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Biomedical subjects

H Kito

Publications and source records attributed to H Kito.

At least 37 records · Page 2Linked to original sources

Augmentation of allergic reactions by several pesticides.

The augmentative effects of several pesticides on histamine release from mast cells of rats that had been sensitized passively by anti-dinitrophenol (DNP) monoclonal IgE antibodies were investigated in vitro. Various pesticides, especially phenthoate (PAP), chlornitrofen (CNP) and paraquat (PQ), increased histamine release. This increase was not observed in histamine release with non-antigen or induction by calcium ionophore A23187 or compound 48/80. Passive cutaneous anaphylaxis (PCA) was examined, and an increase of PCA was observed with PAP and PQ, but not with CNP, while an increase of tumor necrosis factor-alpha (TNF-alpha) production was observed with CNP and PQ, but not PAP. These results suggest that various pesticides as environmental pollutants exacerbate allergic diseases.

Anaphylaxis↗

Biomarker and morphological characteristics of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis.

BACKGROUND: Viruses may induce primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), but it may not be possible to discriminate between these two in patients with a negative family history. Among these HLH cases, fulminant and fatal virus-associated hemophagocytic syndrome (VAHS) occurs mostly in relation to Epstein-Barr virus (EBV) infection. Although the immunological characteristics of EB-VAHS were previously reported, data on non-EB-VAHS were sporadic and fragmentary. This study has compared the clearly distinguishable groups of EBV-positive vs. EBV-negative HLH cases. PROCEDURE: Among 26 patients with EBV-related HLH and 12 patients with non-EBV HLH, peripheral blood mononuclear cell (PBMC) subsets and serum concentrations of cytokines at the active phase of the disease were compared. Blood and bone marrow smears were also compared. RESULTS AND CONCLUSIONS: The frequency of the CD3+HLADR+ subset in PBMC (median 34.3% vs. 4.8%), of serum concentrations of interferon (IFN)-gamma (median 105 U/ml vs. 2.4 U/ml), and of soluble interleukin-2-receptor (sIL-2R) (median 14,700 U/ml vs. 3,412 U/ml) were significantly different between these two groups. Morphological characteristics were noted for EBV-related HLH cases. Mortality also differed between these two groups, 9/26 vs. 0/12 (P = 0.05). Data indicate pronounced immunological imbalance and poor prognosis in EBV-related HLH cases. These parameters could be useful for determining an EBV involvement as well as risk factors in the early care and treatment of HLH patients.

Adolescent↗

Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro.

We investigated the inhibitory effect of eggplant (Solanum melongena var. marunasu) extract on human fibrosarcoma HT-1080 cell invasion of reconstituted basement membrane [Matrigel (MG)]. We found that the effective component of the plant extract was delphinidin, a flavonoid pigment contained in the peel. The extract and delphinidin did not affect tumor cell adhesion to MG or haptotactic migration to MG. HT-1080 secretes matrix metalloproteinase(MMP)-2 and MMP-9, which degrade extracellular matrix as part of the invasive process. Delphinidin slightly inhibited the activity of MMPs, which may have been responsible, in part, for the inhibition of tumor cell invasiveness.

Anthocyanins↗

Cyclooxygenase expression in bovine aortic endothelial cells exposed to cyclic strain.

The aim of this study was to investigate the effect of cyclic strain on cyclooxygenase (COX)-1 and 2 expression in bovine aortic endothelial cells (EC). EC, subjected to 10% average strain at 60 cycle/min, were analyzed for induction of COX by Northern blot analysis and confirmed by analysis of promoter activity in transient transfection experiments. Exposure of EC to cyclic strain induced promoter activity and expression of COX-2 but not of COX-1. The extent of induction, however, was lower than that seen with stimulation of 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or lipopolysaccharide (LPS). These results demonstrate that, unlike shear stress, cyclic strain does not affect COX-1 expression and is a weak inducer of COX-2 promoter activity in bovine aortic EC with minimal effect on mRNA expression.

Animals↗

Inhibition effect of propargylglycine on human fibrosarcoma HT-1080 cell invasiveness.

