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Biomedical subjects

T Higashi

Publications and source records attributed to T Higashi.

At least 145 records · Page 8Linked to original sources
PubMed1997

Effects of mineral fibers on the expression of genes whose product may play a role in fiber pathogenesis.

To determine which factors are useful for the risk assessment of man-made fibers, we examined the gene expression of proinflammatory cytokines, growth factors, manganese superoxide dismutase (MnSOD), and inducible nitric oxide synthase (iNOS) in mineral fiber-exposed rats by means of reverse transcription-polymerase chain reaction (RT-PCR). Male Wistar rats received a single intratracheal instillation of either saline (control) or two types of fibers (2 mg of Union Internationale Centre le Cancer (UICC) chrysotile or alumina silicate refractory ceramic fiber [RCF]). Expression of interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), platelet-deriving growth factor-A, (PDGF-A), platelet-deriving growth factor-B (PDGF-B), transforming growth factor beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), MnSOD, and iNOS mRNA from lung and lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM) were assessed by RT-PCR. Among these factors, IL-1 alpha, TNF-alpha, IL-6, bFGF, and iNOS would be the possible parameters for the risk assessment of fibers. In a follow-up study, we investigated the time course (3 days, 1 week, 1 month, and 3 months) of expression of IL-1 alpha and TNF-alpha by LPS-stimulated AM exposed to mineral fibers in vivo. Male Wistar rats were instilled intratracheally with saline or fibers (2 mg of Union Internationale Contre le Cancer UICC crocidolite or potassium octatitanate whisker [TW]). The expression of IL-1 alpha mRNA by fibers was greatest in TW, crocidolite, chrysotile, and RCF-instilled rat AM, in that order. The increase of IL-1 alpha and TNF-alpha mRNA in AM peaked at 1 month and 3 days after exposure to crocidolite or TW, respectively. The expression of IL-1 alpha by fibers (crocidolite, chrysotile, TW, and RCF) may be a good indicator of the pathologic potential of fibers.

Administration, Inhalation↗
PubMed1997

Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and cigarette smoke in vivo.

To determine the effect of mineral fibers and cigarette smoke on remodeling of lung tissues, we examined matrix metalloproteinase-1 (MMP-1), MMP-2, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-2, and types I and IV collagen mRNA levels from rat lungs exposed to mineral fibers and/or cigarette smoke in vivo. Male Wistar rats (10 weeks of age) were given a single intratracheal instillation of 2 mg of chrysotile or alumina silicate ceramic fibers (RCF). Animals were then exposed to cigarette smoke (side stream) 5 days per week for 4 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Exposure to cigarette smoke induced increases in MMP-1 and TIMP-1 mRNA levels and decreased TIMP-2 and type I collagen mRNA levels in lung. Chrysotile or RCF stimulated the expression of MMP-1 mRNA in the lung. The mineral fibers and cigarette smoke had more than additive effects on the expression of MMP-2 and TIMP-1 in the lung. These data suggest that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix may be associated with the remodeling of lung tissues induced by mineral fibers and/or cigarette smoke.

Administration, Inhalation↗
PubMed1997

The receptor for advanced glycation end products mediates the chemotaxis of rabbit smooth muscle cells.

Long-term incubation of proteins with glucose leads to advanced glycation end products (AGEs) with fluorescence and a brown color. We recently demonstrated immunologically the intracellular AGE accumulation in smooth muscle cell (SMC)-derived foam cells in advanced atherosclerotic lesions. To understand the mechanism of AGE accumulation in these foam cells, we have now characterized the interaction of AGE proteins with rabbit-cultured arterial SMCs. In experiments at 4 degrees C, 125I-labeled AGE-bovine serum albumin (AGE-BSA) showed a dose-dependent saturable binding to SMCs with an apparent dissociation constant (Kd) of 4.0 microg/ml. In experiments at 37 degrees C, AGE-BSA underwent receptor-mediated endocytosis and subsequent lysosomal degradation. The endocytic uptake of 125I-AGE-BSA was effectively inhibited by unlabeled AGE proteins such as AGE-BSA and AGE-hemoglobin, but not by acetylated LDL and oxidized LDL, well-known ligands for the macrophage scavenger receptor (MSR). Moreover, the binding of 125I-AGE-BSA to SMCs was affected neither by amphoterin, a ligand for one type of the AGE receptor, named RAGE, nor by 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole-hexanoic acid-BSA, a ligand for the other AGE receptors, p60 and p90. This indicates that the endocytic uptake of AGE proteins by SMCs is mediated by an AGE receptor distinct from MSR, RAGE, p60, and p90. To examine the functional role of this AGE receptor, the migratory effects of AGE-BSA on these SMCs were tested. Incubation with 1-50 microg/ml of AGE-BSA for 14 h resulted in significant dose-dependent cell migration. The AGE-BSA-induced SMC migration was chemotactic in nature and was significantly inhibited (approximately 80%) by an antibody against transforming growth factor-beta (TGF-beta), and the amount of TGF-beta secreted into the culture medium from SMC by AGE-BSA was sevenfold higher than that of control, indicating that TGF-beta is involved in the AGE-induced SMC chemotaxis. These data suggest that AGE may play a role in SMC migration in advanced atherosclerotic lesions.

