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Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 235 records · Page 13Linked to original sources
PubMed1996

Weight reduction regresses left ventricular mass regardless of blood pressure level in obese subjects.

The effects of weight reduction on left ventricular mass in obese normotensive and hypertensive subjects were investigated. Previous studies have shown that weight reduction in hypertensive (HT) obese patients is associated with decreased left ventricular mass (LVM) and decreased blood pressure (BP). This study was performed to examine whether weight reduction would also regress LVM in normotensive (NT) obese subjects and to clarify the mechanisms of these effects if they occurred. A weight-reduction program consisted of mild exercise and mild hypocaloric intake. M-mode echocardiography was performed to estimate the LVM. After the 12-week intervention, the mean reductions in body weight (BW) in the NT (n = 11) and HT (n = 11) groups were 4.9 kg (p < 0.005) and 4.6 kg (p < 0.0005), respectively. Systolic, diastolic, and mean BP were significantly reduced by 13, 9, and 11 mm Hg, respectively, in the HT group. By contrast, no significant changes in systolic, diastolic, or mean BP were observed in the NT group. LVM was significantly reduced from 176 +/- 26 gm to 159 +/- 26 gm (p < 0.05) in the HT group and from 167 +/- 33 gm to 145 +/- 34 gm (p < 0.02) in the NT group. These results suggest that weight reduction in obese subjects by mild exercise and mild hypocaloric intake can lead to a reduction in LVM, regardless of whether the subjects have normal or high blood pressure.

Adult↗
PubMed1996

Ca(2+)/calmodulin-dependent protein kinase II inhibitor KN-62 inhibits adrenal medullary chromaffin cell functions independent of its action on the kinase.

KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), inhibited significantly catecholamine secretion and tyrosine hydroxylase activity stimulated by acetylcholine in cultured bovine adrenal medullary cells. KN-62, however, showed an additional inhibitory effect on acetylcholine-induced 45Ca2+ influx, which is essential for functional responses. Carbachol-stimulated 22Na+ influx, veratridine-induced 22Na+ influx, and 56 mM K(+)-evoked 45Ca2+ influx were also attenuated by KN-62. Inhibitions by KN-62 of these ion influxes were correlated closely with those of catecholamine secretion. KN-04, which is a structural analogue of KN-62 but does not inhibit CaM kinase II activity, elicited inhibitory effects on the three kinds of stimulant-evoked ion influxes with an inhibitory potency similar to KN-62. These results suggest that KN-62 inhibits catecholamine secretion and tyrosine hydroxylase activation due to mainly its ion channel blockade on the plasma membrane rather than the inhibition of CaM kinase II activity in the cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Life-threatening cardiac involvement throughout life in a case of Costello syndrome.

Costello syndrome is characterized by poor postnatal growth, mental retardation, curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata. Patients with Costello syndrome have a high incidence of cardiac involvement, such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The importance of cardiac involvement in Costello syndrome has not been strongly emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both serious forms of cardiac involvement. We report the case of a Japanese girl with Costello syndrome, who experienced life-threatening cardiac involvement throughout her life.

Anus Neoplasms↗
PubMed1996

Salivary duct carcinoma: a clinicopathologic study of three cases with a review of the literature.

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located in the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intraductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comedolike necrosis was observed. Immunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S-100 protein, alpha-smooth muscle actin or muscle specific actin. Ultrastructurally, intracytoplasmic lumina with microvilli, a moderate number of mitochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of the patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be differentiated from low-grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.

Adenocarcinoma↗
PubMed1996

Effects of glucose deprivation on NMDA-induced current and intracellular Ca2+ in rat substantia nigra neurons.

