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Biomedical subjects

N Yoshida

Publications and source records attributed to N Yoshida.

At least 217 records · Page 12Linked to original sources
PubMed1998

Exercise-induced abnormal blood pressure responses are related to subendocardial ischemia in hypertrophic cardiomyopathy.

OBJECTIVES: We examined by thallium-201 scintigraphy whether exercise-induced abnormal blood pressure response (BPR) is related to myocardial ischemia. BACKGROUND: Hemodynamic instabilities during exercise in patients with hypertrophic cardiomyopathy (HCM) are considered to be caused by abnormal reflex control of vascular resistance. METHODS: In 105 patients with HCM, exercise thallium scintigraphy was performed by means of a multistage, symptom-limited bicycle ergometer exercise test. RESULTS: Eighty-eight patients had normal BPR (> or = 25 mm Hg from baseline to peak exercise), and 17 had abnormal BPR (<25 mm Hg). Clinical characteristics including age, the prevalence of obstruction, New York Heart Association functional class and echocardiographic measurements were similar between the two groups. Left ventricular end-diastolic pressure was significantly higher in patients with abnormal BPR than in those with normal BPR (18+/-8 vs. 14+/-5 mm Hg, p < 0.05). Exercise-induced perfusion abnormalities including fixed and reversible perfusion defects, and left ventricular cavity dilatation (LVCD) were identified in 72 (69%) of 105 study patients. Left ventricular cavity dilatation indicates subendocardial hypoperfusion and is a marker of diffuse subendocardial ischemia. The prevalence of fixed or reversible perfusion defects was similar between the two groups. Patients with abnormal BPR had the higher prevalence of LVCD as compared to those with normal BPR (47.1 vs. 10%, p < 0.0002). Multiple logistic regression analysis revealed that LVCD was independently associated with abnormal BPR (odds ratio 3.76, 95% confidence interval 1.61 to 8.76). CONCLUSIONS: Exercise-induced abnormal BPRs in patients with HCM are related to subendocardial ischemia during exercise.

Adolescent↗
PubMed1998

An experimental evaluation of effects and side effects of asymmetric face-bows in the light of in vivo measurements of initial tooth movements.

By using a magnetic sensing system, the translational and rotational molar movements under the application of various asymmetric face-bows were measured two-dimensionally in human subjects to evaluate their primary effects and side effects. The asymmetric face-bow designs tested were three types of power arm face-bows, swivel offset face-bow, and internal hinge face-bow. Although all face-bow designs were considered to be effective in achieving asymmetric distalizations of the molars, they generated lateral displacements that may lead to an undesirable crossbite. The swivel offset face-bow may produce unexpected results and its fabrication is complicated. The internal hinge face-bow is remarkably effective for asymmetric molar distalizations. Unfortunately, it causes a strong crossbite tendency on the molar to be more distalized. Therefore the use of the power arm face-bow is thought to be relatively recommendable because it showed an acceptable asymmetric effect and is easily fabricated from a commercially available face-bow. It is concluded that all asymmetric face-bows generate lateral forces as side effects as long as the force delivery system with a combination of an asymmetric face-bow and a neck strap or head cap is applied. The current study suggests a method whereby the side effect of asymmetric face-bows can be eliminated.

Adult↗
PubMed1998

Neutrophils, lipid peroxidation, and nitric oxide in gastric reperfusion injury in rats.

Nitric oxide (NO) modulation of ischemia-reperfusion injury was investigated by measuring lipid peroxide and neutrophil accumulation in rat stomachs treated with NG-nitro-L-arginine (L-NNA), a specific NO synthase inhibitor. Ischemia-reperfusion injury was induced in the rat stomach. Treatment with L-NNA for 3 days at a dose of 3 mg/kg/day significantly enhanced this injury. This enhancement was reversed by the simultaneous administration of L-arginine at a dose of 30 mg/kg/day. Both thiobarbituric acid (TBA)-reactive substances, an index of lipid peroxidation, and myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, were increased in the gastric mucosa after ischemia-reperfusion. L-NNA treatment enhanced these increases in TBA-reactive substances and MPO activity. The increase in the area of gastric erosions correlated closely with accumulation of TBA-reactive substances as well as the increase in MPO activity. Enhancement of ischemia-reperfusion injury by L-NNA treatment was inhibited by injection with anti-neutrophil antibody, anti-platelet activating factor (PAF) antagonist, and anti-leukotriene B4 (LTB4) receptor antagonist. In addition, the increase in TBA-reactive substances and MPO activity was decreased by these antibodies or antagonists. Enhancement of reperfusion-induced gastric mucosal injury associated with inhibition of NO synthesis may involve neutrophil infiltration and lipid peroxide accumulation in the gastric mucosa, mediated by PAF and LTB4.