Effect of propargylglycine (2-Amino-4-pentynoic acid, PPG) on invasive property of human fibrosarcoma HT-1080 cell was investigated. PPG treatment of HT-1080 significantly reduced the total cellular metallothioneins (MTs) contents, and the resistance of HT-1080 against heavy metals toxicity decreased with the decrease of the MTs contents. The HT-1080 cell invasion to reconstituted basement membrane Matrigel (MG) was inhibited by the PPG treatment in a PPG concentration-dependent fashion. The inhibition was due to the lowering of HT-1080 cells attachment to MG and degradation activity of matrix metalloproteinases (MMPs) secreted from HT-1080 by the PPG treatment. However, the chemotactic ability of the PPG treated HT-1080 was enhanced. Our results suggest that MTs concentration levels in a malignant tumor cell are closely related to its invasiveness, and if MTs level of tumor cell can be controlled, cancer metastasis may be able to be controlled.

Alkynes↗

Cyclic strain is a weak inducer of prostacyclin synthase expression in bovine aortic endothelial cells.

Recent studies indicate that hemodynamic forces such as cyclic strain and shear stress can increase prostacyclin (PGI2) secretion by endothelial cells (EC) but the effect of these forces on prostacyclin synthase (PGIS) gene expression remains unclear and is the focus of this study. Bovine aortic EC were seeded onto type I collagen coated flexible membranes and grown to confluence. The membranes and attached EC were subjected to 10% average strain at 60 cpm (0.5 sec deformation alternating with 0.5 sec relaxation) for up to 5 days. PGIS gene expression was determined by Northern blot analysis and protein level by Western blot analysis. The effect of cyclic strain on the PGIS promoter was determined by the transfection of a 1-kb human PGIS gene promoter construct coupled to a luciferase reporter gene into EC, followed by determination of luciferase activity. PGIS gene expression increased 1.7-fold in EC subjected to cyclic strain for 24 hr. Likewise, EC transfected with a pGL3B-PGIS (-1070/-10) construct showed an approximate 1.3-fold elevation in luciferase activity in EC subjected to cyclic strain for 3, 4, 8, and 12 hr. The weak stimulation of PGIS gene expression by cyclic strain was reflected in an inability to detect alterations in PGIS protein levels in EC subjected to cyclic strain for as long as 5 days. These data suggest that strain-induced stimulation of PGIS gene expression plays only a minor role in the ability of cyclic strain to stimulate PGI2 release in EC. These findings coupled with our earlier demonstration of a requisite addition of exogenous arachidonate in order to observe strain-induced PGI2 release, implicates a mechanism that more likely involves strain-induced stimulation of PGIS activity.

Animals↗

Invasive properties of cadmium-resistant human fibrosarcoma HT-1080 cells.

Invasive properties of tumor cells having acquired heavy metal resistance were investigated. We selected the cadmium-resistant (Cd-R) cells from human fibrosarcoma HT-1080 cells. Total metallothionein levels in cytosol of HT-1080 Cd-R cells were significantly higher than original lines, and were of a highly resistant potency to cytotoxicity of cisplatin, as well as heavy metals. The HT-1080 Cd-R cells showed higher invasiveness into recombinant basement membrane Matrigel. However, HT-1080 Cd-R cells were inferior in locomotion ability. Significant differences in adhesive ability to extracellular matrix proteins were not observed between HT-1080 and HT-1080 Cd-R cells. High invasiveness of HT-1080 Cd-R cells was caused by their extremely strong enzymatic activities. High level of 92kDa matrix metalloproteinase-9 (MMP-9) was recognized from the conditioned medium of HT-1080 Cd-R cells, whereas 72kDa MMP-2 was secreted equally from both cell lines. Our investigation suggests that drug resistance acquired through the mechanisms of cellular metal-tolerance may promote malignancy and tumor metastasis during cancer chemotherapy.

Cadmium↗

Effect of metallothioneins on transformation of gelatinase A from human fibroblast WI-38 cells.

The effect of metallothioneins (MTs) on gelatinase A activity was investigated. The collagenolytic activity of gelatinase A from human fibroblast WI-38 cells was enhanced by the addition of MTs. This enhancement may be caused by the transformation of the inactive 62 kDa intermediate species of gelatinase A to the 59 kDa active enzyme. This enhancement was also observed in the conditioned medium of WI-38 cells exposed to heavy metals, but intracellular 72 kDa pro-gelatinase A did not change. Furthermore, degradation of gelatinase A occurred in the reaction between gelatinase A with substrate and MTs. Our results suggest that MTs may be an endogenous activator of gelatinase A, and may provide a host factor in cancer metastasis.

Animals↗

Biocompatible coatings for luminal and outer surfaces of small-caliber artificial grafts.

