Biomedical subjects

K Hino

Publications and source records attributed to K Hino.

At least 37 records · Page 2Linked to original sources

PubMed2000

Epstein-Barr virus-encoded poly(A)(-) RNA supports Burkitt's lymphoma growth through interleukin-10 induction.

Akata and Mutu cell lines are derived from Burkitt's lymphoma (BL) and retain the in vivo phenotype of Epstein-Barr virus (EBV) expression that is characterized by expression of EBV-determined nuclear antigen 1 (EBNA1), EBV-encoded RNAs (EBERs) and transcripts from the BAM:HI A region (BARF0). We found that EBV-positive Akata and Mutu cell clones expressed higher levels of interleukin (IL)-10 than their EBV-negative subclones at the transcriptional level. Transfection of an individual EBV latent gene into EBV-negative Akata cells revealed that EBERs were responsible for IL-10 induction. Recombinant IL-10 enabled EBV-negative Akata cells to grow in low (0.1%) serum conditions. On the other hand, growth of EBV-positive Akata cells was blocked by treatment either with an anti-IL-10 antibody or antisense oligonucleotide against IL-10. EBV-positive BL biopsies consistently expressed IL-10, but EBV-negative BL biopsies did not. These results suggest that IL-10 induced by EBERs acts as an autocrine growth factor for BL. EBERs, EBER1 and EBER2, are non-polyadenylated RNAs and are 166 and 172 nucleotides long, respectively. The present findings indicate that RNA molecules could regulate cell growth.

Burkitt Lymphoma↗

PubMed2000

Augmentation of cancellous screw fixation with hydroxyapatite composite resin (CAP) in vivo.

The fixation of fractured bone with screws is important for orthopedic surgery, however, rigid fixation often cannot be attained in elderly patients with osteoporosis. Recently, we developed a new injectable, nonresorbable bone cement (CAP) that possesses mechanical and biological properties superior to those of polymethylmethacrylate (PMMA) cement. CAP can directly bond with bone without intervening fibrous tissue, and the peak curing temperature is 46 degrees C. In this study, we assessed the effects of CAP and PMMA cement on the augmentation of screw fixation in vivo. A cancellous screw was placed in the proximal metaphysis of rabbit tibiae. One side of each tibia was randomly selected to be augmented with CAP or PMMA. The contralateral side received a screw without cement (control). Of the 36 rabbits included in this study, 9 rabbits from each group were sacrificed and the tibial constructs retrieved 1 or 3 months after the initial operation. The screws were then pulled out to failure. The values of the pullout force of the screws augmented with CAP and PMMA were higher than those of the control specimens at both 1 month (319 +/- 58 N for CAP vs. 105 +/- 41 N for control; p < 0.05, 284 +/- 100 N for PMMA vs. 132 +/- 71 N for control; p < 0.05) and 3 months (387 +/- 109 N for CAP vs. 196 +/- 107 N for control; p < 0.05, 372 +/- 145 N for PMMA vs. 242 +/- 100 N for control; p > 0.05) after the operation. However, the average increase in the pullout force between CAP and PMMA augmentation was not statistically significant at either time. The values of energy absorption augmented with CAP and PMMA were also higher than those of the control specimens at both 1 month (129 +/- 54 N*mm for CAP vs. 19 +/- 10 N*mm for control; p < 0.05, 145 +/- 95 N*mm for PMMA vs. 28 +/- 21 N*mm for control; p < 0.05) and 3 months (172 +/- 58 N*mm for CAP vs. 44 +/- 41N*mm for control; p < 0.05, 185 +/- 198 N*mm for PMMA vs. 67 +/- 49N*mm for control; p > 0.05) after the operation. However, there were also no significant differences in energy absorption between the two types of cement augmentation. On the other hand, a significant increase was not observed in stiffness among the CAP, PMMA, and respective control groups at either 1 month (626 +/- 133 N/mm for CAP vs. 441 +/- 180 N/mm for control; p < 0.05, 577 +/- 87 N/mm for PMMA vs. 450 +/- 121 N/mm for control; p > 0.05) or 3 months (622 +/- 144 N/mm for CAP vs. 600 +/- 204 N/mm for control; p > 0.05, 633 +/- 175 N/mm for PMMA vs. 630 +/- 168 N/mm for control; p > 0.05) after the operation, except in the average increase between CAP augmentation and its control 1 month after the operation. These results suggested that a cancellous screw fixation augmented with CAP, as well as PMMA, was effective compared with the unaugmented control in vivo. Because of its biocompatibility and low curing temperature, CAP can be used clinically to augment cancellous screw fixation.

