Search PubMed⌕ Search

Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 505 records · Page 28Linked to original sources

Dual effects of angiotensin II on the plasminogen/plasmin system in rat mesangial cells.

Previous studies indicate that angiotensin II (Ang II) stimulates extracellular matrix synthesis through induction of transforming growth factor-beta (TGF-beta) expression. Here we investigate Ang II effects on the plasmin protease system. Plasmin both degrades extracellular matrix itself and activates metalloproteinases which then degrade collagens. Plasmin production is determined by the balance between plasminogen activators (PA) and their inhibitors (PAI-1,2). The data presented here indicate that Ang II treatment of mesangial cells in culture markedly increases PAI-1 gene transcription and PAI-1 mRNA levels but does not change the half life of PAI-1 mRNA. Increased PAI-1 protein was detected 24 hours after Ang II stimulation with a concomitant decrease of PA activity. To determine whether these effects were mediated by TGF-beta, cells were coincubated with Ang II and neutralizing antibody to TGF-beta. Induction of PAI-1 at four hours was not altered but the prolonged effect of Ang II on PAI-1 protein synthesis was markedly diminished. Thus, Ang II acts both through rapid, direct transcriptional up-regulation of the PAI-1 gene and through induction of TGF-beta, providing sustained changes in the PAI-1/PA system, which would favor extracellular matrix accumulation by inhibiting turnover. These data provide further evidence that Ang II can act as a potent fibrogenic molecule independent of its effects on blood pressure.

Angiotensin II↗

Huge solitary osteochondroma at T11 level causing myelopathy: case report.

A solitary osteochondroma of the vertebral column is rare, and also it will rarely cause neurological deficits. Myelopathy from a tumour usually presents insidiously with neurological deficits. We report a case of a huge solitary osteochondroma at T11 level with an acute onset of myelopathy induced by a minor trauma. MRI findings of a spinal osteochondroma has rarely been described. In our patient, the MRI demonstrated an outer osteochondral layer and an ossified centre of the mass. A literature review has also been undertaken.

Bone Neoplasms↗

Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis.

OBJECTIVE: Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time-course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis. DESIGN: Two year prospective follow-up study in patients with Graves' disease. PATIENTS: Ten consecutive patients with Graves' disease (seven males and three females, of mean (+/-SEM) age 39.3 +/- 3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex- and age-matched patients with the disease in remission served as controls. MEASUREMENTS: Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and alkaline-phosphatase (ALP) as markers of bone formation. RESULTS: Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89 +/- 0.16 before therapy, higher than those of 0.49 +/- 0.12 in the controls (P < 0.0001); the indices gradually decreased to 1.00 +/- 0.20 (12 months) and 0.48 +/- 0.12 (24 months). Lumbar BMD Z-scores increased from -0.22 +/- 0.46 to 0.21 +/- 0.47 (12 months) and 0.68 +/- 0.48 (24 months) (P = 0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, -396%, P < 0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months. CONCLUSIONS: Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4-8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.

Adolescent↗

Analysis of the decaprenyl diphosphate synthase (dps) gene in fission yeast suggests a role of ubiquinone as an antioxidant.

Schizosaccharomyces pombe produces ubiquinone-10 whose side chain is thought to be provided by the product generated by decaprenyl diphosphate synthase. To understand the mechanism of ubiquinone biosynthesis in S. pombe, we have cloned the gene encoding decaprenyl diphosphate synthase by the combination of PCR amplification of the fragment and subsequent library screening. The determined DNA sequence of the cloned gene, called dps, revealed that the dps gene encodes a 378-amino-acid protein that has the typical conserved regions observed in many polyprenyl diphosphate synthases. Computer-assisted homology search indicated that Dps is 45 and 33% identical with hexaprenyl diphosphate synthase from Saccharomyces cerevisiae and octaprenyl diphosphate synthase from Escherichia coli, respectively. An S. pombe dps-deficient strain was constructed. This disruptant was not able to synthesize ubiquinone and had no detectable decaprenyl diphosphate synthase activity, indicating that the dps gene is unique and responsible for ubiquinone biosynthesis. The S. pombe dps-deficient strain could not grow on either rich medium supplemented with glycerol or on minimal medium supplemented with glucose. The dps-deficient strain required cysteine or glutathione for full growth on the minimal medium. In addition, the dps-deficient strain is more sensitive to H2O2 and Cu2+ than the wild type. These results suggests a role of ubiquinone as an antioxidant in fission yeast cells.

Alkyl and Aryl Transferases↗

Three-dimensional structure of Escherichia coli branched-chain amino acid aminotransferase at 2.5 A resolution.

