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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 577 records · Page 32Linked to original sources

Assessment of currently available low-density lipoprotein apheresis systems.

It has already been 10 years since the introduction of low-density lipoprotein (LDL) apheresis technologies. They have been established as technically and medically feasible for long-term treatment and economically acceptable, and their long-term treatment effects have been determined. Currently, there are efforts to develop more selective LDL removal systems. However, after 10 years of research, it is time to carefully review this strategy. The approach may have become too specific in light of the multiple macromolecules involved in the pathogenesis of atherosclerosis. In this paper, the six currently available LDL apheresis systems (plasma exchange, double filtration plasmapheresis, thermofiltration, LDL chemical adsorption (Kaneka system), LDL immunoadsorption, and the heparin-induced extracorporeal LDL precipitation [HELP] system) were reviewed and scored from various points of view such as effectiveness, simplicity, safety, and cost performance. Finally, each system was assessed from the global point of view in relation to the pathogenesis of lipid-related diseases.

Blood Component Removal↗

Pharmaceutical evaluation of carbamazepine modifications: comparative study for photostability of carbamazepine polymorphs by using Fourier-transformed reflection-absorption infrared spectroscopy and colorimetric measurement.

The tablet surface was evaluated without physical damage by means of Fourier-transform infrared reflection-absorption spectroscopy (FT-IR-RAS) and colorimetric measurement (colour difference, delta E) of the carbamazepine polymorphs I, II and III, after photodegradation at two irradiation intensities (3.0 and 12.0 J cm-2s-1) under a near-UV fluorescent lamp. The surface of sample pellets of all crystalline forms turned gradually from white to yellow-orange upon exposure to light, and the discoloration rate of form II was faster than that of forms I and III, indicating that form II was the most unstable of the three. The major photoproducts were identified by HPLC, NMR and MS analyses. The carbamazepine content on the surface of the tablet was determined based on the absorption at 1685 cm-1 attributable to C=O stretch vibration in the FT-IR-RAS spectra before and after irradiation by a near-UV fluorescent lamp. The semilogarithmic plots of the photodegradation profiles of the various polymorphs were straight lines, including the induction period, indicating that degradation of the drug on the surface followed first-order kinetics. The induction periods of all forms were not significantly different. However, the degradation rate constant of form II at 12.0 J cm-2s-1 was 5.1 and 1.5 times larger than those of forms I and III, respectively.

Calorimetry, Differential Scanning↗

Chromosomal mapping of mouse 5S rRNA genes by direct R-banding fluorescence in situ hybridization.

The mouse 5S rRNA gene was mapped by direct R-banding fluorescence in situ hybridization (FISH) with biotinylated probes. Two genomic fragments amplified by PCR from total genomic DNA of BALB/c mice and Mus spretus, a 0.16-kb fragment that included the 121-bp 5S rRNA gene and a 1.6-kb fragment that included the whole spacer region, were used for chromosomal mapping of the 5S rRNA gene. Both fragments hybridized to a single locus on a pair of autosomal chromosomes of BALB/c mice. The major cluster of mouse 5S rRNA genes was assigned to the most terminal R-negative to R-positive bands of the E region of mouse Chromosome 8, which is homologous to the linkage of the 5S rRNA gene on the long arm of human chromosome 1. The location of the 5S rRNA gene was mapped in five laboratory strains, in wild mice of six Mus musculus subspecies (domesticus, brevirostris, musculus, bactrianus, castaneus, and molossinus) derived from 10 separate localities, and in four different Mus species (spretus, hortulanus, spicilegus, and caroli), using FISH. The 5S rRNA cluster mapped to the same position on the chromosomes of all mouse species and subspecies studied. These results suggest that the location of the mouse 5S rRNA gene on the distal telomeric region of Chromosome 8 is evolutionarily conserved. In comparison, the chromosomal assignments of centromeric 18S-28S rRNA genes are highly variable among the different M. musculus subspecies and Mus species.

Animals↗

Cardiorenal and neurohumoral effects of endogenous atrial natriuretic peptide in dogs with severe congestive heart failure using a specific antagonist for guanylate cyclase-coupled receptors.

