[Molecular biology and multifunctional aspects of nm23/NDPK].
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Animals↗
Biomedical subjects
K Okada
Publications and source records attributed to K Okada.
Thrombopoietin supports in vitro erythroid differentiation via its specific receptor c-Mpl in a human leukemia cell line.
Thrombopoietin (TPO) acts on megakaryopoiesis and erythropoiesis in vitro and in vivo. We isolated a novel subline, UT-7/GMT, from the human leukemia cell line UT-7/GM (N. Komatsu, et al., Blood, 89: 4021-4033, 1997). A small population of UT-7/GM cells positively stained for hemoglobin (Hb) after a 7-day exposure to TPO. More than 50% of TPO-treated UT-7/GMT cells positively stained for Hb. Using UT-7/GMT cells, we examined how TPO promotes hemoglobinization. TPO induced tyrosine phosphorylation of the TPO receptor but not the erythropoietin (EPO) receptor. There was no competition between TPO and EPO for binding to EPO receptor. These findings suggest that TPO has a direct effect on hemoglobinization via a specific receptor on UT-7/GMT cells. Isoelectric focusing demonstrated that TPO induced fetal and adult Hb synthesis, whereas EPO induced embryonic, fetal, and adult Hb synthesis. Thus, our data suggest that TPO has a distinct action on erythropoiesis.
Binding, Competitive↗
Tumor localization studies and surgical treatment in patients with insulinoma.
In the present study, we retrospectively reviewed thirteen consecutive patients with insulinomas including 2 reoperations at our department for insulinomas, from the viewpoint of preoperative localization studies, surgery and long term follow-up. The results of the preoperative localization studies proved to be percutaneous transhepatic portal venous sampling (PTPVS) 6/7, angiography 8/15, ultrasonography (US) 6/11, endoscopic ultrasonography (EUS) 4/4, computed tomography (CT) 3/10, and magnetic resonance imaging (MRI) 2/2. The tumor was visualized by intraoperative ultrasonography (IUS) in 6 of 6 patients (100%). Six patients underwent enucleation, 6 patients underwent distal pancreatectomy, 2 patients underwent subtotal (80%) distal pancreatectomy, and one patient a pylorus preserving pancreaticoduodenectomy (PPPD). Two patients, one of whom belonged to the MEN-I group, underwent reoperations because they had multiple adenomas. The development of iatrogenic diabetes occurred in the case of 3 patients. These results suggest that the use of selected preoperative localization studies (PTPVS and probably EUS) may be very helpful for detecting insulinoma, and that IUS is an essential part of the operative exploration for insulinoma. Our data may further indicate the need for an aggressive surgical procedure in the case of multiple adenoma or insulinoma in MEN-I.
Adult↗
A case of abdominal aortic aneurysm associated with systemic lupus erythematosus.
A case of abdominal aortic aneurysm associated with systemic lupus erythematosus (SLE) is reported. A 45-year-old woman with a 18-year history of SLE was admitted with severe lumbago radiating to the bilateral inguinal region. CT and DSA showed a dumbbell shaped true aneurysm of the abdominal aorta. An aorto-biiliac Y shaped graft replacements was performed. SLE is rarely associated with aneurysm of the great arteries. We could find only 4 reports of abdominal aneurysm associated with SLE. Common features were the young age of the patient, the long term of the systemic disease, and administration of corticosteroid therapy for a relatively long period of time. We speculate that atherosclerosis, hypertension, and corticosteroid may all work in concert, possibly together with aortic wall involvement or vasculitic damage, to produce the rare abdominal aneurysm in SLE.
Aortic Aneurysm, Abdominal↗
Nine patients with hepatocellular carcinoma surviving for more than six years after treatment, including two patients who have survived without recurrence after hepatic lobectomy.
Of patients treated for hepatocellular carcinoma (HCC) accompanied by liver cirrhosis at our University Hospital between 1985 and 1990, clinical background factors in nine patients (7.0% of all patients) who survived for more than six years were examined to clarify the conditions that facilitate long-term survival. In particular, we describe two cases among these patients who have survived without the recurrence of a liver tumor for more than six years after hepatic lobectomy. In eight of nine patients, surgery was performed as the initial treatment. In seven patients, HCC was solitary and there was no portal invasion. Six patients were evaluated as Stage I according to clinical staging. Furthermore, the two patients without recurrence after treatment have been taking immunostimulators since their initial treatment until the present. The above observations suggest that surgical treatment should be considered in patients in whom hepatic reserve capacity is well maintained despite a tumor size greater than 2 cm. Subsequent recurrence should be detected earlier, and percutaneous ethanol injection therapy (PEIT) with a focus on maintaining liver function should be repeated. In addition, multi-disciplinary treatment including medication with immunostimulators is beneficial.
