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Biomedical subjects

K Mitsui

Publications and source records attributed to K Mitsui.

At least 73 records · Page 4Linked to original sources

[A case of asynchronous renal cell carcinoma, hepatocellular carcinoma and residual ureteral cancer].

A case of asynchronous triple cancer in an 88-year-old male is reported. Six years ago, he had received left radical nephrectomy for renal cell carcinoma, and 2 years ago partial hepatectomy for hepatocellular carcinoma detected by follow-up computed tomography (CT). During the post-operative follow-up, no metastasis of either the renal or hepatic carcinoma was detected. On February 12, 1997 he presented with macroscopic hematuria. Cystoscopy revealed a tumor emerging from the left ureteral orifice, while CT and magnetic resonance imaging (MRI) revealed a tumor mass in the left exterior of bladder. Diagnosis of residual ureter tumor, we performed both left ureterectomy and partial cystectomy. Histological diagnosis revealed transitional cell carcinoma of the residual ureter (G2 > G3, pT1, pV0, pL0, pR0). Convalescence was uneventful and 10 months after the operation, he is alive with no recurrence or metastasis. We stress the importance of careful follow-up not only to perceive the recurrence or metastasis of renal cancer but also to detect cancer in other parts of the body.

Aged↗

Cloning and characterization of novel CIS family genes.

We have reported two JAK-signaling modulators, CIS (cytokine-inducible SH2 protein) and JAB (JAK2 binding protein), which are structurally related. Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search. We also found at least two additional candidates of this gene family in the database. These genes were induced by erythropoietin and granulocyte-macrophage colony stimulating factor in certain hematopoietic cell lines. The SH2 domain and a C-terminal 40 amino acid region, designated the CIS homology domain (CH domain), are highly conserved in this family, while the N-terminal regions of these proteins share little similarity. A yeast two-hybrid assay and in vitro and in vivo binding assays revealed that in addition to JAB, CIS3 bound to the JAK2 tyrosine kinase domain (JH1), although the interaction of CIS3 with the JAK2-JH1 domain was much weaker than that of JAB. Transient expression of JAB and CIS3, but not other CISs, strongly inhibited leukemia inhibitory factor (LIF)-induced STAT3-reporter gene activation in 293 cells. Furthermore, constitutive overexpression of JAB and CIS3 in M1 leukemia cells prevented LIF-induced differentiation and growth arrest. Although the physiological function remains to be investigated, CIS family genes could play a role in the negative regulation of cytokine signaling by interacting with specific targets.

Amino Acid Sequence↗

A new protein containing an SH2 domain that inhibits JAK kinases.

The proliferation and differentiation of cells of many lineages are regulated by secreted proteins known as cytokines. Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases. Cytokine-induced receptor dimerization leads to the activation of JAKs, rapid tyrosine-phosphorylation of the cytoplasmic domains, and subsequent recruitment of various signalling proteins, including members of the STAT family of transcription factors, to the receptor complex. Using the yeast two-hybrid system, we have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine-inducible SH2 protein. Interaction of JAB with Jak1, Jak2 or Jak3 markedly reduces their tyrosine-kinase activity and suppresses the tyrosine-phosphorylation and activation of STATs. JAB and CIS appear to function as negative regulators in the JAK signalling pathway.

Amino Acid Sequence↗

CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation.

We searched for immediate early cytokine responsive genes and isolated a novel gene, CIS (Cytokine Inducible SH2 containing protein) that is induced in hematopoietic cells by a subset of cytokines including interleukin-2 (IL-2), IL-3, and erythropoietin (EPO). The mutant IL-2 receptor that fails to activate STAT5 could not induce CIS, suggesting that STAT5 is involved in the cytokine-inducible expression of CIS. We cloned the 5'-flanking region of the CIS gene and found that about 200 bases upstream of the transcription-initiation site contain four potential STAT5 binding sites (MGF boxes). Luciferase reporter assays showed that these MGF boxes were essential for EPO-dependent promoter activity. Expression of STAT5 and the EPO receptor in HEK293 cells conferred EPO-dependent activation of the CIS promoter. These data indicate that CIS is a target of the JAK-STAT5 pathway of cytokine receptors. CIS contains an SH2 domain and binds to tyrosine-phosphorylated EPO and IL-3 receptors. In HEK293 cells expressing STAT5 and the EPO receptor, EPO-dependent tyrosine phosphorylation of STAT5, as well as EPO-dependent CIS-promoter activation, was suppressed when CIS was coexpressed. Moreover, the induction of oncostatin M, another STAT5 target, as well as the tyrosine-phosphorylation of STAT5, were partially suppressed by CIS expression in Ba/F3 cells. Thus, CIS is a feedback modulator of STAT5; its expression is induced by STAT5 and it negatively modulates STAT5 activation.

