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Biomedical subjects

T Shimamura

Publications and source records attributed to T Shimamura.

At least 145 records · Page 8Linked to original sources
PubMed1992

A new highly sensitive immunoassay for cytokines by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA).

Non-isotopic immunoassays for human tumor necrosis factor alpha (TNF alpha) and human interleukin-6 (IL-6) were established by employing the dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) system based on the time-resolved fluoroimmunoassay technique with europium-labeled antibody. Compared to enzyme-linked immunosorbent assays and bioassays, the sensitivity and range of measurement were significantly increased by applying the DELFIA systems to TNF alpha and IL-6. TNF alpha was measurable from 100 fg/ml to 10 ng/ml with the TNF alpha-DELFIA and IL-6 was measurable from 100 fg/ml to 1 ng/ml with the IL-6-DELFIA.

Antibodies, Monoclonal↗
PubMed1992

Somatically mutated IgG anti-DNA antibody clonally related to germ-line encoded IgM anti-DNA antibody.

Among 15 anti-DNA antibody-producing hybridomas derived from a single NZB X NZW F1 mouse, an IgM and an IgG were shown to use the same VH gene of the Q52 family. Using a combination of two primers both consisting of a mixture of oligonucleotides (one complementary to the 5' end of VH segment and one to the 3' end of VH segment of Q52 family) we determined the sequences of several members of germ-line VH genes in the Q52 family derived from NZB and NZW strains. Comparison of the sequences with those of cloned VH cDNA obtained from the hybridomas revealed that the VH sequence of the IgM anti-DNA antibody was identical to that of a cloned NZW germ-line VH gene, except for the priming sites. In contrast, the VH sequence of the IgG counterpart contained somatically mutated nucleotides. Because the IgG anti-DNA antibody showed a higher DNA binding activity than did the IgM antibody, we conclude that these changes in nucleotide sequences were induced and selected through an antigen-driven mechanism as is the case in a normal immune response. It is tempting to speculate that the germ-line encoded, low-affinity IgM autoantibody undergoes somatic mutations and isotype switching, resulting in generation of pathogenic, high-affinity autoantibodies in autoimmune diseases.

Amino Acid Sequence↗
PubMed1992

Stimulation of human monocyte and polymorphonuclear cell iodination and interleukin-1 production by epigallocatechin gallate.

(-)Epigallocatechin gallate (EGCg) stimulated iodination of human peripheral blood monocytes, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells, dependent on time, dose, and temperature. However, EGCg did not affect iodination of nonadherent peripheral blood mononuclear cells, red blood cells, or 11 other cultured cell lines. Although various immunoregulators such as lipopolysaccharide (LPS), opsonized zymosan, 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor stimulated PMN iodination to varying degrees, their ability to stimulate monocyte iodination was much lower than that of EGCg. Washout experiments demonstrated that contact with EGCg for less than 60 min irreversibly stimulated PMN and monocyte iodination. EGCg also potently stimulated the production of interleukin-1-like factor by monocytes. The data suggest that EGCg is a strong in vitro stimulant of human phagocytes.

Adjuvants, Immunologic↗
PubMed1992

Enhancement of lymphocyte proliferation by mouse glandular kallikrein.

Mouse glandular kallikrein (mGK) strongly enhanced the spontaneous and mitogen-induced proliferation of lymphocytes. Both blast formation and 3H-TdR incorporation were dose-dependently enhanced at the same time many cells were killed. The enhancing activity was independent of EGF, because EGF-binding proteins (mGK-9 in mGK-6,9 mixture and mGK-13), renal kallikrein (mGK-6) and human kallikrein all displayed the same enhancement. A serine proteinase inhibitor, diisopropyl fluorophosphate, could block the enhancement by mGK. The new function suggests that mGK is important in the immune system as a regulatory molecule.

Animals↗
PubMed1992

Mitogenic activity of (-)epigallocatechin gallate on B-cells and investigation of its structure-function relationship.

