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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 865 records · Page 48Linked to original sources

Cloning of a cDNA associated with acute and chronic hepatitis C infection generated from patients serum RNA.

In order to clone hepatitis C (blood-borne non-A, non-B hepatitis) virus, lambda gt11-cDNA library was constructed from RNA extracted from 100 liters serum collected from 1,047 donors with elevated ALT levels and negative for hepatitis B virus-DNA. The library was immunoscreened on Y1090 cells with pooled serum obtained from patients with acute hepatitis C or chronic hepatitis C. By screening 29 clones specific for Japanese hepatitis C infection were isolated. The specificity of these clones for hepatitis C infection was determined by panels constructed in 3 laboratories. Of these, 12 clones were specific for American hepatitis C infection as well. The nucleotide sequence (201 bp) of one of them was determined to be unique compared to known human viruses including hepatitis A virus, hepatitis B virus and hepatitis D virus. Southern blot analysis showed the absence of the sequence of the human genome in the clone. The predicted amino acid sequence is rich in residues of lysine, arginine, glutamic acid and asparagine, while lacking leucine, cysteine and methionine.

Acute Disease↗

Changes in serum levels of hepatitis B virus markers after interferon treatment.

The effect of interferon (IFN) treatment on serum levels of pre-S antigens [pre-S(1) antigen, pre-S(2) antigen, polymerized human serum albumin receptor (pAR)] which are coded by the pre-S region of hepatitis B virus DNA (HBV-DNA), and HBV-markers was analyzed in 23 patients with chronic hepatitis B. One year after IFN treatment, 4 patients (Group C) became HBeAg negative. Six patients (Group B) transiently became HBeAg-negative, but reverted to HBeAg positive. Thirteen patients (Group A) remained HBeAg positive. All of the patients remained HBsAg-positive. Initiation of IFN treatment was rapidly followed by reduction or loss of DNA-P in the serum whether the patients became HBeAg negative or remained positive, and whether serum transaminase (S-GPT) levels became normal or not after IFN treatment. Group C patients, in whom pre-S antigens decreased rapidly during IFN treatment and disappeared before S-GPT levels normalized, became HBeAg negative one year after IFN treatment. Anti-pAR was detected in three out of these 4 patients. In contrast, Group A and Group B patients, in whom pre-S antigens decreased slowly during IFN treatment and did not disappear in spite of those patients being transiently negative for HBeAg and DNA-P, remained HBeAg positive with elevated S-GPT levels one year after IFN treatment. Anti-pAR was almost undetectable. These results suggest that testing for pre-S antigens is more useful for determining the prognosis of patients with chronic hepatitis B treated with IFN than testing for HBsAg, HBeAg and DNA-P.

Adolescent↗

Immunotherapy using Freund's adjuvant and recombinant interleukin-2 combined with transarterial chemoembolization for hepatocellular carcinoma.

A new immunotherapy for hepatocellular carcinoma (HCC) using Freund's adjuvant and recombinant interleukin-2 (IL-2) combined with conventional transarterial chemoembolization therapy was performed. In 16 patients with HCC and one patient with metastatic liver cancer receiving this therapy, decrease and suppression of reelevation of alpha-fetoprotein after therapy was observed. Disappearance of tumor thrombi of HCC in the main portal vein was observed in a patient, and decrease of carcinoembryonic antigen was also observed in a patient with metastatic liver cancer. The present therapy using Freund's adjuvant and IL-2 is likely to open a new avenue for the treatment of patients with advanced liver cancer.

Aclarubicin↗

SPECT images using 99mTc(V)-DMS in lung metastasis of osteosarcoma.

Color images of single-photon emission computed tomography (SPECT) using technetium-99m(V) dimercaptosuccinic acid (99mTc(V)-DMS) were demonstrated in a patient with lung metastases from osteosarcoma. SPECT image using 99mTc(V)-DMS could be useful for the detection of lung metastasis from osteosarcoma.

Adult↗

An aberrant retinal pathway and visual centers in Xenopus tadpoles share a common cell surface molecule, A5 antigen.

