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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 739 records · Page 41Linked to original sources

Effect of rebamipide on lipid peroxidation and gastric mucosal injury induced by indometacin in rats.

The protective effect of rebamipide (CAS 11911-87-6), a novel anti-ulcer agent, was investigated in rats with hemorrhagic erosions on the glandular stomach induced by intragastric administration of 25 mg/kg of indometacin. Pretreatment with 100 mg/kg of rebamipide significantly inhibited the increase in total area of erosions in the stomach and the increase in lipid peroxides in the gastric mucosa. Rebamipide also inhibited the in vitro increase of lipid peroxides in the gastric mucosal homogenates induced by free radical initiators. These results indicate that rebamipide's protective effect against indometacin-induced gastric mucosal injury may result, in part, from its antioxidant effect, which inhibits lipid peroxidation.

Alanine↗

[Comparative clinical study in metastatic liver cancer between intra-arterial infusion of mitomycin C alone and intra-arterial infusion of mitomycin C combined with PJ-203 (degradable starch microspheres)].

In the present comparative study, we examined an intra-arterial chemotherapy combined with PJ-203 in 60 patients with liver cancer metastasized from gastrointestinal cancer, using an intra-arterial chemotherapy alone as the control. Sixty patients who had been registered by telephone contact were allocated to groups either treated with the intra-arterial chemotherapy alone or with PJ-203 combined, 30 patients each. Mitomycin C was used as the anticancer drug and given at the dose of 8mg/m2 per time. The dose of PJ-203 was 600 +/- 300 mg as degradable starch microspheres. A significantly higher response rate (CR + PR/complete cases) of 54.5% (p = 0.021) was noted in the PJ-203 combined group, as compared to 20.0% for the control group. The 50% survival duration was 282 and 214 days for the PJ-203 combined group and control group, respectively, with no significant difference being noted between the two groups. Principal adverse reactions such as pain, gastrointestinal symptoms and fever were statistically more frequent (p < 0.01) in the PJ-203 combined group than in the control group. Among the abnormal laboratory values, the incidence of decreased leukocytes was significantly lower (p = 0.022) in the PJ-203 combined group than in the control group. One of the patients concomitantly treated with PJ-203 died of drug-induced hepatitis, which was probably attributed to mitomycin C. However, overall utility assessment was significantly better (p = 0.002) in the PJ-203 combined group.

Adult↗

[A case of malignant fibrous histiocytoma of jejunal origin with marked response to cisplatin, ifosfamide and adriamycin].

A case of malignant fibrous histiocytoma (MFH) of jejunal origin with brain and lung metastases was treated by jejunal resection. Four courses of sequential chemotherapy that combined cisplatin, ifosfamide and adriamycin were performed starting on day 20 following operation. Both brain and lung metastases showed marked reduction in size, and toxicity was minimal.

Antineoplastic Combined Chemotherapy Protocols↗

[Peripheral polyneuropathy due to sarcoidosis in a patient with intrathoracic, ocular and skin lesions].

Sarcoidosis is a multisystem disorder of unknown etiology presenting most frequently with bilateral hilar lymphadenopathy (BHL), pulmonary infiltration, and ocular and skin lesions. Neurological manifestations are found in about 5% of patients with systemic sarcoidosis. We report the case of a 58-year-old woman with neurosarcoidosis manifesting as isolated, peripheral polyneuropathy. This is a rare neurological manifestation. Two years before admission, she was found to have an abnormal chest radiograph showing BHL, and pulmonary sarcoidosis was diagnosed by lung biopsy. Six months later, she noted facial erythematous lesions, and lupus pernio was confirmed by skin biopsy. Fifteen months before admission, she developed visual disturbance of the right eye caused by sarcoid-uveitis. Two months before admission, she complained of paresthesia and weakness of limbs. She was admitted for nerve-biopsy. Sural nerve biopsy revealed sarcoid granulomas in the epineurial space, periangitis and axonal degeneration. Neurologically, the diagnosis of mononeuritis multiplex without cranial nerve palsy was made. Treatment with 30 mg prednisolone daily was initiated, and neurological and extraneurological improvement was noticeable within two weeks of treatment. The dose was carefully lowered over several months.

Female↗

Quantitation and typing of serum hepatitis C virus RNA in patients with chronic hepatitis C treated with interferon-beta.

