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Biomedical subjects

K Mikami

Publications and source records attributed to K Mikami.

At least 73 records · Page 4Linked to original sources

DT-diaphorase as a critical determinant of sensitivity to mitomycin C in human colon and gastric carcinoma cell lines.

Mitomycin C (MMC), a known cytotoxic agent, requires cellular enzyme-mediated activation for effective antitumor activity. To study the bioreductive enzymes responsible for MMC activation in tumor cells, we examined the enzyme activities of DT-diaphorase (DTD) and NADPH:cytochrome P-450 reductase in 13 colon and gastric carcinoma cell lines and then compared these activities to the respective cellular MMC sensitivity. We found that cell lines with nonexistent or marginal DTD activity, such as St-4 and MKN7, showed resistance to MMC, in comparison to cell lines with DTD activity ranging from 210 to 1420 nmol/min/mg protein. No correlation was found between NADPH:cytochrome P-450 reductase activity and MMC sensitivity in these cell lines. To confirm the role of DTD in cellular MMC sensitivity, we constructed an expression vector containing NQO1, a gene that codes for DTD, and transfected the vector into St-4 cells expressing no DTD activity. Several transfectant clones with DTD activity from 144 to 2085 nmol/min/mg protein were obtained. All of the transfectants showed 5-10-fold higher sensitivity to MMC compared to the parental St-4 cells. Consistent with the MMC sensitivity, we also found that MMC-DNA adduct was formed more extensively in the NQO1 transfectants than in the St-4 cells. These results indicate that DTD activity is required for effective cytotoxicity of MMC in colon and gastric carcinoma cells.

Antibiotics, Antineoplastic↗

Alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9-producing gallbladder cancer.

We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A 63-year-old man was diagnosed with gallbladder cancer with metastases to the liver, based on ultrasonography and computed tomography of the abdomen showing multiple tumorous lesions in the liver and a thickened gallbladder wall. Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1 ng/ml CEA, 11,704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ ml PIVKA II. AFP in the present case showed an increase in Concanavalin A-nonbinding fraction and an increase in Lens culinaris lectin-binding fraction by affinity column chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder cancer consisting of papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the papillary adenocarcinoma portion of the primary focus and metastatic tumor cells in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9 were detected mainly in the tubular adenocarcinoma portion.

Antigens, Tumor-Associated, Carbohydrate↗

[Neuroendocrine cell carcinoma of the urinary bladder: a case report].

We report a case of neuroendocrine cell carcinoma of the urinary bladder. The patient was a 70-year-old man, complaining of pollakisuria. Cystoscopy and computerized tomography revealed a nonpapillary tumor. The tumor was removed by transurethral resection. Because of muscular invasion (T2) and histological grade, total cystectomy and ileal conduit were carried out. Examination of the resected specimen indicated pathological TO. He rejected our proposal to have chemotherapy. Twelve months post-operatively he was alive without recurrence.

Aged↗

[A case of advanced gastric cancer with multiple liver metastasis successfully treated with combination chemotherapy using UFT, CDDP and etoposide].

We reported a 66-year-old male patient with advanced gastric cancer accompanied by multiple liver metastasis, who responded to combination chemotherapy using UFT, CDDP and etoposide. The patient was administered three courses of 600 mg/body UFT po daily, 50 mg/body CDDP iv and 50 mg/body etoposide iv on days 1 and 8 every 4 weeks. As a result, both the primary and metastatic tumors decreased remarkably in size. Adverse reactions were leukocytopenia (Grade 2), thrombocytopenia (Grade 1) and nausea (Grade 1). he is alive 16 months after the beginning of therapy in a condition of partial response (PR). This combination therapy seemed to be effective for advanced gastric cancer.

Adenocarcinoma↗

[Pulmonary eosinophilic granuloma with relatively rapid progression and remission].

