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Biomedical subjects

S Hayashi

Publications and source records attributed to S Hayashi.

At least 289 records · Page 16Linked to original sources
PubMed1999

Intercellular signaling initiated by nitric oxide produced in heat-shocked human glioblastoma cells.

The accumulation of inducible nitric oxide synthase was caused by heat shock of human glioblastoma T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells cocultivated with heat-shocked T98G cells, which was suppressed by the addition of aminoguanidine to the medium. The accumulation of these proteins was observed in A-172 cells after exposure to the conditioned medium of heat-shocked T98G cells, which was completely blocked by the addition of 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide to the medium. In addition, the accumulation of these proteins in A-172 cells was induced by the administration of S-nitroso-N-acetylpenicillamine to the medium. Finally, the thermosensitivity of A-172 cells was reduced in the conditioned medium of heat-shocked T98G cells compared with conventional fresh growth medium. Our findings demonstrate that the accumulation of stress-induced proteins and thermoresistance in NO recipient cells cocultivated with heat-shocked NO donor cells is induced through an intercellular signal transduction pathway initiated by NO without cell-to-cell interactions such as gap junctions.

Brain Neoplasms↗
PubMed1999

Mast cell degranulation in rat mesenteric venule: effects of L-NAME, methylene blue and ketotifen.

Mast cells are present in proximity to the microvessels, and on stimulation with inhibition of NO synthesis, are a rich source of numerous inflammatory mediators. A microcirculatory study was undertaken to clarify whether nitric oxide (NO) and activation of guanylate cyclase is involved in degranulation of perivascular mast cells in the rat mesenteric venule, and whether oral administration of ketotifen suppress the degranulation. Intravital microscopy was used to monitor the rates of adherence and extravasation of leukocytes in single unbranched venules with diameters between 25 and 35 microm of rat mesentery. Leukocyte rolling velocity, red blood cell velocity, vessel diameter and blood pressure were also measured. Mast cell degranulation was quantified within 30 microm from the venule. NG-nitro-L-arginine methyl ester (L-NAME) at an intravenous dose of 30 mg kg-1 increased the number of degranulated cells, while its enantiomer, D-NAME at the same dose had no effect. Superfusion with methylene blue (MB), an inhibitor of soluble guanylate cyclase, at 50 microm elicited similar degranulation of the mast cells. The degranulation was associated with increased adhesion of leukocytes to the endothelium and the slowed rolling. Pretreatment with ketotifen at an oral dose of 1 mg kg-1 inhibited mast cell degranulation in responses to either L-NAME or MB. It is conceivable that guanylate cyclase for NO production pathway in endothelial and/or mast cells is involved in the mast cell degranulation process, and the process or subsequent action of NO may be preserved by ketotifen, eliciting down-modulation of mast cell activation.

Animals↗
PubMed1999

Improvement of eosinophilic heart disease after steroid therapy: successful demonstration by endomyocardial biopsied specimens.

A 62-year-old man with acute eosinophilic endomyocarditis developed congestive heart failure. The biopsy specimens revealed degranulated eosinophils and eosinophil cationic protein (ECP) in the endocardium, and in activated eosinophils and the myocardial interstitium. On electronmicroscopy, a characteristic cardiac myocytolytic change showing disruption at the intercellular junctional site was observed. After steroid treatment, clinical symptoms, systolic dysfunction and laboratory data dramatically improved. In the subsequent biopsy specimens, eosinophilic infiltration and ECP disappeared. Steroid therapy provided a beneficial effect in preventing the progression of cardiac damage. This effect was clearly documented by histochemical studies of the serial endomyocardial biopsy samples.

Biopsy↗
PubMed1999

Surgical strategy for abdominal aortic aneurysm with concurrent symptomatic malignancy.

In an attempt to improve the guidelines for concurrent management of concomitant abdominal aortic aneurysm (AAA) and symptomatic malignancy, a retrospective study was undertaken. A total of 186 AAA repairs were performed electively, and 25 patients (13.4%) had concurrent symptomatic malignancy from April 1986 to March 1997. Fourteen patients underwent a one-stage operation, including five abdominoperineal rectal resections, four subtotal gastrectomies, three total gastrectomies, and two right hemicolectomies. Eleven others underwent a two-stage operation, including four with total gastrectomy and left hemicolectomy followed by AAA repair, as well as two with right hemicolectomy and one with left hemicolectomy prior to AAA repair. There were no operative deaths or severe postoperative complications. Of the 25 patients, 22 (88.0%) are still alive during follow-up ranging from 8 months to 11 years. Our surgical approach to both lesions is as follows: (1) Using the transperitoneal approach alone, subtotal gastrectomy and abdominoperineal rectal resection can be safely done simultaneously. (2) Although total gastrectomy can also be performed concurrently, the approach used for each lesion is separate. (3) Colorectal resection is generally done separately. However, a one-stage operation can be performed using the thromboexclusion procedure for AAA repair in patients with right-sided colonic cancer or a temporary transverse colostomy for left-sided colorectal cancer.

