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Biomedical subjects

G Toda

Publications and source records attributed to G Toda.

At least 37 records · Page 2Linked to original sources

The right ventricular outflow tract as an unusual location for an implantable defibrillator electrode in a patient with arrhythmogenic right ventricular dysplasia.

A 41-year-old woman with arrhythmogenic right ventricular dysplasia (ARVD) underwent the implantation of an implantable cardioverter-defibrillator (ICD), in which the defibrillator electrode was unusually located in the right ventricular (RV) outflow tract. Although fractionated electrograms were demonstrated in the RV apex, which is the usual site for ICD electrodes, normal electrograms were recorded in the RV outflow tract during an electrophysiologic study. An electrode with a screw-in tip was used to fix the implant in the RV outflow tract and obtain successful defibrillation. If normal electrograms are recorded in the RV outflow tract, the site may prove to be an alternative location for an ICD electrode even for ARVD patients.

Adult↗

[Treatment of chronic hepatitis C patients complicated with the other disease].

Because of relatively low efficacy, considerable side effect and high cost, HCV infected patients complicated with the other disease(patients with hematologic dysorders, chronic renal failure on hemodialysis, HIV co-infection and collagen disease) have been excluded from large trials evaluating the efficacy of IFN or in combination with ribabirin. So, little is known about treatment of these patients. We analyzed the medical literature focusing on treatment of HCV infection in these patients, to suggest conclusion about indication based on tolerance and efficacy. In case the other disease is well controlled and long term sevival is expected, treatment should be required based on the evaluation of liver function test including liver pathology for preventing liver disease from developing terminal stage. Further studies are needed to better define HCV therapies in these patients.

Collagen Diseases↗

[Gamma-glutamyltranspeptidase (gamma-GT)].

gamma-GT is a membrane-bound enzyme which plays a role in the metabolism of glutathione and facilitates amino-acid transport. gamma-GT is located in several tissues such as the kidney, pancreas and liver. Serum gamma-GT activity is induced by hepatobiliary diseases, especially alcoholic liver diseases and cholestasis, not by renal diseases. Isoenzymes specific for hepatocellular carcinoma are demonstrated by electrophoresis. A new method of measuring serum gamma-GT specific for hepatocellular carcinoma was recently reported.

Animals↗

Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C. A long term follow-up study after histologic diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs more frequently in patients with hepatitis C virus (HCV)-related chronic liver disease than those with hepatitis B virus-related disease. It is important to assess the factors affecting the development of HCC. METHODS: A long term follow-up study involving patients with chronic HCV was performed retrospectively. A total of 153 patients diagnosed between June 1981 and November 1990 with chronic HCV with or without cirrhosis by liver biopsy were enrolled in a long term follow-up study (average, 99.4 months) and the cumulative incidence rate of HCC and factors affecting the appearance of HCC were examined. RESULTS: The 5-year cumulative incidence rate was 9%, the 10-year cumulative incidence rate was 23%, and the 15-year cumulative incidence rate was 42%. The annual rate of incidence increased as the follow-up period progressed. The authors selected ten variables and investigated their effect on the incidence rate of HCC, including age, gender, habitual heavy drinking, positivity of antibody against hepatitis B virus surface antigen, treatment with interferon (IFN) during the follow-up period, maximum and minimum serum alanine aminotransferase levels during the follow-up period, histologic staging, grading, and irregular regeneration of hepatocytes. Of the 10 variables, age (> 50 years), habitual heavy drinking, and histologic staging were determined to be independent risk factors according to multivariate Cox proportional hazards regression analysis. IFN therapy by itself was not found to be an independent factor affecting the appearance of HCC. CONCLUSIONS: In patients with chronic HCV, the annual incidence rate of HCC appeared to increase as the follow-up period progressed. According to the results of the current study, the factors that independently affected the development of HCC were age, habitual heavy drinking, and histologic staging.

Adult↗

RAR and RXR expression by Kupffer cells.

Retinoids are known to modulate macrophage differentiation, proliferation, and function including cytokine gene expression. However, signaling of retinoic acid (RA), a biologically active metabolite of vitamin A, in Kupffer cells has not been characterized. This study reports mRNA expression by rat Kupffer cells of RA receptor (RAR) and retinoid X receptor (RXR) subtypes and their binding activities to the RA responsive element (RARE) or retinoid X responsive element (RXRE). Total RNA and nuclear proteins were extracted from Kupffer cells immediately following isolation from livers of normal male Wistar rats. Competitive PCR demonstrated relative mRNA expression of RAR and RXR subtypes in the order of beta>alpha>gamma for and alpha>beta>gamma, respectively. It also demonstrated that the RXR alpha and beta mRNA levels were 5- to 10-fold higher in Kupffer cells than in hepatic stellate cells while RAR mRNA expression was shown to be similar for all the subtypes in both cell types. Gel mobility shift assays of nuclear extracts with labeled RARE and RXRE probes showed distinct binding activities for both responsive elements, which were effectively displaced with cold probes in excess but not with an unrelated oligonucleotide. A supershift assay with an antibody against RARalpha or RXRalpha has confirmed the contribution of both receptors to RARE binding and that of the RXRalpha to RXRE binding activity. These results represent the first demonstration of RA signaling at the nuclear level in Kupffer cells.

