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Biomedical subjects

Y Matsunaga

Publications and source records attributed to Y Matsunaga.

At least 37 records · Page 2Linked to original sources
PubMed2000

Complete disappearance of recurrent hepatocellular carcinoma with peritoneal dissemination and splenic metastasis: a unique clinical course after surgery.

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We report a case of complete disappearance of intrahepatic, peritoneal and splenic metastases in HCC after hepatectomy using treatment with tegafur and uracil (UFT). The effect of UFT alone was not likely to have caused the disappearance of this tumour because HCC recurrence advance markedly within 5 months of surgery despite oral administration of UFT. This case demonstrates a unique postoperative clinical course that suggests spontaneous regression of HCC. This is the first case of complete disappearance of unresectable HCC with peritoneal seeding and splenic metastasis.

Aged↗
PubMed2000

Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris.

A new enzyme-linked immunosorbent assay can detect 10 pg/ml of human hepatocyte growth factor (HGF). Circulating HGF was significantly higher in patients with unstable angina (296+/-184 pg/ml, mean+/-SD, n=36) than in healthy volunteers (201+/-64 pg/ml, n=250, p<0.0001). Individual concentrations exceeded the mean control value +2 SD (329 pg/ml) in 12 of the 36 (33%) patients with unstable angina. The present study indicates that this new, sensitive HGF assay can successfully detect thrombosis in patients with unstable angina.

Adolescent↗
PubMed2000

[Expression of cyclin E in postmitotic cells in the central nervous system].

Cyclin E, a member of G1 cyclins, is expressed specifically at the G1 to S phase in proliferating cells and promotes the entry into S phase by binding and activating a specific cyclin-dependent kinase, cdk2. To investigate the regulatory mechanisms of the cell cycle in the developing central nervous system (CNS), this study was conducted to analyze expression of cyclin E and other G1 cyclins/cdks in the developing and adult mice and rats. Western blotting and in situ hybridization indicate that both mRNA and protein of cyclin E are expressed in the developing CNS, and are also detected in adulthood when no expression of other G1 cyclins and cdks is observed. Immunohistochemical analysis reveals that, during development of the cerebral cortex, cyclin E protein is expressed not only in proliferating regions but also in differentiating regions where cells are mitotically negative, and that subcellular localization of cyclin E protein changes from the nucleus to the cytoplasm during postnatal development of CNS. Cyclin E forms a complex with cdk5 which is activated by a neuron-specific regulatory subunit, p35, and cyclin E/cdk5 complex was detected mainly in the cytoplasm, although no cyclin E-associated kinase activity was detected in the adult CNS. These results indicate that cyclin E is expressed in terminally differentiated neurons which are already withdrawn from the cell cycle, and suggest a novel role for cyclin E in postmitotic neurons in the CNS in addition to its role in cell cycle regulation in proliferating neuroblasts.

Animals↗
PubMed2000

[Surgery for lung cancer in octogenarians].

Twenty-five octogenarians with lung cancer underwent resection: 15 lobectomies, 3 segmentectomies, and 7 wedge resections. There were two operative deaths (8%) and one hospital death (4%). The complication rate was 26%. All complications occurred in cases with lobectomies. The cumulative 5-year survival rate was 47.4%, 57% for patients for curative and relative non-curative surgery, and 0% for absolute non-curative surgery. It is considered that limited operation for lung cancer in octogenarians is acceptable.

Adenocarcinoma↗
PubMed1999

Autocrine induction of substance P mRNA and peptide in cultured normal human keratinocytes.

In this study, we have demonstrated that normal cultured keratinocytes (KCs) could generate significant endogenous substance P (SP) in a dose- and time-dependent response to exogenous SP by sensitive ELISA assay and express preprotachinin-a mRNA by RT-PCR and Southern blotting. We performed immunohistochemical analysis to confirm the presence of SP in cultured keratinocytes. In contrast, adrenaline, acetylcholine, histamine and CGRP induced only low amount of SP from cultured normal human KCs. This is the first report that SP can be induced by skin epithelial cells in response to exogenous SP and KC derived SP might play an important role in induction and acceleration of certain cutaneous diseases.

Acetylcholine↗
PubMed1999

Mixed ductal-endocrine carcinoma of the pancreas presenting as gastrinoma with Zollinger-Ellison syndrome: an autopsy case with a 24-year survival period.

