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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 613 records · Page 34Linked to original sources
PubMed1994

In vitro selection of optimal DNA substrates for ligation by a water-soluble carbodiimide.

We have used in vitro selection to investigate the sequence requirements for efficient template-directed ligation of oligonucleotides at 0 degrees C using a water-soluble carbodiimide as condensing agent. We find that only 2 bp at each side of the ligation junction are needed. We also studied chemical ligation of substrate ensembles that we have previously selected as optimal for ligation by RNA ligase or by DNA ligase. As anticipated, we find that substrates selected with DNA ligase ligate efficiently with a chemical ligating agent, and vice versa. Substrates selected using RNA ligase are not ligated by the chemical condensing agent and vice versa. The implications of these results for prebiotic chemistry are discussed.

Base Sequence↗
PubMed1994

Renal clearance of lomefloxacin is decreased by furosemide.

The interaction between lomefloxacin, a new quinolone, and furosemide, a loop diuretic, has been examined. Oral lomefloxacin 200 mg and furosemide 40 mg were given together or separately to 8 healthy subjects, and blood and urine samples were obtained over the following 12 h. The plasma concentrations of lomefloxacin following coadministration with furosemide were higher than after lomefloxacin alone and its AUC was increased, and its total and renal clearances were decreased. No change in the pharmacokinetics of furosemide was found after coadministration of lomefloxacin. As quinolones and furosemide are reported to be excreted in urine by the renal tubular anion transport system, the present results suggest that the renal tubular secretion of lomefloxacin is diminished by furosemide. It is not clear whether this pharmacokinetic interaction might be clinically important.

Adult↗
PubMed1994

A case of meningioangiomatosis without von Recklinghausen's disease. Report of a case and review of 13 cases.

Meningioangiomatosis is rare disease and is classified as hamartoma in central neurofibromatosis. Unlike most cases of meningioangiomatosis, the very rare case reported here was not associated with von Recklinghausen's disease. We could find only 12 previous cases reported in the literature. A review was carried out of the clinical features, imaging characteristics, and histopathological findings in those 12 plus ours for a total 13 cases. Several types of convulsion were identified as clinical symptoms in 11 of the 13 cases. They were treated surgically. Prognosis was satisfactory in most cases. Proliferation of small blood vessels accompanied by endothelial cells with glial tissue as background and proliferation of fibroblasts or meningothelial cells in the perivascular space were observed to be the most frequent histopathological features.

Adolescent↗
PubMed1994

MRI-based quantitative assessment of the hippocampal region in very mild to moderate Alzheimer's disease.

We investigated the hippocampal region in six patients diagnosed with possible Alzheimer's disease (AD), eight patients with probable AD, and eight age-matched controls, using a high-resolution magnetic resonance imaging technique. Coronal T1-weighted images were used for area measurements of the hippocampal formation (HF), parahippocampal gyrus (PHG), and temporal lobe (TL), normalised to cranial area. Both the normalised HF and PHG were significantly smaller in both AD groups than in the controls, but did not differ between patients with possible and probable AD. The normalised TL was significantly smaller in patients with probable AD than in those with possible AD and controls, but did not differ in patients with possible AD and controls. We conclude that hippocampal and parahippocampal atrophy occurs in early AD, and is more useful than neocortical atrophy for early detection of the disease. At a more advanced stage, the neocortical area is involved.

Aged↗
PubMed1994

Growth inhibition of subcutaneously transplanted human glioma by transfection-induced tumor necrosis factor-alpha and augmentation of the effect by gamma-interferon.

Using subcutaneous solid tumors produced by U251-MG human glioma cells, we studied the in vivo transfection of the cells with the tumor necrosis factor-alpha (TNF-alpha) gene delivered by means of liposomes. When the tumor had become 7 mm in diameter, liposomes with entrapped TNF-alpha gene were injected into the center of the subcutaneous tumor. We found that mRNA of transfection-induced TNF-alpha, which was expressed in the tumor tissue, was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) method and its protein was demonstrated by enzyme-linked immunoassay. Growth of the tumor was inhibited when the injection was carried out five times at every other day. The growth-inhibitory effect by transfection-induced TNF-alpha was much remarkable as compared with exogenous TNF-alpha and the effect was enhanced by the intraperitoneal injection of gamma-interferon (IFN-gamma) 12 h prior to intratumoral injection of the liposomes.

