Biomedical subjects

K Yanagi

Publications and source records attributed to K Yanagi.

At least 73 records · Page 4Linked to original sources

PubMed1997

Importance of intra-abdominal visceral fat accumulation to coronary atherosclerosis in heterozygous familial hypercholesterolaemia.

OBJECTIVES: Hyper-low-density lipoprotein (LDL)-cholesterolaemia is a potent risk factor for coronary atherosclerosis. We have recently demonstrated that a cluster of risk factors including insulin resistance, glucose intolerance, hypertriglyceridaemia, and hypertension based on intra-abdominal visceral fat accumulation are closely related to coronary artery disease. In the current study, we evaluated the relationship between visceral fat accumulation and the severity and distribution of coronary atherosclerosis in familial hypercholesterolaemia (FH). DESIGN: The effect of visceral fat accumulation on coronary lesions and risk factors in patients with FH was investigated. SUBJECTS: Thirty-one male patients with heterozygous FH who underwent coronary angiography. MEASUREMENTS: Abdominal fat distribution was estimated by a cross-sectional computed tomographic scan at the umbilical level. Plasma lipid, glucose and insulin concentrations and blood pressure were measured. A 75 g oral glucose tolerance test was also performed. RESULTS: The patients were divided into two groups according to the degree of visceral fat accumulation. Fifteen patients had high visceral fat accumulation (High VF group) and 16 patients had normal visceral fat accumulation (Normal VF group). Body mass index (BMI) and subcutaneous fat area were significantly higher in the high VF group. Baseline serum triglyceride was significantly higher and baseline low-density lipoprotein (LDL)-cholesterol and reduction of LDL-cholesterol during treatment were significantly lower in High VF group. Fasting plasma glucose and insulin concentrations, and systolic and diastolic pressures were significantly higher in the High VF group. Significant correlations were found between visceral fat area and the sum of the glucose and insulin concentration during an oral glucose tolerance test. Visceral fat area was significantly correlated with the severity of coronary stenosis index. Distal coronary lesions were significantly more frequent in the High VF group. Moreover, the correlation between the visceral fat area and coronary stenosis index was found to be independent of age, BMI, and subcutaneous fat area by multiple regression analysis. CONCLUSIONS: Visceral fat accumulation is a potent cardiovascular risk factor in heterozygous FH.

Abdomen↗

PubMed1997

Analysis of T cell receptor Vbeta usage in the autoimmune sialadenitis of non-obese diabetic (NOD) mice.

The NOD mouse develops spontaneous autoimmune sialadenitis besides a well characterized T cell-mediated autoimmune insulitis. We used reverse transcriptase-polymerase chain reaction (RT-PCR) to analyse the repertoire of T cell receptor (TCR) Vbeta chain genes expressed in the isolated infiltrating cells from affected salivary glands. Immunohistochemical analysis showed that the vast majority of inflammatory infiltrates in the salivary glands were CD4+ Vbeta8+ and CD4+ Vbeta6+ T cells, whereas CD8+ T cells and B220+ B cells were fewer in number. Predominant expression of the Vbeta8 and Vbeta6 gene segment was detected in the infiltrating cells in the salivary glands very early, and age-related diversity of TCR Vbeta gene usage was observed. Single-strand conformation polymorphism (SSCP) analysis demonstrated a strikingly symmetrical distribution of expanded clones in the PCR products of the Vbeta8 and Vbeta6 gene in the cells infiltrating the salivary glands. Nucleotide sequencing of amplified TCR Vbeta cDNA revealed that T cell clonotypes had a high incidence of identical clones, indicating that the immune response in NOD sialadenitis is driven by common stimuli. These findings suggest that in spontaneous autoimmune sialadenitis of NOD mice, there may be a restricted usage of TCR Vbeta elements in the early stage of the autoimmune lesion to recognize self-antigen in organ-specific autoimmune sialadenitis.

Amino Acid Sequence↗

PubMed1997

High incidence of autoimmune dacryoadenitis in male non-obese diabetic (NOD) mice depending on sex steroid.

