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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 487 records · Page 27Linked to original sources

Effect of cogrinding with various kinds of surfactants on the dissolution behavior of phenytoin.

The physicochemical properties of phenytoin (PHT) combined with various kinds of surfactants at 40 w/w % such as sodium lauryl sulfate (SLS), sodium deoxycholate (DCNa), and the sucrose ester of stearic acid (SE) by a cogrinding method were investigated by X-ray diffraction analysis, Fourier transformed infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and dissolution kinetics in 2nd fluid (Japanese Pharmacopoeia XII, pH 6.8, 37 degrees C). All X-ray diffraction peak intensities of the coground mixtures were decreased by grinding, and the product with DCNa grinding for 3 h transformed into a noncrystalline solid, but the products with SE and SLS were not. The solubilities of ground products with SLS and SE were almost the same as those of respective physical mixtures. However, the apparent solubility of ground products with DCNa was 28.7 times higher than that of the physical mixture.

Calorimetry, Differential Scanning↗

Chronic cholecystitis following hemobilia due to traumatic intrahepatic injury.

We report a patient who presented with colicky abdominal pain, hematemesis, and melena following a blunt abdominal injury sustained in an automobile accident. Serologic tests suggested liver dysfunction and computed tomography (CT) revealed dilatation of the intrahepatic bile duct. Duodenoscopy demonstrated hemobilia originating from the duodenal papilla of Vater. Angiography revealed a pseudoaneurysm of the hepatic artery and angiographic embolization sucessfully stopped the hemorrhaging. However, even following the angiographic embolization, the patient remained symptomatic and repeat CT demonstrated thickening of the gallbladder wall and a lesion resembling a blood clot. We strongly suspected cholecystitis and performed a laparoscopic cholecystectomy. Grossly, the resected specimen revealed wall thickening with a congested mucosa and three blood clots; histologically, these changes were consistent with a diagnosis of chronic cholecystitis. The clinical message of this paper is that patients should be observed for this usual complication of hemobilia after liver injury.

Adolescent↗

A genomic clone containing a telomere array maps near the centromere of mouse chromosome 6.

A lambda clone of mouse DNA containing a short array of telomere hexamers has been localized by FISH to a region close to the centromere of Chromosome (Chr) 6. Amplification of DNA with primers flanking an SSR showed that most inbred strains carry one of two alleles, although five other alleles were found among the inbred strains and 11 other alleles were found in wild-derived mice. Analysis of the DNA from four Robertsonian translocations suggests that the amplified sequence is still present in these chromosomes. The finding of two fragments associated with the Sig mutant suggests that the clone lies within a congenic region created when the mutant, obtained in a (C3H x 101)F1, was backcrossed to C57BL/6J. This region might include all or part of the centromere. Comparison of the segregation of the amplification product with the segregation of centromeric heterochromatin in an interspecies backcross, (C57BL/6 x M. spretus)F1 x M. spretus, (BSS) shows 1/72 recombinants with the centromeric heterochromatin, while 1/62 recombinants occurred in a BSB backcross. Analysis of other loci at the proximal end of Chr 6 gives the combined map Hc6-0.73-D6Mit86-0.73-D6Rp2-2.2-D6Mitl-2.2-Wn t2-3.0-Cpa. Data from a third cross show that Cola2 lies between D6Mit82 and D6Rp2. The portion of the telomere array, Tel-rs3, that has been sequenced contains only 13/31 repeats of the consensus sequence. A variety of sequence changes from the consensus hexamer suggests that this array has been removed for a long time from evolutionary pressures to retain the TTAGGG sequence.

Animals↗

A huge immature cervical teratoma in a newborn: report of a case.

A neonate with a large cervical mass was transferred to our hospital at 4 days of age. A computed tomography scan showed a contrast-enhanced solid mass with multiple cystic elements and fine calcification. Ultrasonography also revealed a predominantly solid mass with calcification, containing multiple cysts. These studies suggested a teratoma, but could not rule out a hemangioma. The tumor was removed on the 12th day of life. A pathological study revealed an immature teratoma that demonstrated fetal type cartilage and an immature neural tube. The operative complete removal of a cervical teratoma in neonates is recommended as soon as possible. The management of a pediatric cervical teratoma should also be similar to that of a sacrococcygeal teratoma. The incidence of cervical teratoma in all pediatric teratomas ranges from 2.3%-9.3% in the West, and from 1.6%-8.3% in Japan.