Amino Acid Sequence↗

Cell cycle arrest and apoptosis of leukemia cells induced by L-asparaginase.

Apoptotic cell death of murine leukemia cells induced by E. coli L-asparaginase was studied. Deprivation of L-asparagine from the culture of L5178Y cells by L-asparaginase caused the fragmentation of chromosomal DNA of the leukemia cells within 24 h. Prior to the degradation of DNA, cell cycles of L5178Y cells were found to be arrested in G1 phase, and evidence of the DNA strand breaks was initially observed in G1 phase cells as early as 8 h after the asparaginase treatment. Therefore, apoptosis of leukemia cells induced by L-asparaginase is an event that is associated with the cell cycle arrest in G1 phase.

Animals↗

[In vitro antifungal activity of rilopirox, a new hydroxypyridone antimycotic agent].

In vitro antifungal activities of rilopirox (RIL), a new topical hydroxypyridone antifungal agent, were studied against 7 species (31 strains) of yeast-like fungi and 15 species (17 strains) of mycerial fungi from stock cultures of a wide range of medically important fungi. Tests were carried out by the liquid dilution method using Neopeptone dextrose broth with ciclopirox olamine (CPO) and oxiconazole nitrate (OCZ) as reference drugs. RIL exhibited a broad spectrum of antifungal activities; the MIC of RIL against yeasts were about 1 microgram/ml, those against other fungi were 0.5-4 micrograms/ml. Antifungal activities were similar to CPO, and compare to OCZ, RIL showed characteristically little differences in its activities against different species or strains of target organisms.

Antifungal Agents↗

Mechanical unfolding of alpha2-macroglobulin molecules with atomic force microscope.

alpha2-Macroglobulin was derivatized with a sulfhydryl cross-linker and sandwiched between a mica substrate and a silicon nitride tip, both coated with gold, of an atomic force microscope and force curve measurement was carried out. An extensive downward deflection of the cantilever was observed in the retracting realm of the curve, when and only when the substrate was covered with the derivatized protein. The result was interpreted in terms of the mechanical stretching and unfolding of a single or a few protein molecules.

Cross-Linking Reagents↗

The pleiotropic effect of the GTS1 gene product on heat tolerance, sporulation and the life span of Saccharomyces cerevisiae.

We investigated whether or not the potential clock gene, GTS1, of the yeast Saccharomyces cerevisiae, shows pleiotropic effects on the yeast cellular processes. We tested the efect of the Gts1 protein on heat tolerance, sporulation and life-span, by characterizing the phenotypes of transformants with different copy numbers of the gene. We found that the Gts1 protein affects the capacity of heat tolerance in the stationary phase and the speed leading to sporulation in a gene-dose dependent manner, and that both inactivation and overexpression of the gene shortened the life-span of yeast. These results supported the notion that GTS1 affects the biological clock of the yeast S. cerevisiae, although this cannot be definitively concluded because the strain cannot be synchronized with circadian or ultradian rhythms.

Fungal Proteins↗

Preoperative radiotherapy and surgery for advanced thymoma with invasion to the great vessels.

From 1983 to 1994, 12 advanced thymomas with invasion to the great vessels were initially treated by irradiation (mean dose, 18.3 Gy) and subsequent surgical resection. In nine patients, complete resection was possible by concomitant resection of the surrounding tissues, mainly pericardium and/or brachiocephalic vein. Histologically, all tumors showed prominent fibrosis. Ten patients also received postoperative radiotherapy (mean dose, 42.3 Gy). Tumor-related deaths occurred in only two patients; one who did not receive postoperative irradiation 21 months and one who had viable cells at the surgical margin 10 months after operation. However, there were also 2 patients who died of respiratory failure due to operation and/or irradiation, one 45 days and the other 7 years after the treatment. Preoperative radiotherapy could facilitate complete resection of the advanced thymomas. The prognosis of the patients treated with preoperative radiotherapy seemed fair if followed by adequate resection and subsequent irradiation.

