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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 397 records · Page 22Linked to original sources

Morphologic differences of the vascular buds in the vertebral endplate: scanning electron microscopic study.

STUDY DESIGN: Vascular buds in rabbit vertebral endplates were examined by scanning electron microscopy of corrosion casts. OBJECTIVES: To examine morphologic differences between vascular buds in two regions of the vertebral endplate (inner anular and nucleus pulposar). SUMMARY OF BACKGROUND DATA: Vascular buds are specific structures present at the vertebral endplate that are important as nourishing channels. There is a significant difference in permeability between the lateral portion (inner anular) and the central portion (nucleus pulposar) of the endplate, the latter usually being permeable and the former being impermeable. Morphologic differences between vascular buds in the two regions have not been investigated previously. METHODS: Eight 20-week-old rabbits were used. Vascular buds in rabbit vertebral endplates were examined by scanning electron microscopy of corrosion casts. RESULTS: The vascular buds in the region of the inner anulus form simple loops, but those in the area near the nucleus pulposus exhibit swollen and complex coil-like loops. Although they differ structurally, the average number of vascular buds per area does not vary between the two regions. CONCLUSIONS: We suggest that the morphologic difference between the vascular buds in the two regions (inner anular and nucleus pulposar) plays a principal role in permeability at the endplate.

Animals↗

Molecular cloning and characterization of Byp, a murine receptor-type tyrosine phosphatase similar to human DEP-1.

Novel murine cDNAs encoding a receptor-like protein tyrosine phosphatase, termed Byp (HPTP beta-like tyrosine phosphatase) were cloned. The putative Byp protein consists of 1238 amino acids, which possesses a single catalytic domain in the cytoplasmic region. The extracellular region comprises eight repeats of a fibronectin type III module and contains multiple N-glycosylation sites. The byp mRNA was 7.7-kb long and expressed in every tissue examined, its level being high in the brain and kidney. Transfection of the byp cDNA expression plasmid into COS7 cells resulted in the expression of a 220-kDa tyrosine phosphorylated protein. Furthermore, co-expression of Byp and the Src family kinase Fyn increased the level of tyrosine phosphorylation of Byp, suggesting that Byp was tyrosine-phosphorylated by Fyn. Finally, the byp gene was located to mouse chromosome 2E1-2 and rat chromosome 3q32-33.

3T3 Cells↗

Mechanism of left atrial enlargement related to ventricular diastolic impairment in hypertension.

BACKGROUND AND HYPOTHESIS: Systemic hypertension is the leading cause of left ventricular (LV) hypertrophy. The present study aimed to investigate the mechanism of left atrial (LA) enlargement in patients with hypertensive heart disease during cardiac catheterization. METHODS: Data were obtained from eight control subjects and seven patients with hypertensive heart disease. Left atrial and LV pressures from catheter-tip micromanometer, and LA and LV volumes from biplane cineangiograms were analyzed during the same cardiac cycle. RESULTS: Left atrial maximal volume were 93 +/- 26 ml in patients with hypertensive heart disease and 63 +/- 12 ml in control subjects (p < 0.05). In patients with hypertensive heart disease, time constant of LV relaxation was significantly greater than that in controls (54 +/- 18 vs. 31 +/- 16 ms, respectively; p < 0.01). Left atrial maximal volume correlated with time constant of LV relaxation (r = 0.86, p < 0.01). The ratio of LV filling volume before LA contraction to LV stroke volume in patients with hypertensive heart disease was significantly lower than that in control subjects (65 +/- 13 vs. 76 +/- 7%, respectively; p < 0.05). On the other hand, the ratio of LV filling volume during LA contraction to stroke volume in patients with hypertensive heart disease was significantly higher than that in controls (35 +/- 13 vs. 24 +/- 7%, respectively; p < 0.05). Left atrial volume before LA contraction in patients with hypertensive heart disease was significantly larger than that in controls (74 +/- 22 vs. 47 +/- 10 ml, respectively, p < 0.01). During LA contraction, LA work was significantly increased in patients with hypertensive heart disease compared with that in controls (274 +/- 101 vs. 94 +/- 42 mmHg. ml, respectively; p < 0.001). Left atrial work showed significant correlation with LA volume before LA contraction (r = 0.75, p < 0.01). CONCLUSION: Left ventricular diastolic filling was impaired in patients with hypertensive heart disease. Enlargement of left atrium might be attributed to the impairment of blood flow from left atrium to left ventricle due to the increased LV stiffness.

