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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 649 records · Page 36Linked to original sources

Role of neutrophil-endothelial cell interactions in gastric mucosal injury induced by aspirin.

Recent studies have indicated that aspirin promotes neutrophil adherence to endothelium via CD11/CD18-dependent interactions with intercellular adhesion molecule 1, which subsequently leads to neutrophil-mediated cell injury. The objectives of the present study were to determine the role of neutrophil-endothelial cell interactions and lipid peroxidation in aspirin-induced gastric mucosal injury in rats. Oral administration of aspirin and HCl produced hemorrhagic erosions in the stomach of rats. Myeloperoxidase (MPO) activity in the gastric mucosa, an index of neutrophil infiltration, significantly increased 3 h after aspirin administration. The concentration of thiobarbituric acid-reactive substances (TBA-RS) in the gastric mucosa, an index of lipid peroxidation, increased slightly 3 h after aspirin administration. In rats treated with antineutrophil serum, both the total area of gastric erosions and MPO activity were significantly reduced. In addition, pretreatment with anti-CD18 monoclonal antibodies significantly attenuated gastric mucosal damage and inhibited the increases in both MPO activity and TBA-RS in the gastric mucosa after aspirin administration. These observations suggest that CD18-dependent neutrophil-endothelial cell interactions and lipid peroxidation play an important role in the pathogenesis of gastric mucosal lesions induced by aspirin.

Animals↗

Effects of oxygen radical scavengers on the quality of gastric ulcer healing in rats.

Oxygen free radicals have been implicated in the pathogenesis of gastrointestinal mucosal injury. However, their effect on the quality of experimental gastric ulcer healing has not been investigated previously. Gastric ulcers were produced on the anterior wall of the stomach of rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcers were treated with scavengers for 6 weeks. Rats received either a daily dose of 20,000 U/kg of recombinant human Cu,Zn-SOD, a 1% solution of DMSO administered orally ad libitum, or 50 mg/kg/day of allopurinol administered orally. The quality of ulcer healing was evaluated by histologic and biochemical parameters: ulcer area, lipid peroxide levels, abnormality of regenerated mucosa, angiogenesis, and fibrosis as assessed by Azan staining, mucin content as assessed by the PAS-positive area, and polymorphonuclear leukocyte (PMN) infiltration. The treatments with SOD, DMSO, or allopurinol did not affect the ulcer area or lipid peroxide levels in the gastric mucosa, and SOD did not affect the histologic abnormality score, PMN infiltration in regenerated mucosa, the collagen fiber proliferation index, or the PAS-positive mucous score. DMSO and allopurinol significantly increased the collagen fiber proliferation index and the PAS-positive mucous score compared with controls. These results indicate that scavenging hydroxyl radicals or inhibiting xanthine oxidase enhances the quality but not the speed of gastric ulcer healing.

Animals↗

IL-2 can support growth of CD8+ T cells but not CD4+ T cells of human IL-2 receptor beta-chain transgenic mice.

We have generated transgenic mice expressing the human (h) IL-2R beta-chain on lymphoid cells under the control of the mouse H-2Kd promoter. Spleen cells and thymocytes of the transgenic mice were cultured in the presence of 5 nM hIL-2. After a 10-day culture, the expanded populations were analyzed by flow cytometry and shown to be composed of CD8+ T cells and gamma delta T cells. Surprisingly, CD4+ T cells of the transgenic mice did not proliferate in response to hIL-2, although the CD4+ T cells expressed the transgenic hIL-2R beta-chain as well as the endogenous gamma-chain on their surface and bound 125I-labeled IL-2. When CD4+ T cells of the transgenic mice were stimulated with anti-CD3 mAb, the CD4+ T cells proliferated in response to hIL-2. These findings suggest that CD4+ T cells may require another triggering signal to respond to IL-2 even when IL-2Rs are expressed. By contrast, CD8+ T cells and gamma delta T cells respond to IL-2 as long as IL-2Rs are expressed.

