PubMed Health⌕ Search

Biomedical subjects

G Yamada

Publications and source records attributed to G Yamada.

At least 127 records · Page 7Linked to original sources

Clinical application of electrocardiographic computer model.

A three-dimensional computer model was developed to stimulate the ventricular depolarization and repolarization in a clinical setting. The ventricle is composed of approximately 50,000 units arranged in a cubic close-packed structure and the specialized conduction system is distributed so as to obtain the excitation sequence resembling normal ventricular depolarization. The normal distribution of action potential waveforms with the longest duration on the endocardium and the shortest on the epicardium is used in the model. The heart model is mounted in a homogeneous torso model, and the body surface potential distribution generated by the electric dipoles is calculated using the boundary element method. The QRST waveforms corresponding to the normal and some abnormal heart conditions, such as bundle branch block, myocardial infarction, apical hypertrophic cardiomyopathy, and Wolff-Parkinson-White syndrome, is obtained by assuming the abnormal area with altered electrical properties. Thus the three-dimensional computer model may provide further insight into the genesis of the clinical electrocardiogram.

Bundle-Branch Block↗

Effects of booster HB vaccine in preventing hepatitis B virus infection from mother to child.

Hepatitis B immune serum 200 IU was injected intramuscularly to 127 infants born to hepatitis B e antigen positive mothers immediately after birth and at two months of age, and if necessary at four months. HB adjuvant vaccine 20 micrograms was injected subcutaneously at three, four, and six months. If antibodies to hepatitis B surface antigen were 2(2) or less, one to four doses of booster vaccine 20 micrograms were given. The first booster vaccination was given in 8.7% of cases by the age of one year, in 19.3% by 18 months, in 23.9% by 24 months, and in 36.2% by 30 months; thus 2-to-3-year-old infants were more frequently vaccinated than younger ones. This implies that 80%-90% of infants could be protected from vertical transmission of hepatitis B virus (HBV) up to the age of three years, if a booster vaccine was given to those born to HBeAg positive mothers not later than 24 months. Infants obtained enough antibody to prevent HBV infection by receiving one booster vaccination in 34 cases, by two in nine, by three in five, and by four in two.

Carrier State↗

Immunoelectron microscopic observation of alpha-fetoprotein synthesis in human non-malignant liver tissues using immunoperoxidase methods.

Alpha-fetoprotein (AFP) synthesis in non-malignant liver tissue of 34 patients with chronic hepatitis or liver cirrhosis, some of whom also had hepatocellular carcinoma (HCC), was studied by light and ultrastructural immunohistochemistry using peroxidase-labeled anti-human AFP. Simultaneously, the serum level of AFP was measured in these patients by radioimmunoassay. AFP-positive cells were identified in non-malignant liver tissue of 7 patients with elevation of serum AFP. AFP was demonstrated in several hepatocytes which were clustered in hepatic lobules, and also in some bile ductular cells which were distributed in the periphery of portal tracts. In an immunoelectron microscopic study of AFP-positive hepatocytes, dense reaction products of anti-AFP were localized in the membranes and cisternae of rough endoplasmic reticulum (r-ER), perinuclear space (PNS) and Golgi apparatus. The prominent feature of AFP-positive hepatocytes was abundant r-ER encompassing many mitochondria. As to AFP-positive bile ductular cells, they had scanty cytoplasm and few intracytoplasmic organelles and were surrounded by basement membrane. AFP was focally localized in the r-ER of such bile ductular cells. These observations suggest that AFP can be produced by malignant and non-malignant liver cells and that in non-malignant liver tissues, AFP can be produced by two distinct cell types; bile ductular cells and hepatocytes themselves.

Biopsy↗

Intranuclear inclusion bodies in liver of chronic hepatitis B with delta infection.

Seventy-two patients with HBsAg-positive chronic hepatitis were studied for serum antibody to delta antigen (anti-HD) by radioimmunoassay. Delta antigen (HDAg) in liver of the 72 patients was also studied immunohistochemically using peroxidase-labeled anti-HD. In one of the 72 patients, high titers of anti-HD and intrahepatic HDAg were detected. In this patient, HDAg was localized mainly in nuclei and occasionally in the cytoplasm of hepatocytes. By immunoelectron microscopy, HDAg was observed diffusely in some hepatocytic nuclei, but their nucleoli, perichromatin and heterochromatin were devoid of HDAg. Occasionally, inclusion body-like ring-shaped or irregularly shaped aggregates of HDAg were observed in nuclei. At higher magnification, these aggregates consisted of an HDAg-positive amorphous substance and microtubular structures. In their vicinity, scattered HDAg-positive granules were also present. By conventional electron microscopy, similar inclusion bodies composed of a clustered amorphous substance and microtubular structures 10-20 nm in diameter, together with 20-30 nm irregular granules were observed in hepatocyte nuclei, but no core of Dane particles were found. These novel intranuclear structures were not observed in other patients with chronic hepatitis B. It is suggested that they may represent the characteristic ultrastructure associated with delta infection.

