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Biomedical subjects

S Iino

Publications and source records attributed to S Iino.

At least 73 records · Page 4Linked to original sources
PubMed1998

Persistent viremia after recovery from self-limited acute hepatitis B.

To define the duration of viremia in the course of acute hepatitis B, we semiquantitatively determined the levels of hepatitis B virus (HBV) DNA in the sera, using polymerase chain reaction (PCR) coupled with Southern blotting, of non-immunocompromised patients with self-limited acute hepatitis B. In the sera of 10 of 11 patients, HBV DNA, which was presumably coated with viral proteins, was detected for a long period after recovery, even at the final observation times, which ranged from 6 to 19 months after disease onset. To characterize the mode of HBV that was present in serum, we immunoprecipitated immune complexes in sera by the addition of anti-human immunoglobulin G (IgG) and determined the levels of HBV DNA separately in the supernatants and pellets. In the acute phase of hepatitis B, high levels of HBV DNA were detected both in the supernatants and pellets at comparative levels. After the convalescent phase, the amount of HBV DNA in the supernatant decreased with respect to that in the pellets. It is notable that, in most cases, serum HBV persisted as a form of immune complex even after the seroconversion to antibody to hepatitis B surface antigen (anti-HBs). These data suggest that the replication of HBV may persist in some organs, most likely in the liver or peripheral blood cells, for a long period after recovery from acute hepatitis B, and the data indicate the possible transmission of HBV from organ transplantation donors who exhibit serological markers of past infection only.

Acute Disease↗
PubMed1998

Cyclic ADP-ribose and the regulation of calcium-induced calcium release in eggs and cardiac myocytes.

Cyclic ADP-ribose (cADPR) is a cyclic metabolite of NAD+ synthesised in cells and tissues expressing ADP-ribosyl cyclases. Although it was first discovered in sea-urchin egg extracts as a potent calcium mobilizing agent, subsequent studies have indicated that it may have a widespread action in the activation of calcium-release channels in such diverse systems as mammalian neurones, myocytes, blood cells, eggs, and plant microsomes. In this review we focus on recent work suggesting that cADPR enhances the sensitivity of ryanodine-sensitive calcium-release channels (RyRs) to activation by calcium, a phenomenon termed calcium-induced calcium release (CICR). Two roles for cADPR in calcium signaling are discussed. The first is as a classical second messenger where its levels are controlled by extracellular stimuli, and the second mode of cellular regulation is that the levels of intracellular cADPR may set the sensitivity of RyRs to activation by an influx of calcium in excitable cells. These two possible actions of cADPR are illustrated by considering the signal transduction events during the fertilization of the sea-urchin egg and the modulation of CICR during excitation-coupling in isolated guinea-pig ventricular myocytes, respectively.

Adenosine Diphosphate Ribose↗
PubMed1998

Special smooth muscle cells along the submucosal surface of the guinea pig colon with reference to its spontaneous contractions.

Antiperistalses occur from the flexure region of the guinea pig colon. We previously demonstrated that the circular muscle at the mesenteric border of the flexure region produced spontaneous regular contractions and found special smooth muscle cells believed to be pacemakers along the submucosal surface of the circular muscle layer. In this study, we revealed bipolar- and multipolar-type special smooth muscle cells along the submucosal surface of the muscle layer. Their slender cell processes contacted each other and formed a cellular network. Caveolae, filament structures expressing smooth muscle actin, vimentin, some desmin, and basal lamina were prominent features. The special smooth muscle cells corresponded to c-Kit-immunopositive cells and so-called interstitial cells or interstitial cells of Cajal in other reports. Their population was larger in the flexure region and the proximal colon than in the distal colon. The circular muscle layer at the flexure region was thicker than in other regions. The contraction in the flexure region showed the highest frequency and regularity. The dense population of special smooth muscle cells at the flexure region and thicker muscle layer may make the mechanical contraction more regular. The antiperistalsis from the flexure region could be explained in relation to the highest frequency of the pulsating contraction.

Actins↗
PubMed1998

Neurocalcin-like immunoreactivity in the rat esophageal nervous system.

