Search PubMed⌕ Search

Biomedical subjects

T Shiota

Publications and source records attributed to T Shiota.

At least 91 records · Page 5Linked to original sources
PubMed1996

Role of extracellular matrix in experimental vasospasm. Inhibitory effect of antisense oligonucleotide on collagen induction.

BACKGROUND AND PURPOSE: Although it has been suggested that collagen plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no constructive research to prove it directly. In this study we stopped the transcription of the procollagen type I gene by introducing antisense oligonucleotides for its mRNA in a rat femoral artery model of vasospasm induced by blood and assayed the changes in the vasoconstrictive activity of the vessel and expression of the procollagen mRNA. METHODS: We applied antisense, sense, or missense oligonucleotides, located at the carboxyl propeptide region for alpha 1(I) procollagen mRNA, onto the femoral artery in a rat femoral artery model of vasospasm. The diameter of the artery was measured by angiography. The transcription level of the procollagen gene in the arterial tissue was assayed by use of reverse transcription-polymerase chain reaction. Morphological change in the artery was observed with aldehyde-fuchsin-Masson-Goldner staining. RESULTS: In the model, when the artery was exposed to antisense oligonucleotides in pluronic gel for 5 days to prevent arterial contraction, the contraction was inhibited at a significant level (76.0% +/- 5.6) when compared with that in control experiments using sense oligonucleotides (64.0% +/- 2.4), missense oligonucleotides (63.5% +/- 3.5), or gel alone (62.1% +/- 5.8). The application of antisense oligonucleotide resulted in a marked decrease in alpha 1(I) procollagen mRNA expression as determined by polymerase chain reaction, indicating that the collagen reduction by antisense oligonucleotides occurred at the transcription level. Histological staining suggested that collagen accumulation at the site in the artery where antisense oligonucleotide had been administered was indeed less than that in the control artery. CONCLUSIONS: The results indicate that the induction of procollagen type 1 could cause pathogenesis of the arterial contraction induced by blood in a rat femoral vasospasm model.

Animals↗
PubMed1996

Cathepsin B in the growth of colorectal cancer: suppressive effect of leupeptin on the growth of DMH-induced rat colon neoplasm.

Cathepsin B, a thiol protease, has been reported to be involved in cancer progression and metastasis. The suppressive effects of two kinds of protease inhibitors, leupeptin and dietary camostate (FOY-305), on tumorigenesis and progression in 1, 2-dimethylhydrazine (DMH)-induced rat colon neoplasm were examined in relation to tissue cathepsin B activity. Male Donryu rats were treated with leupeptin or FOY-305 during or after the administration of DMH. There were no significant differences in average tumor numbers among all DMH-treated groups. However, the percentage of small tumors was significantly higher in the group in which leupeptin was supplied during DMH administration. This trend was not recognized in the FOY-305-treated groups. The ratio of cathepsin B activity in the tumors to that in the tumor-bearing tissue (T/Tb) was significantly increased with increasing tumor size (P = 0.009). The cathepsin B activity levels in the tumor-bearing mucosa in the groups which received leupeptin or FOY-305 following DMH treatment were both significantly lower than that in the group which received neither protease inhibitor (P = 0.046 and P = 0.0067, respectively). The results obtained indicate that leupeptin may have suppressed tumor growth by lowering the tissue cathepsin B activity.

1,2-Dimethylhydrazine↗
PubMed1996

Cathepsin B in the growth of colorectal cancer: increased activity of cathepsin B in human colorectal cancer.

Cathepsin B, a thiol protease, is involved in cancer metastasis. To clarify the role of cathepsin B in tumor progression in human colorectal cancer, the relationship between its activity, immunohistochemical staining, and clinical tumor progression was investigated. Cathepsin B activity in adenocarcinomas was significantly elevated compared with that in the tumor-bearing tissue. Furthermore, the tumor/tumor-bearing tissue (T/Tb) ratio of the activity was significantly higher than that of colorectal adenoma. Immunohistochemical studies demonstrated intense staining in the cancerous tissue. With respect to the clinical stage of tumors, the activity tended to be higher in tumors that had invaded the serosa or subserosa than in those that invaded the proper muscle. The results suggest that cathepsin B participates in the progression of human colorectal cancer, and its increased expression is a sensitive marker of the differentiation between colorectal adenoma and adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Inhibition of vascular contraction by intracisternal administration of preproendothelin-1 mRNA antisense oligoDNA in a rat experimental vasospasm model.