(-)Epigallocatechin gallate (EGCg), the main constituent of green tea, strongly enhanced the direct plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in vitro and showed strong mitogenic activity for mouse splenic B-cells but not for splenic T-cells and thymocytes. The enhancement of B-cell proliferation was not mediated by macrophages since their removal did not eliminate the activity. Among the derivatives of catechin examined, (+)catechin (C); (-)epicatechin (EC); (-)-epigallocatechin (EGC); (-)epicatechin gallate (ECg); (-)epigallocatechin gallate (EGCg); and theaflavin digallate (TF3), only the derivatives with the galloyl group (ECg, EGCg, and TF3) displayed significant enhancement of the spontaneous proliferation of B-cells. Structural analogs of the catechin and galloyl groups were also examined in the system. Gallic acid and tannic acid induced some enhancement, but rutin, pyrogallol and caffeine did not. The results indicate that the galloyl group on EGCg was responsible for enhancement. However, the basic conformations of the catechins are also important, because ECg, EGCg, TF3, gallic acid, and tannic acid had quite different potencies to induce B-cell proliferation.

Adjuvants, Immunologic↗
PubMed1992

Effects of pirenzepine and hexamethonium on adrenal catecholamine release in responses to endogenous and exogenous acetylcholine in anesthetized dogs.

We investigated the way in which hexamethonium and pirenzepine, a selective muscarinic (M) 1 receptor antagonist, modify the release of catecholamines from dog adrenal gland in response to endogenous and exogenous acetylcholine (ACh) in vivo. Output of epinephrine (EPI), and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. Intraarterial (i.a.) injections of ACh (1.5 and 3 micrograms) or muscarine (3 and 6 micrograms) into the phrenicoabdominal artery and splanchnic nerve stimulation (SNS, 3 Hz) produced marked increases in EPI and NE output. Hexamethonium (1 mg/kg intravenously, i.v.) inhibited the increases in EPI and NE output in response to exogenous ACh and SNS. Pirenzepine (10 micrograms/kg i.v.) inhibited the ACh-induced increases in EPI and NE output but did not modify the SNS-induced increases. The muscarine-induced increases in EPI and NE output were also inhibited by pirenzepine. These results indicate that the exogenous ACh-induced release of adrenal catecholamines is mediated through both nicotinic and M1 receptors, in contrast to the predominant mediation of nicotinic receptors in response to endogenous ACh.

Acetylcholine↗
PubMed1992

Light chain nephropathy in a 19-month-old boy with AIDS.

A 19-month-old boy with AIDS developed clinically unexplainable proteinuria. Biopsied renal tissue was examined by light microscopy, transmission electron microscopy, and immunofluorescence. Findings included an increase of mesangial matrix with occasional nodular sclerosis, mesangial hypercellularity, and glomerular deposits of kappa and lambda light chains. There were deposits of kappa, but not lambda, light chains in the arteriolar walls, and around the tubular and interstitial capillary basement membranes. Quantitative urinary immunoelectrophoresis revealed an extremely high urinary concentration of kappa light chain. These changes are diagnostic of light chain nephropathy. The rarity of light chain nephropathy in childhood and its occurrence in a patient with AIDS make this case unusual.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Protective activity of tea and catechins against Bordetella pertussis].

We examined the bactericidal activity of tea and catechins against Bordetella pertussis. Green tea, black tea and coffee showed marked bactericidal activity at their concentrations in beverages, while pu-erh tea killed the bacteria in a moderate way. (-) Epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) showed also marked bactericidal activity. Green tea and black tea also effectively blocked the adhesion of B. pertussis to HeLa and CHO cells, whereas ECGg and TF3 could not. EGCg and TF3 markedly inactivated leuco-lymphocytosis promoting activity of pertussis toxin. Black tea showed slight but significant inactivation of the activity, whereas green tea showed no inactivation. These results suggest that green tea, black tea, EGCg and TF3 might act as prophylactic agents against pertussis infection.

Animals↗
PubMed1992

[Antimicrobial and microbicidal activities of tea and catechins against Mycoplasma].

We examined tea extracts, (-) epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) for their antimicrobial and microbicidal activities against Mycoplasma. Green tea and black tea showed antimicrobial activities against M. pneumoniae. At a concentration of 0.2% green tea and black tea showed microbicidal activities against M. pneumoniae and M. orale but not against M. salivarium. Extracts of pu-erh tea showed a slight microbicidal activity against M. pneumoniae and M. orale. EGCg purified from green tea and TF3 from black tea markedly showed microbicidal activities against M. pneumoniae. M. orale and M. salivarium. These results suggest that tea and catechins can be used as prophylactic agents against Mycoplasma pneumoniae infection.

Biflavonoids↗
PubMed1992

Effects of pravastatin on cholesterol metabolism in Watanabe heritable hyperlipidemic rabbits.