Animals↗
PubMed1998

Defective NK cell activity and Th1 response in IL-18-deficient mice.

IL-18 is a cytokine that is secreted from activated macrophages and induces IFNgamma production. To investigate the in vivo role of IL-18, we generated IL-18-deficient mice. In Propionibacterium acnes (P. acnes)-primed IL-18-deficient mice, LPS-induced IFNgamma production was markedly reduced, despite normal IL-12 induction. Natural killer cell activity was significantly impaired. Th1 cell response after injection of P. acnes or Mycobacterium bovis (bacillus Calmette-Guerin [BCG]) was significantly reduced. Similar results were observed in IL-12-deficient mice. Interestingly, Th1 response was induced after BCG infection in IL-12-deficient mice. We therefore generated mice lacking both IL-18 and IL-12. In these mice, NK activity and Th1 response were further impaired. This demonstrates the important role of both IL-18 and IL-12 in NK activity, as well as in in vivo Th1 response.

Animals↗
PubMed1998

High extracellular Ca2+ and Ca2+-sensing receptor agonists activate nonselective cation conductance in freshly isolated rat osteoclasts.

The effects of an increase of extracellular and intracellular Ca2+ on the membrane properties were examined in freshly isolated rat osteoclasts using the perforated patch-clamp method. Spread-type osteoclasts plated on a cover glass predominantly displayed an inwardly rectifying K+ current in a normal saline solution. Application of an extracellular high-Ca2+ solution transiently increased the membrane conductance in 15 (71%) of 21 osteoclasts. The external high Ca2+-induced current reversed at the membrane potential of -4.8+/-2.4 mV (n=8). The change of intracellular Cl-concentration did not affect the reversal potential, suggesting that the response was due to a nonselective cation conductance. Application of a calcium ionophore, ionomycin (3 micromol/L), continuously increased the membrane conductance, and the reversal potential was -12.5+/-5.0 mV (n=5). Extracellularly applied neomycin (100 micromol/L) and Gd3+ (100 micromol/L), which are agonists of Ca2+-sensing receptor (CaR), also increased the membrane conductance. These results suggest that rat osteoclasts detect high extracellular Ca2+ by an extracellular Ca2+-sensing mechanism functionally similar to the CaR in the cell surface, release Ca2+ from the internal stores, and display the activation of Ca2+-dependent cation channels in the cell membrane.

Actins↗
PubMed1998

Role of active oxygen species and lipid peroxidation in mepirizole-induced duodenal ulcers in rats.

The role of active oxygen species and lipid peroxidation in the pathogenesis of duodenal ulcers induced by mepirizole was investigated in rats. Oral administration of mepirizole (200 mg/kg) resulted in ulcer lesions in the proximal duodenum. Thiobarbituric acid-reactive substances (TBA-reactive substances), an indicator of lipid peroxidation, also significantly increased in the duodenal mucosa. Myeloperoxidase (MPO) activity in the duodenal mucosa, a sign of polymorphonuclear leukocyte (PMN) accumulation, significantly increased. Combination treatment with polyethylene glycol-modified Serratia Mn-SOD and catalase significantly decreased the size of the ulcers and TBA-reactive substances in the duodenal mucosa. Allopurinol, a xanthine oxidase inhibitor, also reduced the size of duodenal ulcers. Both the size of the ulcers and the increase in TBA-reactive substances in the duodenal mucosa were significantly lower in PMN-depleted rats. Mepirizole increased the surface expression of adhesion molecule CD18 on PMNs in vitro. These results suggest that lipid peroxidation, mediated by active oxygen species generated from xanthine oxidase and PMNs, plays an important role in the pathogenesis of duodenal ulcers induced by mepirizole.

Allopurinol↗
PubMed1998

Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres.

