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Biomedical subjects

H Obata

Publications and source records attributed to H Obata.

234 records · Page 13Linked to original sources
PubMedDate not supplied

Prognosis of primary hepatocellular carcinoma.

Prognosis of 600 consecutive patients with hepatocellular carcinoma was analyzed in relation to treatment. They were divided into three stages based on four parameters of advanced disease: ascites, tumor greater than 50% of the two-dimensional size of the liver, serum albumin below 3 gm per dl, and serum bilirubin above 3 mg per dl. Stage I had none of these signs; Stage II one or two signs, and Stage III three or all signs. Of 600 patients, 98 had resection, 333 had nonsurgical treatment (158 treated by intraarterial chemotherapy, 94 systemic chemotherapy, 77 transcatheter embolization, and 4 others) and 169 no treatment. The median survival of untreated patients was only 1.6 months from diagnosis, and no untreated Stage III patient lived more than 3 months; there was a median survival of 0.7 month. Surgically treated patients lived significantly longer than nonsurgical patients of comparable stages; median survival was 19.6 months in the former and 2.8 months in the latter. Whereas Stage I patients did fairly well without treatment, chemotherapy significantly prolonged survival of patients of Stages II and III. These results suggest that early diagnosis and hepatic resection improve prognosis in patients with hepatocellular carcinoma in the areas where this cancer frequently emerges unicentrically. In view of the generally poor prognosis, liver transplantation is recommended when resection is not possible or indicated, and before extrahepatic metastasis occurs.

Adolescent↗
PubMedDate not supplied

Dual color fluorescence analysis of peripheral T cell subsets in hepatitis B virus-induced liver disease.

By using dual color fluorescence analysis, peripheral T cells can be divided into four different subsets, Leu-2a+15+, Leu-2a+15-, Leu-3a+8+ and Leu-3a+8- cells. The ratio of these T cell subsets in hepatitis B virus-induced hepatitis patients was studied and compared with that of controls. No significant difference was found in acute hepatitis and chronic hepatitis, but an elevation of Leu-2a+15- (29.5 +/- 2.8% vs. 18.8 +/- 4.1%, p less than 0.05) as well as a reduction of Leu-2a+15+ cells (3.2 +/- 0.7% vs. 10.4 +/- 3.2%, p less than 0.05) were found in fulminant hepatitis patients. In addition, serial studies of two fulminant hepatitis patients revealed that the imbalance of these two Leu-2a cells was only found in the acute phase, but not in the recovery phase. These results indicate that the imbalance of these two Leu-2a cells is associated with the clinical status of patients with fulminant hepatitis.

Acute Disease↗
PubMedDate not supplied

A rat model of postthoracotomy pain: behavioural and spinal cord NK-1 receptor assessment.

PURPOSE: To develop a new rat model of postthoracotomy pain for investigating its mechanisms and clarifying neurochemical changes. METHODS: Male Wistar rats were randomly assigned to three groups that underwent either fourth and fifth intercostal nerve ligation, cutting of the fourth and fifth ribs, or a sham operation in which only pleura was cut. For behavioural response assessment during the following month, pinch and touch were used as mechanical stimuli, and acetone was used as a cold thermal stimulus. In addition, (125)I-substance P autoradiography was used to determine neurokinin (NK) receptor density in spinal cord laminae I and II at one to six weeks after surgery. RESULTS: In rats with nerve ligation, hypersensitivity to noxious and non-noxious stimuli continued throughout the month. The "mirror phenomenon" was observed. The lowest threshold was obtained in the dorsomedial portion of the T4 dermatome on the side of surgery. In rats with rib cutting, a lowered threshold to noxious and non-noxious stimuli was observed for two weeks. In rats with sham operations, hypersensitivity was seen only at postoperative day one. NK-1 receptor density on the side of operation increased significantly in rats with nerve ligation from day seven to 28. Receptor density was highest on day 14 (22.97 +/- 1.04 fmol x mg(-1) tissue vs. control, 16.22 +/- 0.43), representing a 50% receptor excess on the side of ligation compared to the contralateral side. CONCLUSION: Intercostal nerve damage induces long-term postthoracotomy pain and an increase of spinal NK-1 receptors in rats. This model may be useful for investigation of postthoracotomy pain.

Animals↗
PubMedDate not supplied

Expression of transforming growth factor-beta superfamily receptors in developing rat eyes.

