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Biomedical subjects

T Shimamura

Publications and source records attributed to T Shimamura.

At least 127 records · Page 7Linked to original sources

[Inhibition of the infectivity of influenza virus by black tea extract].

We determined whether black tea extract inhibits the infectivity of influenza virus to mice. When mice were inoculated intranasally with 10(5.3) PFU influenza viruses (10(1.3) LD50), their body weight decreased and all died within 10 days. Whereas, when mice were inoculated i.n. with the mixture of influenza viruses and 2% (w/w) black tea extract, 5 min after mixing, all mice showed normal body-weight increase and survived. Neutralizing antibody to influenza virus was not detected in nine of 10 survived mice. The results indicate that black tea extract at beverage concentration (2% w/w) inhibits almost completely the infectivity of influenza virus to mice and that in vivo reversion of the tea-inactivated influenza virus does not occur.

Animals↗

Effect of lipopolysaccharide on mouse mast cell induction by a splenic cell culture system.

We have previously reported a method of mast cell induction by long-term culture of mouse spleen cells without using exogenous mast cell growth factor (Z.-Q. Hu, T. Yoshida, and T. Shimamura, J. Immunol. Methods 149:173, 1992). Supernatants recovered from the long-term cultures contain endogenous interleukin 3 and soluble stem cell factor. These were assessed by the capacity of the recovered supernatants to foster the growth of a mast cell growth factor-dependent cell line and by neutralizing antibodies. Besides the soluble factors, cell-to-cell contacts mediated by membrane stem cell factor on splenic stromal cells and c-Kit receptors on mast cells also affect mast cell induction. Different lots of fetal calf serum (FCS) were examined to determine a possible trigger for cytokine production. FCS can be divided into mast cell-inducible and noninducible sera by this process. However, not all FCS lots contain mast cell growth factor. The mast cell-inducible lots contain lipopolysaccharide (LPS) confirmed by a Limulus assay. Polymyxin B can neutralize the mast cell induction activity. Non-mast cell-inducible FCS can be converted to inducible FCS by adding exogenous LPS. The results indicate that LPS as a trigger of cytokine production is responsible for mast cell induction.

Animals↗

[Efficacy of transarterial embolization combined with percutaneous ethanol injection therapy for recurrent hepatocellular carcinoma].

One hundred and eighty-nine patients with hepatocellular carcinoma (HCC) underwent hepatectomy since 1987 to 1992 in our institute. Recurrences were detected on residual liver in 84 patients up to December 1993. Sixty-seven of 84 patients were treated with re-resection (group-O, n = 11), transarterial embolization (TAE) combined with percutaneous ethanol injection therapy (PEIT) (group-TP, n = 13), TAE alone (group-T, n = 34) and intraarterial chemotherapy (group-IA, n = 9). Among these 67 cases, the efficacy of treatment for recurrences was investigated. There was no significant difference in age, positive ratio of hepatitis B virus, ICG R15 and percentage of underlying liver cirrhosis among the 4 groups. However, the frequency of patients with 2 nodules or less, was significantly higher in group-O than in other groups. Cumulative 1-, 2- and 3-year survival rates (%) were 88.9, 64.8 and 51.9 in group-O, 92.1, 55.4 and 55.4 in group-TP, 70.9, 49.6 and 31.0 in group-T, and 16.9, 0 and 0 in group-IA, respectively. The survival rate after recurrences in group-TP was higher than in group-IA and group-T, and almost equivalent to that of group-O. Either re-resection or TAE combined with PEIT might assure- a favorable prognosis in patients with recurrent HCC.

Carcinoma, Hepatocellular↗

Mast cells display natural suppressor activity partially by releasing transforming growth factor-beta.

We have previously reported a method for inducing natural suppressor (NS) cells by long-term culture of normal adult mouse spleen cells. The NS cells were further identified as mucosal or immature mast cells by morphology, cytochemistry, histochemistry and function. A cloned immature mast cell line was also confirmed to have NS activity. As NS cells, the cell line suppressed non-specifically the plaque-forming cell (PFC) response. The NS cell-free supernatant was partially enriched by chromatography and some fractions suppressed the PFC response and thymocyte proliferation. Heat treatment of the fractions failed to deplete the suppressive activity. The fractions were confirmed, by immunoblotting analysis, to contain transforming growth factor (TGF)-beta. Recombinant human TGF-beta was also able to suppress the PFC response and thymocyte proliferation. Neutralizing anti-TGF-beta reversed the suppression by both human TGF-beta and the fraction. From the above results, it is clear that mast cells displayed NS activity, at least partially, through the release of TGF-beta.

Animals↗

[Efficacy of benzimidazole-type drugs on alveolar echinococcosis (AE)].