Cell Nucleus↗

Regulation of cytokine gene expression: gene activation in type I IFN and IL-2 systems.

Cytokines represent essential soluble mediators in cell-to-cell communication and they are known to play crucial roles in many biological processes, including viral infection, inflammation and immunity. We have been focusing on two cytokine systems, the interferon (IFN) and interleukin 2 (IL-2) systems each of which respectively plays a key role in viral infections and the immune response. In both cases, expression of those cytokines and, in the case of IL-2 system, the receptor is tightly regulated at the transcriptional level. Recent studies in our laboratory as well as others have uncovered the mechanism(s) operating in the regulation of those genes and have provided further insights on how the two cytokine systems operate and what is the biological significance of gene regulation in these systems. Here, we summarize the current understanding of the IFN system and IL-2 system in the context of host defense against viral infections and T cell neoplasms, respectively.

Amino Acid Sequence↗

Retroviral expression of the human IL-2 gene in a murine T cell line results in cell growth autonomy and tumorigenicity.

In mature T lymphocytes (T cells) the regulated expression of the genes for interleukin-2 (IL-2) and its receptor (IL-2R) constitutes an essential part in controlling the cell growth. Evidence has been provided which suggests the involvement of an aberrant function of the IL-2 system in developing T cell neoplasms, particularly the adult T cell leukemia/lymphoma (ATL). As an approach to examine the extent of the IL-2 system contribution to T cell neoplasms, we created the experimental conditions wherein both IL-2 and IL-2R are expressed constitutively in a murine T cell line. We made use of a retroviral vector to infect an IL-2-dependent CTLL-2 line and lead to the expression of human IL-2. Here, we show that the virus-infected cells not only proliferate in vitro in the absence of exogenously supplied IL-2 under certain conditions, but also develop tumors (lymphomas) in nude and syngeneic mice.

Animals↗

Immunohistochemical study of fibronectin, lysozyme, and alpha-fetoprotein (AFP) in human hepatocellular carcinoma.

We have immunohistochemically localized fibronectin, lysozyme and alpha-fetoprotein (AFP) in 21 human hepatocellular carcinoma (HCC) tissues obtained by surgical resection at both light and electron microscopic levels. Three distinct distribution patterns of fibronectin (sinusoidal, periacinar, and pericellular patterns) were observed. The sinusoidal and periacinar patterns were mainly observed in HCC of pseudoglandular or trabecular patterns and of Edmondson's grade I or II, whereas the pericellular pattern was observed in HCC of compact or trabecular patterns and of Edmondson's III grade, suggesting that the pericellular fibronectin was rather associated with undifferentiated HCC. Electron microscopic observation of the pericellular fibronectin showed fibronectin to be present in the dilated intercellular spaces where microvilli were moderately developed. We observed intracytoplasmic staining of fibronectin in 2 of the 21 HCC cases. By immunoelectron microscopy, fibronectin was observed in the endoplasmic reticulum (ER) of some HCC cells. In the 21 HCC cases, lysozyme-positive cancer cells were observed in 10 cases, and AFP in 6 cases. At the ultrastructural level, lysozyme was identified in the ER and the perinuclear spaces of HCC cells, suggesting that lysozyme was synthesized by these cells. Lysozyme-positive cases tended to be more frequently observed in cases with the pericellular pattern of fibronectin rather than those with sinusoidal or periacinar patterns.

Adult↗

Monoclonal antibodies identifying antigens on distinct domains of rat hepatocytes.

To aid in evaluating the functional significance of various domains of the hepatocyte plasma membrane, we have developed monoclonal antibodies that react with three different antigens on the surface of rat hepatocytes. One antigen is present on the sinusoidal-lateral plasma membrane but is absent from the bile canalicular membrane. On the basis of apparent molecular weight and ability to bind a desialylated glycoprotein, this antigen may be the asialoglycoprotein receptor. It was also identified immunocytochemically on the sinusoidal-lateral plasma membrane of human hepatocytes. The second antigen is present only on the bile canalicular membrane, whereas the third is present on the entire cell surface of rat hepatocytes. Our monoclonal antibodies may be useful in investigations of the sorting mechanisms of hepatocyte membrane proteins and the pathogenesis of certain liver diseases.

Animals↗

Immunohistochemical study of HLA class 1 antigens on the hepatocytes of patients with chronic hepatitis B.