We report an autopsy case of mixed ductal-endocrine carcinoma of the pancreas presenting as gastrinoma with Zollinger-Ellison syndrome. A 38-year-old Japanese male was found to have Zollinger-Ellison syndrome and pancreatic gastrinoma, and gastrectomy and resection of the pancreatic tumor were performed. However, hypergastrinemia persisted, and the patient died of disseminated carcinomatosis at 62 years of age, 24 years after the onset of Zollinger-Ellison syndrome. At autopsy, the main tumor was present in the residual pancreas, and metastases were noted in many organs. In the pancreas and other organs, ductal and endocrine carcinoma areas were mixed and there was a gradual transition between the two. No acinar differentiation was noted. The ductal elements were positive for mucins and carcinoembryonic antigen but negative for neuroendocrine markers, while endocrine elements were positive for chromogranin A and synaptophysin and to a lesser extent for gastrin, but negative for mucins and carcinoembryonic antigen. The ductal elements comprised about 30% of the tumor cells, and endocrine elements 70%. According to the revised World Health Organization classification, our case was diagnosed as mixed ductal-endocrine carcinoma. Our case is rare because the tumor manifested as gastrinoma with Zollinger-Ellison syndrome and the patient survived for 24 years. To the best of our knowledge, no such case has been reported. Our case suggests that pancreatic endocrine tumors may evolve into mixed ductal-endocrine carcinomas.

Adult↗
PubMed1999

The vast majority of gastric T cells are polarized to produce T helper 1 type cytokines upon antigenic stimulation despite the absence of Helicobacter pylori infection.

Helicobacter pylori infection is associated with chronic infiltration by various cell types, including T cells, whose cytokine production may regulate the inflammatory reaction as well as local immune response to the bacterium. We prospectively analyzed the constituents of the cellular infiltrates and the cytokines produced by T cells in antral biopsies obtained from 73 subjects with and without H. pylori infection, before and after eradication therapy, and compared them with a histological grade of gastritis. We found that T cells predominated in cell number, followed by granulocytes/monocytes and plasma cells in both H. pylori-infected and H. pylori-uninfected subjects. Despite the absence of H. pylori infection, more than 70% of gastric CD4-positive T cells obtained from uninfected tissue produced interferon-gamma (IFN-gamma) in the cytosol. Upon receptor cross-linking of a CD3 and a CD28 molecule, T cells in both infected and uninfected tissue continuously secreted a far greater amount of IFN-gamma than those in peripheral blood mononuclear cell controls for a period of cell culture, whereas the increase in interleukin-4 (IL-4) was very small, and no increase in IL-2 secretion was seen. In H. pylori-infected patients, IFN-gamma secretion was correlated with the grade of mononuclear cell infiltration and decreased to an uninfected control level after eradication therapy. We did not see the effect of eradication on IL-4 secretion. Anti-H. pylori antibody of the IgG2 subclass was remarkably increased in H. pylori-infected subjects. These results together suggest that gastric T cells are already differentiated to produce a large amount of IFN-gamma by a mechanism unrelated to H. pylori infection. H. pylori infection appeared to activate T cells to secrete even more IFN-gamma, which may contribute to maintaining a perpetual inflammation in H. pylori-infected stomach.

Adult↗
PubMed1999

Parvovirus B19 infection induces apoptosis of erythroid cells in vitro and in vivo.

OBJECTIVE: intrauterine parvovirus B19 infection is related to non-immune hydrops fetalis, the pathogenesis of which is based on the strict tropism of B19 for erythroid precursor cells and the massive destruction of the infected erythroid cells, although the mechanism of beta19-induced cytotoxicity has not been studied in detail. The purpose of this study is to provide empirical evidence that beta19 induces apoptosis of erythroid cells both in vitro and ill vivo. METHODS: we analysed culture cells infected in vitro by B19 and tissues of nine cases of hydrops fetalis caused by B19 intrauterine infection by histological and biological methods. RESULTS: cells infected iil vitro by B19 showed nuclear changes characteristic of apoptosis by light microscopic examination and DNA extracted from the infected cells was fragmented. Electron microscopic examination showed the nuclei of infected cells contained crescent-shaped clumps of heterochromatin with increased density and double staining with anti-B1 9 antibody and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) confirmed apoptosis of individual cells. Tissues of cases of hydrops fetalis caused by B19 contained erythroid cells with nuclear inclusions and characteristic nuclear changes of apoptosis by light microscopy. The double-staining confirmed apoptosis of erythroid cells in the tissues. Immunohistochemical analysis with antibodies against cellular factors involved in apoptosis showed that caspase3, p53 and p21 were positive in infected cells.

