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Biomedical subjects

T Shiota

Publications and source records attributed to T Shiota.

At least 19 recordsLinked to original sources

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

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

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

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

[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

Age and sex-dependent alterations of serum amylase and isoamylase levels in normal human adults.

Total amylase and salivary- and pancreatic-type isoamylase levels were assayed in sera from 606 apparently healthy adults of different sex and age groups. There were significant differences in both total amylase and isoamylase levels, depending on age and sex, one of the characteristics being that levels of these three enzymes were significantly higher in the elderly group in both men and women than in other age groups. Another feature was that all of these enzyme levels were significantly greater in women in the third and fourth decade than in men. Age and sex differences should be taken into consideration in the evaluation of mild hyperamylasemia.

Adolescent

Treatment of hepatocellular carcinoma by transcatheter hepatic arterial injection of radioactive iodized oil solution.

After 12 days of culture, VX2 carcinoma cells were inoculated into the liver of 16 rabbits; 14 days later, 131I-labeled iodized oil ([131I]-Lp) suspended in lipiodol was injected into the hepatic artery. Selective accumulation of the contrast material in the tumor for an extended time was evident on X-rays and hepatic scintiphotographs. The antitumor effect was remarkable. [131I]-Lp agents warrant further examination for their clinical usefulness. Internal radiation therapy by transcatheter hepatic arterial injection of [131I]-Lp (group A) was evaluated in 9 patients with hepatocellular carcinoma (HCC, tumor stage III or IV) associated with liver cirrhosis (LC) and compared with combination therapy of Lp-TAE (group B) in 18 patients with HCC (tumor stage III or IV) associated with LC. In group A, serum AFP levels dropped rapidly in eight of the nine patients who had an elevated initial level of more than 500 ng/ml. The average reduction in tumor size was 50% in eight cases as determined by computed tomography. Histological examination of one resected liver specimen at 3 months after the third injection of [131I]-Lp revealed microscopic features highly suggestive of a radiation effect in the [131I]-Lp-containing area. The 1-year survival value for patients with HCC was estimated at 49.0% using the Kaplan-Meier method. The survival of patients treated with internal radiation therapy tended to be better than that of those treated with Lp-TAE (P = 0.119).

Aged

Effectivity and safety of mannitol treatment for acute hepatic failure in rats.

In rats with D-galactosamine-induced hepatic failure, 14C-D-mannitol transport into the brain was accelerated through an increase of vesicular transport via the blood-brain barrier and thus brain mannitol contents increased. However, the osmolarity of the brain tissue changed little and the mortality was decreased by mannitol infusion to acute hepatic-failure rats. Experimental data indicate the effectivity and safety of hypertonic mannitol therapy for cerebral edema in acute hepatic failure.

Animals

Lifetime data analysis of disease and aging by the Weibull probability distribution.

We applied the Weibull distribution to the life-table and age-patterns of diseases in Japan. The life-table follows a composite Weibull distribution composed of initial failure and two stage wear-out failure periods. The extension of lifespan during the past century is manifested as increases in the scale parameters in all three periods and the shape parameters in the wear-out periods with female predominancy. The shape parameters of diseases show time-independent sex-dependent specific values. When consistent changes are observed, such as increases in the shape parameters of tuberculosis and pneumonia, legitimate causes such as prevention and repair at the societal and medical level are present. Cancer and arteriosclerosis share a common range of shape parameters suggesting analogous underlying biological processes. An analysis of the epidemiology of human aging and disease by the Weibull distribution discloses intrinsic properties of man as a biological organization as well as a societal presence.

Adolescent

Intraluminal ultrasound imaging through a balloon dilation catheter in an animal model of coarctation of the aorta.

BACKGROUND: Controversy still exists over the optimal balloon size, extent of vascular disruption, and long-term results of balloon dilation therapy for coarctation of the aorta. Intravascular ultrasound imaging has been used in patients with coronary artery disease to provide further insight into the anatomy of atherosclerotic lesions and the results of angioplasty and atherectomy. Initial observations of the results of balloon dilation of coarctations with intravascular ultrasound imaging have shown prominent dissections of the inner vascular layers that are often not detected by angiography. The purpose of this study was to test a new transballoon catheter ultrasonic imaging system capable of on-line direct visualization of lumen diameter and vessel wall structure for imaging before, during, and after dilation in an acute animal model of aortic coarctation. METHODS AND RESULTS: Abdominal aortic coarctations were created surgically in three 14-19-kg mongrel dogs by using Teflon gauze ties. The 6.8F ultrasound balloon catheter was placed percutaneously in the right femoral artery through a 9F sheath. Ultrasound imaging allowed measurement of the coarctation diameter, characterization of the vessel wall structure, localization of the stenosis, and placement of the midportion of the balloon at the narrowest area. Imaging through the balloon was performed through several dilations (five to eight per animal), and after balloon deflation, it provided information on postdilation diameter, intimal tears, long-segment dissections, and intramural thrombi, findings that were confirmed at postmortem examination. CONCLUSIONS: The results of this study demonstrate that imaging with a new intraballoon ultrasound device is feasible during inflation to therapeutic dilation pressures; it allows visualization of the changes in diameter and vascular wall structure after serial dilations without having to recross the obstructed area. Adaptation to larger balloon sizes and lower frequencies should make this system applicable to interventional catheterizations in patients with congenital cardiac and vascular lesions.