Aged↗
[Clinical staging of prostate cancer].
Clinical staging of prostate cancer was reviewed on the basis of TNM classification edited by UICC in 1997. In this revision, (1) T1c was newly categorized among T1 for cases of high PSA level without any abnormal sign of DRE, (2) T2 was subdivided into T2a and T2b in accordance with unilateral or bilateral nodule in the prostate, respectively, (3) T3 was also subdivided into T3a with capsular invasion and T3b with seminal vesicle invasion. It is hoped that present classification will become useful tools for the detection of the tumor burden cancer patients.
Humans↗
[Clinical significance of prostate specific antigen and gamma-seminoprotein ratio for diagnosing prostate cancer].
It has been reported that prostate specific antigen and gamma-seminoprotein ratio (PSA/gamma-Sm ratio) is an useful means for distinguishing benign prostatic hyperplasia and prostate cancer if serum PSA is measured by Eiken-PSA method. We studied the clinical significance of PSA/gamma-Sm ratio when using Markit-M-PSA method. PSA/gamma-Sm ratio had no superiority over PSA alone for detecting prostate cancer. The present results suggest that the clinical significance of PSA/gamma-Sm ratio can be varied by various PSA-assay kits.
Biomarkers, Tumor↗
[Fluorodeoxyglucose positron emission tomography in diagnosis of untreated prostate cancer].
Fluorodeoxyglucose positron emission tomography (FDG-PET) has been utilized since glucose metabolism in cancer tissue is considered to relate to its malignant potential. We evaluate the application of FDG-PET to prostate cancer. FDG uptake of cancer tissues was higher with higher Gleason grade, advanced clinical stage and higher serum PSA value than that with lower Gleason grade, localized clinical stage and lower serum PSA value. The measurement of glucose metabolism in the prostate using FDG-PET was suggested to be useful for evaluation of the biological malignant potential of prostate cancer. It may serve as a predictive factor for prognosis and may be useful in determining the effectiveness of hormonal therapy in prostate cancer.
Fluorodeoxyglucose F18↗
[Reevaluation and potential therapeutic effects of estrogen therapy to prostate cancer patients].
Survival time of 65 patients with stage D2 prostate cancer who were treated by estrogen with or without antiplatelet drugs was examined. Survival time of 37 patients with antiplatelet drugs was significantly longer than that of 28 histological control ones. The frequency of death of cardiovascular disease in the former group decreased to 5.3%. Next, progression free time of the 37 patients was compared to the time of 37 patients treated by antiandrogen therapy. The former one was better than the latter. However, survival time after relapse of the estrogen group was shorter than the control. These results suggest that estrogen therapy improved by a combination of antiplatelet drugs has to be reevaluated and contains specific therapeutic effects differing from antiandrogen therapy.
Antineoplastic Agents, Hormonal↗
[A study on androgen deprivation therapy prior to radical prostatectomy with special reference to the tumor volume].
BACKGROUND: The aim of this study is to analyze correlation between the tumor volume (TV) and the final pathological stage in patients undergoing neoadjuvant therapy. PATIENTS AND METHODS: Twenty-six patients underwent radical prostatectomy alone (group S). The remaining 28 patients had undergone neoadjuvant therapy (group N) which mainly consisted of LH-RH agonist. TV and the final pathological stage were retrospectively reviewed. RESULTS: The likelihood of positive surgical margin was statistically higher in group S than in group N (p = 0.009). The correlation between TV and the pathological stage was observed not only in group S (rho = 0.646, p = 0.0012) but also in group N (rho = 0.716, p = 0.0002). The mean TV was statistically smaller in group N in patients with baseline PSA level more than 10.1 ng/ml (p = 0.024). CONCLUSION: A decrease in tumor volume caused by neoadjuvant therapy may play an important role in reducing the likelihood of positive surgical margin.
Antineoplastic Agents, Hormonal↗
[Two cases of adrenal myelolipoma diagnosed by ultrasonically guided percutaneous biopsy].
