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Biomedical subjects

K Matsuda

Publications and source records attributed to K Matsuda.

At least 217 records · Page 12Linked to original sources

Thiazolidinedione induces the adipose differentiation of fibroblast-like cells resident within bovine skeletal muscle.

To investigate the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in adipocyte formation within the skeletal muscle of beef cattle, fibroblast-like cells were isolated from the longissimus muscle of cattle and cultured with activators of murine PPARgammaA thiazolidinedione T-174, which is a specific ligand for PPARgamma, stimulated adipose differentiation (evaluated by counting differentiated adipocytes under microscopic observation) in a dose-dependent fashion. A peroxisome proliferator Wy14,643 which strongly activates the alpha isoform of murine PPAR also stimulated differentiation but its potency was weaker than that of T-174. Unexpectedly, 15-deoxy-Delta12,14-prostaglandin J2, which is believed to be an endogenous ligand for PPARgamma, could not induce adipose differentiation in doses which have been found to be effective on rodent cells. Immunoblotting analysis confirmed the significant expression of PPARgamma protein in fibroblast-like cell cultures prepared from bovine skeletal muscle. In conclusion, bovine skeletal muscle contains adipose precursor cells expressing functionally active PPARgamma.

Adipocytes↗

Differential diagnosis of dysplasia-associated lesion or mass and coincidental adenoma in ulcerative colitis.

PURPOSE: This study was undertaken to investigate factors that influenced differential diagnosis of dysplasia-associated lesion or mass and coincidental adenoma in patients with ulcerative colitis. METHODS: Among 346 patients with ulcerative colitis who underwent colonoscopy between 1979 and 1995, 27 patients had macroscopic neoplastic lesions and were divided into two groups: those with dysplasia-associated lesion or mass (16 patients) and those with adenoma (11 patients), each being categorized by the presence and absence of dysplasia in the flat mucosa adjacent to the elevated lesions, respectively. RESULTS: Thirteen of 27 patients had dysplasia-associated lesion or mass detected by colonoscopic biopsy; 10 of these patients underwent colectomy, and all had dysplasia-associated lesion or mass in the colectomy specimens. Two patients whose biopsy findings were adenoma had an unsuspected dysplasia-associated lesion or mass in the operative specimens. In the remaining 12 patients, the macroscopic lesions were excised during colonoscopy because of clinical and colonoscopic evidence of adenoma. One of them was proved to have dysplasia-associated lesion or mass, and the other 11 were confirmed as having adenoma in the polypectomy specimens. Patients with dysplasia-associated lesion or mass were significantly younger (P < 0.05), had longer duration of ulcerative colitis (P < 0.01), and had more extensive disease (P < 0.005) than those with adenoma. The colonoscopic appearance was plaque-like in 13, sessile in 13, and pedunculated in 2 of the 28 lesions with dysplasia-associated lesion or mass, whereas it was plaque-like in only 1 and sessile or pedunculated in 15 of the 16 lesions with adenoma (P < 0.001). The mean size of the lesions that were considered to be dysplasia-associated lesions or mass and adenoma was 1.8 and 0.5 cm, respectively (P < 0.0001). CONCLUSIONS: Colonoscopic biopsy for detection of dysplasia in the flat mucosa adjacent to macroscopic neoplastic lesions is an appropriate preoperative approach to distinguish dysplasia-associated lesions or mass from adenomas in patients with ulcerative colitis. The statistically significant variables that influenced the differential diagnosis were age, duration of disease, extent, tumor size, and tumor colonoscopic appearance.

Adenoma↗

A schwannoma of the cecum: case report and review of Japanese schwannomas in the large intestine.

