Biomedical subjects

M Hori

Publications and source records attributed to M Hori.

At least 73 records · Page 4Linked to original sources

PubMed2001

Hepatoid adenocarcinoma of the stomach.

Although gastric cancer occurs frequently in Japan, few cases of hepatoid adenocarcinoma, a cancer with an extremely poor prognosis, have been reported. Here, we describe a 67-year-old Japanese man referred to our hospital with suspected gastric cancer. Gastrointestinal fiberscopy revealed an elevated lesion with a central depression on the lesser curvature, extending from the antrum to the body of the stomach. On the preoperative examinations, abdominal computed tomography scan, magnetic resonance imaging, and abdominal ultrasonography revealed multiple metastases to the liver and no cirrhotic change. The serum level of alpha-fetoprotein (AFP) was markedly elevated (10,084 ng/ml). After a diagnosis of AFP-producing gastric cancer with multiple liver metastases was made, total gastrectomy, without liver resection, was performed. Microscopically, the tumor showed two main histological features. The main part of the tumor resembled moderately differentiated hepatocellular carcinoma, and the rest showed fetal-type adenocarcinoma. Some parts of the hepatoma-like lesion showed periodic acid-Schiff (PAS)-positive granules. Furthermore, the tumor showed diffuse immunohistochemical positivity for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. According to these histopathological findings, the tumor was diagnosed as hepatoid adenocarcinoma of the stomach. Although anastomotic leakage occurred postoperatively and the liver metastases have increased in size, the patient remains alive 11 months after the operation. Because of the poor prognosis for this histological type of tumor, accurate diagnosis of hepatoid adenocarcinoma is important, and long-term follow-up is required. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.

Adenocarcinoma↗

PubMed2001

Dopamine and serotonin uptake inhibitors on the release of dopamine and serotonin in the nucleus accumbens of young and aged rats.

Nucleus accumbens (ACC) of young (4 months old) and aged (24 months old) Wistar rats were perfused with dopamine (DA) uptake blocker, cocaine, or the serotonin (5-HT) selective reuptake inhibitor, fluoxetine, through the microdialysis probe membrane, used to assess the dopamine transporter (DAT) or serotonin transporter (SERT) modulation. The basal extracellular DA release in the ACC was significantly lower in aged rats than young rats. Analysis of DA and 5-HT concentrations in the ACC with increased positive GFAP revealed that DA and DOPAC levels of aged rats were decreased to 55 and 60% of those in young rats, respectively. After co-perfusion with cocaine, both DA and 5-HT releases in the ACC were increased in the young and aged groups. However, the magnitude of the increased DA release was lower in aged rats than young rats. Co-perfusion with fluoxetine showed lower magnitude of the increased DA release in aged rats. It appears that the DAT and SERT system responds initially to ACC cell loss with age, and that especially ACC DAT in the aged rat is more degenerative compared with the young rats. These findings suggest that the serotonergic system with SERT in the remaining ACC neurons show an early adaptive response and resistance to the normal aging and maintain the multiple regulatory system in the ACC despite neural loss since the dopaminergic neurons in the aged animals are vulnerable to aging.

Aging↗

PubMed2001

Combined histologic and molecular features reveal previously unappreciated subsets of lymphoma in AKXD recombinant inbred mice.

Hematopoietic neoplasms developing in AKXD recombinant inbred, NFS.V(+) and ICSBP knockout mice were assessed using morphologic, cytologic and molecular criteria that relate these disorders to human lymphoma and leukemia. Lymphoma types included precursor T-cell and B-cell lymphoblastic, small lymphocytic, splenic marginal zone, follicular, and diffuse large cell (DLCL). In addition to previously defined subtypes of DLCL composed of centroblasts or immunoblasts, two additional subtypes are defined here: lymphoblastic lymphoma like (LL) and lymphoma characterized by a histiocytic reaction (HS). DLCL(HS) were distinguished from true histiocytic lymphomas by the presence of clonal Ig gene rearrangements.

Animals↗

PubMed2001

Heart rate elevation and diabetic retinopathy in patients with type 2 diabetes mellitus and normoalbuminuria.