Cartilage↗

Abnormal integrity of the nucleolus associated with cell cycle arrest owing to the temperature-sensitive ubiquitin-activating enzyme E1.

A mouse cell mutant, ts85, containing the temperature-sensitive ubiquitin-activating enzyme was arrested in G2 phase at the non-permissive temperature. In the arrested cells, azure C, a nucleolus-specific stain, revealed a U-shaped or ring-shaped arrangement of nucleolar lobes with an unstained region in the center. Silver staining of the nucleolar organizer region (NOR) and fluorescence in situ hybridization (FISH) with rDNA both gave signals in azure C-positive regions. Electron microscopic examination revealed a cloud of unidentified electron-dense particles (diameter approximately 70 nm) in the azure C-negative center space. When the arrested cells were released into M-phase, we observed the association of NOR-bearing chromosomes with a pulverization-like abnormality. FISH with rDNA and NOR silver staining demonstrated that the pulverization-like abnormality was restricted to NORs. The frequent occurrence of persistent nucleolar material in prophase and prometaphase of the stressed cells after release indicated a delayed dissociation of the nucleolus that brought about the abnormal chromosomes in M-phase. ts85 cells transfected with the mouse E1 cDNA recovered growth at the non-permissive temperature and no longer showed abnormal nucleolar morphology. It seems that the ubiquitin system plays a role in the dissolution of the nucleolus, possibly involving the NOR-bearing chromosomes.

Animals↗

Increased plasma alpha (1 --> 3)-L-fucosyltransferase activities in patients with hepatocellular carcinoma.

Alpha (1 --> 3)-L-fucosyltransferase (alpha 1,3FT) activity was determined in plasma of patients with chronic liver diseases, namely, chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), The plasma alpha 1,3FT activity was significantly higher (p < 0.01) in chronic liver diseases than that in normal controls. The enzyme activity in plasma of patients with HCC was also significantly higher than that in LC (p < 0.05) or that in CH (p < 0.01). However, no significant difference was observed in the enzyme activity between LC and CH. Plasma alpha 1,3FT activity in patients with HCC was not significantly changed before and after transcatheter arterial embolization. In addition, the enzyme activity in the homogenate of the cirrhotic liver tissue was higher than that in the preparation of the hepatoma tissue in the same patient. These results suggest that the increased plasma alpha 1,3FT activity in patients with HCC reflects mainly the enzyme activity of cirrhotic liver tissue, not that of hepatoma tissue. The significance of the elevated levels of plasma alpha 1,3FT and its decreased hepatoma tissue activity in patients with HCC, compared with that in LC, remains to be clarified.

Aged↗

Cryopreservation of wild mouse spermatozoa.

Spermatozoa of wild mice from China, Czechoslovakia, Denmark, India, Japan and Switzerland were frozen and stored at -196 degrees C. After thawing, intact oocytes were inseminated in vitro with relatively high motility frozen-thawed mouse spermatozoa from Czechoslovakia, Denmark and India, while oocytes with a partially dissected zona were inseminated with low motility frozen-thawed spermatozoa from China, Japan and Switzerland. Embryos developing to the 2-cell stage from oocytes fertilized with frozen-thawed spermatozoa were transferred to the oviducts of female recipients on the first day of pseudopregnancy (day when a vaginal plug was confirmed). Successful embryo development to the 2-cell stage was 46 to 67%. Offspring resulted from 17 to 51% of these transferred 2-cell embryos.

Journal Article↗

Responses of the medial prefrontal cortex to stimulation of the amygdala in the rat: a study with laminar field potential recording.

