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Biomedical subjects

K Mikami

Publications and source records attributed to K Mikami.

At least 55 records · Page 3Linked to original sources

The modular structure and function of the wheat H1 promoter with S phase-specific activity.

Two histone H1 genes, TH315 and TH325, were isolated from a wheat genomic library. Nucleotide sequence analysis and comparison with other histone gene promoters revealed that the promoters of both genes contain many characteristic motifs conserved among plant histone H1 genes. They are 6 novel short stretches, named CS1 to CS6, and already documented elements or their relatives such as Oct, Oct-like (OLS), Nona-like (NonaLS), CCAAT box, and TATA box. Transient expression experiments with the TH315 promoter/GUS chimeric gene and its mutagenized derivatives showed that two Oct motifs, OLS, and CCAAT box are positive cis-acting elements. NonaLS and CS4 were suggested to be positive cis-acting elements and CS5 and CS6 to be negative elements. An Oct motif and CCAAT box constitutes a type III element and the 202-bp sequence containing these elements from -128 to +74 of the TH315 gene was shown to be sufficient to confer S phase-specific expression. The type III element is found in all plant histone H1 and H2B genes, suggesting that it is a subtype-specific element. Most plant histone genes have one of the type I, II, and III elements. We propose to classify the plant histone genes into three classes, based on the context of Oct in the promoters.

Amino Acid Sequence↗

Immunological quantitation of DT-diaphorase in carcinoma cell lines and clinical colon cancers: advanced tumors express greater levels of DT-diaphorase.

NAD(P)H:quinone oxidoreductase (DT-diaphorase; DTD) plays a major role in activating mitomycin C (MMC) in human colon and gastric carcinoma cell lines. Thus, measurement of DTD in clinical tumor samples could be beneficial in designing adjuvant chemotherapy. We explored immunological quantitation of DTD protein using a monoclonal antibody against DTD, demonstrating a close correlation between protein expression and enzyme activity of DTD in colon and gastric carcinoma cell lines and in colorectal tumor samples. This indicates that such immunoblot analysis is a simple alternative method for quantitating DTD in clinically excised samples. In most colorectal tumor samples, the tumors expressed larger amounts of DTD than did the peripheral normal tissues, suggesting a selective toxicity of MMC toward tumor cells. Also tumors with nodal metastases showed significantly higher DTD levels than did tumors without metastasis. These results raise the possibility that DTD expression is related to tumorigenesis and malignant progression of colorectal tumors. Measurement of DTD by the immunological method described here could be beneficial in designing a rational adjuvant chemotherapy with MMC.

Adenocarcinoma↗

Singly dehydroxylated A-ring analogues of 19-nor-1alpha,25-dihydroxyvitamin D3 and 19-nor-22-oxa-1alpha,25-dihydroxyvitamin D3: novel vitamin D3 analogues with potent transcriptional activity but extremely low affinity for vitamin D receptor.

1Alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] mediates its biological activities through specific binding to the nuclear vitamin D receptor (VDR). The VDR, bound to 1alpha,25(OH)2D3, forms a heterodimer with a nuclear accessory factor, retinoid X receptor (RXR), and the complex subsequently binds to specific nucleotide sequences or a vitamin D-responsive element (VDRE) to induce gene transcriptions. Thus, an ideal analogue of 1alpha,25(OH)2D3 for therapeutic applications has been considered to be one which has a high binding affinity for VDR, thus forming a stable VDR/RXR complex, and binding strongly to VDRE. By contrast, we report here evidence contrary to this hypothesis. Several singly dehydroxylated A-ring analogues of 19-nor-1alpha,25-dihydroxyvitamin D3 and 19-nor-22-oxa-1alpha,25-dihydroxyvitamin D3, all of which have an extremely low binding affinity for VDR, and some of which lack the 1alpha-hydroxyl group that is considered to be essential for VDR-mediated gene expression, have greater or equivalent potencies to 1alpha,25(OH)2D3 for inhibiting the proliferation and inducing the differentiation of HL-60 cells, as well as inducing the transactivation of a luciferase reporter gene combining a rat 25-hydroxyvitamin D3 24-hydroxylase gene promoter containing two VDREs. The present findings open interesting possibilities as to the role of the VDR in the genomic action of 1alpha,25(OH)2D3 and the development of new 19-nor-analogues of 1alpha,25(OH)2D3.