Neurocalcin is a newly identified neuronal calcium-binding protein. We tried here to investigate the immunohistochemical distribution of neurocalcin in the rat esophagus. Nerve cell bodies having neurocalcin immunoreactivity were found throughout the myenteric plexus. In the myenteric ganglia, two types of nerve terminals showed neurocalcin immunoreactivity. One was varicose terminals containing numerous small clear vesicles and forming a synapse with nerve cells. The other terminals were characterized by laminar or pleomorphic structure and many mitochondria. These laminar terminals were supposed to be sensory receptors of the esophageal wall. In the motor endplates of the striated muscles, nerve terminals containing many small clear vesicles and mitochondria also had neurocalcin immunoreactivity. After left vagus nerve cutting under the nodose ganglia, the number of immunopositive thick nerve fibers, laminar endings and nerve terminals on the striated muscles decreased markedly. Retrograde tracing experiments using Fast Blue showed extrinsic innervation of esophagus from ambiguus nucleus, dorsal motor nucleus of vagus, superior cervical ganglia, celiac ganglia, nodose ganglia and dorsal root ganglia. In the celiac ganglia, nodose ganglia and dorsal root ganglia, retrogradely labeled nerve cells were neurocalcin-immunoreactive. Neurons in the celiac ganglia may project varicose terminals, while nodose and dorsal root neurons project laminar terminals. Although cell bodies of motoneurons in the ambiguus nucleus lacked neurocalcin immunoreactivity, these neurons may contain neurocalcin only in the nerve terminals in the motor endplates. Neurocalcin immunoreactivity is distributed in many extrinsic and intrinsic neurons in the esophagus and this protein may play important roles in regulating calcium signaling in the neurons.

Animals↗
PubMed1998

Localization of the adenomatous polyposis coli tumour suppressor protein in the mouse central nervous system.

The adenomatous polyposis coli gene is mutated in familial adenomatous polyposis and in sporadic colorectal tumours. The adenomatous polyposis coli gene product is a 300,000 mol. wt cytoplasmic protein that binds to at least three other proteins; beta-catenin, a cytoplasmic E-cadherin-associated protein; hDLG, a human homologue of the Drosophila discs large tumour suppressor protein and glycogen synthase kinase 3 beta, a mammalian homologue of the Drosophila ZESTE WHITE 3 protein. The adenomatous polyposis coli gene is highly expressed in the brain, suggesting that it may be involved in nerve function. Here we show that adenomatous polyposis coli is localized in the pericapillary astrocytic endfeet throughout the mouse central nervous system. Adenomatous polyposis coli is also localized in the astrocytic processes in the cerebellar granular layer, and displays concentrated expression in the terminal plexuses of the basket cell fibres around Purkinje cells. Adenomatous polyposis coli is further expressed in neuronal cell bodies and/or nerve fibres in the olfactory bulb, hippocampus, brain stem, spinal cord and dorsal root ganglia. Adenomatous polyposis coli is demonstrated to be co-localized with beta-catenin and/or hDLG in neurons and nerve fibres, but not in astrocytes. From these results, adenomatous polyposis coli is suggested to participate in a signal transduction pathway in astrocytes which is independent of beta-catenin and hDLG, and also in regulation of neuronal functions in association with beta-catenin and hDLG.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Analysis of conserved ambisense sequences within GB virus C.

No analysis has been done of the ambisense of GB virus C (GBV-C). When the anti-genomes of 16 reported sequences of GBV-C were analyzed, nucleotide codons 1758 and 1402 within the anti-genome were conserved initiation and stop codons, respectively. Nucleotide sequences were also determined within the same region of 22 GBV-C strains. The anti-genomes of 38 sequences were translated and a consensus sequence was determined. In accordance with the consensus sequence, overlapping peptides were synthesized and used for the detection of anti-synthetic peptide antibodies by ELISA. The positivity of antibodies among sera with GBV-C RNA was significantly higher than among sera without GBV-C RNA (66.7% vs. 15.6%), regardless of the simultaneous presence of hepatitis B surface antigen or antibodies to hepatitis C virus (P < .05). These results indicated that a novel protein associated with GBV-C might be expressed from the ambisense of this virus.