Responses generated in the prelimbic-infralimbic cortices (areas 32 and 25) by stimulation of the basolateral amygdala were studied by means of laminar field potential recordings. Based on the analysis of wave forms and depth potential profiles of the responses, three constituent responses were identified: (1) a surface-positive potential with a short onset latency (mean, 4.5 ms) and a long duration (ca. 70 ms) that reversed the polarity at a depth of 400 microns; (2) a surface-positive potential with a mean onset latency of 15 ms and a duration of 20 ms that reversed to a negative potential at a depth of 300 microns; and (3) a long-latency (ca. 20 ms) superficial-negative potential that reversed to a positive potential at depths below 400 microns. Lesion experiments ruled out the possibility that impulse traffic via the thalamic mediodorsal nucleus (MD) contributed to the responses. Amygdala stimulation also produced responses in the insular cortex, but they did not contaminate the responses in the mesial cortex. It is proposed that impulses originating from the amygdala provide excitation for cortical pyramidal cells at a short latency at deeper layers, but with considerable delays at upper and superficial layers, in the medial prefrontal cortex (mPFC).

Amygdala↗

Novel functions of phosphatidylinositol 3-kinase in terminally differentiated cells.

Importance of phosphatidylinositol 3-kinase (PI 3-kinase) in signalling pathways leading to growth stimulation has already been reviewed in this journal and others. Evidence has now been accumulating that PI 3-kinase is involved in transmission of activation signals in terminally differentiated cells, especially signals starting from receptors which have no intrinsic tyrosine kinase domain. The pioneer works showed the presence of PI 3-kinase activity and the accumulation of the reaction products of PI 3-kinase correlated with the cell responses. However, these studies were done in only limited cell responses such as respiratory burst in neutrophils and degranulation in platelets. Recent finding of a potent and selective inhibitor of PI 3-kinase, wortmannin, reported from three independent groups including us, gave a new and powerful tool not only to confirm the suggested functions but also to reveal new functions of PI 3-kinase such as histamine release from antigen-stimulated mast cells/basophils and glucose uptake in insulin-stimulated adipocytes. Nearly one hundred papers which describe the action of wortmannin on various cells have been reported during one year after the publication of the discovery of wortmannin as PI 3-kinase inhibitor, suggesting possible involvement of the enzyme in the diverse cell responses besides cell proliferation.

Androstadienes↗

KT-5720 reverses multidrug resistance in variant S49 mouse lymphoma cells transduced with the human MDR1 cDNA and in human multidrug-resistant carcinoma cells.

T-25-Adh cells, cell variants derived from S49 mouse lymphoma, were transduced with a retrovirus containing the human MDR1 cDNA. The resultant cells (HU-1) are cross-resistant to colchicine, doxorubicin, vinblastine and actinomycin D, and their resistance to colchicine is reversed by verapamil. HU-1 cells were used to screen several protein kinase modulators for their ability to reverse multidrug resistance. Among the tested indole carbazole (K-252a) family of protein kinase inhibitors, only the antibiotic alkaloid KT-5720 (9-n-hexyl derivative of K-252a) could overcome the multidrug resistance of HU-1 cells and KB-V1 human carcinoma cells. Since other protein kinase A, C and G modulators did not reverse multidrug resistance in the tested multidrug-resistant cells, the chemosensitising activity of KT-5720 on these cells is apparently independent of its kinase inhibitory effects. Since KT-5720 fully reversed multidrug resistance at non-toxic concentrations, it might be a candidate for clinical chemosensitisation in combination chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Growth-blocking peptide titer during larval development of parasitized and cold-stressed armyworm.

