensinergic circuit from the SFO to the MnPO between WKY and SHR and imply that a disorder in the neural circuit may contribute, in part, to hypertension.

Angiotensin II↗
PubMed1995

Transplantation of basal forebrain cells of foetal rats into the subarachnoid space: improvement of disturbance of passive avoidance memory due to injury of nucleus basalis magnocellularis.

Basal forebrain cells of foetal rats were transplanted into the subarachnoid space of adult rats harbouring a kainic acid-induced unilateral lesion in the nucleus basalis magnocellularis. Passive avoidance response tests were performed eight weeks after the transplantation, and the results were compared with those of lesioned but non-transplanted rats and of non-lesioned control rats. Although acquisition impairments did not improve, retention impairments were significantly ameliorated in the transplanted rats. Histologically, transplanted foetal neurons survived and grew very well over the cortical surface, and exhibited facilitated neuritic elongation on acetylcholinesterase staining. Choline acetyl-transferase-immunoreactive neurons were found along the needle track as well as in the subarachnoid graft tissues. The results seem to indicate that not the re-innervation from the graft to the host cortex but the diffusional supply of neurotransmitters and/or their synthetic enzymes and neurotrophic factors were responsible for improvement of memory deficits. The subarachnoid space proved to be an adequate place for growth of transplanted neuronal and glial cells for reasons of ample supply of oxygen and nutrition and of low tissue pressure.

Animals↗
PubMed1995

The phylogenetic relationships of Eeniella nana Smith, Batenburg-van der Vegte et Scheffers based on the partial sequences of 18S and 26S ribosomal RNAs (Candidaceae).

Two strains of Eeniella nana were examined for their partial base sequences of 18S and 26S rRNAs. In the partial base sequences of 18S rRNA (positions 1451 through 1618, 168 bases) the strains of E. nana have five, five, four and eleven base differences with those of Dekkera bruxellensis (type species), D. anomala (and Brettanomyces anomalus), D. naardenensis and D. custersiana, respectively. In the 26S rRNA partial base sequencings (positions 1611 through 1835, 225 bases and positions 493 through 622, 130 bases) the base differences were 46, 43, 34 and 40 and the percent similarities were 53-54, 51-54, 56-57 and 51-53, respectively. The sequence data obtained are discussed phylogenetically and taxonomically, especially on retention of the generic name Eeniella.

Base Sequence↗
PubMed1995

Genotyping of isolates of Taylorella equigenitalis from thoroughbred brood mares in Japan.

Profiles of the genomic DNA of 104 strains of T. equigenitalis isolated from brood mares with contagious equine metritis in Hokkaido during the breeding seasons from 1980 to 1993, as well as those of five strains (SS28, EQ56, EQ59, EQ70 and HH139) previously isolated in Japan were examined after restriction digestion and crossed-field gel electrophoresis. These profiles were essentially identical to each other and the various isolates and strains appeared to have a common genotype, designated 'genotype J', with respect to two restriction enzymes, ApaI and NotI. These results suggest a common source for all these isolates obtained over the course of more than 10 years in Japan.

Animals↗