Luminal and outer surfaces of small-caliber vascular grafts at an early implantation period may require completely opposite cellular responses: minimal cellular adhesion and fibrin formation for a luminal surface versus potent cellular adhesion and migration and matrix generation for an outer surface. Differentiated biocompatible design of luminal and outer surfaces into small-caliber artificial grafts may lead to successful healing. We molecularly designed photocurable extracellular matrices (ECMs): photocurable chondroitin sulfate (CS) and hyaluronic acid (HA) for the luminal surface coating and photocurable gelatin for the outer surface coating. All of them were partially derivatized with photodimerizable groups such as thymine, cinnamate, and coumarin groups and converted to produce water-insoluble gels upon ultraviolet irradiation. In vitro study showed that platelet adhesion on photogelled CS and HA was significantly reduced, whereas endothelial cells adhered well on photogelled gelatin. These materials were individually coated and photogelled onto respective surfaces of artificial grafts (inner diameter [ID], 5 mm). During acute-phase implantation into dogs for up to 1 week, minimal cell adhesion was observed on the luminal surface, which was uniformly covered by photogelled CS or HA. Heparin impregnation of photocured ECM reduced fibrin formation. On the other hand, enhanced tissue ingrowth was noted at the outer surface. Although these ECM-coated grafts need further improvement in molecular design and coating techniques, photocurable ECMs may contribute to successful healing and a high patency rate of small-caliber artificial grafts.

Animals↗

Enhanced invasiveness of tumour cells after host exposure to heavy metals.

The invasiveness of tumour cells to heavy metal-exposed host cells or tissues was investigated. Human fibrosarcoma cell invasion of heavy metal-treated fibroblast or endothelial cell was enhanced in a treatment-time-dependent manner although tumour cell attachment to host cells was not affected. This enhancement was correlated with an increase in metallothioneins in the cytosol of fibroblasts or endothelial cells. Mouse melanoma cell invasion of organ samples obtained from syngeneic mice who had been administered heavy metals was also enhanced. The results suggest that heavy metal-induced metallothioneins serve as a host-derived factor in malignant disease and closely relate to metastasis.

Animals↗

Enhancement of the mutagenicity of amino acid pyrolysates by phthalate esters.

The ability of phthalic acid, phthalic acid anhydride, and various phthalate esters to enhance the mutagenicity of many amino acid pyrolysates was observed with the Ames test (Salmonella typhimurium TA98), but not the SOS Chromotest. Phthalate enhancement of the mutagenicity of 4-nitroquinoline-1-oxide, 2-nitrofluorene, and benzo[a]pyrene was not observed with either test. The mutagenicity-enhancing ability may be related to the induction of enzymes such as P450IIB, that metabolize amino acid pyrolysates. By quantitative structure activity relationship (QSAR) analysis, a good correlation was observed between the mutagenicity-enhancing activity of phthalates and their octanol-water partition coefficients.

1-Octanol↗

Short-term outcome of a new modification of the Bentall operation: Carrel patch and inclusion technique.

Leakage around the coronary ostia continues to be the major complication of composite graft replacement of the ascending aorta and aortic valve. To reinforce coronary anastomosis and reduce the operating time, a new modification of the Bentall operation was developed. This procedure involves dissecting full-thickness coronary buttons while leaving the epicardium on the aortic wall and complete wrap of the composite graft by the tailored aortic wall (Carrel patch and inclusion technique). Since March 1983, this approach has been performed in 12 patients (group A) and other Bentall-type operations in 22 (group B). Time affected by haemostasis was 28 min less in group A than in B (P = 0.23). Blood loss and blood transfusion during surgery and hospitalization were significantly lower in group A than B. Significantly less leakage occurred in group A than in B. On the basis of these short-term results, the Carrel patch and inclusion technique is considered to be an accurate time- and blood-saving procedure.

Adult↗

Dose-response relationship between total cadmium intake and metallothioneinuria using logistic regression analysis.