Animals↗

Case selection for interferon treatment of hepatitis C.

To establish a case selection algorithm for the treatment of hepatitis C, predictive factors were studied and reported articles were reviewed and analysed. Because of the relatively poor efficacy of interferon (IFN) monotherapy, which is ineffective in 60-70% of patients, case selection at present is determined by the likelihood of attaining a sustained response (SR; defined by normalizing serum ALT and eliminating serum HCV RNA after treatment) to therapy. According to the present study, viral load and genotype, and IL-10 and IL-1ra serum levels, are the most predictive of achieving SR after IFN monotherapy given in a comparatively high dose regimen for 6 months. In addition, reported studies with logistic analyses were carefully reviewed and analysed for the most effective predictive factors of case selection. The results again indicated that viral load and HCV-genotype (serotype). were closely related to SR. Age, gender, and histological changes at treatment were also considered for case selection. These results, however, relate solely to IFN-monotherapy. Future development of more effective strategies for treating hepatitis C could alter the exclusion criteria for IFN treatment and will negate the need for the case selection algorithm discussed here.

Algorithms↗

Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation.

A CD4(+) T cell subpopulation defined by the expression levels of a particular cell surface molecule (e.g. CD5, CD45RB, CD25, CD62L or CD38) bears an autoimmune-preventive activity in various animal models. Here we show that the expression of CD25 is highly specific, when compared with other molecules, in delineating the autoimmune-preventive immunoregulatory CD4(+) T cell population. Furthermore, although CD25 is an activation marker for T cells, the following findings indicate that immunoregulatory CD25(+)CD4(+) T cells are functionally distinct from activated or anergy-induced T cells derived from CD25(-)CD4(+) T cells. First, the former are autoimmune-preventive in vivo, naturally unresponsive (anergic) to TCR stimulation in vitro and, upon TCR stimulation, able to suppress the activation/proliferation of other T cells, whereas the latter scarcely exhibit the in vivo autoimmune-preventive activity or the in vitro suppressive activity. Second, such activated or anergy-induced CD25(-) spleen cells produce various autoimmune diseases when transferred to syngeneic athymic nude mice, whereas similarly treated normal spleen cells, which include CD25(+)CD4(+) T cells, do not. Third, upon polyclonal T cell stimulation, CD25(+)CD4(+) T cells express CD25 at higher levels and more persistently than CD25(-)CD4(+) T cell-derived activated T cells; moreover, when the stimulation is ceased, the former revert to the original levels of CD25 expression, whereas the latter lose the expression. These results collectively indicate that naturally anergic and suppressive CD25(+)CD4(+) T cells present in normal naive mice are functionally and phenotypically stable, distinct from other T cells, and play a key role in maintaining immunologic self-tolerance.

Animals↗

Left ventricular aneurysm without coronary artery disease, incidence and clinical features: clinical analysis of 11 cases.

OBJECTIVE: To examine the incidence, underlying disease and clinical features of left ventricular aneurysm (LVA) not related to coronary artery occlusion. METHODS: Retrospective review of consecutive patients who underwent both left ventriculography and coronary angiography. PATIENTS: LVA was confirmed in 11 of 2,348 consecutive patients (0.47%). RESULTS: The location of LVA was mainly in the apical region (81.8%). In five of the 11 patients (45.5%), the underlying heart disease was hypertrophic cardiomyopathy (HCM), including 4 patients of dilated phase and one patient of midventricular type. The serial ECG changes from left ventricular hypertrophy to abnormal Q wave and endomyocardial biopsy were useful for the differential diagnosis of these cases against myocardial infarction. The underlying disease of the remaining patients was: myocarditis (2 patients), arrhythmogenic right ventricular dysplasia (1 patient), Chagas' disease (1 patient), glycogen storage disease (1 patient), and sarcoidosis (1 patient). Ventricular tachycardia appeared in 9 of 11 cases (81.8%) including 2 patients with sustained ventricular tachycardia. CONCLUSION: LVA formation without coronary artery disease was a rare phenomenon. The underlying disease was varied but the incidence of hypertrophic cardiomyopathy in the dilated phase was comparatively high. Ventricular tachycardia was a significant complication in these patients.

Adult↗