The NOD mouse develops spontaneous autoimmune lesions in the lacrimal and salivary glands, besides a well characterized T cell-mediated autoimmune pancreatic beta cell lesion. We report unique pathological findings developed in the lacrimal glands as an autoimmune dacryoadenitis of NOD mice in contrast to those found in the salivary glands and pancreas. A high incidence of autoimmune lesions in the lacrimal glands was observed exclusively in male NOD mice at any age. Histology of autoimmune dacryoadenitis in male NOD mice showed severe destructive changes compared with those observed previously as an autoimmune lesion in the lacrimal glands. Castration in male NOD mice significantly decreased the incidence of autoimmune dacryoadenitis, and testosterone treatment with castration also increased the incidence of autoimmune lesions. Oestrogen treatment with castration did not increase the incidence, but tamoxifen treatment without castration significantly increased the incidence of autoimmune dacryoadenitis in NOD mice. In addition, we detected up-regulation of local cytokine genes (IL-1beta, tumour necrosis factor-alpha (TNF-alpha), IL-2, interferon-gamma (IFN-gamma), IL-6, IL-10, and IL-12 p40) during the course of autoimmune dacryoadenitis. These data suggest that in spontaneous autoimmune dacryoadenitis of male NOD mice there may be an intimate relationship with sex steroids, particularly testosterone, in the development and progression of autoimmune lesions, and autoreactive Th1 cells secrete up-regulated cytokine genes, including IL-10 and IL-12.

Animals↗

PubMed1997

Packed-bed type reactor to attain high density culture of hepatocytes for use as a bioartificial liver.

In an attempt to develop a bioartificial liver using cultured hepatocytes, we investigated the short-term and long-term viability and metabolic functions of hepatocytes cultured in a new type of packed-bed type reactor using reticulated polyvinyl formal (PVF) resin as a supporting material. Perfusion culture experiments using this reactor, as well as monolayer cultures using conventional collagen-coated Petri dishes as control experiments, were performed. It was found that the highest density of immobilized hepatocytes attained with PVF resin was on the order of 10(7) cells/cm3 PVF and that hepatocytes cultured in this type of module for up to a week showed a sufficient level of liver-specific metabolic functions, such as ammonium metabolism, urea-N synthesis, and albumin secretion, to be comparable to those in the monolayer culture. It is concluded that the packed-bed reactor system utilizing PVF resin is a promising means to develop a bioartificial organ using hepatocytes.

Alanine Transaminase↗

PubMed1997

A human monoclonal antibody which inhibits the coaggregation activity of Porphyromonas gingivalis.

A B-cell line producing a human monoclonal antibody (HuMAb) against a recombinant 40-kDa outer membrane protein (OMP) of Porphyromonas gingivalis was constructed by in vivo immunization of a severe combined immunodeficiency C.B.-17/Icr mouse, which had been injected with human peripheral blood lymphocytes, with recombinant 40-kDa OMP and subsequent Epstein-Barr virus immortalization of B cells isolated from the spleen of the mouse. This HuMAb inhibited coaggregation between P. gingivalis vesicles and Actinomyces naeslundii cells.

Animals↗

PubMed1997

Inactivation of human viruses by povidone-iodine in comparison with other antiseptics.

Inactivation of a range of viruses, such as adeno-, mumps, rota-, polio- (types 1 and 3), coxsackie-, rhino-, herpes simplex, rubella, measles, influenza and human immunodeficiency viruses, by povidone-iodine (PVP-I) and other commercially available antiseptics in Japan was studied in accordance with the standardized protocol in vitro. In these experiments, antiseptics such as PVP-I solution, PVP-I gargle, PVP-I cream, chlorhexidine gluconate, alkyldiaminoethyl-glycine hydrochloride, benzalkonium chloride (BAC) and benzethonium chloride (BEC) were used. PVP-I was effective against all the virus species tested. PVP-I drug products, which were examined in these experiments, inactivated all the viruses within a short period of time. Rubella, measles, mumps viruses and HIV were sensitive to all of the antiseptics, and rotavirus was inactivated by BAC and BEC, while adeno-, polio- and rhinoviruses did not respond to the other antiseptics. PVP-I had a wider virucidal spectrum, covering both enveloped and nonenveloped viruses, than the other commercially available antiseptics.

Adenoviridae↗

PubMed1997

[Telomere DNA and telomerase of lymphoma-derived cell lines--telomere hypothesis for cell growth control].