Antibodies, Viral↗
PubMed1998

Relationship between infection with hepatitis C virus and hepatocellular carcinoma in Japan.

The number of deaths due to HCC is increasing in Japan. Males in particular have seen a marked increase in the past 20 years, and HCV infection accounts for this increase. In patients treated with IFN and followed up for more than 12 months, HCV clearance was achieved in 29.8% and sustained normalization of ALT levels was achieved in 41.4% following IFN therapy. The incidence of HCC following IFN treatment is dependent on the effect of IFN on ALT levels. The incidence of HCC was low in patients with sustained normalization of ALT levels following IFN therapy, regardless of whether or not HCV had been eradicated. In the future, in addition to the development of therapies to eradicate HCV, treatments to lower ALT levels will also be important.

Alanine Transaminase↗
PubMed1998

[The clinical significance of plasma tissue plasminogen activator (t-PA) levels in severe acute or fulminant hepatitis].

We studied the tissue plasminogen activator (t-PA) levels in the plasma of patients with acute hepatitis (AH), severe acute hepatitis (AHs) and fulminant hepatitis (FH). Plasma t-PA levels were measured consecutively on the first, third and seventh days of hospitalization. Plasma t-PA levels were markedly higher in AHs and FH than in AH (p < 0.05, p < 0.01, respectively) on the first day, but did not differ significantly between AHs and FH on this day. The t-PA levels decreased markedly on the third and seventh days in AHs (both p < 0.05), but did not change from the first day to the third and seventh days in FH. The t-PA levels on the third and seventh days were higher in FH than in AHs (both p < 0.05). There was a significant increase in the plasma t-PA level before an episode of encephalopathy in FH compared with levels in AHs. These observations suggest that t-PA level may be useful as a prognostic parameter in patients with acute hepatic injury.

Acute Disease↗
PubMed1998

Heterogeneity in E2 region of GBV-C/hepatitis G virus and hepatitis C virus.

GB virus C/hepatitis G virus (GBV-C/HGV) is related distantly to hepatitis C virus (HCV). HCV has a hypervariable region (HVR), and exists as quasispecies in vivo. Although GBV-C/HGV also has replaceable amino acids in the presumed antigenic region, the existence and fluctuation of population of heterogeneous virus have not been evaluated. In this study, the heterogeneity of GBV-C/HGV and HCV was investigated by the single-strand conformation polymorphism (SSCP) analysis in six concomitantly infected patients. Two patients were observed for 4 years without any treatment, and four were treated with interferon-alpha (IFN). By SSCP analysis, amplicons of GBV-C/HGV RNA were separated into 1-5 bands on gels for each patient. The amplicons had different nucleotide but the same amino acid sequences in the presumed antigenic region. The amplicons of HCV RNA, separated into 1-4 bands, had different nucleotide and amino acid sequences in the HVR. In the two patients without treatment, the predominant strain of GBV-C/HGV was unchanged for the 4 years. In the four patients administered IFN, some strains of GBV-C/HGV disappeared after IFN therapy, whereas other strains persisted. The mean genetic distance among GBV-C/HGV strains represented by SSCP analysis was significantly lower than that of HCV (P < 0.05). The data indicate that: 1) GBV-C/HGV can be devoid of antigenic drift unlike HCV; 2) GBV-C/HGV has no HVR as seen in HCV in the presumed antigenic region; and 3) the sensitivity to IFN differs among GBV-C/HGV strains in the same hosts, as with HCV.

Adult↗
PubMed1997

Three different GB virus C/hepatitis G virus genotypes. Phylogenetic analysis and a genotyping assay based on restriction fragment length polymorphism.

