Search PubMed⌕ Search

Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Usefulness of chemotherapy with CPT-11 in clinic for three colorectal cancer in terminal stage].

In our clinic we performed chemotherapy with CPT-11 in three cases of non-resectable advanced colorectal cancer, including two cases of multiple liver metastasis and one case of multiple lung metastasis, and obtained various alleviating effects. Heretofore two factors. 1. direct effect and 2. longevity effects, have been focused on when evaluating the effect of various chemotherapy regimens. However, the symptoms of these patients were alleviated by the chemotherapy without obtaining either of the two effects. Furthermore, their performance statuses were improved. It is therefore sufficiently beneficial for patients in the terminal stage to undergo the chemotherapy. The patient in the terminal stage should be taken care of in the clinic rather than in the hospital. At present, safe and effective therapies on an ambulant basis have not been established. It will now be necessary for us to evaluate the many accumulated cases. It is conceivable that chemotherapy with CPT-11 in the clinic would be extremely useful for patients in the terminal stage for the purpose of improving the QOL, if the dose and administration interval of CPT-11 are given sufficient attention.

Ambulatory Care↗
PubMed2000

GST-pi gene-transduced hematopoietic progenitor cell transplantation overcomes the bone marrow toxicity of cyclophosphamide in mice.

Autologous transplantation of bone marrow cells (BMCs) transduced with the multidrug resistance 1 (MDR1) gene or dihydrofolate reductase (DHFR) gene has already been applied in clinical chemoprotection trials. However, anticancer drugs frequently used in high-dose chemotherapy (HDC), such as alkylating agents, are not relevant to MDR1 or DHFR gene products. In this context, we have previously reported that glutathione S-transferase-pi (GST-pi) gene-transduced human CD34(+) cells showed resistance in vitro against 4-hydroperoxicyclophosphamide, an active form of cyclophosphamide (CY). In the present study, a subsequent attempt was made in a murine model to evaluate the effectiveness of transplantation of GST-pi-transduced BMCs to protect bone marrow against high-dose CY. The gene transfection was carried out retrovirally, employing a recombinant fibronectin fragment. Transfection efficiency into CFU-GM was 30%. After the transplantation, recipient mice (GST-pi mice) received three sequential courses of high-dose CY. As the chemotherapy courses advanced, both shortening of recovery period from WBC nadir and shallowing of WBC nadir were observed. In contrast to the fact that three of seven control mice died, possibly due to chemotoxicity, all seven GST-pi mice were alive after the third course, at which point the vector GST-pi gene was detected in 50% of CFU-GM derived from their BMCs and peripheral blood mononuclear cells. When BMCs obtained from these seven mice were retransplanted into secondary recipient mice, 20% of CFU-GM from BMCs showed positive signals for vector GST-pi DNA after 6 months. These data indicate that the GST-pi gene can confer resistance to bone marrow against CY by being transduced into long-term repopulating cells.

Animals↗
PubMed2000

Subcutaneous treatment of p-tert-octylphenol exerts estrogenic activity on the female reproductive tract in normal cycling rats of two different strains.

Effects of p-tert-octylphenol (OP), an endocrine disrupting chemical (EDC), on the female reproductive tract of normal cycling Fischer 344 (F344) and Donryu rats were investigated. OP was subcutaneously injected at concentrations of 12.5, 25, 50 or 100 mg/kg for 28 days. The most notable changes were the disappearance of normal cyclicity in the 50 mg/kg or more OP-treated groups of both the strains, and the appearance of persistent estrus (PE) evident on examination of vaginal smears in the 100 mg/kg groups of both the strains, the effects being time- and dose-dependent. In PE rats of both the strains, the uterine morphology deviated from the normal for each estrous stage of the cycling rats, and proliferation in the endometrium was slightly increased. The data for uterine weights, luminal epithelial cell-heights and/or numbers of epithelial cells in the endometrium demonstrated equivocal alteration. In both the strains, the serum 17beta-estradiol (E2) levels were decreased with 50 mg/kg of OP or more. Serum concentrations of the administrated chemical were dose and duration-dependently increased in all the treated groups of both the strains. The results demonstrate that subcutaneous administration of OP at doses of 50 mg/kg or more exerts time- and dose-dependent estrogenic activity on the reproductive tract of normal cycling female Donryu and F344 rats, indicating similar qualitative sensitivity to the effects in both the strains. Vaginal cytology may be the most sensitive endpoint for the detection of estrogenic activity of potential EDCs using adult cycling rats.