Animals↗

Molecular characterization of a cDNA encoding a novel small GTP-binding protein from Arabidopsis thaliana.

A full-length cDNA clone encoding a novel Rab protein AtRab alpha of the monomeric small GTP-binding protein family has been isolated from Arabidopsis thaliana. AtRab alpha has 210 amino acids with a calculated molecular mass of 23.3 kDa. The highest homology was found to Rab1x and Rab1y from Lotus japonicus. Southern blot analysis of genomic DNA indicated that AtRab alpha was encoded by a single copy gene. Northern blot analysis showed that expression of the AtRab alpha mRNA was rich in stems and roots, but poor in leaves and flowers, which is different from the expression pattern of other Arabidopsis Rab genes.

Amino Acid Sequence↗

Endoscopic monitoring of operative procedures during cardiac surgery.

Both intracardiac repair and fine anastomotic procedures are hard to visualize in the sterile operative field. To overcome this problem, we have recently developed an endoscope video system for intraoperative monitoring in open heart surgery. The endoscope can be introduced into the cardiac cavity in a sterile fashion and thus be used to visualize intracardiac lesions as well as the operative procedures. This endoscopic video monitoring system is considered to be useful not only for thoracic surgery but also for cardiac surgery as well.

Adolescent↗

Basic study of the portable fatigue meter: effects of illumination, distance from eyes and age.

Several aspects of a new, small and inexpensive fatigue assessment tool, the Portable Fatigue Meter (PFM), were studied. In the first experiment the effects of room illumination and distance between the PFM and the eyes on critical flicker fusion frequency (CFF) values were examined. The results revealed that the PFM CFF value varied significantly as a function of the distance between the indicator and the eyes, but it was not affected by room illumination. The effect of ageing on the PFM CFF value was assessed in a second experiment. The results suggested that PFM CFF values are significantly smaller in middle-aged females than in younger females.

Adult↗

[A case of paratesticular rhabdomyosarcoma with a paraaortic lymph node metastasis].

A case of paratesticular rhabdomyosarcoma in a 22-year-old male is reported. Radiological examination revealed a gross metastatic mass in the paraaortic lymph node. Right high orchiectomy was followed by chemotherapy consisting of cisplatin, vincristine, cyclophosphamide and adriamycin (IRS-III regimen 35). A complete response was seen 4 months after start of therapy. However, recurrent disease developed in the same paraaortic lymph node 25 months postoperatively. The patient died of tumor progression 11 months later.

Adult↗

[A case of renal cell carcinoma associated with ossification].

A 40-year-old woman presented with left lumbar pain. A plain abdominal roentgenogram showed patchy calcifications dispersed in a diameter of 7.5 cm at the lower pole of the left kidney. Computed tomography and angiography revealed a hypovascular tumor 10 cm in diameter. A left radical nephrectomy was performed. Histopathological diagnosis was renal cell carcinoma, clear cell subtype, pT2N0M0, accompanied with marked stromal calcification. The patient remains free of recurrence 42 months postoperatively. This is the 26th case reported in the Japanese literature.

Calcinosis↗

[A case of unresectable pancreatic cancer successfully treated with continuous venous daily infusion of 5-FU and low-dose CDDP].

This case was a 61-year-old male diagnosed with pancreatic cancer who had a celiotomy. The tumor invasion involved the pancreas body and head. Ultrasonograph examination revealed that all the celiac artery, supramesenteric artery, and portal vein were occluded in the tumor. Because of the unresectability of the tumor, a palliative operation was carried out, and during the following 9 months he was given UFT 300 mg daily. Because abdominal ascites accompanied the tumor growth, the patient underwent combination chemotherapy of cisplatin 5 mg/day x 5/week and continuous infusion of 5-fluorouracil 250 mg/day for 4 weeks. Remarkable reduction of the abdominal ascites and decline of the tumor markers (CEA, CA19-9) was observed in the course of the chemotherapy. Bone marrow function was suppressed by the agents, but granulocyte colony stimulating factor (G-CSF) was very effective for recovery from the damage. Two months after discharge, abdominal ascites recurred. The patient received the same serial chemotherapy for 6 weeks, and now is followed as an outpatient.

Antineoplastic Combined Chemotherapy Protocols↗

[Mass screening for prostatic cancer].

