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Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 91 records · Page 5Linked to original sources
PubMed2001

Rapid decrease of plasma HCV RNA in early phase of twice daily administration of 3 MU doses interferon-beta in patients with genotype 1b hepatitis C infection: a multicenter randomized study.

Virological response to interferon (IFN) is poor in patients with plasma levels of HCV RNA higher than 1 Meq/ml and genotype 1b hepatitis C viral infection. In 60 patients, a randomized control study was conducted to compare 3 MU of IFN-beta twice daily for four weeks (group A) and 6 MU once a day for four weeks (group B) followed by a four-week administration of 6 MU once a day. The plasma levels of HCV RNA, determined by an amplicore-monitor method, for patients in group A were significantly lower than those for group B at the fourth and eighth day of IFN administration, and complete virological responses were noted in two patients from group A but none in group B. It is concluded that twice daily administration of 3 MU IFN-beta is more effective than once a day 6 MU in the early phase of IFN therapy.

Female↗
PubMed2001

Two novel single-nucleotide polymorphisms of the Caspase-9 (CASP9) gene in the Japanese population.

We identified two single-nucleotide polymorphisms (SNPs) in the human Caspase-9 (CASP9) gene (1p36.3), which encodes an apoptosis-related cysteine protease, by screening all exons and exon-intron boundaries. These SNPs were present in coding regions. One of coding SNPs reflected an amino-acid substitution; an A to G transition at codon 221 in exon 5 would encode arginine instead of glutamine. As the gene is implicated in apoptotic cascade, the polymorphic sites will serve as useful markers for genetic studying of disorders affecting immune response and cancer susceptibility in humans.

Caspase 9↗
PubMed2001

Role of nitric oxide in inflammation.

A number of laboratories have sought to elucidate the role of nitric oxide (NO) in both acute and chronic inflammatory diseases. It is now well appreciated that NO can influence many aspects of the inflammatory cascade ranging from its own expression to recruitment of leucocytes to the effected tissue. With the advent of mice selectively deficient in the various isoforms of nitric oxide synthase (NOS), the role that NO may play in various disease states can now be examined in vivo. One such syndrome that has gained much attention in recent years is ischaemia and reperfusion-induced tissue injury. Ischaemia-reperfusion (I/R) injury is an important clinical consideration in situations such as transplantation, trauma, liver or bowel resection and haemorrhagic shock. A hallmark of I/R is the production of reactive oxygen species (ROS) during the reperfusion phase and it is thought that the production of ROS mediate much of the post-ischaemic tissue injury. This review will examine the current state of knowledge regarding the regulatory mechanisms by which NO can influence various aspects of the inflammatory cascade as well as its role in a model of I/R injury in vivo.

Animals↗
PubMed2001

Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon.

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.

Adult↗
PubMed2001

Pre-emptive renal transplantation in children.

BACKGROUND: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). METHODS: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. RESULTS: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. CONCLUSION: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy.

Acute Disease↗
PubMed2001

Asynchronous (heterochronic) bilateral renal infarction associated with primary antiphospholipid syndrome.

We report the rare case of a 51-year-old man with asynchronous (heterochronic) bilateral renal infarction associated with primary antiphospholipid syndrome. He was treated for right renal infarction, but 2 months later, while under anticoagulant treatment, he had a recurrence on the other side of the renal infarction. The laboratory work-up confirmed antiphospholipid syndrome. Six months later the patient has not experienced any new thrombotic episodes and is receiving oral anticoagulants and antiplatelet therapy.

