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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 181 records · Page 10Linked to original sources
PubMed2000

Microsatellite instability in patients with multiple primary cancers of the gastrointestinal tract.

BACKGROUND: Little is known about the genetic alterations in multiple primary cancers of the gastrointestinal tract. Microsatellite instability (MSI) is frequently observed in hereditary non-polyposis colorectal cancer (HNPCC), and multiple primary cancers is a feature of this syndrome. AIMS: To identify MSI incidence, target gene mutation, and mismatch repair (MMR) protein status in patients with multiple primary cancers of the gastrointestinal tract. SUBJECTS: Fifty seven cancers from 22 Japanese patients with multiple primary cancers of the stomach, duodenum, colon, and rectum. METHODS: MSI was examined at 5-7 microsatellite loci. Mutation analysis for TGFbetaRII, IGFIIR, and BAX was performed in cancers with MSI. MMR protein status was examined by immunohistochemical analysis using a monoclonal antibody against hMSH2 and hMLH1. RESULTS: MSI was observed in 16 of 22 patients (73%) and in 29 of 57 lesions (51%). High frequency MSI (MSI-H) was found often in patients with multiple cancers in the same organ (p = 0.042), especially in multiple gastric cancer patients (p = 0.038). In contrast, patients with multiple cancers in different organs had a tendency to show low frequency MSI (MSI-L) or microsatellite stable (MSS) phenotype. Both target gene mutation and decreased expression of MMR protein were found only in seven lesions of three patients with MSI at more than four microsatellite loci. CONCLUSIONS: These results suggest that genetic instability may play an important role in the development of multiple gastrointestinal cancers but there may be different genetic alterations between multiple gastrointestinal cancers of the same and different organs.

Aged↗
PubMed2000

Myelodysplastic syndrome with clonal eosinophilia accompanied by eosinophilic pulmonary interstitial infiltration.

We report a case of de novo myelodysplastic syndrome with clonal eosinophilia (MDS-Eo) and eosinophilic pulmonary interstitial infiltration, confirmed by autopsy. Cytogenetic study using Giemsa banding identified 47,XY,+1,der(1;7)(q10;p10),+8 in the marrow cells. Simple Giemsa staining revealed the same chromosomal aberration in metaphase spreads with eosinophilic granules, indicating the clonal proliferation of eosinophils. To our knowledge, our case is the 6th reported case of MDS-Eo with cytogenetically confirmed clonal eosinophilia, and the first autopsy of MDS-Eo. A review of the literature combined with our findings suggests that this type of chromosomal aberration might be involved in the as yet unknown pathogenesis of MDS-Eo.

Aged↗
PubMed2000

Scleroderma associated with anemia and thrombocytopenia that responded well to cyclosporin.

A 55-year-old woman came to our hospital because of cutaneous sclerosis of the limbs in September 1996, and was diagnosed with scleroderma based on a skin biopsy. In August 1997, the cutaneous sclerosis became progressive (hemoglobin level, 4.3 g/dl; platelet count, 7 x 10(9)/l). The laboratory results were positive for the direct Coombs test, bone marrow aspiration showed a dry tap, and the bone marrow biopsy showed marked fatty marrow. Indium-111 bone marrow scintigraphy showed a markedly decreasing uptake. These findings indicated bone marrow hypoplasia associated with hemolytic anemia. After prednisolone therapy (60 mg) was initiated, the direct Coombs test became negative but the blood cell count did not increase. Then, 300 mg of cyclosporin was initiated and anemia and thrombocytopenia improved. The cyclosporin dosage was gradually decreased and the patient's hematological condition was good, although the cutaneous sclerosis changed only a little. This is a rare and interesting case of a patient with scleroderma associated with bone marrow insufficiency and hemolysis who responded well to cyclosporin.

Anemia, Hemolytic↗
PubMed2000

Primary malignant lymphoma of the central nervous system presenting with ascites and pleural effusion.

A 70-year-old woman was admitted to our hospital owing to ascites and pleural effusion. Though malignant cells (B-cell type lymphoma) were detected in both the ascites and pleural effusion, neither lymph node swelling nor a tumor was detected upon chest, abdominal and pelvic computed tomography (CT). After weekly THP-COP therapy for 8 weeks, the ascites and pleural effusion completely disappeared. Two years after the first admission, she was re-admitted because of a disturbance of consciousness, and a brain tumor was detected on CT scan. The immunohistological and genetic data for the brain tumor were identical to those of the malignant cells in the pleural effusion and ascites detected 2 years previously. Whereas the symptoms at onset of a primary lymphoma of the central nervous system (CNS) are usually neurological ones, in this rare case of primary CNS lymphoma, the symptoms at onset were the ascites and pleural effusion without neurological symptoms.

