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Biomedical subjects

G Yamada

Publications and source records attributed to G Yamada.

At least 109 records · Page 6Linked to original sources

Four cases with intrafamilial clustering of hepatitis C virus infection.

Four hepatitis C patients with intrafamilial clustering of hepatitis C virus (HCV) infection are reported. Antibodies to C100-3 antigen, capsid protein of HCV and GOR epitope were tested to detect histories of HCV infection. Transmission of HCV from mother to children, from father to children, and from wife to husband was implicated. Of all family members studied, three were positive for all antibodies, one for only antibody to capsid protein, two for antibodies to capsid protein and GOR epitope but negative for antibody to C100-3 antigen and one vice versa.

Adult↗

[A case of pulmonary eosinophilic granuloma with involvement of the ocular fundus].

A 37-year-old man was admitted to our hospital because of abnormal shadows on chest X-ray film at routine medical examination. The chest X-ray showed diffuse granular shadows in the bilateral upper and middle lung fields. Chest CT showed multiple cystic lesions and nodular lesions. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed. Electron microscopic examination of BAL fluid revealed Langerhans' cells, and lung tissue specimen obtained by TBLB showed granuloma with infiltration of histiocytes and eosinophils. During the clinical course, the patient complained of cough and decrease of right visual acuity in association with an increase of abnormal shadows on chest X-ray. The lung disease gradually resolved after the cessation of smoking in spite of no therapy. In the right eye, an exudative lesion with retinal elevation was noted in the ocular fundus. Corticosteroid administration was effective for the treatment of this lesion. There was no pathological evidence of the right ocular lesion. However, the correlation of its clinical course with the lung disease suggests a relationship between the ocular lesion and pulmonary eosinophilic granuloma.

Adult↗

Impact of interleukin-2-receptor-targeted cytotoxins on a unique model of murine interleukin-2-receptor-expressing malignancy.

DAB486IL-2 is a genetically engineered fusion protein consisting of a portion of diphtheria toxin fused to human IL-2. It is specifically cytotoxic for tumor cells which bear high-affinity IL-2 receptors (IL-2R). DAB389IL-2 is a similarly constructed hybrid protein which is smaller than DAB486IL-2 and is slightly more potent in vitro. We have developed a murine model of IL-2R-expressing malignancy to study the in vivo efficacy of these genetically engineered cytotoxins. Following intravenous administration of CP3 cells, C57BL/6 mice develop tumors which are lymphatic in distribution. When mice are injected i.v. with 10(6) CP3 cells, 90% of the animals show signs of observable tumor by day 10 to 20; death occurs in 50% of untreated animals by day 30. Intravenous treatment of mice with DAB486IL-2 (10 micrograms daily for 10 days), beginning 24 hr after administration of CP3 cells, increases mean survival time by approximately 50%. In comparative studies, DAB389IL-2 is more potent in vivo than DAB486IL-2, with approximately 90% of treated animals with no evidence of tumor at 60 days. The mechanism of action of tumor inhibition by DAB486IL-2 is specific, since treatment of animals which have IL-2R-negative EL4 tumors has not resulted in increased survival time. In addition, treatment of such tumors with DAglu53B486IL-2, a fusion protein which can bind to the IL-2R but is incapable of inhibiting protein synthesis, is ineffective.

Animals↗

Specific depletion of the B-cell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice.

Interferons (IFNs) are well known both as antiviral proteins and as potent regulators of cell growth and differentiation. In fact, IFNs inhibit growth of various normal and transformed cell types. Previously, a nuclear factor, IRF-1 (interferon regulatory factor 1), which binds to type I IFN and some IFN-inducible gene promoters, was identified and cloned. Since the IRF-1 gene is both virus and IFN inducible, an intriguing issue is raised as to whether the IRF-1 gene is functioning in IFN-mediated regulation of cell growth and differentiation. In this study, we generated transgenic mice carrying the human IRF-1 gene linked to the human immunoglobulin heavy-chain enhancer. In the transgenic mice, all the lymphoid tissues examined showed a dramatic reduction in the number of B lymphocytes (B cells). Preparation and analysis of bone marrow cells from the chimeric mice indicated that the bone marrow is the effective site for specific depletion of the B-cell population. In fact, transgenic bone marrow cells cocultured with a bone marrow-derived stromal cell line revealed an altered B-cell maturation pattern.

Animals↗

The integrity of the conserved 'WS motif' common to IL-2 and other cytokine receptors is essential for ligand binding and signal transduction.