A 66-year-old Japanese man had a positive fecal occult blood test at a regular check-up, and a large polypoid mass was detected in the cecum by barium enema study. Colonoscopy showed a submucosal tumor with ulcer protruding into the cecal lumen. A large-forceps biopsy specimen was taken from the bottom of the ulcer. With the tentative diagnosis of neurogenic tumor, ileocecal resection was performed. The tumor showed spindle-cell proliferation in a concentric or fascicular pattern. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein, and they had intracytoplasmic periodic acid Schiff (PAS)-positive crystalloids. The mitosis count was low (about 1 per 20 high-power fields). The pathological diagnosis of this tumor was benign gastrointestinal schwannoma. A large number of schwannoma cases have been reported since 1910 when Verocay reported it as a true tumor that stemmed from Schwann cells and did not contain neuroganglion cells. However, gastrointestinal schwannomas are rare, and schwannomas of the large intestine are extremely rare. We reviewed 40 cases already reported in Japan and this present case in order to clarify the clinicopathological features of this tumor.

Aged↗

Isolation and structural analyses of positional isomers of 6(1),6m-di-O-alpha-D-mannopyranosyl-cyclomaltooctaose (m = 2-5) and 6-O-alpha-(n-O-alpha-D-mannopyranosyl)-alpha-D-mannopyranosyl- cyclomaltooctaose (n = 2, 3, 4, and 6).

Eight positional isomers of 6(1),6m-di-O-alpha-D-mannopyranosyl-cyclomaltooctaose (gamma CD) (m = 2-5) and 6-O-alpha-(n-O-alpha-D-mannopyranosyl)-D-mannopyranosyl-gamma CD (n = 2, 3, 4, and 6) in a mixture of products from gamma CD and D-mannose by condensation reaction of alpha-mannosidase from jack bean were isolated by HPLC. The structures of four isomers of 6-O-alpha-(n-O-alpha-D-mannopyranosyl)-D-mannopyranosyl-gamma CD were elucidated by NMR spectroscopy. On the other hand, four positional isomers of 6(1),6m-di-O-alpha-D-mannopyranosyl-gamma CD were determined by LC-MS analysis of degree of polymerization of the branched oligosaccharides produced by enzymatic degradation with bacterial saccharifying alpha-amylase (BSA), and combination of BSA and glucoamylase. Similarly cyclomaltodextrin glucanotransferase also digested these isomers.

Carbohydrate Conformation↗

Troglitazone, a new antidiabetic agent possessing radical scavenging ability, improved decreased skin blood flow in diabetic rats.

Troglitazone is a new class of antidiabetic agent possessing radical scavenging ability similar to vitamin E. Because of this ability, it is expected to improve decreased nutritive capillary blood flow in diabetes. In the present study, we investigated the effects of troglitazone on skin blood flow(SBF) in normal and streptozotocin(STZ)-induced diabetic rats. Effects of troglitazone on vasodilation, PGI2 and PGE2 production were also assessed in perfused hindlimb, isolated rat aorta rings and 3T6 fibroblasts, respectively. SBF at the base of the tail was decreased in STZ diabetic rats (2.1+/-0.2 ml/min/100 g) compared with normal rats (3.8+/-0.2 ml/min/100 g). This decrease of SBF was significantly improved (2.9+/-0.2 ml/min/100 g) by troglitazone treatment (approximately 220 mg/kg/day) for 7 days in STZ diabetic rats without alleviating hyperglycemia. Similar troglitazone treatment (approximately 160 mg/kg/day for 7 days) tended to increase SBF (approximately 30%) even in normal rats. In normal rats, subcutaneous administration of troglitazone (60 mg/kg) acutely increased SBF and, this increase was suppressed by 70% with pretreatment (10 mg/kg s.c.) of indomethacin, cyclooxygenase inhibitor, suggesting that troglitazone increases skin blood flow predominantly by increasing PGI2 and PGE2 production. In hindlimb perfusion under fixed flow rate, troglitazone infusion (20 microM) significantly decreased perfusion pressure by 13%, which reflects vasodilation of blood vessels. This decrease of perfusion pressure was inhibited by concomitant infusion of indomethacin but not N-monomethyl-L-arginine, inhibitor of nitric oxide synthase. In vitro studies, using isolated rat aorta rings, revealed that troglitazone (4.5 to 45 microM) increases PGI2 production by 31 and 70%, respectively. In 3T6 fibroblast (a component of skin tissue), troglitazone at a low dose of 0.3 microM increased PGI2 and PGE2 by 200% and 25%, respectively. Overall all, these results suggest that troglitazone increases nutritive SBF probably by virtue of its radical scavenging thus the resulting in an increase in PGI2 and PGE2 production in blood vessels and fibroblast. Troglitazone may alleviate impaired microcirculation in diabetic patients through these effects.

