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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 145 records · Page 8Linked to original sources
PubMed2001

Hepatic necrosis with cholestasis induced by long-term voglibose administration.

A 76-year-old woman admitted to our hospital for jaundice had been treated for diabetes mellitus with insulin for 9 years and voglibose had been added for the 39 months preceding admission. Elevated serum bilirubin and transaminase concentration began to normalize with initiation of corticosteroid treatment 1 week after discontinuation of voglibose. In the in vitro testing of the patient's peripheral blood, lymphocytes showed stimulation by voglibose. In dramatic contrast to an initial liver biopsy specimen that demonstrated cholestasis with submassive and zonal necrosis, the follow-up specimen was normal 1 year later. We believe that patients treated with voglibose should be monitored long-term with monthly determinations of transaminases and bilirubin in serum.

Aged↗
PubMed2001

Shoulder stiffness: a common adverse effect of HMG-CoA reductase inhibitors in women?

Muscle symptoms are known as adverse effects of HMG-CoA reductase inhibitors but their incidence is reported to be low. We treated a case of shoulder stiffness related to such a drug, which prompted us to preliminarily survey its incidence. We found that nearly one-tenth of women (6/66) taking such drugs reported drug-related shoulder stiffness. Shoulder stiffness is a very common symptom, while drug-induced shoulder stiffness is generally unknown. Many cases involving such an adverse effect may thus be overlooked. We present 2 typical cases here.

Aged↗
PubMed2001

Microflora investigation experiment.

Many microorganisms were isolated from condensed water, wiping and scratching of cabin wall and air sampler in Russian space station Mir by Russian astronauts Lazutkin et al. in February 1997 as part of NASDA "First MIR Utilization Space Experiment (JMIR)". For example, there were about 2 x 10(6) cells/ml in condensed water sample No. 1 isolated from the transfer-docking compartment of Crystal module. We tried the colony isolation, pure culturing and identification from these sampled microorganisms. After the bacteria separated from filamentous fungi and yeasts were observed using the phase contrast optical microscopy and gram stain method, twenty-one kinds of biochemical characters, e.g., oxidase test, activity of beta-galactosidase and fermentation of glucose etc., were investigated on the isolated bacteria. Then, we found Serratia liquefaciens and Yersinia enterocolitica and the chemoheterotroph Pseudomonadaceae, Stenotrophomonas maltophila. Furthermore, using ultraviolet (UV) lamp we tried the isolation of radioresistant bacteria, we found the radioresistant Sphingomonas paucimobilis (90.8% identification) by comparing with radioresistant Escherichia coli B/r strain. Considering Mir environment under cosmic radiation, this radioresistant S. paucimobilis might be the mutant from radiosensitive one. Following papers were published [see text].

Bacteria↗
PubMed2001

Goadsporin, a chemical substance which promotes secondary metabolism and Morphogenesis in streptomycetes. II. Structure determination.

The structure of goadsporin was determined by using spectroscopic techniques. NMR analysis revealed that goadsporin consists of 19 amino acids, two of which are dehydroalanines (Deala), and six of which are cyclized to oxazoles (Oxz) and thiazoles (Thz) by dehydrative cyclization and dehydrogenation from serine, threonine and cysteine. NMR analysis established seven partial structures, and their sequence was determined by CID-MS/MS. Negative mode FAB-MS/MS gave product ions arising from charge-remote fragmentation that allowed determination of the sequence of the amino acid components as AcNH-Ala-MeOxz-Val-Deala-MeOxz-Ile-Leu-Thz-Ser-Gly-Gly-MeOxz-Leu-Deala-Oxz-Ala-Gly-Thz-Val-OH. The chiral amino acids were determined by the advanced Marfey's method to have L-configurations.

Anti-Bacterial Agents↗
PubMed2001

[Hopkins syndrome: oral prednisolone was effective for the paralysis].

We describe here a 5-year-old girl who presented flaccid paralysis of the left upper limb after recovery from bronchial asthma. T2-weighted magnetic resonance imaging of the cervical cord revealed a focal high intensity area in the left anterior horn at the C6-C7 level. She was treated with oral prednisolone, and paralysis resolved within two months. Thirty cases of Hopkins syndrome have been reported so far, but its cause remains unknown. Early administration of prednisolone might ameliorate paralysis in this syndrome.