Animals↗
PubMed1997

Shear bond strengths of a single-step bonding system to enamel and dentin.

An experimental primer was developed as a single-step bonding system for resin-modified glass ionomer cements (GIC). Efficacy of this primer on adhesion of resin-modified GICs and resin composite to enamel and dentin was evaluated by shear bond test and SEM observation. Good bond strengths to enamel were obtained (> 11 MPa), whereas significantly low bond strengths to dentin were obtained using a single coat of the primer. However, double-coating improved the bond strengths to dentin (> 8 MPa). SEM observations indicated that the primer functioned as a mild conditioner to remove the smear layer on enamel or dentin surfaces. A hybrid layer was observed at the cross-sectional view of the GIC/dentin interface. These findings suggested that good adhesion to enamel and dentin could be achieved using a single-step bonding system.

Bisphenol A-Glycidyl Methacrylate↗
PubMed1997

The multiple roles of macrophage scavenger receptors (MSR) in vivo: resistance to atherosclerosis and susceptibility to infection in MSR knockout mice.

Both type I and type II MSRs are integral membrane proteins containing a collagenous domain and elicit an extraordinarily wide range of ligand binding capability. They were found during the search for the molecule(s) responsible for the accumulation of modified LDL during atherogenesis. However, all prior the evidence relating to their physiological and pathophysiological roles in vivo had been indirect. Targeted disruption of the MSR gene results in a reduction in the size of atherosclerotic lesions in an apo E deficient animal. Macrophages from MSR deficient mice exhibit a marked decrease in modified LDL uptake in vitro, whereas modified LDL clearance from plasma remains normal, suggesting that there are alternative mechanisms for the uptake of modified LDL from the circulation. In addition, MSR knockout mice are more susceptible to L. monocytogenes and HSV-1 infection, indicating a role for MSR in host defense against various pathogens.

Animals↗
PubMed1997

[Combined superior-transseptal approach to left atrial myxoma].

A 60-year-old woman was referred to our hospital for treatment of an intracardiac tumor Echocardiography revealed a 47 x 30 mm tumor in the left atrium which had a short stalk attached to the atrial septum. At operation, a large left atrial myxoma was extirpated using a combine superior transseptal approach. Through this incision, exposure of the left atrial myxoma and it stalk was excellent and removal of the myxoma was easily performed with minimal minpulation. Postoperative arrhythmias related to the operative procedures were not observed. The patient recovered uneventfully. The operative technique and indications of the combined superior transseptal approach to the left atrium are discussed in this paper.

Cardiac Surgical Procedures↗
PubMed1997

[Elevation of serum creatine kinase in the patients with Kanemi Yusho].

18.9% of the patients with Kanemi Yusho showed an elevation of serum creatine kinase, however, the cause is still unknown. The relation between exercise, dehydration, thyroid hormone and concentration of PCB was studied. Dehydration, hyperexercise and PCB affected the elevation of creatine kinase. No relation between PCB and thyroid hormone or creatine kinase and thyroid hormone was observed. PCB may change the permeability of muscle plasma membrane.

Creatine Kinase↗
PubMed1997

[Basic and clinical studies of oral barium sulfate preparations for CT].