Anticoagulants↗
PubMed2001

Different expressivity of a ventricular essential myosin light chain gene Ala57Gly mutation in familial hypertrophic cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy (HCM) is a clinically and genetically heterogeneous disease of the sarcomere. Molecular genetic studies have shown that familial HCM involves mutations in 8 different genes that encode proteins of the myofibrillar apparatus. METHODS: We thoroughly searched these genes to find the mutations in 38 probands of unrelated families with familial HCM. RESULTS: We found a novel missense mutation that resulted in Ala57Gly amino acid substitution of the ventricular essential myosin light chain (vMLC1) gene in two unrelated Korean families with familial HCM and one Japanese patient. The mutated site is located in the putative helix-loop-helix region (named EF-hand domain) of the calcium-binding site that is highly conserved in vMLC1 isoforms across the various species. The phenotype of this mutation in the affected families is a classic asymmetric septal hypertrophy, and the disease penetrance in genotyped members older than 18 years is 78%. In one Korean family a 42-year-old woman and two brothers (34 and 38 years old) with the mutation had fully expressed the disease, but two sisters (39 and 29 years old) with the mutation had no phenotypic expression of HCM. CONCLUSIONS: Ala57Gly mutation in the vMLC1 gene may exhibit the classic form of familial HCM and widely different penetration of the disease phenotype in the family members with mutation, especially in women.

Adult↗
PubMed2001

The gluteal-fold flap for vulvar and buttock reconstruction: anatomic study and adjustment of flap volume.

The ideal skin-flap reconstruction provides functional preservation and a good cosmetic outcome in both the reconstructed site and the donor site. Although various flaps are used for reconstruction of the vulvar and buttock region, there are disadvantages associated with each. In 1996, Yii and Niranjan reported the gluteal-fold flap for vulvar reconstruction. As presently used, this flap is bulky, particularly in obese patients or when used for hemilateral reconstruction. Thinning the flap has been considered impossible because of the obscurity of the blood supply. In the study presented here, the pedicle vessels of this flap were studied in eight cadavers; the authors found that the flap is nourished by a direct cutaneous system of the internal pudendal artery and vein. Accordingly, adjustment of the flap volume was believed to be possible, with the exception of the adipose tissue containing the pedicle vessels. The authors have since used 14 thinned flaps for seven vulvar, one vaginal, and two buttock defects in 10 patients. All flaps survived completely. Good functional and cosmetic results were achieved with hemilateral or bilateral flaps in vulvar or buttock reconstruction. In the buttock in particular, the usefulness of this flap for anal and pelvic-floor reconstruction was demonstrated. The scar at the donor site, concealed in the gluteal fold, was acceptable. The gluteal-fold flap is very useful for various vulvar and buttock reconstructions because it can be adjusted to the required volume.

Adult↗
PubMed2001

Study on free radicals and pancreatic fibrosis--pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor.

The exact mechanisms of the development of pancreatic fibrosis are still unknown. To clarify the relationship between pancreatic fibrosis and free radicals, the effect of the administration of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DDC), on pancreatic fibrosis in rats was studied. A single intraperitoneal injection of 500 mg/kg of DDC significantly reduced SOD activity and significantly increased lipid peroxidation products in the pancreas, showing no histologic changes of inflammation or necrosis. Repeated administration of 500 mg/kg DDC, twice a week, caused inter- and intralobular fibrosis with atrophy of acinar cells in the pancreas for at least 2 weeks without fibrosis of the liver and kidney. Administration of allopurinol showed preventive effects against DDC-induced pancreatic fibrosis. In conclusion, repeated administration of DDC, which caused pancreatic fibrosis, is a new experimental model of pancreatic fibrosis from the viewpoint of oxidative stress.

Allopurinol↗
PubMed2001

Increased incidence of bone metastases in hepatocellular carcinoma.

