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Biomedical subjects

M Shiraishi

Publications and source records attributed to M Shiraishi.

At least 19 recordsLinked to original sources

Large optical nonlinearity of semiconducting single-walled carbon nanotubes under resonant excitations.

We measured third-order nonlinear susceptibility (chi(3)) spectra in semiconducting single-walled carbon nanotubes (SWNTs) by the Z-scan method. |Imchi(3)| is remarkably enhanced under resonant excitation to the lowest interband transition, reaching 4.2 x 10(-6) esu and 1.5 x 10(-7) esu in SWNTs grown by the laser ablation and HiPco methods, respectively. A comparison of the transient absorption changes evaluated by degenerate and nondegenerate pump-probe measurements suggests that the resonant enhancement of |Imchi(3)| is dominated by a coherent process rather than by saturation of absorption.

Journal Article↗

Usefulness of switching to cabergoline from other dopamine agonists in patients with advanced Parkinson's disease.

Problems associated with long-term treatment of advanced Parkinson's disease (PD) include motor complications and psychotic and autonomic symptoms. We switched patients from bromocriptine (BR) or pergolide (PER) to cabergoline (CB) therapy and investigated CB's usefulness in alleviating such problems. Subjects were 30 patients (mean age 68.2 years; 13 receiving BR, 17 PER) with PD complicated by effects of long-term treatment but in whom their dose of dopamine (DA) agonist was contraindicated due to adverse reactions. Patients were switched to CB over a 2-4-week period. Hoehn-Yahr and Unified Parkinson Disease Rating Scale (UPDRS) I-IV "on" and "off" scores improved in both the BR and PER groups. CB was not discontinued due to adverse reactions in any patient. In conclusion, switching to CB is useful in patients in whom it is problematic to increase their dose of DA agonist due to motor complications or psychotic symptoms of advanced PD.

Aged↗

Periodic structures and diurnal variation in blood pressure and heart rate in relation to microgravity on space station MIR.

Four Russian crew members were studied on space station MIR, and blood pressure (BP) and heart rate (HR) data were continuously collected. BP and HR data were collected on earth 1 day before orbital flight to the space station, then at weeks 8, 16 and 24 during space flight, and again 1 or 2 days after returning to earth. Time serial data for BP and HR were analyzed by spectral analysis with the MemCalc system (Suwa Trust, Sapporo, Japan). Periodic structures of diurnal variation in systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were compared at 24-hour, 12-hour and 8-hour intervals, these being determined as the main periodic components for the assessment of BP and HR variability. The 24-h mean levels of SBP and HR during space flight were unchanged. Waking SBP was not different from pre-flight values. During sleep, in-flight changes in HR did not differ from pre-flight values. SBP during sleep in orbit increased to over pre-flight values. Waking DBP was reduced during flight. The SBP and HR phases over a 24-hour cycle were shortened with a more pronounced shortening in weeks 8 and 16 compared with pre-flight values, and at week 24 recovered to preflight values. The 12, 8-hour-cycle remained unchanged, and were similar to pre-flight values. At the space station, the astronauts' mission was carried out under strict control of sleeping and waking hours; therefore, their 24-hour schedule is an artificially constructed situation. Main periodicity structures were maintained by strict control of lifestyle during long-term space flight. The conclusions reached were as follows: 1) SBP levels during sleep in a space environment increased compared with those on earth; 2) the periodicity phase of BP and HR shifted toward to 24-hour cycle as a result of long-term space flight, even though these periods shortened after a few months compared with pre-space flight values.

Adult↗

Blood pressure variability during 120-day head-down bed rest in humans.

Influence of physical inactivity and microgravity to periodic structure of blood pressure was studied. Six healthy males were kept under head-down bed rest (HDBR) for 120 days. Blood pressure and heart rate (HR) were recorded by a portable sphygmomanometer and a Holter electrocardiogram, respectively. The results were analyzed by spectrum analysis. Phase, amplitude and acrophase of systolic blood pressure (SBP) by approximately 24, 12 and 8 h were measured before, 60, 120 day and after HDBR. The phase at 24, 12 and 8 h did not show significant changes during HDBR, and acrophase showed a tendency to shift to 14:00 after HDBR. Amplitude for 24 h tended to attenuate during bed rest (BR), and significantly increased after BR. The results of this study suggest that the circadian rhythm of SBP and HR were maintained by strict control of sleep, awakening and food intake in microgravity model of a long-term BR state. However, the tendency to decrease 24-h cyclic amplitude of SBP appeared to be the rhythmic modulation related to cardiovascular deconditioning.

Adaptation, Physiological↗

Quantitative changes in yolk protein and other components in the ovary and testis of the sea urchin Pseudocentrotus depressus.

