Biomedical subjects

H Shinohara

Publications and source records attributed to H Shinohara.

At least 109 records · Page 6Linked to original sources

PubMed1999

Coronary flow velocity immediately after reperfusion reflects myocardial microcirculation in canine models of acute myocardial infarction.

Recent reports indicate that the coronary microcirculation is sometimes injured, despite successful reperfusion in acute myocardial infarction (AMI). However, it is difficult to evaluate the coronary microcirculation immediately after reperfusion by using only angiography. The purpose of this study was to examine the relationship between the pattern of coronary blood flow velocity and myocardial microcirculatory injury immediately after reperfusion in AMI. The authors recorded the left circumflex coronary flow velocity by using the Doppler guide wire method 10 minutes after reperfusion in a canine model of AMI. In addition, myocardial contrast echocardiography was performed with the injection of contrast medium into the left circumflex coronary artery before clamping of the coronary artery and 15 minutes after release of the clamp. From these images, the ratio of the normalized gray-level postreperfusion to preclamping in the contrast-enhanced area was determined. It was compared with coronary flow velocity variables. In the 10 dogs with a diastolic-to-systolic velocity ratio (DSVR) < 4.0, this velocity ratio 10 minutes after reperfusion correlated positively (r = 0.75, p < 0.01) with the normalized gray-level ratio. However, the remaining three dogs with a DSVR > or = 4.0 markedly deviated from this pattern. Coronary flow velocities in the three dogs were characterized by a greater decrease in systolic flow velocity and occurrence of early systolic retrograde flow. Myocardial contrast echocardiographic images in these three dogs demonstrated a lower normalized gray-level ratio. In conclusion, the coronary flow velocity pattern immediately after reperfusion may reflect myocardial microcirculatory injury.

Albumins↗

PubMed1999

Fibrinolytic factors, serum lipid and C-reactive protein predicting cardiac events in Japanese patients with coronary atherosclerotic lesions.

Although disturbances of the fibrinolytic system and serum lipid, and the presence of inflammation, may be risk factors for coronary artery disease (CAD), few reports have investigated these relationships in Japanese patients. Data on 106 patients (79 men and 27 women, mean age 62.3 years) with atherosclerotic lesions on the coronary angiogram were evaluated prospectively to identify whether the factors were useful in predicting the risk of coronary events during a follow-up of 50+/-4 months. Of the 106 patients who were followed, 11 patients had coronary events (4 acute myocardial infarction and 7 unstable angina pectoris). In univariate Cox analyses, a high level of tissue-plasminogen activator (t-PA), apolipoprotein CII, C-reactive protein (CRP), and a low level of high-density lipoprotein-cholesterol (HDL-C) was each associated with a significant increase in the risk of future cardiac events. The stepwise model of Cox proportional hazards analysis selected only a high level of t-PA and CRP as predictors of cardiac events. Controlling for any risk factor did not lower the relation between t-PA and the risk of cardiac events, whereas the relative risk of cardiac events in CRP was not significant when controlled for HDL-C. Thus, in prospective data obtained from a cohort of Japanese patients with coronary atherosclerotic lesions, the elevation of t-PA was an independent predictor of subsequent cardiac events. The prognostic role of CRP in cardiac events was related to a low level of HDL-C.

Angina Pectoris↗

PubMed1999

The mouse vertebrae: changes in the morphology of mouse vertebrae exhibit specific patterns over limited numbers of vertebral levels.

The mouse vertebrae from the cervix to the tip of the tail were characterized and anatomical features that have been lacking were added to the classical description. The vertebrae consist of six long-range and fourteen short-range substructures, with the foveal process being a newly identified substructure. The caudal transverse process, cranial hemal process and hemal ridge are substructures that are clearly defined in the mouse. Each long-range and short-range substructure has several specific morphological features such as length, width, area, shape and angle. These features exibit a crescendo, plateau or decrescendo pattern over a limited number of vertebral segments that ranges from just a few to twenty. The variety of substructural combinations and the constant changes in the morphological features lead to the fact that no single vertebra has the same morphology as any other. An analysis of the patterns of changes in morphology provides some insight into the genetic plan for the metameric body axis.