Growth-blocking peptide (GBP) has been isolated for the first time from the haemolymph of the host armyworm Pseudaletia separata whose development was halted in the last larval instar stage by parasitization with the parasitoid wasp Cotesia kariyai. Recent studies demonstrated that GBP not only exists in the plasma (haemolymph without cells) of parasitized last instar larvae, but also in the plasma of nonparasitized penultimate (5th) instar larvae. Monoclonal antibodies were prepared to measure the titers of GBP in nonparasitized and parasitized larval plasma. One of three monoclonal antibodies raised against GBP, which is the most specific for GBP, was used to quantify the concentration of plasma GBP. As this antibody recognized two plasma peptides other than GBP in crude plasma fractions, each plasma peptide fraction was separated by a reversed phase HPLC, and then plasma GBP level was measured by ELISA. The highest level of plasma GBP detected on Day 0 of the penultimate instar larvae was gradually decreased throughout the larval growth except for the temporary increase on Day 0 of last larval instar. After parasitization on Day 0 of last larval instar, two peaks of plasma GBP titer were detected during the last larval instar, one day and six days after parasitization. This characteristic increase and decrease in plasma GBP level was also observed by transferring last instar larvae of the armyworm from 25 to 10 degrees C, as a result of which larvae delayed pupation by more than 15 days. From these results, it is reasonable to propose that plasma GBP in lepidopteran larvae might control certain upstream steps in a cascade of events leading to pupation; thus, an elevated level of plasma GBP interferes with normal metamorphosis from larvae to pupae.

Amino Acid Sequence↗

Solution structure of endothelin B receptor selective antagonist RES-701-1 determined by 1H NMR spectroscopy.

The three-dimensional structure of the endothelin B receptor (ETB) selective antagonist RES-701-1 has been determined by 1H NMR in deuterated dimethyl sulphoxide. RES-701-1 consists of 16 amino acid residues with a novel internal linkage between the beta-carboxyl group of Asp9 and the alpha-amino group of Gly1. The structural calculations were carried out with the combined use of distance geometry and simulated annealing. The result indicates that RES-701-1 adopts an extraordinary folding; the 'tail' (Trp10-Trp16) passes through the 'ring' region (Gly1-Asp9). Several critical NOEs directly support this extraordinary folding. The folding of RES-701-1 turned out to be the same as that Frèchet et al. calculated for RP 71955 which possesses the same internal linkage as RES-701-1. The obtained structure suggested that the region consisting of Thr6, Ala7, Tyr14 and Tyr15 and/or, the region consisting of Asn2, Tyr14 and Tyr15 are involved in a binding with ETB.

Amino Acid Sequence↗

Radiosensitivity and effects of repair inhibitors for X-ray-induced chromosomal damage in mouse zygotes in S and G2 phases.

The potentiation effects of arabinofuranosyl cytosine (ara-C), hydroxyurea, 3-aminobenzamide, and caffeine on the yield of chromosome aberrations were examined at the first-cleavage metaphase in mouse zygotes irradiated with X-rays in S and G2 phases (7.5 and 12 h after insemination respectively) in vitro. Potentiation effects were found in both S and G2 for all chemicals except ara-C. Caffeine completely released G2 arrest, which was not overcome by any other chemicals, and enhanced chromosome aberrations most effectively. Caffeine enhanced chromosome aberrations more in G2 irradiation than in S irradiation, and the frequency of chromatid-type aberrations was remarkably enhanced in G2 irradiation. The results in this study demonstrated an existence of two types of caffeine effects in the mouse zygotes irradiated in S and G2; a cancellation of G2 arrest and direct inhibition of DNA repair pathways. The chromosomal damage induced in G2 was effectively repaired by a repair pathway, which is affected by caffeine, on the other hand, the progression of cell cycle, not repair inhibition, was a major factor of caffeine effect on the yield of chromosome aberrations in S irradiation.

Animals↗

Hepatocyte growth factor suppresses the onset of liver cirrhosis and abrogates lethal hepatic dysfunction in rats.

Heptic fibrosis/cirrhosis is a common hepatic disease characterized by the hyper-accumulation of connective tissue components, and hepatic necrosis. Chronic alcohol ingestion, viral infection, and metabolic disorders are contributing factors and there has been no effective treatment. Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is a long-sought hepatotrophic factor for liver regeneration. Administration of human recombinant HGF into rats with hepatic fibrosis/cirrhosis caused by dimethylnitrosamine (DMN) elicited mitogenic action for hepatocytes, stimulated hepatic collagenase activity, and prevented the onset and progression of hepatic fibrosis/cirrhosis. Accumulation of fibrous tissue components in the liver due to DMN-treatment were markedly decreased in HGF-injected rats. Moreover, HGF completely abrogated death caused by severe hepatic cirrhosis and dysfunction. We postulate that HGF may prove to be an effective treatment for human liver fibrosis/cirrhosis and for chronic hepatic failure.