Animals↗
PubMed1994

Cardiomyopathy and angiopathy in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.

In four patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) in which mutated mitochondrial deoxyribonucleic acid was seen, hypertrophic cardiomyopathy and angiopathy was demonstrated by echocardiography, dipyridamole stress scintigraphy, and cardiac catheterization. On stress scintigraphy with dipyridamole, three patients showed hypoperfusion in the early image and a "filling-in" pattern in the late image. However, coronary angiography did not demonstrate narrowing of the large vessels in these patients. Light and electron microscopy of endomyocardial biopsy specimens indicated abnormal mitochondria, with marked increase in the number and size of mitochondria in endothelium. Modified Gomori's trichrome staining in biopsied endomyocardial specimens revealed a red-purple deposit similar in appearance of the ragged-red fibers in skeletal muscle, a characteristic finding of mitochondrial disease. Deterioration of complex I in the mitochondrial electron transfer system, which is widely observed in various mitochondrial diseases, appeared in biopsied skeletal muscle of our patients, indicating deficiency of some subunits of complex I. These results indicate that mitochondrial diseases such as MELAS show not only cardiomyopathy but also angiopathy. We speculate that proliferation of mitochondria leads to narrowing of the lumen of arterioles, which might be responsible for the ischemic findings observed scintigraphically.

Adolescent↗
PubMed1994

Elevated serum and urinary thrombomodulin levels in patients with non-insulin-dependent diabetes mellitus.

Increased plasma levels of soluble thrombomodulin have been reported in several disorders as a marker for vascular endothelial damage. Serum and urinary thrombomodulin levels were measured in 79 patients with non-insulin-dependent diabetes mellitus. Both levels were significantly higher (23.5 +/- 6.1 ng/ml and 146.6 +/- 64.9 ng/ml, respectively) than those of normal healthy controls (18.8 +/- 3.1 ng/ml, P < 0.001, and 96.8 +/- 60.3 ng/ml, P < 0.01). Serum thrombomodulin levels increased in keeping with urinary albumin levels. In urine thrombomodulin was lower in the macroalbuminuria group than in the microalbuminuria group, suggesting two mechanisms: intravascular overproduction and impaired renal clearance. Both serum and urinary thrombomodulin levels in diabetic patients might be predictors for very early nephropathy.

Adult↗
PubMed1994

Dextran sulfate, a competitive inhibitor for scavenger receptor, prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Dextran sulfate competes with binding of modified LDL to the scavenger receptor in macrophages. To elucidate the role of dextran sulfate in the atherosclerotic process, 100 mg of dextran sulfate in drinking water was given to 5 Watanabe heritable hyperlipidemic (WHHL) rabbits for 12 months starting at age 4 months. During the experimental period, there were no significant differences in plasma cholesterol levels between dextran sulfate-treated and untreated rabbits. After 12 months' treatment, accumulation of cholesterol ester in total aorta was significantly suppressed in dextran sulfate-treated rabbits as compared with untreated rabbits (71.4 +/- 22.3 vs. 42.7 +/- 16.5 mg/g dry weight, P < 0.05). Furthermore, lesion area with atherosclerotic plaques in treated rabbits was significantly less than that in untreated rabbits (59.7 +/- 24.5 vs. 30.4 +/- 14.4%, P < 0.05). These results indicate that dextran sulfate might prevent the progression of atherosclerosis by competitively inhibiting the binding of modified LDL to scavenger receptors.

Animals↗
PubMed1994

Olivopontocerebellar atrophy studied by positron emission tomography and magnetic resonance imaging.