Animals↗

PubMed1999

The size and position of the sacral hiatus in man.

The position and size of the sacral hiatus were examined in sixteen human vertebral specimens. The cranial margin of the sacral hiatus was located caudal to the level of the fourth sacral vertebra in 75% of sacra examined; thus this level is considered to be the representative border for the formation of the vertebral arch. The developmental significance of the sacral hiatus was discussed.

Adolescent↗

PubMed1999

The musculature of the mouse tail is characterized by metameric arrangements of bicipital muscles.

This is the first report, to our knowledge, of the full characterization of the musculature of the mouse tail. Bicipital muscles form a major part of the tail musculature. The tail tendons originate with fusiform muscle from the dorsal and ventral lumbo-sacro-coxal regions and are inserted into the coccygeal vertebrae (extrinsic muscles of the tail). Each coccygeal vertebra has short muscles that terminate on the adjacent vertebrae (intrinsic muscles of the tail). The short muscle and its corresponding tail tendon are joined, thereby forming a bicipital muscle that is inserted into the coccygeal process. A geographical correspondence is strictly maintained between the origin of the tendon in the lumbo-sacro-coxal region and the insertion of the bicipital muscle in the coccygeal vertebrae. In other words, the organization of the tail musculature is based upon repetitions of fusion between the extrinsic and intrinsic muscles at each coccygeal vertebral level. This design is referred to as the metameric arrangement of the bicipital muscles. The organization, arrangement and function of muscles in the tail have features in common with those muscles in the digits of the human extremities.

Anatomy, Artistic↗

PubMed1999

[Assessment of a new non-invasive cerebral blood flow determination method using the brain uptake ratio of 99mTc-ECD].

We modified the method of calculating brain uptake ratio (BUR) reported previously, and devised a new non-invasive cerebral blood flow measurements for 99mTc-ECD that does not require blood sampling. This method yields BUR that is not influenced by the gamma camera type and the choice of acquisition-reconstruction conditions, when corrected by the SPECT/Planar cross calibration coefficient. A good correlation was observed between the BUR obtained by this method and the cerebral blood flow (CBF) obtained by the 123I-IMP continuous arterial blood sampling method. And based on these results, it is now possible to convert BUR to CBF. This method is applicable to small field type of gamma cameras, and it is expected to be useful as a routine test.

Brain↗

PubMed1999

Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases.

BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. To clarify the possible involvement of the BRCA1 protein in mammary carcinogenesis in sporadic and hereditary forms, we have analyzed the BRCA1 protein expression pattern in five breast epithelial cell lines, including a BRCA1-deficient cell line, and 162 breast cancer tissue samples [including 108 sporadic, 35 hereditary (BRCA1 status unknown), and 19 BRCA1-associated cases] from Japanese women. Twelve anti-BRCA1 antibodies were tested by fixation conditions, in which nuclear localization of BRCA1 protein was preserved, and by specificity of the antibodies, which was evaluated in BRCA1-deficient cancer cells. Using monoclonal antibodies applicable to immunohistochemical analysis of paraffin-embedded tissue sections, we found high-level expression of BRCA1 protein in normal mammary epithelium and various degrees of reduced expression in breast cancer cells. Of the 19 BRCA1-associated breast cancer tissues, 15 (79%) showed reduction (8 cases) or complete loss (7 cases) of nuclear expression. Thirty (28%) of 108 sporadic and 6 (17%) of 35 hereditary carcinomas showed reduced BRCA1 protein expression. Reduction of BRCA1 protein expression in sporadic carcinomas was associated with solid-tubular phenotype, with poor tubular differentiation, and with an overexpression of c-erbB-2 protein, which is one of the prognostic factors in breast cancer. Our data suggest that reduced expression of BRCA1 protein may play an important role in mammary carcinogenesis, not only in BRCA1-associated breast carcinomas, but also in sporadic carcinomas, and also suggest that mechanisms other than mutation may be involved in its reduced expression.