BACKGROUND: Activating transcription factor-4 (ATF4)--also termed CREB2, C/ATF, and TAXREB67--is a basic-leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family. In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP-1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation. In order to assess the in vivo essential role of ATF4, we have generated mice lacking ATF4 by gene targeting. RESULTS: ATF4-deficient mice exhibited severe microphthalmia. Although ATF4-deficient eyes revealed a normal gross lens structure up to embryonic day 14.5, later on the ATF4-deficient lens, degenerated due to apoptosis without the formation of lens secondary fibre cells. Retinal development was normal in the mutant mice. The lens-specific expression of ATF4 in the mutant mice led not only to the recovery of lens secondary fibres but also to the induction of hyperplasia of these fibres. CONCLUSION: These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation.

Activating Transcription Factor 4↗
PubMed1998

Demonstration of double-chambered right ventricle on myocardial perfusion SPECT.

A 19-year-old man with a double-chambered right ventricle (DCRV) and an associated ventricular septal defect was admitted to the hospital for surgical correction. Preoperative study of myocardial perfusion with Tc-99m tetrofosmin SPECT depicted the two chambers of the right ventricle. There was a substantial differential in the radioactive uptake between these two chambers. The inflow and outflow chambers with different peak-pressures (94 and 18 mm Hg) showed different uptakes reflecting the pressure difference, which was intense in the inflow chamber and weak in the outflow.

Adult↗
PubMed1998

Involvement of lipid peroxidation in free fatty acid-induced isolated rat pancreatic acinar cell injury.

It was reported that free fatty acids degraded from triglycerides by lipase may play a major role in acute necrotizing or hyperlipidemia-induced pancreatitis. We hypothesized that this injury may be related to the peroxidation of cell membrane phospholipids and tested this hypothesis using isolated pancreatic acini. Pancreatic acini were prepared from male Sprague-Dawley rats by collagenase digestion. Linoleic acid was added (0.1-1.0 mM) to the acinar cell suspension to induce cell injury. Acinar cell damage was measured by lactate dehydrogenase release and by trypan blue exclusion. Phosphatidylcholine hydroperoxide and alpha-tocopherol in the acinar cells were measured. Protective effects of alpha-tocopherol (0.5, 5.0 mM) against this type of cell injury were also evaluated. When isolated acinar cells were treated with linoleic acid, a significant decrease in viability was observed in a time- and dose-dependent manner. In addition, the levels of phosphatidylcholine hydroperoxide after treatment of 0.5 mM of linoleic acid were increased and levels of alpha-tocopherol were decreased significantly. alpha-Tocopherol significantly ameliorated both cellular injury (p < 0.01) and increases in phosphatidylcholine hydroperoxide (p < 0.01). These data suggest that lipid peroxidation of the cellular membrane is an important component of the pancreatic cell injury mediated by free fatty acids.

Animals↗
PubMed1998

Enhancement of anti-tumor activity of natural killer cells by BALL-1, a B cell lymphoma line.

The anti-tumor activity of human peripheral blood mononuclear cells (PBMC) against various tumor cell line cells (K562, Daudi, KMG-2, and KATOIII) was enhanced by coculture with irradiated BALL-1, but not with other irradiated B cell line cells (NALM-1, Namalwa, and Daudi). PBMC cocultured with BALL-1, however, failed to exhibit evident cytotoxicity against autologous concanavalin A-induced lymphoblasts. The enhancement of the anti-tumor activity seemed not to be correlated with EBNA and HLA-DR expression on B cell line cells. Monoclonal antibodies (mAbs) against interleukin (IL)-2, interferon-gamma, IL-12, IL-15, tumor necrosis factor-alpha and lymphotoxin showed little or no suppression of the anti-tumor activity of PBMC treated with irradiated BALL-1. Furthermore, the culture supernatants of BALL-1 failed to enhance the anti-tumor activity of PBMC, suggesting no involvement of soluble factors in the induction of the anti-tumor activity. The anti-tumor activity of PBMC treated with BALL-1 was synergistically enhanced by an additional IL-2 stimulation. Periodate-lysine-paraformaldehyde-fixed, but not ethanol- or acetone-fixed, BALL-1 could significantly enhance the anti-tumor activity. Furthermore, BALL-1-derived membrane fraction, but not that of Daudi, enhances the anti-tumor activity. It was thus suggested that some membrane glycoproteins on the cell surface of BALL-1 play a crucial role in the induction of the anti-tumor activity. By analysis using mAbs against human leukocytes, we found that depletion of CD11b, CD16, and CD56-positive cells resulted in decreased anti-tumor activity, suggesting that the main effector cells in the BALL-1-induced anti-tumor activity were natural killer (NK) cells. The present results thus raise the possibility that BALL-1, probably via membrane glycoproteins, modulates NK cell-mediated anti-tumor activity.

