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Biomedical subjects

Y Hata

Publications and source records attributed to Y Hata.

At least 181 records · Page 10Linked to original sources
PubMed1996

Local Recurrence after Conservative Surgery for Breast Cancer.

The advent of limited operative therapy for breast cancer has produced both good cosmetic results and local recurrence. In our department we treated 38 cases with conservation surgery for early stage breast cancers between February 1988 and October 1994, and local recurrence occurred in 2. PATIENT 1. A 56-year-old-woman had a 1 x 0.8 cm tumor in the C region of the left breast. A quadrantectomy with axillary dissection (level 2) was performed as the margin of the nipple side was negative, followed by entire breast irradiation (50 Gy). Approximately four years after the first operation she developed a local recurrence in the CD region of the breast. A salvage mastectomy with subclavicular lymph node dissection was performed. After the second operation she appears to be healthy. PATINENT 2. A 54-year-old-woman noticed a 1 cm tumor located in the EAC region of the left breast. Excisional biopsy showed solid-tubular carcinoma. The distance between the nipple and the tumor was only 0.7 cm. A wide excision with axillary dissection (level 2) was performed as the margin of the nipple side was negative on the frozen section. Neither irradiation of the entire breast nor the adjuvant chemotherapy could be performed. After a three and a half year follow up local recurrence beneath the operative scar was recognized, and an additional wide excision was performed. A half year has passed since the second operation, there have been no signs of recurrence and she appears to be healthy. In conclusion, we experienced two local recurrences in 38 cases of breast conservation surgery for early breast cancers. One patient had multicentric cancers with histologically different types: mucinous and noninvasive ductal carcinoma, and another had a very short distance between the nipple and the tumor and did not undergo chemotherapy or radiotherapy.

Journal Article↗
PubMed1996

CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins.

Neurexins are neuronal cell surface proteins with hundreds of isoforms. In yeast two-hybrid screens for intracellular molecules interacting with different neurexins, we identified a single interacting protein called CASK. CASK is composed of an N-terminal Ca2+, calmodulin-dependent protein kinase sequence and a C-terminal region that is similar to the intercellular junction proteins dlg-A, PSD95/SAP90, SAP97, Z01, and Z02 and that contains DHR-, SH3-, and guanylate kinase domains. CASK is enriched in brain in synaptic plasma membranes but is also detectable at low levels in all tissues tested. The cytoplasmic domains of all three neurexins bind CASK in a salt-labile interaction. In neurexin I, this interaction is dependent on the C-terminal three residues. Thus, CASK is a membrane-associated protein that combines domains found in Ca2+ - activated protein kinases and in proteins specific for intercellular junctions, suggesting that it may be a signaling molecule operating at the plasma membrane, possibly in conjunction with neurexins.

Animals↗
PubMed1996

Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin.

Munc-18/n-Sec1/rbSec1 interacts with syntaxin and this interaction inhibits the association of vesicle-associated membrane protein (VAMP)/synaptobrevin and synaptosomal-associated protein of 25 kDa (SNAP-25) with syntaxin. Syntaxin, VAMP, and SNAP-25 serve as soluble N-ethylmaleimide-sensitive fusion protein attachment protein (SNAP) receptors essential for docking and/or fusion of synaptic vesicles with the presynaptic plasma membrane. Genetic analyses in yeast, Caenorhabditis elegans, and Drosophila suggest that Munc-18 is essential for vesicle transport. On the other hand, protein kinase C (PKC) stimulates Ca2+-dependent exocytosis in various types of secretory cells. However, the modes of action of Munc-18 and PKC in vesicle transport have not been clarified. Here, we show that recombinant Munc-18 is phosphorylated by conventional PKC in a Ca2+- and phospholipid-dependent manner in a cell-free system. About 1 mol of phosphate is maximally incorporated into 1 mol of Munc-18. The major phosphorylation sites are Ser306 and Ser313. The Munc-18 complexed with syntaxin is not phosphorylated. The PKC-catalyzed phosphorylation of Munc-18 inhibits its interaction with syntaxin. These results suggest that the PKC-catalyzed phosphorylation of Munc-18 plays an important role in regulating the interaction of Munc-18 with syntaxin and thereby the docking and/or the fusion of synaptic vesicles with the presynaptic plasma membrane.