AE patients can be cured only by complete excision of the lesions. In Europe and the United States, however, benzimidazole-type drugs have been reported to be effective. We treated 37 patients (20 males and 17 females, mean age of 45.9 years) with mebendazole (MBZ) (n = 17) or albendazole (ABZ) (n = 20) according to the WHO chemotherapy protocol, and compared adverse reactions, drug concentrations, serological parameters, and measurable lesions by CT scan and/or X-ray examination. In the MBZ group, serological parameters were unaffected. One patient each had hepatic disorder and alopecia (12%), and 5 lesions in the liver and 3 in the lung gradually increased in size (105% in 1 year, 112% in 2 years), and showed NC (no response) in 6, PD (progressive disease) in 2. One case of released biliary obstruction were judged as PR (partial response) (Response rate: 11.1%). In the ABZ group, no adverse reactions were found and ELISA level decreased significantly in 10 out of 12 patients. One lesion in the liver, 3 in the lung, 1 in the chest wall and 1 in the retropancreatic region reduced in size significantly (Mean: 56%) (PR 3, NC 3; Response rate: 50.0%). ABZ was safer and more effective than MBZ.

Adult↗

[Morphological study of the axial view of the cervical spinal cord by MR images].

To investigate the morphological changes in the cervical spinal cord in patients with cervical myelopathy, we examined the axial anatomy of the cervical spinal cord and the spinal canal using MRI and CT scans. This study involved 35 patients (mean age = 56.8) with cervical myelopathy and 118 adult normal volunteers (mean age = 48.1) as controls. The transverse area of the spinal cord was measured on MR images (T1 images), while the transverse area of the spinal canal was measured on CT. In normal subjects, the transverse area, the sagittal diameter, and the coronal diameter of the spinal cord showed a significant positive correlation with body height, and a significant negative correlation with age. No significant difference was identified between males and females. The transverse area, the sagittal diameter, the coronal diameter, and the ratio of the sagittal/coronal diameter of the spinal cord and the spinal canal showed significant positive correlations among each other in normal subjects, but no significant correlation was noted in the patients with cervical myelopathy. There was no significant difference between the normal subjects and the patients in the transverse area or in the ratio of the sagittal/coronal diameter of the spinal cord at the levels without cord compression. However, the transverse area of the spinal canal in the patients with myelopathy was significantly smaller than that of normal subjects. In conclusion, a poor or no correlation between the size of the spinal cord and the spinal canal is a frequent finding in patients with myelopathy. Furthermore, this study suggests that patients with myelopathy present a narrow spinal canal more frequently than do normal subjects.

Adult↗

Cytolytic activity of intestinal intraepithelial lymphocytes in germ-free mice is strain dependent and determined by T cells expressing gamma delta T-cell antigen receptors.

We have compared the cytolytic activities and the cellular compositions of the intestinal intraepithelial lymphocyte (i-IEL) populations in three different combinations of conventional (CV) and germ-free (GF) mice. Cytolytic activity of i-IELs expressing gamma delta T-cell antigen receptors (TCRs) is strain dependent in CV mice (high vs. low), and this strain-dependent variability is unaltered in the GF condition. Although absolute numbers of gamma delta i-IELs are slightly decreased, the composition of CD8 alpha alpha+ and CD4-CD8- subsets and the usage of TCR gamma- and delta-chain variable gene segments by gamma delta i-IELs remain the same in GF mice. By contrast, cytolytic activity of alpha beta TCR-expressing i-IELs is uniformly high in CV mice but attenuated sharply in the GF condition. A conspicuous decrease in the total numbers of alpha beta i-IELs is also noted, and CD8 alpha beta+ and CD4+CD8+ subsets are reduced, whereas the CD8 alpha alpha+ subset is expanded in GF mice. These results indicate that microbial deprivation preferentially influences the alpha beta i-IEL population to decrease and become noncytolytic but has little effect on the pool size or characteristics of gamma delta i-IELs. Consequently, cytolytic activity of freshly isolated i-IELs from GF mice is determined by T cells expressing gamma delta TCRs and is found to be strain dependent.

Animals↗

Bactericidal catechins damage the lipid bilayer.

The mode of antibacterial action of, the green tea (Camellia sinensis) extracts, (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin (EC) was investigated. Strong bactericidal EGCg caused leakage of 5,6-carboxyfluorescein from phosphatidylcholine liposomes (PC), but EC with very weak bactericidal activity caused little damage to the membrane. Phosphatidylserine and dicetyl phosphate partially protected the membrane from EGCg-mediated damage when reconstituted into the liposome membrane with PC. EGCg, but not EC, caused strong aggregation and NPN-fluorescence quenching of PC-liposomes and these actions were markedly lowered in the presence of negatively charged lipids. These results show that bactericidal catechins primarily act on and damage bacterial membranes. The observation that Gram-negative bacteria are more resistant to bactericidal catechins than Gram-positive bacteria can be explained to some extent by the presence of negatively charged lipopolysaccharide.