The 5'-untranslated region (5'-UTR) sequences of 33 GB virus C/hepatitis G virus (GBV-C/HGV) obtained from different geographic areas were determined through reverse-transcription polymerase chain reaction and dideoxy chain termination sequencing, the alignment of sequences, the estimation of the number of nucleotide substitution per site, and construction of phylogenetic trees. The 5'-UTR of GBV-HGV was found to be heterogeneous, with 70.9-99.5% homology. Three distinct phylogenetic branches were observed consistently in all phylogenetic trees. GBV-C is the prototype for one, HGV for another, and there is a new branch which consisted of GBV-C/HGV isolates from Asia. Genotype-specific restriction sites for the restriction enzymes, ScrFI and BsmFI, were identified, and a simple restriction fragment polymorphism analysis was developed for genotyping. These data provide evidence that GBV-C/HGV consists of three different genotypes. Our simple genotyping assay will also provide a tool for epidemiological studies of GBV-C/HGV infection.

Base Sequence↗
PubMed1997

Clonotypic analysis of T cells in patients with autoimmune and viral hepatitis.

The immunopathogenesis of autoimmune hepatitis (AIH), and the role of T cells in the onset and maintenance of this disease, are still unclear. Since T cells expand clonally after stimulation by an antigen, it is important to analyze the behavior of T cells at a clonal level. We have established recently a novel system, using reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism (SSCP) that allows the identification of clonal accumulation of T cells in a lymphocyte population. Using this system, we demonstrated that oligoclonal T cells were accumulated in the liver of patients with AIH, and that identical T-cell clonotypes were detected in two different regions of the liver, although these features were also observed in cases with viral hepatitis. Only in cases with AIH, however, nearly all identical T cells were found to belong to CD8+ subset and there were very few CD4+ T cells in this population. Our results suggest that common antigens presented to CD8+ T cells in the context of HLA class I molecule are distributed diffusely in the liver of AIH. These findings also suggest that antigens recognized by CD4+ T cells may be relatively heterogeneous in the liver with AIH.

Adult↗
PubMed1997

Heterogeneous distribution of neurocalcin-immunoreactive nerve terminals in the mouse adrenal medulla.

Neurocalcin is a novel calcium-binding protein found in bovine brain tissue. We investigated immunoreactivity for neurocalcin in the mouse adrenal medulla using light and electron microscopy. The immunoreactivity was present in nerve fibers, nerve terminals, and ganglion cells in the adrenal medulla, but chromaffin cells, sustentacular cells, and Schwann cells were negative in reaction. Nerve bundles containing neurocalcin-immunoreactive fibers passed through the adrenal cortex and extended into the medulla. Immunopositive nerve fibers branched off and projected varicose terminals around the chromaffin cells. These varicose terminals contained small and large-cored vesicles and made synapses with the chromaffin cells. We performed paraformaldehyde-induced fluorescence-histochemical studies for catecholamine combined with immunohistochemical studies for neurocalcin. Neurocalcin-immunoreactive nerve terminals were more abundant at noradrenaline (fluorescent) cell-rich regions than at adrenaline (non-fluorescent) cell-rich regions. These results show that neurocalcin-immunoreactive nerves mainly innervate noradrenaline-containing chromaffin cells in the mouse adrenal medulla and that neurocalcin may regulate synaptic function in the nerve terminals.

Adrenal Medulla↗
PubMed1997

Biochemical and morphological changes in the liver during isolated liver perfusion with double bypass using automatic blood pumps.

Isolated organ perfusion is used in clinical practice for chemotherapy in adults with malignant tumors. However, it has not been performed in children because of the size mismatch with the adult circuits. The authors have previously studied isolated liver perfusion in small animals using the self-regulating extracorporeal membrane oxygenation circuit. The present study was designed to investigate the biochemical and morphological changes in the liver during isolated liver perfusion with double bypass using automatic blood pumps. Isolated liver perfusion was performed with bypass between the hepatic and portal veins in seven weanling Yorkshire swine weighing 8.2 to 12.2 kg, at a flow rate of 20 mL/min/kg for up to 4 hours. Venous blood from the intestine and lower body was bypassed to the superior vena cava. As a result, perfusate glutamic pyruvic transaminase and lactate concentrations did not change during liver perfusion. On gross inspection, the surface of the liver was mottled. Microscopically, normal histology of the hepatic parenchyma and portal tract structures was preserved. Transmission electron microscopy showed no gross structural abnormalities in most of the hepatocytes for up to 4 hours. However, swelling of the mitochondria and smooth endoplasmic reticulum was seen occasionally in a very small number of the hepatocytes after more than 3 hours of perfusion. Glycogen granules decreased with time in some animals. Isolated liver perfusion at 20 mL/min/kg of perfusion flow can be performed safely for up to 4 hours with nearly intact hepatocellular function and morphology.

