Search PubMed⌕ Search

Biomedical subjects

J Suzuki

Publications and source records attributed to J Suzuki.

At least 109 records · Page 6Linked to original sources
PubMed2000

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts.

Acute rejection and graft arteriopathy in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by several cytokines and adhesion molecules. Nuclear factor-kappa B (NFkappaB) is critical in the transcription of multiple genes involved in inflammation and cell proliferation. To test the hypothesis that NFkappaB decoy can attenuate acute rejection and arteriopathy, we performed single intraluminal delivery of NFkappaB decoy into murine cardiac allografts using a hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE)-liposome method. No decoy or scrambled decoy transfer was performed for control. Hearts were heterotopically transplanted from BALB/c to C3H/He mice (major mismatch group) and from DBA/2 to B10.D2 mice (minor mismatch group). Nontreated or scrambled decoy transfected allografts of the major mismatch group were acutely rejected, while NFkappaB decoy prolonged their survival. While severe cell infiltration and intimal thickening with enhancement of inflammatory factors were observed in untreated or scrambled decoy-treated allografts of minor mismatch group at day 28, NFkappaB decoy attenuated these changes. We conclude that NFkappaB is critically involved in the development of acute as well as chronic rejection of the transplanted hearts. NFkappaB decoy attenuates both acute rejection and graft arteriopathy by blocking the activation of several genes.

Animals↗
PubMed2000

Kinesin is involved in regulation of rat pancreatic amylase secretion.

BACKGROUND & AIMS: Kinesin has recently been localized to zymogen granules of pancreatic acini and is suggested to participate in exocytosis of exocrine pancreas. We examined the function of kinesin in regulated exocytosis of pancreatic acini in this study. METHODS: Kinesin function in exocytosis was examined by introducing hexahistidine-tagged recombinant kinesin protein and antikinesin monoclonal antibody into streptolysin-O-permeabilized acini. Intracellular localization of introduced recombinant kinesin was investigated by immunohistochemistry. Interaction between recombinant kinesin and the microtubule network was confirmed by nocodazole pretreatment of acini. Kinesin regulation by secretagogues was investigated by examining their effect on adenosine triphosphatase (ATPase) activity of endogenous kinesin. RESULTS: Recombinant kinesin enhanced calcium-stimulated amylase release from streptolysin-O-permeabilized acini. Introduced recombinant kinesin was localized to both the microtubule network and zymogen granule. Nocodazole pretreatment of acini abolished the enhancing effect of recombinant kinesin on calcium-stimulated amylase release. Antikinesin antibody inhibited amylase release stimulated by the combination of calcium and cyclic adenosine monophosphate (cAMP) but not that stimulated by calcium alone. Secretin and 8-bromo-cAMP increased ATPase activity of endogenous kinesin. CONCLUSIONS: Kinesin plays a stimulatory role in regulated exocytosis of pancreatic acini and is involved in stimulus-secretion coupling through a cAMP-dependent pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Effect of serial extraction alone on crowding: spontaneous changes in dentition after serial extraction.

We examined changes in dentition after serial extraction in subjects who wore no appliances to determine the relationships between changes in dentition and improvement in dental crowding. Mandibular dental casts and lateral cephalograms from 31 subjects who had undergone serial extraction without orthodontic treatment were analyzed at 3 stages: before extraction of the deciduous canines (T1), after extraction of first premolars (T2), and at the end of the observation period (T3). Although movements of the first molar cusp and apex from T2 to T3 were significantly greater than from T1 to T2, movements of the incisor cusp and apex from T1 to T2 were significantly greater than from T2 to T3. The first molar tipped mesially from T1 to T2 but tipped distally from T2 to T3. The distal tipping of the incisor from T1 to T2 was significantly greater than from T2 to T3. These results suggest that the main changes in dentition from T1 to T2 are different from those from T2 to T3. The correlations between the annual change in the canine movement or tipping from T2 to T3 and the annual change in the irregularity index at the same time were significant. These results suggest that the canine movement or tipping contributed to the correction of the anterior crowding from T2 to T3.

Analysis of Variance↗
PubMed2000

Properties of quadruplex oligonucleotides with anti-HIV-1 activity.