To investigate the role of heart rate (HR) and blood pressure (BP) for diabetic retinopathy, 24-h ambulatory HR and BP were monitored for 162 in patients with type 2 diabetes and normoalbuminuria. The fundus was assessed as no retinopathy, simple diabetic retinopathy (SDR) and proliferative retinopathy (PDR). Comparing the highest with the lowest quartile of diabetic duration, the relative risk for retinopathy was 9.3 and for nocturnal HR, it was 3.6. Comparison among three retinopathy groups (no retinopathy, group 1, n=122; SDR, group 2, n=24; Pre-PDR or PDR, group 3, n=16) showed that 24-h and nocturnal HR were significantly higher in group 3 (80+/-9 and 71+/-9 beats per min) than in group 2 (73+/-8 and 64+/-8) and group 1 (72+/-7 and 60+/-7). In multiple logistic analysis, the odds ratio of diabetic duration and nocturnal HR to the existence of retinopathy was 1.17 (95% CI, 1.10-1.25, P=0.00001) and 1.11 (95% CI, 1.05-1.17, P=0.0002). We concluded that diabetic retinopathy is related to diabetic duration and high heart rate in type 2 diabetes mellitus with normoalbuminuria. Heart rate elevation may be a predictor of advanced retinopathy.

Albuminuria↗

PubMed2001

Renin angiotensin system-dependent hypertrophy as a contributor to heart failure in hypertensive rats: different characteristics from renin angiotensin system-independent hypertrophy.

OBJECTIVES: This study aimed to characterize the difference between renin angiotensin system (RAS)-dependent and RAS-independent hypertrophy and their differential contribution to the transition to heart failure. BACKGROUND: Hypertensive left ventricular (LV) hypertrophy develops with RAS activation in the heart; however, LV hypertrophy develops even without RAS activation. METHODS: Left ventricular geometry and function were assessed in Dahl salt-sensitive rats placed on an 8% NaCl diet from seven weeks old (hypertensive rats) and in those placed on an 0.3% NaCl diet (control rats, n = 8). The hypertensive rats were randomized to no treatment (n = 8) or treatment with the angiotensin type 1 receptor (AT1R) antagonist candesartan (1 mg/kg per day, n = 10) after the baseline echocardiography study. RESULTS: From 7 to 13 weeks, AT1R blockade at a subdepressor dose did not restrain the development of LV hypertrophy but prevented narrowing of LV diastolic dimension, leading to the normalization of abnormally decreased end-systolic wall stress in the untreated rats. Progressive development of LV hypertrophy in spite of lower than normal end-systolic wall stress (excessive hypertrophy) after 13 weeks was suppressed by the AT1R blockade. Elevation of LV end-diastolic pressure and prolongation of Tau were associated with histological evidence of myocyte hypertrophy and massive interstitial fibrosis in the untreated rats, and none of these was evident in the treated rats. CONCLUSIONS: Renin-angiotensin system activation and AT1R signaling may be dispensable for the development of early adaptive LV hypertrophy and closely linked to the transition to heart failure.

Animals↗

PubMed2001

Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study.

OBJECTIVES: To test our hypothesis that the development of vulnerable plaques is not limited to the culprit lesions, but is a pan-coronary process, we directly observed all three major coronary arteries by angioscopy and evaluated the prevalence of yellow plaques in patients with myocardial infarction (MI). BACKGROUND: Although pathologic studies have suggested that the disruption of atheromatous plaque plays a major role in the development of acute MI, the prevalence of yellow plaques in the whole coronary arteries of patients with MI has not been clarified. METHODS: Thirty-two patients undergoing follow-up catheterization one month after the onset of MI were prospectively and consecutively enrolled in this study. The prevalence of yellow plaques and thrombus in the major coronary arteries was successfully evaluated in 20 patients (58 coronary arteries, 21 culprit lesions) by coronary angioscopy. The diameter stenosis (DS) of the culprit lesions and the maximal diameter stenosis (maxDS) of nonculprit segments were angiographically measured for each coronary artery. RESULTS: The DS of the culprit lesions and maxDS were 27 +/- 17% and 19 +/- 13%, respectively. Yellow plaques and thrombus were detected in 19 (90%) and 17 (81%) of 21 culprit lesions, respectively. Yellow plaques were equally prevalent in the infarct-related and non-infarct-related coronary arteries (3.7 +/- 1.6 vs. 3.4 +/- 1.8 plaques/artery). However, thrombus was only detected in the nonculprit segments of one (2%) coronary artery. CONCLUSIONS: In patients with MI, all three major coronary arteries are widely diseased and have multiple yellow though nondisrupted plaques. Acute MI may represent the pan-coronary process of vulnerable plaque development.

