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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 145 records · Page 8Linked to original sources

Cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous NIDDM.

AIM: Angiotensin converting enzyme inhibitors and alpha1-adrenergic blockers improve insulin sensitivity, the mechanism of which was considered, at least in part, to be due to the increased blood flow to muscle. The present study aimed to clarify whether cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in a model of spontaneous non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHODS: OLETF rats were divided into the two groups at the age of 16 weeks: the cilostazol-supplemented group (cilostazol 40 mg/kg/day) and the normal-diet group. As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Oral glucose tolerance test and hyperinsulinemic euglycemic clamp was performed at the ages of 23 and 25 weeks, respectively. Serum levels of lipids and leptin were measured. RESULTS: Body weight and abdominal fat was increased in OLETF rats but cilostazol supplementation did not alter them. Insulin sensitivity, as measured by the hyperinsulinemic euglycemic clamp technique, was significantly decreased in OLETF rats (glucose infusion rate: 73.5 +/- 10.0 vs. 41.5 +/- 9.8 micromol/min/kg body weight, p < 0.01). Cilostazol supplementation improved insulin sensitivity partially but significantly 51.0 +/- 5.7 micromol/min/kg body weight, p < 0.05) in OLETF rats at 25 weeks of age, although it did not decrease serum levels of glucose, lipids or leptin. However, this effect was not observed in non-diabetic rats. CONCLUSION: Cilostazol, which is used in diabetic patients for the treatment of obstructive disease of artery, is expected to have a beneficial effect on insulin sensitivity in NIDDM.

Abdomen↗

Gestational changes in endothelin-1-induced receptors and myometrial contractions in rat.

The present experiments were performed to characterize the gestational changes in endothelin (ET)-1-induced myometrial contractions and ET receptors in rat. ET-1-induced contractions were composed of two types: increases in resting tone and rhythmic contractions. The increase in resting tone was decreased at 7 days of gestation, but increased at 20 days. The increase in amplitude and frequency of rhythmic contractions remained unchanged during days 7-14 of gestation. Continuous rhythmic contractions were not produced by ET-1 near the term. Both contractions were inhibited by the antagonists BQ 123 and Ro 46-2005 but not by RES 701-1 or BQ 788. In binding studies, total binding sites of [1251]-ET-1 were unchanged, however higher affinity binding sites appeared during pregnancy in addition to the lower affinity sites. The specific [125I]-ET-1 binding in non-pregnant and pregnant myometrium was completely inhibited by unlabelled ET-1 and Ro 46-2005. In contrast, the proportion which was inhibited by BQ 123 was decreased during pregnancy. In conclusion, characteristic gestational changes were the augmentation of ET-1-induced increased resting tone near term, and the appearance of high affinity ET-1 binding sites and an increase in BQ 123-resistant ET-1 binding sites during pregnancy. Further investigations are needed to understand the physiological role of these changes.

Animals↗

Tc-99m ethyl cysteinate dimer SPECT and 2-[F-18]fluoro-2-deoxy-D-glucose PET in Alzheimer's disease. Comparison of perfusion and metabolic patterns.

PURPOSE: This study compared Tc-99m ethyl cysteinate dimer (ECD) SPECT images with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) PET images in the same patients with Alzheimer's disease and determined whether ECD SPECT is as useful as FDG PET clinically. METHODS: Ten patients with probable Alzheimer's disease (mean +/- SD: age, 71 +/- 5.2 years; 6 women and 4 men; Mini-Mental State Examination score, 19.2 +/- 5.3) were evaluated in this study. Both ECD SPECT and FDG PET were performed within 1.5 months in each patient. RESULTS: ECD SPECT showed a reduction in parieto-temporal perfusion in 8 of the 10 patients, whereas FDG PET showed a reduction in temporoparietal metabolism in 9. The ECD images showed greater radiotracer uptake in the cerebellum and occipital lobe than did FDG images. The contrast between the radiotracer uptake in the sensorimotor area and that in the parietotemporal region was not as great in the ECD images as it was in the FDG images. CONCLUSION: Although ECD SPECT may not be superior to FDG PET, it is useful for the clinical evaluation of patients with Alzheimer's disease.

Aged↗

Identification of carbonic anhydrase IV and VI mRNA expression in human pancreas and salivary glands.