Amino Acid Sequence↗
PubMed1996

Constitutive expression of hepatocyte growth factor may maintain the sheet construction of gastric epithelial cells through facilitating actin-myosin contractile system.

Previously, we have demonstrated that hepatocyte growth factor (HGF) plays an important role in the repair process of gastric ulcer, showing that HGF expression is specifically increased at gastric ulcer edge. In the present study, we demonstrated the constitutive expression of HGF mRNA in normal mucosa, which is as much as 0.1-1.0 attomole/micrograms total RNA. In order to evaluate the hypothesis that HGF might have some role in maintenance of gastric mucosa or prevention of injury initiation, we developed an in vitro model using rabbit gastric epithelial cell in primary culture. 1% ethanol destroys the cell to cell contact to disrupt the monolayer sheet of the cells without causing any damage to cell viability, indicating that irritants may initiate the mucosal injury. HGF remarkably prevented the disruption induced by the ethanol without eliciting proliferation or migration. This action of HGF was suppressed by actin selective inhibitor, cytochalasin B, indicating that it was mediated by an actin-myosin contractile system. In conclusion, constitutively expressed HGF may prevent the initiation of gastric epithelial disruption, which is dependent on some sort if mobile action of the cells.

Actins↗
PubMed1996

Distinct Ca(2+)-dependent properties of the first and second C2-domains of synaptotagmin I.

Synaptotagmin 1 (SytI) is a synaptic vesicle protein that binds Ca2+ and is essential for fast, Ca(2+)-dependent neurotransmitter release in the hippocampus, suggesting that it serves as a Ca2+ sensor for exocytosis. Although SytI has two cytoplasmic C2-domains, only the first C2-domain was shown to exhibit Ca2+ regulation; it binds phospholipids and syntaxin in a Ca(2+)-dependent manner. By contrast, the second C2-domain is inactive in these assays and only binds putative interacting molecules in a Ca(2+)-independent manner. We have now discovered in a yeast two-hybrid screen for SytI-interacting molecules that the C2-domains of SytI interact with themselves. Using immobilized recombinant C2-domains from SytI and SytII, we found that only the second but not the first C2-domains of these synaptotagmins are capable of affinity-purifying native rat brain SytI and that this binding is Ca(2+)-dependent, suggesting that only the second C2-domain is capable of a Ca(2+)-triggered self-association. A relatively high Ca2+ concentration (> 100 microM) is required for binding in the presence of Mg2+; Sr2+ and Ba2+ but not Mg2+ can substitute for Ca2+. Our data suggest that the second C2-domain of SytI is also a Ca(2+)-regulated domain similar to the first C2-domain but with distinct binding activities.

Animals↗
PubMed1996

Crystallization and preliminary x-ray crystallographic studies of L-2-haloacid dehalogenase from Pseudomonas sp. YL.

The dimeric L-2-haloacid dehalogenase from Pseudomonas sp. YL, (subunit mass, 26179 Da), has been crystallized by vapor diffusion, supplemented by repetitive seeding, against a 50 mM potassium dihydrogenphosphate solution (pH 4.5) containing 15% (w/v) polyethylene glycol 8,000 and 1% (v/v) n-propanol. The crystals belong to the monoclinic space group C2 with unit cell dimensions of a = 92.21 angstrom, b = 62.78 angstrom, c = 50.84 angstrom, and beta = 122.4 degrees, and contain two dehalogenase dimers in the unit cell. They are of good quality and diffract up to 1.5 angstrom resolution.

