Biomedical subjects

N Hayashi

Publications and source records attributed to N Hayashi.

At least 109 records · Page 6Linked to original sources

PubMed2001

Characterization of hepatitis B virus surface antigen-specific CD4+ T cells in hepatitis B vaccine non-responders.

AIM: To study the mechanisms of hepatitis B vaccine non-response, we examined hepatitis B virus surface antigen (HBsAg)-induced proliferation of peripheral blood mononuclear cells (PBMC) obtained from hepatitis B (HB) vaccinees. METHODS: Subsequently, we have examined the features of HBsAg-reactive CD4+ T cells in HB vaccine non-responders (NR). Based on serum antibodies to HBsAg (anti-HBs) titers, we divided these vaccinees into three groups: high responder (HR), middle responder (MR) and non-responder (NR), and examined HBsAg-induced proliferation of their PBMC. RESULTS: We found that the in vitro response of PBMC to stimulation with HBsAg was correlated with their serum anti-HBs titer (mean stimulation index was 10.71 in HR, 4.37 in MR and 1.96 in NR). However, by the deletion of CD8+ T cells, the increased response was observed in two of four NRs. CONCLUSIONS: The present results have also shown that at least four distinct HBsAg-reactive CD4+ clones existed (variable gene of T cell receptor beta (V beta) 17 + clone restricted with HLA-DR locus (DR4), V beta 8 + clone restricted with HLA-DQ locust (DQ7), and both V beta 5.1 + clone and V beta 20 + clone restricted with either DR9 or DQ3) in NRs. The results demonstrated that heterogeneous HBsAg-reactive CD4 clones existed in some HB vaccine NRs.

Adult↗

PubMed2001

Significance of serum soluble Fas antigen level in chronic hepatitis C patients treated with interferon: relationship to the therapeutic response.

BACKGROUND AND AIM: Fas system-mediated cytotoxicity is thought to be involved in the development of liver injury in hepatitis C virus (HCV) infection. In this study, we investigated serum soluble Fas antigen levels in chronic hepatitis C patients treated with interferon and their correlation with the therapeutic response. METHODS: The subjects were 67 chronic hepatitis C patients who underwent a 24-week course of alpha-interferon therapy. Patients were categorized into three groups; sustained responders (n = 22), transient responders (n = 24), and non-responders (n = 21), according to changes in the serum alanine aminotransferase level during and after therapy. The viral genotype, viremic level and diversity in the hypervariable region were examined before therapy. Serum soluble Fas antigen levels were assayed by using serum samples taken at the beginning and the end of therapy. RESULTS: In the univariate analysis, serum soluble Fas antigen levels tended to be higher in non-responders (10.0 +/- 3.4 ng/mL) than in sustained responders (8.5 +/- 3.0 ng/mL) and transient responders (8.2 +/- 2.1 ng/mL; P = 0.13 and P < 0.05). The non-response to therapy was observed in eight of the 15 (53%) patients with serum soluble Fas antigen > or = 11 ng/mL, compared with 13 of the 52 (25%) patients with serum soluble Fas antigen < 11 ng/mL (P < 0.05). As for the multivariate analysis, the only significant factor contributing to the sustained response was a low HCV viremic level (P = 0.0046). Significant factors contributing to the non-response were a high serum alanine aminotransferase (P = 0.0407) and a high serum soluble Fas antigen level (P = 0.0483). CONCLUSIONS: High production levels of soluble Fas antigen may be associated with a poor response to interferon therapy in chronic hepatitis C patients.

Adult↗

PubMed2001

Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein alone and those seropositive for des-gamma-carboxy prothrombin alone.