Both male and female sea urchins accumulate the major yolk protein (MYP; the most abundant yolk granule protein in sea urchin eggs) in the nutritive phagocytes of immature gonads before gametogenesis. In this study, quantitative changes in MYP as well as in other biochemical components in the ovary and testis were examined in the course of gametogenesis in Pseudocentrotus depressus. Before gametogenesis, both the ovary and testis contained large quantities of proteins, lipids and polysaccharides. MYP reached about 80% of total protein in both sexes. In the testis, MYP decreased rapidly as spermatogenesis proceeded, and the fully mature testis contained little MYP; the levels of lipids and polysaccharides also decreased. In contrast, the levels of nucleic acids and proteins other than MYP increased markedly. In the ovary, MYP decreased gradually as oogenesis proceeded, and the fully mature ovary contained less than half of the initial amount of MYP. Polysaccharides also decreased, whereas proteins other than MYP increased. These results, taken together with those from other studies, suggest that MYP serves as a protein reserve that accumulates before gametogenesis and is used as material for synthesizing new substances constituting gametes in both male and female sea urchins.

Animals↗

Acquisition of a gastric or duodenal phenotype on heterotropic transplantation of esophagus and bladder tissues in F344 rats.

Cell differentiation is very important but not well understood. In the present study the ability of various tissues to newly-differentiate when transplanted into the fundus or the duodenum in rats was tested. Pieces of esophagus, bladder, diaphragm and trachea from 8-week-old male F344 rats were transplanted into the gastric fundus or duodenum of females and examined after 3 or 6 months. While the diaphragm was not recognizable as a muscle layer in either the stomach or the duodenum, the esophagus and trachea persisted, the latter with the presence of cartilage. Esophagus grafts transplanted into the glandular stomach and duodenum, newly-differentiated into gastric and duodenal mucosa, respectively. Goblet cells with alcian-blue positive mucin appeared in bladder tissue implanted into the duodenum. Six months after the operation, their numbers had increased and cytoplasm alkaline phosphatase (ALP) positivity was noted. Gastrointestinal and also bladder stem cells may thus have multipotential ability for differentiation and may be able to newly-differentiate when transplanted into different environments in the gastrointestinal tract.

Animals↗

Potent and selective inhibition of the human Na+/H+ exchanger isoform NHE1 by a novel aminoguanidine derivative T-162559.

We isolated Na+/H+ exchanger (NHE)-deficient Chinese hamster ovary (CHO-K1) cells stably expressing human NHE isoforms (hNHE1, hNHE2 and hNHE3) and established an assay system for measuring their Na+/H+ exchange activity by monitoring intracellular pH alterations. Using this assay system, we demonstrated that the acylguanidine derivatives, cariporide and eniporide, cause selective inhibition of hNHE1 (IC50 value of 30 nM for cariporide, IC50 value of 4.5 nM for eniporide). Furthermore, we found that a novel synthetic aminoguanidine derivative, T-162559 ((5E,7S)-[7-(5-fluoro-2-methylphenyl)-4-methyl-7,8-dihydro-5(6H)-quinolinylideneamino] guanidine dimethanesulfonate), causes a selective inhibition of hNHE1 with more potent activity than cariporide and eniporide (IC50 value of 0.96 nM). This compound did not affect Na+/HCO3- cotransport and Na+/Ca2+ exchange.

Animals↗

Improved hepatic microcirculation by human soluble urinary thrombomodulin in the xeno-perfused porcine liver.

PURPOSE: Both the protein C/thrombomodulin system and the heparin/anti-thrombin III system are major physiological anticoagulant systems, which may also play a major role in preserving the hepatic microcirculation in xenogeneic liver transplantation. To compensate for the functional incompatibilities of the porcine thrombomodulin (TM)-cofactor activity beyond species for human thrombin, soluble human TM protein was tested in xenogeneic perfusion of the porcine liver. MATERIALS AND METHODS: The livers were harvested from adult female pigs and perfused through the portal vein (PV) and hepatic artery (HA) for 2 hr, with fresh human blood in group 1 (n=5), fresh porcine blood (10 units/ml) in group 2 (n=5), and fresh human blood with TM (50,000 units/1.5 l) in group 3 (n=5). The tissue PO2 level, tissue blood flow, PV and HA pressures were all continuously monitored. Circulating perfusate and liver tissue samples were periodically obtained for blood chemistry and histologic analyses. RESULTS: The activated protein C (aPC) level was significantly elevated in the TM-treated group 3 (47.5%+/-3.5% at preperfusion and 51%+/-2.8% after 120 min of perfusion) in comparison to group 1 (32.3%+/-7.2% and 35.3+/-12.0%). The hepatocyte enzyme release of aspartate aminotransferase (AST) was suppressed significantly more in group 3 (238.2+/-107 IU/l), than in group 1 (672.3+/-160 IU/l) at 2 hr after reperfusion. In group 3, the tissue PO2 levels and tissue blood flow also remained significantly higher throughout the perfusion. The platelet counts in the perfusate remained significantly higher in group 3 (37.1% to 74.3% of the preperfusion level) than in group 1 (4.4% to 14.7%), after 0 to 80 min of perfusion. According to the histologic findings, the degree of interlobular hemorrhaging and congestion decreased remarkably more in group 3 than in group 1. CONCLUSION: These findings thus indicated that soluble thrombomodulin protein extracted from human urine remarkably improved hepatic microcirculation in the xenoperfused porcine liver. The thrombomodulin/protein C system might, thus, play an important role in restoring the physiological anticoagulant system in the xenoperfused porcine liver.