In order to evaluate the role of histocompatibility antigen (HLA) class 1 antigens in the pathogenesis of liver cell necrosis, HLA class 1 antigens on hepatocytes were studied in the liver biopsy materials from 20 patients with chronic hepatitis B by the peroxidase-labeled antibody method using a monoclonal antibody to human HLA-A, B, C (Cappel Laboratories). Both increased expression of HLA class 1 antigens on the hepatocytes and decreased distribution of intrahepatic hepatitis B core antigen (HBcAg) were observed in patients with an exacerbation of the inflammatory activity. These findings suggest that expression of HLA class 1 antigens on the hepatocytes may be increased when an exacerbation of inflammatory activity develops, and may be compatible with the concept that expression of these antigens plays and important role for the lysis of hepatitis B virus (HBV)-infected liver cells by cytotoxic T cells. Furthermore, in seven patients, expression of HLA class 1 antigens was studied in the liver before and after treatment with human lymphoblast interferon (IFN)-alpha, recombinant IFN-alpha or IFN-beta. Increased expression of HLA class 1 antigens was observed in patients with decreased intrahepatic HBcAg and DNA-P in sera after IFN treatment. These results also suggest that the increase of HLA class 1 antigens by IFN may be related to the immune mechanism for the effective elimination of HBV.

Adult↗

Effects of adenine arabinoside on cellular immune responses in patients with chronic hepatitis B.

The lymphocyte subsets in the peripheral blood and in liver biopsies from 4 patients with chronic hepatitis B obtained about 2-7 weeks before and after treatment with adenine arabinoside (Ara-A) were studied by a peroxidase-labeled antibody method using monoclonal antibodies against Leu-1, Leu-2a, Leu-3a, Leu-7 and Leu-10 antigens. In the peripheral blood, the percentage of Leu-2a+ (cytotoxic/suppressor) cells was significantly reduced and the ratio of Leu-3a+ (helper/inducer) to Leu-2a+ cells was increased after the treatment with Ara-A. In the liver biopsies, the numbers of Leu-1+ (pan T) and Leu-2a+ cells were significantly decreased after the treatment with Ara-A. As a result, the Leu-3a+/Leu-2a+ ratio was significantly elevated in the liver after the therapy. The majority of lymphocytes distributed at sites of hepatocytic necrosis were positive for Leu-2a. The reduced numbers of Leu-1+ and Leu-2a+ cells after the treatment were mainly due to the decrease of these cells infiltrating to the sites of hepatocytic necrosis. The numbers of other subsets (Leu-3a+, Leu-7+ and Leu-10+) changed without any specific tendency both in the peripheral blood and in the liver biopsies after the treatment. With respect to viral replication, most of the patients showed a decrease of serum DNA polymerase activity or demonstrable intrahepatic HBsAg and HBcAg after the treatment. These data suggest that T cell-mediated cytotoxicity against HBV-infected hepatocytes is diminished after treatment with Ara-A.

DNA-Directed DNA Polymerase↗

Development of a monoclonal antibody identifying an antigen which is segregated to the sinusoidal and lateral plasma membranes of rat hepatocytes.

We developed a monoclonal antibody to the plasma membrane of rat hepatocytes. Immunoelectron microscopic characterization of an antigen identified by our antibody revealed that the antigen was present diffusely on the sinusoidal and lateral plasma membranes of hepatocytes but absent from the bile canalicular membrane. Sinusoidal lining cells (Kupffer cells and endothelial cells) were devoid of the antigen. Within hepatocytes, the antigen was present in the Golgi complexes, segments of endoplasmic reticulum and small vesicle-like structures. The development of the monoclonal antibody to the segregated membrane antigen of the hepatocyte in this study provides a reliable marker of specific membrane domains for use of isolation of plasma membrane surfaces and is a useful tool for investigation of the transferring mechanisms of membrane proteins to their destinations.

Animals↗

Tubular structures in the hepatic nuclei of a patient with delta agent.

Liver biopsy specimens obtained from a 31-year-old female with delta-positive hepatitis were studied by routine electron microscopy. In several nuclei of hepatocytes, there were filamentous or microtubular structures 15 to 20 nm in diameter, in the vicinity of which, round particles, probably cross sections of tubular ones, were seen. In these nuclei, irregular granules approximately 20 to 30 nm in diameter were also found in clusters. However, cores of Dane particles were not found in such hepatocytes. These intranuclear microtubular structures may be associated with delta agent.

Adult↗

Ultrastructural observation of alpha-fetoprotein producing cells in human hepatocellular carcinoma using immunoperoxidase methods--comparison with fetal liver.

The precise sites of alpha-fetoprotein (AFP) synthesis and ultrastructural features and differences of AFP-producing cells were observed in periodate-lysine-paraformaldehyde fixed, frozen liver tissues from four human hepatocellular carcinoma (HCC) patients and three human fetuses using the direct (horseradish peroxidase-labeled Fab' fraction of anti-human AFP) immunoperoxidase method. We demonstrated that AFP was located in the membrane and cisternae of rough endoplasmic reticulum, membrane-bound ribosomes, perinuclear space and Golgi apparatus. The location and intensity of immunoreaction products of AFP in hepatoma cells varied from cell to cell and case to case, while these features tended to be regular in fetal hepatocytes. We did not observe ultrastructural differences between AFP-producing and non-producing cells adjacent to each other. These observations indicate that AFP production does not occur in morphologically distinct cell populations of hepatoma tissue and that hepatoma tissue is functionally much more heterogeneous than fetal liver.

Aged↗