Telomere is the specialized structure of chromosome end. Telomeric DNA is essential for stabilization of linear double-stranded DNA molecules. Human telomeric DNA comprises the tandem repeat (AATGGG)n. Telomeres of normal somatic cells shorten progressively on every cell division, and telomere length is considered to determine cellular proliferative capacity. Most normal cells except germ line cells lack telomerase activity. Evidence of telomerase reactivation in human cancer cells was reported in 1994. The telomere hypothesis of aging and cell immortalization has drawn much attention in recent years. We examined telomere DNA and telomerase activity of Burkitt's lymphoma cell lines and EBV-infected proliferating B lymphocytes. All of these cells had varied average size of TRFs and the cell lines of lymphoma origin showed elevated telomerase activity.

Burkitt Lymphoma↗

PubMed1997

Investigation of Vicia graminea lectin- and Vicia unijuga lectin-binding glycoproteins as novel oncofetal antigens in cyst and ascitic fluids of human ovarian tumors in benign, dysplastic, and malignant stages.

Perchloric acid-soluble fractions (PASFs) were obtained from cyst fluids of human benign ovarian mucinous cystadenoma, benign dermoid cyst, "borderline" mucinous cystadenoma, and malignant ovarian clear cell carcinoma, and from fluids of malignant embryonal carcinoma and malignant serous cystadenocarcinoma. PASFs from benign lesions did not react with Arachis hypogaea lectin (PNA), Vicia graminea lectin (VGA), or Vicia unijuga lectin (VUA). PASFs from "borderline" lesions reacted with PNA but did not react with VGA and VUA. PASFs from malignant tumors reacted with PNA, VGA, and VUA. These PASFs did not react positively against anti-M or -N sera. These results show that VGA- and VUA-binding glycoprotein (Vgu glycoprotein) exist in PASFs from malignant ovarian tumors, and that PNA-binding glycoprotein was present in PASFs from malignant and "borderline" ovarian tumors. Furthermore, we found the existence of Vgu glycoprotein in PASFs from various human cancer cell lines; however, the antigens were not found in PASFs from benign human cell lines.

Antigens, Neoplasm↗

PubMed1996

Synergistic effect of aurintricarboxylic acid and triflavin in a photochemically induced thrombosis model in rats.

We report here the synergistic antithrombotic effect of aurintricarboxylic acid in combination with a snake venom-derived disintegrin, triflavin, in a photochemically induced thrombosis model in rats. The time to initiation of thrombus was prolonged by i.v. bolus injection of aurintricarboxylic acid at 10 mg/kg. In contrast, time to occlusion was dose-dependently prolonged by both agents, this prolongation being significant with aurintricarboxylic acid at 10 mg/kg i.v. and with triflavin at more than 3 mg/kg i.v. Interestingly, the combination of aurintricarboxylic acid at 3 mg/kg i.v. and triflavin at 1 mg/kg i.v. prolonged not only the initiation of thrombus, but also the time to occlusion.

Animals↗

PubMed1996

Effector mechanism of experimental autoimmune sialadenitis in the mouse model for primary Sjögren's syndrome.

We have recently established a new animal model for primary Sjögren's syndrome in NFS/sld mutant mice thymectomized 3 days after birth (3dTX) bearing an autosomal recessive gene with sublingual gland differentiation arrest. In this study, we analyze developing mechanisms of experimental autoimmune sialadenitis (EAS) in the mouse model, focusing on local expressions of cytokine and cell adhesion molecule genes by reverse transcriptase-polymeric chain reaction (RT-PCR) and immunohistochemistry, kinetic analysis of splenic lymphocytes expressing activation markers, and I-Aq class-II molecules by flow cytometry (FACS). We found up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-6, IL-10, IL-12p40) and cell adhesion molecule genes (ICAM-1, LFA-1, CD44, Mel-14) in the salivary glands from mice with EAS by RT-PCR, which were supported by immunohistochemistry. FACS analysis demonstrated that a significant proportion of splenic CD4+ T cells express activation markers (CD44, LFA-1, Mel-14low, CD45RB(low)) at a high level and an increase in expression of B220+ B cells bearing I-Aq class-II molecules. These data suggest that spontaneous EAS in 3dTX NFS/sld mutant mice may be triggered by an in situ activation of autoreactive CD4+ T cells comprising unique cytokine profile (high levels of IL-2, IFN-gamma, IL-10, and IL-12p40 mRNA) in the salivary glands.

Animals↗

PubMed1996

Mechanism of the development of autoimmune dacryodenitis in the mouse model for primary Sjögren's syndrome.