We report 2 cases of adrenal myelolipoma which were diagnosed definitively by ultrasonically guided percutaneous biopsy to waive surgery. In case 1, a 39-year-old man presented with abdominal pain. A right adrenal mass was detected by abdominal ultrasonography. In case 2, a 64-year-old man presented with nocturia. A space-occupying lesion above the left kidney was detected by excretory pyelography. Both cases were suspected of adrenal myelolipoma by ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI). The tumor size was 4 x 4 x 3 cm and 5 x 4.5 x 4 cm in cases land 2, respectively. In both cases percutaneous needle biopsy using ultrasonically guided puncture was performed. Histology showed a complex of hematopoietic and adipose tissues, corresponding to adrenal myelolipoma. The course has been uneventful without surgery for 58 months and 24 months, respectively. Percutaneous adrenal biopsy was useful to establish the definitive diagnosis and to select treatment options.
Adrenal Gland Neoplasms↗
[A case of cyclosporin responsive myasthenia gravis with an invasive thymoma].
We report a patient with myasthenia gravis (MG) accompanied by invasive thymoma which we treated with cyclosporin. The patient was a 42-year-old woman who was admitted to our hospital because of diplopia and left blepharoptosis. Thymectomy was undertaken but it was incomplete because the thymoma had already invaded other tissues. Following thymectomy, the antibody level for acetylcholine receptors (AChR) gradually increased and generalized weakness and dyspnea emerged. The symptoms did not improve with ADOC chemotherapy and steroid pulse. Treatment with cyclosporin (200 mg/day) was initiated after plasmapheresis and the symptoms improved and AChR antibody levels subsided. There has not been a recurrence of the thymoma after 28 months. In conclusion, treatment with cyclosporin may be more effective than other treatments in patients with inveterate MG that is accompanied by thymoma.
Adult↗
Effect of the angiotensin-converting enzyme inhibitor enalapril on post-transplant erythrocytosis.
Post-transplant erythrocytosis (PTE) is increasingly recognized as a complication of kidney transplantation. In this study we report the effect of the angiotesin-converting enzyme (ACE) inhibitor enalapril on hematocrit (Ht) and erythropoietin in four patients with PTE. Four renal allograft recipients with Ht greater than 51% were studied. Treatment was initiated with enalapril administered orally at a dose of 2.5 mg/day. All the patients had an increase of hemoglobin (Hb) (17.7 +/- 0.64 g/dl), Ht (54.5 +/- 1.29%) and red blood cell count (RBC) (584 +/- 19.2 x 10(4)/microliter). All patients responded to enalapril in 8 weeks with a significant decrease of Hb, Ht, and RBC. In one patient, the downward trend was more rapid and sustained, and treatment had to be discontinued to prevent the development of anemia. Serum erythropoietin showed normal in all four patients and remained unchanged during the study, even after discontinuation of enalapril treatment. Serum creatinine remained relatively stable throughout the study. These results suggest that PTE may not be dependent upon circulating erythropoietin and that enalapril treatment may be an effective treatment of PTE without renal dysfunction.
Adult↗
Three different approaches to spinal cord monitoring for the prediction of spinal cord ischemia during thoracic aortic aneurysm surgery.
We report the case of a 66-year-old man who had a descending thoracic aneurysm, diagnosed as aortitis syndrome. He subsequently underwent an aneurysmectomy under simultaneous sensory and motor spinal cord monitoring. Spinal cord ischemia was diagnosed during prosthetic replacement of the aneurysm by changes in evoked spinal cord potentials and motor evoked potentials from the lumbar spinal cord enlargement and 2 pairs of intercostal arteries were reconstructed at the level of T9 and 10. After surgery, the patient developed paraparesis below T10, but the resulting neurological deficits were overcome with postoperative rehabilitation. Simultaneous monitoring of evoked spinal cord potentials and motor evoked potentials were useful in evaluating spinal cord ischemia during aortic aneurysm surgery and in determing whether intercostal arteries should be reconstructed.
Aged↗
The Arabidopsis HY5 gene encodes a bZIP protein that regulates stimulus-induced development of root and hypocotyl.