To clarify the role of endothelin-1 (ET-1) in the etiology of hemolysate-induced contraction of vessels, the authors introduced antisense oligoDNA for preproendothelin-1 (ppET-1) messenger RNA in a rat model of vasospasm. Phosphorothioate antisense oligoDNAs for ppET-1 were injected into the cisterna magna. Fluorescein isothiocyanate-labeled phosphorothioate antisense oligoDNAs were proven by fluorescence chasing to be incorporated into the vascular wall. Striking inhibitory effects of experimental vasospasm were observed in the basilar artery (BA) in which the oligoDNAs were injected. The vascular contraction was significantly inhibited by oligoDNAs after 20 minutes of hemolysate exposure, which suggested that ET synthesis started approximately 20 minutes after hemolysate stimulation. Expression of ppET-1 in the BA in which the spasm was inhibited was markedly suppressed at the transcription level. The results indicate that ET-1 may play an important role in hemolysate-induced vasoconstriction in rats. In addition, the antisense approach in the cerebrospinal fluid might be a useful tool for preventing cerebral vasospasm.

Animals↗
PubMed1995

Factors influencing pulmonary venous flow velocity patterns in mitral regurgitation: an in vitro study.

OBJECTIVES: The aim of this study was to investigate factors affecting pulmonary venous flow patterns in mitral regurgitation. BACKGROUND: Although pulmonary venous flow velocity patterns have been reported to be helpful in assessing the severity of mitral regurgitation, the influence of regurgitant jet direction, pulmonary venous location and left atrial pressures on pulmonary venous flow patterns has yet to be clarified. METHODS: The mitral regurgitant jet was produced by a pulsatile piston pump at 10, 30 and 40 ml/beat through a circular orifice, whereas the pulmonary venous flow was driven by gravity. Four different patterns of pulmonary venous flow and mitral regurgitation were examined. The V wave pressure was set at 10, 30 and 50 mm Hg and pulmonary venous flow velocity at 30 cm/s. Color and pulsed Doppler recordings were obtained with a VingMed 800 scanner interfaced with a computer facilitating digital analysis. RESULTS: The decrease in the velocity time integral of pulmonary venous flow was more prominent for any given volume of mitral regurgitation at higher left atrial pressure. When the mitral regurgitant jet was directed toward the pulmonary vein, a more prominent decrease in the velocity time integral was seen, especially for severe mitral regurgitation (40 ml) with high left atrial pressure (95% vs. 55%, p < 0.001); and the time to peak deceleration of forward flow was significantly shorter (485 vs. 523 ms, respectively, p < 0.01). Also, two different types (laminar and turbulent) of reversed pulmonary venous flow were observed. CONCLUSIONS: Multiple factors, including jet direction, mitral regurgitant volume and left atrial pressure, determine the effect of mitral regurgitation on pulmonary venous flow velocity patterns.

Blood Flow Velocity↗
PubMed1995

Potent inhibitors of acyl-CoA:cholesterol acyltransferase. Structure-activity relationships of novel N-(4-oxochroman-8-yl)amides.

Novel N-(4-oxochroman-8-yl)amide derivatives 1 were synthesized and tested for their ability to inhibit rabbit small intestinal ACAT (acyl-CoA:cholesterol acyltransferase) in vitro and to lower serum total cholesterol in cholesterol-fed rats in vivo. Among the synthesized compounds, N-(7-alkoxy-4-oxochroman-8-yl)amide derivatives showed potent ACAT inhibitory activity both in vitro and in vivo. The structure-activity relationships of these N-(4-oxochroman-8-yl)amides and related compounds are discussed on the basis of these two assays. The carbonyl group at position 4 of the 4-chromanone was essential for potent ACAT inhibitory activity. N-(Chromon-8-yl) derivatives were less potent than N-(4-oxochroman-8-yl) derivatives. An alkoxy group at position 7 of the 4-chromanone moiety was important for potent ACAT inhibitory activity. In the N-(7-alkoxy-4-oxochroman-8-yl)amide derivatives, another necessary factor to elicit the potent ACAT inhibitory activity was lipophilicity of the molecules. The highly lipophilic acid amides N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide (35) and 4-[[6-(4-chlorophenoxy)hexyl]oxy]-N-(7-methoxy-4-oxochroman-8- yl)benzamide (63) showed potent activity. Introduction of a highly lipophilic alkoxy group at position 7 of the 4-chromanone moiety instead of methoxy group also resulted in potent activity. In this case, highest inhibitory activity was obtained by N-[7-(decyloxy)-4-oxochroman-8-yl]-2,2-dimethylpropanamid e (65). The most potent compound, N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide (35, TEI-6522), showed significant ACAT inhibitory activity (rabbit small intestine IC50 = 13 nM, rabbit liver IC50 = 16 nM), foam cell formation inhibitory activity (rat peritoneal macrophage IC50 = 160 nM), and extremely potent serum cholesterol-lowering activity in cholesterol-fed rats (61% at a dose of 0.1 mg/kg/day po).