Animals↗

PubMed1999

[Hypertensive heart disease with left ventricular diastolic dysfunction demonstrating restrictive hemodynamics: a case report].

A 47-year-old man with hypertensive heart disease and left heart failure due to left ventricular diastolic dysfunction was admitted to our hospital because of emergent hypertension. Chest radiography on admission showed slight cardiomegaly and mild pulmonary congestion with right pleural effusion Echocardiography showed concentric hypertrophy and normal contraction of the left ventricular wall Pulsed Doppler left ventricular inflow velocity wave and pulmonary venous flow velocity wave disclosed restrictive filling patterns. After Ca antagonist, nitrate, and diuretics were administered, blood pressure was normalized, and left ventricular inflow velocity wave showed the relaxation abnormality pattern and pulmonary venous flow velocity wave showed the normal pattern. Radioiodinated iodine-123 metaiodobenzyl guanidine (123I-MIBG) imaging in the state of normalized blood pressure showed decreased heart to mediastinum ratio and increased washout rate. Left heart catheterization and angiography revealed normal end-diastolic pressure and coronary arteries, but coronary flow reserve evaluated with Doppler flow wire and intracoronary adenosine triphosphate administration was impaired: Plasma level of atrial and brain natriuretic peptides, which were markedly elevated on admission, decreased with the improvement of heart failure. Doppler flow velocity patterns, plasma levels of atrial natriuretic peptide and brain natriuretic peptide, cardiac sympathetic nerve activity, and coronary flow reserve might be useful for evaluating the severity of left ventricular diastolic dysfunction in patients with hypertensive heart disease.

Atrial Natriuretic Factor↗

PubMed1999

Oral administration of the immunomodulator JBT-3002 induces endogenous interleukin 15 in intestinal macrophages for protection against irinotecan-mediated destruction of intestinal epithelium.

We recently reported that p.o. administration of the new synthetic bacterial lipopeptide JBT-3002 can protect mice from irinotecan (CPT-11)-induced intestinal injury, but the mechanism was not known. Because interleukin-15 (IL-15) is associated with maintenance of intestinal epithelial cell integrity, we examined whether p.o. administration of JBT-3002 elevates expression of this monocyte-derived cytokine. Four daily i.p. injections of 100 mg/kg CPT-11 were effective against liver metastases produced by CT-26 murine colon cancer cells, but severe damage to the intestinal epithelium and early death of the mice also resulted. Three consecutive daily p.o. doses of JBT-3002 prior to i.p. injection of irinotecan prevented the undesirable side effects of irinotecan without reducing its ability to eradicate liver metastases. Immunohistochemical analyses of the intestines of mice treated with JBT-3002 and CPT-11 demonstrated an increase in the number of dividing cells in the crypts and enhanced expression of IL-15 in lamina propria cells; the increase correlated with increased expression of the IL-15 gene as determined by semiquantitative reverse transcriptase-PCR. In vitro studies demonstrated that JBT-3002 induced expression of IL-15 in peritoneal macrophages but not in normal intestinal epithelial cells (IEC-6). Moreover, the presence of IL-15 decreased irinotecan-mediated cytotoxicity of IEC-6 epithelial cells. These data show that the p.o. administration of JBT-3002 induces expression of IL-15 by macrophages in the lamina propria, which can prevent irinotecan-induced injury to the intestinal mucosa.

Adjuvants, Immunologic↗

PubMed1998

A bifunctional hybrid molecule of the amino-terminal fragment of urokinase and domain II of bikunin efficiently inhibits tumor cell invasion and metastasis.