Aged↗
PubMed2000

15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-gamma agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-gamma in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-gamma in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-gamma by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the synthetic PPAR-gamma ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-gamma ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ(2) were more potent than troglitazone. These findings suggest that PPAR-gamma may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ(2), may be useful in the treatment of RA.

Animals↗
PubMed2000

Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages.

There is evidence that macrolide antibiotics are effective in the treatment of chronic airway inflammatory diseases, probably through actions other than their antibacterial properties. In order to determine whether macrolides affect the nitric oxide-generating system in the respiratory tract, rat pulmonary alveolar macrophages (PAMs) were studied in vitro. The release of NO was assessed by direct measurement with a specific amperometric sensor for this molecule, and the expression of type II NO synthase (NOS) messenger ribonucleic acid (mRNA) was determined by Northern blotting. Incubation of PAMs with lipopolysaccharide from Escherichia coli and recombinant human interferon-gamma caused release of NO, which was accompanied by induction of type II NOS mRNA. The release of NO was reduced by coincubation of cells with the macrolides erythromycin, clarithromycin and josamycin in a concentration-dependent manner, the maximal inhibition being 73+/-10, 81+/-6 and 84+/-9%, respectively, but was not altered by amoxycillin or cefaclor. These macrolides likewise inhibited the induction of type II NOS mRNA, whereas no inhibitory effects were observed with amoxycillin or cefaclor. These results suggest that macrolide antibiotics specifically inhibit type II NO synthase gene expression and consequently reduce NO production by rat pulmonary alveolar macrophages, which might result in attenuation of airway inflammation.

Amoxicillin↗
PubMed2000

Chemiluminescence because of the production of reactive oxygen species in the lungs of newborn piglets during resuscitation periods after asphyxiation load.

Reactive oxygen species are regarded as a possible cause of many diseases. However, there are few reports offering in vivo and in situ proof of the direct involvement of reactive oxygen species in the pathogenesis of disease. In the present study, the luciferin derivative 2-methyl-6-[4-methoxyphenyl]-3,7-dihydroimidazo [1,2-alpha] pyrazin-3-one (MCLA) was used to investigate the amount of reactive oxygen species produced during resuscitation after asphyxiation load in newborn piglets. The animals were first asphyxiated by stopping respiration for 4 min, and then resuscitated using 100% oxygen. When physiologic saline solution was administered, lung surface chemiluminescence had a mean value of 2, whereas with MCLA, a maximum luminescence of 580 was seen, demonstrating the possibility of measuring reactive oxygen species in vivo and in situ using MCLA. In a group in which resuscitation after acute asphyxiation was performed with 21% oxygen, the relative maximum lung surface chemiluminescence was 59.5+/-39, whereas that for a group in which resuscitation was performed using 100% oxygen had a significantly higher value of 186.1+/-72.5. Consequently, ventilation and especially resuscitation by 100% oxygen may represent a potential danger.

Animals↗
PubMed2000

Phylogenetic relationship of six Glycyrrhiza species based on rbcL sequences and chemical constituents.

The nucleotide sequences of ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G. echinata, G. macedonica and G. pallidiflora have been determined to construct their phylogenetic tree. Based on these sequences, the six Glycyrrhiza species were divided into two groups: three, G. glabra, G. uralensis, and G. inflata, which produce glycyrrhizin as a major saponin, and the others, G. echinata, G. macedonica and G. pallidiflora, which produce macedonoside C as a major saponin. Among the three glycyrrhizin-producing species, only two nucleotide substitutions were observed between the rbcL sequences of G. glabra and G. uralensis, and the sequence of G. uralensis was identical to that of G. inflata, indicating that G. uralensis and G. inflata are closely related. Among the three macedonoside C-producing species, only one nucleotide substitution was observed between those of G. echinata and G. macedonica, indicating that these two species are also closely related.

DNA, Plant↗
PubMed2000

A novel method of preparing amine-modifying C-4' oxidized nucleotide.

A novel method of preparing C-4' oxidized nucleotide, a monomeric model of an alkali labile lesion (1) has been studied. The C-4' selenated 4a and 4b were found to be effective in preparing 3, a monomeric model of 1, by the reaction with NBS (N-bromosuccinimide). The successive reaction of 3 with amine at room temperature afforded the alpha,beta-unsaturated gamma-methylene-gamma-lactam (2) in good yield.

Bromosuccinimide↗
PubMed2000

Plasma concentrations of an angiotensin-converting enzyme inhibitor, benazepril, and its active metabolite, benazeprilat, after repeated administrations of benazepril in dogs with experimental kidney impairment.