We examined 9 patients with olivopontocerebellar atrophy (OPCA) using positron emission tomography and magnetic resonance imaging (MRI). Regional cerebral blood flow and oxygen metabolism were compared with the findings in 10 normal age-matched volunteers. The volumes of the basis pontis and the cerebellar hemispheres were quantitated by MRI to assess the relationship between morphological changes of the pons or cerebellum and the cerebellar circulation and metabolism. In the patients with OPCA, cerebellar hemispheric blood flow and oxygen metabolism were significantly lower than in the normal volunteers. Pontine volume showed a significant correlation with the cerebellar blood flow and the metabolic rate of oxygen. In contrast, the cerebellar hemispheric volume showed no correlation with either of these parameters. Our results suggest that the disruption of pontocerebellar pathway may contribute to the reduction of both blood flow and oxygen metabolism in the cerebellum of OPCA and that detection of cerebellar circulatory impairment without marked cerebellar atrophy by neuroimaging may be suggestive of OPCA.

Adult↗
PubMed1994

A clean-up method for analysis of trace amounts of microcystins in lake water.

A clean-up method using high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) was developed to pursue trace amounts of microcystins in lake water. The method consisted of the combined usage of octadecyl silanized (ODS) silica gel and silica gel cartridges. In the first clean-up process, the retention behavior of microcystin RR on ODS silica gel cartridge was carefully observed together with microcystin LR, and 10% water-methanol was chosen as the best solvent system to elute microcystins from the ODS silica gel cartridge. Because many impurities still remained in the desired fraction from the raw water even after the clean-up with ODS silica gel, an additional clean-up process was developed using various cartridges. As a result of extensive experiments, the second clean-up process using silica gel cartridge was established, and the impurities were effectively eliminated. The present method including a tandem cartridge system allowed a precise analysis of microcystins in water samples from three different lakes at a 0.02 ppb level.

Chromatography, High Pressure Liquid↗
PubMed1994

Clinical evaluation of 33 patients with histologically verified germinoma.

We evaluated 33 patients with histologically verified germinoma between 1978 and 1992. The patients consisted of 23 men and 10 women between 6 and 32 years of age. All patients underwent either biopsy, partial resection, or total resection. All patients received radiotherapy, and all had a complete remission. Recurrence occurred in three patients. Two recurrences were outside of the irradiated area. Though there were four deaths, none were caused by germinoma. Three resulted from the inadequate hormonal replacement. Accurate staging of patients with germinoma using magnetic resonance imaging (MRI), including whole spinal MRI, and development of a radiochemotherapy or chemotherapy method that preserves the hypothalamic-pituitary axis function are needed.

Adolescent↗
PubMed1994

Plasma lipid abnormalities and risk factors for coronary artery disease in Japanese subjects with diabetes mellitus and glucose intolerance.

We evaluated the plasma lipid levels of 3163 subjects including subjects with non-insulin-dependent diabetes mellitus (NIDDM), insulin-dependent diabetes mellitus (IDDM), impaired glucose tolerance (IGT), and normal glucose tolerance. Furthermore, we performed 100 g oral glucose tolerance tests on 2113 subjects, and analyzed the relationships of risk factors for coronary artery disease to glucose intolerance. Mean plasma cholesterol and triglyceride levels were highest in NIDDM (213 mg/dl and 148 mg/dl), and plasma HDL-cholesterol level was lowest in IGT and NIDDM (42 mg/dl), as compared to those in normal subjects (cholesterol, 200 mg/dl; triglycerides, 109 mg/dl; HDL-cholesterol, 52 mg/dl). Multiple regression analysis demonstrated a significant relationship of either blood pressure, plasma triglyceride or HDL cholesterol level to plasma insulin and glucose response after glucose loading.

Adult↗
PubMed1994

Effect of freeze-dried poly-L-lactic acid discs mixed with bone morphogenetic protein on the healing of rat skull defects.

Porous poly-L-lactic-acid discs were prepared by a freeze-drying method (FDPLLA). During preparation of the discs, semipurified bone morphogenetic protein (BMP) was mixed with the poly-L-lactic acid (500 micrograms BMP per disc). The discs were implanted in the skull defects of rats and retrieved after 2 or 4 weeks. With the FDPLLA/BMP discs, new bone formation was observed at 2 weeks after implantation. On the other hand, plain FDPLLA discs failed to produce new bone formation even at 4 weeks after implantation. Calcium content of the retrieved FDPLLA/BMP discs was statistically higher than that of plain FDPLLA discs. These results suggest that FDPLLA may be an effective delivery system for BMP and that the FDPLLA/BMP disc may potentially have usefulness as a bone graft substitute.