Animals↗

The localization of pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactivity in the hypothalamo-pituitary region of an elasmobranch, stingray, Dasyatis akajei.

Pituitary adenylate cyclase activating polypeptide (PACAP), a member of the secretin/glucagon/vasoactive intestinal polypeptide family of peptides, exists as 38-residue (PACAP 38) and truncated 27-residue (PACAP 27) forms, which play various roles in mammals. Recently, we isolated and characterized PACAPs with sequences very similar to that of tetrapod PACAP from the brains of two teleosts, the blue-spotted stargazer Gnathagnus elongatus and the stargazer Uranoscopus japonicus, and located PACAP-like immunoreactivities in the preoptic area, neurohypophysis and medulla oblongata of both species. In this study, PACAP-like immunoreactivity in the brain of an elasmobranch, the stingray Dasyatis akajei, was examined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and Western blotting analysis and its distribution in the hypothalamo-pituitary region was studied immunohistochemically using the peroxidase-antiperoxidase method. The anti-PACAP 27 serum reacted with a single band of whole brain extract with a molecular weight of ca 5000. PACAP-like immunoreactive (LI) neuronal cell bodies were found in the nucleus medius hypothalami and PACAP-LI nerve fibers and terminals were seen from the nucleus to the caudal floor of the infundibular region. These results suggest that PACAP-like peptide may be present and function as a regulatory factor in the hypothalamo-pituitary region of the elasmobranch brain.

Animals↗

Purification and primary structure of pituitary adenylate cyclase activating polypeptide (PACAP) from the brain of an elasmobranch, stingray, Dasyatis akajei.

Pituitary adenylate cyclase activating polypeptide (PACAP) was isolated from ovine hypothalami and found to exist as two amidated forms with 38 (PACAP 38) and 27 (PACAP 27) residues. The amino acid sequences of PACAPs isolated from the vertebrates, such as a bird, a frog and teleost fish, appear to be well conserved. In the present study, we attempted to isolate PACAP from the brain of an elasmobranch fish, Dasyatis akajei (stingray), which belongs to the Chondrichthyes (cartilaginous fish), by extraction of the acetone-dried powder with acetic acid, followed by successive high-performance liquid chromatography (HPLC) on a gel-filtration, a cation-exchange and two reverse-phase columns. Purification was monitored by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and Western blotting analysis using an anti-PACAP 27 serum. The PACAP thus obtained consisted of 44 residues. The amino acid sequence of the comparable portion of its N-terminal 38 residues showed 92%, 89%, 89%, and 82% identity with those of mammalian, chicken, frog and teleost PACAPs with 38 residues, respectively. The extra six C-terminal residues of the stingray resembled those of tetrapod and teleost PACAP precursors which were deduced from the respective cDNAs. These results indicate that PACAP, which has an amino acid sequence showing high similarity with those of tetrapod and teleost PACAPs, is present in the elasmobranch brain.

Amino Acid Sequence↗

Effects of homologous natriuretic peptides in isolated skin of the bullfrog, Rana catesbeiana.