A 53-year-old woman with a smoking history of 20 pack-years was admitted to the hospital because of dry coughing and exertional dyspnea that had progressed over the previous 3 months. A chest X-ray film taken one month before the onset of symptoms was almost normal. Diffuse small nodular shadows with infiltration were evident one month after the onset of symptoms, and increased rapidly until admission to the hospital. Eosinophilic granuloma was diagnosed histologically after thoracoscopy. The symptoms, chest X-ray findings and pulmonary-function data improved spontaneously after admission to the hospital and the nodular shadows had a almost completely disappeared by 5 months later; the patient continued to smoke. The present case is unique and valuable because it shows the natural course of eosinophilic granuloma from the onset of symptoms to remission.

Eosinophilic Granuloma↗

[Pulmonary cavernous hemangioma--identification of its endothelial cell origin by immunohistological staining].

A 45-year-old woman was referred to our hospital because of a tumorous shadow in the S10 segment of the left lung. A chest computed tomography (CT) scan showed a nodular lesion with a slightly irregular margin and no contrast enhancement. CT-guided aspiration biopsy was tried but did not result in a histological diagnosis. The tumor was excised during video-assisted thoracoscopic surgery. Histological examination of the specimen revealed cavernous hemangioma. Most cells lining the lumen of the cavernous structure stained positively for von Willebrand factor antibody and negatively for anti-epithelial membrane antigen antibody, which suggests that the tumor was associated with endothelium. To the best of our knowledge, this is the first report of a case in which the diagnosis of pulmonary cavernous hemangioma was confirmed with an immunohistological study.

Antibodies↗

Developmental and tissue-specific regulation of the gene for the wheat basic/leucine zipper protein HBP-1a(17) in transgenic Arabidopsis plants.

Wheat basic/leucine zipper protein HBP-1a(17) binds in vitro specifically to ACGT motif-containing cis-acting elements, such as the type I element of plant histone promoters and the G-box of hormone- and light-inducible promoters. To address the in vivo function of HBP-1a(17), we isolated and structurally analyzed the HBP-1a(17) gene and examined its expression in transgenic Arabidopsis plants. The HBP-1a(17) gene is composed of 14 exons; the basic region and leucine zipper are encoded by separate small exons, as is the case for other bZIP protein genes. The G-box of the HBP-1a(17) promoter bound specifically to HBP-1a(17) and its related HBP-1a isoforms, suggesting that the HBP-1a(17) gene may be autoregulated, although the binding affinity of these proteins in vitro is very low. In Arabidopsis plants, activation of the HBP-1a(17) promoter was highly restricted to photosynthetically active mesophyll, and guard cells and vascular bundles of vegetative leaves. Etiolation of transgenic plants resulted in inhibition of expression of the HBP-1a(17) promoter. Indeed, the HBP-1a(17) promoter contains several sequence elements homologous to cis-acting elements conserved in light-inducible promoters. It is, therefore, assumed that the HBP-1a(17) gene is light regulated and that HBP-1a(17) is involved in light-responsive gene transcription via the G-box.

Amino Acid Sequence↗

[Clinical assessment for prognostic factors related to recurrence and progression in superficial bladder cancer].

PURPOSE: The objective of this assessment is to identify prognostic factors of recurrence and disease progression of primary superficial transitional cell carcinoma of the bladder. PATIENTS AND METHODS: TUR-Bt was performed in 150 patients with initial superficial bladder cancer, of which pathological diagnosis was pTa or pT1 transitional cell carcinoma. The recurrence and progression free survival was examined. The clinicopathological factors analyzed were as follows: grade, pT, tumor size, tumor number and tumor form. RESULTS: Median follow-up period was 39 months (range 3-184). The age distribution was from 25 to 98 years old with the average of 67. The patients were 122 males and 28 females. Recurrence was observed in 72 patients. The 5-year recurrence free rate for all cases were 41.6%. The factors found to be of significance for the prognosis for recurrence were tumor size (1 cm <) and tumor multiplicity (p < 0.01). Progression was seen in 15 patients; 8 invasive tumors, 2 lymph node metastases and 5 distant metastases. Twelve cases of those died of cancer. The 5-year progression free rate for all cases were 87.0%. The prognostic factors related to progression found in this study were G3, pT1 and sessile form (p < 0.01). There was no significant difference in recurrence free rate between cases with and without postoperative therapy; UFT p.o., ADM i.i. (intravesical instillation), ADM + Ara-C i.i. and PEP + 5-FU + Ara-C i.i. CONCLUSION: Tumor size more than 1 cm and tumor multiplicity were the high risk factors about recurrence. So were G3, pT1 and sessile form about progression.