Crystallography, X-Ray↗
PubMed1996

An in vitro invasion model for human renal cell carcinoma cell lines mimicking their metastatic abilities.

We developed a modified in vitro invasion assay system using monolayers of vascular endothelial cells. A type I collagen gel was formed in plastic dishes, and overlaid with type IV collagen. Calf pulmonary arterial endothelial (CPAE) cells were seeded onto these plates, and incubated until they reached confluence. Five human renal cell carcinoma cell lines with various metastatic potentials in vivo were then seeded on the monolayer CPAE cells, and their colony formation and invasion activities were examined for 9 days. At day 4, the highly metastatic cell lines increased the number of colony foci on monolayer CPAE cells several fold higher than their poorly metastatic counterpart. The horizontal spreading patterns were also different between poorly and highly metastatic cell lines. On day 9, the number of carcinoma foci that penetrated the monolayer of CPAE cells and type IV collagen sheets into type I collagen gels in highly metastatic cell lines greatly increased as compared with that of poorly metastatic cell lines. Our in vitro invasion assay using monolayer CPAE cells would be useful to evaluate protease activities and colony formation during invasion.

Animals↗
PubMed1996

Logistic character of myocardial twitch force curve: simulation.

We found that the isovolumic pressure-time curve of the canine left ventricle closely fitted the difference of two logistic function curves and that the isovolumic relaxation-pressure curve segment was more reliably characterized by a logistic time constant than by the conventional exponential time constant. We therefore hypothesized that the calcium (Ca) transient and the Ca-troponin (Tn) binding and crossbridge (CB) kinetics underlay the logistic character of the ventricular isovolumic pressure curve. We tested this hypothesis with a computer simulation of a simple Ca and CB kinetics model of myocardial isometric twitch force development. We assumed the instantaneous number of attached CBs that was theoretically given as the difference between the cumulative CB attachment and detachment curves. We radically changed the Ca transient, Ca-Tn binding, and CB kinetic parameters. We always found that both the cumulative CB attachment and detachment curves closely fitted logistic functions. The difference curve of these two best-fit logistic functions closely fitted the theoretical F curve with certain combinations of the Ca transient, the Ca-Tn binding, and the CB kinetic parameters. These results seem to support our hypothesis.

Animals↗
PubMed1996

Lateral suprasylvian visual cortex is activated earlier than or synchronously with primary visual cortex in the cat.

To explore functional connectivity between area 17 and posteromedial lateral suprasylvian (PMLS) area of the cat cerebral cortex, we carried out cross-correlation analysis of spike trains of neurons recorded simultaneously from both areas of anesthetized, paralyzed cat. Most of correlated pairs had peaks which indicate that PMLS cells were activated earlier than or simultaneously with their partners in area 17, suggesting that 'backward' as well as synchronous activation operates between these cortical areas.

Animals↗
PubMed1996

Reduction of progressive burn injury by a stable prostaglandin I2 analogue, beraprost sodium (Procylin): an experimental study in rats.

Beraprost sodium is a chemically stable prostaglandin I2 analogue with antiplatelet and vasodilator actions. Burn injury causes thrombosis and vessel occlusion by increasing the blood viscosity and by thermal damage to the vascular network in the dermis. A vascular response also occurs in the uninjured dermis surrounding the site of injury. Diminished blood flow and spreading tissue oedema lead to progressive ischaemia and necrosis around the burn site (zone of stasis), with the final necrotic tissue area being larger than the initial one. If blood flow could be restored in the zone of stasis, secondary tissue damage would be minimized. In this study, we examined the effects of a prostaglandin I2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn injury in rats. Twenty male Sprague-Dawley rats weighing an average of 450 g were burned with a comb-shaped brass probe that produced a row of three burns measuring 10 x 30 mm each and two intervening unburned areas measuring 5 x 30 mm each. The rats were divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Skin blood flow was measured with a laser Doppler flowmeter, and the development of oedema as well as the area of necrotic tissue were also determined. The extent of skin necrosis and oedema were significantly reduced in the beraprost sodium-treated rats, and blood flow in the zone of stasis was increased. These findings demonstrate that prostaglandin I2 plays an important role in burn injury and that beraprost sodium can reduce secondary necrosis in the zone of stasis.