Anti-Inflammatory Agents↗
PubMed2001

DNA methylation profiles of lung tumors.

Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. We determined the frequency of aberrant promoter methylation of the p16, adenomatous polyposis coli (APC), H-cadherin (CDH13), glutathione S-transferase P1 (GSTP1), O6-methylguanine-DNA-methyltransferase (MGMT), retinoic acid receptor beta-2 (RAR beta), E-cadherin (CDH1), and RAS association domain family 1A (RASSF1A) genes in 198 tumors consisting of small cell lung cancers [SCLCs (n = 43)], non-small cell lung cancers [NSCLCs (n = 115)], and bronchial carcinoids (n = 40). The profile of methylated genes in the two neuroendocrine tumors (SCLC and carcinoids) were very different from that of NSCLC. However, whereas the overall pattern of aberrant methylation of carcinoids was similar to that of SCLC, carcinoids had lower frequencies of methylation for some of the genes tested. There were also significant differences in the methylation profiles between the two major types of NSCLC, adenocarcinoma and squamous cell carcinoma. We performed cluster analysis and found that SCLCs clustered with other SCLCs and carcinoids but not with NSCLCs, whereas the NSCLCs tended to cluster together. Within NSCLCs, adenocarcinomas and squamous cell carcinomas clustered with their respective histological types. Finally, we compared the methylation profiles of SCLC and NSCLC tumors and their respective cell lines (n = 44). In general, methylation frequencies were higher in tumor cell lines, but these differences were seldom significant. Thus, tumor cell lines appear to be suitable models to study aberrant DNA methylation. We conclude that SCLC, carcinoids, squamous cell carcinomas, and adenocarcinomas of the lung have unique profiles of aberrant methylation. Our findings should help us understand differences in the pathogenetic mechanisms of lung cancers.

Adenomatous Polyposis Coli Protein↗
PubMed2000

Human impact on the environment in Japan and New Zealand: a comparison.

Because of its proximity to Asia, Japan has been populated by humans for a much longer time period than New Zealand and has a much higher population density. The similarity in geology and tectonic setting of the two island groups has forced both peoples to confront similar environmental hazards but this was achieved in different ways. During the Edo period (1600-1868) when contact with outside countries was limited, the Japanese adapted their agricultural practices to the environment and developed an agricultural system that corresponds closely to the ideals of sustainability. Indeed, it can be argued that the farming lifestyle of the Edo period was the most advanced way of life that can be adopted without depleting stock resources. Following the Meiji restoration in 1868, the policy of rapid industrialization led to many environmental mistakes, particularly after World War II. By the end of the 1960s, Japan was the world's most polluted country. The situation has subsequently improved greatly from this low point but much remains to be done. New Zealand was initially occupied by the Maori over 1000 years ago. They did more environmental damage than was previously thought, particularly in burning off bush and destroying the bird life. However, it was the colonization of New Zealand by the Europeans after 1840 that led to the greatest environmental damage with their introduction of farming methods unsuited to the conditions. Although the need for better scientific planning of land use practices within New Zealand is recognized, sustainable management of the environment remains a distant goal. More detailed study of the agricultural methods and lifestyles adopted in Japan during the Edo period could help in defining the concept of sustainability.

Agriculture↗
PubMed2000

Sterol regulatory element-binding protein-1 is regulated by glucose at the transcriptional level.

In vivo studies suggest that sterol regulatory element-binding protein (SREBP)-1 plays a key role in the up-regulation of lipogenic genes in the livers of animals that have consumed excess amounts of carbohydrates. In light of this, we sought to use an established mouse hepatocyte cell line, H2-35, to further define the mechanism by which glucose regulates nuclear SREBP-1 levels. First, we show that these cells transcribe high levels of SREBP-1c that are increased 4-fold upon differentiation from a prehepatocyte to a hepatocyte phenotype, making them an ideal cell culture model for the study of SREBP-1c induction. Second, we demonstrate that the presence of precursor and mature forms of SREBP-1 protein are positively regulated by medium glucose concentrations ranging from 5. 5 to 25 mm and are also regulated by insulin, with the amount of insulin in the fetal bovine serum being sufficient for maximal stimulation of SREBP-1 expression. Third, we show that the increase in SREBP-1 protein is due to an increase in SREBP-1 mRNA. Reporter gene analysis of the SREBP-1c promoter demonstrated a glucose-dependent induction of transcription. In contrast, expression of a fixed amount of the precursor form of SREBP-1c protein showed that glucose does not influence its cleavage. Fourth, we demonstrate that the glucose induction of SREBP could not be reproduced by fructose, xylose, or galactose nor by glucose analogs 2-deoxy glucose and 3-O-methyl glucopyranose. These data provide strong evidence for the induction of SREBP-1c mRNA by glucose leading to increased mature protein in the nucleus, thus providing a potential mechanism for the up-regulation of lipogenic genes by glucose in vivo.