Animals↗

PubMed2000

Mechanical evaluation of a bio-active bone cement for total hip arthroplasty.

A new bio-active bone cement, known as CAP, has been developed as an alternative to acrylic bone cement. CAP has improved mechanical properties, with a high modulus that is over five times that of PMMA. The effects of this high modulus are examined by finite element analysis, when the CAP is used in place of PMMA to fix the femoral component in total hip prostheses. The results show a higher tensile stress of 8.76 MPa in the CAP cement, compared with 1.99 MPa in the PMMA cement. However, it is also shown that CAP has a superior fatigue strength of approximately 40 MPa, obtained from a cyclic loading test.

Arthroplasty, Replacement, Hip↗

PubMed2000

Hepatitis viral infection in Behçet's disease.

To elucidate the role of hepatitis viruses in the pathogenesis of Behçet's disease (BD), we measured hepatitis viral markers (anti-hepatitis A (anti-HA), HBsAg, anti-HBs, anti-HBc) and viral nucleic acids (hepatitis B virus (HBV)-DNA, hepatitis C virus (HCV)-RNA, GB virus C (GBV-C)-RNA, TT virus (TTV)-DNA) in the sera of 68 BD patients along with 76 blood donors matched for age and sex. Positivity of anti-HA in patients with BD (36.8%) was lower than that in blood donors (68.0%). Both anti-HCV and HCV-RNA were detected in only one (1.5%) patient with BD and in none of the blood donors. The prevalence ratios of HBsAg, anti-HBs, anti-HBc in both groups were similar (2.9:0, 16.2:15.8 and 17.7:19.7%, respectively). However, serum HBV-DNA was detected more frequently in BD patients (8/68; 11.8%) than in blood donors (2/76; 2.6%) (P<0.05). The prevalence of GBV-C-RNA was also higher in patients with BD (4/68; 5.9%) compared with blood donors (0%). However, characteristics and clinical features are similar between GBV-C-RNA-positive and -negative groups. With respect to the prevalence of TTV-DNA, there was no significant difference between BD patients (23.5%) and blood donors (30.3%). Our study indicates that HBV and GBV-C infection might be related to BD, although the role of these viruses remains to be investigated.

Journal Article↗

PubMed2000

Predication of axillary lymph node metastasis by intravenous digital subtraction angiography in breast cancer, its correlation with microvascular density.

Accurate predication of axillary node status by non-invasive diagnostic method would be of great value in cases of breast cancer. There have been few reports advocating digital subtraction angiography (DSA) as specifically advantageous for the detection of lymph node metastasis. IV (intravenous)-DSA was carried out on 42 patients with breast carcinoma using a DSA system with a matrix of 1024 x 1024 pixels. When a mass became stained in the axilla, it was considered to be metastatic. An immunohistochemical technique with JC70 antibody to platelet/endothelial cell adhesion molecules was used to evaluate the microvascular density (MVD) of the axillary lymph nodes. IV-DSA achieved a 76.2% sensitivity, 85.7% specificity, and 81.0% accuracy. The average MVD with JC70 antibody was 97.7 +/- 44.4 in metastatic and 62.9 +/- 23.6 in nonmetastatic nodes. MVD was significantly higher in the cancerous than in the noncancerous regions within lymph nodes. The MVD was 105 +/- 38.4 in DSA-N(+) cases and was 57.8 +/- 21.9 in DSA-N(-) cases, and the difference was statistically significant. In conclusion, IV-DSA is a useful diagnostic modality for detection of axillary lymph node metastasis. This new modality predicts lymph node status by assessing the neovascularization of the lymph node.

Adult↗

PubMed2000

Early mutation of precore (A1896) region prior to core promoter region mutation leads to decrease of HBV replication and remission of hepatic inflammation.

