Search PubMed⌕ Search

Biomedical subjects

T Osada

Publications and source records attributed to T Osada.

At least 91 records · Page 5Linked to original sources

Neurite-promoting effect of alpha 2-macroglobulin in rat cerebral cortex is mainly associated with alpha 2-macroglobulin receptor.

It has been reported that alpha 2-macroglobulin (alpha 2 M), known as a plasma protease inhibitor, promotes neurite outgrowth of cultured neurons from rat cerebral cortex. The neurons dissociated from 17-day embryonic (E17) rat cerebral cortex were cultured in the medium containing methylamine-modified alpha 2M labeled with fluorescein isothiocyanate (MA- alpha 2 M-FITC). The modified alpha 2 M was taken up by neurons and localized mainly at the base of neurites. The fluorescence intensity of internalized MA- alpha 2 M-FITC in the cell was correlated to the degree of neurites extension. An immunocytochemical study using anti-alpha 2 M receptor (alpha 2 MR) polyclonal antibody showed that the neurons cultured for a longer period were stained weaker than those cultured for a shorter period. Many alpha 2 MRs were expressed when the neurons were likely to be extending the neurites well. From the developmental study of rat cerebrum, the expression of alpha 2 MR reached a maximum at postnatal 2 days (P2) when the neurons started to exhibit active neurite extension. These observations led us to conclude that neurite promoting effect of alpha 2 M acts through alpha 2 M-alpha 2MR binding and/or the following uptake of alpha 2 M.

Animals↗

Human colorectal carcinomas specifically accumulate Mr 42,000 ubiquitin-conjugated cytokeratin 8 fragments.

Recent studies have shown that various tumor cells accumulate ubiquitin (Ub)-conjugated proteins, the profiles of which differ from those of normal cells. To identify the Ub-conjugated proteins accumulated specifically by human carcinoma cells, a two-dimensional immunoblot analysis of 31 surgically resected human primary colorectal carcinoma tissues was performed using an anti-Ub monoclonal antibody, KM691. Two distinct Mr 42,000 and 45,000 proteins in the Triton X-insoluble fractions of carcinoma tissues reacted with this antibody, whereas only one Mr 45,000 protein reacted in normal tissues. The Mr 42,000 Ub-conjugated proteins were specific to carcinoma tissues from 25 patients (80.6%). One of the purified Mr 42,000 proteins was digested with Achromobacter protease I. This protein was identified as a cytokeratin 8 (CK 8) fragment based on both molecular mass determination and molecular mass searching of Achromobacter protease I-digested fragments of proteins registered in a protein sequence data base. Two-dimensional immunoblot analysis with an anti-CK 8 antibody confirmed that all of the Mr 42,000 proteins were CK 8 degradation products. These results demonstrate that human colorectal carcinomas specifically accumulate Mr 42,000 Ub-conjugated CK 8 fragments. This accumulation was observed frequently not only in advanced (18/22, 81.8%), but also in early stage cases (7/9, 77.8%), suggesting that it occurs even in the early stages of colorectal carcinoma progression.

Adult↗

Comparison of serum hepatitis C virus RNA concentration by branched DNA probe assay with competitive reverse transcription polymerase chain reaction as a predictor of response to interferon-alpha therapy in chronic hepatitis C patients.

A study was carried out to assess the correlation between the serum concentration of hepatitis C virus RNA (HCV-RNA) in patients with chronic hepatitis, as measured by competitive reverse transcription polymerase chain reaction (cRT-PCR) and branched DNA probe assay (bDNA), and response to interferon-alpha (IFN alpha) therapy. The serum HCV-RNA concentration was evaluated by both cRT-PCR and bDNA in 54 patients who had received a total dose of 480 MU of IFN alpha. HCV subtypes were also identified in all patients. The measurement of serum HCV-RNA concentration by bDNA correlated significantly with that of cRT-PCR. The concentration of HCV-RNA in subtype 1 patients was significantly higher than that in subtype 2 patients when measured by bDNA, but not when measured by cRT-PCR. The correlation of HCV-RNA concentration between bDNA and cRT-PCR was associated with both subtypes 1 and 2. The difference in serum HCV-RNA concentration between complete and incomplete responders was more significant when measured by bDNA probe assay than by cRT-PCR. Moreover, only 1 of 26 patients with a HCV-RNA concentration of more than 1 x 10(6) eq/ml as measured by bDNA probe assay attained a complete response, while 19 of 28 patients with that of less than 1 x 10(6) eq/ml achieved it. Measurement of serum HCV-RNA concentration by bDNA probe assay was a better predictor of clinical response of IFN alpha therapy than measurement by cRT-PCR.