Adult↗

[A case of a ureteral polyp resected transurethrally].

We report a case of fibroepithelial polyp of right ureter. The patient was a 36-year-old man, complaining of macrohematuria. An excretory urogram and retrograde pyelogram revealed a filling defect of the middle third of ureter, but it did not show hydronephrosis. We observed the ureter by transurethral ureteroscopy and found a ureter polyp with a slender stalk. We resected the polyp transurethrally. The pathological diagnosis was a fibroepithelial polyp. This suggests that the endourological technique is a useful method for diagnosis and treatment in patients with a urinary tract filling defect.

Adult↗

[Evaluation of surgical treatment for bone metastatic lesion in renal cell carcinoma].

Ten renal cell carcinoma (RCC) patients with bone metastatic lesions were treated in the Kyoto Prefectural University of Medicine between January, 1977, and December, 1992. Surgical treatment for the metastatic lesion was performed on 4 patients, while conservative treatment was performed on the other 6 patients. Surgical treatment made the patients painless consecutively, resulting in higher activities of daily life. However, recurrence of RCC developed in all the cases between 2 and 7 years later. Surgical treatment for the metastatic lesion was considered to be only a palliative therapy for RCC with bone metastasis and the indication should be limited to patients expected to have a good prognosis.

Adult↗

Closure of leaks by fibrin gluing. Effects of various application techniques and temperatures.

This study was performed to determine the differences in covering power obtained with fibrin gluing using three different methods, layered, mixing, and spraying. The experimental system consisted of a 2 x 2 cm plastic plate with a hole 1 mm in diameter, a plastic syringe, and a digital manometer. The internal pressure of the syringe barrel was measured with the digital manometer. Five minutes after fibrin glue membranes (1 mm in thickness) had been prepared on the plastic plate with the layered, mixing, or spray method, the plunger of the syringe was pushed slowly, and the maximum internal pressure in the syringe barrel was measured, just before the breakage of the membrane. Experiments were performed five times at each four temperatures, 12 degrees C, 17 degrees C, 22 degrees C and 37 degrees C. Covering power of fibrin glue membranes (units: mmHg; atmospheric pressure 760 mmHg) were as follows: 1) Layered method (12 degrees C: 810.0 +/- 68.6, 17 degrees C: 769.0 +/- 10.2, 22 degrees C: 812.0 +/- 112.4, 37 degrees C: 773.6 +/- 24.4). 2) Mixing method (12 degrees C: 956.6 +/- 219.3, 17 degrees C: 972.4 +/- 243.5, 22 degrees C: 1045.2 +/- 233.0, 37 degrees C: 1059.0 +/- 220.2). 3) Spray method (12 degrees C: 1010.0 +/- 231.1, 17 degrees C: 1144.4 +/- 170.6, 22 degrees C: 1148.0 +/- 234.7, 37 degrees C: 1250.0 +/- 111.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Partial purification and some properties of gamma-glutamyl peptide-hydrolysing enzyme from Actinobacillus actinomycetemcomitans.