Antibodies, Monoclonal↗
PubMed1998

Effects of cytokines and minocycline on subacute lung injuries induced by repeated injection of lipopolysaccharide.

Pathological changes were seen in the lungs of ddY mice one week after repeated intraperitoneal injections of lipopolysaccharide (LPS) of Klebsiella pneumoniae. The infiltration of polymorphonuclear cells (PMN), mainly neutrophils, and lymphocytes into the alveolar septum, the infiltration of PMN into perivascular areas and microthrombi were recognized in this murine model. The blood levels of TNF alpha and IL-1 alpha did not rise at this time, suggesting that the most important cytokine promoting inflammation one week after LPS stimulation was neither TNF alpha nor IL-1 alpha. In the lungs of mice administered minocycline together with LPS, lymphocyte infiltration of alveoli and perivascular areas as well as microthrombi were suppressed. The blood levels of TNF alpha, IL-1 alpha, IL-4 and IL-6 were elevated in these groups, suggesting the suppression of pathological changes to be associated with the anti-inflammatory effect of IL-6 and/or persistent elevation of TNF alpha and/or IL-1 alpha levels. In conclusion, subacute pathological changes in the lung were induced by repeated intraperitoneal injections of LPS to mice. These pathological changes were suppressed by minocycline, suggesting the anti-inflammatory effects of this antibiotic to be the result of stimulating certain cytokines.

Animals↗
PubMed1998

Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates 'reserve cells'.

When a proliferating myoblast culture is induced to differentiate by deprivation of serum in the medium, a significant proportion of cells escape from terminal differentiation, while the rest of the cells differentiate. Using C2C12 mouse myoblast cells, this heterogeneity observed upon differentiation was investigated with an emphasis on the myogenic regulatory factors. The differentiating part of the cell population followed a series of well-described events, including expression of myogenin, p21(WAF1), and contractile proteins, permanent withdrawal from the cell cycle and cell fusion, whereas the rest of the cells did not initiate any of these events. Interestingly, the latter cells showed an undetectable or greatly reduced level of MyoD and Myf-5 expression, which had been originally expressed in the undifferentiated proliferating myoblasts. When these undifferentiated cells were isolated and returned to the growth conditions, they progressed through the cell cycle and regained MyoD expression. These cells demonstrated identical features with the original culture on the deprivation of serum. They produced both MyoD-positive differentiating and MyoD-negative undifferentiated populations once again. Thus the undifferentiated cells in the serum-deprived culture were designated 'reserve cells'. Upon serum deprivation, MyoD expression rapidly decreased as a result of down-regulation in approximately 50% of the cells. After this heterogenization, MyoD positive cells expressed myogenin, which is the earliest known event of terminal differentiation and marks irreversible commitment to this, while MyoD-negative cells did not differentiate and became the reserve cells. We also demonstrated that ectopic expression of MyoD converted the reserve cells to differentiating cells, indicating that down-regulation of MyoD is a causal event in the formation of reserve cells.

Animals↗
PubMed1998

Structures of three new oleanene glucuronides isolated from Lathyrus palustris var. pilosus and hepatoprotective activity.

Three new saponins, named palustrosides I, II and III, together with azukisaponins II, V and soyasapogenol B monoglucuronide, were isolated from the aerial parts of Lathylus palustris L. var. pilosus Ledeb. The structures of palustrosides I, II and III were identified as 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosides of soyasapogenol E, abrisapogenol E, and bredemolic acid 28-O-beta-D-glucopyranoside, respectively, by spectroscopic and chemical methods. As part of our studies on hepatoprotective drugs, we also examined the hepatoprotective effects of these saponins towards immunologically induced liver injury in primary cultured rat hepatocytes. The activity of the disaccharide group was greater than that of the trisaccharide group. This information regarding the structure-activity relationships substantiated previously obtained data. Structure-hepatoprotective relationships for the sapogenol moiety suggested that the hydroxyl group at C-30 reduces the hepatoprotective effect. On the other hand, the carbonyl group at C-22 may be equivalent to a hydroxyl group at C-22 in terms of hepatoprotective action. Oleanolic acid-type saponins also exhibited hepatoprotective action.