Animals

Transesophageal echocardiography in infants and children with congenital heart disease.

TEE applications for children and infants with congenital heart disease are now clinically established and TEE is being used in most major pediatric cardiovascular centers. This technology has evolved to the point that it is capable of providing diagnostic quality imaging, even for small infants. With expanding technology and increasing experience, new and more sophisticated applications will be found for pediatric TEE.

Child

Rat liver nodules induced by 2-acetylaminofluorene lose an ability to take up indocyanine green in the process of hepatocarcinogenesis.

Indocyanine green (ICG) was injected into rat liver nodules induced by 2-acetylaminofluorene (2-AAF) via portal vein. The relationship between ICG staining and cell atypism of liver nodules was examined by means of histology and DNA flow cytometry. After 2-AAF administration, many small nodules appeared on the liver surface. All hyperplastic nodules were ICG stained until 10 weeks after the administration, but some nodules were not stained after 14 weeks. ICG-stained nodules histologically consisted of benign tissues and borderline lesions, and many of them showed "diploidy" in DNA cytometry. ICG-unstained nodules consisted of hepatocellular carcinoma (HCCs) and borderline lesions, and many of them showed "aneuploidy". In this way, it has been suggested that HCC could derive from hyperplastic nodules and that they might lose an ability to take up ICG in the process of hepatocarcinogenesis. Immunohistochemical staining for glutathione-S-transferase alpha (GST-alpha), a carrier protein of ICG in hepatocytes, was well correlated with ICG staining in the nodules, suggesting that the loss of ICG uptake in HCC was partly due to the decrease of GST-alpha. Moreover, the appearance of ICG unstained and aneuploid nodules was significantly inhibited in rats which were fed on diet containing Syosaiko-to after the administration of 2-AAF. Chemopreventive effect of Syo-saiko-to on hepatocarcinogenesis was identified.

2-Acetylaminofluorene

Prognostic assessment of fulminant hepatitis from indication criteria for liver transplantation.

The clinical outcome in 15 patients with fulminant hepatitis was predicted by the indication criteria for liver transplantation used in five different transplantation centers. Fifty-four to 100% of 13 fulminant hepatitis patients died who were fulfilled with these criteria for transplantation. Most of the patients died within five to nine days after the decision of liver transplantation was made. Takahashi's score of prognostic assessment for fulminant hepatitis decreased rapidly during the time when all the different criteria in transplantation centers were fulfilled. However, two survival cases with the acute type of fulminant hepatitis were incorrectly judged to be transplanted by the two criteria. The Cambridge's criterion for liver transplantation predicted the prognosis of fulminant hepatitis most correctly; sensitivity was 84.6% and specificity 100%.

Acute Disease

Multiple organ failure in patients with fulminant hepatitis and in post-operative patients with liver cirrhosis.

Multiple organ failure (MOF) appeared during the course of nine cases with fulminant hepatitis, and it was compared with that of seven cirrhotic patients with post-operative hepatic failure. The number of organs failed was 4.9 and 3.6 on average in fulminant hepatitis and post-operative cirrhosis, respectively. All the patients died in less than nine days following the occurrence of MOF. Gastrointestinal bleeding was more frequently observed in fulminant hepatitis cases than in cirrhotic patients. In post-operative cirrhotics, hepatic failure occurred later and the elevation of serum total bilirubin was mild and slow. Renal failure and/or gastrointestinal bleeding was observed prior to death in fulminant hepatitis cases, and cardiac failure and hepatic failure in post-operative cirrhotics. These organ failures resulted in death, although extensive and multimodal treatments were carried out in both groups of patients.

Adult

Cerebral edema during hepatic encephalopathy in fulminant hepatic failure.

Thirteen out of 18 patients with fulminant hepatitis developed cerebral edema macroscopically confirmed at autopsy. Cerebral bleeding and herniation were also observed in 38 and 8% of edema cases, respectively. No significant difference was found in the clinical backgrounds (age, sex, laboratory data) of patients with and without cerebral edema. Respiratory distress (100% of edema cases, p less than 0.05), abnormal pupils (89%, p less than 0.10), convulsions (61%) and tachycardia unrelated to fever (60%) were more frequently observed in cerebral edema cases than in those without edema. The frequency of convulsions increased as hepatic encephalopathy progressed, and the frequency of respiratory distress and abnormal pupils in edema cases was significantly higher at the coma grade V of hepatic encephalopathy. Tachycardia was detected early, even at the mild grades of hepatic encephalopathy. These results suggest that symptoms due to cerebral edema such as convulsions, abnormal pupils and respiratory distress should be distinguished from those due to hepatic encephalopathy in fulminant hepatitis patients.

Adult