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Biomedical subjects

S Ishiguro

Publications and source records attributed to S Ishiguro.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryo genesis and roles for mandibular chondrogenesis].

Quail-chick chimera experiments have shown a contribution of carnial neural crest cells to the craniofacial skeletal elements. Moreover, tissue interactions between epithelial-mesenchymal interaction during early facial process development are required for both skeletal differentiation and morphogenesis. In this study, it was observed that Msx homeobox containing genes expressed in the facial process were important molecules of cartilage morphogenesis. Rat cDNAs were isolated and encoded by Msx-1 and -2, and then the expression patterns using in situ hybridization were investigated during early rat face development. These genes were correlatively expressed in the cranial neural crest forming area (E 9.5 dpc) and the facial process (E 12.5 dpc). Antisence inhibition of Msx genes in the E 12.5 mandibular process exhibited the alteration of their gene expression and cartilage patterns. Antisence inhibition of Msx-1 induced lack of the medial portion of cartilage, and antisence inhibition of Msx-2 enhanced chondrogenesis of mandibular process under the organ culture condition. Thus it was concluded that expression of Msx genes during mandibular process development comprises important signals of chondrogenesis.

Animals↗
PubMed1999

[Renal oncocytoma with cystic degeneration: a case report].

A 45-year-old man was referred to our department because of a right renal mass which was incidentally found at a health screening. Ultrasound sonography, computerized tomography and magnetic resonance imaging showed a hypovascular tumor 3 cm in diameter with the fluid at the upper pole of the right kidney, implicating that the tumor was renal cell carcinoma originating from a renal cyst wall, or with central necrosis. A radical nephrectomy was therefore performed. The tumor was dark-brown and contained brown fluid. The histopathological findings showed renal oncocytoma with cystic degeneration.

Adenoma, Oxyphilic↗
PubMed1998

KAI1/CD82 expression in nonsmall cell lung carcinoma is a novel, favorable prognostic factor: an immunohistochemical analysis.

BACKGROUND: The KAI1/CD82 gene, the product of which is a member of the transmembrane-4 superfamily, is a suppressor of metastasis; as a result, it is inversely associated with tumor progression and is a favorable prognostic factor in some tumors. This study was performed to determine the prognostic value of KAI1/CD82 protein levels in nonsmall cell lung carcinoma (NSCLC). In addition, levels of KAIl/CD82 expression in metastatic lesions were determined and compared with those in primary NSCLC lesions. METHODS: KAI1/CD82 expression in 200 NSCLC patients who underwent potentially curative surgery was immunohistochemically detected with C33, an anti-KAI1/CD82 monoclonal antibody. According to the degree of KAI1/CD82 positive cancer cells within the tumor tissue, each sample was classified as KAI1/CD82 positive, KAI1/CD82 reduced, or KAI1/CD82 negative. RESULTS: Sixty-five samples (32.5%) were KAI1/CD82 positive, 31 (15.5%) were reduced, and 104 (52%) were negative. There was no significant association between KAI1/CD82 expression and clinicopathologic factors, but patients who were positive for KAI1/CD82 expression had significantly favorable prognoses for overall survival (P = 0.0026) and disease free survival (DFS; P = 0.0007) compared with the other groups. In particular, among patients with adenocarcinoma, similar results were even more significant. In multivariate analysis, immunohistochemical KAI1/CD82 expression in patients with NSCLC was an independent prognostic factor for overall survival and DFS; in those with adenocarcinoma, it was an even more valuable factor. In some patients with NSCLC, especially those with adenocarcinoma, KAI1/CD82 expression levels in metastatic lesions were diminished compared with levels of expression in the primary lung lesions. CONCLUSIONS: The immunohistochemically determined level of KAI1/CD82 expression in NSCLC cells within tumor tissue appears to be a favorable prognostic factor for overall survival as well as DFS. The results of this study suggest that decreased KAI1/CD82 expression may be associated with tumor progression and enhanced metastatic potential in some patients with this disease.

Adult↗
PubMed1998

Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations.

Among 222 primary colorectal cancers we examined, 58 showed no detectable APC mutations by the protein truncation test. We screened those 58 tumors for somatic mutations in the beta-catenin gene. Although amino acid substitutions in serine or threonine residues in exon 3 had been reported, we found no such mutations; however, in seven tumors, we detected somatic interstitial deletions of 234-760 bp, each of which included all or part of exon 3. Short nucleotide sequences at both ends of each deletion were either identical or complementary, indicating that repeated or inversely repeated sequences were involved in the somatic rearrangements. Reverse transcription-PCR experiments using RNAs isolated from three of these seven tumors detected transcripts that lacked exon 3, in addition to the normal transcript. In one of these cases, we confirmed accumulation of aberrant beta-catenin protein in cytoplasm and nuclei of cancer cells by Western and immunohistochemical analyses. This result suggested that, in the absence of a peptide encoded by exon 3, beta-catenin is stabilized and has a dominant oncogenic effect on colorectal tumorigenesis.