Animals↗

Antitumor effect of ischemia-reperfusion injury induced by transient embolization.

The effect of ischemia-reperfusion, induced by the transient embolic agent degradable starch microspheres (DSMs) on tumor tissue was investigated from the standpoint of active oxygen species. Rabbits with VX2 carcinoma received regional infusion of DSMs by transcatheter angiography, and it was confirmed that DSMs occluded tumor vessels. Blood flow in the tumors decreased rapidly immediately after the DSM treatment and returned to the original level within 40 min. The size of tumors did not change after a single infusion of DMS, while five repeated DSM treatments led to a significant reduction in tumor size. This reduction in tumor size was prevented by the treatment of rabbits with superoxide dismutase and catalase, indicating that the generation of active oxygen species in the tumor was involved in the mechanism of action of DSMs. Thiobarbituric acid-reactive substances also increased in the tumors after DSM infusion, and this increase was also inhibited by treatment with superoxide dismutase and catalase. In conclusion, the antitumor effect of the transient embolic agent DSM is secondary to the phenomenon of ischemia-reperfusion injury. In addition, active oxygen species and lipid peroxidation are possible causes of ischemia-reperfusion injury.

Animals↗

Effect of menthol on cytosolic Ca2+ levels in canine airway epithelium in culture.

Intracellular Ca2+ concentration ([Ca2+]i) in canine cultured tracheal epithelium in response to cyclic alcohols was measured by a fura-2 method. Menthol rapidly increased [Ca2+]i in a concentration-dependent fashion, the maximal increase from the baseline levels and the concentration of menthol required to produce a half-maximal effect (EC50) being 148 +/- 23 nM (mean +/- SE, p < 0.001) and 0.3 mM, respectively, whereas other cyclic alcohols including menthone and cyclohexanol had no effect. The menthol-induced increase in [Ca2+]i was not affected by verapamil but partially inhibited by low Ca2+ medium in the presence of EGTA. These results indicate that menthol specifically increases cytosolic Ca2+ in airway epithelium, which may be derived from intracellular Ca2+ stores.

Animals↗

Spinal cord tumor appearing as unusual pain.

STUDY DESIGN: The authors report two cases of spinal cord tumors characterized by unusual pain, which is recurrent abdominal pain or cervical angina. METHODS: These unusual pains were improved after removal of tumors in the patients. CONCLUSIONS: The authors conclude that the pain was caused by vascular compression, bleeding in the tumor, or incomplete block of the cerebrospinal fluid flow. They recommend the use of osteoplastic laminectomy, because anatomic structure and spinal function should be preserved in young patients.

Abdominal Pain↗

Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes.

The gamma chain of the interleukin-2 (IL-2) receptor is shared with the functional IL-4 receptor and is causatively related to X-linked severe combined immunodeficiency (XSCID), which is ascribed to a profound T cell defect. Studies with monoclonal antibodies specific for the IL-2 receptor gamma chain showed that the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells. Participation of the gamma subunit in more than one receptor may enable the elucidation of the mechanisms of XSCID development and lymphocyte differentiation.

Animals↗

Supra- and juxtatrigeminal inhibitory premotor neurons with bifurcating axons projecting to masseter motoneurons on both sides.