Pravastatin, a competitive inhibitor of hydroxymethylglutaryl CoA reductase (HMG CoA reductase) is a potent hypocholesterolemic agent in humans as well as experimental animals, including the Watanabe heritable hyperlipidemic (WHHL) rabbit, lacking low density lipoprotein (LDL) receptor activity. We studied the effect of pravastatin on several aspects of cholesterol metabolism in WHHL rabbits. Cholesterol synthesis was measured by intraperitoneal injection of radioacetate and determination of its incorporation into the nonsaponifiable lipid fraction of liver, plasma, adrenal glands and gonads. A single dose of pravastatin (25 mg/kg) caused statistically significant inhibition of hepatic cholesterol synthesis at 2, 6, 12, and 24 hours following oral administration. By 48 hours, the inhibitory effect of the drug was no longer demonstrable. The pattern of radioactivity in the plasma was similar to that in the liver. The drug had no statistically significant effect on cholesterol synthesis in adrenal glands and gonads, suggesting a selective effect on the liver. Cholesterol absorption was studied after simultaneous oral administration of [3H] cholesterol and [14C] beta-sitosterol. Pravastatin, 50 mg/kg for 10 days had no effect on fecal excretion of the radiolabelled steroids over 4 days. At 24 hours the plasma level of [14C] cholesterol was 1/3 that of control in pravastatin treated animals (p < 0.05) but did not undergo an accelerated decline over 6 days. The activity of acyl CoA: cholesterol acyltransferase (ACAT) in intestinal mucosa and the concentration of hepatic cholesterol were similar in animals treated over one year with pravastatin 50 mg/kg/day or with placebo. Our data do not allow us to make definitive conclusions about the effect of pravastatin on cholesterol absorption but are compatible with the hypothesis that the drug inhibits the hepatic synthesis as well as the assembly of cholesterol into lipoproteins.

Absorption↗
PubMed1992

[Problem of the long-term arterial infusion therapy with implantable reservoir for unresectable hepatocellular carcinoma].

Arterial infusion therapy with implantable reservoir was performed for forty-seven cases with unresectable hepatocellular carcinoma since 1986-1991. The one-year survival rate of cases of arterial infusion therapy with implantable reservoir was 50.6% and the 2-year survival rate was 37.8%. The survival rate was 51.4% and 32.2%, respectively, in the TAE cases for the same period. Considering the kinds of reservoirs used for HCC, the survival curve of 23 cases with double lumen reservoir showed a significantly better pattern than that of 24 cases with the usual single lumen reservoir (p less than 0.05). Cumulative usable rate of reservoir was 78.6% at one year, and 42.4% at two years (Kaplan-Meier method). Therapy after the reservoir was unusable, particularly with arterial obstruction by catheter, was restricted because arterial infusion therapy was impossible. It is considered very important to retain the hepatic artery because arterial infusion therapy is mainly for unresectable hepatocellular carcinoma.

Antineoplastic Agents↗
PubMed1992

Early morphological changes of tubules in rats with chronic renal failure.

We investigated the early changes of tubules and effect of the oral adsorbent, AST-120, on the early changes of tubules in rats with chronic renal failure. Sprague-Dawley rats were divided into two groups with and without AST-120, after 3/4 nephrectomy. Although there were no significant differences in levels of blood urea nitrogen, serum creatinine, creatinine clearance, inulin clearance, para-aminohippuric acid clearance and urinary N-acetyl-beta-D-glucosaminidase at week 8 between the two groups, the amount of 24-hour urinary protein excretion and the direct systolic blood pressure at week 8 were significantly decreased in the group with AST-120. Examinations by light microscopy at week 8 revealed that proteinaceous casts in the tubules, tubular dilatation and infiltration of monocytes into the interstitium in the group with AST-120 were less prominent than those in the group without AST-120. A significant difference in numbers of proteinaceous casts was noted at week 8 between the two groups. In rats with chronic renal failure at the early stage, it is concluded that the formation of proteinaceous casts, resulting in tubular damage, is increased and that AST-120 delays the occurrence of proteinaceous casts by delaying the increase in urinary protein excretion.

Adsorption↗
PubMed1991

Proliferation of natural suppressor cells in long-term cultures of spleen cells from normal adult mice.