PURPOSE: To ascertain the role played by the transforming growth factor (TGF)-beta superfamily in retinal development by determining the changes in the expression patterns of their receptors during development of the normal rat retina. METHODS: The expression of type I and type II receptors of the TGF-beta superfamily was observed at the protein level in rat eyes at embryonic age 17 days (E17), at birth (P0), at postnatal days 3, 6, 9, and at 11 weeks (P3, P6, P9, and adult, respectively). RESULTS: Activin type I receptor and BMP type IB receptor were first detected in P6 and P3 retinas, respectively, at the protein level, and activin type II receptor was first detected in the P0 retina. The other receptors (TGF-beta type I and II receptors, activin type IB receptor, BMP types IA and II receptors) were detected at E17. The period from P0 to P9 corresponded to the period of dynamic changes in the rat retinal development. CONCLUSION: The results suggest that the expression of TGF-beta superfamily is regulated along with retinal development and may be related to retinal development.

Activin Receptors, Type I↗
PubMedDate not supplied

Multiplicity of newly established monoclonal antibodies against hepatocellular carcinomas.

To identify tumour-associated cell surface antigens of human hepatocellular carcinoma (HCC), we established three monoclonal antibodies against a well established human HCC line, hu-H2. One of these, designated as KY-1, reacted with several HCC lines and a majority of peripheral blood lymphocytes. A second monoclonal antibody, KY-2, reacted only with HCC cell lines but not with others. With this KY-2 antibody, which was highly specific for HCC, HCC tissue was positively stained. A third monoclonal antibody, KY-3, reacted with HCC lines and many other malignant cell lines, but not with non-malignant cells. These results indicate that at least three different tumour-associated molecules are expressed on human HCC.

Antibodies, Monoclonal↗
PubMedDate not supplied

Dual colour fluorescein analysis of peripheral blood T cells in auto-immune chronic active hepatitis.

Both CD4 and CD8 T cells are subdivided into two phenotypically distinct sublineages via another two T cell markers, Leu-8 and CD11b antigens. The proportions of these four T cell subsets, CD4+Leu8+, CD4+Leu8-, CD8+11b+ and CD8+11b-, were studied in patients with auto-immune chronic active hepatitis (CAH) and compared with disease controls (hepatitis B surface antigen positive chronic active hepatitis) and healthy controls. We found that the proportion of CD4+Leu8+ cells was significantly reduced compared with controls (P less than 0.01), whereas those of the other cells were almost identical in all 3 groups. The absolute number of these CD4+Leu8+ cells was also lower than that of controls (P less than 0.01). Thus, the present study suggests that a reduced number of CD4+Leu8+ cells is associated with the aberrant immune response in auto-immune CAH.

Adolescent↗
PubMedDate not supplied

A defective autologous mixed lymphocyte reaction in patients with idiopathic portal hypertension.

The aetiology of idiopathic portal hypertension or hepatoportal sclerosis is unknown. In view of the indirect evidence for underlying immunologic abnormalities 14 patients (all middle-aged females) were studied. Various auto-antibodies were demonstrated in seven patients and high levels of serum immunoglobulins, either IgG, IgM or IgA were present in ten patients. T cell responsiveness to stimulation with either autologous or allogeneic non-T cells was examined in nine of 14 idiopathic portal hypertension patients and compared with responsiveness in patients with posthepatitic cirrhosis and splenomegaly, and healthy controls. Patients with cirrhosis had levels of T cell responsiveness which were not significantly different from those in healthy controls in both autologous and allogeneic mixed lymphocyte reactions. A distinctly reduced autologous mixed lymphocyte reaction was observed in all idiopathic portal hypertension patients. These data indicate that, like many other autoimmune diseases, abnormal serological features and impaired autoreactive T cell responsiveness exist in patients with idiopathic portal hypertension.

Antibodies, Antinuclear↗
PubMedDate not supplied

Loss of heterozygosity on chromosome 16 in hepatocellular carcinoma.

In order to understand the molecular genetics of human hepatocellular carcinoma (HCC) a common chromosomal abnormality in HCC was examined using restriction fragment length polymorphism (RFLP) analysis. Sixty-eight HCC specimens were examined for loss of heterozygosity at 11 different chromosomal arms including 1p, 5p, 11p, 11q, 13q, 14q, 15q, 16p, 16q, 18q, and 19q. Losses were not detected on chromosome 1, 5, 14, 15 or 19, and the frequencies of losses were low (11-19%) for chromosomes 11, 13 and 18. In contrast, loss of heterozygosity was frequently observed for three different loci on chromosome 16, the HBA locus at 16p13.3 (22%), the MT2 locus at 16q21-22.1 (15%) and the HP locus at 16q22.1-22.2 (39%). There was no remarkable difference in the frequencies of loss of heterozygosity at these loci among HBV related HCC, HCV related HCC and neither virus (NBNC) related HCC. Thus, the results indicate that at least three different genetic abnormalities in chromosome 16 are commonly observed in various HCC, and that this chromosome may have some important role(s) in recessive genetic changes which generate this tumour.