Aged↗
PubMed1999

Spontaneously hyperlipidemic (SHL) mice: Japanese wild mice with apolipoprotein E deficiency.

During inbreeding of Japanese wild mice (Mus musculus molossinus), we established a strain of mice with severe cutaneous xanthomatous lesions. Since those mice showed high plasma cholesterol values, we named them spontaneously hyperlipidemic (SHL) mice; total cholesterol values of these mice (even when fed on conventional low-fat diet) are unusually high throughout the life span. The xanthomatous lesions appear in palms and distal extremities of forelimbs as early as 4 weeks after birth, and continue to expand to chest, abdomen, and face until the mice die before 14 months of age. Histological examination of these lesions revealed cholesterol crystal deposits, an infiltration of foam cells or macrophages, while that of the vascular system revealed atherosclerosis in the aortic sinus. Immunoblot and Northern blot analyses failed to detect apolipoprotein E (APOE) expression in these animals. Consistent with these findings, Southern blot analysis found disruption of the Apoe gene in SHL mice. Phenotypes of SHL mice, however, were distinct from those of Apoetm1Unc (hereafter Apoe-/-) mice, whose Apoe gene was disrupted by homologous recombination; hypercholesterolemia and xanthoma were more severe in SHL mice than in Apoe-/- mice, while atherosclerosis was milder in SHL mice. These distinctions suggest that there are modifier genes for the phenotypes. Alternatively, other gene(s), besides the Apoe gene, may be mutated in SHL mice. In either case, comparative genetic and molecular dissection of SHL mice will provide a good opportunity to understand the genetic basis for hyperlipidemia and atherosclerosis.

Animals↗
PubMed1999

Snail-type zinc finger proteins prevent neurogenesis in Scutoid and transgenic animals of Drosophila.

Scutoid is a classical dominant gain-of-function mutation of Drosophila, causing a loss of bristles and roughening of the compound eye. Previous genetic and molecular analyses have shown that Scutoid is associated with a chromosomal transposition resulting in a fusion of no-oceli and snail genes. How this gene fusion event leads to the defects in neurogenesis was not known until now. Here have found that snail is ectopically expressed in the eye-antennal and wing imaginal discs in Scutoid larvae, and that this expression is reduced in Scutoid revertants. We have also shown that the expressivity of Scutoid is enhanced by zeste mutations. snail and escargot encode evolutionarily conserved zinc-finger proteins involved in the development of mesoderm and limbs. Snail and Escargot proteins share a common target DNA sequence with the basic helix-loop-helix (bHLH) type proneural gene products. When expressed in the developing external sense organ precursors of the thorax and the eye, these proteins cause a loss of mechanosensory bristles in the thorax and perturbed the development of the compound eye. Such phenotypes resemble those associated with Scutoid. Furthermore, the effect of ectopic Escargot on bristle development is antagonized by coexpression of the bHLH gene asense. Thus, our results suggest that the Scutoid phenotype is due to an ectopic snail expression under the control of no-oceli enhancer, antagonizing neurogenesis through its inhibitory interaction with bHLH proteins.

Animals↗
PubMed1999

Deficiency of SHP-1 protein-tyrosine phosphatase activity results in heightened osteoclast function and decreased bone density.