We quantified serum hepatitis C virus RNA titers and determined hepatitis C virus subtypes in chronic hepatitis C patients treated with interferon-beta to investigate relationships among serum ALT response, serum hepatitis C virus titer and hepatitis C virus subtype. Of 146 chronic hepatitis C patients who received interferon-beta therapy, 24 patients with sustained serum ALT normalization (complete responders) and 26 patients without serum ALT normalization (nonresponders) were randomly selected. Detection, typing and quantitation of hepatitis C virus were performed by means of the "single-tube" polymerase chain reaction method. Of the 24 complete responders, 21 (87.5%) became negative for hepatitis C virus RNA, whereas 21 (80.8%) of the 26 nonresponders remained positive. Hepatitis C virus infections with types I, II, III, IV, II + III and III + IV occurred in 0 (0%), 22 (51.2%), 10 (23.3%), 1 (2.3%), 7 (16.5%) and 3 (7.9%) patients, respectively. The mean pretreatment hepatitis C virus RNA titer of complete responders (0.4 +/- 2.0 x 10(4) CID50/ml) was significantly lower than that of nonresponders (3.8 +/- 4.5 x 10(4) CID50/ml) (p < 0.01). Regardless of HCV subtype, patients with more than 10(4) CID50/ml of HCV did not show serum ALT normalization, whereas complete serum ALT response was seen in most cases with less than 10(2) CID50/ml HCV. These results show that mixed infections with different hepatitis C virus subtypes appear to be more common than previously reported and that the pretreatment serum level of hepatitis C virus RNA is a more important predictor of outcome of interferon therapy than is virus genotype.

Adult↗

[Experimental acute lung injury in guinea pigs after aerosol challenge with sonicated Pseudomonas aeruginosa whole cells].

Acute hemorrhagic alveolitis was elicited in the lungs of guinea pigs by aerosol challenge with sonicated P. aeruginosa whole cells. Histological findings showed the severe inflammatory changes, which were characterized by the inflammatory infiltration of alveolar macrophages (AM), polymorphonuclear leukocytes (PMN) and eosinophils in the peribronchial and the alveolar space at 8 hours after the challenge. A marked increase of PMN as well as AM was noted in the bronchial alveolar lavage fluid (BALF) at 8 hours after the challenge and the increase of the numbers of AM and PMN in the BALF remained until 24 hours after challenge. The complement titer (CH50) and C3 component in the serum decreased at the early stage, and CH50 maintained low level and C3 component increased gradually. Polyethyleneglycol precipitation-complement consumption test (PEG-CC) of the BALF showed the existence of immune complexes formed in the airway after aerosol inhalation. These data suggest that the immune complexes of P. aeruginosa activate the complement system in the lungs, which is followed by the infiltration of inflammatory cells. Guinea pigs which were pretreated with cobra venom factor significantly reduced the extent of the inflammatory changes in the lungs. The results suggests that the complement system might act as an important factor of the acute lung injury in this model.

Administration, Inhalation↗

[Clinical studies on S-1108 in the field pediatrics].

Clinical studies on S-1108, a new oral cephem antibiotic, were carried out in the field of pediatrics. The following results were obtained. 1. The peak plasma level of S-1006 when administered after meal at a dose of 4 mg/kg was 2.47 micrograms/ml at an hour, and the serum half-life was 0.81 hour. The 4 hours urinary excretion rate of S-1006 was 35.7%. 2. S-1108 was administered to 15 children with various infections (3 patients with pneumonia, 3 with acute bronchitis, 4 with scarlet fever, 2 with acute tonsillitis, 1 with phlegmon and 2 with urinary tract infections). The overall clinical efficacy rate was 100%. 3. Side effects or abnormal laboratory test values were not observed except for diarrhea in 1 and eosinophilia in 1.

Absorption↗

[Effect of intra-arterial chemotherapy combined with degradable starch microspheres against liver cancer--a study by experimental VX2 liver tumor model].

We investigated the anticancer effect and pharmacokinetics of doxorubicin hydrochloride(ADR, 1 mg/kg) and mitomycin C (MMC, 0.2 mg/kg) given intra-arterially in combination with a temporary embolizing material, degradable starch microspheres (DSM, 5 mg/kg), to rabbits in which VX2 tumors had been implanted into the liver. The results revealed that the anticancer effect of ADR and MMC was potentiated by concomitant treatment with DSM in comparison to intra-arterial drug therapy alone. The tumor growth inhibition rate in both groups was about 87%. There was a tendency of higher intra-tumour ADR concentrations after ADR and DSM than after ADR alone. When we measured the serum levels of ADR and MMC over 45 min., it was indicated that exposure of the drugs to the systemic circulation was inhibited by the combination with DSM. In these experiments, GOT and GPT values increased temporarily after intra-arterial chemotherapy combined with DSM, but decreased gradually later to normal or close to the normal levels. These results indicate that intra-arterial chemotherapy combined with DSM causes a temporary blood flow blockade and the resulting regional retention of the cytotoxic agents, provides a more potent anticancer effect than drug therapy alone.