Inhibitory neurons participating in the bilateral disynaptic inhibition of jaw-closing motoneurons by stimulation of unilateral trigeminal sensory branches were searched for in the reticular formation around the trigeminal motor nucleus in cats anaesthetized with pentobarbital. Extracellular recordings were made from neurons which responded orthodromically after a monosynaptic latency to single shock stimulation of the ipsilateral infraorbital and/or inferior alveolar nerves. Direct inhibitory connection with contralateral masseter motoneurons was demonstrated in reticular neurons by the spike-triggered averaging technique, i.e., by averaging the intracellular potentials of a contralateral masseter motoneuron with respect to spontaneously occurring spikes of a reticular interneuron. By intraaxonal injection of neurobiotin, electrophysiologically identified inhibitory premotor reticular neurons were found to project to and to terminate in the trigeminal motor nuclei on both sides. Termination in the contralateral motor nucleus was demonstrated for four neurons that showed the peripheral input pattern stated above. The results provide hard evidence for contralaterally projecting interneurons in the reticular formation, participating in peripherally evoked disynaptic inhibition of masseter motoneurons on the contralateral side. Given the previously reported findings that the supratrigeminal region contains neurons which project to the ipsilateral motor nucleus and mediate disynaptic inhibition of masseter motoneurons, it is suggested that the supratrigeminal region contains bilaterally projecting interneurons, mediating peripherally evoked disynaptic inhibition of masseter motoneurons on both sides.

Animals↗

Expression of the mouse interleukin-2 receptor gamma chain in various cell populations of the thymus and spleen.

Expression of the gamma chain, which is shared among functional receptor complexes for interleukin (IL)-2, IL-4 and IL-7, was examined with hematopoietic cells in mouse thymus and spleen by flow cytometry. The gamma chain was expressed in cell populations from the spleen. Stimulation with concanavalin A and lipopolysaccharide caused fluctuation in expression of the gamma chain in T and B cells, respectively. T lineage cells developing in the adult thymus expressed the gamma chain. Fetal thymus at day 15 contained mostly immature thymocytes, which also expressed the gamma chain. These results demonstrate that the gamma chains is widely expressed in T lineage cells, probably indicating that the gamma chain plays a role not only in the proliferation of mature hematopoietic cells but also in the development of immature cells through signal transduction as a common receptor subunit for multiple cytokines.

Animals↗

Fatigue and recovery of phosphorus metabolites and pH during stimulation of rat skeletal muscle: an evoked electromyography and in vivo 31P-nuclear magnetic resonance spectroscopy study.

31P-nuclear magnetic resonance spectroscopy and evoked electromyography were applied to rat skeletal muscle to examine the mechanism of muscle fatigue and the recovery of muscle phosphorus metabolites and pH during fatigue. When the sciatic nerve was electrically stimulated at 1 Hz, the contraction force of the gastrocnemius muscle decreased gradually to 46% of the maximal force, accompanied by a decrease in phosphocreatine (PCr) and a corresponding increase in inorganic phosphate (P(i)) and diprotonated inorganic phosphate (H2PO4-). Neither the amplitudes of compound muscle action potentials (CMAP) nor muscle pH changed significantly. At 10-Hz stimulation, contraction force rapidly decreased to 26% of maximal force, accompanied by a decrease in PCr and increases in P(i) and H2PO4-. Muscle pH decreased for a few minutes, then gradually recovered during continued stimulation. The amplitude of the CMAP also decreased for a few minutes and then reached steady values. At 100-Hz stimulation, the contraction force decreased to 6% of the maximal force and there was a decrease in the amplitude of the CMAP. However, the changes in the phosphorus metabolites and pH were transient and recovered to the control value during the stimulation. These results indicated that fatigue at 1 and 100-Hz stimulation was mainly caused by the change in phosphorus metabolite concentrations and electrical failure, respectively, and that fatigue at 10-Hz stimulation might have been due to both of these factors. These results also indicated that electrical failure might have been the cause of the recovery of the phosphorus metabolites and pH during 100-Hz stimulation and of pH during 10-Hz stimulation.

Action Potentials↗

Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon.