Two mass screening programs for prostatic cancer (PC) have been conducted at our institution. The first program, based on transrectal ultrasonography (TRUS), was performed between 1975 and 1995 in a total of 16,313 men over 55 years of age. Those showing abnormal findings on TRUS were referred to the secondary urological examination including needle biopsy of the prostate. PC was detected in 93 men (0.6%) and 43 of them were in the early stage. In 1995, a new mass screening program for PC was performed in an urban area of Kyoto. Of 3,749 men over 55 years of age who took the annual health checkup organized by the government, 2,387 wished to receive this screening. The primary examination consisted of Delfia prostate specific antigen (PSA) assay of dried blood samples on a filter paper. Men with PSA levels > 4.0 and < or = 10.0 ng/ml showing abnormal findings on TRUS and/or digital rectal examination, or PSA density > 0.15, underwent 6 sextant biopsies under transrectal ultrasonography, as well as men with PSA levels > 10.0 ng/ml. PSA levels were < or = 4.0 in 2,217 men, > 4.0 and < or = 10.0 in 107, and > 10.0 in 43. Prostatic biopsy was performed in 102 men. PC was detected in 28 men (1.2%) and 17 of them were in the early stage. These findings suggest that the PSA-based mass screening program for PC combined with the annual health checkup is suitable for future "national-level" screening.

Adult↗

[A case of retroperitoneal fibrosarcoma in the perirenal space].

A case of retroperitoneal fibrosarcoma is reported. A 52-year-old man with the complaint of left abdominal mass was referred to our hospital. Computed tomography showed a left retroperitoneal tumor surrounding the left kidney in the perirenal space. Angiography showed some feeding vessels from the branch of the posterior segmental artery of the left kidney. The tumor was completely resected with the left kidney, but para-aortic lymph node metestases were found. Histopathological diagnosis was a retroperitoneal fibrosarcoma with lymph node metastases. The patient died of the disease 3 months after the operation.

Fibrosarcoma↗

[Renal cell carcinoma diagnosed by ring-like growth of preexistent calcification: a case report].

A 53-year-old woman was referred for further examination of a left renal cyst detected ultrasonographically during a health checkup. Computerized tomography (CT) scan and magnetic resonance imaging revealed an irregular cystic mass at the center of the left kidney as well as a calcified lesion at the left upper pole. Angiography and cyst puncture confirmed the cystic mass to be unilocular and benign. However, followup CT scan after 22 months demonstrated enlargement of the calcification into a ring-like configuration 3 cm in diameter. Since the lesion showed neovascularity on angiography, radical nephrectomy was performed. Histopathological diagnosis was renal cell carcinoma, alveolar type, common type at the center, but solid type, spindle cell type at the periphery.

Calcinosis↗

[Descending necrotizing mediastinitis secondary to retropharyngeal abscess--a case report].

A 69-year-old man complained of a sore throat, neck swelling, and disturbance of swallowing with dyspnea. He underwent tracheostomy and cervical drainage. The plain chest roentgenogram and CT scans suggested mediastinitis, so he was transferred to our hospital. Cultures revealed a mixed aerobic and anaerobic infection. On hospital day 2, the neck was explored and pus was found in the connective tissue. Despite drainage and intravenous panipenem with betamipron and clindamycin, he remained febrile and a mediastinal abscess was seen on repeat CT. On hospital day 10, reexploration of the mediastinum was done through cervical and right thoracotomy incisions. A large amount of pus was drained from the posterior mediastinum and its necrotic tissue was debrided. Myocardial infarction occurred intraoperatively, but the patient was successfully resuscitated. Following this procedure, the patient's condition and radiologic findings gradually improved. Cultures of the drain fluid became negative, and he was discharged on hospital day 103. In conclusion, both transcervical drainage and aggressive mediastinal exploration via thoracotomy are essential to salvage a patient with descending necrotizing mediastinitis. CT scanning is useful for early diagnosis of mediastinitis and for follow up.

Aged↗

[DT-diaphorase].