Apoptosis↗
PubMed1999

Argatroban increases nitric oxide levels in patients with peripheral arterial obstructive disease: placebo-controlled study.

Intravenous argatroban infusion therapy is widely used for the restoration of peripheral microcirculation in patients with peripheral arterial obstructive disease (PAOD). We investigated the effect of argatroban infusion therapy on plasma levels of nitric oxide (NO) and nitrosylhemoglobin (HbNO) in patients with PAOD compared with a placebo-treated PAOD group. The chemiluminescence method was used to determine plasma NO and HbNO. Argatroban was administered as a continuous intravenous infusion for 60 minutes and repeated daily over a period of 2 weeks in 10 patients with PAOD. Treatment significantly improved the clinical signs and symptoms. Serial thermograms showed a 1-2 degrees C rise in the temperature of the affected legs in all patients immediately after intravenous argatroban infusion therapy. Enhancement of the peripheral circulation was maintained after the end of argatroban infusion for up to 90 minutes despite elimination of argatroban from the circulation. Furthermore, there was a progressive and significant increase in the mean concentration of plasma NO in PAOD patients after commencement of argatroban infusion (baseline, 58.0 +/- 13. 7;90 minutes after infusion, 65.7 +/- 13.4 microM; P < 0.01). HbNO significantly increased from a baseline value of 1063 +/- 126 to 1460 +/- 250 nM at 30 minutes after infusion (P < 0.01). However, the level of HbNo decreased thereafter, although it remained significantly elevated, even at 90 minutes after the end of argatroban infusion. Our results suggest that argatroban may lead to increased HbNO and plasma NO, and this may contribute to the improved microcirculation in PAOD patients.

Aged↗
PubMed1999

Marked histiocytosis in the portal tract in a patient with reactive hemophagocytic syndrome: An autopsy case.

We report an autopsy case of reactive hemophagocytic syndrome with peculiar liver histology. A 71-year-old female was diagnosed as having acute myelogenous leukemia and treated with chemotherapy. During her course, methicillin-resistant Staphylococcus aureus (MRSA) was noted in blood culture and she was diagnosed as having MRSA sepsis. She died of respiratory failure 5 months after the onset of leukemia and 10 days after the MRSA sepsis. Ante-mortem liver function tests were within normal ranges. At autopsy, myeloblastic leukemia cells positive for CD13 were present in the bone marrow and, to a much lesser extent, in the spleen and liver. Numerous histiocytes of a bland appearance with erythrophagocytosis were noted in the bone marrow and spleen. The histiocytes were positive for CD68, but negative for S-100 and lysozymes. In the liver, many histiocytes of bland appearance with erythrophagocytosis and CD68 positivity were present in the portal tracts with no Kupffer cell hyperplasia. There were no hepatocellular degeneration, fatty changes or sinusoidal dilations. We consider that this histiocytosis was associated with MRSA infection and diagnosed this as infection-associated hemophagocytic syndrome. In previously reported cases, hemophagocytosis in hyperplastic Kupffer cells was the main liver change of reactive hemophagocytic syndrome. The present case suggests that marked histiocytosis in portal tracts only may be a main feature of liver changes in reactive hemophagocytic syndrome and that such cases may not show abnormal liver function tests.

Aged↗
PubMed1999

Peribiliary capillary plexus around interlobular bile ducts in various chronic liver diseases: An immunohistochemical and morphometric study.

Peribiliary capillary plexus (PCP) is a network of capillaries which arise from the hepatic artery surrounding the intrahepatic bile ducts. We immunohistochemically investigated the density of PCP around interlobular bile ducts in various chronic liver diseases including primary biliary cirrhosis (PBC) (n = 47), autoimmune hepatitis (AIH) (n = 12), chronic hepatitis B (n = 16), chronic hepatitis C (n = 19), liver cirrhosis due to hepatitis B virus (n = 13), liver cirrhosis due to hepatitis C virus (n = 20), alcoholic hepatitis (n = 20), alcoholic liver cirrhosis (n = 17), using human liver biopsies fixed in formalin and embedded in paraffin wax. PCP was immunohistochemically detected by an endothelial marker, the CD34 antigen. The number of PCP per duct was 1.21 +/- 0.18 in normal livers. Compared with normal liver, vasopenia was observed in PBC and AIH, the number in which was 0.93 +/- 0.34 (P < 0.0001) and 0.82 +/- 0.38 (P < 0.005) per duct, respectively. In contrast, increased number of PCP was observed in liver cirrhosis due to hepatitis B or C virus, alcoholic hepatitis, and alcoholic liver cirrhosis, the number in which were 1.59 +/- 0.37 (P < 0.005), 1.55 +/- 0.52 (P < 0. 02), 1.38 +/- 0.23 (P < 0.02) and 1.61 +/- 0.33 (P < 0.002) per duct, respectively. These data suggest that PCP may be destroyed in autoimmune liver diseases, including PBC and AIH, but PCP may proliferate in other inflammatory and alcoholic liver diseases.