Animals↗
PubMed2000

Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene.

Recent data suggest that sterol regulatory-binding protein (SREBP)-1c plays a key role in the transcriptional regulation of different lipogenic genes mediating lipid synthesis as a key regulator of fuel metabolism. SREBP-1c regulates its downstream genes by changing its own mRNA level, which led us to sequence and analyze the promoter region of the mouse SREBP-1c gene. A cluster of putative binding sites of several transcription factors composed of an NF-Y site, an E-box, a sterol-regulatory element 3, and an Sp1 site were located at -90 base pairs of the SREBP-1c promoter. Luciferase reporter gene assays indicated that this SRE complex is essential to the basal promoter activity and confers responsiveness to activation by nuclear SREBPs. Deletion and mutation analyses suggest that the NF-Y site and SRE3 in the SRE complex are responsible for SREBP activation, although the other sites were also involved in the basal activity. Gel mobility shift assays demonstrate that SREBP-1 binds to the SRE3. Taken together, these findings implicate a positive loop production of SREBP-1c through the SRE complex, possibly leading to the overshoot in induction of SREBP-1c and its downstream genes seen in the livers of refed mice. Furthermore, reporter assays using larger upstream fragments indicated another region that was inducible by addition of sterols. The presence of the SRE complex and a sterol-inducible region in the same promoter suggests a novel regulatory link between cholesterol and fatty acid synthesis.

Animals↗
PubMed2000

Effect of left ventricular wall mass on Doppler filling patterns in the developing normal human heart.

To assess gestational age- and growth-related changes in left ventricular (LV) size, LV wall, and LV transmitral flow velocity patterns, 2-dimensional (2-D) and Doppler echocardiographic studies were performed in 89 normal fetuses aged 16 to 38 weeks. Serial studies were designed in 7 fetuses. Variables measured from 4-chamber views were chamber areas and myocardial wall areas. From these measurements, area shortening fraction and ratio of myocardial wall area to end-diastolic chamber area were calculated. LV end-diastolic chamber area and myocardial wall area increased exponentially with advancing gestational age (r = 0.88 and 0.90, respectively, p < 0.001). Area shortening fraction showed no significant changes with gestational age. Ratio of myocardial wall area to LV end-diastolic chamber area decreased gradually with increasing gestational age (r = -0.77, p < 0.001). With increasing gestational age, mitral peak velocities of early diastole increased (r = 0.82, p < 0.01) with little change in peak velocity during atrial contraction. Multiple regression analysis showed that age-related increases in peak velocity of early diastole were related to advancing gestational age and also to decreases in ratio of myocardial wall area to LV end-diastolic chamber area. Low peak filling velocities during early diastole in younger fetuses may be related partly to relative increase in LV wall mass. The gestational age-related decreases in LV wall mass may be one of the important mechanisms of gestational age-related alterations in diastolic properties, especially relaxation processes.

Blood Flow Velocity↗
PubMed2000

The effect of a Rho kinase inhibitor Y-27632 on superoxide production, aggregation and adhesion in human polymorphonuclear leukocytes.