A phosphorothioate oligonucleotide composed of deoxyguanosine and thymidine was identified as an inhibitor of HIV-1 infection at an early stage of the HIV-1 replication cycle in vitro. The phosphodiester and phosphorothioate chimeric oligonucleotides were found to be potent inhibitors of several steps of HIV-1 infection: the interaction with CD4 and the chemokine receptor, the reverse transcriptase activity, and the integrase activity. To elucidate the mechanism of the anti-HIV-1 function of these oligonucleotides in terms of their structure, we focussed on their G-serial sequences and investigated the characteristics of their solution structures. These oligonucleotides were proved to be able to adopt G-quadruplex structures by UV and CD measurements. We presume that the anti-HIV-1 activities of these oligonucleotides are consequently attributable to G-quadruplex formation.

Anti-HIV Agents↗
PubMed2000

Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol.

Sarcolemma integrity is stabilized by the dystrophin-associated glycoprotein complex that connects actin and laminin-2 in contractile machinery and the extracellular matrix, respectively. Interruption of the connection by the primary gene defect or acquired pathological burden can cause cardiac failure. The purposes of the present study were to verify whether dystrophin is disrupted in acute myocardial injury after the isoproterenol overload (10 mg/kg) and to examine its relation to myocardial cell apoptosis in rats. This injury from 4-16 h at the subendocardium was accompanied by dystrophin disruption and dislocation from subsarcolemma to cytoplasm, which were confirmed by immunohistology and Western blotting. However, delta-sarcoglycan was thoroughly preserved in sarcolemma. The dystrophin degradation preceded the appearance of apoptotic cells and exactly coincided with the transferase-mediated dUTP-biotin nick end labeling-positive cardiomyocytes (TUNEL), as was verified by double-staining. These data suggest that beta-adrenergic stimulation induces dystrophin breakdown followed by apoptosis.

Adrenergic beta-Agonists↗
PubMed2000

FTY720 prevents development of experimental autoimmune myocarditis through reduction of circulating lymphocytes.

FTY720 is a new immunosuppressant agent and selectively decreases the number of circulating lymphocytes. In this study, we compared the effects of FTY720 with those of tacrolimus on experimental autoimmune myocarditis (EAM) in rats. A significant decrease in circulating lymphocyte counts was noted after a single administration of FTY720 in normal rats. At day 0, 7-week-old male Lewis rats were immunized with purified porcine cardiac myosin emulsified in complete Freund's adjuvant. FTY720 or tacrolimus was administered intraperitoneally daily. The number of myocarditis-affected areas in the FTY720 treatment groups with doses of 0.1 mg/kg/ day was significantly lower than those in control groups at days 14 and 28. In addition, at day 28, the myocarditis-affected areas in the FTY720 treatment group were significantly smaller than those in the tacrolimus treatment group receiving the same dose. Effects of early administration (days 0-10) and delayed administration (days 11-20) of FTY720 also were examined. At day 28, the myocarditis-affected areas in the early therapy group were significantly lower than those in the control group. In conclusion, we demonstrated that the development of EAM could be prevented by FTY720. These data also indicated that lymphocyte-mediated immunity is critically involved in the development of EAM.

Analysis of Variance↗
PubMed2000

Role of nitric oxide in the epileptogenesis of EL mice.

PURPOSE: To understand the role of nitric oxide (NO) in the regulation of seizures, we measured the extracellular levels of the NO metabolites nitrite and nitrate as indices of NO generation in the parietal cortex, hippocampus, and temporal cortex of EL mice. Furthermore, alterations of neuronal, endothelial, and inducible nitric oxide synthetase (nNOS, eNOS, and iNOS, respectively) were observed to correlate them with epileptogenesis. METHODS: EL mice of 20 weeks and 30 weeks of age (before and after the establishment of epileptogenesis, respectively) were used. Nitrite was quantified using the specific absorbancy of diazo dye. NOS isoenzymes (nNOS, iNOS, and eNOS) were also investigated in the hippocampus during development until mice were 30 weeks old. Samples (total protein, 8.33 to 8.43 microg) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified by immunoblotting. RESULTS: EL mice that experienced repetitive seizures showed a remarkable increase in nitrite in the hippocampus at 30 weeks of age compared with EL mice that had no experience of seizures. nNOS and iNOS were major and minor components, respectively, and both increased in parallel with the development of epileptogenesis. eNOS was not detectable. CONCLUSIONS: Excess iNOS (and subsequent increase in harmful NO) and deficient eNOS (and subsequent decrease in NO identified as an endothelium-derived relaxing factor) may work together to form a focus complex.