Animals↗

Free radical scavenging activity of the novel anti-ulcer agent rebamipide studied by electron spin resonance.

The anti-free radical action of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, CAS 11911-87-6), a novel anti-ulcer agent, was investigated by electron spin resonance spectroscopy. A spin trapping method using 5,5-dimethyl-1-pyrroline-N-oxide showed that rebamipide dose-dependently decreased both the intensity of the hydroxyl radical spin adduct signal generated by the Fenton reaction and the intensity of the superoxide spin adduct generated from opsonized zymosan-stimulated neutrophils. A kinetic study showed that the second order rate constant for the reaction between rebamipide and hydroxyl radicals at pH 7.8 was 2.24 x 10(10) mol l-1 s-1. These results indicate in vitro antioxidant properties of rebamipide which is active as hydroxyl radical scavenger and inhibitor of superoxide production in neutrophils.

Alanine↗

[A case of true human tail accompanied with spinal lipoma].

Human tails have been attributed to a disturbance in fetal tail regression which normally occurs at the gestation age of about 6 weeks. To date, more than 100 cases of human tails have been reported. However, reports of true human tails, which involve the coccygeal vertebrae, are rare. We recently encountered a patient with a true human tail which involved the coccygeal vertebrae and was accompanied by lumbar spinal lipoma and spina bifida. A four-year-old boy was brought to our clinic with complaints primarily of painful mass. The boy had no neurological abnormalities. Physically, a tail bone projected, slightly in the lumbar area, with a linear depression in the center. A hard tail bone was palpable subcutaneously. A soft mass was palpable in the lumbar region, which was accompanied by hemangioma on the superficial layer of the skin in this region. On X-ray films, the tail bone lacked the normal curvature and it projected linearly in the posterior direction. CT scans revealed spina bifida at the level below L2. MRI disclosed spina bifida (at the level below L2), spinal lipoma and a tethered cord. During surgery, the tail bone was first resected over a distance of one and a half vertebral bodies. The lumbar tumor, which continued into the spinal canal, was removed as completely as possible after incision of the dura mater. To free the tethered cord, the tensioned, hypertrophic filum terminale was dissected. Although the morphological diagnosis of this condition is easy, the high incidence of complication by other anomalies makes it essential to perform thorough preoperative examinations with CT and MRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

[Porphyrias].

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Adolescent↗

Relative abundance and the relationships between aniline, phenol and catechol degraders in fresh water.

Relative abundance and relationships between aniline, phenol and catechol degraders were investigated in unpolluted and polluted fresh waters in Osaka prefecture, Japan. Phenol and catechol degraders were found more frequently compared to aniline degraders. The results indicate that these degraders were more abundant in polluted waters than in unpolluted waters. Aniline degraders isolated from the Ina River water showed a higher capability of degrading catechol than phenol. Analysis on sequence homology among these three kinds of degraders indicated a possible relationship between aniline degraders and certain strains of both catechol and phenol degraders.

Alcaligenes↗

Spontaneous heat shock protein synthesis by alveolar macrophages in interstitial lung disease associated with phagocytosis of eosinophils.

Synthesis of heat shock proteins (HSPs) is induced in all cells and tissues after exposure to elevated temperatures, or a variety of other types of injury, including oxidative injury. We have previously reported that stress proteins are induced in monocytes-macrophages during phagocytosis of red blood cells. Receptor-mediated phagocytosis is associated with activation of the respiratory burst, generation of the lipid mediators of inflammation, and increased production of cytokines. Similar activation events have been described in the alveolar macrophage (AM) during pulmonary fibrosis. We therefore analysed the pattern of proteins synthesized by human AMs recovered by bronchoalveolar lavage (BAL) in interstitial lung disease, both under basal conditions and after in vitro exposure to heat or hydrogen peroxide (H2O2). In two out of the 17 cases studied, we observed a high alveolar eosinophilia (10 and 24%, respectively) and phagocytosis, by the AMs, of eosinophilic material. Whereas exposure to heat or H2O2 induced in all AMs the synthesis of the classical HSPs, in these two cases, we found spontaneous synthesis of HSPs and of a 32 kD oxidation-specific stress protein, haeme oxygenase (HO). Exposure of AM to purified eosinophil-derived proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), alone or in combination, did not induce stress protein synthesis, further suggesting that phagocytosis is involved in this induction. Stress protein synthesis by AMs may represent a new cellular marker of pulmonary injury and eosinophilic inflammation, and an autoprotective mechanism against oxidative stress.