A gamma-glutamyl peptide-hydrolysing enzyme was partially purified from Actinobacillus actinomycetemcomitans. The enzyme required metal ions, and 1 to 2 mM Mn2+ ions, especially, were essential for hydrolytic reaction. Its distribution by treatment of cells with lysozyme-EDTA suggested that the enzyme was a membrane-bound protein. The pI of the enzyme was in range of pH 5.1 to 5.6, and the apparent Km value for gamma-glutamyl-p-nitroanilide was 3.0 x 10(-4) M. The enzyme hydrolysed specifically gamma-glutamyl residues from the N-terminal of gamma-glutamyl compounds such as gamma-Glu-Met, gamma-Glu-Ala, gamma-Glu-Leu and gamma-Glu-Tyr, but did not catalyse the transpeptidation reaction. Neither free amino acids such as Ala-, Pro-, Gly- and Leu-p-nitroanilide nor alpha-glutamyl derivatives were hydrolysed. Its activity was strongly inactivated by metal chelators (EDTA or o-phenanthroline) and amino acids (Glu, Gln). In addition, the activity was specifically inactivated by gamma-glutamyl affinity-labelling reagents such as AT-125, 6-diazo-5-oxo-L-norleucine and azaserine, which are inhibitors of the gamma-glutamyl donor sites of mammalian gamma-glutamyl transpeptidase. Antibodies against bovine kidney gamma-glutamyl transpeptidase decreased the activity of the bacterial enzyme by 65%. These results suggested that the active sites in the bacterial enzyme were similar to those in mammalian gamma-glutamyl transpeptidase.

Aggregatibacter actinomycetemcomitans↗

[A case report of pericardial diverticulum in the upper mediastinum: surgical treatment of two cases].

Pericardial cyst and diverticulum are commonly found in areas of cardiophrenic angles. In this article, we reported on two operated cases (54-year-old female, 43-year-old male) with pericardial diverticula in upper mediastinum. On their chest CT films, well circumscribed cystic lesions were seen in the right (case 1) and left (case 2) upper mediastinum. Based on findings of imaging modalities such as CT, MRI and transesophageal ultrasonography, the lesions were suspected of benign cystic tumors such as bronchogenic cyst, lymphatic cyst, esophageal cyst and pericardial cyst. However, definite diagnoses were made by thoracotomy. Even though the cystic lesion is recognized in the upper mediastinum, pericardial diverticulum should be considered as its diagnosis as well as bronchogenic cyst, lymphatic cyst, esophageal cyst.

Adult↗

[Benign hemorrhagic renal cyst diagnosed by endoscopic biopsy: a case report].

A case of benign renal hemorrhagic cyst in a 73-year-old man is reported. Ultrasonography, computed tomography and magnetic resonance imaging revealed a solid mass in the left renal cyst. Percutaneous puncture of left renal cyst was carried out followed by endoscopic biopsy of the intracystic masses. Specimens showed no malignancy. As we could not rule out malignancy, left partial nephrectomy was performed. The surgical specimen was free from malignancy by pathological examination. Thus endoscopic biopsy of intracystic tumor indicated the correct diagnosis.

Aged↗

Potential transcription regulatory sequences in a promoter region of the wheat basic/leucine zipper protein HBP-1b(c38) gene.

A gene encoding the wheat transcription factor HBP-1b(c38) and its promoter region have been structurally analyzed. Protein-DNA interaction studies indicated the specific binding of the hexamer motif ACGTCA found in the promoter to the HBP-1b isoforms including HBP-1b(c38), suggesting that transcription of the HBP-1b(c38) gene may be autoregulated.

Base Sequence↗

Transport of cyclosporin A across the brain capillary endothelial cell monolayer by P-glycoprotein.