To evaluate the relationship between mutations and clinical courses, we investigated precore (preC) and core promoter (CP) mutations and serum HBV DNA levels in HBe-antibody-positive HBV carriers. Fifty-six asymptomatic carriers (ASC), 29 patients with chronic hepatitis who showed normal ALT levels for more than two years (CH-ASC), 31 patients with chronic hepatitis (CH), and 32 patients with hepatocellular carcinoma (HCC) were studied. Almost all patients (99.2%) had mutations in either CP or preC. Mutation only in preC (A1896) was present in 52.2% with ASC, 25.0% with CH-ASC, 16.1% with CH, and 8.0% with HCC, and was significantly higher in ASC (P < 0.01). The patients with only preC mutation showed low HBV DNA levels in each clinical stage. The mutation of preC (A1896) prior to the mutation of CP might control the replication of HBV, which leads to the remission of hepatitis.

Adult↗

PubMed2000

Hepatitis C virus quasispecies and response to interferon therapy in patients with chronic hepatitis C: a prospective study.

We prospectively examined whether the complexity of hepatitis C virus (HCV) quasispecies is related to the response to interferon (IFN) therapy. Among 64 patients who had histologically proven chronic hepatitis and were treated with natural IFN-alpha, 53 patients were analysed. The other 11 patients discontinued therapy because of adverse effects of IFN. The complexity of the hypervariable region 1 (HVR 1) in quasispecies was determined using both clone number determined by fluorescence single-strand conformation polymorphism (SSCP) and nucleotide diversity determined by direct sequencing. These parameters were measured not only before treatment but also at completion and 6 months after therapy, if serum HCV RNA was detectable. This population of patients was different from the general Japanese population with regard to the high prevalence of patients infected with genotype 2a or 2b (49%), who had a higher viral load than those with genotype 1b (P = 0.021). Twenty-two patients (41.5%) were sustained responders. Genotype non-1b (P = 0.0009) and a smaller clone number (P = 0.008) were significantly associated with a sustained response. In multivariate analysis, these variables were independently associated with a sustained response (i.e. genotype: odds ratio 6.84, 95% CI 1.84-30. 12; and clone number: odds ratio 1.26, 95% CI 0.99-1.68). The clone number and nucleotide diversity did not change significantly between pretreatment and at completion or 6 months after therapy. These results suggest that lower complexity of HVR 1 quasispecies predicts a preferable response to IFN therapy that is independent of viral load, especially in the population of the relatively high prevalence of patients infected with genotype 2.

Adolescent↗

PubMed2000

Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and artepillin C.

The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated from the measurement of renal thiobarbituric acid-reactive substances (TBARS) or histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10 mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the renal proximal tubules, and gave rise to RCC 12 months later. A protective effect from carcinogenicity was observed in mice given propolis or Artepillin C. Furthermore, the mice given Fe-NTA only developed multiple cysts composed of precancerous lesions with multilayered and proliferating large atypical cells. Mice treated with propolis and Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe-NTA in mice.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

GB virus C/hepatitis G viremia and antibody response to the E2 protein of hepatitis G virus in hemodialysis patients.

The aim of this study was to assess the relationship between the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) RNA and that of antibody to the putative E2 protein (anti-E2) in hemodialysis patients. GBV-C/HGV RNA in serum was detected by a reverse transcription polymerase chain reaction (RT-PCR) assay, and anti-E2 was measured in 244 hemodialysis patients by enzyme-linked immunosorbent assay using recombinant E2 protein. The GBV-C/HGV RNA level was determined by competitive RT-PCR with an interval of 1 year. GBV-C/HGV RNA, anti-E2. and both together were detected in 11 (4.5%), in 19 (7.8%), and in 3 patients (1.2%), respectively. Comparison of clinical characteristics between GBV-C/HGV RNA-positive patients and negative patients revealed the longer duration of hemodialysis (9.8 years vs. 6.0 years; p < 0.05), and the greater frequency of anti-hepatitis C virus (HCV) (63.6% vs. 20.3%; p < 0.05) and HCV RNA (36.4% vs. 12.9%; p < 0.05) in GBV-C/HGV RNA-positive patients. The GBV-C/HGV RNA levels of patients who were positive for anti-E2 remained under detection limit (< 10(2) copies/mL), whereas only one of eight patients who were negative for anti-E2 showed a GBV-C/HGV RNA level under detection limit (p < 0.05). The presence of anti-E2 in serum was associated with loss of detectable GBV-C/HGV RNA or with a very small amount of HCV RNA in hemodialysis patients.

Antibodies, Viral↗

PubMed2000

Salivary excretion of N-nitrosodimethylamine in dogs.