In order to examine the safety of an angiotensin-converting enzyme (ACE) inhibitor in dogs with impaired renal excretion route, benazepril was administered orally, and plasma concentrations of benazeprilat, the active metabolite of benazepril, were determined in dogs with renal mass reduction (1/4th kidney) created by right-side nephrectomy and ligation of branches of the left renal arteries. Five dogs were administered benazepril orally at a given dose (0.5 mg/kg body weight) and 4 other dogs received 20 times that dose (10 mg/kg body weight) once daily for 15 consecutive days before (intact kidney period) and after (1/4th kidney period) creation of kidney impairment. Six control dogs received surgical treatment, but no drug. After creating a 1/4th kidney, plasma urea nitrogen and creatinine concentrations increased to approximately 30 mg/dl and 2.0 mg/dl, respectively, and renal plasma flow and glomerular filtration rate decreased to 37% and 30% of pre-treatment values, respectively. However, these parameters did not change significantly during the 1/4th kidney period both in the 0.5 mg/kg and 10 mg/kg groups. In the 0.5 mg/kg group, plasma benazeprilat concentrations increased to approximately 20 ng/ml to 340 ng/ml 2 hr after each administration, and there were no significant differences between the plasma benazeprilat concentrations during the intact and 1/4th kidney periods. In the 10 mg/kg group, plasma benazeprilat concentrations varied in the individual dog, but did not increase with the days of administration, and were not significantly different on each administration day between the intact and 1/4th kidney periods in either dose group. The AUCs(0-24) of plasma benazeprilat concentrations determined on the 15th administration day were not different between the intact and 1/4th kidney periods in dogs of either dose group. Plasma ACE activities decreased after drug administration in dogs of both groups. Benazepril seemed to have a high safety, and the adjustment of dosage regimen might not be needed in dogs with mild to moderate renal function impairment because the drug was excreted both from the kidneys and liver.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effect of a thromboxane A(2) antagonist on sputum production and its physicochemical properties in patients with mild to moderate asthma.

STUDY OBJECTIVE: To determine the effects of a specific thromboxane A(2) (TxA(2)) receptor antagonist, seratrodast, on asthma control and airway secretions. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. PATIENTS: Forty-five patients with mild to moderate asthma who had been continuously expectorating sputum of > 20 g/d. Patients with a current pulmonary infection or taking oral corticosteroids, antibiotics, or mucolytic agents were excluded from the trial. INTERVENTIONS: Following a 2-week run-in period, while pulmonary function, sputum production, and mucociliary function were assessed, patients were assigned to receive seratrodast, 40 mg/d, or placebo for 6 weeks. MEASUREMENTS AND RESULTS: During the treatment period, the changes in FEV(1) and peak expiratory flow (PEF) were not different between the two patient groups, but there were significant reductions in diurnal variation of PEF (p = 0.034), frequency of daytime asthma symptoms (p = 0.030), and daytime supplemental use of beta(2)-agonist (p = 0.032) in the seratrodast group. For sputum analysis, seratrodast treatment decreased the amount of sputum (p = 0.005), dynamic viscosity (p = 0. 007), and albumin concentration (p = 0.028), whereas it had no effect on elastic modulus or fucose concentration. Nasal clearance time of a saccharin particle was shortened in the seratrodast group at week 4 (p = 0.031) and week 6 (p = 0.025), compared with the placebo group. CONCLUSION: Blockade of TxA(2) receptor has minimal effects on pulmonary function, but may cause an improvement in mucociliary clearance by decreasing the viscosity of airway secretions.

Adult↗
PubMed2000

Transport of peroxisomal proteins synthesized as large precursors in plants.

Plant peroxisomes contain at least four proteins, namely, citrate synthase, malate dehydrogenase, long-chain acyl-CoA oxidase, and 3-ketoacyl-CoA thiolase, which are synthesized as large precursors with an N-terminal cleavable presequence. Each presequence has a conserved domain (R[I/L/Q]-X5-HL) that is homologous to peroxisomal targeting signal 2 from mammals and yeasts. In addition, a cysteine residue is found at the C-terminal ends of the presequences, whose function has not yet been described. The authors analyzed the function of the presequences and the conserved amino acids using transgenic Arabidopsis plants, which accumulate beta-glucuronidase carrying the presequence of the peroxisomal proteins from plants. Immunological and immunocytochemical studies on the transgenic plants showed that a conserved sequence in the extrapeptides is essential for targeting to peroxisomes, and a cysteine residue at the cleavage site is involved in the processing of the presequence. These results suggest that the presequences of the peroxisomal proteins function as targeting signals, and are necessary for the recognition of the processing.

Amino Acid Sequence↗
PubMed2000

Functional transformation of plant peroxisomes.