Mice homozygous for the motheaten (Hcphme) or viable motheaten (Hcphme-v) mutations are deficient in functional SHP-1 protein-tyrosine phosphatase and show severe defects in hematopoiesis. Comparison of femurs from mev/mev mice revealed significant decreases in bone mineral density (0.33 +/- 0.03 mg/mm3 for mev/mevversus 0.41 +/- 0.01 mg/mm3 for controls) and mineral content (1.97 +/- 0.36 mg for mev/mevversus 10.64 +/- 0.67 for controls) compared with littermate controls. Viable motheaten mice also showed reduced amounts of trabecular bone and decreased cortical thickness. These bone abnormalities were associated with a 14% increase in numbers of multinucleated osteoclasts and an increase in osteoclast resorption activity. In co-cultures of normal osteoblasts with mutant or control bone marrow cells, numbers of osteoclasts developing from mutant mice were increased compared with littermate control mice. Although mev/mev osteoclasts develop in the absence of colony-stimulating factor (CSF)-1, nevertheless cultured osteoclasts show increased size in the presence of CSF-1. CSF-1-deficient osteopetrosis (op/op) mutant mice develop severe osteosclerosis. However, doubly homozygous mev/mevop/op mice show an expansion of bone marrow cavities and reduced trabecular bone mass compared with op/op mice. Western blot analysis showed that several proteins that were markedly hyperphosphorylated on tyrosine residues were detected in the motheaten osteoclasts, including a novel 126-kd phosphotyrosine protein. The marked hyperphosphorylation of a 126-kd protein in motheaten osteoclasts suggests that this protein depends on SHP-1 for dephosphorylation. These findings demonstrate that the decreased SHP-1 catalytic activity in me/me and mev/mev mice results in an increased population of activated osteoclasts and consequent reduction in bone density.

Animals↗
PubMed1999

Gastric ulcers in SCID mice induced by Helicobacter pylori infection after transplanting lymphocytes from patients with gastric lymphoma.

BACKGROUND & AIMS: Several studies have indicated that host factors are important in Helicobacter pylori-induced gastroduodenal diseases. We examined the pathological role of host immune responses in H. pylori infection by reconstituting components of the human immune system into severe combined immunodeficient (SCID) mice by transplantation of peripheral blood mononuclear cells (PBMCs) from H. pylori-infected patients. METHODS: PBMCs obtained from patients with mucosa-associated lymphoid tissue (MALT) lymphoma were injected intraperitoneally into SCID mice, designated MALToma-hu-SCID mice. One month after transplantation, H. pylori was administered orally to the mice. The mice were killed and examined for pathological changes and immunologic features. RESULTS: Human lymphocytes were detected in hu-SCID mice, and T- and B-cell functions were preserved for 1 month. Administration of H. pylori led to gastric ulcers with bleeding in the MALToma-hu-SCID mice. The gastric mucosa of control mice injected with Escherichia coli or transplanted with PBMCs from patients with peptic ulcers or gastritis or from healthy volunteers showed no pathological changes. CONCLUSIONS: Host immune responses against H. pylori appear to be involved in the development of gastric ulcers in patients who have MALT lymphoma.

Animals↗
PubMed1999

Eye-head coordination abnormalities and regional cerebral blood flow in Alzheimer's disease.

1. Three patients with Alzheimer's disease (AD) and three healthy controls (HC) were examined for eye-head coordination. Regional cerebral blood flow (rCBF) was measured in AD patients. 2. Eye-head coordination was analyzed using a Vision analyzer, and magnetic sensors. The authors measured the rCBF with 123I-IMP, and 99mTc-ECD SPECT. 3. AD reduced gaze accuracy and head movements, and prolonged the latency of saccade as compared to HC. AD patients had a tendency to focus on the target by using eye movements only. 4. AD reduced the rCBF in the inferior parietal part and the visual area, relative to the motor area. Damage of these areas may have caused the eye-head coordination disorders in the AD patients.

Adult↗
PubMed1999

Celiomesenteric anomaly with concurrent aneurysm.

We describe a rare case of a celiomesenteric anomaly with concurrent aneurysm. The patient, a 53-year-old man, had no abdominal pain or discomfort. The presence of a celiac artery aneurysm was suspected on the basis of the results of abdominal computerized tomographic scanning and echo ultrasound scanning performed because of proteinuria. Intra-arterial digital subtraction angiographic results showed the anomaly and aneurysm. Because of the risk of rupture of the aneurysm, the lesion was repaired surgically, with the placement of an interpositional prosthetic graft. We found no previous reports of celiomesenteric anomaly with concurrent aneurysm repaired with prosthetic graft.

Aneurysm↗
PubMed1999

Purification of nuclear DNA from single hair shafts for DNA analysis in forensic sciences.