Carcinogenic N-nitroso compounds (NOCs) are not only ingested from the environment but are also formed endogenously from precursors. It has been reported that nitrate, an NOC precursor, has an enterosalivary cycle and that the cycle increases the chance of exposure to NOCs. However, there is no information on the salivary excretion of NOCs. In the present study, the toxicokinetics of N-nitrosodimethylamine (NDMA) in dogs was evaluated, focusing on the salivary excretion. Following intravenous injection of 2 mg/kg NDMA, the plasma concentration showed a monoexponential decline, and the total body clearance and apparent distribution volume were greatly in excess of the hepatic plasma flow and total body water, respectively. A high concentration of NDMA was immediately detected in the plasma after oral administration of the same dose, and the oral bioavailability was almost 100%. NDMA was rapidly excreted into the saliva after both treatments, and the concentration in saliva was higher than that in the plasma. These results suggest that NDMA also has an enterosalivary cycle: NDMA is partially excreted from blood into saliva, delivered into the gastrointestinal tract by swallowing the saliva, and then completely reabsorbed into the systemic circulation. This concept was also supported by kinetic analysis based on a compartment model. The enterosalivary cycle of NDMA cannot be ignored in the risk assessment of carcinogenesis.

Animals↗

PubMed2000

Assay of DNA photolyase activity in spinach leaves in relation to cell compartmentation-evidence for lack of DNA photolyase in chloroplasts.

Spinach cyclobutane pyrimidine dimer (CPD)-specific DNA photolyase was successfully detected in leaf extracts by an assay system for plant photolyase using an improved enzyme-linked immunosorbent assay (ELISA) which was newly introduced by novel horseradish peroxidase (HRP)-linked CPD specific monoclonal antibodies. The assay system includes two main steps: a photorepair reaction of CPD introduced in substrate DNA and measurement of CPD remained after the photorepair by the improved ELISA. When CPD- induced salmon sperm DNA was used as a substrate, high CPD-photolyase activities were observed in the enzyme fraction prepared from whole spinach leaf extracts, but not from chloroplast extracts. This strongly suggests that spinach CPD-specific photolyases are localized in cell compartments other than chloroplasts.

Animals↗

PubMed2000

[Undifferentiated blastic cell crisis of chronic myelogenous leukemia with myeloblastic tumor in the skin].

A 54-year-old female, who had been treated for 4 years in the chronic phase of chronic myelogenous leukemia (CML) was admitted for management of a CML blastic crisis. Blast cells showed strong positive expression of CD7 and HLA-DR, and weakly expressed CD2, CD5 and CD10, as well. The cells were peroxidase negative in peripheral blood and bone marrow. An undifferentiated blastic crisis was diagnosed and she was treated with Interferon-alpha and VP(vincristine 2 mg/week; prednisolone 30 mg/day). A 5-7 mm in diameter tumor in the skin of the anterior right chest appeared one week after VP therapy. The tumor consisted of blasts which were CD13, CD33 and peroxidase positive, unlike the peripheral undifferentiated blasts. This is a rare case of mixed blast crisis with an increase in undifferentiated blasts in peripheral blood and bone marrow, and myeloblastic tumor formation in the skin.

Blast Crisis↗

PubMed2000

[Clinical utility of transcription mediated amplification-hybridization protection method(TMA-HPA) for the detection of HBV DNA: a comparison with the branched DNA probe assay].

The clinical utility of the TMA-HPA method for the detection of HBV DNA was evaluated by comparing results with the branched DNA probe(b-DNA) assay. Sera from 135 biopsy-confirmed HBV carriers were included in the study. Dilution tests with two representative sera revealed the sensitivity of the TMA-HPA method to be 100-fold higher than that of the b-DNA assay. Among the 135 test sera, HBV DNA measurements obtained by the two assays showed a high degree of correlation(r = 0.861, p < 0.0001). Of the 72 sera which tested positive for HBe antigen, 71 and 67 were positive for HBV DNA when tested by TMA-HPA and b-DNA assay, respectively. In contrast, of the 63 which tested negative for HBe antigen, 42 were positive for HBV DNA when tested by TMA-HPA, and only 19 were positive when tested by b-DNA assay(p < 0.05). Among HBe antigen-positive HBV carriers, HBV DNA levels as determined both TMA-HPA and b-DNA assay showed an inverse relationship with pathological stage, but among HBe antigen-negative HBV carriers, no such tendency was observed. Based on these results, it is felt that the detection of HBV DNA by TMA-HPA is useful for the evaluating anti-viral therapeutic effect in HBV carriers, and in estimating a prognosis.