Alleles↗
PubMedDate not supplied

Clinical evaluation of a newly established anti-HCV assay for the diagnosis of hepatitis C in Japan.

To develop a more dependable method of diagnosing hepatitis C, serum anti-hepatitis C virus (HCV) was examined by using a new assay (anti-HCV second generation). The results were compared with those of either the conventional assay (anti-HCV first generation) or HCV-RNA analysis. With the first generation assay, anti-HCV was detected in 69% of post-transfusion acute hepatitis (AH), 44% of sporadic AH, 50% of needlestick exposed AH, 72% of chronic hepatitis (CH), 77% of liver cirrhosis (LC) and 86% of hepatocellular carcinoma (HCC). These results were remarkably increased by using the second generation assay (92% in post-transfusion AH, 72% in sporadic AH, 100% in needlestick exposed AH, 96% in CH, 96% in LC and 97% in HCC). Furthermore, in the early stages of AH (from 1-5 weeks after onset), anti-HCV was not detected in all 18 patients by the first generation assay, but was found in 10 of them by using the second generation assay. The failure to detect anti-HCV with the first generation assay was mainly due to a lack of the core region coding peptide (C22-3) in this assay. In the AH-resolving group, anti-HCV second generation did not disappear, but the titre tended to be lower than that in the CH-developing group. Thus, the second generation assay for anti-HCV was considered to be a more useful tool for not only the diagnosis of hepatitis C but also for determining prognosis.

Adult↗
PubMedDate not supplied

Prevalence of primary sclerosing cholangitis and other liver diseases in Japanese patients with chronic ulcerative colitis.

An association between primary sclerosing cholangitis (PSC) and chronic ulcerative colitis (CUC) is well known in Western countries, but there have been no reports on this association in Japan. We reviewed 163 consecutive CUC patients (91 males and 72 females) diagnosed from 1984 to 1990 at Tokyo Women's Medical College. Abnormal liver function tests were found in 42 patients with CUC (25.8%), but chronic liver disease was only diagnosed in seven patients (4.3%). Among these seven patients, there were four with PSC, one with small-duct PSC, one with transfusion-associated chronic hepatitis and one with Type B liver cirrhosis. No relationship was found between the documented colonic manifestations of CUC and the presence of PSC. The four PSC patients did not have a longer history of CUC at the time of diagnosis of PSC than CUC patients without PSC. At the time of PSC diagnosis, two patients were asymptomatic, one presented with right upper quadrant pain, and the other had fatigue. Three patients were diagnosed as having CUC before the onset of PSC (range 2-13 years), and the other patient had both diseases simultaneously. All four had a good prognosis. Thus PSC was the most common chronic liver disease associated with CUC in our series, and it was present in all our CUC patients with alkaline phosphatase levels exceeding twice the upper limit of normal and mild transaminase elevation.

Adolescent↗
PubMedDate not supplied

Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma: relationship to histological grade.

Proliferating cell nuclear antigen (PCNA), also known as cyclin, is an auxiliary protein of DNA polymerase-delta and is found only in the nuclei of proliferating cells in the late G1 and S phases. The proliferation of hepatocellular carcinoma (HCC) by immunohistochemical staining for PCNA using paraffin sections of 20 surgically resected HCC specimens was analysed. The mean percentage of PCNA-positive nuclei in the HCC tissue was 10.3% in grade I of Edmondson and Steiner's classification, 25.5% in grade II, 28.4% in grade III and 41.5% in grade IV. In early HCC, we observed only a few PCNA-positive tumour cells. However, PCNA-positive nuclei were numerous in the tumour thrombi found in portal vein branches, in regions of extracapsular tumour growth, and in the inner nodules of tumours with a nodule-in-nodule formation. Proliferating cell nuclear antigen positivity was correlated with an increase of the nucleocytoplasmic ratio of tumour cells as determined by image analysis. Our findings showed that PCNA positivity was correlated with the histological grade and invasiveness of HCC, suggesting that this antigen may be used as an indicator to predict tumour invasion in patients with HCC.