Natural suppressor cells were induced by culturing spleen cells from normal adult mice for 2 to 3 wk. The suppressor cells were large in size, nonadherent and nonspecifically suppressed the plaque-forming cells response of fresh spleen cells to SRBC in vitro. The suppressive activity of the cells was not affected by treatment with indomethacin or anti-Thy-1, anti-Ig, anti-Ia, or anti-asialoGM1 plus complement. Phenotype analysis by FACS showed that Thy-1, L3T4, Ly-2, CD3-epsilon, TCR-alpha beta, Ig, B220, Ia, and asialoGM1 Ag were all absent in the suppressor cells, although they were wheat germ agglutinin receptor positive. The suppressor cells did not demonstrate cytotoxicity against either YAC-1 or P-815 cells. Enriched large cell populations from fresh normal spleens expressed the same phenotypes and also exhibited the suppressive activity. These findings suggest that a minor population of natural suppressor cells exist in the normal adult mouse spleen and they proliferate during the in vitro culture of spleen cells.

Animals↗
PubMed1991

Analysis of interleukin 6 (IL-6)/IL-6 receptor system using monoclonal anti-IL-6 antibodies.

To investigate the IL-6/IL-6 receptor system, we obtained five murine monoclonal antibodies against human IL-6, which neutralize its biological activity. We classified them into two groups (Type I mAb and Type II mAb) according to the epitopes they recognized. These two types of antibodies showed no difference in the manner in which they neutralized IL-6 activity, but they differed in the way they inhibited the binding of IL-6 to its receptor. While Type I mAb inhibited IL-6 binding to its receptor completely, Type II mAb inhibited only partially, even at a concn of Type II mAb sufficient to neutralize biological activity. Scatchard plot analysis revealed that in the case of the human myeloma cell line, the U266 cell, which showed two-phase binding of IL-6 to its receptor, the high affinity binding disappeared and the affinity of the low affinity binding decreased in the presence of Type II mAb. These results suggest that Type I mAb neutralizes IL-6 activity by the blocking of IL-6 binding to its receptor directly. In contrast, Type II mAb neutralizes IL-6 activity not by direct blocking of IL-6 binding to its receptor, but by modulating the binding affinity of IL-6 to its receptor, that is, inhibiting the formation of high affinity binding in IL-6 receptor system. This also indicates that the formation of high affinity may be necessary to transduce the IL-6 signal.

Antibodies, Monoclonal↗
PubMed1991

The protective activity of tea against infection by Vibrio cholerae O1.

Extracts of black tea exhibited bactericidal activity against Vibrio cholerae O1. The tea extract inhibited the haemolysin activity of V. cholerae O1, El Tor and the morphological changes of Chinese hamster ovary cells induced by cholera toxin. Tea extract also reduced fluid accumulation induced by cholera toxin in sealed adult mice and by V. cholerae O1 in ligated intestinal loops of rabbits. These findings suggest that tea has protective activity against V. cholerae O1.

Animals↗
PubMed1991

Pravastatin decreases serum lipids and vascular cholesterol deposition in Watanabe heritable hyperlipidemic (WHHL) rabbits.

The effects of long term administration of pravastatin (a competitive inhibitor of hydroxymethylglutaryl CoA reductase) were assessed by measuring serum lipids and aortic and coronary atherosclerosis in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Six-month-old WHHL rabbits were given either 50 mg/kg/day of the drug or vehicle. The rabbits were sacrificed following 6 or 12 months of treatment and serum cholesterol and triglycerides and aortic cholesterol and hydroxyproline were measured. Atherosclerotic plaques in the aorta and coronary arteries were quantified with morphometric methods. Mean serum cholesterol +/- SEM (n) in the control vs. pravastatin groups after 6 months were: 535 +/- 34 (11) vs. 411 +/- 22 (12) (p less than 0.005) and after 12 months 458 +/- 43 (9) vs. 309 +/- 29 mg/dl (12) (p less than 0.005). In the pravastatin group, percent aortic area covered with plaque and aortic cholesterol content were reduced 35% (ns) and 55% (p less than 0.05) at 6 months, and 26% (ns) and 44% (ns) at 12 months, respectively. Little difference was found in serum triglycerides and aortic hydroxyproline in the 2 groups. There was strong correlation of serum cholesterol with aortic cholesterol content (r = 0.61, p less than 0.003) and with the percent aortic plaque area (r = 0.67, p less than 0.001), at 12 months. Morphometric analysis of wall thickness and lumen area of major coronary arteries revealed no significant differences in the 2 groups. In conclusion, pravastatin effectively lowered the serum cholesterol level in an animal model defective in low density lipoprotein receptors; this reduction was strongly correlated with amelioration of such atherosclerotic processes as lipid deposition and plaque formation.

Animals↗