Animals↗
PubMed1996

Histologic findings and prognosis of uveal malignant melanoma in japanese patients.

PURPOSE: To determine factors of uveal malignant melanoma that would help to predict prognosis in Japanese patients. METHODS: From 1969 to 1994, 23 eyes with uveal malignant melanoma were enucleated from 23 Japanese patients, and 16 of these patients were studied. In the 16 patients, enucleated eyes were evaluated for tumor characteristics, including cell type and microvascular architecture. Patient records were reviewed for follow-up therapy and outcome. Mortality rate was evaluated four years after enucleation. RESULTS: In Japanese patients with uveal malignant melanoma, the average tumor size was larger (average largest diameter, 11.36 mm; average increase, 6.25 mm) and the average patient age was younger (55.2 years old) than previously reported for white populations. Patients with spindle cell type melanoma tended to have a better prognosis than those with epithelioid cell type (four-year mortality rates: spindle cell type, 0%; mixed cell type, 43%; epithelioid cell type, 66%). Microvascular architecture patterns interpreted as either network or closed loop patterns were associated with a poorer prognosis (network pattern, P = .03; closed loop pattern, P = .005). CONCLUSIONS: The prognosis for Japanese patients with uveal malignant melanoma is poorer, and epithelioid cell-type melanoma is more common, than has been reported in white populations. Mitotic figures are well correlated with poor prognosis, as are two microvascular patterns, the network pattern and the closed loop pattern.

Adult↗
PubMed1996

The effect of Beraprost sodium on the survival of subcutaneous transferred jejunum after vascular pedicle interruption in a rat model.

Beraprost sodium, a stable PGI2 analog, having antiplatelet aggregation and vasodilating actions, was tested in a rat subcutaneous heterotopic jejunal model for its ability to improve survival after vascular pedicle interruption. Forth Sprague-Dawley rats were divided into four groups: Group 1 (control, ligation of pedicle on postoperative day 5); Group 2 (Beraprost sodium, ligation on day 5); Group 3 (control, ligation on day 7); and Group 4 (Beraprost sodium, ligation on day 7). The resulting viability rates were: Group 1 = 0 percent, Group 2 = 40 percent, Group 3 = 30 percent, Group 4 = 90 percent. These results indicate that the administration of Beraprost sodium facilitates the neovascularization of the transferred intestine and shortens the time required for viability of the transferred tissue, after interruption of the vascular pedicle.

Abdominal Muscles↗
PubMed1996

A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects.

A placebo-controlled study was conducted to test the effect of Calpis (Calpis Food Industry Co, Ltd, Tokyo, Japan) sour milk, i.e., a milk fermented with a starter containing Lactobacillus helveticus and Saccharomyces cerevisiae, on the blood pressure of 30 elderly hypertensive patients, most of whom were taking antihypertensive medication. Subjects were randomly assigned to two groups. One group ingested daily 95 mL of the sour milk for 8 wk, and the other group ingested the same amount of artificially acidified milk as a placebo for 8 wk. In the sour-milk group, systolic blood pressure decreased significantly 4 and 8 wk after ingestion, by 9.4 +/- 3.6 mm Hg (mean+/- SE, P < 0.05) and 14.1 +/- 3.1 mm Hg (P < 0.01), respectively. The diastolic blood pressure also decreased significantly, by 6.9 +/- 2.2 mm Hg (P < 0.01), by 8 wk after ingestion of the sour milk began. No significant changes in blood pressure were observed in the placebo group. The decrease in systolic and diastolic blood pressure in the sour-milk group tended to be greater than in the placebo group. No marked changes were observed in other indexes, including pulse rate, body weight, and blood serum variables in both groups.