We investigated the involvement of p160ROCK (a Rho-associated coiled coil-forming protein kinase), one of Rho kinases on superoxide anion production (O(2)(-) production), aggregation and adhesion of human polymorphonuclear leukocytes under physiological condition, using a selective p160ROCK inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632). Y-27632 inhibited the O(2)(-) production stimulated by phorbol-12-myristate-13-acetate (PMA) in a dose-dependent manner. Stauroprorine blocked the PMA-induced O(2)(-) production while wortmannin did not. Y-27632 also inhibited the O(2)(-) production by guanosine 5'-O-(3-thiotriphosphate) (GTP(gamma)S) 100 microM. N-formyl-Met-Leu-Phe (fMLP)-induced O(2)(-) production was not influenced by Y-27632, but was inhibited by wortmannin. The enhanced O(2)(-) production by Ca-ionophore A23817 and thapsigargin was not inhibited by Y-27632. Y-27632 did not change the basal intracellular Ca(2+) concentration nor its elevation stimulated by fMLP. Polymorphonuclear leukocytes aggregation induced by PMA was dose-dependently decreased by Y-27632 while their aggregation stimulated by fMLP was enhanced by the agent. Polymorphonuclear leukocytes adhesion induced by PMA or fMLP was not influenced by Y-27632.These results suggest that p160ROCK is involved in the PMA-induced O(2)(-) production and aggregation in human polymorphonuclear leukocytes. This kinase might locate in downstream of protein kinase C in polymorphonuclear leukocytes.

Adult↗
PubMed2000

Chromatographic determination of the absolute configuration of an acyclic secondary alcohol using difluorodinitrobenzene

A chromatographic determination method was developed for the absolute configuration of an acyclic secondary alcohol using the characteristic functions of 1,5-difluoro-2,4-dinitrobenzene (FFDNB). This method relies on the formation of the fixed favorable conformation of a secondary alcohol-DLA (2,4-dinitrophenyl-5-leucinamide) derivative and its recognition by ODS silica gel. The secondary alcohol reacted first with FFDNB under mild basic conditions, and L-leucinamide or DL-leucinamide was then introduced into the secondary alcohol-FDNB derivative. Because the conformations of the resulting alcohol-DLA derivatives were rigidly fixed by the dinitrobenzene plane, the absolute configuration at the asymmetric carbon of the secondary alcohol tested can be definitely deduced by the elution behavior of both of the diastereomers in the HPLC and/or LC/MS. One of the diastereomers has the cis (Z)-type arrangement of two more hydrophobic substituents of the alcohol and leucinamide moieties, the more hydrophobic side chain and isobutyl groups, to the plane of the dinitrobenzene, whereas another diastereomer has the opposite arrangement (trans (E)-type). Therefore, the cis arrangement interacts more strongly with the ODS silica gel and has a longer retention time than that of the trans-type arrangement. This established method was successfully applied to various chiral acyclic secondary alcohols including chloramphenicol and 4-hydroxyphenyllactic acid. Finally, the limitations of this method were also examined.

Journal Article↗
PubMed2000

A new tumor-rejection antigen recognized by cytotoxic T lymphocytes infiltrating into a lung adenocarcinoma.

Lung cancer is the most commonly occurring malignancy worldwide and one of the few that continues to show an increasing incidence. To understand the molecular basis of host immunity against lung cancer, we investigated tumor antigens recognized by HLA-A24-restricted CTLs established from T cells infiltrating into lung adenocarcinoma and report a new gene coding for antigens recognized by the CTLs. The mRNA of this gene was expressed at different levels in all of the malignant cells tested (high in adenocarcinomas and gliomas and low in esophageal cancers and malignant hematological disease). It was also expressed at the different levels in each of a panel of normal tissues (high in the thymus, low in peripheral blood mononuclear cells, and lowest in the stomach, small intestine, and skeletal muscle). This gene encodes a Mr 60,000 nuclear protein with 414 deduced amino acids. The three peptides at positions 158-165, 170-179, and 188-196 were recognized by the CTLs. One peptide at position 188-196 had the ability to induce HLA-A24-restricted and tumor-specific CTLs in peripheral blood mononuclear cells of lung cancer patients. These CTLs, however, did not lyse HLA-A24+ PHA-activated T cells in which the mRNA of this gene was highly expressed, even in the presence of excess amounts of a corresponding peptide in culture. These results suggest that this gene product and peptide could be applicable to specific immunotherapy of lung cancer patients.

Adenocarcinoma↗
PubMed2000

A sequence-ready BAC clone contig of human chromosome 10p15 spanning the loss of heterozygosity region in glioma.