1. The effects of glucose deprivation on N-methyl-D-asparate (NMDA)-induced current (INMDA) and the intracellular free Ca2+ concentration ([Ca2+]i) in the acutely dissociated rat substantia nigra neurons were investigated using the nystatin-perforated patch-clamp technique under voltage clamp and the microfluometry with a fluorescent probe, Indo-1. 2. Application of NMDA induced a peak and a successive steady-state inward current, and an outward current immediately after washout at a holding potential of -40 mV. The amplitudes of the three current components of INMDA were increased by increasing the concentrations of NMDA with half-maximum concentrations (EC50s) of 1.1 x 10(-4) M, 1.2 x 10(-4) M, and 1.6 x 10(-4) M, respectively. 3. The reversal potentials of the peak inward and outward currents were -4 +/- 3 (SE) mV and -76 +/- 2 mV, respectively. The latter was close to the theoretical K+ equilibrium potential (-82 mV). 4. The outward current was potentiated by increase in extracellular Ca2+ concentration and was blocked by Cs+ internal solution and suppressed by 5 x 10(-3) M tetraethylammonium chloride and 10(-7) M charybdotoxin, indicating that it was Ca(2+)-activated K+ current. 5. Application of NMDA increased [Ca2+]i in a concentration-dependent manner with an EC50 of 3.9 x 10(-5) M. 6. Depriving the external solution of glucose induced a slowly developing outward current and increased the basal level of [Ca2+]i. It also prolonged the NMDA-induced outward current without affecting the peak inward current, and prolonged the NMDA-induced increase in [Ca2+]i without changing the peak [Ca2+]i. 7. These findings suggest that the deprivation of glucose did not affect the NMDA-induced influx of Ca2+ into the cells, but it inhibited Ca2+ clearance by affecting the efflux of Ca2+ to the extracellular space, reuptake into the intracellular Ca2+ stores, and/or active extrusion from intracellular stores.

Animals↗
PubMed1996

Effects of dietary vegetable oils on behavior and drug responses in mice.

Previously, we noted significant differences in the behavioral patterns of mice fed safflower oil with a very low alpha-linolenate/linoleate ratio and perilla oil with a high alpha-linolenate/linoleate ratio from mothers to offsprings. In this report, we compared the behavior and drug responses in mice fed diets containing six different vegetable oils-corn, rapeseed, soybean, safflower, perilla and a mixture of perilla and safflower oils- for a relatively short period: 8 months after weaning. Soybean oil is a component of most conventional diets and was used as a control. The alpha-linolenate/linoleate ratios of the oils appeared to affect the locomotor activities in a wheel cage: the activity decreased in the order of safflower, the mixture (1:1) and the perilla oil groups. However, the rapeseed oil group exhibited much higher locomotor activity than that expected from the alpha-linolenate/linoleate ratio. Additionally, the rapeseed oil group exhibited unusual behavior patterns, including higher ambulation and rearing activities, faster acquisition of the water maze task and slower habituation behavior as compared with the control group. Susceptibility to pentobarbital anesthesia tended to be higher in the rapeseed oil group. The differences in the alpha-linolenate/linoleate ratios of these oils alone do not account for the observed differences in the behavioral patterns among the six dietary groups. Although we cannot exclude the possibility that the observed behavioral anomaly is due to the unique fatty acid composition of rapeseed oil, we speculate that a factor(s) other than fatty acids in rapeseed oil affected nervous system functions.

Analgesics↗
PubMed1996

Biliary hamartomas simulating multiple hepatic metastasis on imaging findings.

We encountered a 62-year-old female with advanced gastric cancer, in whom multiple nodular lesions in the liver, which were depicted as small low density areas, less than 5 mm in diameter, on computed tomography and demonstrated as a heterogenic pattern on ultrasonograms. This patient was suspected to have multiple liver metastases of gastric cancer. She deteriorated gradually and died of respiratory failure due to lung metastasis. At autopsy these hepatic nodular lesions were biliary hamartomas. Biliary hamartoma is a lesion usually identified microscopically, and there have been only 8 cases including ours, which were depicted on images. Along with a remarkable advance in imagings, it should become more important to differentiate biliary hamartoma from malignant hepatic neoplasms on images.

Bile Duct Diseases↗
PubMed1996

Role of tissue inhibitors of metalloproteinase in diabetic nephropathy.

We evaluated the role of tissue inhibitors of metalloproteinase-1 (TIMP-1) in patients with diabetic nephropathy by comparing the serum and urine TIMP-1 levels with those of renal biopsy specimens. A total of 35 diabetic patients were divided into four groups, D0, DI, DII and DIII-IV, according to the severity of diffuse glomerular lesions using Gellman's criteria. Using serum and 24-hour urine specimens, TIMP-1 was measured by a sandwich enzyme immunoassay. Serum and urinary TIMP-1 showed significant increases in association with the progress of glomerular diffuse lesions. There was no correlation between serum TIMP-1 and serum creatinine, creatinine clearance, serum and urinary beta 2-microglobulin, urinary NAG, HbA1c, or urinary TIMP-1. There was a significant correlation between urinary TIMP-1 and urinary albumin, and was a significant correlation between urinary TIMP-1 and urinary NAG. We conclude that TIMP-1 has a potential role in the regulation of glomerular matrix accumulation in diabetic nephropathy.