BACKGROUND: There has been no comparative study of the clinicopathological features of HCC patients who are seropositive for alpha-fetoprotein (AFP) alone and those who are seropositive for des-gamma-carboxy prothrombin (DCP) alone. The authors, thus, performed this comparative study. METHODS: The clinicopathological features of patients with solitary hepatocellular carcinoma (HCC), who underwent a hepatectomy were compared among the four below groups according to the seropositivity of AFP and DCP: group A, seronegative for both AFP below 20 ng/mL and DCP below 40 mAU/mL; group B, seropositive for AFP above 100 ng/mL and seronegative for DCP; group C, seronegative for AFP and seropositive for DCP above 100 mAU/mL; and group D, seropositive for both AFP and DCP. RESULTS: Group B patients showed a higher incidence of HCC with an indistinct margin, and a somewhat higher incidence of small HCC less than 2 cm in greatest dimension compared with group C patients. By contrast, group C patients had a higher frequency of HCC with a distinct margin compared with that of an indistinct margin, large tumors more than 3 cm compared with that of small tumors less than 2 cm, and a somewhat higher frequency of moderately to poorly differentiated HCC compared with that of well-differentiated HCC. Our HCC cases showed advanced clinicopathological features in the order of group C, group B and group A. Groups C and D patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP alone demonstrated clinicopathological features of less advanced HCC compared with those who were seropositive for DCP alone.

Adult↗

PubMed2001

Effects of stereotactic radiosurgery on metastatic brain tumors of various histopathologies.

Although reports have been published describing clinical results in a large series of patients with metastatic brain tumors treated by stereotactic radiosurgery (SRS), clinical neuropathological correlation has rarely been available. The present paper describes three autopsy cases and one surgical case treated with linear accelerator based radiosurgery. The cases comprised a lung cancer, a rectal cancer, an osteosarcoma, and a malignant melanoma. Histological sections of each tumor were analyzed by light microscopy based on the Ohosi and Shimosato's histopathological classification of the effects of radiation therapy. In three cases (pulmonary squamous cell carcinoma, rectal adenocarcinoma and osteosarcoma), a large area of the tumors consisted of coagulation necrosis and non-viable tumor cells, while coagulation necrosis and non-viable tumor cells comprised a very small part of the malignant melanoma. Histopathological type of the metastatic brain tumor may be one of the factors influencing outcome after SRS.

Adenocarcinoma↗

PubMed2001

Schizophrenic outpatient perceptions of psychiatric treatment and psychotic symptomatology: an investigation using structural equation modeling.

Schizophrenic patient perceptions of treatment have clinical value and deserve detailed psychiatric investigation. The present study sought a model indicating statistically estimated cause-effect relationships of perceptions and psychotic symptomatology of outpatients with schizophrenia by applying a method of structural equation modeling. The perceptions included in this model were patient satisfaction with treatment, perceptions of their treating psychiatrists, and patient-role perception. Scores of Positive and Negative Syndrome Scale and poor insight measures were added to the model as possible influential factors. The constructed model revealed that the poor insight exerted a major influence on the patient-role perception that had small effects on the reliable therapist perception and the satisfaction. It was also shown that satisfaction was chiefly determined by the reliable therapist perception that was formed in the treatment relationship, rather independently of the other construct. These findings were valuable in terms of their implications for understanding the makeup of the perceptions and the strategy for interventions to improve them.

Adult↗

PubMed2001

Severe hepatitis caused by Epstein-Barr virus without infection of hepatocytes.

Although hepatitis is a common feature of primary Epstein-Barr virus (EBV) infection, severe liver injury is rare and its pathogenesis is unclear. A previously healthy girl developed severe hepatitis with prolonged jaundice. Serologic examination showed that she had primary infection with EBV. An extremely high Epstein-Barr viral load was observed in her peripheral blood. The viral load decreased in parallel with symptomatic improvement. Histologic examinations showed spotty necrosis of the liver parenchyma and infiltration by CD8(+) T cells. The CD8(+) T cells, not hepatocytes, were positive for EBV. Possible mechanisms of viral hepatitis without infection of hepatocytes are discussed.

Antigens, Viral↗

PubMed2001

Detection of hepatitis C virus in the bile and bile duct epithelial cells of hepatitis C virus-infected patients.