In CT examination of the abdomen and pelvis, oral iodinated contrast agents and oral barium sulfate preparations are now being used to improve diagnostic accuracy, and studies have been carried out on their clinical usefulness. Although helical CT has come into wide spread use recently, most studies have used the ordinary type of CT. There have been no reports on studies using barium sulfate preparations with helical CT. We, therefore, prepared several barium sulfate preparations with different concentrations and particle diameters, and conducted a basic study to determine the optimal conditions for helical CT. In addition, we conducted a similar study using the ordinary imaging method for comparison with helical CT. Based on the results of these studies, we conducted a clinical study with several volunteers to find the most suitable barium sulfate preparation. Our basic study compared Baritop CT and Gastrografin, and a concentration of 1.5%-2.0% was found suitable. In our examination of particle size using animal intestines, fine particles were found to be most appropriate. Although little difference was observed between the helical procedure and the ordinary imaging procedure, the possible development of artifacts specific to the helical procedure was suggested. In the clinical study, the 2.0% preparation tended to show better contrast and a better filling rate for the upper abdominal organs than the 1.5% preparation. However, little difference in artifacts was found between them. The artifacts tended to be intensified when barium migrated toward the distal portion of the small intestine. Judging from these results, a 2.0% fine particle preparation appeared to be suitable for examination of the upper abdominal organs. For organs in the pelvic region, preparations with a lower concentration were considered suitable.

Administration, Oral↗
PubMed1997

Expression of glucose transporters in human pancreatic tumors compared with increased FDG accumulation in PET study.

UNLABELLED: Although overexpression of GLUT-1 glucose transporter has already been reported in human cancers, the mechanism of glucose entry into pancreatic cancers remains unknown. To evaluate the relationship between GLUT glucose transporters and FDG uptake, FDG-PET was performed in 34 preoperative patients (mean age, 60.9 yr) with suspected pancreatic tumors, including 28 malignant and 6 benign tumors. METHODS: FDG uptake at 50 min after injection of 185 MBq of [18F]FDG with >5 hr of fasting was semiquantitatively analyzed as standardized uptake values (SUVs). The GLUT expression was studied by immunohistochemistry of paraffin sections from these tumors after operation using anti-GLUT-1, -2, -3, -4 and -5 antibodies to obtain immunohistochemical grading ("strong," "weak" and "negative") by three experienced physicians. RESULTS: Of 26 malignant tumors proved by histological examination, 23 (88%) tumors were positive for the expression of GLUT-1 glucose transporter, and 17 (61%) showed strong expression. On the other hand, 13 (46%), 0 (0%), 9 (36%) and 13 (46%) malignant tumors were positive for the expression of GLUT-2, -3, -4 and -5 glucose transporters, respectively. Three of six benign tumors showed strong GLUT-1 expression. Concerning GLUT-2, -3, -4 and -5, only one benign tumor showed positive GLUT-5 expression. Thus, GLUT-1 showed relatively high sensitivity but low specificity (50%) for detecting malignant tumors, whereas GLUT-2, -3, -4 and -5 had lower sensitivities but higher specificities. Correlations between SUVs and grading of GLUT immunoreactivity were significant in GLUT-1 (strong, 4.49 +/- 2.95; weak, 3.42 +/- 1.21; negative, 2.52 +/- 0.84) (p < 0.05) but not in the remaining four GLUT transporters. CONCLUSION: These data indicate that GLUT-1 has a significant role in the malignant glucose metabolism and may contribute to the increased uptake of FDG in PET imaging in patients with pancreatic tumor.

Adult↗
PubMed1997

[Application of Internet technology in public health].

Recent advances in telecommunication technology have been enormous. Application of this technology in public health has the potential to markedly improve global health through better surveillance and information systems. With this assumption the GHNet was established in 1994 by representatives from academia, WHO, Pan American Health Organization, the World Bank, NASA, IBM, and AT & T. The GHNet consists of seven components: 1) promotion of networking with the Internet among people in public health; 2) disease tele-monitoring; 3) distance learning system with the internet; 4) connection of non-governmental health organizations; 5) training cyberdocs who are educated in both public health and telecommunications; 6) establishment of an electronic scientific research server; and 7) a home page on the World Wide Web (WWW). In order to effectively incorporate the Internet into the field, connectivity and knowing how to use it are of critical concern. More and more facilities are connected to the Internet in Japan. However, few courses teaching how to utilize the Internet are provided for people in this field. An Internet training course for people in public health was held as joint venture of the World Health Organization (WHO) and the Global Health Network (GHNet) on October 31, 1996, at the 55th Annual Meeting of Japanese Society of Public Health. Most of the participants for the course were from local public health departments and very few had previous experience with the Internet before the course. During this course participants learned how to use e-mail, how to find health resources on the WWW, how to construct a home page, and how the Internet could be utilized to improve public health, with their computers actually hooked to the Internet. From this experience, we found that this kind of course is feasible and beneficial and hope that this course would serve as a model for training people in public health.

