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K Hino

Publications and source records attributed to K Hino.

At least 19 recordsLinked to original sources
PubMed1999

Species difference in simultaneous transport and metabolism of ethyl nicotinate in skin.

The objective of this research was to compare the characteristics of skin permeation and metabolism of ethyl nicotinate (EN) among humans and several animal models. In vitro simultaneous skin permeation and metabolism experiment of EN was done in side by side diffusion cells at 37 degrees C. An EN hydrolysis experiment was carried out using skin homogenate and kinetic parameters (Vmax and K(m)) were estimated by computer data-fitting to Michaelis-Menten equation. Both EN and a metabolite, nicotinic acid (NA), were detected in all receiver solutions in permeation studies and no significant chemical hydrolysis was found, indicating that enzymatic hydrolysis of EN occurred during the skin permeation process. Difference in total (EN + NA) flux, from EN-saturated solution, was less than double among various species. The ratio of NA flux to total flux was highest for rat (0.94) followed by hairless rat, mouse, human and hairless mouse (0.76, 0.23, 0.19 and 0.13), and thus a great species difference was found in skin esterase activity. Total flux increased linearly with increase in donor concentration for all species. For hairless rat, mouse and hairless mouse, NA fluxes increased with increase in EN donor concentration and reached a plateau, suggesting that metabolic saturation occurred in skin. Species difference in NA fluxes and EN donor concentration in which the NA flux reached a plateau were also found. In rats, kinetic parameters for EN hydrolysis using skin homogenate were significantly higher than those in mice. These results suggest that species difference in permeation profiles of EN might primarily reflect the difference in esterase activity. To predict skin permeability in human using an animal model, the species difference in skin metabolism should be taken into consideration.

Animals↗
PubMed1999

Differences in hypervariable region 1 quasispecies of hepatitis C virus in human serum, peripheral blood mononuclear cells, and liver.

Hepatitis C virus (HCV) has been reported to potentially replicate in peripheral blood mononuclear cells (PBMCs), but direct information on the pathogenic implication of HCV infection in PBMCs is still limited. To investigate this issue, we compared the complexity of HCV quasispecies in serum, PBMCs, and livers of 13 patients with type C chronic liver disease. Hypervariable region 1 (HVR 1) was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were subcloned and sequenced. Considerable differences in the complexity of HVR 1 quasispecies were found in the serum, PBMCs, and liver in all patients, and the predominant sequences from each source were mutually different in 3 (23%) patients. An amino acid sequence unique to each source existed as well as a sequence common to serum and PBMCs, common to serum and livers, or common to PBMCs and liver. These results suggest infection of PBMCs by HCV, and that HCV in PBMCs may be differently exposed to host immunity from that in liver.

Adult↗
PubMed1999

Factors predicting progression to cirrhosis and hepatocellular carcinoma in patients with transfusion-associated hepatitis C virus infection.

The clinical progression of chronic hepatitis C is not uniform throughout the entire period of infection and is more rapid in patients with advanced histologic disease. Our study was designed to identify factors contributing to progression to cirrhosis and hepatocellular carcinoma by taking the entire period of infection into consideration. Two hundred thirteen patients with transfusion-associated hepatitis type C chronic liver disease were included in this study. They did not have either a history of antiviral therapy or any other potential causes of chronic liver disease except for transfusion. Hepatitis C virus genotype 1b was detected in 144 (68%) patients, followed by 2a in 51 (24%), 2b in 11 (5%), 1a in 4 (2%), and coinfection with 1b and 2a in 3 (1%). The log-rank test in the Kaplan-Meier method revealed that the cumulative percentage of cirrhosis-free or hepatocellular carcinoma-free patients became significantly lower as the transfusion age went up. Patient age at the time of transfusion was the only independent factor related to disease progression in multivariate analysis using Cox's proportional hazards model. Thus age at transfusion should be taken into consideration in designing the optimal follow-up schedule and therapy in patients with posttransfusion-associated chronic hepatitis C.

Adult↗
PubMed1998

Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group.