Animals↗
PubMed1995

Effects of pulmonary venous flow direction on mitral regurgitation jet area as imaged by color Doppler flow mapping. An in vitro study.

BACKGROUND: Although the effects of adjacent walls and left atrial pressure on mitral regurgitation (MR) jet area imaged by color Doppler have been examined, few data exist regarding the influence of pulmonary venous (PV) filling flow on regurgitant jets. Therefore, we designed a left atrial model to examine the relation between PV flow direction and MR jet area. METHODS AND RESULTS: The left atrial chamber (7.6 cm in diameter) was built with a PV inflow (1.0 cm in diameter) and mitral valve regurgitant orifice in the same plane. The MR jet was simulated as fixed in volume and velocity (3.5 m/s) and directed with a pulsatile pump into the left atrial model. PV flow with a constant velocity (30 cm/s) was driven by gravity (83 cm H2O). With left atrial mean pressure at either 10, 30, or 50 mm Hg, four flow patterns were examined: (1) PV flow away from the mitral valve, MR jet toward the pulmonary vein; (2) PV flow toward the mitral valve, MR jet toward the pulmonary vein; (3) PV flow away from the mitral valve, MR jet away from the pulmonary vein; and (4) PV flow toward the mitral valve, MR jet away from the pulmonary vein. MR color Doppler images were recorded with a 3.5-mHz frequency transducer and at 7-kHz pulse repetition frequency. For each condition, we compared jet area, length, and width of the MR signal. MR jet areas for conditions 3 and 4 were larger at 10 mm Hg than at 30 or 50 mm Hg left atrial pressure. Especially at the lower pressures, PV flow diminished the MR jet area in condition 4 compared with that in condition 3, such that MR jets were smaller in condition 4. In conditions 1 and 2, the jets were imaged at an oblique angle and were smaller than in conditions 3 and 4 (P < .001), but they were not significantly different from each other as imaged. CONCLUSIONS: In this model, factors including the direction of PV flow, the direction of MR as relates to the angle of interrogation, and the level of left atrial pressure influenced the size of MR jets. The effect of PV flow direction was diminished by increased left atrial pressure. PV flow directed away from the mitral valve was associated with larger MR jets than when PV flow was directed toward it (condition 4), probably because of jet distortion and flattening.

Blood Flow Velocity↗
PubMed1995

Changes in transmitral and pulmonary venous flow patterns in the first day of life.

The purpose of this study was to see the relationship between changes in pulmonary venous flow velocities and those in transmitral flow velocities during the first day of life. A serial Doppler echocardiography was performed in 24 normal neonates at 2, 12, and 24 hours of age. The size of the ductus arteriosus was 4.3 +/- 0.5 mm at 2 hours and 2.1 +/- 0.7 mm at 12 hours, and closed in 21 of 24 neonates at 24 hours. The peak systolic pulmonary venous flow (peak S), peak diastolic pulmonary venous flow (peak D), peak D/S, peak velocity at early diastolic filling (peak E), and peak E/A, which were high at 2 hours, decreased significantly at 12 hours but remained constant thereafter. The size of the ductus arteriosus was found to be correlated with peak S, peak D, and peak D/S. There was a direct correlation between peaks E and D (r: 0.64, p < 0.01) as well as a direct correlation between peaks E/A and D/S (r: 0.36, p < 0.05). These results indicate that the diastolic pulmonary venous flow is determined by the same factors that influence the transmitral flow. These waveforms may reflect the increase in pulmonary circulatory volume by left-to-right shunting through the ductus arteriosus.

Blood Flow Velocity↗
PubMed1995

Relation of left atrial V-wave/left ventricular systolic pressure ratio to mitral regurgitant volume.