The pathobiology of hepatitis C virus (HCV) in the biliary system has not been clarified yet, although bile duct damage is a histological finding characteristic of chronic hepatitis C. In this study, we examined whether HCV infects bile ducts and is released into the bile. Twelve patients positive for serum HCV antibody were examined in this study, and eight were seropositive for HCV RNA by polymerase chain reaction (PCR). For those who underwent abdominal surgery, the bile was aspirated from the gall bladders by fine needle puncture. Five underwent wedge liver biopsy. Series of saline-diluted bile were assayed for HCV RNA by PCR to determine the HCV RNA titers. To examine HCV expression in the biliary system, the liver specimens were immunostained using monoclonal antibodies to the HCV proteins. HCV RNA was detected in the bile of 5 patients with high serum HCV RNA load (> or = 2.5 Meq/mL). Comparison of viral loads between serum and bile revealed that the HCV RNA level in the bile was as high as that in serum. Furthermore, immunohistological study showed that bile duct epithelial cells were infected with HCV. In contrast, HCV was not found in either the bile or bile duct of patients seronegative for HCV RNA or with low serum HCV load (< or = 1.1 Meq/mL). These findings suggest that the biliary system is involved in the pathobiology of HCV and that the bile is as highly infectious as the serum.

Aged↗

PubMed2001

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm.

It is well known that chronic inflammatory conditions involving the bile ducts predispose to the development of bile duct carcinoma, although the relationship between chronic inflammation and malignant transformation is unclear. In this study, by combining immunohistochemistry and computer imaging techniques, we quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of epithelial cells according with their histopathological backgrounds. This technique revealed that the highest levels of COX-2 were expressed in bile duct carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous and abundant. Moderate levels of COX-2 protein expression were also observed in noncancerous epithelial cells with inflammatory reaction, but the staining intensity was heterogeneous among the positive cells exhibiting inflammation. In contrast, only scattered weak reactivity of COX-2 protein was observed in the noncancerous bile duct epithelial cells without inflammatory reaction. Moreover, bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very strong expression of COX-2 protein, that was comparable with carcinoma cells. On the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells in inflammatory regions and tumor progression in this cancer. The data also suggest that COX-2 selective inhibitors might have therapeutic effects not only on bile duct carcinoma, but other hepatobiliary carcinomas.

Animals↗

PubMed2001

Disease recurrence after living liver transplantation for primary biliary cirrhosis: a clinical and histological follow-up study.

We describe the recurrence of primary biliary cirrhosis (PBC) in recipients of living liver transplants. We are not aware of similar previous reports. Because most donors for living liver transplantation (LLT) are blood relatives with close HLA matches, the recurrence of PBC in transplant recipients might offer additional insights in the pathogenesis of the condition. We studied 6 women (age, 29 to 61 years) with PBC who survived LLT for at least 1 year. Tests for antimitochondrial autoantibody (AMA), antipyruvate dehydrogenase complex-E2, immunoglobulin G (IgG) anti-M2, and IgM anti-M2 had confirmed the diagnosis. Donors were blood relatives in 5 instances, and one donor who was not a blood relative still had multiple HLA matches with the recipient. After LLT, we observed a decrease in AMA titers, but within 1 year, these titers increased again in 5 of the 6 patients to pre-LLT levels or greater. Immunoblotting analysis of the anti-M2 protein profile failed to show loss of bands and showed new bands in 3 of 6 patients. Histologically, strong evidence of recurrent PBC was found in 2 patients, and findings compatible with PBC were present in 1 additional patient. All 6 patients are doing well, without symptoms of recurrent PBC (median time post-LLT, 35.5 months; range, 12 to 50 months).

Adult↗

PubMed2001

Endoscopic induction of mucosal fibrosis by argon plasma coagulation (APC) for esophageal varices: A prospective randomized trial of ligation plus APC vs. ligation alone.