Anti-Bacterial Agents↗

The analysis of internal image-bearing anti-idiotypic monoclonal antibody in relation to carcinoembryonic antigen.

Five anti-Id mAb (Ab2) were prepared from a BALB/c mouse immunized with anti-carcinoembryonic Ag (CEA) mAb MA208 (Ab1) in a syngeneic system. These anti-Id mAb appear to recognize unique idiotopes at the combining site of mAb MA208, because they were specifically reactive with mAb MA208 and showed the inhibitory activity against the binding of mAb MA208 to CEA. These anti-Id mAb were divided into three groups: group 1 (M7-625), group 2 (M7-413, M7-914), and group 3 (M7-049, M7-418), according to the analysis of anti-anti-Id antibodies (Ab3) induced with each anti-Id mAb (Ab2). Anti-anti-Id mAb M7-625 antisera (Ab3) reacted with purified CEA in binding assay and in Western blot analysis, and competed with Ab1 binding to CEA. Furthermore, the binding of anti-Id mAb M7-625 (Ab2) to mAb MA208 (Ab1) was inhibited with CEA, indicating that Ab2 mimicks the structure of the epitope in CEA which was recognized with Ab1. These serologic findings suggest that anti-Id mAb M7-625 carries the internal image of the Ag. According to the amino acid sequences of CDR 1, 2, and 3 of the mAb M7-625 variable region, there exists a homology of amino acid sequences between CDR2 in the H chain (5 amino acids of 10) and CDR3 in the L chain (3 amino acids of 9) of mAb M7-625 and domain III of CEA (545-554).

Amino Acid Sequence↗

Somatic diversification and affinity maturation of IgM and IgG anti-DNA antibodies in murine lupus.

Molecular events occurring during the process of generation of pathogenic immunoglobulin (Ig)G anti-DNA antibodies in systemic lupus erythematosus (SLE) were studied using a newly established method. We analyzed the Ig variable (V) region gene sequence and DNA-binding activity of IgM and IgG anti-DNA monoclonal antibodies (mAb) from individual SLE-prone (NZB x NZW) F1 mice. The first event appeared to be clonal selection and expansion of IgM anti-DNA clones, in which several clones had intraclonal V gene mutations. Although the number of mutations was small, the mutated IgM clones were associated with an increase in DNA-binding activity. The somatic mutations located in complementarity-determining regions (CDR) and in framework regions (FR) of V genes were apparently related to changes in DNA-binding activity. IgG anti-DNA clones that progressively increased in number with aging had numerous somatic mutations in the V region genes and there was a pair of clones which showed an intraclonal accumulation of mutations, in association with increase in the DNA-binding activity. All these findings show that somatic mutations associated with affinity maturation of the V region begin immediately before isotype-switching from IgM to IgG of the clones that have been selected and expanded, in an antigen-driven manner and/or by other forces. We propose that further accumulations of intraclonal somatic hypermutation, in association with selection and expansion of high affinity IgG clones, may lead to formation of highly pathogenic anti-DNA antibodies.

Age Factors↗

Inhibition of the infectivity of influenza virus by tea polyphenols.

(-)Epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) (1-10 microM) inhibited the infectivity of both influenza A virus and influenza B virus in Madin-Darby canine kidney (MDCK) cells in vitro. Study by electron microscope revealed that EGCg and TF3 (1 mM) agglutinated influenza viruses as well as did antibody, and that they prevented the viruses from adsorbing to MDCK cells. EGCg and TF3 more weakly inhibited adsorption of the viruses to MDCK cells. EGCg and TF3 (1-16 microM) also inhibited haemagglutination by influenza viruses. These findings suggest that tea polyphenols bind to the haemagglutinin of influenza virus, inhibit its adsorption to MDCK cells, and thus block its infectivity.

Animals↗

Influence of factors in the digestive tract on the progression of chronic renal failure.

To elucidate the mechanisms by which factors in the digestive tract influence the progressive chronic renal failure in rats, we employed the oral adsorbent, AST-120, which can adsorb certain uremic toxins in the gastrointestinal fluid. Administration of AST-120 firstly delayed the appearance of systemic hypertension, secondly delayed the increase in the amount of urinary protein excretion, and finally delayed the emergence of glomerular hypertrophy and glomerulosclerosis. The data obtained did not provide evidence for an inhibitory effect of AST-120 on hypertension. Our results therefore suggest that a pressor substance or its precursor exists in the digestive tract of rats with chronic renal failure.