OBJECTIVES: Recently, we often encounter hepatocellular carcinoma patients with bone metastases. We therefore examined the changes in the incidence of bone metastases in hepatocellular carcinoma from 1978 to 1997 and tried to identify the characteristic clinical features. We also discuss the reasons for the increased incidence of bone metastasis in hepatocellular carcinoma. METHODS: A total of 673 patients with hepatocellular carcinoma during the period 1978-1997 were studied. Bone metastasis was screened by bone scintigraphy, and bone lesions were confirmed by plain radiography, computed tomography and/or magnetic resonance imaging. The serum levels of the C-terminal telopeptide of type 1 collagen, which represent osteoclastic bone resorption, were also measured. RESULTS: The incidence of bone metastasis during the decade 1988-1997 was significantly higher than that during the period 1978-1987. The median survival time of patients with hepatocellular carcinoma during 1988-1997 was also significantly longer than that during 1978-1987. Portal thrombus was found in about half of the patients with bone metastases. The most common site of bone metastases was the vertebra followed by the pelvis, rib and skull in that order. All bone lesions depicted by plain radiograph, computed tomography and/or magnetic resonance imaging were of the osteolytic type, and the serum levels of C-terminal telopeptide of type 1 collagen were significantly elevated in the patients with bone metastases. CONCLUSIONS: The increased incidence of bone metastasis in hepatocellular carcinoma in the decade 1988-1997 is first attributed to the prolonged survival rate of hepatocellular carcinoma patients due to recent progress in both the diagnosis and treatment of the disease. Dissemination of hepatocellular carcinoma cells to the vertebra through the portal vein-vertebral vein plexuses due to the presence of portal thrombus and/or portal hypertension may be related to a higher incidence of bone metastasis in hepatocellular carcinoma. Both an early diagnosis and timely treatment of bone metastases are thus called for in the follow-up of hepatocellular carcinoma patients.

Adult↗
PubMed2001

Down-regulation in multiple human cancers of a novel gene, DMHC, from 17q25.1 that encodes an integral membrane protein.

Frequent observations of allelic loss in chromosomal band 17q25.1 in a variety of human cancers have suggested that one or more tumor suppressor genes are present in that region. Moreover, a genetic locus for hereditary focal non-epidermolytic palmoplantar keratoderma, a condition associated with cancer of the esophagus (TOC; Tylosis with Oesophageal Cancer), lies in the same region. We screened cell lines derived from a variety of human cancers by reverse transcription-polymerase chain reaction (RT-PCR) to detect alterations in expression of genes within the region in question, by examining expressed sequence tags located there. These experiments identified an 1834-bp full-length cDNA encoding a novel, 441-amino acid integral membrane protein with seven putative transmembrane domains. This gene showed loss or extreme decrease of expression in 6 of 10 uterine cancer-cell lines, 2 of 11 hepatic cell carcinoma-cell lines, 2 of 7 lung cancer-cell lines, 1 of 6 gastric cancer-cell lines, and 1 of 10 breast cancer-cell lines. (We named it DMHC ("down-regulated in multiple human cancers").) Our results suggest that loss of expression of DMHC at 17q25.1 may play an important role in development of variety of human cancers.

Amino Acid Sequence↗
PubMed2001

Different susceptibility of each L-myc genotype to esophageal cancer risk factors.

To understand the relationship between the L-myc genotypes and esophageal cancer risk, a polymerase chain reaction-based restriction fragment length polymorphism analysis was performed on 91 Japanese patients with esophageal cancer and 241 non-cancer outpatients. No significant difference in the distribution of genotypes was observed between patients and controls; 18.7% LL genotype, 56.0% LS and 25.3% SS among patients, and 24.5%, 55.6% and 19.9%, respectively, among controls. Frequency of the s-allele in patients (0.533) was slightly higher than in controls (0.477), but the difference was not statistically significant. However, the odds ratios (ORs) for smoking or heavy drinking were markedly higher in SS and LS genotypes than in LL genotype; age-sex-adjusted ORs for smoking was 7.57 in the SS genotype, 6.40 in the LS genotype and 1.77 in the LL genotype. Age-sex-adjusted ORs for heavy drinking were 19.78, 18.20 and 7.40, respectively. The age-sex-adjusted ORs for both factors combined were 12.77, 18.45 and 1.44, respectively. These results suggested that the L-myc polymorphism might modify the effects of lifestyle factors on esophageal cancer risk.

Aged↗
PubMed2001

In situ detection, isolation, and physiological properties of a thin filamentous microorganism abundant in methanogenic granular sludges: a novel isolate affiliated with a clone cluster, the green non-sulfur bacteria, subdivision I.