BACKGROUND/AIMS: Corticotropin-releasing hormone (CRH) is a regulator of the hypothalamic-pituitary-adrenal axis and a coordinator of the gastrointestinal response to stress. In addition to its central effects, CRH has peripheral effects on the immune system. CRH is present in several human tissues, such as the brain, spinal cord, adrenal medulla, lung, liver, peripheral blood leukocytes, as well as the gastrointestinal tract. The current study examined the local production of CRH in the normal human colon. METHODS: Normal human colonic tissues obtained by endoscopic biopsy were immunostained with anti-CRH and anti-5-hydroxytryptamine antibody and analyzed for CRH messenger (m)RNA by a reverse-transcribed polymerase chain reaction method and by in situ hybridization. RESULTS: Immunoreactive CRH and CRH mRNA were detected in the colonic mucosal cells in the neighborhood of the base of the crypts. The mucosal cells that expressed CRH mRNA also immunostained with anti-5-hydroxytryptamine antibody. CONCLUSIONS: Normal human colonic mucosal enterochromaffin cells produce CRH. CRH in the colonic mucosa may play a role in the modulation of the intestinal immune system and/or other gastrointestinal functions basally during stressful conditions.

Adolescent↗

Anti-obesity and anti-diabetic effects of CL 316,243, a highly specific beta 3-adrenoceptor agonist, in yellow KK mice.

The anti-obesity and anti-diabetic effects of CL 316,243, a highly specific beta 3-adrenoceptor agonist (beta 1: beta 2: beta 3 = 0:1:100,000), were evaluated in obese diabetic yellow KK mice and C57Bl control mice. The study compound was fed through a gastric tube at a rate of 0.1 mg/kg/day for 2 weeks. The following parameters were compared in the treated and control animals given distilled water: brown adipose tissue thermogenesis, resting metabolic rate, insulin receptors in adipocytes, and blood glucose and serum insulin levels during a glucose overloading test. CL 316,243 significantly increased brown adipose tissue thermogenesis and resting metabolic rate in both yellow KK mice and C57Bl controls. The amount of white adipose tissue decreased, although food intake was not affected. The effects contributed to the mitigation of obesity in yellow KK mice. CL 316,243 also increased the concentration of insulin receptors and decreased the levels of serum insulin and blood glucose during the glucose overloading test in yellow KK mice. These observations suggest that CL 316,243 possesses anti-obesity and anti-diabetic effects and consequently may be useful for treating obesity as well as non-insulin-dependent diabetes mellitus in obese persons, without causing excessive side effects.

Animals↗

Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress.

We tested the hypothesis that nicotine possesses an antistress action by measuring the turnover of norepinephrine (NE), a reliable indicator of sympathetic nervous system activity, in the interscapular brown adipose tissue (IBAT) and heart of mice treated with nicotine injections, immobilization stress, or nicotine + immobilization stress, vs. untreated controls. Nicotine enhanced the sympathetic activity in the IBAT and heart, and induced a loss of body weight. Immobilization-related stress accelerated sympathetic activity in the IBAT and heart more strongly than did nicotine loading alone. Pretreatment with nicotine suppressed the sympathetic activity induced by immobilization stress to the same extent as that observed after administering nicotine alone. Thus, these results appeared to support our hypothesis.

Adipose Tissue, Brown↗

Effects of aldehyde-modified proteins on mesangial cell-matrix interaction.

We examined the effect of aldehyde-modified matrix macromolecules on mesangial cell function in vitro, using incubated rat glomerular mesangial cells. Laminin and fibronectin were modified by incubation for 24 h with 50 mM glycolaldehyde (GA), a highly reactive cross-linking glycation product, with or without equimolar aminoguanidine. GA-modified laminin and fibronectin caused marked inhibition of cell adhesion. Cell spreading was reduced on the GA-modified laminin. In contrast, the GA-modified fibronectin had no effect on cell spreading. The study of thymidine incorporation by mesangial cells showed that the GA-modified fibronectin had a diminished mitogenic activity against cells. The content of advanced glycation end-product (AGE), which was determined by fluorescence at 370 nm excitation and 440 nm emission wavelength, increased and intermolecular cross-links appeared in the GA-modified proteins. To a large extent, aminoguanidine restored the structural alterations and functional deteriorations described above. We conclude that GA-modified matrix proteins diminish their functional properties against mesangial cells and affect cellular functions.

Acetaldehyde↗