The effects of frog atrial (fANP), brain (fBNP) and C-type natriuretic peptide (fCNP) on transepithelial ion transport were investigated in the bullfrog, Rana catesbeiana. The transepithelial potential difference (PD) and short-circuit current (Isc) of the abdominal skin were measured according to the technique of Ussing and Zerahn. When the abdominal skin was exposed to homologous natriuretic peptides (NPs) at concentrations ranging from 4 x 10(-13) to 5 x 10(-7) M, no significant changes in PD or Isc were observed. The influence of the NPs on the arginine vasotocin (AVT)-induced increase in Isc was then examined. Treatments with ANP and BNP (4 x 10(-9)-4 x 10(-8) M) inhibited the increase in the AVT (10(-8) M)-induced Isc. Furthermore, fCNP I and fCNP II (5 x 10(-13)-5 x 10(-7) M) did not significantly inhibit the increase in the AVT-induced Isc. The cyclic GMP analog, 8-BrcGMP, (> 10(-4) M) with AVT inhibited the increase of AVT-induced ISc, as well as fANP and fBNP. HS-142-1, an inhibitor of particulate guanylyl cyclase, (10(-5) g ml-1) significantly reduced the inhibitory action of fANP on the increase of AVT-induced Isc. These results suggest that fANP and fBNP act through the guanylyl cyclase systems to increase cellular cGMP and modulate AVT-induced epithelial transport in a concentration-dependent manner. It is also suggested that fCNPs have no effect on the natriferic response in the skin of the bullfrog.

Animals↗

Increase in the peripheral lymphocyte populations expressing CD54 (ICAM-1) after hyperthermic isolated limb perfusion in patients with malignant melanoma: an analysis of four cases.

The lymphocytes isolated from perfused or non-perfused circulations before, during, and after hyperthermic isolated limb perfusion (HILP) in the four patients with malignant melanoma were analysed for the expression of CD54 (ICAM-1), CD58 (LFA-3), CD4, CD8, HLA class I and class II in order to investigate the mechanism(s) of the activation of such immunocompetent cells as natural killer (NK)-cells or T-lymphocytes by HILP. It was thus found that the lymphocyte populations expressing CD54 increased significantly 1 day after HILP in the four patients examined. The lymphocyte populations expressing CD58 apparently increased. It was also found that the NK-cell and T-lymphocyte activities increased during or after HILP in the present four cases as observed previously in the other melanoma patients. These results indicate that our HILP system may augment the immunological activities through the mechanisms of the induction of CD54 or CD58 expression in the peripheral lymphocytes of the melanoma patients who receive HILP.

Adult↗

Granulocyte colony-stimulating factor (G-CSF) dependent hematopoiesis with monosomy 7 in a patient with severe aplastic anemia after ATG/CsA/G-CSF combined therapy.

We report a case of secondary myelodysplastic syndrome (MDS) with monosomy 7, which evolved from severe aplastic anemia (SAA) after long-term use of granulocyte colony-stimulating factor (G-CSF). A 36 year old female was admitted for detailed examination and treatment of pancytopenia. SAA was diagnosed based on hypoplastic bone marrow and a normal chromosome study. She was treated with anti-thymocyte globulin (ATG), ciclosporin A (CsA) and G-CSF, which resulted in gradual improvement of not only the myeloid but also the erythroid-megakaryocyte series. However, bone marrow dysplasia with monosomy 7 was observed after 7 months of a combination therapy of immunosuppressant and G-CSF, which prompted the discontinuation of G-CSF administration. Thereafter, bone marrow hypoplasia gradually progressed, resulting in a second aplastic crisis. During this process, the proportion of marrow cells showing monosomy 7 decreased, and the proportion with normal karyotype increased. Re-administration of G-CSF induced a trilineage, though dysplastic, hematological response; but the monosomy 7 positive population increased again. These observations indicated the presence of G-CSF dependent hematopoiesis associated with monosomy 7 in this patient. Although many G-CSF related MDS/AML cases with this leukemia-specific abnormal karyotype have been reported with emphasis on the harmful effects of G-CSF, G-CSF was useful even after the appearance of monosomy 7 as a means of avoiding life-threatening infection in this patient.

Adult↗

Effects of the alpha subunit on imidacloprid sensitivity of recombinant nicotinic acetylcholine receptors.