Aged↗

PubMed2001

Predictive factors for development of the no-reflow phenomenon in patients with reperfused anterior wall acute myocardial infarction.

OBJECTIVES: We sought to elucidate the clinical factors related to the development of no-reflow phenomenon after successful coronary reperfusion in patients with an acute myocardial infarction (AMI). BACKGROUND: Myocardial contrast echocardiography revealed that the no-reflow phenomenon is observed in some patients with a reperfused AMI, and those patients usually have poor functional and clinical outcomes. It is still unknown what clinical factors are related to the development of the no-reflow phenomenon. METHODS: Myocardial contrast echocardiography was performed 15 min after successful coronary reperfusion therapy in 199 patients with an anterior wall AMI who underwent successful coronary reperfusion with primary coronary angioplasty within 24 h after the onset of AMI. Multiple logistic regression analysis was used to identify independent predictors of the no-reflow phenomenon. RESULTS: Seventy-nine patients showed the no-reflow phenomenon. Univariate analysis indicated that pre-infarction angina within 48 h before symptom onset, Killip class, Thrombolysis in Myocardial Infarction flow grade 0 on the initial coronary angiogram, the number of abnormal Q-waves and the wall motion score (WMS) on the echocardiogram obtained at hospital admission are related to the no-reflow phenomenon. Multivariate logistic regression analysis revealed that all of these factors, except for Killip class, are independent predictive factors of the no-reflow phenomenon. CONCLUSIONS: Development of the no-reflow phenomenon is related to the severity of myocardial damage (number of Q-waves), the size of the risk area (WMS) and the occlusion status of infarct-related artery. In addition, ischemic preconditioning (pre-infarction angina) seems to be the factor that attenuates the no-reflow phenomenon.

Adult↗

PubMed2001

The healing process of infarct-related plaques. Insights from 18 months of serial angioscopic follow-up.

OBJECTIVES: To clarify the healing process of disrupted culprit plaques of acute myocardial infarction (MI), we serially observed the culprit plaques for 18 months after the onset of acute MI by angioscopy. BACKGROUND: Although it has been reported that disruption of the yellow plaque and subsequent thrombosis cause acute MI and that the thrombogenicity of the plaque lasts for a month, the healing process of the plaque after disruption has not been clarified. METHODS: Eighty-five patients with acute MI were prospectively and consecutively enrolled. Angioscopic studies were performed immediately and at 1, 6 and 18 months after successful reperfusion. The prevalence of yellow plaques and thrombus was examined. The color grade of the plaque was determined as 0 (white), 1 (light yellow), 2 (yellow) or 3 (bright yellow). RESULTS: Although yellow plaque was present at the culprit lesion in most patients throughout follow-up, its color grade was reduced from one to six months (1.9 +/- 0.6 vs. 1.1 +/- 0.7, p = 0.0003) after reperfusion, especially in the patients without hyperlipidemia (HL). The incidence of thrombus was 92.5% immediately after reperfusion, which was reduced significantly to 63.8%, 4.8% and 11.8% at 1, 6 and 18 months, respectively. The incidence of thrombus (77.8% vs. 45.0%, p = 0.03) at one month was higher in the patients with diabetes mellitus (DM). CONCLUSIONS: The healing process of yellow plaques at the culprit lesions of MI was detected by angioscopy as reductions of color grade and thrombogenicity at six months and partially at one month after the onset of acute MI. This healing process appears to deteriorate by complicating cases of DM or HL.