Adult↗

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

Little contribution of GB virus C to the development of primary hepatocellular carcinoma in Japan.

RNA of GB virus C was searched for in sera from 109 patients with primary hepatocellular carcinoma. It was detected in 11 patients (10%), and was more frequent than in 3 of 342 blood donors (0.9%) (P < 0.001). The 11 patients included 4 of 29 patients (14%) with hepatitis B surface antigen and 7 of 74 patients (9%) with antibody to hepatitis C virus. RNA of GB virus C was not detected in any of 4 patients without hepatitis B surface antigen or antibody to hepatitis C virus. These results suggest that GB virus C may contribute little to the development of primary hepatocellular carcinoma in Japan.

Carcinoma, Hepatocellular↗

PubMed1999

Clinical implications of mutations C-to-T1653 and T-to-C/A/G1753 of hepatitis B virus genotype C genome in chronic liver disease.

Among many mutational "hot spots" on hepatitis B virus (HBV) genome, A-to-T1762 and G-to-A1764 within the core promoter have been underscored in view of disease association as well as viral expression/replication. Although to a lesser extent, C-to-T1653 and T-to-V(C/A/G)1753 were also noteworthy in our previous study. To assess the clinical significance of these mutations, we determined the nucleotide sequence of an HBV DNA fragment covering these sites in HBsAg-positive blood donors (n = 160) and patients with chronic hepatitis (n = 66), liver cirrhosis (n = 45), and hepatocellular carcinoma (n = 58), most of whom were infected with genotype C HBV (subtype adr). In cases where HBe antigen was positive, the frequency of T1653 and/or V1753 showed a striking increment from chronic hepatitis patients (18%) to liver cirrhosis and/or hepatoma patients (82%), whereas that of T1762/A1764 was already high in chronic hepatitis patients (76%). In HBe antigen-negative cases, by contrast, significant difference in the frequency of T1653/V1753 mutants was found between blood donors (22%) and chronic hepatitis patients (67%). Our results suggest that T1653/V(particularly C)1753 mutants are more closely associated than T1762/A1764 with the progression of liver disease from chronic hepatitis to cirrhosis in HBe antigen-positive patients. A system of site-directed mutagenesis PCR RFLP was constructed to diagnose T1653 and C/A1753 more conveniently. Detecting T1653 and C/A1753 by this method would contribute to the differential diagnosis of HBV-associated liver disease.

Base Sequence↗

PubMed1999

Failed adoptive immunity transfer: reactivation or reinfection?

A 26-year-old female bone marrow transplant (BMT) recipient was hepatitis B surface antigen (HBsAg) and hepatitis B e antibody (HBeAb) positive. The donor, her human leucocyte antigen (HLA)-compatible sister, was HBsAg negative but hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) positive. Twelve weeks post-BMT the patient became HBsAg negative, as determined using a monoclonal antibody-based assay. At 16 weeks post-BMT, HBsAg became undetectable by monoclonal and polyclonal immunoassay with seroconversion to HBsAb; however, at 24 weeks post-BMT the patient again became HBsAg positive. Both the recipient and the donor were retrospectively tested by hepatitis B virus (HBV) polymerase chain reaction (PCR) and found to be positive. The recipient displayed variants at amino acids 4 and 47 of the surface (S) gene prior to BMT. These mutations were not detected 32 weeks post-BMT when the S gene sequence was identical to that of an adr prototype. The donor was found to have four unique amino acid substitutions at positions 30, 98, 101 and 210 of the S gene. However, in vitro-expressed HBsAg from the donor was detected by commercial kits and an immunofluorescence assay, indicating that antigenic alteration did not explain HBsAg negativity. This donor highlights the value of PCR as the gold standard test for current HBV infection. It also demonstrates that discordance between two commercial HBsAg assays may not always be caused by antigenic variants. The second episode of hepatitis may theoretically have been caused by reactivation, selection of an escape mutant by HBsAb, reinfection or recombination. We suggest it was reactivation because none of the donor variants was seen in the recipient post-BMT.

Adoptive Transfer↗