A monoclonal antibody A5 (MAb-A5), which was raised against Xenopus tadpole tectal cells, recognizes a cell surface-related protein molecule (A5 antigen) expressed on the visual centers of Xenopus tadpoles (S. Takagi, T. Tsuji, T. Amagai, T. Takamatsu, and H. Fujisawa, 1987, Dev. Biol. 122, 90-100). The present immunohistochemistry using MAb-A5 indicated that, in addition to the visual centers, A5 antigen was expressed on the general somatic sensory tract in the medulla and spinal cord of Xenopus tadpoles. As the general somatic sensory tract has been shown to be a pathway for ectopically transplanted retinal axons (M. Constantine-Paton and R. R. Capranica, 1976, J. Comp. Neurol. 170, 17-32; M. J. Katz and R. J. Lasek, 1979, J. Comp. Neurol. 183, 817-832), we examined whether retinal axons transplanted close to the spinal cord or medulla preferentially grow into the A5 antigen-positive general somatic sensory tract. We performed eye transplantation at embryonic stages and detected precise locations and trajectories of transplanted retinal axons within the medulla and spinal cord in tadpoles after filling retinal axons with horseradish peroxidase (HRP). HRP histochemistry in combination with MAb-A5 immunohistochemistry indicated that almost all HRP-filled transplanted retinal axons joined the A5 antigen-positive general somatic sensory tract. These findings suggest the involvement of A5 antigen in specific cell-cell recognition between retinal axons and their targets.

Animals↗

Blood group antigens in the intrahepatic biliary tree. II. Type 1 chain N-acetyllactosamine-related carbohydrate antigens in the proliferated bile ductules.

The expression of the carbohydrate antigens related to type 1 chain N-acetyllactosamine (1NAcLc) in the proliferated bile ductules was immunohistochemically examined in liver tissues of 10 cases of chronic hepatitis (CH), 9 of liver cirrhosis (LC) and 8 of alcoholic hepatitis. The ductular expression of the examined blood group antigens was essentially the same among these pathological conditions. The backbone structure, i.e., 1NAcLc (Gal beta 1----3GlcNAc beta 1----3Gal beta 1----3R), was not detected in the proliferated ductules as in the normal bile ductules. Its fucosylated structures (Le(a), Le(b) and type 1 chain H) were more strongly expressed in the proliferated ductules than in the normal ductules. Sialyl-Le(a) which was not found in the normal ductules was detected weakly but definitely in the proliferated ductules. Besides proliferated ductules, single or small numbers of epithelial cells expressing the 1NAcLc-related antigens were found intralobularly. This suggests possible migration of biliary epithelial cells into the hepatic lobules. In conclusion, within the proliferated bile ductules (a) synthesis of the 1NAcLc-related antigens is increased compared to the normal ductules, (b) the backbone structure is completely sialylated or fucosylated as in the normal ductules and (c) alpha 1----4fucosylation of sialyl-1NAcLc, i.e., sialyl-Lea, formation occurs despite its absence in the normal ductules.

Adolescent↗

Immunohistochemical determination of growth fraction in human tumors.

The growth fraction in 93 cases of human tumors was estimated by an immunohistochemical staining using Ki-67. The tumors consisted of the following: 14 oral cancers, 14 breast cancers, 9 gastric cancers, 9 uterine cancers, 8 ovarian cancers, 6 colo-rectal cancers, 6 thyroid cancers, 5 esophagus cancers and 22 miscellaneous tumors. Regional labeled cells were predominantly found in the periphery of the tumor nests in squamous cell carcinomas. However, in adenocarcinomas the labeled cells were randomly distributed in tumor cell nests. The Ki-67 labeling index varied greatly from case to case (almost 0 to 50.9% with an average of 17.3%), even within the same organ group. The growth fraction was independent of the histological pattern, although thyroid cancers showed a lower labeling index than other malignant tumors. The labeling indices in benign tumors were lower than those in malignant tumors. The usefulness of this method for the estimation of biological behavior of human tumors is suggested.

Adenocarcinoma↗

An expression of squamous cell carcinoma-related antigen in oral cancers.

The relationship between serum level and stainability of squamous cell carcinoma-related antigen (SCC-Ag) in carcinoma of the oral cavity was examined. The amount of serum SCC-Ag was measured in 60 of 97 patients by a radioimmunoassay system. 63.3% showed elevated serum SCC-Ag levels above 2.0 ng/ml. The specimens taken from 97 patients with oral squamous cell carcinoma (SCC) were stained with a monoclonal antibody against the SCC-Ag by using an immunoperoxidase method. Tumor cells with keratinization in well-differentiated SCC stained well with the antibody, whereas cells without keratinization in poorly-differentiated SCC stained weakly, or not at all. Serum levels of the antigen were significantly higher in cases of invasive cancers, but serum levels of antigen correlated with neither the degree of morphological differentiation of the tumor, nor with the intracellular content of the antigen. These observations suggest that the parenchymalstromal relationship is one of the decisive factors in determining the serum SCC-Ag level.