We previously showed that very thin filamentous bacteria affiliated with the division green non-sulfur bacteria were abundant in the outermost layer of thermophilic methanogenic sludge granules fed with sucrose and several low-molecular-weight fatty acids (Y. Sekiguchi, Y. Kamagata, K. Nakamura, A. Ohashi, H. Harada, Appl. Environ. Microbiol. 65:1280-1288, 1999). Further 16S ribosomal DNA (rDNA) cloning-based analysis revealed that the microbes were classified within a unique clade, green non-sulfur bacteria (GNSB) subdivision I, which contains a number of 16S rDNA clone sequences from various environmental samples but no cultured representatives. To investigate their function in the community and physiological traits, we attempted to isolate the yet-to-be-cultured microbes from the original granular sludge. The first attempt at isolation from the granules was, however, not successful. In the other thermophilic reactor that had been treating fried soybean curd-manufacturing wastewater, we found filamentous microorganisms to outgrow, resulting in the formation of projection-like structures on the surface of granules, making the granules look like sea urchins. 16S rDNA-cloning analysis combined with fluorescent in situ hybridization revealed that the projections were comprised of the uncultured filamentous cells affiliated with the GNSB subdivision I and Methanothermobacter-like cells and the very ends of the projections were comprised solely of the filamentous cells. By using the tip of the projection as the inoculum for primary enrichment, a thermophilic, strictly anaerobic, filamentous bacterium, designated strain UNI-1, was successfully isolated with a medium supplemented with sucrose and yeast extract. The strain was a very slow growing bacterium which is capable of utilizing only a limited range of carbohydrates in the presence of yeast extract and produced hydrogen from these substrates. The growth was found to be significantly stimulated when the strain was cocultured with a hydrogen-utilizing methanogen, Methanothermobacter thermautotrophicus, suggesting that the strain is a sugar-fermenting bacterium, the growth of which is dependent on hydrogen consumers in the granules.

Animals↗
PubMed2001

Role of alveolar macrophages in Candida-induced acute lung injury.

Recent studies have shown that alveolar macrophages (AMs) not only act as phagocytes but also play a central role as potent secretory cells in various lung diseases, including pneumonia and acute respiratory distress syndrome. The behavior of AMs during disseminated candidiasis, however, is insufficiently elucidated. This study is the first to report disseminated candidiasis in AM-depleted mice and to analyze the effect of AMs on Candida-induced acute lung injury. While all AM-sufficient mice died by day 2 after infection with Candida albicans, no mortality was observed among AM-depleted mice. Unexpectedly, the CFU numbers of C. albicans isolated from the lungs of AM-depleted mice were significantly higher than those for C. albicans isolated from AM-sufficient mice. The lung wet-to-dry weight ratio was lower for AM-depleted mice than for AM-sufficient mice, although this difference was not significant. We found that bronchoalveolar lavage fluid (BALF) from AM-depleted mice in candidemia contained fewer neutrophils than BALF from AM-sufficient mice. In addition, myeloperoxidase activities in lung homogenates of AM-depleted mice were significantly lower than those in homogenates of AM-sufficient mice. A significant decrease in levels of murine macrophage inflammatory protein 2 (MIP-2), a potent chemoattractant for neutrophils, was noted in lung homogenates from AM-depleted mice compared with levels in homogenates from AM-sufficient mice. Immunohistochemical studies using anti-MIP-2 antibodies revealed that AMs were the cellular source of MIP-2 within the lung during candidemia. We observed that AM depletion decreased levels of AM-derived neutrophil chemoattractant, alleviated acute lung injury during candidemia, and prolonged the survival of mice in candidemia, even though clearance of C. albicans from the lungs was reduced.