Evaluation of mitral regurgitation is difficult whether invasive or noninvasive methods are used. The determination of the regurgitant volume itself cannot be done in clinical practice with reasonable accuracy. In six sheep with chronic mitral regurgitation, left ventricular and left atrial pressures were recorded with high-fidelity catheters. The regurgitant volume was measured directly with electromagnetic flow probes positioned at the mitral annulus and around the ascending aorta, balanced against each other. A total of 24 hemodynamic states were obtained varying preload and afterload by fluid expansion and angiotensin infusion. On the basis of these studies, the pressure ratio of the V wave divided by the left ventricular systolic pressure is proposed as an index of regurgitant volume. A good correlation was found between this ratio and the regurgitant volume (r = 0.75). The ratio is easily recorded during routine heart catheterization.

Animals↗
PubMed1995

Color flow Doppler determination of transmitral flow and orifice area in mitral stenosis: experimental evaluation of the proximal flow-convergence method.

To evaluate the in vivo accuracy of color Doppler flow-convergence methods for determining transmitral flow volumes and effective orifice areas in mitral stenosis, we studied two models for flow-convergence surface geometry, a hemispheric (HS) model and an oblate hemispheroid (OH) model in a chronic animal model with quantifiable mitral flows. Color Doppler flow mapping of the proximal flow-convergence region has been reported to be useful for evaluation of intracardiac flows. Flow-convergence methods in patients with mitral stenosis that use HS assumption for the isovelocity surface have resulted in underestimation of actual flows. Chronic mitral stenosis was created surgically in six sheep with annuloplasty rings (group 1) and 11 sheep with bioprosthetic porcine valves (group 2). Hemodynamic and echocardiographic/Doppler studies (n = 18 in group 1; n = 21 in group 2) were performed 20 to 34 weeks later. Left ventricular inflow obstruction was of varied severity, with mean transmitral valve gradients in group 1 ranging from 1.3 to 18 mm Hg and in group 2 ranging from 6.3 to 25.6 mm Hg. Although transmitral flows derived by both geometric flow convergence models showed significant correlations with reference cardiac outputs, the correlations for the OH model were better than those for the HS model (group 1, r = 0.86 for the OH model vs r = 0.72 for the HS model; group 2; r = 0.84 for the OH model vs r = 0.62 for the HS model). The OH model was also superior to the HS model in determining effective orifice areas compared to reference orifice areas determined by postmortem planimetry of anatomic orifices (group 1 only, r = 0.64 for OH vs 0.58 for HS), by the Gorlin and Gorlin formula (group 1, r = 0.63 for OH vs 0.72 for HS; group 2, r = 0.82 for OH vs 0.76 for HS), and by the Doppler pressure half-time method (group 1, r = 0.76 for OH vs 0.69 for HS; group 2, r = 0.84 for OH vs 0.62 for HS).(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1995

Doppler evaluation of severity of mitral regurgitation: relation to pulmonary venous blood flow patterns in an animal study.

OBJECTIVES: This study examined the influence of regurgitant volume on pulmonary venous blood flow patterns in an animal model with quantifiable mitral regurgitation. BACKGROUND: Systolic pulmonary venous blood flow is influenced by atrial filling and compliance and ventricular output and by the presence of mitral regurgitation. The quantitative severity of the regurgitant volume itself is difficult to judge in clinical examinations. METHODS: Six sheep with chronic mitral regurgitation produced by previous operation to create chordal damage were examined. At reoperation the heart was exposed and epicardial echocardiography performed. Pulmonary venous blood flow waveforms were recorded by pulsed Doppler under color flow Doppler guidance using a Vingmed 750 scanner. The pulmonary venous systolic inflow to the left atrium was expressed as a fraction of the total inflow velocity time integral. Flows across the aortic and mitral valves were recorded by electromagnetic flowmeters balanced against each other. Pressures in the left ventricle and left atrium were measured directly with high fidelity manometer-tipped catheters. Preload and afterload were systematically manipulated, resulting in 24 stable hemodynamic states. RESULTS: Simple logarithmic correlation between the regurgitant volume and size of a positive or negative pulmonary venous inflow velocity time integral during systole was good (r = -0.841). By stepwise linear regression analysis with pulmonary venous negative systolic velocity time integral as a dependent variable compared with the regurgitant volume, fractional shortening, left atrial v wave size, systemic vascular resistance and left ventricular systolic pressure, only contributions from v wave size and regurgitant volume (r = 0.80) reached statistical significance in determining pulmonary venous negative systolic flow. CONCLUSIONS: Evaluation of systolic pulmonary venous blood flow velocity time integral can give valuable information helpful for estimating the regurgitant volume secondary to mitral regurgitation.