Adult↗

K252a and staurosporine microbial alkaloid toxins as prototype of neurotropic drugs.

K252 family of alkaloid toxins-kinase inhibitors are the most widely used compounds in biological research on the role of protein kinases in cellular transduction systems, biological functions and pathophysiology of neurological disorders. The wide research interest in these toxins is due to their potency in inhibiting cellular protein kinases. However, lack of kinase specificity is one of their major drawbacks. Synthesis of new K252 derivatives can be expected to open up a new generation of kinase inhibitors. Staurosporine might be considered as a prototype neurotropic drug in view of its ability to induce neurite outgrowth and to increase tau protein levels. Because it mimics some of the neuroprotective effects of NGF and might blocks certain signals required to enhance cellular levels and/or beta amyloid processing, staurosporine might play a beneficial role in the treatment of Alzheimer's disease. The ability of staurosporine to promote neuronal regeneration and brain cholinergic neurons survival has been also demonstrated in animal studies (Nabeshima et al., 1991). The beneficial effects of K252a on the experimental autoimmune encephalomyelitis (EAE) disease mice model and it's ability to supress macrophage activation suggest an important role of protein kinases inhibitors as immunosupressive agents. These results may also point to the potential clinical relevance of K252 microbial toxins as prototypes for the development of new drugs for the management of neuronal diseases.

Animals↗

Cloning and chromosomal mapping of the mouse DNA-dependent protein kinase gene.

Severe combined immune deficiency (scid) mice are assumed to have two types of abnormalities: one is high radiosensitivity and the other is abnormal recombination in immunoglobulin and T-cell receptor genes. The human chromosome 8 q1.1 region has an ability to complement the scid aberrations. Moreover, the localization of the subunit DNA-dependent protein kinase [DNA-PKcs] participating in DNA double-strand break repair in the same locus was clarified. In scid mouse cells, the number of DNA-PKcs products and extent of DNA-PK activity remarkably decrease. These observations gave rise to the assumption that DNA-PKcs is the scid factor itself. In order to determine whether the DNA-PKcs gene is the scid gene, we isolated the mouse DNA-PKcs gene and investigated its chromosomal locus by fluorescence in situ hybridization (FISH). Consequently, it became clear that the mouse DNA-PKcs gene existed in the centromeric region of mouse chromosome 16, determined by cross-genetic study, as a scid locus. This finding strongly suggests that mouse DNA-PKcs is the scid gene.

Amino Acid Sequence↗

Recurrent inhibition in amygdalo-cortical projection neurons of the rat via collaterals of fast-conducting axons.

On stimulation of the medial prefrontal cortex (mPFC) of the rat, the amygdala neurons projecting to the mPFC exhibited an IPSP, which caused IS-SD blockage in the antidromic spikes of these neurons. The IPSP was not preceded by EPSP, but was not monosynaptic in nature. Its onset latencies were mostly confined to within 10 ms, which was shorter than the time for orthodromic conduction from the mPFC to the amygdala. The findings indicated that the IPSP was produced via recurrent collaterals of the amygdalo-cortical projection neurons. In view of the wide range of distribution of the time for antidromic conduction in the amygdalo-cortical projection neurons (3.4-27.2 ms), the projection neurons with a fast-conducting axon were considered to be responsible for the mPFC-evoked recurrent IPSP.

Amygdala↗

MS-271, a novel inhibitor of calmodulin-activated myosin light chain kinase from Streptomyces sp.--I. Isolation, structural determination and biological properties of MS-271.

A novel cyclic peptide, MS-271, was isolated from the culture broth of an actinomycete, Streptomyces sp. M-271 as an inhibitor of smooth muscle myosin light chain kinase (MLCK). MS-271 inhibited the MLCK from chicken gizzard with an IC50 value of 8 microM. MS-271 did not inhibit cyclic AMP-dependent protein kinase, protein kinase C or calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase at concentrations up to 400 microM. The primary structure of MS-271 was identical to that of siamycin I, an anti-HIV peptide isolated from a microbial source.