Carcinoma↗
PubMed1998

Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.

Amino Acid Sequence↗
PubMed1998

Regulation of intracellular calcium concentrations by calcium and magnesium in cardioplegic solutions protects rat neonatal myocytes from simulated ischemia.

The effects of calcium and magnesium ions in cardioplegic solutions on cardioprotection and intracellular calcium ion handling during ischemia and reoxygenation were investigated in cultured neonatal rat myocardial cells. Myocytes were subjected to simulated ischemia for 60 min at 37 degrees C in hyperkalemic cardioplegic solutions containing various concentrations of calcium and magnesium ions, followed by 30 min of reoxygenation. For each Ca2+ concentration (0.1, 0.6, 1.2, or 2.4 mM), the Mg2+ concentration was either 0, 1.2, 8, or 16 mM. The increase in intracellular Ca2+ concentration during ischemia and reoxygenation was suppressed by the addition of magnesium ion, independent of cardioplegic Ca2+ concentration. The recovery of spontaneous contraction rate and enzyme leakage (creatine phosphokinase and lactate dehydrogenase) during both ischemia and reoxygenation correlated with the degree of inhibition of intracellular Ca2+ accumulation. However, in the 0.1 mM Ca2+ groups in which the Mg2+ concentration was greater than 8 mM, the intracellular Ca2+ concentration increased during reoxygenation in a dose-dependent fashion of Mg2+, and was associated with increased enzyme leakage. The findings suggest that in immature cardiac myocytes, the concentrations of Ca2+ and Mg2+ present in cardioplegic solutions control the intracellular Ca2+ concentration during ischemia and reoxygenation, which, in turn, influences the cardioprotective effect of the cardioplegic solution.

Animals↗
PubMed1998

Perioperative changes in plasma brain natriuretic peptide concentrations in patients undergoing cardiac surgery.

The plasma concentrations of brain natriuretic peptide (BNP), a cardiac hormone, were measured in 30 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) during the perioperative period. BNP concentrations remained unchanged until 6 h after the cessation of bypass, and were elevated 12, 24, and 48 h post-bypass (P < 0.0001 versus baseline). They had returned to the baseline values when measured 3 weeks postoperatively. The preoperative plasma BNP concentration correlated significantly with the left ventricular ejection fraction (r = -0.895). The peak plasma BNP concentration 24 h after bypass correlated with the cardiac index (r = -0.64), stroke volume index (r = -0.62), injection rate of dopamine hydrochloride (r = 0.65), and aortic crossclamp time (r = 0.57). There was also a significant correlation between the preoperative BNP concentration and the plasma BNP concentration 24 h post-CPB. These findings led us to conclude that the plasma concentrations of BNP become markedly and acutely elevated after cardiac surgery with CPB, and reflect the state of left ventricular function. Moreover, the severity of acute heart failure after cardiac surgery can be predicted by the preoperative plasma BNP concentration.

Cardiac Surgical Procedures↗
PubMed1998

rim2 (recombination-induced mutation 2) is a new allele of pearl and a mouse model of human Hermansky-Pudlak syndrome (HPS): genetic and physical mapping.

A mouse mutation, rim2, is one of a series of spontaneous mutations that arose from the intra-MHC recombinants between Japanese wild mouse-derived wm7 and laboratory MHC haplotypes. This mutation is single recessive and characterized by diluted coat color and hypo-pigmentation of the eyes. We mapped the rim2 gene close to an old coat color mutation, pearl (pe), on Chromosome (Chr) 13 by the high-density linkage analysis. The pearl mutant is known to have abnormalities similar to Hermansky-Pudlak syndrome (HPS), a human hemorrhagic disorder, characterized by albinism and storage pool deficiency (SPD) of dense granules in platelets. A mating cross of C57BL10/Slc-rim2/rim2 and C57BL/6J-pe/pe showed no complementation of coat color. Additionally, characteristics similar to SPD were also observed in rim2. Thus, rim2 appeared to be a new allele of the pe locus and serves as a mouse model for human HPS. We have made a YAC contig covering the rim2/pe locus toward positional cloning of the causative gene.

Albinism, Oculocutaneous↗
PubMed1998

A new mutation Rim3 resembling Re(den) is mapped close to retinoic acid receptor alpha (Rara) gene on mouse chromosome 11.