Adsorption↗

[Adjuvant hepatic arterial chemotherapy on hepatocellular carcinoma with THP-adriamycin and carboplatin].

We studied the effect of adjuvant hepatic arterial chemotherapy with THP-adriamycin (THP) and carboplatin (CBDCA) in patients with hepatocellular carcinoma (HCC). Fifteen patients were treated by intraarterial infusion of THP 30 mg on the second and third week after hepatectomy. CBDCA 450 mg was further injected on the fourth week (group A). Intrahepatic arterial administration of the drug was carried out through the subcutaneously implanted reservoir; one to five courses of the protocol were performed (average 2 times). Transient leukocytopenia occurred in six cases, liver dysfunction in one case, duodenal ulcer in one case and occlusion of the catheter connected reservoir in three cases. Forty-two patients not treated with this protocol postoperatively were employed as historical control (group B). There were no significant differences between group A and B in operative procedures, tumor stage, clinical stage, tumor size and other histopathological findings including nuclear DNA ploidy pattern. The two-year cumulative disease-free survival rate was 78% in group A, which was significantly better than the 55% of group B (p < 0.05). It may be concluded that intrahepatic arterial chemotherapy using THP and CBDCA plays an important role to prevent recurrences of the tumor after hepatectomy in patients with HCC.

Antibiotics, Antineoplastic↗

The establishment of an interleukin-6-dependent myeloma cell line (FLAM-76) carrying t(11;14)(q13;q32) chromosome abnormality from an aggressive nonsecretory plasma cell leukemia.

A new myeloma cell line designated FLAM-76 was established from a patient with an aggressive nonsecretory plasma cell leukemia. The cell line exhibited morphologic features of flaming cells and contained an abundant eosinophilic cytoplasm with many dilated cisternae of rough endoplasmic reticulum. FLAM-76 cells were positive for cytoplasmic kappa (kapp)-type immunoglobulin but did not secrete it into the culture medium. The cells proliferated in the presence of exogenous interleukin-6 (IL-6) and more than 800 pg/ml of IL-6 was necessary for their continuous growth. The cells did not grow without IL-6, and they did not produce IL-6. Thus, the growth of FLAM-76 appeared to be regulated by the paracrine mechanism of IL-6. Alpha-interferon (alpha-IFN) inhibited the IL-6-dependent growth of FLAM-76 in doses greater than 1000 U/ml. FLAM-76 cells expressed CD38 (OKT10) and cell adhesion-associated antigens such as CD44 and CD54 (ICAM-1). Chromosome analysis revealed FLAM-76 to have a hypodiploid chromosome constitution with t(11;14)(q13;q32) abnormality, which frequently is seen in neoplasms of B-cell origin. Immunoglobulin (JH and Ck) gene rearrangement (but no BCL-1 gene rearrangement) was found in this cell line.

Aged↗

Effect of semi-random mutagenesis at the C-terminal 4 amino acids of human interleukin-6 on its biological activity.

The carboxyl(C)-terminus of human interleukin-6 (hIL-6) has a critical role in the expression of the biological activity of this cytokine. To define the structure-function relationships of this region, semi-random mutagenesis of the C-terminal Leu181-Arg182-Qln183-Met184 sequence of hIL-6 was performed. The mutants were produced in Escherichia coli, renatured, and purified. Alterations of the C-terminal 4 amino acids caused a significant reduction of the proliferative effect of the mutants on MH60.BSF2 and KT-3 cells, and also led to a drastic decrease in receptor binding affinity. These results suggest the importance of a positively charged residue at position 182 or 183 and an alpha-helix at position 181 for the biological activity of hIL-6.

Amino Acid Sequence↗

Induction and identification of mast cells from long-term culture of mouse spleen cells without conditioned medium.

A simple method is described for the preparation of large numbers of mast cells from mouse spleen cells in vitro. Mouse spleen cells were cultured with RPMI 1640 medium supplemented with 10% FCS and 2-ME. Half of the total volume of the medium was changed every 4-5 days. Mast cell numbers increased with the culture time and reached a peak between 16 and 20 days. Using this method, 2 x 10(6) mast cells could be induced from 1 x 10(7) nucleated normal spleen cells. T cells and supernatant derived from ConA-stimulated T cells were unnecessary for mast cell induction. Phenotype analysis by FACS showed that Thy1,2, L3T4, Ly-2, Ig, B220, Asialo GM1, and WGA receptors were all negative but functional IgE receptors were positive. The granules in the cells could be stained by alcian blue but not by safranin. There was 1.632 +/- 0.024 micrograms stored histamine in 1 x 10(6) of the cells. Histamine was released from the cells in an antigen-induced and IgE-mediated process. Compound 48/80 and A23187 induced degranulation of the cells, and the mast cells were able to respond to ConA.

Animals↗