Aged↗

PubMed2001

Evaluation of regional liver damage by magnetic resonance imaging with superparamagnetic iron oxide in rat liver.

The purpose of this study was to investigate whether regional liver damage could be detected by means of enhanced MR imaging with a superparamagnetic iron oxide (SH U 555A) in an ischemia-reperfusion model of rat liver. Ischemic liver damage was induced in the right lobe by vascular clamping for 0 (sham), 30 (I-30), 60 (I-60), and 90 minutes (I-90). There was no significant difference in relative enhancement (RE) between the ischemic and nonischemic lobes in the sham, I-30 and I-60 groups, while RE of the ischemic lobe was significantly lower than that of its nonischemic counterpart in the I-90 group as seen on SH U 555A enhanced proton density spin echo images (P < 0.05). Histological examination revealed that iron deposits were significantly smaller in the ischemic than the nonischemic lobe in the I-90 group (P < 0.05), although there was no significant difference in the number of Kupffer cells. Our results indicate that severe regional liver damage can be evaluated by MR imaging with SH U 555A.

Animals↗

PubMed2001

cDNA array hybridization reveals cardiac gene expression in acute ischemic murine hearts.

PURPOSE: Although cDNA array technique has recently become available in the cardiovascular field, it has not yet been established what kind of genes in the myocardium are expressed by acute ischemia. Since many substances contribute to the pathophysiology of acute ischemic hearts, we investigated transcription responses of murine hearts to ischemia using cDNA array representing 18,376 genes. METHODS AND RESULTS: In 29 male mice, we ligated the proximal site of the left coronary artery for 60 min. In 14 mice, we performed the sham operation without the ligation of the left coronary artery. After 60 min, the hearts were excised to obtain mRNA, and we performed cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10-fold, 11 known genes were upregulated 5.0- to 9.9-fold, and 32 unknown genes were upregulated over 5.0-fold compared to sham-operated controls. In contrast, 11 known genes and 7 unknown genes were downregulated to levels below 0.2-fold. For 9 of the 13 known genes of which expression was increased as analyzed by cDNA array, subsequent Northern blot analysis also revealed an increase in expression. CONCLUSION: Using cDNA array analysis we found that cardiac expression of 24 known and 39 unknown genes was modulated by acute ischemic stress, and appeared to be related to the pathophysiology of ischemic hearts. These results show that cDNA array analysis may provide a new molecular insight to the pathophysiology of acute ischemic hearts.

Animals↗

PubMed2001

Benidipine, a long-acting Ca channel blocker, limits infarct size via bradykinin- and NO-dependent mechanisms in canine hearts.

Amlodipine increases NO levels in coronary vessels and aorta via bradykinin-dependent mechanisms in vitro. We have previously reported that a long-acting Ca channel blocker, benidipine, increases cardiac NO levels in ischemic canine hearts, suggesting that benidipine may also protect against ischemia and reperfusion injury via bradykinin- and NO-dependent mechanisms. We examined this possibility. In open chest dogs, the left anterior descending coronary artery was perfused with blood through a bypass tube and was occluded for 90 min followed by 6 hours of reperfusion. Infarct size was assessed by TTC staining at 6 hours of reperfusion. When benidipine doses of 50, 100, and 200 ng/kg/min were infused via the bypass tube between 10 min prior to the onset of ischemia and after 60 min of reperfusion, systemic blood pressure did not change significantly. Infarct size decreased with the administration of benidipine (50, 100, and 200 ng/kg/min) when compared to the untreated condition (24.8+/-2.5, 17.3+/-3.1, and 16.5+/-2.0 vs. 43.4+/-5.6%, respectively) associated with the increased release of NO and bradykinin in the coronary venous blood upon reperfusion. Myeloperoxidase activity of the myocardium increased after 6 hours of reperfusion, which was attenuated by benidipine. The limitation of infarct size and the increase in myeloperoxidase activity were completely blunted by either L-NAME or HOE140. There were no significant differences in collateral blood flow assessed by the microsphere method after 45 min of ischemia for any of the groups. Thus, we conclude that the Ca channel blocker, benidipine, limits infarct size via bradykinin- and NO-dependent mechanisms.