A new mouse mutation, recombination-induced mutation 3 (Rim3), arose spontaneously in our mouse facility. This mutation exhibits corneal opacity as well as abnormal skin and hair development resembling rex denuded (Re(den)) and bareskin (Bsk). Large-scale linkage analysis with two kinds of intersubspecific backcrosses revealed that Rim3 is mapped to the distal portion of Chromosome (Chr) 11, in which Re(den) and Bsk have been located, and is very close to the retinoic acid receptor, alpha (Rara). The genes, keratin gene complex-1, acidic, gene 10, 12 (Krt1-10, 12), granulin (Grn), junctional plakoglobin (Jup) and Rara, all of which regulate growth and differentiation of epithelial cells, are genetically excluded as candidate genes for Rim3, but are clustered in the short segment on mouse Chr 11.

Animals↗
PubMed1998

Multidrug-resistant recurrent breast cancer which responded to medroxyprogesterone acetate showing a remarkable improvement in the quality of life: report of a case and the role of team medical care.

We herein report the case of a patient with recurrent breast cancer who showed a remarkable improvement in her quality of life (QOL) as a result of a good response to medroxyprogesterone acetate (MPA). A 43-year-old Japanese woman developed bone metastases 3 years after surgery. Subsequent radiotherapy and chemoendocrine therapy with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and tamoxifen all failed, and she could not sit up because of bone metastases. The performance status (PS) on admission was grade 4. After admission, delirium accompanied with sensory and visual hallucination caused by intense anxiety occurred, and a continuous consultation by psychiatrists was necessary. MPA treatment at the dose of 1200 mg/day alleviated the bone pain, thus improving her PS to grade 1. Her appetite also improved, while her mental state stabilized. A bone scintigram revealed an improvement of bone metastases, and the tumor markers also returned to normal values. The patient thus showed a pronounced improvement in her QOL due to both MPA treatment and team medical care. The role of the medical staff as well as the importance of their cooperation in achieving an improvement in the QOL of cancer patients is also discussed.

Adult↗
PubMed1998

Intraoperative cytodiagnosis for detecting a minute invasion of the portal vein during pancreatoduodenectomy for adenocarcinoma of the pancreatic head.

During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we frequently encountered cases in which the superior mesenteric-portal venous confluence (SMPVC) was involved with cancer. With regard to the indication of the concomitant SMPVC resection, as suggested by recent papers, a better long-term outcome would be expected if the cancer invasions were limited to the tunica adventitia or media of the SMPVC wall. Since this raised fears whether such a small SMPVC invasion was always detectable by macroscopic inspection alone, we have performed an intraoperative cytology on the touch smear of the exposed SMPVC wall for 23 patients with pancreatic head cancer. All of their SMPVCs were separated from the pancreatic head and appeared to be intact at a macroscopic level. As a result of the cytologic examination, however, 7 patients (30%) were newly diagnosed as having cancer cells on the SMPVC wall, and they received an additional resection of the SMPVC. Postoperative histology indicated that cancer invasion into the SMPVC wall was present in 6 of the 7 patients, and that the cancer invasions were limited in the tunica adventitia in 5 patients and to the tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC resection, our intraoperative cytology on the touch smear of the SMPVC is worth performing more actively on the macroscopically intact-looking SMPVC during resection of pancreatic cancer.

Adenocarcinoma↗
PubMed1998

Potentiation of retinoic acid-induced differentiation of HL-60 cells by prostaglandin EP2 receptor.

Human promyeloid HL-60 cells are differentiated by all-trans retinoic acid (RA) to granulocytes, and prostaglandin (PG) E2 potentiates the RA-induced differentiation. Here we examined which subtype of PGE receptors was involved in this potentiating activity of PGE2. Northern blot analysis demonstrated that HL-60 cells expressed three subtypes of PGE receptor, EP2, EP3, and EP4. Among various EP agonists, and EP2-selective agonist, butaprost, preferentially potentiated the RA-induced differentiation of HL-60 cells. Butaprost not only decreased the half-maximal concentration of RA but also increased the maximal level of the differentiation. Butaprost concentration-dependently stimulated the cAMP formation, and 8-Br-cAMP strongly potentiated the RA-induced differentiation. These results demonstrate that the EP2 receptor enhances the RA-induced differentiation of HL-60 cells via stimulation of adenylate cyclase.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Myoepithelioma of the lung: report of two cases and review of the literature.

Myoepithelial tumors occur mainly in the salivary glands, the sweat glands or the breast, but uncommonly in the lung. Herein, we describe two cases of myoepithelioma of the lung. Both patients were 58-year-old men, in whom the tumors were located in the right-upper bronchus and in the left-upper bronchus, respectively, with endobronchial growth pattern. Surgery was performed, but metastasis occurred into the forearm and hip muscles in the former case, and into the liver in the latter. Histologically, the tumor in the former was a spindle-plasmacytoid type, and that in the latter was a plasmacytoid type in part with squamous differentiation. Based on histochemical, immunohistochemical and ultrastructural analyses, both were compatible with myoepithelioma. The clinicopathological uniqueness of this neoplasm is discussed, together with a review of reports of this disease in the literature.