BACKGROUND: To elucidate the extent of the compensatory role of endogenous atrial natriuretic peptide (ANP) in severe congestive heart failure (CHF), we examined the changes in hemodynamics and neuroendocrine and renal functions after incremental administration of an ANP antagonist, HS-142-1 (HS), in dogs with CHF. METHODS AND RESULTS: We assessed the effects of HS on the suppression of plasma and urinary cGMP levels as a marker of endogenous ANP activity in dogs without CHF. Bolus injections of 0.3 and 1.0 mg/kg HS reduced plasma cGMP levels to 77% and 60% and urinary cGMP excretion to 78% and 61% of the relevant control levels, respectively. Then the study was performed in dogs with CHF induced by chronic rapid ventricular pacing, and the plasma ANP level was sixfold higher than that in the controls. Hemodynamic, hormonal, and renal variables were determined both before and after subsequent incremental administration (0.3, 1.0, and 3.0 mg/kg every 30 minutes) of HS. HS lowered the plasma and urinary cGMP levels dose dependently to 32% and 37% of the control levels, respectively. Mean arterial, pulmonary capillary wedge, and right atrial pressures and cardiac output did not change significantly. However, plasma renin activity, aldosterone level, and norepinephrine level increased rapidly to 226%, 179%, and 252% of the control values, respectively. Urine flow rate and urinary sodium excretion were significantly inhibited, with no concomitant change in glomerular filtration rate or renal plasma flow. CONCLUSIONS: These findings suggest that endogenous ANP contributes to the suppression of the activation of the renin-aldosterone system and sympathetic nervous activity and body fluid retention but that the vasodilative action of this peptide is attenuated in advanced CHF.

Animals↗

Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor.

Atrial natriuretic peptide is an important peptide hormone of cardiac origin that functions to regulate cardiac preload via the regulation of sodium excretion. This natriuretic action occurs through activation of the particulate guanylyl cyclase-linked natriuretic peptide-A receptor. HS-142-1 is a newly discovered antagonist of the natriuretic peptide-A receptor that permits insight into the functional role of atrial natriuretic peptide in cardiorenal homeostasis. The first objective of this study was to define for the first time the intrarenal action of HS-142-1 on exogenous atrial natriuretic peptide-mediated natriuresis in anesthetized normal dogs. In group 1 (n = 6), which received intravenous atrial natriuretic peptide at 100 ng/kg per minute, intrarenal HS-142-1 (0.5 mg/kg bolus) attenuated atrial natriuretic peptide-induced increases in glomerular filtration rate, urine flow, sodium excretion, and renal cyclic GMP generation and decreases in distal tubular sodium reabsorption. The second objective was to determine whether endogenous atrial natriuretic peptide participates in the regulation of basal sodium excretion. In group 2 (n = 6), intrarenal HS-142-1 alone decreased both absolute and fractional sodium excretion and renal cyclic GMP generation and increased distal tubular sodium reabsorption. These studies demonstrate that HS-142-1 markedly attenuates exogenous atrial natriuretic peptide-mediated natriuresis via enhancement of distal tubular reabsorption and blunting of increases in glomerular filtration rate. Second, the current studies support a functional role for endogenous atrial natriuretic peptide in the regulation of basal sodium excretion.

Animals↗

Augmented receptor-mediated Ca2+ mobilization causes supersensitivity of contractile response to serotonin in atherosclerotic arteries.

We have previously reported that atherosclerotic arteries obtained from Watanabe heritable hyperlipidemic (WHHL) rabbits exhibit a marked increase of contractile response to serotonin (5-hydroxytryptamine [5-HT]) and ergonovine and that these augmented contractile responses to specific agonists may play an important role in the pathogenesis of vasospasm. In the present study, we investigated whether supersensitivity to 5-HT in atherlosclerotic arteries was due to an increase in 5-HT receptor-mediated Ca2+ mobilization or to an increase in Ca2+ sensitivity of the contractile elements. We measured simultaneously both isometric tension and [Ca2+]i in fura 2-loaded aortic smooth muscle strips from control and WHHL rabbits. Muscle tension in the high K+ (72.7 mmol/L)-stimulated states and [Ca2+]i in both resting and high K(+)-stimulated states did not differ between control and WHHL rabbits. In atherosclerotic aortas from WHHL rabbits, the dose-response curves of both tension and [Ca2+]i for 5-HT were shifted to the left at lower threshold concentrations and one-half maximally effective dose. The maximum response of contraction produced by 5-HT in WHHL rabbits was augmented compared with that in control rabbits (123 +/- 17% versus 33 +/- 7% of the 72.7 mmol/L K(+)-induced contraction, P < .001). The maximum response of [Ca2+]i produced by 5-HT was also augmented in WHHL rabbits compared with control rabbits (29 +/- 4% versus 10 +/- 0.9% of the 72.7 mmol/L K(+)-induced [Ca2+]i, P < .001). In contrast, the responses of contraction and [Ca2+]i to phenylephrine were similar between control and WHHL rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In situ demonstration of the HTLV-I genome in the spinal cord of a patient with HTLV-I-associated myelopathy.

Using polymerase chain reaction (PCR) and in situ hybridization, we investigated the HTLV-I genome in the CNS of an HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient with a 20-year disease duration. Neuropathologically, there was severe white matter degeneration throughout the spinal cord, but lymphocytic infiltrates were not evident in any lesion. PCR amplification of the pX region of HTLV-I DNA detected its sequence in the spinal cord and all extra-CNS tissue samples. In situ hybridization using probes complementary to the pX and gag regions detected the HTLV-I genome in the cytoplasm and nucleus of cells in the thoracic cord. The findings indicate a direct involvement of HTLV-I in the neurodegeneration of HAM/TSP.