Animals↗

Clinical relevance of the concentrations of both pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer.

BACKGROUND: Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5'-fluorouracil (5-FU), which exerts an anti-cancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). We examined the possible correlation of the tissue concentrations of both PyNPase and DPD with the clinicopathological features of colorectal cancer. METHODS: In 36 cases of colorectal cancer, the concentrations of both PyNPase and DPD in fresh-frozen samples from either tumor or normal tissue were quantified using ELISA. RESULTS: The concentration of PyNPase was found to be significantly higher in the tumor than in the normal tissue (p = 0.001), whereas DPD showed no difference. The tumor/normal tissue ratio of PyNPase was higher in advanced stage cases, and also in the presence of liver metastasis, lymph node metastasis and vessel invasion (each p < 0.05). On the other hand, the tumor/normal tissue ratio of DPD was also higher in advanced stage cases and also in the presence of vessel invasion (each p < 0.05), thus indicating a poor response to 5-FU. The PyNPase/DPD ratio, which is known to be correlated with the tissue concentration of 5'-DFUR, was higher in the tumor than in the normal tissue (p = 0.001). CONCLUSIONS: The tumor/normal tissue ratios of both PyNPase and DPD might be useful candidates for predicting the prognosis of colorectal cancer. The PyNPase/DPD ratio was higher in the tumor tissue than in the normal tissue; however, further investigations are needed to clarify the effectiveness of fluoropyrimidine therapy.

Colorectal Neoplasms↗

Case of metastatic breast cancer from esophageal cancer.

Metastasis to the breast from extramammary malignancies is rare. This is the third case report of metastatic breast cancer from esophageal cancer. We report the clinical, radiographic, and pathologic findings of a 57-year-old woman who underwent esophagectomy for esophageal cancer and developed metastatic cancer 2 years later. Pathologic examination of a resected specimen of the breast revealed squamous cell carcinoma invading the mammary glands. Estrogen receptor and axillary lymph node metastasis were negative with immunostaining. She is alive 6 months after the modified radical mastectomy.

Breast Neoplasms↗

[A case of sepsis by Neisseria meningitidis beginning with pneumonia during a trip abroad].

A 62-year-male presented a high fever and a dry cough during a trip to Australia. He was admitted to a hospital as soon as be returned to Japan. The next day after returning to Japan, he was transferred to our hospital with septic shock and loss of consciousness. Neisseria meningitidis was cultured from his blood. N. meningitidis is rare in Japan. However its seems common, in some foreign countries. With these findings, it can be postulated that N. meningitidis might be one of the etiological agents of the imported infectious disease.

Humans↗

Inhibitory effects of small-molecule CCR5 antagonists on human immunodeficiency virus type 1 envelope-mediated membrane fusion and viral replication.

We established a human immunodeficiency virus type 1 (HIV-1) envelope (Env)-mediated membrane fusion assay and examined the small-molecule CCR5 antagonist TAK-779 and its derivatives for their inhibitory effects on HIV-1 Env-mediated membrane fusion and viral replication. The membrane fusion assay is based on HIV-1 long terminal repeat-directed beta-D-galactosidase reporter gene expression in CD4- and CCR5-expressed HeLa (MAGI-CCR5) cells after cocultivation with effector 293T cells expressing HIV-1 Env. Inhibition of HIV-1 replication was also determined in MAGI-CCR5 cells infected with the corresponding cell-free HIV-1. TAK-779 effectively suppressed R5 HIV-1 (strain JR-FL) Env-mediated membrane fusion as well as viral replication. Its 50% inhibitory concentrations (IC(50)s) for membrane fusion and viral replication were 0.87 +/- 0.11 and 1.4 +/- 0.1 nM, respectively. These values corresponded well to the IC(50) for (125)I-RANTES (regulated on activation, T cell expressed, and secreted) binding to CCR5 (1.4 nM). The inhibitory effects of 18 TAK-779 derivatives on membrane fusion differed from one compound to another. However, there was a close correlation among their inhibitory effects on membrane fusion, viral replication, and RANTES binding. The correlation coefficient between their IC(50)s for membrane fusion and viral replication was 0.881. Furthermore, since this assay depends on Env expressed in the effector cells, it is also applicable to the evaluation of CXCR4 antagonists. These results indicate that the HIV-1 Env-mediated membrane fusion assay is a useful tool for the evaluation of entry inhibitors.

