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Biomedical subjects

T Tsujii

Publications and source records attributed to T Tsujii.

At least 109 records · Page 6Linked to original sources

Hepatitis C virus infection in patients with chronic liver diseases.

Antibodies against hepatitis C (HCV) in 512 patients were measured by an enzyme immunoassay (Ortho-HCV ELISA). The frequency of anti-HCV was 80%, 86%, 85% in nonB (NB) chronic hepatitis (CH), cirrhosis (LC), hepatocellular carcinoma (HCC), respectively; 70%, 90% in alcoholic (AL) LC, HCC; 15%, 33%, 58% in hepatitis B (HB) CH, LC, HCC, respectively. Anti-HCV positive cirrhotics had a shorter survival time and earlier development of HCC than anti-HCV negative cirrhotics. The findings suggest that HCV is a major cause of NB chronic liver diseases and may play a pathogenetic role in AL and HB liver diseases.

Adult↗

Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis.

Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Child's grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Child's grade B disease. On the other hand, only 2 of 10 cases with Child's grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver.

Bile Acids and Salts↗

Inhibitory effect of dietary iron deficiency on the induction of putative preneoplastic foci in rat liver initiated with diethylnitrosamine and promoted by phenobarbital.

The effects of dietary iron deficiency on induction of putative preneoplastic, gamma-glutamyltransferase (GGT)-positive hepatocyte focal lesions in the liver of rats treated with diethylnitrosamine (DEN) followed by phenobarbital (PB) were investigated. Male Fischer 344 rats of 4 weeks old were placed on an iron deficient (ID) diet containing less than 5 p.p.m. of iron or an iron supplemented (IS) diet containing 180 p.p.m. of iron throughout experimental period of 12 weeks. Both groups of rats were administered 200 mg kg-1 body weight of DEN by a single intraperitoneal injection at Week 4 followed by PB mixed into each diet at a concentration of 0.05% from Week 6 to the final sacrifice at Week 12 when induction of GGT-positive foci was quantitatively analysed. On the ID and IS diets, respective numbers of GGT-positive foci were 6.3 and 14.2 cm-2. The sizes of foci were not altered by the iron content of the diet. The present results indicate that iron plays a role in the development of preneoplastic foci in the livers of rats initiated with DEN and promoted by PB especially in the initiation phase.

Anemia, Hypochromic↗

Analysis of the immunoactivator sites of parotid protein isolated from bovine parotid glands.

Parotid protein (parotin) was isolated from bovine parotid glands. To analyze the active site of parotid protein, the parotid subunit (PS) was digested by trypsin and then fractionated on a Sephadex G-25 column. Fraction A induced mainly polyclonal antibody responses and interleukin 1 (IL-1)-like activities. FrAA-1, consisting of 58 amino acids (LYILYFFQSDNEDKEKVVRQEEGEE-RITALLMNGSALKQEEWWEKEDTDDTAIVLLK) was isolated from fraction A by chromatography on QAE-Sephadex A-25 columns. FrAA-1 was found to possess IL-1-like activity. There was only 29% homology between FrAA-1 and four IL-1 molecules. When 10- and 20-residue peptides based on the amino acid sequence of FrAA-1 were synthesized, P-10.2 (TDDTAIVLLK) alone exerted an IL-1-like effect on C3H/HeJ thymocytes, whereas P-20.1 (SDNEDKEKVVRQEEGEERIT) alone elicted polyclonal IgM and IgG antibody production in human lymphocytes. These results suggest that the active sites for polyclonal B-cell activator (PBA) and IL-1-like activity have different locations in FrAA-1.

Amino Acid Sequence↗

A potential approach for gene therapy targeting hepatoma using a liver-specific promoter on a retroviral vector.

Recent technological advances made in molecular biology and in vitro culture of human and other mammalian cells have led to broad medical and scientific acceptance of the feasibility of gene therapy for genetic diseases. Cancer might practically be one of the attractive targets for such therapy. For the treatment of cancer, it is important to manipulate the gene of interest such that it is expressed solely in cancer cells. We have developed a tissue-specific gene expression system, based on a tissue-specific promoter on a retroviral vector. A murine ecotropic retroviral vector was constructed in which the Escherichia coli beta-galactosidase gene served as a reporter; it was expressed under control of the albumin enhancer element and promoter. The tissue specificity of this vector was first assessed in vitro, and beta-galactosidase activity was detected exclusively in hepatoma cell lines. This recombinant retrovirus was injected directly into a subcutaneous tumor composed of transplantable murine MH-134 hepatoma cells, and expression of the gene was observed in vivo. Then this recombinant retrovirus was injected via the spleen or directly into the liver, resulting in the gene expression in dividing hepatocytes in partially hepatectomized mice, but not in nondividing hepatocytes in normal mice. Gene transfer specific to dividing hepatocytes and expression by means of retroviral vectors should possess high potential for selective elimination of hepatoma cells surrounded by nondividing normal hepatocytes.