Adult↗
PubMed1996

Induction of renal cell carcinoma in male Wistar rats treated with cupric nitrilotriacetate.

Systemic administration of copper, an essential trace metal in the human body, has never been reported to be carcinogenic in animals. We investigated the induction of tumors by the cupric complex of nitrilotriacetic acid (Cu-NTA) in male Wistar rats. Thirty-two animals received ip injections of Cu-NTA, 3 to 5 mg of copper/kg body weight 5 days a week for 12 weeks, and were kept under close observation. For comparison, 31 animals received ip injections of ferric nitrilotriacetate (Fe-NTA), 5 to 10 mg of iron/kg body weight, and 16 animals received nitrilotriacetic acid (NTA) alone at the molar dose equivalent to Cu-NTA for the same period of time. Sixteen animals were left untreated as controls. Fourteen animals in the Cu-NTA group died of hepatic failure during the treatment period, and renal cell carcinoma (RCC) was induced in eight animals (25%). Of these, four animals died of either pulmonary metastasis or intraperitoneal hemorrhage. A total of 12 RCC were obtained, of which six tumors were > or = 5 mm. The Cu-NTA group yielded fewer RCC and required a longer latent period for their incubation than the Fe-NTA group. Furthermore, the Cu-NTA group showed one hepatocellular carcinoma and one high-grade sarcoma of hepatic origin. No renal or hepatic tumor was observed in the NTA or control groups. The nontumorous part of the kidney treated with Cu-NTA presented hemosiderosis caused by copper-induced hemolytic anemia. This is the first report that systemic administration of copper compounds can induce malignant tumors in animals. Not only copper but also iron may play a role in the Cu-NTA-induced renal carcinogenesis model.

Animals↗
PubMed1996

Characterization of in vivo gene transfer into the arterial wall mediated by the Sendai virus (hemagglutinating virus of Japan) liposomes: an effective tool for the in vivo study of arterial diseases.

Recently, much attention has been paid to the arterial gene transfer technique using several vector systems. In the present study, we experimentally examined the transfection efficiency of the exogenous gene, the duration of gene expression, and the cytotoxic effect of the hemagglutinating virus of Japan (HVJ) liposome on the intact arterial wall to evaluate its effectiveness for the study of arterial diseases. To evaluate the transfection efficiency and duration of gene expression, pSV beta-galactosidase was transferred into the carotid arterial wall of rabbits. The cytotoxic effect of HVJ liposomes on the vascular cell components was also evaluated by a neutral red assay in vitro and scanning electron microscopy in vivo. HVJ liposomes could achieve highly efficient gene transfection into the medial smooth muscle cells of intact arteries at 150 and 760 mmHg of pressure (mean = 85.3% and 93.5% of total smooth muscle cells, respectively) without any inflammatory reaction. The introduced exogenous gene was expressed for at least 14 days. In addition, the cytotoxicity for the arterial smooth muscle cells and endothelial cells induced by HVJ liposome vehicles at routinely used concentrations (5,000 to 10,000 hemagglutinating activity units/ml) was minimal both in vitro and in vivo. As an example, we introduced human vascular endothelial growth factor cDNA, which was driven with cytomegalovirus enhancer and beta-actin promoter, into the rabbit carotid arteries, and it induced not only angiomatoid proliferation of endothelial cells forming irregular vascular channels but also intimal hyperplasia. Based on these findings, we conclude that HVJ liposome-mediated arterial gene transfer is a highly efficient, noninvasive, and effective gene delivery method for the study of vascular disorders.

Animals↗
PubMed1996

[The mechanism of controlling regional cerebral blood flow in patients with localization-related epilepsy].

