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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 217 records · Page 12Linked to original sources
PubMed2000

beta-cyanoalanine production by marine bacteria on cyanide-free medium and its specific inhibitory activity toward cyanobacteria.

In screening the culture broth of marine bacteria collected at Yap (Micronesia), Palau (Belau), and Okinawa (the southwest islands of Japan) for antimicroalgal activity, 37 out of 2,594 bacterial isolates tested were found to produce anticyanobacterial substances against Oscillatoria amphibia NIES-361. One strain, C-979, identified as a Vibrio sp., was selected and cultured in 2.4 liters of marine broth 2216 to identify the bioactive compound produced by the strain. The purified very hydrophilic compound (16.4 mg) was determined to be beta-cyano-L-alanine (L-CNAla) by instrumental analyses and the application of the advanced Marfey method. L-CNAla did not inhibit the growth of bacteria, yeast, or eukaryotic microalgae, but some cyanobacteria were found to be sensitive to L-CNAla at a concentration of 0.4 to 25 microg/ml. The effect of L-CNAla on some other environmental organisms, including invertebrates and a macroalgae, is discussed. CNAla production in marine broth was examined by thin-layer chromatography for the 37 bacterial isolates which produced an anticyanobacterial substance. The broth of 36 of these strains contained CNAla, suggesting the wide distribution of CNAla production by marine bacteria. This is the first report on bacteria that produce CNAla without a supply of the cyanide ion in the medium.

Alanine↗
PubMed2000

Diffusional anisotropy in cranial nerves with maturation: quantitative evaluation with diffusion MR imaging in rats.

PURPOSE: To investigate the correlation between diffusional anisotropy and developmental changes in anatomy, which include myelination, in central and peripheral nerves in an animal model by using quantitative diffusion magnetic resonance (MR) imaging and electron microscopy. MATERIALS AND METHODS: In vivo transverse and longitudinal apparent diffusion coefficients (ADCs) of the optic and trigeminal nerves in 2-10-week-old rats were measured with MR imaging. Then the animals were sacrificed at each time point, and transverse and longitudinal sections of optic and trigeminal nerves were studied with electron microscopy. RESULTS: In the optic nerve, the ADC parallel to the neurofibers increased with development and increased contemporaneously with myelination, while the ADC perpendicular to the nerve did not change. This resulted in a significant increase in diffusional anisotropy. There were no significant changes in ADCs in either direction in the trigeminal nerve. Longitudinal sections of optic nerve showed a marked change in the orientation of each fiber. As development proceeded, the axons, which initially followed tortuous courses, assumed straighter and more parallel orientations. Trigeminal nerves displayed straight parallel courses at 2 weeks that did not change over the study period. CONCLUSION: Changes in fiber anatomy in maturation from tortuous to straighter and more parallel orientation can account for changes in longitudinal ADC and in diffusional anisotropy.

Animals↗
PubMed2000

Effects of pegylated recombinant human megakaryocyte growth and development factor on 5-fluorouracil-induced thrombocytopenia in balloon-injured rats.

We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) affected 5-fluorouracil-induced thrombocytopenia without inducing more severe intimal thickening after injury to rat carotid arteries. Rat carotid arteries were injured using a balloon catheter on day 0. 5-Fluorouracil (100 mg kg(-1)) or vehicle was intravenously administered on day 1 in balloon-injured rats. PEG-rHuMGDF (100 microg kg(-1)) or vehicle was intravenously administered once a day on days 1-5 to balloon-injured rats given 5-fluorouracil or vehicle. 5-Fluorouracil (100 mg kg(-1), i.v.) caused a significant decrease in the platelet count from day 3 and peaked on days 7-9 in balloon-injured rats. PEG-rHuMGDF (100 microg kg(-1), i.v.) reduced this decrease on days 9 and 11. The administration of PEG-rHuMGDF did not accelerate the intimal thickening of balloon-injured arteries in rats treated with 5-fluorouracil compared with control balloon-injured rats. PEG-rHuMGDF did not increase plasma tumour growth factor-beta1 (TGF-beta1) from days 0-9 in balloon-injured rats compared with control balloon-injured rats. These results suggest that PEG-rHuMGDF ameliorated 5-fluorouracil-induced thrombocytopenia without accelerating the intimal thickening of balloon-injured arteries.

Animals↗
PubMed2000

Quantitative structure-activity relationship study of N-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)guanidines as potent Na/H exchange inhibitors.