Amides↗

Cardiovascular effects of static carotid baroreceptor stimulation during water immersion in humans.

We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostatic posture change from seated to supine than water immersion are caused by hydrostatic carotid baroreceptor stimulation. Ten seated healthy males underwent five interventions of 15-min each of 1) posture change to supine, 2) seated water immersion to the Xiphoid process (WI), 3) seated neck suction (NS), 4) WI with simultaneous neck suction (-22 mmHg) adjusted to simulate the carotid hydrostatic pressure increase during supine (WI + NS), and 5) seated control. Left atrial diameter increased similarly during supine, WI + NS, and WI and was unchanged during control and NS. Mean arterial pressure (MAP) decreased the most during supine (7 +/- 1 mmHg, P < 0.05) and less during WI + NS (4 +/- 1 mmHg) and NS (3 +/- 1 mmHg). The decrease in heart rate (HR) by 13 +/- 1 beats/min (P < 0.05) and the increase in arterial pulse pressure (PP) by 17 +/- 4 mmHg (P < 0.05) during supine was more pronounced (P < 0.05) than during WI + NS (10 +/- 2 beats/min and 7 +/- 2 mmHg, respectively) and WI (8 +/- 2 beats/min and 6 +/- 1 mmHg, respectively, P < 0.05). Plasma vasopressin decreased only during supine and WI, and plasma norepinephrine, in addition, decreased during WI + NS (P < 0.05). In conclusion, WI + NS is not sufficient to decrease MAP and HR to a similar extent as a 15-min seated to supine posture change. We suggest that not only static carotid baroreceptor stimulation but also the increase in PP combined with low-pressure receptor stimulation is a possible mechanism for the more-pronounced decrease in MAP and HR during the posture change.

Adult↗

Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway.

We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K(ATP)) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 microM to 1 mM inhibited [(3)H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 microM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K(ATP) mediators. Cromakalim, a K(ATP) activator, and glibenclamide, a K(ATP) inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.

Alkaloids↗

Adrenomedullin inhibits the pressor effects and decrease in renal blood flow induced by norepinephrine or angiotensin II in anesthetized rats.

Adrenomedullin (AM), a hypotensive peptide originally isolated from human pheochromocytoma, has been reported to regulate renal functions. In patients with glomerulonephritis, the serum levels of AM are elevated as well as hypertensive agents norepinephrine (NE) and angiotensin II (AII). The effects of AM on the NE- or AII-induced pressor effects and renal blood flow responses, however, are not well clarified. We examined the effects of AM on blood pressure and renal blood flow induced by NE or AII in anesthetized rats. Arterial blood pressure and renal blood flow were measured using a calibrated pressure transducer and a laser Doppler flowmeter, respectively. Drugs were injected into the tail vein with a syringe. Intravenous administration of AM (1-3 nmol/kg) decreased the arterial blood pressure in anesthetized rats in a dose-dependent manner, whereas it did not affect the renal blood flow. NE or AII administration in anesthetized rats caused both increases in blood pressure and decreases in renal blood flow. Simultaneous administration of AM with NE or All prevented the increasing effects of blood pressure and inhibited the decreases in renal blood flow caused by NE or AII. These findings suggest that AM may have a protective role against the pressor effects and decrease in renal blood flow caused by NE or AII.

Adrenomedullin↗

Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17beta-oestradiol to aromatase gene (Cyp19) knockout mice.

Aromatase P450 (CYP19) is an enzyme responsible for the conversion of androgens to oestrogens. We generated CYP19 knockout (ArKO) mice by targeted disruption of Cyp19 and studied the role of oestrogens in male reproductive ability. Approximately 85% of ArKO males were unable to sire offspring. However, no obvious difference was found in testicular and epididymal weights, numbers of sperm in the epididymis or the ability of sperm to fertilize eggs in vitro between wild-type and ArKO males. An examination of mating behaviour demonstrated that ArKO males showed an impairment in mounting behaviour against sexually mature females. The inability of more than 90% of ArKO males to sire offspring was reversed by repeated subcutaneous injections of 17beta-oestradiol when initiated on the day of birth. The effects of 17beta-oestradiol on reproduction were concentration dependent and evident when supplementation was initiated on day 7, but not on day 15 after birth. These findings suggest that oestrogens acting during neonatal life are required for normal mating behaviour in adulthood.

Age Factors↗