Anti-tumor quinone, including mitomycin C (MMC), needs to be activated by bioreduction to exert its cytotoxic activities. The enzymes underlying this bioreductive activation have been the subject of extensive research on Mitomycin C. Cytochrome P450 reductase, cytochrome b5 reductase, xanthine oxidase, xanthine dehydrogenase and DT-diaphorase (DTD) have been shown to be involved in the reduction of MMC. The relationship between bioreductive enzymes and the cytotoxicity of quinone, however, has not been analyzed yet. In this study, we investigated the relationship between the bioreductive enzymes and the cytotoxicity of MMC. We carried out the following experiments and the following results were obtained. I) We isolated an MMC-resistant variant. This cell showed five-fold resistance to MMC as compared with the parental cell line. DTD was deficient in this resistant cell. II) We have examined the bioreductive enzyme activities of DTD and cytochrome P450 reductase and IC50's of MMC in 13 colon and gastric carcinoma cell lines. A positive correlation was not found between the enzyme activities and MMC sensitivities, but the cells with little or no DTD activity showed higher IC50 values compared to the other cell lines. III) To elucidate directly the role of DTD in MMC sensitivity, we introduced NQO1 gene into St-4 cells. NQO1 gene encodes DTD and St-4 cells have no DTD activity. All of the transfectants showed five- to ten-fold higher sensitivity to MMC as compared to the parental St-4 cells. The above data indicate that DTD is a critical determinant of sensitivity to MMC in aerobic conditions.

Antibiotics, Antineoplastic↗

[Clinical results of combination chemotherapy with cisplatin, vinblastine and bleomycin (pvb) for advanced testicular cancer: evaluation of risk criteria].

Between 1982 and 1991, 24 patients with advanced testicular germ cell tumor were treated by combination chemotherapy with cisplatin, vinblastine and bleomycin (PVB). Based on short-term efficacy of the PVB regimen and long-term prognosis in our patients, we evaluated 4 risk criteria proposed by Indiana University, National Cancer Institute (NCI), Memorial Sloan-Kettering Cancer Center (MSKCC) and European Organization for Research and Treatment of Cancer (EORTC). Clinical staging were IIA in 8 patients, IIB in 8, IIIA in 1, IIIB in 5 and IIIC in 2. Metastases included retroperitoneal lymph node in 20 cases (> 5 cm in 10), lung in 6, bone and liver in each 1. Complete response (CR) was obtained in 12 (50%) patients and partial response (PR) in 9 (38%). According to the stage and metastatic site, CR was achieved in 75%, 38% and 38%of the stage IIA, IIB and III tumors, respectively, and in 60% and 50% of retroperitoneal and pulmonary metastases, respectively. However, neither CR nor PR was recognized for live and bone metastases. Prognosis was assessed with a mean followup period of 88.5 months. Although all 12 patients with CR were alive, 4 of the 9 with PR and all patients on whom the drug was ineffective died of cancer. Accuracy in predicting prognosis was 82%, 75%, 74%, and 63% using the MSKCC, Indiana, NCI and EORTC risk criteria, respectively.

Adolescent↗

[A case of invasive renal pelvic cancer: usefulness of auxiliary diagnosis using fluorescence in situ hybridization].

A 65-year-old man, on whom transurethral resection had been performed twice for bladder cancer in the past, was admitted to our hospital for further Class V urinary cytology examination. A low density area of 1.5 cm in diameter in the left renal pelvis without enhancement was the only abnormal sign on computed tomographic (CT) imaging. Malignant cells were not detected by random biopsy of the urinary bladder. The retrograde pyelogram showed no filling defect on the left renal pelvis or ureter. The cytological diagnosis of the right split renal urine was Class III, and that of the left split renal urine was Class V. Fluorescence in situ hybridization (FISH) analysis, using specific probes for chromosome 8q21.3 and the centromere chromosome 11, was performed on cells from the bilateral split renal urine. Cells collected from the right split renal urine showed a normal disomic pattern, while those from the left split renal urine included an aneusomic pattern with polysomy. Left total nephroureterectomy was carried out. Histopathology proved invasive renal pelvic cancer. Thus FISH analysis may be useful for the localization of renal pelvic or ureteral cancers, which are difficult to diagnose.

Aged↗

[A case of spontaneous rupture of renal cell carcinoma].

Spontaneous rupture of the kidney is uncommon. We report a case of spontaneous rupture of the kidney due to a renal cell carcinoma. A 53-year-old man presented with right renal tumor. Computed tomography demonstrated a 70 mm right renal tumor which involved the entire upper pole of the kidney and extended into the renal vein. A few days later, the patient had sudden severe right flank pain. Computed tomography of the abdomen revealed a large perirenal hematoma of the right kidney. Angiography demonstrated no vascular abnormality. Nephrectomy was performed. The histological examination showed rupture of a renal cell carcinoma in the right kidney.

Carcinoma, Renal Cell↗