To elucidate the mechanism of development in autoimmune lacrimal gland disease, we analyzed different aspects of autoimmune dacryoadenitis in a newly established mouse model for primary Sjögren's syndrome, focusing on the local expressions of cytokine genes, and the repertoire of T cell receptor (TCR) V beta genes transcribed within the inflammatory infiltration in the lacrimal glands. We found that the vast majority of inflammatory infiltration into the lacrimal glands were CD4+ V beta 8+ T cells. We detected the up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-10, IL-12p40) in the lacrimal glands with very early inflammatory lesions by reverse transcriptase (RT)-PCR analysis. The predominant expression of the V beta 8 gene segment was detected from a very early stage, while extensive age-related diversity of TCR V beta gene usage was observed. Single-strand conformation polymorphism (SSCP) analysis demonstrated a distinct and a common binding pattern in the PCR product of the V beta 8 gene on the infiltrating cells during the course of the disease. These data suggest that in autoimmune dacryoadenitis of the mouse model for primary Sjögren's syndrome there may be a restricted usage of TCR V beta elements on a very early stage of the autoimmune lesion to recognize unknown self-antigen, and the autoreactive CD4+ T cells constitute a unique cytokine profile in the autoimmune lacrimal gland disease.

Animals↗

PubMed1996

In vivo role of IL-10 and IL-12 during development of Sjögren's syndrome in MRL/lpr mice.

Expression of local cytokine genes including interleukin 10 (IL-10) and IL-12 was analyzed in the salivary gland tissues of MRL/lpr mice with Sjögren's syndrome. We demonstrate a significant role of IL-10 and IL-12 in vivo during development of Sjögren's syndrome in MRL/lpr mice. IL-10 mRNA expression was detected before the onset of disease and was upregulated during the course of autoimmune sialadenitis by RT-PCR. A predominant level of expression of IL-12 mRNA was also detected earlier in the proinflammatory stage of autoimmune sialadenities. Moreover, MHC class II (I-Ak) mRNA was detected before the onset of inflammatory lesions until older ages in the salivary glands of MRL/lpr mice. These results suggest that endogenous IL-10 and IL-12 may play important roles on immune-mediated destruction of the salivary glands during development of organ-specific autoimmunity in MRL/lpr mice.

Animals↗

PubMed1996

Angiogenic vascular growth in the rat peritoneal disseminated tumor model.

The objective of this study was to provide the first quantitative measurements of the process of vascular growth in the rat peritoneal disseminated tumor model in both arteriolar and venular systems. Male Fischer 344 rats were injected intraperitoneally with 1 x 10(7) cells of colon carcinoma cell line (RCN-9). Three to eleven days after tumor cell inoculation, the rats were subjected to intravital microscopic observation of the mesenteric microcirculation. Accompanying tumor growth, mesenteric windows showed a marked neovascularization. The branching pattern of the vascular network was analyzed based on Horton's law of bifurcation. Arterioles and venules were given an order of branching separately according to the Strahler's nomenclature, and the number of vessel segments (N) having the same order number was counted. A vascular density index (VDI) and a bifurcation ratio (BR) were calculated from a semilogarithmic plot of the vessel density (dividing N by the vascularized area) against vessel order. Values of the VDI in venules (3.1 +/- 0.3 in the tumor-free rats, mean +/- SEM, n = 6) were found to be larger than those in arterioles (1.8 +/- 0.2). These values in both arterioles and venules showed a significant increase with time after the tumor cell inoculation (in venules, 12.3 +/- 1.1 at 9-11 days after the tumor cell inoculation; in arterioles, 5.7 +/- 0.7). Moreover, the rate of increase in the venular VDI was larger than that of the arteriolar VDI. The arteriolar BR remained almost constant (3.8 +/- 0.2 for the tumor-free rats and 4.1 +/- 0.1 for 9-11 days after tumor cell inoculation), whereas the venular BR showed an increase with time (3.0 +/- 0.1 and 3.8 +/- 0.2, respectively). In conclusion, a marked angiogenesis was observed in the mesentery of the rats bearing peritoneal tumors. Neovascularization was found to occur predominantly in the venular system.

Adenocarcinoma↗

PubMed1996

Functional expression of GABA rho 3 receptors in Xenopus oocytes.

Homomeric rat GABA rho 3 receptors were expressed in Xenopus oocytes, and their pharmacological profile was investigated electrophysiologically. GABA activated the rho 3 receptors with an EC50 value of 7.5 microM and a Hill coefficient of 1.6. The GABA-induced current was not antagonized by bicuculline (100 microM), but was blocked by picrotoxin (IC50: 0.68 microM for 100 microM GABA). The current was almost insensitive to pentobarbital, diazepam and a neurosteroid, 3 alpha-OH-DHP. Many of the pharmacological properties of the rho 3 subunit were similar to those of the previously reported rat rho 1 and rho 2 subunits and GABAC receptors.