P-glycoprotein, a multidrug transporter protein, exists in the brain capillary endothelium. To study the function of P-glycoprotein in brain capillary endothelium as a barrier against cyclosporin A, we examined the interaction of cyclosporin A with P-glycoprotein expressed in cultured brain capillary endothelial cells (MBEC4). P-glycoprotein of MBEC4 specifically bound [125I]iodoaryl azidoprazosin, and the binding was inhibited by cyclosporin A and vincristine. Intracellular accumulation of cyclosporin A in MBEC4 was about one-third the amount accumulated in mouse aortic endothelial cells (MAEC3), a cell line that did not express P-glycoprotein. The reduced accumulation of cyclosporin A in MBEC4 was increased by verapamil, a competitive inhibitor of transport function of P-glycoprotein. Cyclosporin A was preferentially transported from basal to apical side when the cell monolayer of MBEC4 was formed; however this transendothelial transport was not observed across cell monolayer of MAEC3. Verapamil inhibited the transendothelial transport of cyclosporin A across the MBEC4 monolayer. Thus P-glycoprotein in brain capillary endothelium could transport cyclosporin A across the endothelium from the basal to the apical side. These observations suggest that P-glycoprotein is involved in the complex function of the blood-brain barrier as a secretory detoxifying transporter of cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The HBP-1 family of wheat basic/leucine zipper proteins interacts with overlapping cis-acting hexamer motifs of plant histone genes.

The type I element (CCACGTCANCGATCCGCG) is a cis-acting element that is essential for the transcriptional regulation of the wheat histone H3 (TH012) gene. The sequence CCACGTCA in the type I element resembles various plant regulatory elements that share an ACGT core sequence, which can be recognized by different basic/leucine zipper (bZIP) proteins. Here we describe the isolation and characterization of wheat cDNA clones encoding three novel bZIP proteins, designated HBP (histone promoter-binding protein)-1a(1), HBP-1a(c14), and HBP-1b(c1). These proteins specifically bind to the ACGT core sequence and, together with previously identified HBP-1a(17) and HBP-1b(c38), constitute a protein family, named the HBP-1 family. Based on their structural characteristics and DNA binding specificities, members of the HBP-1 family can be grouped into HBP-1a and HBP-1b subfamilies. The HBP-1a isoforms are characterized by their N-terminal proline-rich domain and a C-terminal bZIP domain, which binds to the CCACGT motif. In contrast, the HBP-1b isoforms have a bZIP domain at the N terminus, which binds to the ACGTCA motif, and a glutamine-rich domain at the C terminus. All members of both subfamilies interact with the CCACGTCA sequence, but their DNA binding specificities and affinities differ. Since HBP-1a isoforms form heterodimers in all pairwise combinations, heterodimer formation among these bZIP proteins may generate an expanded repertoire of regulatory potential for gene expression in plants.

Amino Acid Sequence↗

Modulation of adriamycin resistance in human breast carcinoma MCF-7 cells in vitro and in vivo by medroxyprogesterone acetate.

The combination effect of adriamycin (ADM) and medroxyprogesterone acetate (MPA) was examined in vitro against human breast carcinoma MCF-7 and its ADM-resistant line (MCF-7/ADM). MCF-7 cells, which are positive for estrogen receptors, progesterone receptors and high-affinity MPA-binding activity, were more susceptible to the growth-inhibitory activity of ADM or MPA than MCF-7/ADM cells. A combination effect of ADM and MPA was observed against MCF-7/ADM cells, which are negative for steroid receptors, and furthermore against human nasopharynx carcinoma KB and its ADM-resistant line KB-A1. This combination effect of ADM and MPA against MCF-7/ADM cells was demonstrated to be synergistic by using the median effect plot method. The activity of MPA was almost equivalent to that of chlormadinone acetate or tamoxifen, greater than that of progesterone, and less than that of verapamil. The accumulation of ADM in MCF-7/ADM cells was enhanced by treatment with 10 microM MPA as well as 10 microM verapamil. The efflux of accumulated ADM from MCF-7/ADM cells was also partially inhibited by treatment with MPA or verapamil. MPA augmented the growth-inhibitory activity of ADM against MCF-7/ADM tumors inoculated into nude mice, although statistical significance was not observed. It is suggested that the clinical advantage of the combination of MPA with ADM against advanced breast cancers may be partly explained by the modulation of ADM resistance by MPA.

Animals↗