Cytoplasmic carbonic anhydrase (CA) II is involved in acid-base balance in a wide variety of tissues. Extracellular CAs, membrane-bound CA IV and excretory CA VI, play a cooperative role with CA II in regulating the luminal pH in kidney and salivary glands, respectively. To extend the evidence into pancreas, we studied messenger RNA (mRNA) expressions of CA IV and CA VI in human pancreas. mRNA expressions of CA II, IV, and VI were studied in human pancreas, kidney, liver, and salivary glands by three different detection methods: reverse transcription-polymerase chain reaction (RT-PCR), RT-PCR-Southern blot, and Northern blot analyses. CA IV mRNA expression was consistently detected in all four tissues except for liver; only RT-PCR-Southern blot successfully identified its expression in liver. In contrast, RT-PCR and RT-PCR-Southern blot identified CA VI mRNA in salivary glands and pancreas, but Northern blot failed to detect its expression in pancreas. There was no detectable signal of CA VI expression in kidney and liver by all detection methods. CA II mRNA expression was consistently detected in all tissues studied. These results indicate that pancreas and salivary glands contain both of CA IV and VI and suggest that the extracellular CA isozymes may form a mutually complementary system with CA II to regulate the luminal pH of the pancreatic duct system.

Blotting, Northern↗

Hepatic damage induced by transcatheter arterial chemoembolization elevates serum concentrations of macrophage-colony stimulating factor.

AIMS/BACKGROUND: This study was undertaken in order to characterize the liver injury induced by transcatheter arterial chemoembolization therapy (TACE) for hepatocellular carcinoma (HCC) and to elucidate-mechanisms involved in the growth of mononuclear phagocytes in injured human liver in vivo. PATIENTS AND METHODS: The serum levels of macrophage-colony stimulating factor (M-CSF) along with clinical parameters were examined in 43 patients with HCC who underwent TACE. Ten patients who underwent angiography alone served as controls. RESULTS: Serum M-CSF increased and peaked on the third day after TACE showing significant correlations (p < 0.001, respectively) with the increases in serum alanine aminotransferase (ALT) and type IV collagen-7S (IVcol-7S). The lipopolysaccharide-stimulated production of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha in peripheral whole blood increased and peaked on the first or on the third day after TACE. In effective cases of TACE, significantly (p < 0.05) greater increases in serum M-CSF were noted as compared with those in ineffective cases. DISCUSSION: The serum levels of M-CSF increased after TACE in correlation with hepatic inflammation and necrosis and increased production of IL-1 beta, TNF-alpha and IL-6 in peripheral whole blood. These results suggest a mechanism by which hepatic injury enhances the production of M-CSF via a cytokine cascade, which results in the proliferation of liver macrophages in vivo.

Adult↗

Sensitivity studies of beam directionality, beam size, and neutron spectrum for a fission converter-based epithermal neutron beam for boron neutron capture therapy.

Sensitivity studies of epithermal neutron beam performance in boron neutron capture therapy are presented for realistic neutron beams with varying filter/moderator and collimator/delimiter designs to examine the relative importance of neutron beam spectrum, directionality, and size. Figures of merit for in-air and in-phantom beam performance are calculated via the Monte Carlo technique for different well-optimized designs of a fission converter-based epithermal neutron beam with head phantoms as the irradiation target. It is shown that increasing J/phi, a measure of beam directionality, does not always lead to corresponding monotonic improvements in beam performance. Due to the relatively low significance, for most configurations, of its effect on in-phantom performance and the large intensity losses required to produce beams with very high J/phi, beam directionality should not be considered an important figure of merit in epithermal neutron beam design except in terms of its consequences on patient positioning and collateral dose. Hardening the epithermal beam spectrum, while maintaining the specific fast neutron dose well below the inherent hydrogen capture dose, improves beam penetration and advantage depth and, as a desirable by-product, significantly increases beam intensity. Beam figures of merit are shown to be strongly dependent on beam size relative to target size. Beam designs with J/phi approximately 0.65-0.7, specific fast neutron doses of 2-2.6x10(-13) Gy cm2/n and beam sizes equal to or larger than the size of the head target produced the deepest useful penetration, highest therapeutic ratios, and highest intensities.

Biophysical Phenomena↗

Effect of disopyramide on left ventricular pressure gradient in hypertrophic obstructive cardiomyopathy in comparison with propranolol--a case report.