Fatal Outcome↗
PubMed1998

The role of thromboxane A2 in regulating porcine basilar arterial tone.

The aim of the present study was to clarify the participation of endogenous arachidonic acid (AA) metabolites in regulating porcine basilar, coronary, pulmonary and mesenteric arterial tones in vitro. A cyclooxygenase inhibitor, indomethacin, relaxed basilar artery but not other arteries examined. Quinacrine (a phospholipase A2 inhibitor), OKY-046 (a thromboxane (TX) A2 synthetase inhibitor) and ONO-3708 (a TXA2/prostaglandin H2 receptor antagonist) produced relaxation in basilar arteries with intact endothelium. Nordihydroguaiaretic acid (a lipoxygenase inhibitor) had no effect on the tone. The amount of TXB2 (a stable metabolite of TXA2) spontaneously released from porcine basilar arteries was 6-10 fold more than those from other arteries. Indomethacin and OKY-046 mostly inhibited the production of TXB2. Endothelial denudation decreased indomethacin-induced relaxation and the amount of TXB2. These results suggest that a vasoconstricting substance(s) is released from endothelial cells and possibly smooth muscle cells in porcine basilar arteries in vitro. The main constricting substance is proposed to be TXA2. On the other hand, several arteries from peripheral vascular beds did not release this vasoconstricting substance.

Animals↗
PubMed1998

Femtomolar bradykinin-induced relaxation of isolated bovine coronary arteries, mediated by endothelium-derived nitric oxide.

We reported previously that bradykinin induces endothelium-dependent relaxation at nanomolar (nM) concentrations in isolated bovine coronary arteries with an intact endothelium. Recently we have found that in the presence of 10 microM indomethacin, femtomolar (fM) concentrations of bradykinin induce endothelium-dependent relaxation in some bovine coronary arteries (approximately 10% of the coronary arteries examined). The present study was designed to characterize the relaxation induced by fM bradykinin. Relaxation was completely abolished by repeated application of fM bradykinin, by 100 microM N(omega)-nitro-L-arginine methyl ester and by 10 microM methylene blue. Relaxation induced by nM bradykinin was partly affected by these treatments. Relaxation induced by both concentrations of bradykinin was inhibited by a B2-kinin receptor antagonist, [Thi5,8, D-Phe7]-bradykinin, in a concentration-dependent manner, but not by a B1-kinin receptor antagonist, des-Arg9, [Leu8]-bradykinin. In the presence of 10 microM captopril, an angiotensin-converting enzyme (ACE) inhibitor, all coronary arteries examined in this experiment showed endothelium-dependent relaxation to fM bradykinin. These results show that some bovine coronary arteries relax in response to fM bradykinin, and this response is mediated predominantly by the release of nitric oxide via stimulation of endothelial B2-kinin receptors. The relaxation may be dependent on ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Prevention of gastric ulcer recurrence with tetraprenylacetone.

BACKGROUND: The role of cytoprotective agents in the treatment of ulcers remains unclear. In the present study we investigated the effect of tetraprenylacetone (TAP), a cytoprotective agent, on healing and recurrence of gastric ulcers infected with Helicobacter pylori and on the mucosal microvascular architecture of healed gastric ulcers. PATIENTS: Ninety-five gastric ulcer patients with H. pylori infection were studied. METHODS: Gastric ulcer patients with H. pylori infection received 20 mg omeprazole (44 patients) or 20 mg omeprazole and 150 mg TAP (46 patients) in random fashion. Ulcer healing was assessed with endoscopy 12 weeks after the start of treatment. The patients with healed ulcer were followed up for another 12 months without further therapy. During endoscopic examination at week 12, biopsy specimens were obtained from healed gastric ulcers, and the gastric mucosal microvascular architecture of the biopsy specimens was observed by means of the alkaline phosphatase staining method. RESULTS: The rate of ulcer healing at week 12 was similar in patients treated with omeprazole with and without TAP. However, at or within 12 months of the start of follow-up observation, ulcers recurred significantly less frequently in patients treated with both omeprazole and TAP than in those treated with omeprazole alone. Alkaline phosphatase staining methods showed that the mucosal microvascular architecture improved significantly more frequently in healed gastric ulcers that had been treated with both omeprazole and TAP than in those treated with omeprazole alone. CONCLUSIONS: Treatment with TAP plus omeprazole significantly decreases ulcer recurrence through TAP's improved mucosal restoration.

Adult↗