Animals↗
PubMed2000

XSIP1, a member of two-handed zinc finger proteins, induced anterior neural markers in Xenopus laevis animal cap.

We characterized Xenopus SIP1 (XSIP1), Smad interacting protein, from activin-treated animal caps by differential screening. The XSIP1 is very similar to mouse SIP1 in the protein coding region including the zinc finger domain and homeodomain. The expression pattern was analyzed by RT-PCR and whole mount in situ hybridization. XSIP1 expression was initially restricted to the dorsal marginal zone in the late gastrula and was subsequently expressed at the lateral edge of neural plate and, in the tailbud stage, in the forebrain, neural tube, and eye. Overexpression of XSIP1 at the animal caps resulted in activation of anterior neural markers without mesodermal markers. Ectopic expression of XSIP1 induced enlargement of neural cells and disordered eye formation. In addition to abnormal head phenotypes, many embryos were short-tailed. Our findings suggest that XSIP1 is a transcriptional repressor, which may be involved in the activin-dependent signal pathway.

Amino Acid Sequence↗
PubMed2000

Intralobar bronchopulmonary sequestration evaluated by contrast-enhanced three-dimensional MR angiography.

Bronchopulmonary sequestration (PS) is characterized by non-functioning lung tissue fed from one or several aberrant systemic arteries. The condition is diagnosed by visualizing the feeding arteries using non-invasive CT, MRI, colour Doppler sonography or conventional angiography. We present a 5-year-old boy in whom intralobar sequestration was diagnosed using contrast-enhanced 3D MR angiography, which visualised fine blood vessels in the thoraco-abdominal region without arterial puncture. This technique is useful for diagnosing PS.

Bronchopulmonary Sequestration↗
PubMed2000

Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome.

Marfan syndrome (MFS; MIM #154700) is a connective tissue disorder characterized by cardiovascular, skeletal, and ocular abnormalities. The fibrillin-1 gene (FBN1; MIM no. 134797) on chromosome 15 was revealed to be the cause of Marfan syndrome. To date over 137 types of FBN1 mutations have been reported. In this study, two novel mutations and a recurrent de-novo mutation were identified in patients with MFS by means of single-strand conformational polymorphism (SSCP) analysis. The two novel mutations are a 4-bp deletion at nucleotide 2820-2823 and a G-to-T transversion at nucleotide 1421 (C474F), located on exon 23 and exon 11, respectively. A previously reported mutation at the splicing donor site of intron 2 (IVS2 G + 1A), which is predicted to cause exon skipping, was identified in a sporadic patient with classical MFS.

Amino Acid Substitution↗
PubMed2000

Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta.

BACKGROUND/AIM: Since patients with high viral load and HCV subtype 1b are known to respond poorly to interferon (IFN) therapy, the viral dynamics of HCV RNA after initiation of interferon therapy were examined in the present study with respect to two different administration regimens, once vs. twice a day. METHODS: Twenty-two patients with chronic hepatitis C confirmed by liver biopsy and with >1 Meq/ml of HCV RNA and HCV subtype 1b were randomly assigned to two different IFN administration regimens (6 million units of IFN once a day or 3 million units of IFN twice a day), and the serum HCV RNA level was serially measured. RESULTS: Graphs of HCV RNA levels vs. treatment time showed an initial rapid fall, followed by a slower clearance phase. Fitting the data to a model for HCV decay proposed by Neumann et al. showed that the treatment efficacy was significantly higher with twice daily administration. Negativity for HCV RNA measured by Amplicor assay in the twice-a-day administration group was 18%, 73% and >89% at 1, 2 and 3 weeks, respectively, in contrast to 0%, 0%, and 18%, respectively, with once-a-day administration. However, a significant reduction of platelet count and albumin level, a marked increase in serum aspartate aminotransferase/alanine aminotransferase, and a high incidence of renal toxicity (proteinuria) were found in patients receiving IFN twice a day in comparison with those receiving it once a day. CONCLUSION: The twice-a-day administration of IFN accelerated the clearance of HCV RNA from serum, leading to a more efficient virological response for patients with chronic hepatitis C, but with a high rate of renal toxicity.