Adult↗
PubMed1999

Gastroprokinetic activity of nizatidine during the digestive state in the dog and rat.

The present study was undertaken to clarify a prokinetic activity of nizatidine (CAS 76963-41-2) during the digestive state as well as gastric emptying of a solid test meal in comparison with cimetidine (CAS 51481-61-9), famotidine (CAS 76842-35-6) and cisapride (CAS 81098-60-4). Intravenous administration of nizatidine (0.3-3 mg/kg) enhanced the motility of the gastric antrum and duodenum during the digestive state. With cimetidine (1-10 mg/kg) and famotidine (0.1-1 mg/kg) enhancement of gastric motility was observed only with the highest dose of cimetidine, and famotidine had no effect. Marked enhancement of gastric motility was observed with cisapride (0.1-0.5 mg/kg). After intraduodenal administration of nizatidine (10 and 20 mg/kg) and cisapride (0.25 and 0.5 mg/kg), they also amplified the contractile activity of the gastric antrum. Gastric emptying of a solid test meal was accelerated by intraperitoneal administration of nizatidine (1-10 mg/kg) to the same extent as cisapride (0.1-1 mg/kg). In addition, even in a model of delayed gastric emptying induced by clonidine, nizatidine, like cisapride, improved the rate of gastric emptying. Neither cimetidine (3-30 mg/kg) nor famotidine (0.3-3 mg/kg) affected the gastric emptying of a solid meal or delayed gastric emptying. These results suggest that nizatidine enhanced gastric motility even during the digestive state, and accelerated gastric emptying of a solid meal, similar to cisapride. Furthermore, nizatidine improved clonidine-induced delayed gastric emptying. These prokinetic activities of nizatidine may by useful for the treatment of abdominal symptoms due to dysmotility and delayed gastric emptying in patients with gastritis and non-ulcer dyspepsia (NUD). In comparison with famotidine and cimetidine, nizatidine may be different from other histamine H2-receptor antagonists and has unique properties other than its gastric antisecretory activity.

Animals↗
PubMed1999

Changes in prevalence of herpes simplex virus type 1 and 2 antibodies from 1973 to 1993 in the rural districts of Japan.

Using the gG-capture ELISA, changes in the seroprevalence of HSV-1 and HSV-2 from 1973 to 1993 were studied for 614 sera collected from general adults living in rural Japan. The HSV-1 seroprevalence for men and women decreased from 75.3 and 80.6% in 1973 to 54.4 and 59.6%, respectively, in 1993. The HSV-2 seroprevalence also decreased from 10.2 and 9.9% in 1973 to 1.8 and 1.2%, respectively, in 1993. Although the decrease in HSV-2 prevalence seemed to be correlated with the general decrease of sexually transmitted diseases in Japan since the 1950s, these findings should not be interpreted as typical, as HSV-2 infections are particularly known to distribute unevenly among populations, according to sexual activity and cohorts.

Adult↗
PubMed1999

Stromal mast cells and nerve fibers in various chronic liver diseases: relevance to hepatic fibrosis.

OBJECTIVE: Recently, mast cells have been postulated to play a role in fibrogenesis in primary biliary cirrhosis (PBC) and alcoholic liver disease (ALD). There are only a few reports on nerve fibers in normal and pathological human livers. METHODS: We simultaneously investigated mast cells and nerve fibers in the stroma by single and double immunostainings and by quantitative morphometry in six normal livers and in 178 liver biopsies of PBC (n = 49), autoimmune hepatitis (n = 12), chronic hepatitis B (n = 37), chronic hepatitis C (n = 41), and ALD (n = 39). RESULTS: The densities of tryptase-positive mast cells, chymase-positive mast cells, and S-100-positive nerve fibers in the stroma were significantly higher in these chronic liver diseases than in normal livers. There were no significant differences in their densities among these chronic liver diseases. The densities of tryptase- and chymase-positive mast cells correlated significantly with degree of fibrosis, and density of nerve fibers correlated roughly with degree of fibrosis. Double immunostainings showed that some mast cells were in close contact with nerve fibers, and that, in selected cases, the percentages of mast cells positive for only tryptase (MC(T)) and those positive for both tryptase and chymase (MC(TC)) were 26% and 74%, respectively. CONCLUSIONS: These results suggest that mast cells and nerve fibers are involved in fibrogenesis in chronic liver diseases, regardless of their etiologies, probably by secreting fibrogenic substances. Some mast cells are innervated, and this innervation may stimulate mast cells to secrete fibrogenic substances, leading to hepatic fibrosis.