We have previously reported that N-(4-isopropyl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-car bonyl)guanidine (4b) methanesulfonate salt (KB-R9032) is a potent and highly water-soluble Na/H exchange inhibitor. In a series of studies on Na/H exchange inhibitors, we designed and synthesized N-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)guanidines (5) as more potent inhibitors with high water-solubility. The design strategy for 5 was based on a quantitative structure-activity relationship (QSAR) study, involving the proportional relationship between the biological activity and hydrophobicity of the ring structure of compounds 4. As expected, compounds 5 showed more potent activity than 4. It was found by using the QSAR analysis that 5 were about five-fold more potent than 4. The increase in potency of compounds 5 well agreed with our previous QSAR analysis result. The most potent derivative was the methanesulfonate salt 5d of the 4-isopropyl derivative (IC50=0.0091 microM). And in addition to the in vitro study, 5d showed significant protective activity against a rat acute myocardial infraction model.

Animals↗
PubMed2000

[A Japanese language version of the health-promoting lifestyle profile].

The development and initial psychometric evaluation of a Japanese version of the Health-Promoting Lifestyle Profile II (HPLP II) is described. The 52-item instrument was translated into Japanese and was found to be culturally relevant and reliable in a pilot study. The Japanese version was then administered to adiverse but predominantly Japanese group of 337 subjects residing in northern Japan. The Japanese version of the HPLP II was evaluated using factor analysis and reliability measurement. Six factors similar to those isolated previously during psychometric assessment of the English language version were extracted. Those six dimensions comprise the HPLP II subscales of: 1. Health responsibility, 2. Spiritual growth, 3. Physical activity, 4. Interpersonal relations, 5. Nutrition, and 6. Stress management. The alpha reliability coefficient for the total scale was 0.94 and the 2-week retest reliability was 0.91; the alpha coefficients for the subscales ranged from 0.70 to 0.87. The Japanese language version of the HPLP II appears to have sufficient validity and reliability for use by researchers who wish to describe the health-promoting components of lifestyle among the Japanese population and to explore differences and similarities in the health-promoting lifestyle of Japanese and American subjects or those of other ethnic groups. Further evaluations of measurement with different populations appears warranted. This instrument will enable researchers to investigate patterns and determinants of health-promoting lifestyle, as well as the effects of interventions to alter the lifestyle.

Health Promotion↗
PubMed2000

Sensory ataxic dominant neuropathy associated with polyarteritis nodosa.

A 68-year-old man with sensory ataxic dominant neuropathy associated with polyarteritis nodosa (PAN) had deep sensory disturbance with unsteady gait and absence of the Achilles tendon reflex. Examination revealed weight loss, elevated CRP level, negative antineutrophil cytoplasm antibodies, decreased M-wave amplitude in the peroneal motor nerve and absence of action potentials in the sural sensory nerve. Sural nerve biopsy revealed a marked loss of myelinated fibers, myelin ovoid formation and necrotizing angiitis of large epineurial arterioles. Renal biopsy revealed global and/or segmental necrotizing angiitis in glomeruli, but not in the arcuate artery. These pathological findings were distinct from those of PAN, particularly microscopic polyangiitis (MPA). Treatment with a steroid improved the deep sensory disturbance, unsteady gait, and CRP level. This case is similar to ataxic neuropathy which can arise from various disorders. This is the first report of a case of sensory ataxic dominant neuropathy associated with MPA in PAN.

Action Potentials↗
PubMed2000

Mortality among persons with a history of Kawasaki disease in Japan: existence of cardiac sequelae elevated the mortality.

OBJECTIVE: To clarify whether patients with Kawasaki disease have a higher death rate than the age-matched healthy population after the disease occurrence. STUDY DESIGN: Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new definite diagnosis of Kawasaki disease. Patients were followed until December 31, 1997, or death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. RESULTS: Of 6576 patients enrolled, 25 (19 males and 6 females) died. The standardized mortality ratio (SMR) was 1.35. In spite of the high SMRs during acute phase, the mortality rate was not high after the acute phase for all patients. Although the SMR after the acute phase was 0.76 for those without cardiac sequelae, 6 males (no females) with cardiac sequelae died during this period and the SMR for the male group with cardiac sequelae was 2.77. CONCLUSION: The mortality rate among males with cardiac sequelae due to Kawasaki disease was 2.8 times as high as in general population, whereas mortality rates for females with the sequelae and both males and females without sequelae were not elevated.

Adolescent↗
PubMed2000

Hyperglycemia exacerbates the effect of ischemia-reperfusion on peripheral nerve in rat.