Adenosine Triphosphate↗

MS-271, a novel inhibitor of calmodulin-activated myosin light chain kinase from Streptomyces sp.--II. Solution structure of MS-271: characteristic features of the "lasso' structure.

MS-271 is a potent inhibitor of smooth muscle myosin light chain kinase (MLCK), obtained from Streptomyces sp. In the previous paper, we reported on the isolation, structural determination and biological properties of MS-271.(1) In this paper, we report on the three-dimensional structure of MS-271 determined by 1H NMR in deuterated dimethyl sulphoxide. MS-271 consists of 21 amino acid residues with a novel internal linkage between the beta-carboxyl group of Asp9 and the alpha-amino group of Cysl, and two disulfide bonds, Cys1-Cys13 and Cys7-Cys19. The internal linkage between the side chain of Asp9 and the alpha-amino group of the N-terminal residue is the same as that of the endothelin B receptor selective antagonist, RES-701-1, that we previously reported. The structural calculations involved the combined use of distance geometry and simulated annealing calculations. The results indicated that MS-271 undergoes extraordinary folding, i.e. the "tail' (Phe10-dTrp21) passes through the "ring' region (Cys1-Asp9) ("lasso' structure). This folding of MS-271 turned out to be the same as the "lasso' structure of RES-701-1. The features of this "lasso' structure are discussed on the basis of comparison between the structures of MS-271 and RES-701-1.

Amino Acid Sequence↗

Mediastinal yolk sac tumor in a young girl: case report and review of the literature.

The authors report a rare case of a female infant who underwent successful treatment of a mediastinal yolk sac tumor. Therapy included four cycles of preoperative PVB (cisplatinum, vinblastine, bleomycin), complete surgical resection of the tumor, and one postoperative cycle of PVB and four cycles of VAC (vincristine, actinomycine, cyclophosphamide) chemotherapy. The successful treatment of this tumor depends on preoperative chemotherapy to reduce the size, followed by complete surgical excision with subsequent postoperative chemotherapy. Recent improvements in the treatment of mediastinal yolk sac tumors are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

C-type natriuretic peptide-mediated coronary vasodilation: role of the coronary nitric oxide and particulate guanylate cyclase systems.

OBJECTIVES: We tested the hypothesis that C-type natriuretic peptide (CNP) mediates coronary vasodilation through activation of cyclic guanosine monophosphate (cGMP) by way of particulate guanylate cyclase. BACKGROUND: CNP has known peripheral vasodilator properties, and preliminary data have suggested that it can function as a coronary vasodilator. METHODS: The actions of CNP were studied in instrumented dogs and in organ chamber rings in the presence and absence of a known antagonist to particulate guanylate cyclase, HS-142-1. Additionally, the actions of HS-142-1 were tested on acetylcholine-mediated coronary vasodilation, and immunohistochemical staining was utilized to localize the presence of CNP in the coronary endothelium. RESULTS: CNP relaxed isolated coronary arteries with (mean +/- SEM 45.9 +/- 7%*) and without (72.0 +/- 7%*) an endothelium (*p < 0.05 for CNP effect alone, p < 0.05 for endothelium vs. no endothelium with CNP). Intracoronary infusions increased coronary blood flow (baseline, 64.6 +/- 5.1 ml/min; CNP-5, 79.9 +/- 6.1*; CNP-20, 103.3 +/- 13.6* [*p < 0.05 vs. baseline value]) and reduced coronary vascular resistance (baseline, 1.6 +/- 0.3 mm Hg/ml per min; CNP-5, 1.4 +/- 0.3*; CNP-20, 1.2 +/- 0.3*). Intracoronary injections increased coronary blood flow (delta baseline coronary flow, 30 +/- 9* ml/min [*p < 0.05]). HS-142-1 significantly attenuated these increases (delta coronary flow, 30 +/- 9* ml/min [CNP] to 14 +/- 6 [CNP + HS-142-1] [p < 0.05 CNP vs. CNP + HS-142-1]) and the relaxation of organ chamber rings (56 +/- 7% [CNP] to 18 +/- 6% [HS-142-1 + CNP]). Finally, CNP was localized to the coronary endothelium and smooth muscle by immunohistochemical staining. CONCLUSIONS: CNP functions as a coronary vasodilator through activation of cGMP by way of particulate guanylate cyclase. CNP-mediated coronary vasodilation is attenuated by intracoronary HS-142-1. Intracoronary HS-142-1 does not affect acetylcholine-mediated coronary vasodilation. These observations support a role for exogenous CNP as a potent coronary vasodilator.