Adult↗
PubMed1999

Changes in seroepidemiological pattern of Helicobacter pylori and hepatitis A virus over the last 20 years in Japan.

OBJECTIVE: The age groups most susceptible to infection and the mode of transmission of Helicobacter pylori (H. pylori) are not yet clear. To contribute to a better understanding of this disease, this study was undertaken to evaluate changes in the seroepidemiological pattern of H. pylori in a group of Japanese people over the last 20 yr sampled in 1974, 1984, and 1994 in comparison with that of the hepatitis A virus (HAV), which was used as a marker of the fecal-oral route of transmission. METHODS: A total of 1015 serum samples were obtained from the National Institute of Infectious Diseases in Tokyo. All of these samples were from healthy persons aged 0-89 yr (442 male and 573 female; median age 35.6 yr), living in seven prefectures in the central part of Japan in 1974, 1984, and 1994. All serum samples were assayed for H. pylori IgG by means of enzyme-linked immunosorbent assay (ELISA). Further, anti-HAV antibodies were assayed by blocking ELISA in the same samples. We investigated the prevalence of H. pylori and HAV for all ages, and the positive rate of H. pylori for infants and children separately. RESULTS: The overall prevalence of H. pylori antibodies was 72.7% (CI 95%, 68.0-77.3) in 1974, 54.6% (CI 95%, 49.1-60.0) in 1984 and 39.3% (CI 95%, 34.1-44.4) in 1994. That of HAV was 57.7% (CI 95%, 52.5-62.8) in 1974, 41.7% (CI 95%, 36.3-47.0) in 1984, and 23.4% (CI 95%, 18.9-27.8) in 1994. The prevalence of both H. pylori and HAV was found to increase with age, whereas there have been clear cohort shifts in the seroepidemiological patterns of both infections over the last 20 yr in Japan. This study shows that there is a slight similarity in the concordance of positive and negative populations between H. pylori and HAV. However, it was very difficult to determine the concordance between H. pylori and HAV infection in this study. CONCLUSIONS: Our data strongly suggest that the highest infection rates for both H. pylori and HAV occur among infants and children in Japan. This study provides evidence that H. pylori and HAV may share a common mode of transmission but that changes in environmental conditions make this very difficult if not impossible to prove with seroepidemiological data.

Adolescent↗
PubMed1999

[Current status of Japanese encephalitis in Japan].

Japanese encephalitis (JE) cases confirmed by serological and/or virological tests, and clinically typical fatal JE cases have been collected using individual report cards in Japan since 1965. A total of 324 confirmed cases (male: 167, female: 157) reported between 1982 and 1996 were analyzed. Annual incidence of JE cases was less than one hundred cases from 1982 to 1991, and less than 10 cases after 1992. Age distribution of the patients was: 0-9 years old, 43 cases (13%); 10-39 years old, 30 cases (9%); 40-69 years old, 161 cases (50%); over 70 years old, 90 cases (29%). The highest incidence in male cases was observed in the age group of 50-59 years, and that in female was in 60-69 years. Most of the patients (95%) were living in the western parts of Japan. No patient was reported from Okinawa, southern-most prefecture of Japan, and from Tohoku-Hokkaido area, northern parts of Japan. The date of onset were distributed from the end of July to the end of October, and the highest incidence was observed in the end of August. Prognosis of the patients were: complete recovery, 99 cases (31%); sequelae, 156 cases (48%); total, 56 cases (17%); unknown, 13 cases (4%). Vaccination histories of patients were reported as vaccinee, 4 cases (1%); incomplete vaccinee, 14 cases (4%); non-vaccinee, 181 cases (56%); unknown, 125 cases (39%). Spread of JE virus in Japan has not been diminished as shown by the data of antibody acquisition of young swine in every summer in Japan. Based on these observations we conclude that JE vaccination has contributed to maintaining the low JE incidence among children in Japan.

Adolescent↗