Adult↗

Surgical resection for small hepatocellular carcinoma.

BACKGROUND: Surgical resection for hepatocellular carcinoma (HCC) can be curative in selected patients, particularly in those with a solitary small HCC (s-sHCC; 2 cm or less in diameter). However, even these patients often have a risk of tumor recurrence or death from underlying liver dysfunction. Therefore it is important to determine which clinicopathologic features are related to the long-term prognosis after resection of s-sHCC. METHODS: Fifty patients with s-sHCC underwent partial hepatectomy at our department between 1977 and 1992. Six (12%) died of liver failure in hospital after operation. Eight clinicopathologic features were examined in the remaining 44 patients with regard to their long-term prognosis by use of univariate and multivariate analyses. RESULTS: The 1-, 3-, and 5-year survival rates were 90%, 75%, and 53%, respectively. The corresponding disease-free survival rates were 80%, 53%, and 30%, respectively. None of the following parameters was significantly related to survival rate or disease-free survival rate: presence of vascular invasion or capsular formation, the distance of free surgical margin (1 cm or more or not), serum alpha-fetoprotein level, positive hepatitis B surface antigen, and preoperative transarterial embolization. Complicated liver function was the only significant factor related to survival rate and disease-free survival rate. CONCLUSIONS: A good hepatic reserve is an important factor in treating patients with s-sHCC by surgical resection, even for a long-term prognosis. Liver transplantation should be considered for patients with severe cirrhosis and s-sHCC, even though a curative resection might be possible.

Adult↗

Histological findings of human leprosy periapical granulomas.

Histological analysis of human leprosy periapical granulomas was conducted to study the histological responses to Mycobacterium leprae. Many Langhans-type giant cells and epithelioid cell tubercles were observed, although M. leprae were not detected in leprosy periapical granulomas. Although numerous T- and B-cells were infiltrated in leprosy periapical granuloma, the T-/B-cell ratio of leprosy is not changed to that of periapical granulomas isolated from normal patients. These findings suggested that human leprosy periapical granulomas develop as a result of immunological responses to M. leprae.

B-Lymphocytes↗

E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma.

In human hepatocellular carcinoma (HCC), the liver is the major target organ of metastasis, which is known as intrahepatic metastasis. To analyze the mechanism of this metastasis, we established two sublines from the human HCC cell line Li7. Subline Li7HM produced multiple liver metastasis, whereas subline Li7NM never did so after intrasplenic injection into nude mice. Two-dimensional gel electrophoresis and immunoblot analysis showed that only Li7NM expressed vimentin and lacked E-cadherin expression, indicating that this clone had undergone epithelial-mesenchymal transition. We then transfected mouse E-cadherin complementary DNA into Li7NM cells and found that the transfectant cells (EM16.21B.3) formed liver metastasis (8/16 mice) after intrasplenic injection and liver tumors (11/13 mice) after intrahepatic injection, whereas the control cell line formed no tumors. These results suggest that E-cadherin plays an important role in the process of intrahepatic metastasis of HCC.

Animals↗

Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus.

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.

Aged↗

Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in transcatheter arterial embolization for urgent control of life-threatening massive bleeding from gastric or duodenal ulcer.