INTRODUCTION: Hypoperfusion around the seizure foci has been reported in interictal CBF studies of partial epilepsy. Hypoperfusion may reflect some interictal pathophysiology characteristic of epilepsy, but the mechanism remains to be elucidated. In order to elucidate the controlling system of rCBF in patients with CPS (complex partial seizure), we measured by positron emission tomography rCBF and CO2 vasoreactivity performing a hyperventilatory task, and made comparisons between the affected and contralateral sides of the temporal lobes in CPS patients and the temporal lobe of normal volunteers. We also measured PaCO2, pH, PaO2 and respiratory rate at rest to elucidate the CBF maintaining system. SUBJECTS: 15 volunteers and 12 medically controlled patients with CPS were examined. The affected side of the brain of the patients was determined by dominance of EEG paroxysm. METHOD: For measuring rCBF, the Shimadzu HEADTOME-IV system (8mm FWHM) and H2(15)O (740-1480 [MBq]/scan) bolus injection method were employed. First a rest scan, then a hyperventilatory task scan was performed, at 20 min. intervals between each scan. During the rest scans, the subjects were required to close their eyes, which were covered through the transmission scan and all the other scans. They were monitered with EEG to insure that they were not asleep. Room lights were dimmed, room sounds were kept to a minimum and noises were damped with earplugs. During the hyperventilatory tasks, the subjects were asked to inspire deeply at a rate of 15/min. for 4.5 min. from 3 min. before the scan up to the end of the 1.5 min. scan, and monitored with a respiratory band around the abdomen. Arterial blood gas pressures (PaCO2, pH and PaO2) were also measured with a blood gas analyzer (Radio Meter ABL 330) at the beginning and at the end of the scans. [HCO3-] was calculated on the formula of Henderson-Hasselbalch. Vascular response to PaCO2 change: VrCO2 was defined as follows: VrCO2 = 100 x (CBFh-CBFr)/CBFr/(PaCO2h-PaCO2r) the subscripts h: hyperventilatory r: resting conditions. RESULTS: Blood gasses, rCBF and corrected-rCBF at rest: In the patients, PaCO2 (mmHg) = 46.11 +/- 2.32, pH = 7.374 +/- 0.020, [HCO3-] (mEq/ml) = 25.98 +/- 1.15, CBF (ml/100g/min) = 45.51 +/- 9.33, corrected-CBF (ml/100g/min) = 40.06 +/- 7.27. In the volunteers, PaCO2 = 40. 67 +/- 2.37, pH = 7.400 +/- 0.021, [HCO3-] = 24.36 +/- 1.66, CBF = 48.76 +/- 8.54, corrected-CBF = 48.02 +/- 9.04. PaCO2 and [HCO3-] in the patients were significantly higher than those in the volunteers. pH and corrected-CBF were significantly lower than those in the volunteers. CBF showed no difference. VrCO2 in the temporal lobe: In the affected side of the patients, VrCO2 = 1.976 +/- 0.54. In the contralateral side of the patients, VrCO2 = 2.145 +/- 0.667. In the temporal lobe of the volunteers, VrCO2 = 2.557 +/- 0.898. In both sides of the temporal lobe of the patients, VrCO2 was significantly lower than those in the volunteers. COMMENTS: The effect of anticonvulsant drugs and the suppressive mechanism around the foci are supposed to reduce CBF of CPS patients. We suppose another mechanism, which is vasoconstriction. A significant difference was noted in CO2-vasoreactivity in the temporal lobe between patients and volunteers. Also no difference was noted in rCBF in the temporal lobe between the volunteers and the patients, when the arteries were maximally constricted with the HIV-task. These two results suggest that vasoconstrictive mechanism may be among the factors for the hypoperfusion seen in the temporal lobe of the patients. In patients, PaCO2, [H+], [HCO3-] were significantly higher compared with the volunteers, which suggests the mechanism of respiratory acidosis. Owing to this hypercapnia, global CBF in the patients is maintained in compensation for the hyperfusion and vasoconstriction seen around the foci. CO2 acts as an anticonvulsant and also reduces glucose metabolites which accumulate around the foci.

Adult↗
PubMed1995

Increased susceptibility of angiographically smooth left anterior descending coronary artery to an impairment of vasoresponse to acetylcholine, and the relation between impaired vasoresponse and low-density lipoprotein cholesterol level.

In the present study, we demonstrated that the angiographically smooth LAD is more susceptible than the LC to an impairment of vasoresponse to acetylcholine, suggesting the more severe endothelial dysfunction in the LAD. We also showed that levels of LDL play a partial but important role on endothelial dysfunction.

Acetylcholine↗
PubMed1995

Effect of lidocaine on alpha 1-adrenoceptors in cultured neonatal rat cardiocytes.