Animals↗

Intestinal mucosa and intra-abdominal lymphoid tissues of the platypus, Ornithorhynchus anatinus.

The morphological features of the intestinal mucosa and intra-abdominal lymphoid tissues of the platypus were examined. The mucosal surface of the intestine was characterized by the formation of large folds instead of the finger-like villi found in placental mammals. The lamina propria of the mucosal fold was well developed and contained numerous lymphocytes, expressing the lymphoid nature which is characteristic of the lamina propria of mammalian intestines. Although numerous well-developed Peyer's patches were observed in the ileum, solitary lymphoid nodules could not be found anywhere in the small intestine. Other intra-abdominal lymphoid tissues, particularly mesenteric lymphoid nodules, were well developed. However, each nodule represented a single follicle in contrast to the mammalian mesenteric lymph node which is composed of numerous follicles fused together. On the basis of the above findings, the tissues in question are considered to be at an evolutionary level preceding that of placental mammals.

Abdomen↗

[BEP (bleomycin, etoposide, cisplatinum) chemotherapy as an induction therapy of advanced extragonadal germ cell tumor].

Five patients with advanced extragonadal germ cell tumor (EGGCT) were treated with cisplatinum + vinblastine + bleomycin (BVP) or cisplatinum + etoposide + bleomycin (BEP) chemotherapy as an induction therapy. All patients had high levels of tumor markers and multiple distant metastasis in poor nutritious conditions. Two patients given BVP therapy died 6 and 9 months after the chemotherapy. By contrast, three patients given BEP therapy achieved complete remission and were surviving longer than one year without any evidences of disease. Granulocytopenic fever was seen soon after the first course of BEP therapy. Prophylactic granulocyte-colony stimulating factor (G-CSF) treatment, enabled two of them to receive full dose chemotherapy without any fever attacks. In conclusion, BEP chemotherapy is effective to EGGCT as well as far advanced testicular tumors and G-CSF treatment is useful for achievement of induction chemotherapy to advanced germ cell tumors.

Adult↗

[Preventive effect of ticlopidine on peplomycin pulmonary fibrosis].

A comparative clinical study examined the preventive effect of ticlopidine hydrochloride (hereinafter referred to as ticlopidine, anti-platelet drug) on Peplomycin sulfate (hereinafter referred to as Peplomycin) pulmonary fibrosis. In clinical evaluation, pulmonary function (PaO2, DLco) and biological fibrosis markers (angiotensin I converting enzyme, type III procollagen peptide, phospholipid) were measured. PaO2 and DLco using ticlopidine showed improvement, but statistical significance was not observed. Changes in biological fibrosis markers due to Peplomycin administration were observed in accordance with earlier experiments. Importantly however, the variance of type III procollagen peptide in the ticlopidine group was significantly suppressed (p less than 0.10). As a result, ticlopidine has the potential to prevent Peplomycin pulmonary side effects during clinical use.

Bleomycin↗

Melano-macrophage centers in the aglomerular kidney of the sea horse (teleosts): morphologic studies on its formation and possible function.

In order to elucidate the process of the formation and possible function of the renal "melano-macrophage centers (MMC)" of fish, light and electron microscopic observations were carried out on the aglomerular kidney of the sea horse, Hippocampus kuda BLEEKER, injected with antigenic horse-spleen ferritin (AF) and nonantigenic carbon particles (CP). Kidneys of the sea horse have well-developed hemopoietic foci in the interstitial tissues surrounding the bundles of renal tubules. Each hemopoietic focus has a small artery in the central area and is framed with the densely arranged sinusoids lined with monolayered macrophages which have no melanin pigments. In the hemopoietic foci free macrophages (M phi) were hardly found, but large clusters of MMC filled with densely packed masses of cell debris with some melanin pigments were encountered. Some of them had degenerated M phi with fibrotic change surrounded by fibroblasts. AF and CP injected intraperitoneally entered quickly into blood vessels and were taken up actively by the sinusoidal M phi. The M phi full of AF or CP left the sinusoidal wall and moved gradually into hemopoietic foci to form the MMC or to fuse with the preexisting MMC. The melanophores in the interstitial connective tissue joined to form the MMC. No specific histologic change suggestive of immune response to the AF was present in and around the MMC. The results indicate that the MMC of fish should be only the aggregates of M phi to digest the ingested materials effectively. The process of formation of MMC and their possible function is discussed.