Alanine Transaminase↗
PubMed1997

Unique spindle cells in the involved ileal segment of rats with congenital aganglionosis.

Protein gene product (PGP) 9.5 is a newly characterized brain-specific protein originally detected by high-resolution two-dimensional electrophoresis of soluble human brain proteins. Immunoreactivity for PGP9.5 was investigated in the small and large intestine of aganglionic mutant and control rats with light microscopy, electron microscopy, and confocal laser scanning microscopy. Immunoreactive spindle-shaped cells were seen in the inner circular muscle layer of the aganglionic ileal segment. The long axes of these spindle cells paralleled the inner circular muscle fibers. PGP9.5-positive spindle cells were positive for enteric actin, and some of them were also positive for vimentin, a relatively specific marker for the special smooth muscle (pacemaker cells). These cells may prove to be a maldeveloped microenvironment of aganglionic segment. However, it is necessary to investigate expression of PGP9.5 in embryonal tissue with an abnormal environment to test this hypothesis. This study showed PGP9.5-positive pacemaker cells in the aganglionic ileal segment in the first time.

Animals↗
PubMed1997

Interferon-alpha therapy in patients dually infected with hepatitis C virus and GB virus C/hepatitis G virus--virological response of HGV and pretreatment HGV viremia level.

BACKGROUND/AIMS: The response to interferon-alpha (IFN) therapy of recently isolated GB virus C and hepatitis G virus (HGV) is still unclear. To investigate the biochemical and virological response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection concomitantly infected with HGV, 196 patients with HCV who had received IFN therapy were retrospectively studied. METHODS: HGV and HCV RNA were detected by reverse transcription nested polymerase chain reaction (RT-PCR). Serum HGV RNA levels were quantified by competitive RT-PCR. The HGV genotype was detected by restriction fragment length polymorphism analysis using the PCR products. RESULTS: Of 196 patients, 16 (8.2%) were positive for both HCV and HGV RNA before IFN therapy. There were no significant clinical and virological differences between the patients with dual infection and those with only HCV infection. During the therapy, a decrease or loss of serum HGV RNA level was observed in these patients. Six months after cessation of the therapy, five of 16 patients became negative for HGV RNA by RT-PCR. The pretreatment HGV RNA level of the patients who lost HGV RNA after cessation of IFN was low (median=10(3) copies/ml), compared to the level (median=10(7) copies/ml, p<0.01) in the patients with positive HGV RNA after the therapy. The HGV genotype of these 16 patients was the same type. CONCLUSIONS: These data suggest that: 1) there is no significant difference in response to IFN therapy between patients with dual and single infection; 2) HGV shows sensitivity to IFN therapy; and 3) in the patients who show a low pretreatment HGV RNA level, serum HGV RNA becomes undetectable by RT-PCR after cessation of IFN therapy.

Adult↗
PubMed1997

Prevalence of hepatitis C virus infection in Nanjing, southern China.

There is little information on the prevalence of hepatitis C virus (HCV) infection in China. The prevalence of HCV infection was determined in 998 subjects (398 with liver disease and 600 without) in the city of Nanjing in southern China. Subjects were tested for anti-HCV antibodies by a second generation assay. We also determined serological HCV genotypes and HCV RNA sequences. Among the 600 subjects without liver disease, 3 (0.5%) were seroreactive for anti-HCV. All were less than 12 years of age and had a history of transfusion. Of the 398 liver disease patients, 20 (5.0%) were seroreactive for anti-HCV. Of 16 patients in whom serological HCV genotype was determined, 10 (62.5%) were infected with HCV type 1, 5 (31.3%) with type 2 and 1 (6.3%) undetermined. HCV genomes sequenced from 2 patients belonged to genotype 2 and were closely related to strains in Beijing and Japan by molecular evolutionary analysis. These results suggest that HCV infection is rare and not a major cause of liver disease in southern China.

Adult↗