Urinary trypsin inhibitor (UTI) inhibits efficiently tumor cell invasion and the formation of metastasis. The anti-metastatic effect is dependent on the COOH-terminal domain II of UTI [UTI-(78-136)-peptide]. To develop a molecule that binds with high affinity to the urokinase (uPA) receptor (uPAR) on tumor cell surfaces, a bifunctional hybrid molecule [uPA-(1-134)-UTI-(78-136)] consisting of the uPAR-binding NH2-terminal fragment [UTI-(78-136)-peptide] of uPA at the NH2-terminus of UTI-(78-136)-peptide was produced in Escherichia coli by genetic engineering. The purified hybrid protein inhibited trypsin and plasmin 2-3-fold less effectively than UTI-(78-136)-peptide and was found to bind to human tumor cells via uPAR, which was confirmed by cell binding and competition experiments. Using a modified Boyden chamber and an artificial basement membrane, Matrigel, it was found that the hybrid protein is very effective at inhibiting invasion by uPAR-expressing human tumor cells. Sensitivities of tumor cells towards the anti-invasive effect of uPA-(1-134)-UTI-(78-136) correlated with the density of uPAR on human tumor cells. Furthermore, in the spontaneous metastasis model, the hybrid protein inhibited the formation of lung and/or lymphatic metastasis by human ovarian carcinoma and choriocarcinoma cells. The hybrid protein was much more effective than uPA-(1-134)-peptide, UTI-(78-136)-peptide, or UTI. We conclude that this approach extends the possibility of applying recombinant protein for therapeutic use in inhibition of human tumor cell metastasis.

Amino Acid Sequence↗

PubMed1998

Structural studies of endohedral metallofullerenes by synchrotron radiation powder diffraction.

The endohedral natures of the metallofullerenes Y@C(82) and Sc(2)@C(8)4 are described based on synchrotron radiation powder diffraction experiments. For structural analysis, a combination of the maximum-entropy method (MEM) and Rietveld refinement was employed to analyse the complicated powder pattern. The obtained MEM charge densities show a clear distinction of the endohedral natures of the mono- and dimetallofullerenes.

Journal Article↗

PubMed1998

The beneficial effect of phosphocreatine accumulation in the creatine kinase transgenic mouse liver in endotoxin-induced hepatic cell death.

Purpose. The purpose of this study was to investigate the relationship between hepatic energy status and liver injury during sepsis, using transgenic mice which express creatine kinase in the liver catalyzing the phosphocreatine/creatine system. Methods. Creatine kinase transgenic mice were fed with normal rodent chow or chow containing 10% creatine for 5 days. Lipopolysaccharide (0.2 mg/kg) combined with d-galactosamine (600 mg/kg) was administered intraperitoneally. Results. Eighty percent of the creatine-fed transgenic mice had survived at 48 h post-d-galactosamine and lipopolysaccharide administration, compared with none of the normally fed transgenic mice. Hepatic phosphocreatine and ATP levels in the normally fed transgenic mice were significantly lower than those in the creatine-fed transgenic mice before and after lipopolysaccharide combined with d-galactosamine was administered. Massive hepatic hemorrhagic necrosis with apoptosis was seen in response to d-galactosamine and lipopolysaccharide in normally fed transgenic mice. These results are consistent with a significant increase in serum aminotransferase at 8 h. In contrast, there were faint necrotic changes in the liver with minimal cellular infiltration in creatine-fed transgenic mice. Conclusions. Maintenance of hepatic ATP levels protects from sepsis-induced liver injury and mortality.

Alanine Transaminase↗

PubMed1998

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of 18FDG, three-dimensional positron emission tomography and rectilinear scan.

We tried to simultaneously obtain the elimination constant of mucociliary clearance and the pulmonary epithelial permeability constant after inhalation of 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) solution by carrying out whole lung positron emission tomography and a rectilinear scan in rabbit experiments. The elimination constant of pulmonary epithelial permeability was obtained from the decrease in the amount of the radioactivity with time in the region of interest (ROI) confined to the lungs, trachea and tracheal cannula in the rectilinear scan. The total elimination constant of the radioactivity in the lungs was obtained from the ROI confined to the lungs in the tomography. The mucociliary clearance rate constant in the lungs was then obtained after subtracting the elimination constant of the pulmonary epithelial permeability from the total elimination constant of the 18FDG in the lungs. The mucociliary clearance constant in the trachea was calculated from the residual radioactivity in the trachea and the mucociliary clearance constant in the lungs. The mean pulmonary epithelial permeability constant was 0.0020% min(-1) obtained from the rectilinear scan. The mean mucociliary clearance constants of the lungs and the trachea were 0.0006 and 0.025% min(-1), respectively. These results indicated that the pulmonary epithelial permeability and mucociliary clearance could be evaluated simultaneously with 18FDG by using three-dimensional positron emission tomography and a rectilinear scan.