The dose-response relationship for environmental cadmium exposure was assessed using logistic regression analysis. The prevalence of metallothioneinuria was employed as a response variable, while age and total cadmium intake, calculated from the average cadmium concentration in rice and duration of residence in the cadmium-polluted area, were used as explanatory variables. The target population comprised of 1843 cadmium-exposed and 240 non-exposed inhabitants of Ishikawa, Japan. The individuals were divided into 96 subgroups by sex, age (4 categories), cadmium concentrations in rice (3 categories) and length of residence in the polluted area (4 categories). Only total cadmium intake had a significant association with the prevalence of metallothioneinuria. In the non-exposed subjects total cadmium intakes corresponding to 2.5% prevalence of metallothioneinuria were calculated. Based on metallothionein levels expressed as either microgram/l urine or microgram/g creatinine, the total intakes were: 2.221 or 2.207 g in men and 2.365 or 0.319 g in women, respectively. Most of these values were similar to those reported by us previously, employing simple regression analysis. It is concluded, therefore, that a maximum allowable intake of about 2 g cadmium is a reasonable estimate for preventing the cadmium-induced renal dysfunction.

Age Factors↗

Isolation of substances from glossy privet (Ligustrum lucidum Ait.) inhibiting the mutagenicity of benzo[a]pyrene in bacteria.

Methanol and hot-water extracts of glossy privet (Ligustrum lucidum Ait.) inhibited the mutagenic activity of benzo[a]pyrene in Salmonella typhimurium TA98 with S9 mix. The methanol extract was fractionated with ether and n-hexane. As the active components, oleanolic and ursolic acids were isolated, which were soluble in ether and insoluble in n-hexane. The hot-water extract was fractionated to water, 60% and 100% methanol fractions. Nuezhenide was isolated from the 60% methanol fraction as the active component.

Antimutagenic Agents↗

The mutagenicity of organotin compounds as environmental pollutants.

The mutagenicity of 14 organotin compounds which have been reported to be environmental pollutants, their environmental metabolites and inorganic tin (SnCl4) was studied. The experiments were carried out by a modification of the conventional Salmonella assay. Each tested chemical was removed by washing the tested strain with phosphate buffer, before the strain with top agar was poured onto minimal glucose agar. By this method, we were able to estimate the mutagenicity of organotin compounds which had antibacterial activity. It was apparent that mono-n-butyltin oxide, n-butyltin trichloride, di-n-butyltin dichloride, tri-n-butyltin chloride, bis-(tri-n-butyltin)-oxide and dimethyltin dichloride were mutagens on Salmonella typhimurium TA100 and bis-(tri-n-butyltin)-oxide showed the highest mutagenicity. With S. typhimurium TA98, di-n-butyltin dichloride was found to be a mutagen.

Environmental Pollutants↗

[Application of cryopreserved allograft to aortic root replacement for valve detachment case due to aortitis].

A 54-year-old male who had received an aortic valve replacement with SJM 23 about 3 years before suffered from an acute cardiac failure because of the valve detachment. From his clinical course, it was diagnosed that the aortic valve insufficiency was complicated by an aortitis. We operated on him by an aortic root replacement using a cryopreserved allograft which we prepared. A donor of the allograft was 35-year-old male, died of a subarachnoidal hemorrhage. We harvested his aortic root at an autopsy and dipped it into a nutrition medium with 10% dimethylsulfoxide. Within 10 hours from his death, we froze the tissue using a program freezer and stored it in a liquid nitrogen for 7 months. After thawing it in 37 degrees C water quickly, we rinsed the graft and used for the operation. The cell viability of the graft was confirmed by a tissue culture. Indication of the allograft valve to an aortitis case is still controversial. We think the allograft is recommendable to valve detachment case due to aortitis, because the softness of the graft decreases a compliance mismatch between the graft and the patient's annulus, which may prevent redetachment. Although we felt concern about redetachment of the conduit due to the weakness of the patient's aortic annulus, no complication regarding the allograft happened at all as yet.

Aortic Valve↗

Mutagenicity from ozonation of humic substances.

Eight structural components of humic substances were ozonated. Mutagenic activity was found using TA100 with and without S9 mix for all ozonated components. p-Hydroxybenzaldehyde was chosen as an important component and ozonation products were determined by gas chromatography-mass spectrometry (GC-MS). Aldehydes, ketones and carboxylic acids were identified as the ozonation products. Among these products, acetaldehyde, formaldehyde, glyoxal, methylglyoxal and glyoxylic acid were recognized to be mutagenic. Furthermore, p-hydroxybenzaldehyde was first ozonated and then chlorinated. A great variety of chlorinated organic compounds, many of which are known mutagens, have been identified by GC-MS in the ether extract. The same compounds have previously been reported as chlorination products of humic substances. Aldehydic products by ozonation were identified from ozonation followed by chlorination of humic substances and p-hydroxybenzaldehyde.

Animals↗