Adult↗

[The biotransformation of NSAIDs: a common elimination site and drug interactions].

Many NSAIDs are eliminated predominantly through hepatic biotransformation in man. We have studied, in human hepatic microsomes, the role of specific cytochrome P450 isozymes in the formation of the major metabolites of oxicam (piroxicam and tenoxicam), phenylacetic (diclofenac) and propionic acid (ibuprofen) derivatives. A common isozyme (P450TB, CYP2C subfamily) controls the major elimination pathway of these NSAIDs. We have also determined, in two in vitro models of P450TB, the affinity for this isozyme of NSAIDs from other chemical classes (acetylsalicylic acid, mefenamic acid and indomethacin). All NSAIDs tested displayed a high affinity (3-300 microM) for cytochrome P450TB. Cytochrome P450TB plays a major role in the elimination of several NSAIDs with different chemical structures. NSAIDs are substrates as well as potential inhibitors of cytochrome P450TB. Their elimination can therefore be reduced by concomitant administration of known inhibitors of P450TB (antifungals, antibacterial sulfonamides, calcium channel blockers).

Anti-Inflammatory Agents, Non-Steroidal↗

Discriminative affinity labelling of opioid receptors by enkephalin and morphiceptin analogues containing 3-nitro-2-pyridinesulphenyl-activated thiol residues.

The thiol groups of leucinthiol, cysteamine and cysteine incorporated into opioid peptides enkephalin and morphiceptin were activated by the 3-nitro-2-pyridinesulphenyl (Npys) group to form mixed disulphides highly reactive to a free thiol. Enkephalin analogues containing Npys-leucinthiol or -cysteine at positions 4, 5 and 6 exhibited high affinities for both mu and delta receptors, while morphiceptin analogues containing Npys-cysteine at positions 4 and 5 showed relatively weak affinity only for mu receptors. When these S-activated opioid peptides were incubated with rat brain membrane preparations, it was found, by binding assay using radiolabelled and non-labelled [D-Ala2,MePhe4,Gly-ol5]enkephalin, that they label mu opioid receptors in a dose-dependent manner. The concentrations required to label half of the receptors were 0.2-2 microM for enkephalins and 10-30 microM for morphiceptins. These results suggested that the thiol group labelled by S-activated enkephalins and morphiceptins is present in the ligand binding site of receptor protein, but not in GTPase-binding protein.

Affinity Labels↗

Secretion of endothelin-1 in human endothelial cell line but not in B cell line by transfection of preproendothelin-1 cDNA.

Stable transformants with preproendothelin-1 (preproET-1) cDNA were established for the study of the regulation of endothelin-1 (ET-1) biosynthesis in human cells. ET-1, a potent vasoconstrictor peptide, is produced by endothelial cells and is secreted into the blood at a low level. Human preproET-1 cDNA was introduced into two immortal human cell lines, t-HUE2, an endothelial cell line, and Raji, a B cell line, with Ecogpt selection. Several stable transformants of t-HUE2 expressed extraordinarily high levels of preproET-1 specific mRNA and secreted ET-1 into serum-free culture medium, while the transformants of Raji cells expressed high levels of ET-1 mRNA, but secreted a negligible amount of ET-1. Immunocytochemical studies of intracellular ET-1 content revealed that there were some defects in the translation or processing of preproET-1 in the B cell line transformants. In addition, the ratio of ET-1 to ET-1 precursor (big ET-1) was much higher in the t-HUE2 transformants than in normal endothelial cells, suggesting that t-HUE2 transformants (for example t-HUE2-1) possess high levels of endothelin converting enzyme (ECE). The establishment of stable transformants producing high levels of ET-1 in serum-free medium will be useful for the study of cell-type-specific translation and processing to mature ET-1, and of the regulatory factors of ECE.

B-Lymphocytes↗