The effect of intravenous administration of disopyramide (total dose 100 mg, bolus 20 mg every 5 minutes) was compared with that of propranolol (total dose 10 mg, bolus 2 mg every 5 minutes) in a patient with hypertrophic obstructive cardiomyopathy. Left ventricular pressure gradient (LVPG) was assessed by continuous wave Doppler flowmetry. LVPG markedly decreased (97 to 16 mmHg), and preejection period (PEP) increased with an increase in heart rate (HR) during disopyramide injection. No changes were observed in LVPG and PEP, and a decrease occurred in HR during propranolol administration. These results indicate that disopyramide produced greater effects on the reduction of LVPG than propranolol, a negative inotropic agent, did.

Aged↗

Evaluation of left atrial wall elasticity using acoustic microscopy.

Left atrial wall elasticity is one of the important factors regulating left atrial stiffness and functions. The authors evaluated left atrial wall elasticity by measuring the sound speed through the left atrial wall, based on the hypothesis that high elasticity tissues will yield larger sound speed values through the tissue, and examined age-associated changes in left atrial wall elasticity. Left atrium specimens were obtained from 30 normal subjects (age, 15-95 years) at autopsy. An acoustic microscope, operating at 450 MHz, was used to measure the sound speed in the endocardium and the myocardium of the left atrium. The sound speeds in endocardium and myocardium demonstrated significant correlation with age (r = 0.74, p<0.0001 and r = 0.47, p<0.01, respectively). These findings indicate that left atrial wall elasticity increased with advancing age. These changes may lead to deterioration of left atrial compliance and eventual left atrial failure in older subjects.

Adolescent↗

Cyclic variation of thickness in an age-related thick mitral valve observed by transthoracic echocardiography.

The cyclic variation of thickness during the cardiac cycle in age-related degenerative mitral valve (MV) has not been reported. Transthoracic echocardiography was used to evaluate the cyclic alteration in MV thickness in 40 patients with age-related MV thickening (diastolic MV thickness > or = 4 mm, age 70 +/- 14 years), 10 with mitral valve prolapse (MVP, age 49 +/- 11 years), 10 with rheumatic mitral stenosis (MS, age 66 +/- 9 years), and 31 control subjects (diastolic MV thickness < or = 3.6 mm, 53 +/- 17 years). After determination of the site of maximal thickness during diastole, the maximal and minimal thickness during systole of the anterior MV were measured. The percent change in MV thickness from diastole to systole (%deltaT) was calculated. The mitral regurgitation (MR) area was measured on color Doppler echocardiogram. The %deltaT (mean +/- sd) in age-related thickened MV and MVP groups were similar and significantly greater than that in control (60 +/- 8%, 61 +/- 6% vs 32 +/- 9%, p < 0.001). MR area was significantly greater in the age-related thickened MV group than that in controls (160 +/- 205 mm2 vs 14 +/- 40 mm2, p < 0.05). The %deltaT in MS (10 +/- 6%) was smallest (p < 0.001). A large cyclic alteration in valvular thickness was observed in the age-related degeneration of the MV and may be the cause of large MR despite no leaflet prolapse. The echocardiographic assessment of cyclic variation of MV thickness is feasible for estimating the histologic damage in thick MV.

Adolescent↗

Tissue characterization of myocardial cells by use of high-frequency acoustic microscopy: differential myocyte sound speed and its transmural variation in normal, pressure-overload hypertrophic, and amyloid myocardium.

The purpose of the present study was to evaluate the acoustic properties of myocytes in normal, pressure-overload hypertrophic, and amyloid myocardium. Myocardial tissue specimens at autopsy were obtained from 10 subjects without cardiovascular disease, six patients with left ventricular (LV) hypertrophy, and six patients with cardiac amyloidosis. Sound speed of myocytes was measured at subendocardial and subepicardial regions in myocardium by use of a high-frequency (450 MHz) acoustic microscope. In normal myocardium, the sound speed of myocytes was significantly higher in subendocardial region (1,728+/-19 m/sec) than in subepicardial region (1,645+/-22 m/sec) (p<0.0001). A significantly higher sound speed of myocytes was observed in the subendocardial region in LV hypertrophic myocardium (1,779+/-19 m/sec) than that in normal myocardium (p<0.001). In amyloid myocardium, a significantly lower sound speed of myocytes was observed in subendocardial (1,560+/-8 m/sec) and subepicardial (1,594+/-48 m/sec) regions than that in respective regions of the normal myocardium (p<0.0001 and p<0.05, respectively). Transmural variation in sound speed of myocytes measured by high-frequency acoustic microscopy existed in normal left ventricle. The differential myocyte sound speed and its transmural variation was observed in LV hypertrophic and amyloid myocardium as compared with normal myocardium. High-frequency acoustic microscopy can be a promising technique for myocardial tissue characterization at the myocyte level.