Animals↗

PubMed1996

Long-term performance of albumin secretion of hepatocytes cultured in a packed-bed reactor utilizing porous resin.

A packed-bed reactor utilizing the porous polymer, polyvinyl formal (PVF) resin, as a supporting material was applied for the long-term culture of rat hepatocytes. Perfusion cultures using this reactor, as well as monolayer cultures, were performed for up to 1 week under 3 different media conditions. When serum-free or epidermal growth factor-containing medium was used, albumin secretion rates showed constant decreases in both the perfusion and the monolayer cultures, and approximately 10% of the activity exhibited on Day 1 was preserved at the end of the cultures. In contrast, the hepatocytes supplemented with serum-containing medium exhibited stable ability of albumin secretion throughout the culture period under the perfusion culture condition using PVF resin. From the microscopic observation, the immobilized hepatocytes in this medium revealed round shapes, and a cluster of cell aggregates was scarcely seen.

Albumins↗

PubMed1996

Immunopathological analysis of mucosal melanocyte distribution in the human lower lip of the elderly.

Mucosal melanocyte distribution in the human lower lip was analyzed immunopathologically using a wide selection of 195 surgical specimens. An age-related increase of mucosal melanocyte distribution was observed in the human lower lip by Fontana-Masson argentaffin stain and S-100 protein immunoreactivity. The mean number of mucosal melanocytes increased gradually with advancing age. A large number of them was found at or beyond the seventh decade of life in both sexes, which was statistically significant compared with those in all other decades (p < 0.01 or < 0.05). In addition, the sex difference in mucosal melanocyte density was statistically significant (p < 0.001) in each decade (men > women). These results suggest that physiological changes in mucosal melanocyte distribution are dependent upon aging and sex difference, and may play an important role in development of melanocytic lesions such as senile lentigo, pigmented nevi, and also intraepithelial malignant melanomas.

Adult↗

PubMed1996

Expression of HLA-DR and cytokine genes on interferon-gamma-stimulated human salivary gland cell line.

Stimulation of a cultured human salivary gland (HSG) cell line by interferon (IFN)-gamma leads to HLA-DR gene expression concomitant with inflammatory cytokine genes such as IL-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6 in vitro. IFN-gamma-induced HLA-DR mRNA expression was clearly detected at 2 h after the stimulation, and thereafter its level of gene expression increased until day 7 on HSG cells by reverse transcriptase (RT)-PCR. Immunofluorescence analysis revealed that cytoplasmic HLA-DR immunoreactivity was detected for the first time at 2 days after the stimulation, and its immunoreactivity increased gradually until day 7, while no immunoreactivity with HLA-DP and HLA-DQ was observed at any of the days. In addition, the expression of IL-1 beta, TNF-alpha, and IL-6 on the IFN-gamma-stimulated HSG cells was detected by immunohistochemistry and RT-PCR analysis. These results indicate that human salivary gland cells can be induced to express HLA-DR mRNA by IFN-gamma concomitant with inflammatory cytokine gene expressions such as IL-1 beta, TNF-alpha, and IL-6.

Cytokines↗

PubMed1996

Metabolism of tetramethrin isomers in rat. III. Stereochemistry of reduced metabolites.

1. Three main urinary metabolites, two isomers of 3-hydroxycyclohexane-1,2-dicarboximide (3-OH-HPI-1 and 2) and 1,2-tetrahydrodicarboxylic acid (TCDA) were purified from rat treated with (1RS, trans)-tetramethrin [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate]. 2. To elucidate the mechanism of formation of these reduced metabolites, the stereochemistry of 3-OH-HPI-1, 3-OH-HPI-2 and TCDA was clarified by chemical reactions, spectroanalysis (nmr) and X-ray analysis. 3. The sole difference in configuration between 3-OH-HPI-1 and 3-OH-HPI-2 was found to be the orientation of the hydroxyl group to the cyclohexane ring, and both of these reduced metabolites showed cis-addition of two hydrogens. In contrast, reduction resulted in the trans form with TCDA. 4. These findings indicate the existence of two different reduction reaction mechanisms in the rat.

Animals↗