Adult↗
PubMed2000

Behavior of mono-, di-, and trihydroxyoctadecenoic acids during mashing and methods of controlling their production.

The behavior of mono-, di-, and trihydroxyoctadecenoic acids was investigated during laboratory-scale mashing under various conditions with a view to controlling their production. Using a malt in which the lipoxygenase activity was at only a trace level (less than 0.01 U/g) or starting the mashing at a higher temperature than that conventionally used (65 degrees C instead of 48 degrees C) significantly decreased the production of these hydroxy fatty acids. Lowering the pH of the mash to inhibit lipoxygenase activity and preventing O2 uptake by the mash using carbon dioxide were also effective in reducing the amounts of these acids produced during mashing. From the viewpoint of industrial-scale beer production, the prevention of O2 uptake by the mash was selected as an appropriate method for reducing oxidation during wort production without affecting the subsequent brewing process or the taste of the finished beer. After introducing oxidation prevention procedures, the content of trihydroxyoctadecenoic acids decreased by about 30% and the foam stability and taste were improved in commercial products brewed using less than 25% malts.

Journal Article↗
PubMed2000

NADPH-protochlorophyllide oxidoreductase in cucumber is encoded by a single gene and its expression is transcriptionally enhanced by illumination.

NADPH-protochlorophyllide oxidoreductase (POR) catalyzes the photoreduction of protochlorophyllide a in the chlorophyll biosynthetic pathway. Recently, two POR genes, the expressions of which were differently regulated by light, were isolated in barley and Arabidopsis, and it is suggested that in angiosperms, the chlorophyll synthesis is controlled by the differential action of the two distinct POR isozymes. Meanwhile, we have isolated POR cDNA from cucumber, and reported that its expression was enhanced by illumination. In this study, we analyzed the gene expression and organization of cucumber POR in more detail. Northern blot analysis with 5'- or 3'-noncoding gene-specific and full length probes and RNase protection assay revealed that cucumber POR mRNA is transcribed from a single gene. Run-on assay revealed that the transcript level of isolated nuclei from illuminated cotyledons was 6-fold that of dark control, indicating that the light-enhanced expression of cucumber POR is caused by transcriptional activation. Using degenerated primers and the genomic DNA of cucumber as template, PCR showed the presence of only one type of fragment encoding cucumber POR. The PCR product was hybridized with the genomic Southern blot from cucumber and only one band was detected under low stringency conditions. From these results, we conclude that there is a single POR gene in cucumber and PORs are organized by different gene families among higher plants, and in cucumber the single POR may play the roles of two POR genes, which are present in other higher plants such as Arabidopsis and barley.

Journal Article↗
PubMed2000

Cloning a novel developmental regulating gene, Xotx5: its potential role in anterior formation in Xenopus laevis.

The vertebrate Otx gene family is related to otd, a gene contributing to head development in Drosophila. In Xenopus, Xotx1, Xotx2, and Xotx4 have already been isolated and analyzed. Here the cloning, developmental expression and functions of the additional Otx Xenopus gene, Xotx5 are reported. This latter gene shows a greater degree of homology to Xotx2 than Xotx1 and Xotx4. Xotx5 was initially expressed in Spemann's organizer and later in the anterior region. Ectopic expression of Xotx5 had similar effects to other Xotx genes in impairing trunk and tail development, and especially similar effects to Xotx2 in causing secondary cement glands. Taken together, these findings suggest that Xotx5 stimulates the formation of the anterior regions and represses the formation of posterior structures similar to Xotx2.