Acute Disease↗
PubMed2001

ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain.

t(8;21) and t(16;21) create two fusion proteins, AML-1-ETO and AML-1-MTG16, respectively, which fuse the AML-1 DNA binding domain to putative transcriptional corepressors, ETO and MTG16. Here, we show that distinct domains of ETO contact the mSin3A and N-CoR corepressors and define two binding sites within ETO for each of these corepressors. In addition, of eight histone deacetylases (HDACs) tested, only the class I HDACs HDAC-1, HDAC-2, and HDAC-3 bind ETO. However, these HDACs bind ETO through different domains. We also show that the murine homologue of MTG16, ETO-2, is also a transcriptional corepressor that works through a similar but distinct mechanism. Like ETO, ETO-2 interacts with N-CoR, but ETO-2 fails to bind mSin3A. Furthermore, ETO-2 binds HDAC-1, HDAC-2, and HDAC-3 but also interacts with HDAC-6 and HDAC-8. In addition, we show that expression of AML-1-ETO causes disruption of the cell cycle in the G(1) phase. Disruption of the cell cycle required the ability of AML-1-ETO to repress transcription because a mutant of AML-1-ETO, Delta469, which removes the majority of the corepressor binding sites, had no phenotype. Moreover, treatment of AML-1-ETO-expressing cells with trichostatin A, an HDAC inhibitor, restored cell cycle control. Thus, AML-1-ETO makes distinct contacts with multiple HDACs and an HDAC inhibitor biologically inactivates this fusion protein.

Amino Acid Sequence↗
PubMed2001

Selected contribution: Effects of gender on reduced-size liver ischemia and reperfusion injury.

Hepatic resection with concomitant periods of ischemia and reperfusion (I/R) is a common occurrence in resectional surgery as well as reduced-size liver transplantation (e.g., split liver or living donor transplantation). However, the I/R induced by these types of surgical manipulations may impair liver regeneration, ultimately leading to liver failure. The objectives of the study were to develop a murine model of reduced-size liver I/R and assess the role of gender in this model of hepatocellular injury. We found that 100% of female mice survived the surgery indefinitely, whereas all male mice had greater initial liver injury and died within 5 days after surgery. The protective effect observed in females appeared to be due to ovarian 17beta-estradiol, as ovariectomy of females or administration of a selective estrogen antagonist to female mice resulted in enhanced liver injury and greater mortality following reduced-size liver I/R. Conversely, 17beta-estradiol-treated male mice exhibited less hepatocellular damage and survived indefinitely. Taken together, these data demonstrate an estrogen-mediated protective pathway(s) that limits or attenuates hepatocellular injury induced by reduced-size liver I/R.

Animals↗
PubMed2001

Is D2 lymphadenectomy in gastrectomy safe with regard to the skill of the operator?

BACKGROUND/AIMS: D2 gastrectomy has been regarded as an inconvenient procedure with high morbidity and no survival benefit in the West. Recent western studies, however, especially from specialist centers, have shown a survival benefit and the safety of D2 gastrectomy. The aim of this study is to clarify the safety of D2 gastrectomy (defined by the Japanese Research Society for the Study of Gastric Cancer), even if carried out by a junior surgeon, and to show that it is not a particularly difficult or special procedure. METHODS: Patients who underwent a typical distal gastrectomy (DG) with D2 resection (n = 344) and total gastrectomy (TG) with D2 resection (n = 111) were analyzed. The subjects were divided into 3 groups according to the postgraduate year of the operator (group I = the surgeon's postgraduate experience was less than 5 years; group II = surgeons with more than 5 years and less than 10 years postgraduate experience; group III = surgeons with more than 10 years postgraduate experience). The rate of postoperative complications and the 5-year survival rate were compared among the 3 groups. RESULTS: The overall operative mortality rate, hospital death rate and the overall rate of postoperative complications were 1.2, 2.0 and 10.2% in DG patients, and 14.4, 0 and 1.8% in TG patients, respectively. There was no significant difference in the operative blood loss, the rate of operative mortality, hospital death rate and postoperative complications among the 3 groups. There was no significant difference in the 5-year survival rate among the 3 groups in each stage. CONCLUSION: The postoperative mortality rate, morbidity rate and 5-year survival rate after a typical D2 gastrectomy were independent of the experience of the operator. It is considered to be a safe and useful procedure in view of the rate of postoperative complications and the long-term survival rate, even if performed by a junior trainee under the supervision of experienced surgeons in a nonspecialized hospital.

Adult↗