Adult↗
PubMed1996

Crystal structure of Serratia protease, a zinc-dependent proteinase from Serratia sp. E-15, containing a beta-sheet coil motif at 2.0 A resolution.

The crystal structure of Serratia protease from Serratia sp. E-15 was solved by the single isomorphous replacement method supplemented with anomalous scattering effects from both the Zn atom in the native crystal and the Sm atom in the derivative crystal, and refined at 2.0 A resolution to a crystallographic R-factor of 0.194. The enzyme consists of N-terminal catalytic and C-terminal beta-sandwich domains, as observed in alkaline protease from Pseudomonas aeruginosa IFO3080. The catalytic domain with a five-stranded antiparallel beta-sheet and five alpha-helices shares a basically common folding topology with those of other zinc metalloendoproteases. The catalytic zinc ion at the bottom of the active site cleft is ligated by His176, His180, His186, Tyr216, and a water molecule in a distorted trigonalbipyramidal manner. The C-terminal domain is a beta-strand-rich domain containing eighteen beta-strands and a short alpha-helix, and has seven Ca2+ ions bound to calcium binding loops. An unusual beta-sheet coil motif is observed in this domain, where the beta-strands and calcium binding loops are alternately incorporated into an elliptical right-handed spiral so as to form a two-layer untwisted beta-sandwich structure. The Ca2+ ions in the C-terminal domain seem to be very important for the folding and stability of the beta-sheet coil structure.

Binding Sites↗
PubMed1996

Effect of beraprost, a stable prostacyclin analogue, on red blood cell deformability impairment in the presence of hypercholesterolemia in rabbits.

We evaluated the effects of orally administered beraprost, a stable prostacyclin analogue, on the rheological behavior of red blood cells (RBC) in the presence of hypercholesterolemia. Rabbits fed a cholesterolrich diet were administered various doses of beraprost or pravastatin. We evaluated rheological behavior of RBC by assessing RBC deformability, using a positive-pressure filtration method. The maximum pressure generated by passing a suspension of RBC through a membrane filter was used as an index of RBC deformability. After animals were fed cholesterol for 16 weeks, the maximum pressure increased significantly from 172 +/- 15 mm Hg at baseline to 261 +/- 18 mm Hg (p < 0.01, n = 24). The reduction in RBC deformability associated with hypercholesterolemia improved dose dependently during 1-h incubation with various doses of beraprost. In ex vivo study, beraprost markedly restored RBC deformability 3 h after its oral administration to 218 +/- 17 mm Hg (n = 9) at a low dose and to 215 +/- 20 mm Hg (n = 9) at a high dose. The effect persisted for at least 2 h. Pravastatin failed to reduce the increased maximum pressure. Findings suggest that beraprost treatment may improve the microcirculation by restoring RBC deformability in the presence of hypercholesterolemia.

Animals↗
PubMed1996

Treatment of nevus Ota: combined skin abrasion and carbon dioxide snow method.

Thirty-seven patients with nevus Ota were treated by skin abrasion-carbon dioxide snow therapy. Data obtained from 24 patients (including 5 infants) who completed treatment were analyzed to determine the number of treatment courses and to assess the outcome by color and histologic type. The 5 infants completing treatment received a mean of 10 courses of carbon dioxide snow therapy. Excluding these infants, the mean number of treatment courses was 3 for skin abrasion and 16 for carbon dioxide snow therapy. The therapeutic outcome was satisfactory, being graded as "excellent" in 6 patients, "excellent to good" in 6 patients, "good" in 10 Patients, and "fair" in 2 patients. None of the patients had a "poor" outcome. Darker lesions were generally less responsive to treatment. Lesions with melanocytes in the superficial dermis showed a better response with fewer courses of treatment. Those with melanocytes throughout the whole dermis generally had a poorer outcome. The results confirm that the benefits of this procedure are limited by the associated pain and the need for great skill and a long treatment duration.

Adolescent↗