1. Imidacloprid is a new insecticide with selective toxicity for insects over vertebrates. Recombinant (alpha4beta2) chicken neuronal nicotinic acetylcholine receptors (AChRs) and a hybrid nicotinic AChR formed by co-expression of a Drosophila melanogaster neuronal alpha subunit (SAD) with the chicken beta2 subunit were heterologously expressed in Xenopus oocytes by nuclear injection of cDNAs. The agonist actions of imidacloprid and other nicotinic AChR ligands ((+)-epibatidine, (-)-nicotine and acetylcholine) were compared on both recombinant nicotinic AChRs by use of two-electrode, voltage-clamp electrophysiology. 2. Imidacloprid alone of the 4 agonists behaved as a partial agonist on the alpha4beta2 receptor; (+)-epibatidine, (-)-nicotine and acetylcholine were all full, or near full, agonists. Imidacloprid was also a partial agonist of the hybrid Drosophila SAD chicken beta2 receptor, as was (-)-nicotine, whereas (+)-epibatidine and acetylcholine were full agonists. 3. The EC50 of imidacloprid was decreased by replacing the chicken alpha4 subunit with the Drosophila SAD alpha subunit. This alpha subunit substitution also resulted in an increase in the EC50 for (+)-epibatidine, (-)-nicotine and acetylcholine. Thus, the Drosophila (SAD) alpha subunit contributes to the greater apparent affinity of imidacloprid for recombinant insect/vertebrate nicotinic AChRs. 4. Imidacloprid acted as a weak antagonist of ACh-mediated responses mediated by SADbeta2 hybrid receptors and as a weak potentiator of ACh responses mediated by alpha4beta2 receptors. This suggests that imidacloprid has complex effects upon these recombinant receptors, determined at least in part by the alpha subunit.

Animals↗

Changes of perilymphatic glutamate and cochlear blood flow following ischemia.

Dynamic changes of perilymphatic glutamate and cochlear blood flow were measured simultaneously in the guinea pig following cochlear ischemia. Glutamate was measured by the microdialysis technique with a probe inserted into the scala tympani at the basal turn. Cochlear blood flow was monitored with a laser-Doppler probe on the lateral wall of the second cochlear turn. Both parameters were measured before and after electrocauterization of the anterior inferior cerebellar artery and other vessels supplying the internal auditory canal. In four animals, glutamate increased with a decline of cochlear blood flow and then decreased with recovery of blood flow. No normalization of glutamate was observed in seven animals with a persistent decrease of blood flow. The results of this study indicate that the glutamate regulating system in the cochlea is dependent on cochlear blood flow.

Animals↗

Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene.

Dihydropyrimidinase (DHP) deficiency (MIM 222748) is characterized by dihydropyrimidinuria and is associated with a variable clinical phenotype. This disease might be associated with a risk of 5-fluorouracil toxicity, although no cases have been reported. We present here both the molecular characterization of the human DHP gene and, for the first time, the mutations causing DHP deficiency. The human DHP gene spans >80 kb and consists of 10 exons. It has been assigned to 8q22, by FISH. We performed mutation analysis of genomic DNA in one symptomatic and five asymptomatic individuals presenting with dihydropyrimidinuria. We identified one frameshift mutation and five missense mutations. Two related Japanese adult subjects were homozygous for the Q334R substitution, whereas two other, unrelated Japanese infant subjects were heterozygous for the same mutation, but this mutation is not common in the Japanese population. A Caucasian pediatric patient exhibiting epileptic attacks, dysmorphic features, and severe developmental delay was homozygous for W360R. Using a eukaryotic expression system, we showed that all mutations reduced enzyme activity significantly, indicating that these are crucial DHP deficiency-causing mutations. There was no significant difference, in residual activity, between mutations observed in the symptomatic and those observed in the asymptomatic individuals.

Adult↗

Activation of microvascular endothelial cells in active ulcerative colitis and detection of inducible nitric oxide synthase.

Endothelial nitric oxide (NO) synthase (NOS) that is expressed constitutively on microvascular endothelium is believed to be essential to systemic and/or local vascular integrity. Endothelial cells (ECs) were reported to express inducible NOS (iNOS) under some conditions iNOS expression indicates vascular activation. In this study we examined microvascular activation using ECs obtained from patients with ulcerative colitis (UC). We cultured ECs from the mesenteries of surgical UC patients and assayed NOS activity by NADPH-diaphorase cytochemistry and immunocytochemistry with an anti-iNOS antibody. Strong NOS activity was demonstrated on the cells from UC patients (5/5), whereas no activity was detected on the cells from cancer patients and human umbilical vein endothelial cells (HUVEC 0/5, 0/5). Strong iNOS activity was detected by immunoreaction, and large amounts of NO generated were detected by the conversion from [14C]arginine to [14C]citrulline (HUVEC 624+/-376 vs. EC-UC 1,492+/-233 dpm). These results suggest the possibility that ECs express spontaneous and continuous iNOS in active UC. They indicate a close relationship of vascular activation with the pathogenesis of UC.