Adrenergic beta-Antagonists↗

PubMed2001

Effect of carbohydrate structure on biological activity of artificially N-glycosylated eel calcitonin.

To reveal the function of the carbohydrate portion of glycopeptides and glycoproteins, we chemo-enzymatically synthesized artificially N-glycosylated derivatives of eel calcitonin and studied their three-dimensional structure and biological activity. The CD and NMR spectra in trifluoroethanol-H(2)O solution showed that the glycosylation did not change the three-dimensional structure. All the derivatives retained the strong in vivo hypocalcemic activity of calcitonin. However, the relative activity was dependent on the structure of the attached carbohydrate. The single GlcNAc attachment best enhanced the activity, while larger carbohydrates decreased the activity. This relative activity order of compounds could be partly explained by their calcitonin-receptor binding affinity, though the affinity of the GlcNAc derivative did not exceed that of calcitonin. The enhanced hypocalcemic activity of the GlcNAc derivative was explained by its altered biodistribution. The GlcNAc attachment caused calcitonin to escape from the trap at the liver during the early circulation. Thus, the glycosylation was shown to modulate the biological activity of calcitonin depending on the carbohydrate structure without a change in the peptide backbone conformation.

Amino Acid Sequence↗

PubMed2001

A case of tacrolimus nephrotoxicity appearing in a second renal transplantation patient.

We experienced a case of a second renal transplantation patient. With the use of cyclosporin, he lost his first graft because of chronic rejection; with the use of tacrolimus, his second graft suffered from drug nephrotoxicity. On his second renal transplantation, his graft function deteriorated and required haemodialysis with the use of tacrolimus. Repeated biopsies did not reveal the typical characteristics of acute tacrolimus nephrotoxicity and acute rejection. His tacrolimus trough level was not high during the clinical course; however, by reducing tacrolimus dosage, his graft function eventually recovered to mild renal dysfunction. This observation was helpful for clinical diagnosis of the functional toxicity of tacrolimus. The case is interesting in considering the functional toxicity of tacrolimus and the difference between tacrolimus and cyclosporin in terms of immunosuppressive and nephrotoxic actions.

Biopsy↗

PubMed2001

Chronic vascular toxicity of doxorubicin in an organ-cultured artery.

1. We investigated the chronic effects of doxorubicin (DXR) on morphological and functional changes in the rabbit mesenteric artery using an organ culture system. 2. In arteries cultured with 0.3 microM DXR for 7 days, the contractions induced by noradrenaline, but not those induced by endothelin-1 or high K(+), were strongly inhibited. This reaction was followed by a decrease in the induction of the alpha(1A)-adrenoceptor without any change in the mRNA level. Inhibition of noradrenaline-induced contractions by DXR was attenuated by superoxide dismutase, and alpha(1A)-adrenoceptor protein expression recovered. 3. In the arteries cultured with 1 microM DXR for 7 days, contractions induced by endothelin-1 or high K(+) and absolute force in the permeabilized muscles were also inhibited. Morphological examinations revealed the existence of concentrated nuclei and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)-positive smooth muscle cells, and internucleosomal DNA fragmentation was also detected, indicating the induction of apoptosis. 4. In the arteries cultured with 10 microM DXR for 7 days, nuclear swelling, karyolysis and random DNA fragmentation indicative of necrosis were observed, and muscle contractility was abolished. 5. These results suggest that 0.3 microM DXR selectively down-regulates the alpha(1A)-adrenoceptor protein expression, resulting in a decrease in the noradrenaline-induced contraction. This down-regulation may be at least partly due to the production of a superoxide radical. DXR also caused a decrease in muscle contractility followed by apoptotic changes at 1 microM and necrotic changes at 10 microM. These changes might be responsible for the disturbance of the circulatory system that is often observed during the course of repetitive chemotherapy.

Animals↗

PubMed2001

Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance.

The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-gamma prior to initiation of interferon-alpha treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-alpha treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-gamma (1 MIU/day) was administered daily for 14 days followed by natural IFN-alpha (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-alpha treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-gamma administration, and tended to return to the pretreatment level after the start of IFN-alpha administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-gamma prior to the initiation of IFN-alpha treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.