Deletion of chromosome 10 is one of the most common chromosomal alterations in glioma. At 10p15, the telomeric region of the short arm of chromosome 10, loss of heterozygosity (LOH) has been frequently observed by microsatellite analysis, suggesting the presence of a tumor suppressor gene. We examined LOH in 34 gliomas on chromosome 10, and frequent LOH on 10p was detected on 10p15, in agreement with deletion mapping studies on chromosome 10. We then constructed a bacterial artificial chromosome (BAC) clone contig covering the critical region, which spanned the interval between D10S249 and D10S533 on 10p15. The map contained 68 BAC clones connected by 74 sequenced tag sites (STSs) and covered approximately 2.7 Mb, with one gap. A total of 74 STSs, including 6 microsatellite markers, 29 expressed sequenced tags (ESTs), and 39 BAC end STSs, were physically arranged. Twenty-eight ESTs were mapped in the interval between D10S249 and D10S559 (approximately 1200 kb), and another EST was mapped in the interval between D10S559 and D10S533 (approximately 1300 kb). This sequence-ready BAC clone contig map will be a basic resource for high-quality sequencing and positional cloning of the putative tumor suppressor gene at 10p15 in glioma.

Base Sequence↗
PubMed2000

Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia.

Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes esterification of cellular cholesterol. To investigate the role of ACAT-1 in atherosclerosis, we have generated ACAT-1 null (ACAT-1-/-) mice. ACAT activities were present in the liver and intestine but were completely absent in adrenal, testes, ovaries, and peritoneal macrophages in our ACAT-1-/- mice. The ACAT-1-/- mice had decreased openings of the eyes because of atrophy of the meibomian glands, a modified form of sebaceous glands normally expressing high ACAT activities. This phenotype is similar to dry eye syndrome in humans. To determine the role of ACAT-1 in atherogenesis, we crossed the ACAT-1-/- mice with mice lacking apolipoprotein (apo) E or the low density lipoprotein receptor (LDLR), hyperlipidemic models susceptible to atherosclerosis. High fat feeding resulted in extensive cutaneous xanthomatosis with loss of hair in both ACAT-1-/-:apo E-/- and ACAT-1-/-:LDLR-/- mice. Free cholesterol content was significantly increased in their skin. Aortic fatty streak lesion size as well as cholesteryl ester content were moderately reduced in both double mutant mice compared with their respective controls. These results indicate that the local inhibition of ACAT activity in tissue macrophages is protective against cholesteryl ester accumulation but causes cutaneous xanthomatosis in mice that lack apo E or LDLR.

Animals↗
PubMed2000

Quantum phase transition of the randomly diluted heisenberg antiferromagnet on a square lattice

Ground-state magnetic properties of the diluted Heisenberg antiferromagnet on a square lattice are investigated by means of the quantum Monte Carlo method with the continuous-time loop algorithm. It is found that the critical concentration of magnetic sites is independent of the spin size S, and equal to the two-dimensional percolation threshold. However, the existence of quantum fluctuations makes the critical exponents deviate from those of the classical percolation transition. Furthermore, we found that the transition is not universal, i.e., the critical exponents significantly depend on S.

Journal Article↗
PubMed2000

Characterization and identification of (CT)n microsatellites in soybean using sheared genomic libraries.

Three small insert (300 to approximately 600 bp) sheared genomic libraries were constructed by pipetting and DNase I treatment of soybean DNA. About 15,000 clones from each library were screened for CT- simple sequence repeats (CT-SSRs). The CT-SSRs were abundant in the soybean genome at an estimated frequency of approximately one SSR per 110 kb of genomic DNA. Following the sequencing of 129 positive clones, the repeat types and frequency of CT repeats among the positive clones were characterized. Forty-nine primer pairs were designed and preliminarily evaluated for their ability to amplify genomic DNA from a set of six varieties, including parents of a mapping family. Amplified products were analyzed by 10% PAGE. Eighty-eight percent of the designed primers were able to amplify all these genomic DNAs using a single PCR profile of 53 degrees C annealing temperature, of which 22 (45%) were polymorphic in the six varieties, and 14 of them were polymorphic in the parents of the mapping family. The polymorphic primer sets were further assessed for allelic information using DNA from 16 soybean cultivars. The average number of alleles was 4, ranging from 2 to 7 with the highest polymorphism information content value 0.84. Fourteen of these SSRs were mapped, using an existing soybean RFLP map. The findings presented here will advance our understanding of the soybean genome, and assist in the mapping genome and discrimination of closely related varieties of this species.

Chromosome Mapping↗