BACKGROUND AND STUDY AIMS: Esophageal varices are treated by endoscopic ligation with or without sclerotherapy. Here we used argon plasma coagulation (APC) to promote mucosal fibrosis and compared the efficacy of ligation plus APC with ligation alone in the treatment of esophageal varices. PATIENTS AND METHODS: Our prospective study included 30 patients with esophageal varices randomly assigned to receive APC after ligation (combined group) and 30 patients assigned to receive ligation only (ligation group). Endoscopic ligation was performed until the varix shrank to F1 without red color sign or smaller. This was followed by induction of fibrosis of the distal esophageal mucosa using APC in the combined group. APC was performed using an argon gas at a flow rate of 1.5-2 l/min and a high frequency arc output of 50-60 W. Treatment outcome and complications were compared between the two groups. RESULTS: The mean follow-up time was 18.5+/-6.8 and 15.8+/-7.7 months (+/- SD) for the combined and ligation groups, respectively. The number of treatment sessions was slightly lower in the ligation group (2.9+/-0.6 vs. 2.5+/-0.6, P<0.05). The number of ligation bands used was not different between the two groups (13.4+/-3.1 vs. 14.9+/-2.4). The cumulative recurrence-free rate at 24 months after treatment in the combined group was significantly higher than in the ligation group (74.2% vs. 49.6%, P < 0.05). A significantly higher incidence of pyrexia was encountered in the combined group (P <0.05), but the incidences of other complications were similar in both groups. CONCLUSION: Our results indicate that endoscopic ligation of esophageal varices combined with APC is superior to ligation alone. Since APC is theoretically well suited for mucosal fibrosis therapy, it can be used for the complete elimination of esophageal varices and for fibrosis of the distal esophageal mucosa.

Argon↗

PubMed2001

Side-to-side arterial anastomosis model in the rat internal and external carotid arteries.

Microvascular anastomosis has become a general and essential technique in the field of vascular reconstructive surgery. Side-to-side microvascular anastomosis is rarely performed by microsurgeons. Laboratory training models are essential for the development and refinement of microsurgical techniques. A new experimental model of a side-to-side "arterial" anastomosis in the rat internal and external carotid arteries is presented, in which 100 percent patency was accomplished immediately, and was maintained 7 days after anastomosis. This model can provide an experimental and training tool for side-to-side anastomosis of small arteries.

Anastomosis, Surgical↗

PubMed2001

Characterization of early gastric cancer and proposal of the optimal therapeutic strategy.

BACKGROUND AND AIMS: The optimal protocol of the treatment for early gastric cancer has not been fully established. The current study was designed to elucidate the relationship between the depth of tumors with or without an ulcer and the presence of lymph node metastasis and to establish the optimal and practical therapeutic strategy for patients with early gastric cancer. PATIENTS AND METHODS: A retrospective analysis of 1051 patients with early gastric cancer treated by gastrectomy with D1 or D2 lymph node dissection was performed. The patients were divided into those with mucosal (M) tumors and those with submucosal (SM) tumors. These 2 groups were subclassified, depending on the coexistence of ulcer or the degree of submucosal invasion, and were characterized in relation to clinicopathologic factors and 5-year prognosis. RESULTS: The incidence of lymph node metastases from SM tumors (19.8%, 85 of 430) was more frequent than that from M tumors (2.3%, 14 of 621) (P <.001). All M tumors with lymph node involvement, including tumors smaller than 1.5 cm in diameter, had ulceration or ulceration scar in the lesions. SM tumors that had invaded less than 200 microm in depth (SM1a) had significantly less lymph node involvement than those with deeper invasion. The node metastases were confined to epigastric lymph nodes (N1) in both M tumors with ulceration or ulceration scar and SM1a tumors. CONCLUSIONS: All macroscopic M tumors without ulceration or ulceration scar should be considered for endoscopic mucosal resection. The need for reoperation for a formal gastrectomy with lymphadenectomy or a limited surgical operation will vary depending on the pathologic analysis of endoscopic mucosal resection specimens (depth of invasion, presence of ulceration).

Adult↗

PubMed2001

Immunofluorescence--still the 'gold standard' in ANA testing?