Animals↗
PubMed1995

Dynamic change in mitral regurgitant orifice area: comparison of color Doppler echocardiographic and electromagnetic flowmeter-based methods in a chronic animal model.

OBJECTIVES: The aim of the present study was to investigate dynamic changes in the mitral regurgitant orifice using electromagnetic flow probes and flowmeters and the color Doppler flow convergence method. BACKGROUND: Methods for determining mitral regurgitant orifice areas have been described using flow convergence imaging with a hemispheric isovelocity surface assumption. However, the shape of flow convergence isovelocity surfaces depends on many factors that change during regurgitation. METHODS: In seven sheep with surgically created mitral regurgitation, 18 hemodynamic states were studied. The aliasing distances of flow convergence were measured at 10 sequential points using two ranges of aliasing velocities (0.20 to 0.32 and 0.56 to 0.72 m/s), and instantaneous flow rates were calculated using the hemispheric assumption. Instantaneous regurgitant areas were determined from the regurgitant flow rates obtained from both electromagnetic flowmeters and flow convergence divided by the corresponding continuous wave velocities. RESULTS: The regurgitant orifice sizes obtained using the electromagnetic flow method usually increased to maximal size in early to midsystole and then decreased in late systole. Patterns of dynamic changes in orifice area obtained by flow convergence were not the same as those delineated by the electromagnetic flow method. Time-averaged regurgitant orifice areas obtained by flow convergence using lower aliasing velocities overestimated the areas obtained by the electromagnetic flow method ([mean +/- SD] 0.27 +/- 0.14 vs. 0.12 +/- 0.06 cm2, p < 0.001), whereas flow convergence, using higher aliasing velocities, estimated the reference areas more reliably (0.15 +/- 0.06 cm2). CONCLUSIONS: The electromagnetic flow method studies uniformly demonstrated dynamic change in mitral regurgitant orifice area and suggested limitations of the flow convergence method.

Animals↗
PubMed1995

Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: effects of a non-peptide antagonist for atrial natriuretic peptide receptor.

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Anemia↗
PubMed1995

Left ventricular regional wall motion in the early neonatal period.

To investigate the changes in regional wall motion of the left ventricle in the early neonatal period, serial echocardiography was performed in normal neonates at 2 and 120 hr after birth. Quantitative analysis of the regional wall motion was performed by the centerline method. We measured right ventricular systolic time intervals, left ventricular stroke volume, flow velocity-time integral of the pulmonary artery, and size of the ductus arteriosus. The ductus arteriosus was 4.5 +/- 0.5 mm at 2 hr but was closed in all subjects by 120 hr. At 2 hr, there was hyperkinesis of the interventricular septum which disappeared by 120 hr. The right ventricular systolic time intervals at 2 hr showed a sign of pulmonary hypertension. At 2 hr, the left ventricular stroke volume was at the highest level and the flow velocity-time intervals of pulmonary artery was at the lowest level. Thus the hyperkinesis of the interventricular septum at 2 hr might reflect the circulatory changes that are characteristic of the early neonatal period.

Blood Flow Velocity↗
PubMed1995

[A case of primary pulmonary B cell lymphoma confirmed by gene analysis].

A 76-year-old man visited our clinic with chest radiographic evidence of a coin lesion in the right middle lung. Chest CT demonstrated an infiltrative shadow mainly in the S4 segment. Lymphoproliferative disorders were suggested by transbronchial lung biopsy. Middle lobectomy was performed. Pathological study showed massive proliferation of mature lymphocytes. Immunoperoxidase studies could not demonstrate a neoplastic monoclonal process. Pseudolymphoma was diagnosed. High molecular weight DNAs were extracted from frozen specimens. Whether genes of immunoglobulins and T-cell receptors were rearranged was investigated using DNA probes against JH and TCR beta-1 receptor gene. One rearranged band was found in the JH chain. No rearranged band appeared in TCR beta-1 chain. B cell lymphoma was diagnosed instead of pseudolymphoma.

Aged↗