Adult↗

Cellular injury score for multiple organ failure severity scoring system.

BACKGROUND: Cellular Injury Score (CIS) is an index of cellular injury, being calculated from three parameters of intracellular metabolism: arterial ketone body ratio, osmolality gap, and blood lactate. METHODS: The usefulness of CIS as a severity scoring system for patients with multiple organ failure was prospectively evaluated in 157 consecutive patients with MOF (58 survivors, 99 nonsurvivors). RESULTS: CISs in nonsurvivors were significantly higher compared with those in survivors throughout the clinical courses. CIS was significantly correlated with the number of failing organs and mortality rate. The optimal cutoff point of CIS from receiver operating characteristics curve analysis was 4 for the maximal value during the clinical course. The changes in CIS well reflected the severity of injury in survivors and nonsurvivors who died within 2 weeks. CONCLUSION: CIS could be a useful index for mortality risk prediction and is potentially applicable as a severity scoring system for individual patients with MOF.

3-Hydroxybutyric Acid↗

Alteration of p53 clonality accompanying colorectal cancer progression.

The aim of this study was to clarify whether or not the status of gene alteration is heterogeneous in intramucosal carcinoma and homogeneous within invasive carcinoma. We selected 10 colorectal carcinoma cases (1 mucosal, 5 submucosal and 4 advanced carcinomas including 2 cases with lymph node metastasis) and analyzed the p53 gene sequence. Six colorectal cancers in this study showed heterogeneity in p53 mutations in cells from the intramucosal part. In the invasive part of a carcinoma, p53 mutation status was homogeneous intratumorally in all cases. These data indicate that, in regard to p53 gene alterations, colorectal cancers can be composed of various subclones when limited to the mucosa, but clonal selection occurs when one of these subclones commences invasion to the submucosa, generating a monoclonal invasive carcinoma.

Adenoma↗

Sucrose permeability as a means of detecting diseases of the upper digestive tract.

The healthy gastric epithelium will not allow easy permeation of a disaccharide-sized molecule such as sucrose. However, during gastric damage, intact sucrose can pass the gastric epithelium and ultimately appear in the urine. We examined the relationship between total urinary sucrose excretion and various diseases. We used 149 patients (105 had upper gastrointestinal disease, 12 had gastric cancer and 32 were normal). Subjects were given a solution containing 100 g sucrose in 450 c.c. water. All urine was collected for 7.5 h. The urinary sucrose concentration was determined by anion exchange high-performance liquid chromatography. Total urinary sucrose excretion was significantly higher in patients with gastric ulcer and those with gastric cancer than in endoscopically normal controls. In the 34 patients with gastric ulcer, the total sucrose excretion was closely correlated with ulcer size. Ulcer location did not affect urinary sucrose excretion. A strong correlation was also observed between sucrose excretion and lesion size in the 12 patients with gastric cancer. The sucrose permeability test may be a relatively sensitive method to detect gastric disease.

Case-Control Studies↗

An infant with Costello syndrome complicated with fatal hypertrophic obstructive cardiomyopathy.

We report a 3-month-old girl with Costello syndrome complicating fatal hypertrophic obstructive cardiomyopathy. She had typical findings of this syndrome, slight dyspnea and persistent wheezing. Doppler echocardiography revealed asymmetric septal hypertrophy and systolic anterior movement of the anterior mitral leaflet. There was grade 1 mitral regurgitation. Although once her heart failure had been controlled medically, she died suddenly following deterioration of her heart condition. Costello syndrome can complicate fatal hypertrophic obstructive cardiomyopathy.

Abnormalities, Multiple↗