Animals↗
PubMed1998

A new oleanene glucuronide having a branched-chain sugar from Melilotus officinalis.

A new oleanene glucuronide called melilotus-saponin O1 (1) was isolated together with three known ones from the roots of Melilotus officinalis (L.) PALLAS (Leguminosae). The structure of 1 was determined to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1--> 3)]- beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl soyasapogenol B by spectroscopic and chemical methods.

Antiviral Agents↗
PubMed1998

Affinity of mosapride citrate, a new gastroprokinetic agent, for 5-HT4 receptors in guinea pig ileum.

We examined the binding affinity of mosapride citrate (mosapride) (4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]me thyl] benzamide citrate), a novel gastroprokinetic agent, for the 5-hydroxytryptamine (5-HT) 4 receptors in guinea pig ileum using a selective 5-HT4-receptor radioligand, [3H]GR113808. In membrane preparations from longitudinal muscle with myenteric plexus in guinea pig ileum, specific [3H]GR113808 binding revealed a single saturable site of high affinity (Kd=0.28 +/-0.02 nM, Bmax = 45+/- 3 fmol/mg protein). Mosapride and other 5-HT4-receptor agonists inhibited the specific binding of [3H]GR113808 in guinea pig ileum. The 5-HT4 agonists examined displayed the following inhibition potency order: BIMU-8 > cisapride > mosapride > renzapride > 5-HT > zacopride > metoclopramide. Mosapride exhibited monophasic inhibition of the specific [3H]GR113808 binding in the ileum (Ki value: 84.2 nM). The presence of mosapride (30 nM) significantly increased the Kd value to 0.44+/-0.05 nM in the Scatchard analysis of [3H]GR113808 binding. Bmax of [3H]GR113808, however, was not affected (48 +/-4 fmol/mg protein) by mosapride. As for the affinity of mosapride, the addition of GppNHp (100microM) slightly increased the Ki value to 104 nM. These results indicate that mosapride has an affinity for 5-HT4 receptors in guinea pig ileum in the radioligand binding study.

Animals↗
PubMed1998

An alpha2-macroglobulin-serine proteinase complex from human carcinomatous ascites and pleural effusion: isolation, monoclonal antibody preparation, and immunohistochemical study.

A protein with the apparent molecular mass of 720 kDa which hydrolyzes anilide substrates of p-guanidino-L-phenylalanine was purified from ascites and pleural effusion of patients with pulmonary, breast, gastric, and ovarian cancers by chromatographic techniques. When this protein was separated on SDS-PAGE on nonreducing conditions, two bands corresponding to 720 and 360 kDa were seen to have gelatin-digestive activity in zymography assay. Moreover, when it separated by SDS-PAGE on reducing conditions, it migrated as several bands up to 180 kDa. The N-terminal amino acid sequence and immunoreactivity of anti-alpha2-macroglobulin polyclonal antibody revealed that the 180-kDa band was intact alpha2-macroglobulin. The hydrolytic activity of this complex was completely inhibited by diisopropyl fluorophosphate (DFP) and p-amidinophenylmethanesulfonyl fluoride. In addition, the 65-kDa protein observed under reducing conditions bound 3H-labeled DFP. These results suggest that the purified protein is a complex of the plasma proteinase inhibitor alpha2-macroglobulin and a serine proteinase. Several monoclonal antibodies were obtained when the purified complex was used as an antigen. One of these antibodies, which was immunoreactive to this complex but not to alpha2-macroglobulin, gave a positive band corresponding to 65 kDa on SDS-PAGE under reducing conditions. Use of this antibody in immunohistochemical studies revealed immunoreactivities in numerous neoplastic tissues with strong activity in advanced gastric cancers (e.g., poorly differentiated adenocarcinoma). In addition, strong cross-reactivity was detected in glandular cells of the fetus intestine.

Adenocarcinoma↗