Adult↗

The nucleolar organizer regions associated protein (Ag-NORs) in salivary gland tumors.

A silver colloid technique used to identify nucleolar organizer regions associated protein (Ag-NORs) has been applied to 20 salivary gland tumors. The method was readily applicable to the preparations of paraffin-embedded sections and the Ag-NORs were enumerated with ease. A significant difference was found between the numbers of Ag-NORs in the nuclei of malignant salivary gland tumors, such as adenoid cystic carcinoma, mucoepidermoid tumor and adenocarcinoma (with a mean of from 2.05 to 2.78 per nucleus) and those of benign salivary gland, such as pleomorphic adenoma, adenolymphoma (Wartin tumor) and clear cell adenoma (with a mean of from 1.47 to 1.72 per nucleus). It is proposed that the Ag-NORs technique, which is rapid, simple, and inexpensive, may be useful in the differential diagnosis of malignant and benign salivary gland tumors.

Antigens↗

Forskolin potentiates myocardial reactive hyperaemia in the open chest dog: the contribution of adenylate cyclase.

Forskolin, a diterpene, directly stimulates adenylate cyclase and also potentiates receptor mediated stimulation of this enzyme by many stimulatory agonists. We exploited the potentiating effect of forskolin to test the hypothesis that activation of adenylate cyclase contributes to myocardial reactive hyperaemia, especially by release of adenosine at the time of brief coronary occlusions. In 10 open chest dogs, intracoronary forskolin infusions which produced plasma concentrations between 0.22 and 0.34 mumol.litre-1 slightly increased coronary blood flow and had no effect on haemodynamics or myocardial metabolism. Under these conditions, though peak reactive hyperaemic flow rates were not affected, forskolin infusions reversibly potentiated repayments of flow debt by 28, 25 and 27% following coronary occlusions of 15 s, 20 s and 30 s, respectively (p less than 0.05). In another seven dogs, after observations of the effects of forskolin (0.16-0.26 mumol), 10 mumol of 8-phenyltheophylline, a potent adenosine antagonist, was infused simultaneously with forskolin into the coronary arteries. Forskolin increased debt repayments by about 23-27% following 15 s, 20 s and 30 s occlusions, but with simultaneous 8-phenyltheophylline, forskolin induced increments in the debt repayments were reduced significantly (p less than 0.05). These results indicate that adenylate cyclase contributes to myocardial reactive hyperaemia, and adenosine has a significant role as metabolic regulator of reactive hyperaemia through activation of adenylate cyclase.

Adenosine↗

Enhanced presynaptic beta 2-adrenoceptor-mediated facilitation of the pressor responses in the prehypertensive SHR.

The effects of beta-adrenoceptor agonists and antagonists on pressor responses of the isolated perfused mesenteric arteries to periarterial nerve stimulation (PNS) in the prehypertensive 4-week-old spontaneously hypertensive rat (SHR) and the age-matched Wistar Kyoto rats (WKY) were examined. The systolic arterial blood pressure (SBP) of SHR and WKY were not significantly different at this young age. The pressor responses of the mesenteric arteries to PNS at various stimulating frequencies, however, were significantly greater in SHR than WKY. Cocaine, isoproterenol (a nonselective beta-adrenoceptor agonist) and salbutamol (a selective beta 2-adrenoceptor agonist) significantly enhanced the pressor responses to PNS in SHR and WKY, with significantly greater increase in SHR than WKY. The nonselective beta-adrenoceptor antagonist (propranolol) and the selective beta 2-adrenoceptor antagonist (ICI 118,551) significantly inhibited the pressor response to PNS in SHR without affecting that in WKY. The selective beta 1-adrenoceptor antagonist (practolol) was without effect on the PNS-induced pressor responses in both SHR and WKY. These results demonstrate that the presynaptic beta 2-adrenoceptor-mediated facilitation of neurogenic pressor response in mesenteric arteries already are enhanced in 4-week-old SHR. In view of the higher concentration of circulating epinephrine (Epi) in prehypertensive SHR, the enhanced facilitatory modulation via presynaptic beta 2-adrenoceptors in prehypertensive SHR may be involved in development of hypertension.

Animals↗

Localized lipodystrophy with panniculitis: light and electron microscopic studies.

A 41-year-old woman with localized lipodystrophy histologically showed lymphohistiocytic inflammation within adipose tissue at the periphery and loss of adipose tissue in the center of the lesion. Ultrastructurally, various degrees of lipophagocytosis by macrophages and giant cells were seen, starting with the projection of cytoplasmic processes into the fat droplet and engulfing pieces of the fat droplet which finally were digested. Laboratory investigations revealed a high serum gamma-globulin level and a positive antinuclear antibody, suggestive of a connective tissue disease or autoimmune disease.