Adult↗

Changes in diastolic regional stiffness of the left ventricle before and after coronary artery bypass grafting.

To evaluate the effect of coronary artery bypass grafting (CABG) on regional diastolic function of the left ventricular wall, we applied the concept of the stiffness constant to the diastolic sigma-ln (1/H) relation, where sigma is the mean wall stress, and H is the wall thickness of the region of concern, and ln (1/H) is the natural logarithm of the reciprocal of wall thickness. We assessed 12 cardiac regions in six patients with coronary artery disease who underwent CABG at the Cardiovascular Hospital of Central Japan between May 1994 and January 1995. Left ventricular pressure and regional wall thickness were measured simultaneously, with a micromanometer-tipped catheter and by two-dimensional echocardiography, respectively, before and after CABG. The stiffness constant (K) was obtained by fitting the diastolic sigma-ln (1/H) data points to an exponential curve with zero asymptote: sigma = Cexp[Kln (1/H)]. Preoperatively, the stiffness constant in the affected region (CABG region) was greater than that in the unaffected region (non-CABG region) (4.79 +/- 2.56 vs 2.95 +/- 0.72). Postoperatively, the stiffness constant in the CABG region was significantly decreased, to 3.21 +/- 1.22. The stiffness constant, which is derived from the sigma-ln (1/H) relation, is useful for the assessment of LV regional diastolic function.

Aged↗

Cherubism: diagnostic imaging and review of the literature in Japan.

Cherubism is a nonneoplastic disease of bone characterized by clinical, bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance. Cherubism may appear in solitary cases or in many members of the family, often in multiple generations. On radiography the lesions have the appearance of bilateral multilocular radiolucent areas. On histopathologic evaluation the lesions show proliferating fibrous connective tissue containing numerous multinucleated giant cells. Since it was first described by Jones in 1933, many cases have been documented without restriction to any one country or ethnic group, but only a few cases have been reported in Japan, apparently because it is rare here. We report a case of cherubism in a 15-year-old boy and review the Japanese literature.

Adolescent↗

Thoracoscopic repair of diaphragmatic hernia.

A 22-year-old woman presented with left subcostal pain and nausea. A radiograph and a computed tomographic scan of the chest revealed diaphragmatic hernia. Thoracoscopic surgery was performed. The herniated organs were put back into the peritoneal cavity and the hernial hilum was closed with interrupted silk suturing.

Adult↗

Hepatic HCV-RNA as a predictor of outcome after interferon therapy in patients with chronic hepatitis C.

Measurement of serum HCV-RNA is a useful index for evaluating the antiviral effect of interferon therapy in chronic hepatitis C. In the present study, we investigated whether the detection of hepatic HCV-RNA after interferon treatment, using a polymerase chain reaction assay, predicted long-term response to therapy in patients with chronic hepatitis C. Thirty-three patients underwent liver biopsies before and after interferon therapy. Histology and clinical courses were compared after treatment. Before therapy, serum and hepatic HCV-RNA was detected in specimens from 32 (97%) and 33 (100%) patients, respectively. Serum HCV-RNA became undetectable in samples from 22 (67%) patients; however, in 10 of these patients (45%), serum HCV-RNA levels relapsed after therapy. Hepatic HCV-RNA became undetectable in 14 patients after therapy and the serum aminotransferase concentration remained within normal limits during and following (24-92 weeks) therapy in 12 of these patients (86%). All 11 patients with detectable hepatic HCV-RNA also had serum HCV-RNA and elevated aminotransferase concentrations refractory to therapy. The absence of hepatic HCV-RNA at the end of interferon treatment thus predicted a long-term complete response to therapy with a sensitivity of 100%, a specificity of 90% and an accuracy of 94%. We conclude that hepatic rather than serum HCV-RNA is a more useful index for the prediction of the long-term efficacy of interferon therapy.

Adult↗

Effect of dietary linoleic, alpha-linolenic and arachidonic acids on lipid metabolism, tissue fatty acid composition and eicosanoid production in rats.