We estimated the usefulness of a mixture of N-butyl-2-cyanoacrylate (NBCA) with lipiodol for transcatheter arterial embolization (TAE) used to control massive bleeding from gastric or duodenal ulcer. Thirty patients who had gastric or duodenal ulcers and massive bleeding that was uncontrollable by endoscopic procedures were included in this study. All patients were subjected to TAE (without NBCA in 23 and with NBCA in seven patients). Coils and/or gelfoam were also used. The achievement of haemostasis, occurrence of rebleeding and the time taken for TAE were compared between patients who received TAE without and with NBCA. Eighteen of 23 patients (78.3%) who received TAE without NBCA and six of seven patients (85.7%) who underwent TAE with NBCA achieved complete haemostasis without rebleeding. The time for TAE was significantly shorter in patients who received NBCA compared with those who did not (P = 0.0095). TAE using NBCA or a combination of NBCA and coils achieved a rapid, complete embolization regardless of vascular distribution or arterial diameter. Thus NBCA is considered to be useful as a secondary embolization material in TAE that is urgently conducted to control massive bleeding from gastric or duodenal ulcers.

Adult↗

Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy.

The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metabolism. The finger flexor muscles of five healthy men (aged 25-31 yr) were monitored by 31P-magnetic resonance spectroscopy for changes in phosphocreatine (PCr), Pi, and pH. Tests were conducted during 15 min of cuff ischemia and during 5 min of submaximal isotonic grip exercise at 10, 20, 30, and 40% of maximal voluntary contraction, one contraction every 4 s. The VO2mus changes were also monitored by near-infrared spectroscopy with continuous wave. The VO2mus during exercise was expressed relative to the resting value. The resting metabolic rate, calculated from the PCr breakdown rate after complete O2 depletion, was 0.0010 (SD) mM ATP/s. During submaximal exercise (pH > 6.9), the VO2mus increased with a rise in intensity (0.036 +/- 0.011, 0.054 +/- 0.016, 0.062 +/- 0.012, and 0.067 +/- 0.020 mM ATP/s during 10, 20, 30, and 40% maximal voluntary contraction, respectively) and showed significant correlation with changes in both calculated ADP and PCr values (r2 = 0.98 and r2 = 0.99, respectively). In conclusion, because of the significant correlation with regulatory metabolites (ADP and PCr) of oxidative phosphorylation, O2 decline rate in immediate postexercise ischemia determined by near-infrared spectroscopy with continuous wave can be utilized for the quantitative evaluation of localized muscle oxidative metabolism.

Adult↗

[The clinical evaluation of hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer employing an implanted port system].

Between 1986 and 1994, 66 patients with unresectable liver metastases from colorectal cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable port system. In this study, 44 patients who received intermittent hepatic arterial infusion of high dose 5-FU (1000mg/m2) were analysed according to a response rate, survival rates, developments of extrahepatic lesions, periods of hepatic arterial infusion, and the rates at home. Two cases (4.5%) achieved a complete response (CR) and 27 cases (61.4%) a partial response (PR). The overall one-year and two-year survival rates were 56.7% and 37.8% respectively. The 50% survival time for all patients was 17.2 months. During the course of observation, extrahepatic lesions developed in 16 of the 39 patients (41.0%) and many responders died due to deterioration of extrahepatic lesions. The over all rates at home were more than 85%. Hepatic arterial infusion of the 5-FU at 1000mg/m2 every week showed a high response rate in colorectal cancer patients with hepatic metastases, and the responders showed a low rate of death due to the hepatic metastases. However, in many patients the prognosis-determining-factor was extrahepatic lesions. Thus, countermeasures were necessary for extrahepatic lesions.

Aged↗

Effect of daily administration period of natural alpha-interferon in patients with chronic hepatitis C.

OBJECTIVE: A randomized, controlled trial was performed to study the effect of the period of daily administration of interferon therapy in patients with chronic hepatitis C. PATIENTS AND METHODS: Sixty-three patients were administered a total dose of 480 MU of natural alpha-interferon, 6 MU each day. In 32 cases, interferon was given daily for 2 wk, followed by intermittent administration (three times a week) for 22 wk. The other 31 patients received daily administration for 8 wk, followed by intermittent administration (twice a week) for 12 wk. The responses were based on the normalization of ALT and the clearance of hepatitis C virus. RESULTS: Although ALT normalized in 37 patients during the administration of interferon, it relapsed after the end of interferon therapy in 20 patients. The other 17 patients achieved sustained normalization of ALT and clearance of hepatitis C virus RNA. Responses did not differ according to the administration period of interferon. CONCLUSIONS: Prolonged daily administration did not improve the responses to interferon therapy when the total dose was the same.

Alanine Transaminase↗