Animals↗
PubMed1994

Effect of KRN2391 on canine ventricular arrhythmia models.

1. KRN2391 (3-30 micrograms/kg, i.v.) produced a decrease in mean blood pressure (MBP) with concomitant increase in heart rate (HR) and change in electrocardiogram (ECG) such as the shortening of PP and PQ intervals and the prolongation of QTc and these changes in HR and ECG were attenuated by pretreatment with propranolol (1 mg/kg) in normal dogs. 2. KRN2391 at 30 micrograms/kg induces neither suppression nor aggravation of ventricular arrhythmias caused by adrenaline and digitalis. 3. In two-stage coronary ligation-induced arrhythmia, KRN2391 inhibited arrhythmia at 48 hr. 4. These results suggest that KRN2391 may be effective on arrhythmia related to ischemia. In addition, it is considered that arrhythmia is not induced even by a high dose of KRN2391 in the normal condition.

Animals↗
PubMed1994

Pharmacological analysis of the inhibitory effects of KRN2391 on endothelin-1-induced contraction in isolated large coronary artery of the pig.

1. The relaxant effect of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridine-carboximidamide-mo nomethanesulfonate (with both K+ channel opener and nitrate actions), nifedipine (Ca2+ channel blocker), nitroglycerin (nitrate) and cromakalim (K+ channel opener) were investigated in isolated porcine large coronary arteries contracted by endothelin-1. These drugs inhibited endothelin-1-induced contraction in a concentration-dependent manner. 2. The relaxation induced by KRN2391 was nearly complete at their maximum effects, but nifedipine and cromakalim could not produce complete relaxation. 3. The concentration-relaxation curves for KRN2391 underwent a rightward shift in the presence of methylene blue or glibenclamide. The concentration ratios of KRN2391 calculated based on EC50 values were 2.8 and 3.7 in the presence of methylene blue and glibenclamide, respectively. 4. The concentration-relaxation curves for nitroglycerin and cromakalin underwent a rightward shift in the presence of methylene blue and glibenclamide, respectively, and the concentration ratios of nitroglycerin and cromakalim were 12.0 and 6.3. 5. These relaxant effects of KRN2391 and nitroglycerin on endothelin-1-induced contraction of porcine coronary artery were greater than those of cromakalim and nifedipine. This potent relaxant action of KRN2391 on endothelin-induced contraction is thought to be based on both a nitrate action and a K+ channel opening action.

Animals↗
PubMed1994

Delayed myelination in a patient with 18q- syndrome.

A Japanese boy with the typical manifestations of 18q-syndrome and delayed myelination on magnetic resonance imaging is described. Cytogenetic investigation revealed a deletion at 18q21.3. Three serial magnetic resonance images demonstrated that myelination in the central nervous system was delayed except for the corpus callosum and brainstem. This pattern of delayed myelination appears to be peculiar to the 18q- syndrome. Because the gene for myelin basic protein has been localized to the distal end of the long arm of chromosome 18, we speculate that the abnormal myelination in our patient was partly due to the failure of expression of the myelin basic protein gene.

Brain↗
PubMed1994

Type VII collagen DNA linkage analysis in a Japanese family with dominant dystrophic epidermolysis bullosa.

Type VII collagen, a major component of anchoring fibrils in the basement membrane zone, is now considered to be a primary genetic factor in the pathogenesis of dominant dystrophic epidermolysis bullosa (DDEB). In this study, we performed genetic linkage analysis in a Japanese family with DDEB using a PvuII polymorphism in the type VII collagen gene. The pedigree consisted of 10 affected and 13 unaffected living individuals and was diagnosed as having Cockayne-Touraine type of DDEB. Electron microscopic examination of the skin demonstrated a diminished number and rudimentary structure of anchoring fibrils. PCR-based detection of PvuII polymorphism resulted in 3 genotypes and co-segregated with DDEB phenotype in this pedigree. The maximum lod score was 2.10 at recombination fraction (theta) of 0. The absence of recombination between DDEB and type VII collagen gene locus, as well as the observation of altered anchoring fibrils, suggested that type VII collagen is a candidate gene for the Japanese family with DDEB, although the lod score was statistically not significant.

Base Sequence↗