Computer Communication Networks↗
PubMed1996

Reperfusion causes significant activation of heat shock transcription factor 1 in ischemic rat heart.

BACKGROUND: The myocardial protective role of heat shock protein (HSP) has been demonstrated, and there has been increasing interest in stress response in the heart. We examined the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during heat shock or ischemia/reperfusion in isolated rat heart. METHODS AND RESULTS: Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element, which is present upstream of all heat shock genes. Induction of mRNAs for HSP70, HSP90, and GRP78 (glucose-regulated protein) was examined by Northern blot analysis. Although the activation of HSF during global ischemia was weak and rapidly attenuated, postischemic reperfusion induced a significant activation of HSF. In addition, although HSP70 mRNA was hardly induced during ischemia, its burst induction was detected during postischemic reperfusion. Supershift assays using specific antisera for HSF1 and HSF2 revealed that ischemia/reperfusion as well as heat shock induced the activation of HSF1 in hearts. Although the expression of HSP70 mRNA during heat shock was more vigorous than the expression during ischemia/reperfusion, the induction of HSP90 mRNA in postischemic reperfusion was significantly greater than that in heat shock. CONCLUSIONS: Our findings demonstrated that reperfusion causes a significant activation of HSF1 in ischemia-reperfused heart. The striking contrast between the induction of HSP70 mRNA and that of HSP90 mRNA suggests the presence of regulatory mechanisms other than HSF.

Animals↗
PubMed1996

Lipoprotein(a) induces cell growth in rat peritoneal macrophages through inhibition of transforming growth factor-beta activation.

To elucidate the atherogenicity of lipoprotein(a) (Lp(a)), we examined its growth-stimulating activity in rat resident peritoneal macrophages. When macrophages were incubated with Lp(a), cell numbers were increased 1.5-fold as compared with control macrophages. Furthermore, apolipoprotein(a) (apo(a)), a plasminogen-like glycoprotein which is covalently attached to a low density lipoprotein-like particle (Lp(a)), also induced macrophage growth, while the growth-stimulating effect of Lp(a-) was negligible. These results suggest that apo(a) plays an active role in the mitogenic activity of Lp(a). Lp(a)-induced macrophage growth was inhibited by exogenously added active transforming growth factor-beta (TGF-beta) dose-dependently, and also by the addition of plasmin, which converts latent TGF-beta to an active form. Moreover, the amounts of endogenous active TGF-beta in the medium were significantly reduced by the incubation with Lp(a). It is evident from these results that Lp(a) induces macrophage growth by inhibiting TGF-beta activation. The capacity of Lp(a) to stimulate macrophage growth shown here could be novel atherogenic function of Lp(a).

Animals↗
PubMed1996

Telomerase as a tool for the differential diagnosis of human hepatocellular carcinoma.

BACKGROUND: Telomerase activation is thought to be essential for the immortality of cancer cells. We measured telomerase activity in human liver samples, including hepatocellular carcinoma (HCC), and evaluated this assay as a tool for the diagnosis of HCC using 21-gauge (21-G)-needle biopsy specimens. METHODS: Ninety-four liver samples (27 HCC, 27 liver cirrhosis, 37 chronic hepatitis, and 3 normal liver) that were surgically resected or biopsied with a 12-gauge Silverman needle and 13 HCC samples that were biopsied with a 21-G needle were analyzed for telomerase activation. RESULTS: Eleven of 29 (38%) tumor-bearing liver samples were weakly telomerase-positive, whereas telomerase activity was observed infrequently in nontumor-bearing liver samples (6 of 35; 17%) and in normal liver samples (0 of 3; 0%). The positivity of surgical samples for well differentiated, moderately differentiated, and poorly differentiated HCC was 88% (7 of 8), 87% (13 of 15), and 0% (0 of 2), respectively. In telomerase-positive HCC, 43% (3 of 7) of well differentiated samples were weakly positive, whereas 92% (12 of 13) of moderately differentiated samples were strongly positive. The difference in the tumor sizes and viral marker status did not affect the activity. The telomerase activity of the 21-G-needle biopsied specimens showed no significant difference from that of the surgical samples. The positive incidence of 21-G specimens was 80% (8 of 10) and 100% (2 of 2) in well differentiated HCC and moderately differentiated HCC, respectively. CONCLUSIONS: An incremental positivity of telomerase was observed during hepatocarcinogenesis. The use of this assay in 21-G-needle biopsy specimens may be useful in clinical examination.