The X-ray crystallographic structure of the branched-chain amino acid aminotransferase from Escherichia coli was determined by means of isomorphous replacement using the selenomethionyl enzyme as one of the heavy atom derivatives. The enzyme is a homo hexamer with D3 symmetry, and the polypeptide chain of the subunit is folded into two domains (small and large domains). The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. The active site structure shows that the following sites can recognize branched-chain amino acids and glutamate as substrates: (1) a hydrophobic core formed by Phe36, Tyr164, Tyr31*, and Val109* for a branched-chain; (2) Arg97 for an acidic side chain of glutamate; and (3) Tyr95 and two main chain NH groups of Thr257 and Ala258 for the alpha-carboxylate of substrates. Although the main chain conformation of the active site is homologous to that of D-amino acid aminotransferase, many of the active site residues are different between them.

Alanine Transaminase↗

A serine/threonine protein kinase gene isolated by an in vivo binding procedure using the Arabidopsis floral homeotic gene product, AGAMOUS.

During the course of characterizing fragments bound to an Arabidopsis floral protein AGAMOUS in vivo, a gene encoding a putative serine/threonine protein kinase was found on one of the fragments. The deduced 426 amino acid residues of the gene, named APK2a, are 65% identical to a previously reported Arabidopsis serine/threonine protein kinase, APK1a. The gene is composed of 6 exons and maps at 10 cM from the upper end of chromosome 1. Northern hybridization experiments indicated that the gene is strongly expressed in leaves, moderately in roots, and very weakly in flowers. Further in situ analysis of the expression in floral buds showed that the APK2a gene is expressed at pedicels, is not expressed at the floral organ primordia of wild type floral buds, but is moderately expressed in the floral organ primordia of the agamous mutant. In vitro binding assay suggest that the AGAMOUS protein binds to a sequence similar to, but different from, the known MADS-binding consensus sequences, the CArG box, located 3' downstream of the APK2a gene. These results suggest that APK2a expression is negatively regulated by the AG protein. A close homologue of the APK2a gene, named APK2b, was also isolated from the Arabidopsis cDNA library. The expression pattern of the APK2b gene differs from that of APK2a. It is strongly expressed in leaves, moderately in flowers, and weakly in roots.

AGAMOUS Protein, Arabidopsis↗

Cloning and functional expression of a novel geranylgeranyl pyrophosphate synthase gene from Arabidopsis thaliana in Escherichia coli.

A gene encoding a novel geranylgeranyl pyrophosphate (GGPP) synthase from Arabidopsis thaliana has been identified and termed GGPS5. The gene has been sequenced and expressed in Escherichia coli. The deduced amino acid sequence showed 64.5% and 57.5% identify with a putative GGPP synthase from Arabidopsis and Capsicum annuum, respectively. GGPP enzymatic activity was detected in E. coli cells expressing the GGPS5 gene in two different ways. One was the direct measurement of GGPP synthase activity in cell extracts and the other was the yellow color production of cells when the GGPS5 gene was co-expressed with crtB, crtI, crtY and crtZ genes derived from Erwinia uredovora.

Alkyl and Aryl Transferases↗

Thyroid hormone stimulates Na(+)-Ca2+ exchanger expression in rat cardiac myocytes.

We investigated whether thyroid hormone directly affects Na(+)-Ca2+ exchanger expression in cardiac myocytes. Cultured neonatal rat cardiocytes were prepared from 1-day-old Sprague-Dawley rats. Intracellular Na+ concentration ([Na+]i) in cardiocytes was measured by using the Na(+)-sensitive dye sodium-binding benzofran isophthalate (SBFI). Na(+)-Ca2+ exchanger messenger RNA (mRNA) and protein expression were assayed by Northern and Western blotting, respectively. Triiodothyronine (T3; 10(-8) M) showed no effect on [Na+]i in cardiocytes, whereas ouabain (100 microM) caused a significant increase in [Na+]i from 11.3 +/- 5.0 to 21.8 +/- 5.0 mM. Exposure of cardiocytes to ouabain caused a rapid increase in Na(+)-Ca2+ exchanger mRNA accumulation, with a maximal twofold elevation at 12 h. The ouabain-induced Na(+)-Ca2+ exchanger mRNA accumulation was still observed in the Ca(2+)-free culture medium. On the other hand, exposure of cardiocytes to T3 induced a gradual increase in Na+ exchanger mRNA accumulation, with a maximal threefold increase at 24 h. Even in Na(+)-free medium, T3 still induced a twofold increase in Na(+)-Ca2+ exchanger mRNA accumulation in cardiocytes. Exposure of cardiocytes to T3 for 24-48 h also caused a marked increase in Na(+)-Ca2+ exchanger protein accumulation. In conclusion, thyroid hormone directly increases cardiac Na(+)-Ca2+ exchanger expression, independent of alterations in Na+ mobilization. These findings suggest also that thyroid hormone and Na+ regulate Na(+)-Ca2+ exchanger gene expression through distinct molecular regulatory pathways.

Animals↗

Increased cell proliferation of urothelium in rat bladder following unilateral nephrectomy.