Adult↗
PubMedDate not supplied

Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue.

To clarify the mechanism of production of des-gamma-carboxy (abnormal) prothrombin (DCP) by hepatocellular carcinoma (HCC), we measured the levels of vitamin K, DCP, immunoreactive prothrombin and the activity of gamma-glutamyl carboxylase in liver tissues from HCC patients and in the medium of cultured human hepatoma cells. There was no significant difference in vitamin K (K1, MK-4) contents between HCC and non-HCC cirrhotic liver tissues. The activity of gamma-glutamyl carboxylase per unit amount of endogenous microsomal prothrombin precursor was decreased in HCC tissue compared with non-HCC liver tissue (positive plasma DCP: 335 +/- 72 vs 372 +/- 67, negative plasma DCP: 370 +/- 84 vs 393 +/- 56 nmol/min per mg prothrombin precursor, P > 0.05), although the total incorporation of 14COOH into microsomal precursor protein was higher in the former. By contrast, levels of DCP and immunoreactive prothrombin in HCC tissue were greater (P < 0.05) than those in non-HCC cirrhotic liver tissue. Furthermore, production of large amounts of immunoreactive prothrombin was observed in human hepatoma cells huH-1 and huH-2, which produced large amounts of DCP. These results suggest that there was excessive synthesis of prothrombin precursors by human HCC tissue and hepatoma cell lines huH-1 and huH-2. Thus, excessive synthesis of prothrombin precursors seems to be the main mechanism of DCP production by HCC.

Aged↗
PubMedDate not supplied

Effect of bunazosin, a selective alpha 1-adrenoceptor blocker, on ischemic myocardium in perfused rat heart.

The effects of bunazosin on the ischemic myocardium were investigated in isolated, perfused working rat hearts. Ischemia decreased the pressure-rate product and tissue adenosine triphosphate and creatine phosphate levels. Reperfusion did not restore the pressure-rate product nor the adenosine triphosphate levels completely. Bunazosin (5 x 10(-7) and 5 x 10(-6) mol/L) preserved the levels of adenosine triphosphate and creatine phosphate after 20 minutes of ischemia and increased the extent of recovery of the pressure-rate product during reperfusion. The results suggest that bunazosin protects the myocardium against ischemic damage.

Adenosine Triphosphate↗
PubMedDate not supplied

Improved preparation of ELISA antigen of infectious bursal disease virus.

Serotype 1 of infectious bursal disease virus (IBDV) adapted to chicken embryo fibroblasts (CEF) was used for the preparation of enzyme-linked immunosorbent assay (ELISA) antigen. After several passages of diluted viruses in CEF cultures, the titer of seed virus increased to 1.2 x 10(8) plaque-forming units/ml. Purified virus prepared from this seed virus had high titers of antigen and was less nonspecific than that from low titer of seed virus in an ELISA. The nonspecific reaction of purified virus decreased further after treatment with Triton X-100. When the specificity of this treated antigen was examined with specific-pathogen-free chicken sera before and during lay and with 14 antisera to some major avian viruses, this ELISA antigen had no nonspecific reaction and was specific to antibodies to serotypes 1 and 2 of IBDV.

Animals↗
PubMedDate not supplied

Experimental infection in specific-pathogen-free chicks with avian reovirus and avian nephritis virus isolated from broiler chicks showing runting syndrome.

Avian reovirus (ARV) and avian nephritis virus (ANV) were individually isolated from runty 10-day-old broiler chicks. The ARV isolate, IR-R, the ANV isolate, IR-N, and the reference strain of ANV, G-4260, were inoculated orally into 1-day-old chicks of two specific-pathogen-free (SPF) chicken lines, 151 and PDL-1. Growth retardation without the presence of gross lesions was clearly observed at 7 and 14 days postinoculation (PI) in chicks of both lines inoculated with the IR-R strain. On the other hand, in chicks inoculated with IR-N strain, growth retardation was observed only in the chicks of line 151 at 7 and 14 days PI. Microscopically, nephritis was observed in both chicken lines at 7 and 14 days PI. When chicks that were inoculated with the IR-N strain at 1 day of age were inoculated with the IR-R strain at 3 days of age, growth retardation was observed in the chicks of line PDL-1 at 10 and 17 days PI. However, the growth retardation was less severe than in the group receiving a single inoculation of the IR-R strain.

Animals↗