Ischemia-reperfusion is known to induce generation of oxygen free radicals (OFRs), thereby resulting in tissue damage. To clarify the pathogenesis of diabetic neuropathy, we examined whether hyperglycemia exacerbates the effects of ischemia-reperfusion on peripheral nerves. Using light microscopy, characteristic pathological changes seen in myelin and axons of nerve fibers were classified into two types: "loose myelin" and "dark axon," respectively. After a 2-hour ischemia and 24-hour reperfusion of sciatic nerves of rats, the concentrations of lipid peroxide and "loose myelin" in the nerves were significantly increased in the diabetic rats, but not in the nondiabetic rats. Thereafter, "dark axon" was significantly increased in both diabetic and nondiabetic rats. "Loose myelin" may be increased as a result of the effects of OFRs produced by ischemia-reperfusion, which are exacerbated by hyperglycemia.

Animals↗
PubMed2000

Telomerase activity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker.

OBJECT: Telomerase activity is responsible for cell immortality. To examine the role of telomerase in the carcinogenesis of human glioblastomas multiforme (GBMs), the authors studied telomerase activity, telomerase component expression, and telomere lengths in 42 GBM samples. METHODS: In all samples, EGFR and MDM2 amplifications and overexpressions were examined using Southern and Northern blot analyses. The p53 mutation was analyzed using polymerase chain reaction-single strand conformational polymorphism and by direct sequence analysis. Specimens of tissues were immunostained with p53, EGFR, and MDM2 antibodies. Allelic loss on chromosomes 17p and 10 was assessed by loss of heterozygosity (LOH) assays. Telomerase activity, expression of its components (human telomerase reverse transcriptase [hTERT], human telomerase RNA component [hTERC], and telomerase-associated protein [TEP1]), and telomere lengths were analyzed using the telomeric repeat amplification protocol (TRAP)-hybridization protection assay, reverse transcription-polymerase chain reaction, and Southern blot analysis. According to the results of assessments of EGFR and MDM2 amplifications, p53 mutation, LOHs in chromosomes 17p and 10, and the clinical course of the disease, the 42 samples were classified into 22 primary and 20 secondary glioblastomas. Twenty-six (61.9%) of all 42 samples demonstrated detectable telomerase activity during the TRAP assay. Secondary GBMs displayed significantly higher levels of telomerase activity and hTERT expression than primary GBMs. Tumors with a p53 gene mutation demonstrated significantly higher telomerase activity than those without a p53 mutation. Four samples with a codon 175 mutation demonstrated an exceptionally high amount of telomerase activity. In secondary GBMs, the increase in telomerase activity and the hTERT expression level correlated with the increased frequency of p53 mutations. There was no significant difference in telomere length between primary and secondary GBMs. CONCLUSIONS: These results suggest that telomerase activity and p53 mutations both play important roles in the multistep carcinogenesis of GBMs. Telomerase activity and hTERT expression may be considered as novel distinctive factors in human GBMs.

Aged↗
PubMed2000

Arisostatins A and B, new members of tetrocarcin class of antibiotics from Micromonospora sp. TP-A0316. II. Structure determination.

Structures of arisostatins A and B were determined by spectroscopic analyses. Arisostatins were found to be new analogs of tetrocarcin A and possess an iso-butanoyldigitoxose unit instead of the acetyldigitoxose one. NMR analyses of arisostatins and tetrocarcin A led to the revision of the anomeric configurations in the tetrasaccharide moiety of tetrocarcin A.

Aminoglycosides↗
PubMed2000

Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in perfused rat liver: involvement of hepatic aldehyde oxidase as a detoxification enzyme.

To elucidate the toxicological relevance of hepatic aldehyde oxidase (AO) as a detoxification enzyme of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), we studied the metabolism and the hepatotoxicity of MPTP in intact rat livers exhibiting different AO activities by using a recirculating perfusion method. In the perfusate during a 90-min recirculation of 1 mM MPTP, the perfused liver from Jcl:Wistar rat, a strain showing high AO activity, generated almost equal amounts of 1-methyl-4-phenylpyridinium species (MPP(+)) and 1-methyl-4-phenyl-5,6-dihydro-2-pyridone (MPTP lactam) as major metabolites, together with 4-phenyl-1,2,3, 6-tetrahydropyridine, 1-methyl-4-phenyl-2-pyridone (MP 2-pyridone) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide. However, a marked decrease of MPTP lactam as well as MP 2-pyridone and a concomitant increase of MPP(+) were caused by coinfusion of 2-hydroxypyrimidine (2-OH PM), a competitive inhibitor of AO, into Jcl:Wistar rat liver. A quite similar metabolic profile was obtained on perfusion of AO-deficient WKA/Sea rat liver. Rather large amounts of MPP(+) were retained in the liver in all cases, but especially in Jcl:Wistar rat in the presence of 2-OH PM. Lactate dehydrogenase leakage into the perfusate from rat liver perfused with 1 mM MPTP was greater in the strain with lower AO activity, WKA/Sea, than in that with higher AO activity, Jcl:Wistar. Furthermore, inhibition of AO in Jcl:Wistar rat in the presence of 2-OH PM caused an enhancement of lactate dehydrogenase leakage. These results suggest that hepatic AO is a key detoxification enzyme for MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