Animals↗

Promoting effect of citrulline in hepatocarcinogenesis: possible mechanism in hypercitrullinemia.

Hypercitrullinemia (adult type), believed to be one of the hereditary urea cycle disorders, is known to be complicated by hepatocellular carcinoma at a high incidence (approximately 14%). We investigated the relationship between this hypercitrullinemia and hepatocarcinogenesis. After the addition of citrulline, incorporation of tritiated thymidine into primary cultured hepatocytes of adult rat increased in a dose-dependent fashion in the range of 0.1 to 5 mmol/L. The citrulline-added group also showed significant increase in ornithine and polyamine contents in hepatocytes. The incidence of epithelial cell foci in the in vivo-in vitro tumor promotion analyzing system significantly rose in the group maintained with 5 mmol/L citrulline and in the group maintained with 1.5 mmol/L phenobarbital. These findings suggest the possibility that citrulline has a promotion effect on hepatocyte proliferation and that at high concentrations it plays the role of a hepatocarcinogenesis promoter.

Amino Acids↗

A novel oral adjuvant for hepatitis B virus (HBV) vaccines.

A plasma-derived HBV vaccine was administered to 86 healthy men ranging in age from 40-56 years. A relatively high rate of nonresponders was found among the men who received the HBV vaccine alone. There was a significantly higher HBs antibody response rate among the vaccinees who received an oral adjuvant (taurine) compared to those not receiving the adjuvant. In the vaccinees who received the oral adjuvant, an in vitro polyclonal antibody response to taurine was detected in 17 (58.6%) of the 29 HBs responders, but in none of the HBs nonresponders. The development of oral adjuvants other than aluminum may be a valuable approach to the study of HBV vaccination.

Adjuvants, Pharmaceutic↗

Effects of acetate on the immune system of mice.

The effects of acetate on antibody production and cell-mediated immunity in mice were investigated. Polyclonal antibody responses could be enhanced in vivo by single intraperitoneal administration of acetate (5 mg/mouse) in C57BL/6 mice but not in DBA/2 mice. No enhancement of antibody production by acetate was also induced in athymic C57BL/6 nude mice and carrageenan-pretreated, macrophage-depleted mice. The inoculation of acetate-nonresponder BDF1 mice with T-cells and peritoneal adherent cells derived from acetate-treated C57BL/6 mice resulted in an enhanced antibody response. These results suggest that acetate increases polyclonal antibody responses in vivo by activating indirectly T-cells and macrophages. Acetate administration increased delayed hypersensitivity to pircryl chloride in C57BL/6 mice but not in DBA/2 mice. Allogeneic mixed lymphocyte reaction (MLR) of T-lymphocytes derived from the spleen of acetate-treated C57BL/6 mice was also enhanced. The natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) were also increased in C57BL/6 mice that were administered acetate. The possible mechanism of the immunopotentiating effect of this chemical is discussed.

Acetates↗

Oral adjuvants for viral vaccines in humans.

The availability of various viral vaccines prompted extensive studies on oral adjuvants. In this study, parotid protein (parotin), taurine and lithium were chosen as safe and potent oral adjuvants for rubella and influenza virus vaccines. The anti-rubella virus antibody titres in persons administered orally with parotin were significantly higher than those of persons with the non-adjuvanted vaccines. The combinations of oral adjuvants were used for vaccination with trivalent influenza vaccines. Each group, receiving taurine, taurine + lithium, taurine + parotin or taurine + parotin + lithium, was higher in the magnitude of increased influenza virus antibody titres than the non-adjuvant control group. Although taurine was shown to be an effective adjuvant in taurine responders but not in taurine non-responders, the combination of taurine, lithium and/or parotin gave higher increased rate of influenza antibody titres than with taurine alone. These results have shown to be a valuable approach to the clinical use of oral adjuvants.

Adjuvants, Immunologic↗

[The clinical usefulness of urinary basic fetoprotein (BFP) in patients with urological malignancies].