Administration, Inhalation↗

PubMed1998

Contribution of carbon monoxide-producing cells in the gastric mucosa of rat and monkey.

Recent studies have shown that carbon monoxide (CO) may function as a gaseous signaling molecule in a similar way to nitric oxide. In the gastrointestinal tract, immunoreactivity against a CO-producing enzyme, heme oxygenase-2 (HO-2), was reported in epithelial cells and neurons of submucosal and myenteric plexus. However, details of the epithelial cells in the gastric mucosa remain unknown. The aim of this study was to clarify if mRNA for HO-2 is expressed in the rat stomach, if HO-2 protein is present in the mucosa, and to define the cell types of the HO-2-immunoreactive cells. HO-2 mRNA and protein were detected in fundic and pyloric mucosa of rat stomach using an RNA protection assay and western blot analysis. Immunohistochemical study showed that HO-2 was localized in parietal cells of the fundic glands and gastrin cells of the pyloric glands of both rat and monkey. The results suggest that HO-2 enzyme is produced in the gastric mucosa, and that CO is released from parietal cells and gastrin cells.

Amino Acid Sequence↗

PubMed1998

Localization of a G protein Gi2 in the cilia of rat ependyma, oviduct and trachea.

In previous studies, the localization of a pertussis toxin-sensitive G protein was demonstrated in ependymal cilia, but the identification of the subtype of G protein was inconsistent. To clarify this issue, we studied the localization of Goalpha, Gi1alpha, Gi3alpha and Gi2alpha in the ciliated ependymal cells and in the cilia of some other tissues of rats using specific antibodies. The cilia of the ependymal cells that line the ventricular cavity of the brain were intensely immunoreactive for Gi2alpha, but not for Goalpha, Gi1alpha or Gi3alpha. Immunoblot analysis demonstrated higher levels of Gi2alpha in the ependymal cilia-rich pellet than in the motor area of the parietal cortex. At the ultrastructural level, the immunoreactivity specific for Gi2alpha was found predominantly in the cilia, but rarely in the microvilli or the basal bodies of ependymal cells. In cross-sections, the immunoreactivity specific for Gi2alpha was observed only in cell membranes, in particular, in the inner electron-dense leaflet of the trilaminar structure. In addition to that in the ependymal cilia, such specific localization of Gi2alpha was observed in the motile cilia in other tissues, including the oviduct and trachea. By contrast, the stereocilia in the ductus deferens were not immunopositive for Gi2alpha. These findings suggest that Gi2 might play an important role in the signal transduction in ciliary membrane-associated function(s) of the ependymal cells, oviduct and trachea.

Animals↗

PubMed1998

Coronary flow velocity patterns immediately after reperfusion reflect the pathologic characteristics of reperfused myocardium in canine models of acute myocardial infarction.

BACKGROUND: It is difficult to evaluate the extent of myocardial injury after successful reperfusion following acute myocardial infarction (AMI). We investigated the relationship between the coronary flow velocity pattern immediately after reperfusion and pathologic characteristics after myocardial reperfusion injury in dogs. METHODS: We measured distal coronary flow velocity variables in the left circumflex coronary artery in a canine model of AMI (n = 12) 10 min after the release of a clamp (3-10 h clamp procedure) using a 0.35 mm Doppler guide-wire. Dogs were divided into two groups according to presence or absence of early systolic retrograde coronary flow. Hearts were excised 2 h after reperfusion and examined histopathologically. RESULTS: The clamping time tended to be longer in dogs with early systolic retrograde coronary flow. Neutrophil infiltration was observed in the myocardium of dogs without systolic retrograde flow (n = 9); hemorrhage was rarely detectable and the myocardium maintained a bundle form. However, the bundle form of the myocardium became rough, and the severity of the incidence of hemorrhage tended to increase as the ratio of the diastolic coronary flow velocity to systolic velocity (DSVR) decreased. Vacuolar degeneration of the myocardium was also observed in hearts with a relatively low DSVR. In the group with systolic retrograde flow (n = 3), hearts were characterized by coagulation necrosis, marked vacuolar degeneration of the myocardium and diffusely distributed red cells in the intermyocytes. Systolic antegrade flow velocity was much reduced in this group, resulting in a markedly increased DSVR. These findings appeared to be related to severe myocardial damage. CONCLUSIONS: Coronary flow velocity patterns immediately after successful reperfusion appear to reflect the pathologic characteristics of the reperfused myocardium in dogs with AMI.