[Brain lesion in congenital myotonic dystrophy].

Congenital myotonic dystrophy (CMyD) affects the brain, causing mental changes and psychomotor retardation. However, the pathophysiology of the brain dysfunctions in CMyD remain to be clarified. We described two cases of CMyD with brain abnormalities. Case 1 was diagnosed as having ventricular dilation at 17 days after birth, and died at 3 years and 6 months. Case 2 was diagnosed as having ventricular dilation at birth, and died at 1 year and 3 months. Pathologically, both cases showed remote hypoxic ischemic brain damage and leptomeningeal glioneuronal heterotopia (LGH). In our patients, the white matter changes may have been caused by perinatal asphyxia, and LGH by embryological abnormalities. Taken our data and those of previous reports together, it is suggested that cerebral abnormalities in CMyD are ascribed to both hypoxic ischemic changes and histogenetic abnormalities.

Asphyxia Neonatorum↗
PubMed2000

Double blind study of the effect of caffeine on the mental calculation.

The double blind study of the effect of caffeine on the mental calculation has been carried out in the practical exercise course for the undergraduate students of clinical pharmacology, in the Medical School, Kyushu University. The results obtained from 1997 to 1999 were summarized and evaluated.

Adult↗
PubMed2000

Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.

Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic basis of clinical diversity of ABL, mutations of the MTP gene have been screened in 4 unrelated patients with ABL. Three novel mutations have been identified: a frameshift mutation caused by a single adenine deletion at position 1389 of the cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation, 2218-2A-->G, in a compound heterozygous form. The frameshift and splice site mutations are predicted to encode truncated forms of MTP. When transiently expressed in Cos-1 cells, the Asn780Tyr mutant MTP bound protein disulfide isomerase (PDI) but displayed negligible MTP activity. It is of interest that the patient having the Asn780Tyr mutation, a 27-year-old male, has none of the manifestations characteristic of classic ABL even though his plasma apoB and vitamin E were virtually undetectable. These results indicated that defects of the MTP gene are the proximal cause of ABL.

Abetalipoproteinemia↗
PubMed2000

[Multimodality therapy for synchronous liver metastases of gastric cancer--significance of aggressive hepatic resection of liver lesions].

We analyzed 15 gastric cancer patients with synchronous liver metastases, and studied the significance of hepatic resection with multimodality therapy. 1. Both gastric and hepatic resections followed by intra-arterial or systemic chemotherapy were performed for six patients, two of whom had intra-operative MCT or EIT. The survival time of four patients without recurrence was 5 Y 4 M, 4 Y 5 M, 2 Y 4 M and 11 M. Two patients died of recurrence in the retroperitoneum or residual liver 3 Y 10 M and 8 M after therapy, respectively. The three-year survival rate was 83%. 2. The longest survival among the five patients treated with gastric resection without hepatic resection followed by intra-arterial or systemic chemotherapy was 1 Y 1 M. 3. Four patients with non-curative factors (P, N, M) were treated with systemic chemotherapy only, and the longest survival was 1 Y 1 M. In conclusion, when local control is obtained during surgery in patients with gastric cancer with synchronous liver metastasis, aggressive hepatic resection supported with MCT or EIT should be performed on liver lesions to improve the prognosis.

Aged↗
PubMed2000

[Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging].

OBJECTIVES: Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5 +/- 6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. METHODS: Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). RESULTS: The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33 +/- 0.22 in chronic heart failure class I, 2.50 +/- 0.34 in class II, 1.95 +/- 0.61 in class III, and 1.39 +/- 0.29 in class IV (p < 0.05). %WR was 24.8 +/- 12.8% in chronic heart failure class I, 23.3 +/- 10.2% in class II, 49.2 +/- 24.5% in class III, and 66.3 +/- 26.5% in class IV (p < 0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. CONCLUSIONS: Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure.

3-Iodobenzylguanidine↗