Basic fetoprotein (BFP) was measured by enzyme immunoassay in the urine of healthy adults and patients with benign or malignant urological diseases. Urinary BFP level in 34 healthy donors was very low (2.75 +/- 2.27 ng/ml). Since the BFP-positive rate is under 5% in healthy donors and, considering diagnostic efficiency for urological malignancies, a urinary BFP-concentration of 15 ng/ml was used as the cut off value. Urinary BFP was positive in 17.0% of 106 patients with benign urological diseases, in 51.9% of 52 patients with bladder cancer, in 75.0% of 8 patients with renal pelvic or ureteral cancer, in 25.0% of 20 patients with prostate cancer, and in 19.0% of 21 patients with renal cell carcinoma. In 60 patients with urothelial carcinomas, urinary BFP was higher in invasive diseases (greater than pT1) than in superficial diseases (p less than 0.05). The BFP level in urine also increased with a higher histological grade. The positive rate of urinary BFP was 78.9% in patients with invasive diseases and 66.7% in patients with grade 3 diseases. In 44 patients with urothelial carcinomas who underwent urinary cytological examination the positive rate was improved from 38.6% (17/44) to 81.4% (37/44) when measurement of urinary BFP was added. BFP in urine was found to be useful as a tumor marker for urothelial carcinomas. In addition, it was demonstrated that combined examination of urinary cytology with urinary BFP was more efficient for diagnosis of urothelial carcinomas.

Adenocarcinoma↗

[Effect of tegafur administration combined with hormonal therapy in patients with newly diagnosed stage D prostatic cancer].

To study the effect of tegafur administration combined with hormonal therapy on the survival rate of newly diagnosed patients with stage D prostatic cancer, 66 patients, 70.9 years old in mean age, were treated from 1979 to 1986. The cancer was proven by the histological or cytological examination of the specimen which was obtained by the needle biopsy and/or aspiration biopsy of the prostate. The histopathological diagnosis of 59 patients was as follows: well differentiated type of adenocarcinoma was observed in 13 patients, moderately differentiated type in 19 cases, poorly differentiated type in 24 cases and mixed type in 3 cases. Daily 600 mg tegafur was administered orally as long as possible from the beginning of the treatment combined with hormonal therapy. Actual and relative 5 year survival rates calculated with Kaplan-Meier's method were 31.2% and 39.2%, respectively. When deaths other than prostatic cancer death were counted as lost cases, the actual survival rate was 47.5%. The present study also demonstrated that there were some factors affecting the patients' prognosis. They were the age of onset of the disease (patients under 64 years old were worse than those over 65 years old; p less than 0.05), performance status (patients with PS from 0 to 2 at the first admission were better than those with PS 3 to 4; p less than 0.025), differentiation of the tumor (well differentiated type was better than moderately; p less than 0.025 or poorly differentiated type; p less than 0.005).

Adenocarcinoma↗

[Multiple malignant schwannoma treated with a multidisciplinary therapy--a case report].

A 32-year-old man, complaining of an abdominal mass, was admitted to hospital where, on undergoing examination, the mass, which had spread widely through the abdominal cavity and the retroperitoneal space, was diagnosed as a malignant schwannoma with a liver metastasis. Thus, a multidisciplinary treatment was initiated and a remission was achieved. Later, however, he developed a multiple, local recurrence and died forty months after onset of his clinical symptoms. Since the prognosis of patients with a malignant schwannoma that do not undergo radical surgery is extremely poor, the authors emphasize the necessity of research for an effective adjuvant therapy.

Adult↗

In vivo depletion of macrophages by desulfated iota-carrageenan in mice.

Almost 90% of the sulfate groups of iota-carrageenan (CGN) was removed with acid-methanol in an attempt to obtain a product which would selectively eliminate macrophages in mice. Desulfated CGN(DS-CGN) failed to induce in vivo polyclonal antibody production in DBA/2 mice. However, the number of phagocytes in the peritoneal cavity, spleen, thymus and lymph node of DBA/2 mice was reduced stringently by DS-CGN treatment. The number of Mac-1 positive cells(macrophages) in DS-CGN-treated mice gradually decreased for at least 7 days after the last injection of DS-CGN. In contrast, the relative proportion of T and B lymphocytes in the lymphoid organs was unaffected by DS-CGN treatment. DS-CGN suppressed antibody responses to SRBC, a T cell and macrophage-dependent antigen, but no such suppressive effect was observed in the polyclonal antibody responses to LPS, a T cell and macrophage-independent B cell activator. Furthermore, the impaired SRBC antibody responses in DS-CGN-treated mice were restored following transfer of adherent cells but not T cells. These experimental results indicate that DS-CGN selectively eliminates macrophages without influencing lymphocyte function in vivo.

Animals↗