Peroxisomes in higher plant cells are known to differentiate into at least three different classes, namely, glyoxysomes, leaf peroxisomes, and unspecialized peroxisomes, depending on the cell types. In germinating fatty seedlings, glyoxysomes that first appear in the etiolated cotyledonary cells are functionally transformed into leaf peroxisomes during greening. Subsequently, the organelles are transformed back into glyoxysomes during senescence of the cotyledons. Flexibility of function is a distinct feature of plant peroxisomes. This article briefly describes recent studies of the regulatory mechanisms involved in the changes of the function of plant peroxisomes.

Adaptation, Biological↗
PubMed2000

Changes in plasma concentrations of inhibin A and inhibin B throughout sexual maturation in the male chimpanzee.

Profiles of circulating plasma inhibin A and inhibin B during sexual maturation in male chimpanzees were investigated by using two-site enzyme-linked immunoassay (ELISA). Plasma concentrations of testosterone and pituitary gonadotropins were also measured. Concentrations of inhibin B, testosterone, luteinizing hormone (LH) and prolactin increased with age throughout prepuberty to adulthood, whereas inhibin A level was low and there were no age-related changes in concentrations of either inhibin A and follicle-stimulating hormone (FSH). Inhibin B showed an inverse correlation with FSH in adult (7 years or order) but not in immature (6 years or younger) male chimpanzees. There was no correlation between plasma levels of FSH and testosterone throughout the period of sexual maturation. However, testosterone levels were positively correlated with inhibin B levels. These results suggest that circulating inhibin B is involved in the regulation of FSH secretion after puberty in adult male chimpanzees, and also that circulating inhibin B is an important form of inhibin as a marker of Sertoli cell function in adult male chimpanzees.

Aging↗
PubMed2000

HLA-associated cellular response to GAD in type 2 diabetes with antibodies to GAD.

Proliferative response of peripheral blood mononuclear cells (PBMC) to glutamic acid decarboxylase (GAD), which has been reported in patients with type 1 diabetes, was measured in type 2 diabetes, especially in patients with antibodies to GAD initially diagnosed as having type 2 diabetes (anti-GAD+ type 2 diabetes). We studied 12 patients with type 1 diabetes, 22 with anti-GAD+ type 2 diabetes, 31 with type 2 diabetes who were negative for anti-GAD (anti-GAD+ type 2 diabetes), and 30 healthy control subjects for cellular responses in vitro to GAD. The mean stimulation index (SI) in response to GAD was significantly higher in type 1 diabetes than in anti-GAD+ type 2 diabetes or healthy controls (1.47+/-0.35 vs. 1.11+/-0.35, P<0.05, and 1.06+/-0.07, P<0.05, respectively). The mean

Adult↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 4). Fadrozole hydrochloride: an oral 2/4-week male reproductive organ toxicity study.

Doses of 0, 30 and 60 mg/kg/day of fadrozole hydrochloride (Afema: non-steroidal aromatase inhibitor, antitumor agent) were given perorally by gavage to HanIbm WIST male rats from 6 or 8 weeks of age for 2 weeks, and from 6 weeks of age for 4 weeks. In all treatment groups, reduced weights of seminal vesicle, prostate and epididymis, and degeneration/necrosis of the pachytene spermatocytes in stages VII or VIII seminiferous tubules, were dose-relatedly observed. Effects could also be assessed quantitatively by staging analysis with the result of a reduction in the numbers of stage VII pachytene spermatocytes at 30 and 60 mg/kg/day. Epididymal sperm examination revealed no treatment-related changes in any groups. The effects of 4-week treatment on male reproductive organs were similar to those of 2-week treatment at the same dose levels, except for the weights of seminal vesicle and prostate, which were more reduced by 4-week treatment than by 2-week treatment. There was no notable difference in detectability of toxicity in male reproductive organs between 2-week treatment from 6 weeks of age and 2-week treatment from 8 weeks of age. It was concluded that the changes observed in the rat male reproductive organs following 4 weeks of treatment with fadrozole hydrochloride could be detected also with 2 weeks of treatment.

Administration, Oral↗
PubMed2000

Prediction of diabetes in Biobreeding/Aburahi rats by the measurement of soluble L-selectin.

L-selectin was initially identified as a homing receptor, recently soluble L-selectin has been used as a marker of the inflammation. Therefore, we investigated the relation between the development of diabetes and serum L-selectin levels in the Biobreeding (BB) rats. Serum L-selectin were measured from 30 days old to the onset of diabetes or to 90 days old in Biobreeding (BB) rats and Wistar Furth (WF) rats. Significant elevation of L-selectin was found in diabetes prone (DP) rats from 45 days old to the onset of diabetes or through 90 days old. No elevation was found in other strain of rats. In histological study, all of DP rats had insulitis and no other strain of rats had it. Therefore, we conclude that the measurement of serum L-selectin could be useful tool to predict the onset of diabetes or presence of insulitis in BB rats.

Age Factors↗