Adolescent↗
PubMed1996

N (epsilon)-(carboxymethyl)lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction.

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological studies have suggested the potential role of AGE in atherosclerosis, aging, and diabetic complications. We previously prepared a monoclonal (6D12) as well as a polyclonal anti-AGE antibody and proposed the presence of a common AGE structure(s) that may act as a major immunochemical epitope [Horiuchi, S., Araki, N., & Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332]. The purpose of the present study was to determine the major epitope. Amino acid analysis of AGE-proteins indicated that N(epsilon)-(carboxymethyl)lysine (CML) was a major modified lysine residue. Immunologic studies demonstrated the positive reaction of 6D12 not only to all CML-modified proteins tested, but also to BSA modified with several aldehydes known to generate a CML-protein adduct, and a linear correlation between the CML contents of CML-BSA and their immunoreactivity to 6D12 up to approximately 8 mol/mol of protein. Further experiments with CML analogs revealed that the epitope of 6D12 is a CML-protein adduct with an important carbonyl group. In contrast to 6D12, our polyclonal anti-AGE antibody showed a significant but much weaker immunoreactivity to CML-BSA, suggesting that the polyclonal antibody contains two populations, one reactive to CML (CML-PA) and the other unreactive to CML (Non-CML-PA). Non-CML-PA separated from CML-PA by CML-BSA affinity chromatography did not react with all CML-modified preparations, but retained its property to react commonly with AGE preparations obtained from proteins, lysine derivatives, and monoaminocarboxylic acids. Therefore, it is clear that a CML-protein adduct is a major immunological epitope in AGE structures, but there still exist other major epitope(s) expressed commonly in AGE-proteins.

Animals↗
PubMed1996

Evident difference in the excitability of the motoneuron pool between normal subjects and patients with spasticity assessed by a new method using H-reflex and M-response.

The excitability of the motoneuron (MN) pool in the resting state was compared between normal control subjects and patients with spasticity resulting from HTLV-I-associated myelopathy, using a new parameter, Hslp/Mslp, and the conventional parameters Hmax/Mmax and Hth/Mth. Differences in the excitability of the MN pool between these two groups reached a high degree of statistical significance only when assessed with the new parameter. This suggests the methodological advantage of the Hslp/Mslp over both Hmax/Mmax and Hth/Mth for evaluation of the excitability of the MN pool in the resting state.

Action Potentials↗
PubMed1996

Orientation of glutaraldehyde-fixed erythrocytes in strong static magnetic fields.

In a uniform static magnetic field up to 8 Telsa, glutaraldehyde-fixed erythrocytes showed an orientation in which their disk plane was perpendicular to the magnetic field. The paramagnetism of membrane-bound hemoglobin was through to contribute significantly to this orientation. The observation of magnetic orientation is directed toward understanding the fundamental microstructural aspects of the erythrocyte.

Cell Polarity↗
PubMed1996

General pattern of lymph node metastasis in early gastric carcinoma.

A reliable method for recognizing lymph node metastasis is indispensable for the attending physician to recommend less extensive treatment for early gastric carcinoma. Here we review 1137 consecutive patients with a single primary lesion, and the incidence and distribution of nodal involvement were investigated for correlations with pathologic findings. The overall incidence of metastasis was 9.5%: 2.6% for mucosal and 16.5% for submucosal carcinomas, a significant difference. The occurrence of metastasis was highest for lesions of the macroscopically mixed type, microscopically diffuse type, and large size. The involved nodes were most frequently found in the perigastric nodes along the lesser and greater curvatures, and it was well correlated with the tumor location, macroscopically depressed/mixed type, cancer depth, and histology. The diffuse-type carcinomas were most likely to metastasize to distant nodes. The distribution of involved nodes for early gastric carcinoma was similar to that for advanced carcinoma, as previously been reported. The submucosal carcinomas in this series had no indications for less extensive treatment, such as endoscopic or laparoscopic limited surgery. These carcinomas should be subject to standard surgery with gastrectomy and combined dissection of lymph nodes, especially node stations 1 and 3 to 8. The mucosal carcinomas sometimes involved the perigastric nodes, and such cases underwent gastrectomy and lymphadenectomy of node stations 1 and 3 to 7. Mucosal carcinomas 10 mm or less in size were negative for lymph node metastasis and were considered appropriate for less extensive treatment.

Carcinoma↗