A usefulness of enzyme immunoassay (EIA)-based antinuclear antibodies (ANA) tests was evaluated in comparison with the immunofluorescence ANA assay (IF-ANA). COBAS-ANA and MBL-ANA were used, in the former a mixture of antigens extracted from HEp-2 cells and multiple recombinant antigens was immobilized on beads as the antigen, and in the latter 9 kinds of purified or recombinant proteins are immobilized on 96-well plates. We first compared an ability to differentiate 258 connective tissue disease (CTD) patients (except rheumatoid arthritis) from 257 healthy subjects between COBAS-ANA and IF-ANA. The sensitivity and specificity of COBAS-ANA were 84% and 94%, respectively, while those of IF-ANA at a cutoff dilution of 1:160 were 81% and 87%. The receiver operating characteristic (ROC) analysis showed a significant superiority of COBAS-ANA to IF-ANA. Moreover, when the cutoff index was set at 0.6, the COBAS-ANA could detect the 8 disease-specific ANAs as well as IF-ANA at a cutoff dilution of 1:40. A possible availability of MBL-ANA in a periodic health examination in certain towns was also demonstrated. Among the 1123 subjects, a total of 145 disease-specific ANAs were detected in 126 subjects. MBL-ANA could catch disease-specific ANAs with almost same efficacy of IF-ANA. Annual survey of the residents by MBL-ANA may lead to a detection of CTD patients. EIA-based ANA tests are very useful for both detecting disease-specific ANAs and screening CTD patients. We believe that EIA-ANA should be the 'gold standard' especially for screening a large number of samples, although there is some room for technical improvement.

Antibodies, Antinuclear↗

PubMed2001

The promoter of mouse transcription repressor bach1 is regulated by Sp1 and trans-activated by Bach1.

The Maf recognition element (MARE) is regulated by both activators and repressors. Bach1 and Bach2 repress MARE-dependent transcription by forming heterodimers with Maf-related oncoproteins. In order to gain an understanding of the regulation of bach1 gene expression, we analyzed the structure of the mouse bach1 gene. Comparison of the exon-intron structure of the bach1 gene with those of other NF-E2-related genes indicated that bach1 and bach2 constitute an evolutionarily distinct subfamily among bZip factors. The bach1 promoter region contains two GC boxes that are important for its basal activity and are bound by Sp1 in K562 cell extracts. In addition, we found an evolutionarily conserved MARE-like element located downstream of the transcription initiation site. Deletion of this element resulted in a higher promoter activity in K562 cells. Bach1 trans-activated its own promoter depending on the presence of the MARE-like element in co-transfection assays. However, Bach1 did not bind to the MARE-like element in electrophoretic mobility shift assays (EMSA). These results suggest that Bach1 activates its own promoter indirectly by inhibiting the putative repressor. Such a positive feedback regulation by the repressor Bach1 may play an important role in maintaining the expression of Bach1 while consolidating repression of other genes with MARE.

Animals↗

PubMed2001

Retreatment effect of NPe6 photodynamic therapy on the normal primate macula.

PURPOSE: To evaluate the safety and efficacy of repeated photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6) on normal primate fovea and choroid. METHODS: Macaca fuscata monkeys were used as experimental subjects. Mono-L-aspartyl chlorin e6 at a dose of 2 mg/kg was administered by intravenous infusion. Laser irradiation was applied within 5 minutes using a 664-nm diode laser at a power output of 5.9 mW (750 mW/cm2), spot size of 1,000 microm, and time of 10 seconds. This resulted in a fluence of 7.5 J/cm2. Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea and posterior fundus near the arcade vessels of each eye. The animals were killed and the eyes were enucleated for histologic study 2 weeks after the last treatment. RESULTS: Limited changes could be observed in the sensory retina under light microscopy. Photoreceptor cells and outer segments were not damaged, even after repeated PDT. Proliferation and duplication of the retinal pigment epithelial cells were common findings. A plaque of fibrous tissue was present, interwoven with retinal pigment epithelial cells in eyes that received repeated PDT. The retinal vessels remained patent even after three sessions of PDT. However, occlusion of the choriocapillaris and the large choroidal vessels was observed after repeated PDT treatment. CONCLUSION: Repeated PDT of healthy nonhuman primate fundi using a hydrophilic photosensitizer (NPe6) shows preservation of the neurosensory retina components and architecture with damage confined to the retinal pigment epithelium and choriocapillaris.

Animals↗

PubMed2001

Formation of rhamnogalacturonan II-borate dimer in pectin determines cell wall thickness of pumpkin tissue.