Animals↗

Interferon-gamma (IFN-gamma) production by human T lymphocytes upon Legionella pneumophila stimulation in vitro.

In vitro immune responses to Legionella pneumophila were investigated. When human peripheral blood lymphocytes (PBL) from healthy volunteers were stimulated with formalin-killed L. pneumophila for 7 days in vitro, strong proliferative responses were observed. The responding cells were shown to be a CD4 T cell subset. It was also found that the CD4 T cells secreted significant amounts of IFN-gamma into the PBL culture supernatant. The production of IFN-gamma and IL-4 by PBL was measured semiquantitatively by reverse transcriptase-assisted polymerase chain reaction (RT-PCR) methods. Formalin-killed or live L. pneumophila-stimulated PBL expressed the mRNA for IFN-gamma but not the mRNA for IL-4. The results suggest that the whole bacterium, as opposed to the supernatant, predominantly stimulates Th1 type helper T cells. The cloned T cells specific for L. pneumophila expressed the mRNA for IFN-gamma but not for IL-4. In contrast to formalin-killed or live L. pneumophila stimulation, when PBL were stimulated with the bacterial culture supernatant, the proliferating T cells produced the mRNA for IL-4 as well as for IFN-gamma. A significant correlation between the proliferative response to formalin-killed L. pneumophila and IFN-gamma release in culture was observed (r = 0.6932, P < 0.001) in PBL from 30 healthy volunteers. From these in vitro studies, it is suggested that the whole L. pneumophila bacterium and their soluble antigens stimulate T cells in a manner which results in a different pattern of cytokine production.

Base Sequence↗

An effective LDL removal filter for the treatment of hyperlipidemia.

On-line membrane plasma fractionation techniques have made semiselective removal of pathological macromolecules practical. However, several problems such as cryogel formation exist when the procedure is performed at ambient temperature. Cryogel formation takes place when heparinized plasma is cooled below 35 degrees C and when it tends to occlude the pore structure of the secondary filter membrane resulting in a poor molecular cut off of the macromolecular filter. Thermofiltration is one of the on-line plasma fractionation techniques used when warming plasma from 37 to 42 degrees C to prevent cryogel formation. Thermofiltration enhanced the performance of the lipofilter (Kuraray 4A) and demonstrated better molecular cut off between low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol than double filtration plasmapheresis (DFPP). An improved lipofilter (Kuraray 5A) has been developed and has shown better molecular cut off between LDL cholesterol and HDL cholesterol than the 4A filter. However, cryogel formation still occurred even using the 5A filter during the DFPP procedure. Thermofiltration maintains the performance of the secondary filter by preventing cryogel formation. Further studies are required to evaluate the enhanced performance of the 5A filter by thermofiltration.

Filtration↗

A thermoconductive and thermoselective leukocyte filter.

Previously, it was reported by our group that the superphysiological temperature of over 43 degrees C affected leukocyte properties. It was speculated that heat treatment might alter the immunological properties of leukocytes. In order to take advantages of this phenomenon, attempts were made to develop a thermoconductive and thermoselective leukocyte filter. A stainless steel fiber was selected for the new material of a leukocyte filter due to its good heat conductance, stability during thermal change, and inertness to any chemicals. Preliminary studies were conducted to evaluate the effect of fiber diameter and temperature on the filtration of blood cells. As a result, more than 99% of white blood cells (WBCs) and platelets were removed utilizing a 4 microns diameter fiber filter. The environmental temperatures of the filtration process were varied to 4, 20, 36, and 50 degrees C for 5 min. Almost 95% of WBCs and platelets were removed at 4, 20, and 36 degrees C. However, the reduction of platelets was remarkably suppressed at 50 degrees C (54%). Additionally, the removal of lymphocytes was significantly lower than that of neutrophils at 50 degrees C (69% vs. 83%; p = 0.0002). These data demonstrate that effective heat treatment and removal of leukocytes are possible with an ultrafine stainless steel fiber filter.

Equipment Design↗