Amino Acid Sequence↗
PubMed2000

Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a specific chemokine to recruit and activate monocytes from the circulation to inflammatory site. In diabetic nephropathy, similar to other glomerulonephropathies, infiltration and activation of monocytes/macrophages in glomerulus have been implicated in the development of glomerular injury. The aim of the present study was to examine a possible relationship of MCP-1 with diabetic nephropathy and to investigate the role of glycated albumin (Gly-Alb) as well as high concentration of glucose (HG) on MCP-1 production by cultured human mesangial cells. METHODS: MCP-1 in serum or urine and urinary albumin (Alb) as well as several clinical parameters such as plasma glucose, serum Gly-Alb, and hemoglobin A1c (HbA1c) were measured after overnight fasting in 16 control subjects and 54 diabetic patients. The relationships between the levels of urinary Alb and urinary or serum MCP-1 and also between the values of respective clinical parameter and urinary MCP-1 levels were analyzed. Next, using cultured human mesangial cells, we investigated the role of Gly-Alb and/or HG on the gene and protein expression of MCP-1. RESULTS: Urinary levels (ng/g creatinine), but not serum levels, of MCP-1 increased in accordance with the extent of albuminuria. In all subjects, there were significant correlations between the urinary levels of Alb and MCP-1 (r = 0.746, P < 0.0001) and between the levels of serum Gly-Alb and urinary MCP-1 (r = 0.475, P < 0.0001). In cultured human mesangial cells, the gene and protein expression of MCP-1 was dose and time dependently up-regulated by Gly-Alb. HG slightly but significantly stimulated MCP-1 expression. The combination of Gly-Alb and HG showed the greatest stimulation in more than an additive manner on MCP-1 production. CONCLUSIONS: This study suggests that facilitated MCP-1 production by mesangial cells in diabetic milieu contributes to the initiation and progression of diabetic nephropathy.

Adult↗
PubMed2000

Safe and efficient gene transfer into porcine hepatocytes using Sendai virus-cationic liposomes for bioartificial liver support.

Establishment of a bioartificial liver support system using genetically modified hepatocytes is a potential approach to improve the treatment of severe liver failure. We describe the development of an efficient ex vivo method of gene transfer into a large number of porcine hepatocytes using hemagglutinating virus of Japan (HVJ)-liposome. The transfection efficiency of HVJ-liposome into isolated porcine hepatocytes attached to microcarrier beads was evaluated by beta-galactosidase (beta-gal) staining, fluorescence activated cell sorting analysis for beta-gal and luciferase assay, respectively. To examine the function and cellular damage of transduced hepatocytes, we used enzyme-linked immunosorbent assay for porcine albumin synthesis, lidocaine clearance test (P-450 activity), aspartate aminotransferase, and lactic dehydrogenase release assays. The optimal conditions for gene transfer into the beads-attached hepatocytes using HVJ-liposome included 4 microg of deoxyribonucleic acid with 200 microg of lipid/2 x 105 cells and exposure duration of 90 min. Under these conditions, beta-gal and luciferase genes were transduced to 2.5 x 108 isolated porcine hepatocytes following attachment to the beads. Positive beta-gal staining was observed in more than 30% of the beads-attached hepatocytes. The gene transfer activity of HVJ-liposome method determined by luciferase activities was about 100-fold of that of the lipofection method. Transfected porcine hepatocytes remained functional without any significant cell damage. Our results demonstrated that HVJ-liposome mediated gene transfer into microcarrier-attached porcine hepatocytes is an efficient and nontoxic method suitable for a bioartificial liver support sytem.

Animals↗
PubMed2000

Expression of NADPH-Protochlorophyllide oxidoreductase gene in fully green leaves of cucumber.

Photoreduction of protochlorophyllide a to chlorophyllide a that is catalyzed by NADPH-protochlorophyllide oxidoreductase (NPR) is only a light-dependent step in overall processes of biosynthesis of Chl in angiosperms. Unlike many other plants, in fully green leaves of cucumber the expression of only a single NPR gene of cucumber was positively regulated by light and developmental age of leaf, and also by diurnal and circadian rhythms. The single NPR gene was shown to be involved in Chl synthesis throughout of the vegetative growth of cucumber (in cotyledons and fully green leaves).

Circadian Rhythm↗