Recent studies have identified a new family of cytokine receptors, which is primarily characterized by the conservation of periodically interspersed four cysteine residues and the W-S-X-W-S sequence ('WS motif') within the extracellular domain. However, the role of such conserved structures still remains elusive, in particular that of the WS motif. Interleukin-2 (IL-2) is known to play a critical role in the clonal expansion of antigen-stimulated T lymphocytes, and the IL-2 signal is delivered by one of the receptor components, the IL-2 receptor beta (IL-2R beta) chain. The IL-2R beta chain, unlike the IL-2R alpha chain, belongs to this receptor family. In the present study, we analyzed the function of the WS motif of IL-2R beta (Trp194-Ser195-Pro196-Trp197-Ser198) with the use of site-directed mutagenesis. Our results indicate the critical role of the two Trp residues in the proper folding of the IL-2R beta extracellular domain and point to the general functional importance of the WS motif in the new cytokine receptor family.

Amino Acid Sequence↗

Immunohistochemical characterization of the lymphocyte and the immunoglobulin-containing cell in the epithelium and the lamina propria of normal human intestines.

In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig)-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum) of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu2a), helper/inducer T (Leu3a), suppressor T (Leu15) and natural killer/K (Leu7) cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs) were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.

Adult↗

Intrafamilial transmission of hepatitis C.

To identify intrafamilial transmission of hepatitis C virus, we tested for antibodies to hepatitis C virus (anti-HCV) in serum samples of 160 family members (12 parents, 17 siblings, 73 children, and 58 spouses) of 76 index patients with chronic hepatitis C. Anti-HCV was detected in 14 of 160 family members (8.75%). This positive rate was significantly higher than the anti-HCV-positive rate in age-matched volunteer blood donors in our district (8.75% vs. 1.42%; P less than 0.01). Among 14 members, 5 had normal liver function tests and 9 had hepatitis C. In 4 of 73 children, anti-HCV was detected (5.48% vs. 0.55%; P less than 0.01). In the two children, transmission from mother to child in their childhood was suspected, and in the other children, transmission was from father to child. Furthermore, 7 of 58 spouses (12.1%) had anti-HCV (12.1% vs. 2.13%; P less than 0.01). These results suggest that intrafamilial transmission, especially horizontal infection may play an important role in the spread of hepatitis C.

Adult↗

Immunoelectron microscopic observation of intrahepatic HBeAg in patients with chronic hepatitis B.

Immune light and electron microscopic studies using monoclonal antibodies have been applied to localize HBeAg in liver biopsy specimens of 19 patients with chronic hepatitis B. Under the light microscope, HBeAg was demonstrated in nuclei, cytoplasm and on the cell surface of hepatocytes. The number of HBeAg-positive hepatocytes correlated well with the serum levels of HBeAg (enzyme immunoassay) and DNA-polymerase. Of 11 patients in whom high numbers of HBeAg-positive hepatocytes were found at the light microscopic level, HBeAg was also studied in hepatocytes at the electron microscopic level. The HBeAg in nuclei was either found as aggregates or dispersed diffusely. In the aggregates of HBeAg, the 27-nm core particles were frequently found. In addition, the antigen was found in the cytosol of some hepatocytes as amorphous mass and in some hepatocytes in the cisternae of perinuclear space, endoplasmic reticulum and Golgi saccules. Occasionally the antigen was found on the membranes of the cell organelles and on the plasma membranes that faced the intercellular and the Disse spaces. These findings suggest that cytoplasmic HBeAg in hepatocytes may be ultrastructurally classified into two different patterns by its distribution, mainly in endoplasmic reticulum or in cytosol. The ratio varied between hepatocytes with these two types of patterns. The titer of serum HBeAg tended to be higher when the corresponding liver biopsy specimens contained more hepatocytes with HBeAg in endoplasmic reticulum than those with HBeAg in the cytosol.

Adult↗

Immunohistochemical study of pre-S(2) antigen in liver and serum of patients with chronic hepatitis B.

To evaluate the significance of pre-S(2) in the liver, the authors studied the relationship between serum and intrahepatic pre-S(2) in 27 patients with chronic hepatitis B. Intrahepatic expression of pre-S(2) was observed under light and electron microscopy and compared with that of HBsAg and HBcAg. All patients were positive for hepatic pre-S(2), and 25 for serum pre-S(2). Intrahepatic pre-S(2) expression was membranous or both membranous and cytoplasmic in 18 cases and was cytoplasmic in 9. The serum levels of pre-S(2) were significantly higher in cases whose intrahepatic pre-S(2) was membranous than in the cytoplasmic cases. These findings indicate that membranous expression of pre-S(2) reflects its secretion into the circulation. Intrahepatic pre-S(2) expression was found almost completely to resemble that of HBsAg on both light and electron microscopy. Membranous pre-S(2) was seen in the liver of 16 of 25 cases who were positive for intrahepatic HBcAg. In detailed studies of membranous pre-S(2) and HBcAg, both membranous pre-S(2) and HBcAg appeared in the liver of all 7 cases before or at the peak of acute exacerbation, but after it, membranous pre-S(2) was not found in 4 of 8 cases. These results suggest that disappearance of membranous pre-S(2) and HBsAg may be related to hepatic cell necrosis in some cases with acute exacerbation.