Aged↗

Dissolution behavior of phenytoin-bile salt complexes prepared by co-grinding.

The physicochemical properties of phenytoin (PHT)-bile salt complexes comprised of sodium dehydrocholate (DHCNa), sodium deoxycholate (DCNa) or sodium cholate (CNa) prepared by co-grinding were investigated by X-ray diffraction analysis, DSC and dissolution kinetics. All X-ray diffraction peak intensities of the co-ground PHT-bile salt [1 mol: 1 mol] mixtures were decreased by grinding for 3 h, and showed a halo pattern of a noncrystalline solid. The solubility of ground products with DCNa, DHCNa and CNa were 212, 56, 68 times higher, respectively, than those of physical mixtures.

Bile Acids and Salts↗

Antitumor effects of antiprogesterones on human meningioma cells in vitro and in vivo.

The presence of the progesterone receptor (PR) in meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone drug, mifepristone, is a potent agent that inhibits the growth of cultured meningioma cells and reduces the size of meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of mifepristone and a new potent antiprogesterone agent, onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in meningiomas in vitro and in vivo was also investigated. Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study, mifepristone and onapristone exhibited cytostatic and cytocidal effects against cultured meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative meningiomas showed no response to any dose of mifeprestone and/or onapristone. In the in vivo arm, meningioma cells, embedded in a collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the tumor volume regardless of the presence or absence of PR's. No histological changes in the meningioma cells suggestive of necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that mifepristone and onapristone have an antitumor effect against meningioma cells via the PR's and/or another receptor, such as the glucocorticoid receptor.

Adult↗

PS-990, a novel neuritogenic compound from Acremonium sp.

A novel compound, PS-990, which induces differentiation of neuroblastoma cells, was isolated from the culture broth of a fungus, Acremonium sp. KY12702. PS-990 inhibited brain calcium calmodulin-dependent cyclic nucleotide phosphodiesterase with an IC50 value of 3 micrograms/ml, and markedly induced neurite extension of mouse neuroblastoma, Neuro2A, at concentrations ranging from 10 to 30 micrograms ml.

Acremonium↗

AS-186 compounds, new inhibitors of acyl-CoA: cholesterol acyltransferase from Penicillium asperosporum KY1635.

AS-186a, b, c, d, and g were isolated from the cultured broth of Penicillium asperosporum KY1635 as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT). IC50 values for the effect of AS-186a, b, c, d, and g against ACAT activity of the microsomes from cholesterol-fed rabbit liver were calculated to be 22.9, 8.2, 11.5, 12.4, and 13.9 microM, respectively. Although AS-186a, and b were identical to penicillide and purpactin A, respectively, AS-186c, d, and g were found to be new compounds.

Animals↗

RES-701-1, a novel and selective endothelin type B receptor antagonist produced by Streptomyces sp. RE-701. I. Characterization of producing strain, fermentation, isolation, physico-chemical and biological properties.

RES-701-1, a novel cyclic peptide endothelin antagonist, was isolated from the culture broth of Streptomyces sp. RE-701. RES-701-1 selectively inhibited the ET-1 binding to type B endothelin receptor (ETB receptor) with an IC50 of 10 nM expressed in CHO cells and blocked the ET-1-induced elevation of intracellular free Ca2+ concentration in ETB receptor-expressing COS-7 cells. Characterization of producing strain, fermentation, isolation, structure, physico-chemical and biological properties of RES-701-1 are described.

Amino Acid Sequence↗

RES-701-1, a novel and selective endothelin type B receptor antagonist produced by Streptomyces sp. RE-701. II. Determination of the primary sequence.

The structure of RES-701-1, a novel microbial endothelin type B receptor antagonist, was determined. Protein chemical data and FAB-MS have identified RES-701-1 to be a cyclic polypeptide consisting of 16 common L-amino acids. This compound is so stable against proteolysis that its enzymatic digestion under standard conditions proved to be very difficult. Therefore, the primary sequence of RES-701-1 was determined by the application of advanced protein chemical methods to be Gly1-Asn2-Trp3-His4-Gly5-Thr6-Ala7-Pro8-++ +Asp9-Trp10-Phe11-Phe12-Asn13- Tyr14-Tyr15-Trp16. The compound is cyclized between the beta-carboxyl group of Asp9 and the alpha-amino group of Gly1.

Amino Acid Sequence↗

MS-282a and MS-282b, new inhibitors of calmodulin-activated myosin light chain kinase from Streptomyces tauricus ATCC 27470.