Plant developmental processes are controlled by both endogenous programs and environmental stimuli. As a photomorphogenetic mutant, hy5 of Arabidopsis has been isolated and characterized. Our detailed characterization has revealed that the mutant is deficient in a variety of stimulus responses, including gravitropic response and waving growth of roots, as well as light-dependent hypocotyl elongation. In the roots and hypocotyl, the hy5 mutation also affects greening and specific cell proliferation such as lateral root formation and secondary thickening. Those phenotypes indicate that the HY5 gene is responsible for the regulation of fundamental developmental processes of the plant cell: cell elongation, cell proliferation, and chloroplast development. Molecular cloning of the HY5 gene using a T-DNA-tagged mutant has revealed that the gene encodes a protein with a bZIP motif, one of the motifs found in transcriptional regulators. Nuclear localization of the HY5 protein strongly suggests that the HY5 gene modulates the signal transduction pathways under the HY5-related development by controlling expression of genes downstream of these pathways.
Amino Acid Sequence↗
New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus.
Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. We have investigated oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus (NIDDM) by urinary 8-OHdG assessments. We determined the total urinary excretion of 8-OHdG from 24 h urine samples of 81 NIDDM patients 9 years after the initial diagnosis and of 100 non-diabetic control subjects matched for age and gender. The total 24 h urinary excretion of 8-OHdG was markedly higher in NIDDM patients than in control subjects (68.2 +/- 39.4 microg vs. 49.6 +/- 37.7 microg, P = 0.001). High glycosylated hemoglobin was associated with a high level of urinary 8-OHdG. The increased excretion of urinary 8-OHdG is seen as indicating an increased systemic level of oxidative DNA damage in NIDDM patients.
8-Hydroxy-2'-Deoxyguanosine↗
Transcription effect of nm23-M2/NDP kinase on c-myc oncogene.
Transactivating factor PuF which interacts with a nuclease hypersensitive element locates upstream from the c-myc gene. PuF was recently identified as being encoded by nm23-H2/ NDP kinase gene [Postel, E. H., Berberich, S. J., Flint, S. J., and Ferrone, C. A. (1993) Science 261, 428-429]. Here we have studied the correlation of expression between c-myc and nm23 genes in vitro. By a comparative study of the expression of 2 genes in cell lines, no direct correlation of kinetics was found. A plasmid containing the human c-myc fragment (c-myc CAT) was cloned upstream from the bacterial chloramphenicol acetyltransferase (CAT) gene. When the murine melanoma cell line was cotransfected with a nm23-M2/ NDP kinase expression vector and c-myc CAT, CAT activity was elevated. In addition, cell cycle phases in the murine cell lines transfected with nm23/NDP kinase were estimated; an alteration of the cell cycle, prolonged S-phase was found in the cell lines transfected with nm23-M2/NDP kinase, whereas human nm23-H2/NDP kinase did not play a role in transactivating the c-myc gene or in S-phase prolongation in murine cell lines. From these results we conclude that the murine nm23-M2 gene transactivates the c-myc gene and controls the cell cycle, S-phase, indirectly via a cellular cofactor in the murine cell line, which does not work with the human nm23-H2 gene.
Animals↗
Serotonin inhibits nitric oxide synthesis in rat vascular smooth muscle cells stimulated with interleukin-1.
We investigated the effects of serotonin (5-hydroxytryptamine; 5-HT) on nitric oxide (NO) synthesis in vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of NO, and the expression of inducible NO synthase protein in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1beta (10 ng/ml) caused a significant increase in nitrite production. 5-HT inhibited nitrite production by interleukin-1beta -stimulated vascular smooth muscle cells in a concentration-dependent manner (10(-8)-10(-5) M). 5-HT-induced inhibition of nitrite production was accompanied by decreased inducible NO synthase protein accumulation in vascular smooth muscle cells. Addition of the 5-HT2 receptor antagonist ketanserin, but not the 5-HT1A receptor antagonist spiroxatrine, inhibited the effect of 5-HT. On the other hand, the 5-HT2 receptor agonist alpha-methyl-5-HT, but not the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin, decreased interleukin-1beta-induced nitrite production by vascular smooth muscle cells. 5-HT significantly increased protein kinase C activity in vascular smooth muscle cells, and the protein kinase C inhibitor calphostin C dose-dependently abolished the effect of 5-HT on nitrite production. After protein kinase C activity was functionally depleted by treatment of cells with phorbol 12-myristate 13-acetate for 24 h, the effect of 5-HT was abolished. These results indicate that 5-HT acts on 5-HT2 receptors and inhibits NO synthesis in interleukin-1beta-stimulated vascular smooth muscle cells at least partially through a protein kinase C-dependent pathway.
Animals↗