Animals↗

PubMed1998

Does light stimulus at eye opening of the developing rat influence retinal expression of GTP-binding protein (G(0))?

We previously hypothesized that light stimulus at eye opening of rats on postnatal days (P) 13 or 14 has an effect on the expression of GTP-binding proteins (G(0) in the retina) because the concentration of G(0) alpha increased rapidly between P10 and P15. This hypothesis was also supported by the findings that the distribution of G(0) alpha in the retina was almost the same as that of adult rats between P10 and P15. In this study, pregnant rats were kept in a dark room after vaginal plugs were identified; they gave birth to their pups in the dark, and their pups were reared by their mothers in the dark. The postnatal rats were sacrificed at P10, P15, P18, P22, P24, P27, and P30. Their retinas were investigated immunochemically and immunohistochemically, using G(0) alpha antibody, and these results were compared with those of the rat pups reared normally. Only G(0) alpha immunoreactivity in the inner nuclear layer of rats reared in the dark room was weaker than in the controls; the distribution of G(0) alpha in the retina did not change, as compared with pups reared in normal conditions. In addition, in pups reared in the dark, G(0) alpha increased rapidly from P10 to P15. However, the concentration of G(0) alpha in the retina of rat pups reared in the dark was significantly low at P22 (p < 0.01) and P30 (p < 0.05), as compared with pups reared in normal conditions. Although the function of G(0) in the retina may have something to do with the light stimulus after eye opening, it appeared that the expression of G(0) was not influenced by light stimulus at eye opening.

Animals↗

PubMed1998

Echocardiographic assessment of right atrial function in patients with myocardial infarction with reference to obstructive lesions of the coronary arteries.

We assessed the relationship between right atrial (RA) function and obstructive lesions of the coronary arteries in 29 patients with recent or old myocardial infarction (MI). Patients were divided into 3 groups according to the location of obstructions as follows: obstruction at the proximal right coronary artery (segments 1 and 2) (RCA proximal group, n=9); obstruction at the distal RCA (segments 3 and 4) (RCA distal group, n=6); and obstruction at the left anterior descending coronary artery (LCA group, n=14). The RA volume and the fractional change in the RA area during atrial contraction (RA %AC) were evaluated by apical 2-dimensional echocardiography. The right ventricular (RV) end-diastolic pressure (RVEDP) was measured in 4 patients in the RCA proximal group and 4 patients in the LCA group. The ejection fraction of the right ventricle (RVEF) was measured by radionuclide angiography or 2-dimensional echocardiography in 7 patients in the RCA proximal group, 5 patients in the RCA distal group, and 7 patients in the LCA group. The RVEF tended to be lower in the RCA proximal group than in the RCA distal and LCA groups. The RA volume was significantly greater in the RCA proximal group than in the LCA group. The RA %AC was significantly smaller in the RCA proximal group than in the RCA distal and LCA groups. There were no significant differences in the early diastolic RV inflow velocity among groups, but the late diastolic RV inflow velocity was significantly lower in the RCA proximal group than in the RCA distal and LCA groups. There was no significant difference in the RVEDP between the RCA proximal and LCA groups. Thus, RA dysfunction in the RCA proximal group appeared to be due to myocardial damage rather than to afterload mismatch. These findings suggest that RA dysfunction may occur in patients with an inferior MI who have an obstructive lesion of the proximal RCA.

Aged↗