Antiviral Agents↗

PubMed2001

Troglitazone enhances glucose uptake induced by alpha-adrenoceptor stimulation via phosphatidylinositol 3-kinase in rat heart.

1. Thiazolidinedione-derived agents have been reported to act as insulin sensitizers by augmenting insulin-dependent stimulation of phosphatidylinositol 3-kinase (PI3K) activity in a specific manner. It has been suggested that alpha-adrenoceptor stimulation mediates glucose uptake through PI3K in the heart. 2. To elucidate whether the thiazolidinedione-derived agent troglitazone (TRO) affects glucose uptake induced by alpha-adrenoceptor stimulation through PI3K, the rate of glucose uptake was quantified from the rate of accumulation of sugar phosphate (d[SP]/dt) using [(31)P] nuclear magnetic resonance spectroscopy after substitution of glucose with 2-deoxyglucose in rat perfused heart. Hearts were stimulated with 100 micromol/L phenylephrine plus 10 micromol/L propranolol (alpha-adrenoceptor stimulation), or 1 micromol/L isoproterenol plus 10 micromol/L phentolamine (beta-adrenoceptor stimulation). 3. The d[SP]/dt in the alpha- and beta-adrenoceptor-stimulated groups (0.45 +/- 0.06 and 0.42 +/- 0.04 micromol/min per g, respectively) was higher than that of the control group (0.27 +/- 0.02 micromol/min per g; P < 0.01). The addition of 2 microg/mL troglitazone to alpha-adrenoceptor stimulation augmented d[SP]/dt (0.72 +/- 0.08 micromol/min per g; P < 0.05 vs the alpha-adrenoceptor-stimulated group), which was effectively blocked by 3 micromol/L wortmannin (0.35 +/- 0.06 micromol/min per g; P < 0.01 vs troglitazone + alpha-adrenoceptor stimulation group). However, addition of troglitazone to beta-adrenoceptor stimulation did not alter d[SP]/dt (0.33 +/- 0.02 micromol/min per g; P = NS vs the beta-adrenoceptor-stimulated group). 4. These results indicate that troglitazone acutely enhances alpha-adrenoceptor stimulation on glucose uptake through a PI3K-dependent pathway, thus possibly improving glucose utilization in a catecholamine-released state.

Adenosine Triphosphate↗

PubMed2001

Generation of hepatitis C virus-specific cytotoxic T lymphocytes from healthy individuals with peptide-pulsed dendritic cells.

BACKGROUND AND AIMS: In hepatitis C virus (HCV) infection, cytotoxic T lymphocytes (CTL) are involved in liver inflammation and contribute to the reduction of viral load. Antibodies for HCV-CTL precursor frequencies (CTLpf) are relatively low in chronic hepatitis C, and this may be related to the poor CTL response in vivo. The aim of this study was to assess the efficacy of dendritic cells (DC) as antigen-presenting cells in CTL generation from low CTLpf. METHODS: To confirm the rationale of using DC to prime naive T cells, five HCV-uninfected individuals were enrolled in the study. We obtained DC by maturation from peripheral progenitors under stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and IL-1alpha. Autologous T cells were cultured with DC or concanavalin-A-induced blasts loaded with four HCV-derived peptides bearing human leukocyte antigen (HLA)-A*0201 or -A24 motifs for 28 days under IL-7 and IL-2 stimulation. The lytic activity against peptide-pulsed targets was assessed by using a [51Cr]-releasing assay. RESULTS: The DC strongly expressed HLA class I, II, B7-1 and B7-2, but not phenotypic markers of T-, B-, natural killer (NK)-cells or monocytes. The CD8-positive, HLA-class I-restricted and HCV peptide-specific CTL were generated with DC from HLA-A antigen-matched subjects, whereas no CTL activity was detected with concavalin (Con-A) blasts. We were thus able to generate HCV specific CTL from naive precursors with peptide-pulsed DC. CONCLUSIONS: This DC-based system can be used to generate CTL of desired antigen specificity, even from a source with low CTLpf.

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↗