Boron (B) deficiency results in inhibition of pumpkin (Cucurbia moschata Duchesne) growth that is accompanied by swelling of the cell walls. Monomeric rhamnogalacturonan II (mRG-II) accounted for 80% to 90% of the total RG-II in B-deficient walls, whereas the borate ester cross-linked RG-II dimer (dRG-II-B) accounted for more than 80% of the RG-II in control plants. The results of glycosyl residue and glycosyl linkage composition analyses of the RG-II from control and B-deficient plants were similar. Thus, B deficiency does not alter the primary structure of RG-II. The addition of (10)B-enriched boric acid to B-deficient plants resulted within 5 h in the conversion of mRG-II to dRG-II-(10)B. The wall thickness of the (10)B-treated plants and control plants was similar. The formation and possible functions of a borate ester cross-linked RG-II in the cell walls are discussed.

Borates↗

PubMed2001

Clinical significance of autoantibody to hepatocyte membrane antigen in type 1 autoimmune hepatitis.

OBJECTIVE: By using HepG2 as flow cytometry target, we have reported that autoantibody to hepatocyte membrane antigen (anti-HMA) was frequently found in autoimmune hepatitis (AIH) patients. In this study, we have examined this autoantibody in relation to clinical features in these patients. METHODS: HepG2 cells were incubated with diluted serum and subsequently with FITC-conjugated antihuman immunoglobulin. The results were expressed as relative fluorescence intensity. The prevalence of anti-HMA was estimated by setting the upper limit of mean +/- 3 SD obtained from healthy subjects. RESULTS: We found that the mean relative fluorescence intensity was 1.67+/-0.5 in AIH with low serum ALT level (group 1 AIH), 4.20+/-1.9 in AIH with high serum ALT level (group 2 AIH), and 1.92+/-0.9 in age-matched chronic hepatitis C virus-positive patients. Their positive rate was 37.5% (three of eight) in group 1 AIH, 95.0% (19 of 20) in group 2 AIH, and 33.3% (four of 12) in chronic hepatitis C patients. In 12 group 2 AIH patients, their mean relative fluorescence intensity was significantly decreased during immunosuppressive therapy. The association between serum ALT level and anti-HMA was confirmed by the facts that a significant direct quantitative relationship existed between these two levels and by serial studies of anti-HMA in four AIH patients. Anti-HMA was also detected in five non-B, non-C hepatitis patients having clinical features resembling those of AIH. CONCLUSIONS: The present results have shown that the anti-HMA was tightly associated with the degree of hepatocyte inflammation and that the measurement of anti-HMA may have some advantage in clinical evaluation of some of non-B, non-C hepatitis patients.

Adult↗

PubMed2001

Upregulation of Reg 1alpha and GW112 in the epithelium of inflamed colonic mucosa.

BACKGROUND AND AIMS: Colonic epithelium is involved in the regulation of intestinal function and mucosal immune responses, and its function is altered in inflammatory bowel disease (IBD). However, a comprehensive analysis of the genetic alterations in inflamed colonic epithelium is not available at present. The aim of our study was to detect genes that are preferentially expressed in inflamed colonic epithelia and clarify the biochemical responses of epithelial cells in inflamed colonic mucosa. METHODS: cDNA representation difference analysis was used to identify candidate genes selectively expressed in inflamed colonic epithelia. Selective expression of these genes in the epithelium of inflamed colonic mucosa, including IBD and non-IBD tissues, was examined by real time polymerase chain reaction and in situ hybridisation. The effect of cell confluence and inflammatory mediators on Reg 1alpha gene expression was examined using a colon cancer cell line (HT29). RESULTS: We identified seven candidate genes that were presumed to be upregulated in the inflamed colonic epithelium. Of these, Reg 1alpha and GW112 were the dominant species and expression of these genes was confined to the crypt epithelium. In vitro studies using a colonic epithelial cell line suggested that cell confluence regulates Reg 1alpha gene expression. CONCLUSIONS: Selective expression of Reg 1alpha and GW112 genes in the crypt epithelium of inflamed colonic mucosa suggests the important regulatory functions of these genes.

Adult↗