Adipose Tissue↗

Binding specificities of heat-labile enterotoxins isolated from porcine and human enterotoxigenic Escherichia coli for different gangliosides.

The binding specificities of heat-labile enterotoxins (LTp and LTh) isolated from porcine and human enterotoxigenic Escherichia coli on human erythrocytes were studied by competitive binding assays using different gangliosides as inhibitors. The binding of 125I-labeled LTp to neuraminidase-treated human type A erythrocytes was most effectively inhibited by ganglioside GM1. Ganglioside GM1 was 11 and 105 times more potent than gangliosides GD1b and GM2, respectively. Gangliosides GD1a, GT1b, and GM3 were much less potent. Similar results were also obtained in competitive binding assays with the 125I-labeled B subunit of LTh and neuraminidase-treated human type B erythrocytes, and in those with 3H-labeled ganglioside GM1 and LTp-coupled Sepharose 4B. The binding of 3H-labeled ganglioside GM1 to LTp was not effectively inhibited by galactose-beta(1----3)N-acetyl-D-galactosamine at the highest concentration used. These findings suggest that the combining sites of LTp and LTh may be specific for at least the galactose-N-acetyl-D-galactosamine-galactose (N-acetyl-neuraminic acid) portion of ganglioside GM1.

ABO Blood-Group System↗

Time-dependent effects of extraluminally-applied oxyhemoglobin and endothelial removal on vasodilator responses in isolated, perfused canine basilar arteries.

The effects of oxyhemoglobin (oxyHb) and removal of the endothelium have been measured in isolated, perfused canine basilar arteries treated with intraluminal vasodilator drugs. In preparations with an intact endothelium, acetylcholine (ACh) produces a biphasic response, where a small vasodilation precedes a vasoconstriction. Calcium ionophore A23187 and thimerosal induce a vasodilation at low doses and a biphasic response at high doses. Sodium nitroprusside (SNP) evokes only a vasodilation. Extraluminally applied oxyHb itself produces a transient vasoconstriction and then a gradual increase in perfusion pressure. After this treatment, the vasoconstriction to ACh was enhanced as was the vasodilation to SNP. Significant attenuation of the vasodilator action of A23187 and thimerosal was also observed. Subsequent removal of endothelium produced no further change in response. This implies that the action of extraluminal oxyHb is to eliminate any endothelium-dependent responses. If cerebral vasospasm after subarachnoid hemorrhage is initiated by hemoglobin released from the clot surrounding the artery, at least one component of its action appears to involve interference with endothelial function.

Acetylcholine↗

Effect of nimodipine on canine cerebrovascular responses to 5-hydroxytryptamine and potassium chloride after exposure to blood.

The stainless steel cannula inserting method was used to investigate the blocking effects of nimodipine on vascular responses to intraluminal administration of 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) before and after application of abluminal blood containing thrombin in isolated and perfused canine basilar arteries. A transient elevation of perfusion pressure was observed initially, and during the course of the experiment the perfusion pressure gradually increased. Nimodipine significantly depressed both transient and prolonged changes of perfusion pressure. Dose-dependent vasoconstriction induced by 5-HT was significantly enhanced, while that evoked by KCl was significantly attenuated for up to 8 hours after the application of blood. Pretreatment with nimodipine inhibited vasoconstriction to 5-HT less effectively than to KCl both before and after application of blood. The proportion of the 5-HT-induced vasoconstriction, which was sensitive to nimodipine, was reduced after application of blood, while no such change was observed in the responses to KCl. It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage of subarachnoid hemorrhage may be mediated mainly by changes in intracellular calcium utilization rather than by the increase of calcium influx through nimodipine-sensitive channels.

Animals↗

Monoclonal antibodies against species-specific antigens in the chick central nervous system: putative application as transplantation markers in the chick-quail chimera.

With the recent progress in transplantation of neuronal tissues, cellular markers are needed to distinguish the grafted cells from the host. To generate monoclonal antibodies (MAb) recognizing species-specific antigens in the chick nervous system, we immunized mice with chick optic nerves and obtained 2 MAb which bind to chick but not to quail neural tissues. MAb-39B11 recognizes the cell surface antigen on the nerve fibers. MAb-37F5 recognizes the cytoplasmic components in several cell types, including ependymal cells and some large neurons. The utility of these MAb as markers for chick cells in the chick-quail chimeric brain and their advantages over conventional markers are discussed.

Animals↗