The typing of nuclear DNA from hair shafts has often been unsuccessful to date. We tried to type one of the nuclear DNA loci, HLA-DQA1, from hair shafts, using an efficient cetyl-trimethyl ammonium bromide (CTAB) precipitation for DNA purification and a sensitive semi-nested PCR. After thorough washing with ethanol and water, hair shafts were digested by proteinase K in the presence of dithiothreitol, followed by a purification step including CTAB-DNA precipitation. The specific region of HLA-DQA1 gene was amplified by the semi-nested PCR, and the amplified products were cloned and sequenced. The HLA-DQA1 genotype was determined by comparing the sequence to the known sequence of each allele. All genotypes of HLA-DQA1 were successfully typed with hair shafts from six known heterozygotes, although one of them showed the predominant appearance of one allele. For correct typing, a template DNA equivalent to a hair shaft of 5 or 10 cm in length was necessary. Without the CTAB-DNA precipitation step, DNA extract from such hair shafts inevitably contains enough melanin to inhibit PCR. The present results suggest that hair shafts can be used for the typing of nuclear DNA loci.

Journal Article↗
PubMed1999

Polymorphisms of the CYP1A1 and GSTM1 gene involved in oral squamous cell carcinoma in association with a cigarette dose.

The genetic polymorphisms of CYP1A1 and GSTM1 genes among 100 Japanese patients with oral squamous cell carcinomas (SCC) were investigated to evaluate the role of genetic susceptibility in carcinogenesis of the oral cavity. The presence of the rare homozygote of CYP1A1, m2/m2, was significantly more frequent in the patient group (15.0%) than the control group (8.0%) (Odds ratio (ORs) = 3.6 95% Confidential Interval (CI): 1.4-9.5). The heterozygotic variant, m1/m2, was also frequently seen in oral SCC patients. This meant that the m2 allele was observed in more than half of the patients. The null genotype of GSTM1 was found in 43.0% of the patient group. This was not significantly different from the controls (40.0%). When the life time cigarette consumption dose of the patients was considered with respect to genotypes of CYP1A1, the mean smoking index (SI) of oral SCC patients with m2/m2 was found to be less than half of the mean SI among the patients with m1/m1 genotype (P < 0.02). The ORs of the m2/m2 genotype was found to be significantly high in a comparison of various subsites of the oral cavity, except for the floor of the mouth. Our results indicate that the rare homozygote of CYP1A1, m2/m2, is associated with increased risk of oral SCC, in particular, at low cigarette dose levels. The results also suggested that the involvement of such susceptibility in oral carcinogenesis might be different between the subsites of the oral cavity.

Adult↗
PubMed1999

Inhibitory effects of roxithromycin on tumor angiogenesis, growth and metastasis of mouse B16 melanoma cells.

We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis, tumor growth and metastasis of mouse B16BL6 melanoma cells. The inhibitory effect of roxithromycin on angiogenesis using mouse dorsal air sac model was dose-dependent, and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. Administration of roxithromycin histologically reduced the development of microvessels and mononuclear cell infiltration. In vivo tumor growth studies demonstrated that intraperitoneal administration of roxithromycin at 20 mg/kg/day and 50 mg/kg/day reduced tumor size of B16BL6 melanoma to about 56% and 33% (experiment 1), 71% and 48% (experiment 2) of that in the respective controls. Roxithromycin also significantly inhibited pulmonary metastasis of B16BL6 cells in a spontaneous system. The inhibitory activities of roxithromycin on angiogenesis, tumor growth and metastasis were compared with those of a potent angiogenesis inhibitor, TNP-470. These data demonstrated that roxithromycin has potent antiangiogenic and antitumor effects and might have possible therapeutic applications.

Air Sacs↗
PubMed1999

Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells.

We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B 16BL6 mouse melanoma and C57BL mouse system. Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose. Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B 16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system. Azithromycin and josamycin, on the other hand, did not inhibit tumor growth or pulmonary metastasis of B16BL6 cells. Immunohistochemistry revealed that roxithromycin and clarithromycin reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. These results suggest that 14-membered ring macrolides have antiangiogenic and antitumor effects and might have possible therapeutic applications.

Angiogenesis Inhibitors↗
PubMed1999

Effects of in vivo soluble selectin gene introduction of lps-induced leukocyte accumulation in the murine lung.

The selectin family adhesion molecules exert a crucial role in accumulation of leukocytes at the site of inflammation. To test the biological effects of soluble selectin on lung inflammation, we introduced an expression plasmid vector of soluble selectin gene via HVJ-liposome into a murine model of LPS-induced lung injury. The myeloperoxidase activity in LPS-injected mice was suppressed by the in vivo injection of soluble P-selectin gene relative to control mice. On the contrary, soluble E- or L-selectin genes did not exert suppressive effects. Our observations suggest that P-selectin plays a crucial role in the initial steps of lung inflammation, and exogenous introduction of soluble P-selectin by in vivo gene transfer method may be a useful strategy for regulating inflammation of the lung.

Animals↗