MS-282a and MS-282b were isolated from the culture broth of Streptomyces tauricus ATCC 27470 as inhibitors of smooth muscle myosin light chain kinase (MLCK). MS-282a and MS-282b inhibited the activity of chicken gizzard MLCK with IC50 values of 3.8 microM and 5.2 microM, respectively. Cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase and protein kinase C were not inhibited by 150 microM MS-282a at all. It is likely that MS-282a blocks MLCK activity by antagonizing calmodulin since 1) the compound inhibited calmodulin-dependent but not calmodulin-independent activity of MLCK; 2) the inhibition of MLCK was antagonized by increasing concentrations of calmodulin, and 3) the compound inhibited calmodulin-dependent cyclic nucleotide phosphodiesterase.

Amino Acid Sequence↗

[Effects of interferon treatment in alcoholic liver injury].

The concentration of Hepatitis C Virus (HCV) in the blood is increased by alcohol drinking and decreased by abstinence. These facts suggested that alcohol abuse may enhance the replication of HCV. The effects of alcohol on HCV replication may be related to increased development of chronic hepatitis to liver cirrhosis and hepatocellular carcinoma in HCV marker positive heavy drinker. These results indicated that HCV positive heavy drinkers must keep abstinence and that these patients have to be treated with interferon.

Adult↗

Metallosis due to abnormal abrasion of the femoral head in bipolar hip prosthesis. Implant retrieval and analysis in six cases.

We report on six cases of metallosis which developed in bipolar hip prosthesis due to ceramic screws used for fixation of bone grafts. Two patients experienced severe metallosis due to abnormal abrasion of the femoral head. At the revision surgery, proliferated black synovia was found. Analyses of the retrieved prostheses revealed numerous small particles of alumina ceramic on the inner surface of the bearing insert of UHMWPE. These particles came from the broken ceramic screws, and scraped away the metallic femoral head resulting in severe metallosis. In four patients, the outer head came into direct contact with ceramic screws and mild metallosis was observed at revision surgery.

Adult↗

Characterization of mouse non-receptor tyrosine kinase gene, HYL.

We previously reported a novel human non-receptor tyrosine kinase gene, HYL (hematopoietic consensus tyrosine-lacking kinase) (Sakano et al., 1994), which consists of each of the SH2 (src homology 2), SH3 and tyrosine kinase catalytic domains. HYL has unique structural features shared with CSK (C-terminal Src kinase). Recently it has also been reported that matk (Bennett et al., 1994) and Ctk (Klages et al., 1994) are isolated as novel kinases with structural similarity to CSK. Comparisons of cDNA sequence indicate the HYL, matk and Ctk are the same gene. We further characterized the mouse HYL genomic structure and HYL mRNA expression in mouse brain. The mouse HYL gene is distributed over 5.8 kb and is composed of 12 exons. The exon-intron organization is almost identical with that of human CSK. The mouse HYL gene was assigned to the R-positive C1 band of chromosome 10 by fluorescent in situ hybridization. RNA in situ hybridization demonstrated the broad distribution of HYL mRNA expression in various neuronal cells. Especially, strong signals were detected in Purkinje cells, pyramidal cells in the hippocampus, granule cells in the dentate gyrus, and mitral cells in the olfactory bulb, indicating that mRNA expression of HYL in brain is very similar to that of SRC-family kinases. These findings establish close relationship between the HYL and CSK genes and also suggest that HYL may play an important role in signal transduction through SRC-family kinases in the central nervous system.

Animals↗

Two novel endopeptidases released into the medium during mating of gametes of Chlamydomonas reinhardtii.

During the mating reaction between mt+ and mt- gametes of Chlamydomonas reinhardtii, two novel endopeptidases, each of which was able to digest the B chain of insulin, were released into the culture medium, together with a gamete lytic enzyme (GLE) which is responsible for digestion of the gametic cell walls. Both endopeptidases and GLE were copurified from the mating medium by column chromatography on DEAE-cellulose and concanavalin A. Gel filtration separated the peptidases, which were unable to digest gametic cell walls, into two fractions, endopeptidase-1 and endopeptidase-2. These enzymes were also separated from GLE, which was unable to digest the B chain of insulin. Endopeptidase-1, with a molecular mass of about 200 kDa, cleaved the B chain of insulin at the Ala14-Leu15 peptide bond, and this activity was inhibited by EDTA. Endopeptidase-2, with a molecular mass of about 110 kDa, digested the peptide at the Leu15-Tyr16 peptide bond and was sensitive to iodoacetate and chymostatin. When the cell walls of gametes of either mating-type were digested prior to mating with exogenously added GLE, the two endopeptidases were released into the medium, a result that suggests that they are stored, like GLE, outside the plasmalemma.

Amino Acid Sequence↗