Animals↗
PubMed2000

Gene therapy for heart transplantation-associated coronary arteriosclerosis.

Cardiac allograft arteriosclerosis, which limits the long-term survival of recipients, cannot be prevented by conventional therapies. The arteriopathy is characterized by diffuse intimal thickening made up of proliferative smooth muscle cells. To test the hypothesis that cell cycle-regulatory genes play crucial roles in the development of this arteriopathy in vivo gene therapy targeting cell division cycle (cdc) 2 kinase was attempted in murine cardiac allografts using hemagglutinating virus of Japan (HVJ)-liposome method. Antisense cdc 2 kinase oligodeoxynucleotide (ODN) was transfected into the allografts by intraluminal injection during the operation and the allografts were harvested at 4 weeks after transplantation. Coronary intimal thickening had developed in sense ODN-treated allografts and ICAM-1 and VCAM-1 were enhanced in these arteries. PDGF mRNA was also detected. Antisense cdc 2 kinase ODN inhibited intimal hyperplasia. These data indicate that antisense cdc 2 kinase modulates gene expression and inhibits smooth muscle cell proliferation of graft arteries.

Animals↗
PubMed2000

Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts.

In skeletal myoblasts, Ras has been considered to be a strong inhibitor of myogenesis. Here, we demonstrate that Ras is involved also in the chemotactic response of skeletal myoblasts. Expression of a dominant-negative mutant of Ras inhibited chemotaxis of C2C12 myoblasts in response to basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and insulin-like growth factor 1 (IGF-1), key regulators of limb muscle development and skeletal muscle regeneration. A dominant-negative Ral also decreased chemotactic migration by these growth factors, while inhibitors for phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase (MEK) showed no effect. Activation of the Ras-Ral pathway by expression of an activated mutant of either Ras, the guanine-nucleotide dissociation stimulator for Ral, or Ral resulted in increased motility of myoblasts. The ability of Ral to stimulate motility was reduced by introduction of a mutation which prevents binding to Ral-binding protein 1 or phospholipase D. These results suggest that the Ras-Ral pathway is essential for the migration of myoblasts. Furthermore, we found that Ras and Ral are activated in C2C12 cells by bFGF, HGF and IGF-1 and that the Ral activation is regulated by the Ras- and the intracellular Ca(2+)-mediated pathways. Taken together, our data indicate that Ras and Ral regulate the chemotactic migration of skeletal muscle progenitors.

Animals↗
PubMed2000

Lambda-carrageenan-induced inhibition of gap-junctional intercellular communication in rat liver epithelial cells.

lambda-Carrageenan, a food additive extracted from red seaweed, is widely used as an emulsifier, stabilizer, or thickener. Previously, it has been shown that carrageenan could play a role in carcinogenesis. However, the mechanism by which it might influence the multimechanism, multistep process of carcinogenesis is not known. Gap-junctional intercellular communication (GJIC) has been associated with maintaining homeostatic regulation of cell proliferation and differentiation. Most cancer cells have dysfunctional GJIC, and many tumor-promoting chemicals, growth factors, and oncogenes can downregulate GJIC. The experiments in this study were designed to test the hypothesis that carrageenan might function as a tumor-promoting chemical by inhibiting GJIC. To test this hypothesis, nontumorigenic rat liver epithelial cells were exposed to carrageenan, and GJIC was measured. Western blot analysis and immunofluorescent staining were used to monitor the phosphorylation and localization of connexin 43. The data revealed inhibition of GJIC by carrageenan similar to that by the well-documented tumor promoter phorbol ester. However, the phosphorylation and localization of connexin 43 were not altered. Although the mechanism by which carrageenan inhibits GJIC is unknown, carrageenan's influence on the carcinogenic process might be via its ability to be a tumor promoter.

Animals↗
PubMed2000

Automatic system for the assay of guanidino compounds to assess uremic status.

An automated system for HPLC-fluorometry of serum guanidino compounds was constructed. This system accomplished simultaneous removal of protein and uremic fluorescences, abundant in the sera of uremic patients, which interfere with the fluorometric assay. This system was applied to the detailed elucidation of the behavior of guanidinosuccinic acid and methylguanidine during and after hemodialysis therapy (HD). The uremic patients who are capable of excreting urine even under hemodialysis therapy showed low serum guanidinosuccinic acid and methylguanidine levels. The prolongation of the interval between HD for one of the patients capable of excreting urine was examined. The levels of guanidinosuccinic acid and methylguanidine did not significantly increase and no hazardous effect was observed by 2 d of prolongation.