Animals↗

Renal role of the endogenous natriuretic peptide system in acute congestive heart failure.

BACKGROUND: Atrial and brain natriuretic peptides exert renal and cardiovascular actions through binding to the natriuretic peptide-A receptor, while C-type natriuretic peptide mediates actions that occur through binding to the natriuretic peptide-B receptor, with subsequent generation of cyclic guanosine monophosphate. This study determined responses of circulating atrial natriuretic peptides in experimental acute heart failure and addressed the hypothesis that elevated circulating atrial natriuretic peptides serve a homeostatic role in regulating sodium excretion and that this action is localized to the glomerulus and distal nephron, sites rich in natriuretic peptide-A receptors. METHODS AND RESULTS: Studies were performed in the absence and presence of HS-142-1, an inhibitor of the natriuretic peptide receptors. Two groups of anesthetized dogs underwent induction of acute heart failure by rapid ventricular pacing, as characterized by decreases in cardiac output and increases in filling pressures with associated elevation of endogenous atrial natriuretic peptides secondary to increases in atrial stretch. In group 1 (n = 5, vehicle intrarenal bolus), despite acute heart failure-mediated decreases in cardiac output, sodium excretion was preserved with maintenance of the glomerular filtration rate and distal fractional sodium reabsorption. In group 2 (n = 5), in response to the natriuretic peptide receptor antagonist, HS-142-1 (0.5 mg/kg intrarenal bolus), sodium excretion (17.0 +/- 4.4 to 5.9 +/- 3.2 microEq/min; P < .05) and glomerular filtration rate decreased (33.0 +/- 3.6 to 21.0 +/- 3.9 mL/min; P < .05) and distal fractional sodium reabsorption increased (98.0 +/- 0.63 to 99.3 +/- 0.25%; P < .05), in association with a decrease in plasma cyclic guanosine monophosphate (13.0 +/- 3.5 to 6.6 +/- 2.9 pmol/mL; P < .05) and renal cyclic guanosine monophosphate generation (1,216 +/- 421 to 466 +/- 208 pmol/min; P < .05). CONCLUSIONS: This study supports a functionally significant role for the endogenous natriuretic peptide system in preserving sodium homeostasis and glomerular filtration rate in acute heart failure.

Acute Disease↗

Comparative evaluation of mean particle size of bulk drug powder in pharmaceutical preparations by Fourier-transformed powder diffuse reflectance infrared spectroscopy and dissolution kinetics.

This paper reports a quantitative correlation between specific FT-IR absorption peak intensity of phenytoin (PTH) to its particle size in the bulk as well as in powder blends. Absorption peak intensity in FT-IR spectra of phenytoin (PHT) increased with decrease of mean particle size of the powders. The relationships between the FT-IR absorbance at 1724 cm-1 of PHT and the specific surface area (Sw) obtained by the BET N2 gas absorption method or the reciprocal of mean particle size (D50) obtained by particle counting of SEM photomicrographs of ground samples showed straight lines, indicating that the absorbance followed the equation log (lo/l) = K1/D50 = K2Sw, where lo and l are intensities of the incident and transmitted light, respectively, and K1 and K2 are constants. In binary mixture of powders containing 50% PHT and 50% lactose, the relationship between the absorbance at 1724 cm-1 of PHT powder and Sw of the reciprocal of D50 also gave a linear plot. The dissolution behaviors of the binary mixture samples were measured in pH 1.2 buffer containing 0.1% sodium lauryl sulfate at 37 degrees C. The data from initial rates of dissolution of the binary mixture was utilized to calculate the particle size (Dg) using the Hixon-Crowell equation, and these particle size values were consistent with those obtained from Sw data as well as the absorbance data by the IR spectral method.

Chemical Phenomena↗