Acoustics↗

Biochemical characterization of 60S acidic ribosomal P proteins associated with CK-II from bamboo shoots and potent inhibitors of their phosphorylation in vitro.

Three effective phosphate acceptors (35, 15 and 13 kDa polypeptides) for casein kinase II (CK-II) in the Superdex CK-II fraction prepared from a 0.5 M NaCl extract of bamboo shoots were selectively purified by glycyrrhizin (GL)-affinity column chromatography (HPLC). These three proteins (p35, p15 and p13) were identified as 60S acidic ribosomal P proteins by determination of their partial N-terminal sequences. CK-II was associated with p35 since the GL-affinity fraction was coprecipitated with an anti-serum against Drosophila CK-IIbeta. Moreover, a derivative (oGA) of glycyrrhetinic acid (GA) and several polyphenol-containing anti-oxidative compounds [quercetin, epigallocatechin gallate (EGCG) and two isoflavones, i.e., 3',4',7-trihydroxyisoflavone (3',4',7-THI) and 8-chloro-3',4',5,7-tetrahydroxyisoflavone (8C-3',4',5,7-THI)] inhibited the CK-II-mediated phosphorylation of 60S acidic ribosomal P proteins in vitro. Quercetin was found to be the most effective compound on CK-II activity since its ID50 was approx. 50 nM. These results suggest that (i) GL-affinity column chromatography is useful for the selective purification of 60S acidic ribosomal P proteins as a heterocomplex associated with CK-II from various cell sources; (ii) natural anti-oxidative compounds with polyphenols, but not GL and GA, act as potent CK-II suppressors; and (iii) CK-II mediates the regulation of the physiological functions of 60S acidic ribosomal P proteins in growing plant cells.

Casein Kinase II↗

Expression of p53 protein and Ki-67 antigen in gingival hyperplasia induced by nifedipine and phenytoin.

BACKGROUND: Although it has been thought that drug-induced gingival hyperplasia is not related to tumorigenesis, recent case reports have shown that squamous cell carcinomas may arise in gingival hyperplasia induced by cyclosporin and phenytoin. The possible implications between the pathogenesis of this disease and tumorigenesis have not been elucidated and remain to be studied. METHODS: We immunohistochemically examined the expression of tumor-related markers such as p53 protein and Ki-67 antigen in 11 hyperplastic gingival tissues induced by nifedipine and phenytoin, as well as 5 control tissues using an avidin-biotin-peroxidase complex method. RESULTS: Two specimens out of 4 nifedipine-induced and 4 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of p53 protein in the nuclei of epithelial cells, while no expression of p53 protein was observed in the epithelia of the 5 non-hyperplastic control tissues. The immunoreactions against p53 protein showed sporadic distribution in the suprabasal layers of hyperplastic epithelia. The mean percentage of epithelial cells expressing Ki-67 antigen in the hyperplastic gingival tissues was more than 10% higher than that in the controls. The expression of Ki-67 antigen was suppressed in the typical rete pegs deeply elongated into lamina propria of hyperplastic gingival tissues. Intense immunostaining of Ki-67 antigen was found in fibroblasts of hyperplastic gingival tissues, while that of the control tissues was negligible. CONCLUSIONS: The expression of p53 protein in gingival hyperplasia suggests that the pathogenesis of this disease is involved with impaired DNA, while the growth arrest observed in the hyperplastic epithelia with typically elongated rete pegs as expressed with Ki-67 antigen may prevent the invasive expansion of epithelial cells undergoing DNA damage within gingival tissues and may consequently suppress tumorigenic progression.

Adolescent↗

[Development and evaluation of a new target heart rate formula for the adequate exercise training level in healthy subjects].