To elucidate the risk factors for liver carcinogenesis and to examine the incidence of hepatocellular carcinoma (HCC) after interferon therapy, 1,022 chronic hepatitis C patients treated with interferon were followed by ultrasonography for 13 to 97 months (median 36 months). Sustained response with prolonged alanine aminotransferase normalization was found in 313 patients, transient response with alanine aminotransferase relapse after therapy in 304, and no response in 405. Forty-six developed HCC, of whom 5 were sustained responders, 9 were transient responders, and 32 were nonresponders. The cumulative incidence of HCC in transient responders was almost equal to that in sustained responders, and it was significantly higher in nonresponders than in sustained and transient responders (P=.0009). The seventh-year cumulative incidence rates of HCC in sustained responders, transient responders, and nonresponders were estimated to be 4.3%, 4.7%, and 26.1%, respectively. However, there was no significant difference in the cumulative incidence of HCC between patients with HCV subtype 1 and 2 (P=.14). Cox regression analysis showed that the risk of HCC development was not elevated in transient responders compared with sustained responders, but that the risk was 7.90-fold higher in nonresponders than in sustained responders (P=.008). Patients > or =55 years of age had a significantly higher risk ratio (4.65) than did those under 55 years of age (P=.006). The risk of HCC development in men was 4.35 times higher than the risk in women (P=.02). However, the degree of fibrosis was not a significant risk factor for the development of HCC (risk ratio, 3.16; P=.052). These results suggest that patients in the high-risk group of HCC after interferon therapy were those who showed no response, those who were older, and those who were male, and that such patients should be carefully followed using ultrasonography.

Adult↗
PubMed1998

Mother-to-infant transmission occurs more frequently with GB virus C than hepatitis C virus.

A total of 107 hepatitis C virus (HCV)-infected pregnant women were screened for GB virus C (GBV-C) RNA in their sera, and 11 (10.3%) were positive. Among 11 infants born to these HCV/GBV-C co-infected mothers, GBV-C RNA was detected in 7 (63.6%) while HCV RNA was found in 1 (9.1%) within 1 year after birth: this difference was statistically significant (p = 0.023). The mothers of infected infants had significantly higher serum titers of GBV-C RNA than those of uninfected infants: 10(6.7 +/- 0.5) vs 10(4.0 +/- 1.0) copies/ml in average (p = 0.001). The baby in whom HCV RNA was found was also positive for GBV-C RNA, and had an elevation in serum transaminase levels, whereas all the other GBV-C infected infants showed no evidence for hepatitis. A family study, performed on 2 of the 7 infected cases, revealed that all the elder siblings of the index infants were also GBV-C RNA-positive. Nucleotide sequence of GBV-C RNA, amplified by PCR from an NS3 region, was completely identical between the mother and the infant within each family, but varied significantly across different families. These results suggest that GBV-C is more easily transmitted from mother to infant than HCV, although hepatitis is not caused thereby.

Base Sequence↗
PubMed1998

Hepatitis B virus genomic sequence in the circulation of hepatocellular carcinoma patients: comparative analysis of 40 full-length isolates.

We determined full-length nucleotide sequence of hepatitis B virus (HBV) genome in sera from 40 Japanese patients with HBsAg-positive hepatocellular carcinoma (HCC), in order to obtain information on HCC-specific characteristics, if any, of the HBV genome. Direct sequencing of the long distance PCR products starting from 50 microliters of serum samples revealed that 95% of our isolates were of genotype C, and that mutations and deletions/insertions were very common. With respect to envelope protein genes, deletions and missense mutations were frequent in preS2, and the determinant a domain of HBsAg was rich in "antibody-escape" mutations. Within the precore/core region, the most remarkable mutation was the replacement of proline of wild type by other amino acids at codon 130 of the core gene, which was found in 58% of our isolates, while precore-stop mutation was found in 45%. Most interestingly, however, about 90% of our isolates had mutations at nt positions 1762 (A-to-T) and 1764 (G-to-A) within the core promoter, which had been implicated in "e-suppressive" phenotype of HBV genome. G-to-A at nt 1613 and C-to-T at nt 1653 within enhancer II and T-to-C/A at nt 1753 within core promoter were also evident: 38%, 53%, and 40%, respectively. It was interesting that some of the characteristics observed in our isolates form HCC patients had been previously implicated in fulminant hepatitis and/or acute exacerbation of chronic hepatitis.

Adult↗
PubMed1998

Enhancement by bufalin of retinoic acid-induced differentiation of acute promyelocytic leukemia cells in primary culture.