Antibodies, Monoclonal↗

Computer simulation of supraventricular tachycardia with the Wolff-Parkinson-White syndrome using three-dimensional heart models.

Supraventricular tachycardias with the Wolff-Parkinson-White (WPW) syndrome have been successfully simulated using a newly developed simulation system. The heart model, including atria and ventricles, was constructed of about 50,000 discrete elements (model cells) in three dimensions with 1.5-mm spatial resolution. The model cells covered all of the types of cells in the actual heart, including the normal myocardium, special conduction system and abnormal cells, such as the bundle of Kent (accessory pathway) and ectopic pacemaker (premature beat). Different model cells were specified by their electrophysiologic parameters, such as action potential, refractory period, and conduction velocity. The WPW syndrome was simulated by setting an accessory pathway between the right atrium and ventricle. Based on this model a premature atrial beat was introduced, which initialized the tachycardia. By adjusting the parameters, three types of reciprocal supraventricular tachycardia were simulated with the reentry circuits (1) formed anterogradely by the A-V node and retrogradely by the accessory pathway, (2) formed anterogradely by the accessory pathway and retrogradely by the A-V node, and (3) confined within the A-V node. Time relations for initializing and maintaining the tachycardias were evaluated. The simulated ECGs were in good agreement with the clinical findings.

Computer Simulation↗

The hepatocellular expression of a carbohydrate antigen 'sialyl Lewis X' in chronic hepatitis. A novel histological marker for active hepatic necroinflammation.

The hepatocellular expression of the carbohydrate antigen sialyl monomeric Lewis X (SMLex) and sialyl oligomeric Lewis X(SOLex) in chronic hepatitis was examined using specific monoclonal antibodies. Both of these sialyl Lewis X (SLex) antigens were membranously expressed in chronic hepatitis in spite of their absence in normal liver. Although SMLex was detected in mild hepatic inflammation, the expression of SOLex was associated only with moderate to severe necroinflammation. Hepatocellular expression of these antigens increased significantly as histological diagnosis advanced. Chronological observation also showed the change of SLex expression according to the histological change. The present observations suggest that hepatocellular SLex is a novel histological marker with a close correlation to the severity of necroinflammation in chronic hepatitis.

Biomarkers↗

Murine interleukin 2 receptor beta chain: dysregulated gene expression in lymphoma line EL-4 caused by a promoter insertion.

The functional, high-affinity interleukin 2 receptor (IL-2R) consists of at least two receptor components, IL-2R alpha (p55) and IL-2R beta (p70-75). The cDNA encoding the murine IL-2R beta has been isolated by using the previously cloned cDNA for human IL-2R beta as a probe. Analysis of the cDNA revealed that the murine IL-2R beta shows a marked homology with the human IL-2R beta and that it is also structurally related to other cytokine receptors such as erythropoietin receptor. The cDNA-directed murine IL-2R beta formed high-affinity IL-2R in conjunction with the endogenous IL-2R alpha in a murine pro-B-cell line and could transduce IL-2-induced growth signal. In mouse lymphoma line EL-4, the IL-2R beta gene was found to be rearranged by the insertion of the long terminal repeat sequence of an intracisternal A particle, giving rise to constitutive expression of the IL-2R beta mRNA.

Amino Acid Sequence↗

Sporadic acute hepatitis in hospital employees: mainly non-A, non-B type.

Eighty-two patients with sporadic acute viral hepatitis were detected at Okayama University Hospital between January 1982 and March 1989. Thirty of them had non-A, non-B hepatitis (NANBH); 20 had hepatitis A (HA); and 32 had hepatitis B (HB). Ten (33%) of NANBH, five (25%) of HA, and nine (28%) cases of HB were hospital employees. Two (20%) of 10 hospital employees with NANBH developed chronic hepatitis. Antibody to hepatitis C virus (anti-HCV, ELISA) was tested in 10 patients with NANBH (five hospital and five non-hospital employees). Forty percent of both hospital and non-hospital employees had anti-HCV. The percentage of hospital employees among patients with NANBH was similar to that of those among patients with HB. Therefore, it appears that NANBH as a disease entity may be a source of a significant occupational hazard in personnel who either examine or care for patients with hepatitis.

Acute Disease↗

[The mean of Downs and northwestern analysis in adults].

An angle analysis and linear analysis are popularly used in clinical orthodontics. Downs analysis and Northwestern analysis are two methods of angle analysis, and the mean values reported by Iizuka in 1963 are still used. However in Japan each generation's constitution (height, weight) tends to increase year by year. For example, the mean height and weight of adult males (23 years old) have increased by 5.0cm and 7.6kg as compared with nearly 20 years ago. Therefore the mean of 20 years ago may not be appropriate. Analytical values at normal occlusion Japanese adults by Kayukawa, Iizuka, Ishikawa, Yamauchi, Miura, Iwazawa and, most recently by Asai in 1973. We obtained these values and determined the validity of currently used values.

Adult↗