Rats were fed semipurified diets containing 10% fat with a constant polyunsaturated/monounsaturated/saturated fatty acid ratio of 1:1:1. This was performed by mixing vegetable oils. Linoleic acid was the sole polyunsaturated fatty acid in the linoleic acid group. The alpha-linolenic and arachidonic acids were contained at the 1% level in the diet at the expense of linoleic acid in the alpha-linolenic acid and arachidonic acid groups, respectively. The concentration of serum triglyceride, phospholipid and liver triglyceride were significantly lower in the alpha-linolenic acid and arachidonic acid groups than in the linoleic acid group. Hepatic phospholipids were significantly higher in the alpha-linolenic acid and arachidonic acid group as compared to the linoleic acid group. Compared to the linoleic acid group, the percentages of arachidonic acid in the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the liver and heart were significantly lower in the alpha-linolenic acid group; in contrast, they were significantly higher in the arachidonic acid group. Dietary arachidonic acid, but not alpha-linolenic acid, resulted in a marked reduction of linoleic acid and increased arachidonic and n-6 docosapentaenoic acids in heart cardiolipin. Platelet thromboxane (TX) A2 production tended to be lower in the alpha-linolenic acid group as compared to the linoleic acid and arachidonic acid groups. There was no difference in TXA2 production between the linoleic acid and arachidonic acid groups. The aortic production of prostacyclin (PGI2) was the same among the three groups. The ratios of TXA2 and PGI2 in the linoleic acid and arachidonic acid groups were comparable, whereas they were significantly higher than that in the alpha-linolenic acid group. The results demonstrate that dietary arachidonic acid enriches the arachidonic acid content in tissue phospholipids more effectively than linoleic acid, whereas the effect on the production of TXA2 and PGI2 was comparable under these experimental conditions.

Animals↗

[A case of resected lung cancer associated with bullous pemphigoid].

The relationship between bullous pemphigoid and malignancies of visceral organs is still controversial. A case of lung cancer associated with bullous pemphigoid is reported. A 63-year-old man admitted hospital because of multiple bullae of the whole body skin and continuous fever. The skin lesions were diagnosed as bullous pemphigoid by the skin biopsy. However, the chest x-ray on admission revealed a large tumor in the left upper lung field. The tumor was diagnosed as a lung cancer by trans-bronchial lung biopsy. The fever withdrew with the administration of prednisolone. The left upper lobectomy of the lung and mediastinal lymph node dissection were performed. The skin lesion disappeared 5 days after the surgery. This clinical course is thought to indicate the relationship of both diseases. Bullous pemphigoid is thought to have many problems during perioperative period, such as hypoproteinemia and delayed wound healing due to administration of the steroid, therefore intensive care is necessary in the perioperative care.

Adenocarcinoma↗

Renal oncocytoma treated by surgical enucleation: a case report.

We experienced a case of renal oncocytoma, in a 46-year-old woman. At a health examination, ultrasonography revealed a right renal tumor, and she was admitted to our hospital for evaluation. From the ultrasonogram, computerized tomography (CT) and angiography, we suspected a renal oncocytoma, but renal cell carcinoma was not completely ruled out. Since the location of the tumor seemed suitable for a local resection, we scheduled a surgical enucleation, but we intended to switch to a radical nephrectomy if examination of a frozen-section suggested renal cancer. Because the frozen findings were suggestive of an oncocytoma without malignancy, the surgical enucleation procedure was completed as scheduled. Pathological findings of the resected specimens were characterized by granular eosinophilic cytoplasm, and rounded nuclei without nuclear pleomorphism or mitotic figures. Electron microscopic studies revealed an increased number of mitochondria. The patient was accordingly diagnosed as having renal oncocytoma. We also reviewed the literature to elaborate procedures for a preoperative diagnosis and therapy for renal oncocytoma.

Adenoma, Oxyphilic↗

[A case of bronchial neurinoma].

Neurinoma of the bronchial tree is extremely rare. We report a case of bronchial neurinoma involving a 21-year-old woman. The patient was admitted due to an abnormal shadow on chest X-ray, with cough and sputum production. Chest CT and MRI showed that the tumor arose from the left lower bronchus and bronchofiberscopic examination revealed complete obstruction of the lower bronchus by a polypoid tumor. A left lower lobectomy was performed based on the histological diagnosis of benign neurinoma and the postoperative course was uneventful. The tumor was 7.0 x 6.0 x 5.0 cm in size and had grown endobronchially without penetrating the bronchial wall. Pathological diagnosis was Antoni A type benign neurinoma. Since malignant or metastasized tumors have been reported in cases of tracheobronchial or intrapulmonary neurinoma, complete surgical resection of bronchial neurinomas should be performed.

Adult↗