Little data is available recommending the adequate exercise level for physical fitness, so we hypothesized that the anaerobic threshold (AT) point is an ideal exercise level. We aimed to determine a new target heart rate formula for the adequate exercise training level in healthy subjects. This study first developed a new formula in 405 subjects (221 males, 184 females, mean age 48.9 +/- 12.3 years). The AT was determined during cycle ergometer exercise with continuous respiratory gas measurements. The correlation of heart rate at the AT to resting heart rate, age and gender was analyzed by the multiple regression method. Based on this correlation, a new formula calculating target heart rate was established as 74.8 + 0.76 x (resting heart rate) - 0.27 x (age) + 7.3 x S (male: 0 or female: 1). This formula was then compared to Blackburn's method in 210 subjects (139 males, 71 females, mean age 44.5 +/- 14.4 years). The difference between the new target heart rate and the heart rate at the AT was significantly lower than that between the target heart rate by Blackburn's method [(220 - age) x 0.7] and the heart rate at the AT (8.8 +/- 6.3 vs 12.7 +/- 8.2 beat/min, p < 0.001). The resting heart rate and gender are important factors in determining the target heart rate for exercise. This new formula indicates the adequate exercise training level more accurately in healthy subjects.

Adult↗

Simple technique of ligation and division of dorsal vein complex during radical retropubic prostatectomy.

A simple technique for ligation and division of the dorsal vein complex during radical retropubic prostatectomy is described. The dorsal vein complex and anterior wall of the membranous urethra were collectively ligated with a "theta theta" suture using 1-0 catgut and then divided during radical retropubic prostatectomy. This technique prevents dislodgment of the catgut during the procedure, enables maximal preservation of the striated urethral sphincter, and guarantees a lower risk of postoperative urinary incontinence.

Catgut↗

[Is hippocampal atrophy a specific change for Alzheimer's disease?].

Although detection of hippocampal atrophy has been proposed for the diagnosis of Alzheimer's disease (AD), atrophic changes in MRI can be found in other dementia diseases. This study was undertaken to determine whether hippocampal atrophy was a specific change for AD. Coronal T 1-weighted images were performed in 36 patients with AD, 40 patients with non-AD including vascular dementia, frontemporal dementia, Parkinson's disease with dementia, dementia with Lewy bodies, progressive supranuclear palsy, and normal pressure hydrocephalus, 9 patients with age-associated memory impairment (AAMI), and 24 control subjects. Hippocampal atrophy was graded subjectively on a 5-point scale. Scores of hippocampal atrophy for AD (2.11 +/- 0.95) and non-AD (1.80 +/- 0.91) were significantly higher than those for controls (0.79 +/- 0.72). Scores for AD were also significantly higher than those for AAMI (1.11 +/- 0.160), but no difference was found between AD and non-AD. These results suggest that hippocampal atrophy is not a specific marker for AD and appears to be a common phenomenon in dementia syndromes.

Aged↗

Establishment of the enzyme-linked immunosorbent assay for connective tissue growth factor (CTGF) and its detection in the sera of biliary atresia.

Connective tissue growth factor (CTGF) is a mitogenic, chemotactic, and cell matrix-inducing factor for fibroblasts. We generated murine monoclonal antibodies against CTGF and established a sandwich enzyme-linked immunosorbent assay (ELISA) for detection of CTGF. By using the ELISA, we confirmed that CTGF was specifically induced in human fibroblasts by TGF-beta but not by PDGF, FGF, IGF-I, or EGF. We also found that the serum levels of CTGF were significantly correlated with the progression of hepatic fibrosis in biliary atresia. These results indicated that CTGF is potentially a useful parameter for monitoring certain types of fibrotic disorders.

Biliary Atresia↗

Telomerase activity in renal cell carcinoma.

BACKGROUND: Telomerase activity has been shown to be increased in numerous tumors and cell lines, although to the authors' knowledge there has been no previous assessment of telomerase activity in renal cell carcinoma (RCC). To examine whether telomerase activity could be used as a biochemical parameter for predicting the behavior of RCC, telomerase activity was quantified in RCC samples and correlated with clinicopathologic findings. METHODS: Telomerase activity was quantified in 50 RCC samples and 21 samples of normal renal tissue using fluorescence-based telomeric repeat amplification. RESULTS: Telomerase activity was detected in 28 of 50 RCC samples (mean +/- standard deviation, 35.03 +/- 18.47 U/microg protein), whereas there was no telomerase activity in 21 normal renal tissue specimens. Telomerase activity in tumors classified as pT4 was significantly higher than in tumors classified as pT1 to pT3. Telomerase activity also correlated with patient age. CONCLUSIONS: Telomerase activity was increased in RCC samples compared with normal renal tissues. Although significant associations were observed between telomerase activity and clinicopathologic parameters, further study is required to determine whether telomerase activity affects the biologic and clinical behavior of RCC.

Adult↗