Adult↗
PubMed2000

Association of matrix metalloproteinase expression and left ventricular function in idiopathic dilated cardiomyopathy.

Myocardial remodeling is an important predictor for the development of dilated cardiomyopathy (DCM). Matrix metalloproteinases (MMPs) are the family of proteins responsible for extracellular remodeling, and tissue inhibitors of metalloproteinases (TIMPs) tightly control their activity. In the present study, the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was determined by immunohistochemistry in right ventricular endomyocardial biopsy samples from 16 patients with idiopathic DCM, and its clinical significance was evaluated by comparison with parameters of cardiac function. To obtain a semi-quantitative assessment of MMP and TIMP expression, the average number of positive cells per high power field was counted. The left ventricular ejection fraction (LVEF) significantly correlated with the expression of both MMP-2 (r=-0.68) and TIMP-2 (r=-0.58). Patients were classified into 2 groups according to the degree of MMP-2 expression: strongly positive and weakly positive. LVEF, left ventricular (LV) end-diastolic pressure, right ventricular end-diastolic pressure, pulmonary capillary wedge pressure and the plasma norepinephrine level were significantly greater in the strongly positive group (p<0.05). In conclusion, the expression of MMPs and TIMPs in the cardiac matrix of patients with idiopathic DCM is closely associated with myocardial remodeling and subsequent deterioration of LV performance. These findings suggest new therapeutic targets for patients with idiopathic DCM.

Adult↗
PubMed2000

Clinical characteristics of female patients with coronary spastic angina: comparison with male patients.

There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.

Aged↗
PubMed2000

Three cases of cat scratch disease diagnosed by indirect immunofluorescence antibody assay and/or polymerase chain reaction of 16S rRNA gene of Bartonella henselae.

Three suspected cases of cat scratch disease were diagnosed by indirect immunofluorescence antibody assay and/or polymerase chain reaction. Patient 1 was a 10-year-old female who presented swelling of the right axillary [corrected] lymph nodes with pain and fever. She kept a kitten, and many scratches were observed on her both legs and dorsum manus. Antibody titers against Bartonella (B.) henselae were 1:32 for IgM 3 weeks after the onset of the symptoms and 1:64 for IgG 8 weeks after the onset. The DNA for 16S rRNA type I of B. henselae was detected from the blood sample obtained 3 weeks after the onset of symptoms by polymerase chain reaction for the first time in Japan. Patient 2 was a 22-year-old female veterinary student with a cat scratch at the bottom of her neck by a male kitten. She developed a papule at the scratch, slight fever, and neck pain. Although both Bartonella-specific IgG and IgM antibodies were negative before the scratch, the IgG antibody titer rose to 1:512 14 weeks after the onset. B. henselae was isolated from the kitten and its DNA found to be for 16S rRNA type I by PCR. Patient 3 was a 23-year-old female veterinary student with a cat scratch on her left forearm. A small reddish papule developed on the scratch, and she experienced swelling of the left axillary [corrected] lymph node and pain. Both the IgG and IgM antibodies against B. henselae were negative before the cat scratch, and the IgG titer rose significantly to 1:128 and 1:1,024 in 2 and 5 weeks, respectively, after the onset of the symptoms.

Adult↗
PubMed2000

Evaluation of the heart with magnetic resonance imaging.

After compensating for two kinds of motion artifacts caused by cardiac beating and respiration, cardiac magnetic resonance (MR) imaging is now feasible for the diagnosis of various cardiac diseases. Taking cost-effectiveness into consideration, this paper reviews the experiences of preferable indications of cardiac MR imaging by demonstrating the characteristic preciseness and uniqueness that play an important role in obtaining time-volume curves consisting of the theoretically most accurate measurements of left and right ventricular volumes, in overall evaluation of the left ventricular apex and the right ventricle, in delineating the wide range of the coronary arterial tree, in measuring the most precise blood flow volume through the cross-sectional images of the vessels, and in assessing the spatial derivative of the blood flow velocity at the vessel wall, i.e., wall shear rate.

Blood Flow Velocity↗