Bufalin, a cardiotonic steroid isolated from the Chinese toad venom preparation Chan'su, has differentiation-inducing activity in several myeloid leukemia cell lines. We examined the effect of bufalin on differentiation of leukemic cells from acute myeloid leukemia (AML) patients in primary culture. Bufalin significantly stimulated functional and morphologic differentiation of leukemia cells in four of 20 cases, suggesting that bufalin alone is only a modest inducer of differentiation of AML cells in primary culture. In contrast, acute promyelocytic leukemia (APL) cells showed synergistic differentiation after treatment with all-trans retinoic acid (RA) and bufalin. In some cases, bufalin restored RA sensitivity to previously resistant APL cells. The effective concentration of bufalin for differentiation-inducing activity in APL cells was lower than for its cardiac action. Combined treatment with bufalin and RA may be more effective than RA alone in differentiation therapy of APL.

Acute Disease↗
PubMed1998

Evolution of hepatitis G virus infection and antibody response to envelope protein in patients with transfusion-associated non-A, non-B hepatitis.

The clinical significance and course of acute hepatitis G virus (HGV) infection were studied by measuring HGV RNA and antibody to HGV envelope protein E2 (HGV-E2 antibody). A total of 59 patients with transfusion-associated non-A, non-B hepatitis, who were followed-up for more than 1 year, were selected retrospectively. HGV RNA was measured by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) was performed, using primer sets, in the 5'-non-coding region of the HGV genome. HGV-E2 antibody was measured by enzyme-linked immunosorbent assay (ELISA) using recombinant E2 protein. Of the 59 patients, 51 (86%) were infected with hepatitis C virus (HCV) and 12 (20%) were infected with HGV; 11 of the 12 with HGV infection were also infected with HCV. HGV viraemia was cleared during the follow-up period in seven of the 12 patients with HGV infection. All these seven patients seroconverted for HGV-E2 antibody just before or just after the clearance of HGV viraemia. In contrast, all five patients without clearance of HGV viraemia were negative for HGV-E2 antibody (P = 0.0013). Of seven patients with continuous HGV viraemia at 1 year from the onset of acute hepatitis, four with HCV RNA showed chronic elevation of alanine aminotransferase (ALT) but three without HCV RNA did not. The severity of acute hepatitis was similar between patients with both HGV and HCV infections and in those with HCV infection alone. The majority of patients with HGV infection cleared the virus during long-term follow-up. Appearance of HGV-E2 antibody was associated with the clearance of HGV viraemia. An abnormal ALT level was noted to depend on HCV infection but not on HGV infection in both the acute and chronic phases of transfusion-associated hepatitis.

Acute Disease↗
PubMed1998

Use of PCR in resolving diagnostic difficulties potentially caused by genetic variation of hepatitis B virus.

AIMS: To assess the relevance of genetic variants of hepatitis B virus (HBV) and to demonstrate the usefulness of the polymerase chain reaction (PCR) in cases of HBV diagnostic difficulty. METHODS: Five serum samples from patients that presented diagnostic difficulty in routine laboratories were sent to a research laboratory for PCR, and if appropriate, S gene sequencing, in vitro expression, and antigenic analysis. RESULTS: The demonstration of HBV in serum by PCR allowed a definitive diagnosis of current infection. One serum sample with poor reactivity in a diagnostic assay had a minor hepatitis B surface antigen (HBsAg) variant and another with very poor reactivity had multiple variants of HBsAg. Transient HBsAg reactivity was observed in a recently vaccinated patient. A hepatitis Be antigen (HBeAg) false positive reaction was noted in a patient from a well defined risk group for HBV. One patient who was strongly HBsAg/HBeAg positive, but anti-hepatitis B core antibody negative, was viraemic. CONCLUSIONS: PCR may become the gold standard for the diagnosis of current HBV infection. HBV variants are responsible for a proportion of diagnostically difficult cases. Modification of commercial assays is necessary to increase the sensitivity of detection of such variants.

Adult↗
PubMed1998

7-(2-Aminomethyl-1-azetidinyl)-4-oxoquinoline-3-carboxylic acids as potent antibacterial agents: design, synthesis, and antibacterial activity.

2-Aminomethyl-1-azetidinyl, -1-pyrrolidinyl, and -1-piperidinyl groups were designed as novel C-7 substituents for potential antibacterial quinolone agents. Of the three substituents, the 2-aminomethyl-1-azetidinyl group (compound 12a) was found to be the most favorable for enhancing the activity of the 6,8-difluoroquinoline molecule 12. Therefore the 2-aminomethyl-1-azetidinyl group was introduced into a variety of quinolines (giving 24-26a, and 28a) and naphthyridines (giving 31a and 32a). Through optical resolution of 1-benzylazetidine-2-carboxamide (19) and chiral synthesis of its R-isomer, both enantiomers of 2-aminomethyl-1-azetidinyl quinolines 12a and 24-26a were also prepared. The most active of all the compounds was 5-amino-6,8-difluoroquinoline (R)-26a. The activity of (R)-26a was more potent than those of the corresponding 1-piperazinyl derivative (3) and sparfloxacin (1), and was comparable to those of the corresponding 3-amino-1-pyrrolidinyl (4), 3-aminomethyl-1-pyrrolidinyl (5), and 3-amino-1-azetidinyl (6) derivatives.