The effect of lidocaine on alpha 1-adrenoceptors in cultured neonatal rat ventricular cardiocytes was studied by binding assay. When the cells were cultured in the presence of lidocaine, the binding of (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone to the cells increased in a concentration- and time-dependent manner. The effect was due to an increase in maximum binding but not due to a change in the dissociation constant for the ligand. The increased number of alpha 1-adrenoceptors returned to the control level after culturing the cells without lidocaine. The stimulating effect on the number of alpha 1-adrenoceptors of lidocaine was also observed in the presence of norepinephrine. Other class I antiarrhythmic drugs such as procainamide. disopyramide, mexiletine and flecainide increased the number of alpha 1-adrenoceptors in the cells. These results suggest that cardiac responsiveness mediated by alpha 1-adrenoceptors is increased by class I antiarrhythmic drugs.

Adrenergic alpha-Antagonists↗
PubMed1995

Mucopolysaccharidosis type IVA: common double deletion in the N-acetylgalactosamine-6-sulfatase gene (GALNS).

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency in N-acetylgalactosamine-6-sulfatase (GALNS). We found two separate deletions of nearly 8.0 and 6.0 kb in the GALNS gene, including some exons. There are Alu repetitive elements near the breakpoints of the 8.0-kb deletion, and this deletion resulted from an Alu-Alu recombination. The other 6.0-kb deletion involved illegitimate recombinational events between incomplete short direct repeats of 8 bp at deletion breakpoints. The same rearrangement has been observed in a heteroallelic state in four unrelated patients. This is the first documentation of a common double deletion a gene that is not a member of a gene cluster.

Base Sequence↗
PubMed1995

Comparison of bone-implant interface shear strength of hydroxyapatite-coated and alumina-coated metal implants.

We performed a transcortical push-out test to determine the effect of surface roughness of hydroxyapatite (HA)-coated implants on bone-implant shear strength in a canine model. Hydroxyapatite- and alumina-coated SUS316L with the same surface roughness (roughness average: Ra = 5 microns) and HA-coated Ti-6A1-4V (Ra = 8.4 microns), sintered HA (Ra = 0.9 micron), and dense alumina (Ra = 1.3 microns) were inserted into the dog's femur. The interface shear strength of the dense alumina was significantly lower than that of other implants at both 4 and 12 weeks after implantation. At 4 weeks after implantation, the interface shear strength of the alumina-coated SUS316L was significantly lower than that of other implants (P < .05) except the dense alumina, but at 12 weeks, there was no significant difference between the implant types except the dense alumina. This indicates that the surface roughness of the HA coating affects the enhancement of the bone-implant interface shear strength at the early period after implantation, and that a surface roughness of several micrometers does not influence the bond strength between bone and HA. A scanning electron microscopic study indicated that in almost all cases at 12 weeks, the failure site after push-out testing was the coating-substrate interface, not the coating-bone interface. Therefore, protection of the coating-substrate interface from direct shear loading is needed.

Alloys↗
PubMed1995

Conditioned media of carcinoma cells cultured in hypoxic microenvironment stimulate angiogenesis in vitro; relationship to basic fibroblast growth factor.

Conditioned media (CM) harvested from human pulmonary squamous cell carcinoma (QG56), pulmonary small cell carcinoma (QG90) and gastric adenocarcinoma (MKN28) cultivated under hypoxic conditions (3% oxygen), enhanced the angiogenic activity in vitro more than those obtained under normoxic cultivation (20% oxygen). The total length of the tube structures formed by bovine capillary endothelial cells (BCEs) in the CM cultured at 3% oxygen was about 1.5 (QG56 and MKN28) or 1.9 (QG90) times longer than that at 20% oxygen. Tube formation was diminished by the preincubation of CM with anti-basic fibroblast growth factor (bFGF) IgG. After performing the fractionations of the CM and the crude extracts of cell lysates cultured using a heparin-Sepharose column, the mitogenic activity in the CM from all cancer cells at 3% oxygen was about twice that of CM at 20% oxygen, while it decreased in the cell lysates at 3% oxygen to about 40% of those at 20% oxygen. This mitogenic activity of BCEs in the CM from all cancer cells was almost totally suppressed by anti-bFGF IgG, but not with anti-vascular endothelial growth factor IgG. Hypoxia is an important factor in tumor angiogenesis by bFGF or bFGF-like molecule(s) derived from tumour cells.

Animals↗