4-Quinolones↗
PubMed1997

Differences in hypervariable region 1 quasispecies between immune complexed and non-immune complexed hepatitis C virus particles.

Antibody to the hypervariable region 1 of hepatitis C virus (HCV) is thought to have neutralizing activity. The complexity of hypervariable region 1 quasispecies was compared between immune complexed and non-immune complexed HCV particles. Immune complexes and non-immune complexes, including intact HCV virions, were separated by differential flotation centrifugation and immunoprecipitation, and immune complexes were observed in 9 of 11 patients with chronic hepatitis C. Considerable differences in both hypervariable region 1 quasispecies and predominant clones were demonstrated between immune complexes and non-immune complexes in 4 patients and not in 5 patients. These results suggest that the specificity of antibody to hypervariable region 1 is related to the formation of immune complexes and that escape mutants with highly different quasispecies are resistant to neutralization by antibody to hypervariable region 1.

Adult↗
PubMed1997

Studies on the contribution of c-fos/AP-1 to arthritic joint destruction.

Features characteristic to rheumatoid joint destruction, including synovial overgrowth and bone resorption, are experimentally produced by augmenting c-fos gene expression. We tested here if arthritic joint destruction was inhibited upon inactivation of the c-fos/AP-1 signal by administering short double-stranded AP-1 DNA oligonucleotides into mice with collagen-induced arthritis to compete for the binding of AP-1 in vivo at the promoter binding site. Arthritic joint destruction was inhibited in a sequence-specific and dose-dependent manner by oligonucleotides containing the AP-1 sequence. The oligonucleotides inhibited gene expression at the transcriptional level. Nucleotide sequences besides AP-1 also appeared to be important structurally for binding of AP-1 onto DNA and for the stability of oligonucleotides against nucleases. Immunohistochemical chase experiment administering biotinylated oligonucleotides into arthritic mice showed that AP-1 oligonucleotides reached the inflamed joint. Thus, activation of c-fos/AP-1 appears essentially important in arthritic joint destruction.

Animals↗
PubMed1997

Reversibility of monocytic differentiation of HL-60 cells by 1alpha,25 dihydroxyvitamin D3.

Although 1alpha,25(OH)2D3 induces HL-60 cells to differentiate into monocytes, whether or not these monocytes revert to native promyelocytes is not clear. To investigate this question, HL-60 cells were treated with 1alpha,25(OH)2D3, and divided into CD14-positive and -negative cells with a cell sorter. These two populations were cultured with or without 1alpha,25(OH)2D3. Sorted CD14-positive HL-60 cells, treated with 1alpha,25(OH)2D3 for 7 days, reverted to CD14-negative cells and promyelocyte-like cells if 1alpha,25(OH)2D3 was removed from the medium. We conclude that the 1alpha,25(OH)2D3-induced differentiation of HL-60 cells into monocytes is reversible, and continuous administration of 1alpha,25(OH)2D3 is required for the differentiation of HL-60 cells.

Calcitriol↗
PubMed1997

Correlation between relative number of circulating low-density hepatitis C virus particles and disease activity in patients with chronic hepatitis C.

Hepatitis C virus (HCV) circulates as particles having differing buoyant densities. Changes in the relative proportions of virus particles of different densities were examined in 19 patients with chronic hepatitis C: 6 without (group A) and 13 with (group B) abnormal serum alanine aminotransferase (ALT) levels. High- and low-density virus particles were separated by differential flotation centrifugation. The numbers of high-density particles consistently exceeded that of low-density particles in all patients in group A, whereas the titers of both types of particles were the same at least once in 7 of 10 patients sampled at two time points in group B. The ALT level significantly increased <2 months later (P < 0.05) when the titers of both types of particles were the same in patients in group B. Thus, we found a correlation between the relative numbers of circulating low-density HCV particles and disease activity in chronic hepatitis C patients.

Adult↗