PURPOSE: The aim of this study is to investigate the effect of unilateral nephrectomy on cell proliferation of normal urinary bladder epithelium in adult rats. MATERIALS AND METHODS: Following unilateral nephrectomy or sham operation 5 rats for each time point were sacrificed and their bladders were removed at 6 and 12 hours and also on 1, 2, 4, 7, 14, 28, and 56 days. Another 5 rats were not operated and served as the control. The percent number of proliferating cell nuclear antigen (PCNA) positive cells and the number of argyrophilic nucleolar organizer regions (AgNORs) were determined for each bladder. RESULTS: In the nephrectomized groups, a significant increase of PCNA expression in urothelial cells of the bladder was found at each sacrifice time with the exception of 28 and 56 days when compared with that of the control and corresponding sham-operated groups. Percent PCNA labeling index (PCNA-LI) reached a peak value of approximately 9.1% on day 2 post operation. From day 4 post nephrectomy, however, PCNA-LI decreased gradually reaching control levels by day 28. No significant difference was found between the control and sham-operated groups. The mean number of AgNOR dots in nephrectomized rats sacrificed on day 1, 2, 4, 7 and 14 post operation was significantly larger than that of the control and corresponding sham-operated groups. CONCLUSION: The results suggest that unilateral nephrectomy temporarily enhances normal urothelial cell proliferation in adult rat bladder.

Animals↗

Postoperative posterior retinal holes after pars plana vitrectomy for primary retinal detachment.

BACKGROUND: Although retinal breaks occur frequently during vitrectomy, the postoperative occurrence of new retinal holes close to the vascular arcade after vitrectomy for rhegmatogenous retinal detachment rarely has been reported. METHODS: Three patients with rhegmatogenous, retinal detachment were treated by vitrectomy. More than 49 days after vitrectomy, posterior retinal holes with no retinal detachment occurred halfway between the vascular arcade and the chorioretinal scar around the extrusion hole or the primary retinal tear. RESULTS: These new holes were effectively managed with photocoagulation. CONCLUSION: New hole formation could be caused by the technique of the internal drainage, the contraction of the photocoagulation scar, or epiretinal membrane contraction. Another possibility is that new holes occur through two opposite tangential traction contractile forces: one induced by the contraction of the photocoagulation scar, the other caused by the contraction of the premacular cortical vitreous attached to the vascular arcade.

Aged↗

Treponema medium sp. nov., isolated from human subgingival dental plaque.

A new Treponema species, for which we propose the name Treponema medium, was isolated from subgingival plaque from an adult with periodontal disease. The morphological characteristics, differential biochemical characteristics, and protein profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels of this organism are described. The guanine-plus-cytosine content of the DNA of T. medium is 51 mol%. The levels of DNA-DNA relatedness of the new species to other Treponema species, including Treponema denticola, Treponema vincentii, Treponema socranskii, Treponema pallidum, and Treponema phagedenis, are less than 30%. A phylogenetic analysis based on 16S rRNA sequences distinguished the new Treponema strain from strains belonging to previously described Treponema species. The type strain of T. medium is strain G7201.

Bacterial Proteins↗

Early detection of prune belly syndrome in utero by ultrasonography.

A report is presented of a male infant with prune belly syndrome (PBS) in whom bladder enlargement was detected by ultrasound (US) as early as 13 weeks of gestation. Subsequent fetal US identified progressive urinary tract dilatation, ascites and oligohydramnios. At 22 weeks, the fetal bladder was drained under US guidance. A gradual resolution of oligohydramnios was detected on US performed after 26 weeks of gestation. Delivery by cesarean section was performed at 34 weeks of gestation. The newborn had typical features of PBS with a vesico-cutaneous fistula but did not show respiratory distress. Imaging studies showed hypoplastic left kidney, slightly dysplastic but functioning right kidney, megaureter, megacystis, vesicoureteral reflux and dilated prostatic urethra. The early detection of genitourinary system abnormalities and serial US suggest that a distal urethral obstruction may be the underlying mechanism of PBS. Spontaneous (or therapeutic) intra-uterine decompression of the bladder might ameliorate obstructive nephropathy and oligohydramnios, allowing adequate lung development.

Adult↗

Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score.

BACKGROUND: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS: The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively. CONCLUSIONS: Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.

Adult↗

Preoperative endocrine therapy for clinical stage A2, B, and C prostate cancer: an interim report on short-term effects. Prostate Cancer Study Group.

BACKGROUND: Preoperative endocrine therapy has been suggested to improve surgical radicality and/or patient prognosis in prostate cancer. METHODS: Patients with clinical stage A2, B, and C prostate cancer were randomized to either group I (n = 113) or group II (n = 111). Group I patients were to receive preoperative endocrine therapy consisting of leuprolide and chlormadinone for 3 months, followed by radical prostatectomy with lymph node dissection. Group II patients were to undergo the surgery before endocrine therapy. RESULTS: Group I patients showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE: 41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to 21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed a significant difference in the rates of down-staging (19.1% in group I versus 3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive lymph node metastasis (20.7% versus 36.5%). No significant difference was detected in operating features. Subgroup analyses indicated that beneficial effects were correlated positively with degree of histologic differentiation and negatively with the basal PSA level. CONCLUSIONS: Preoperative endocrine therapy reduced local extension of prostate cancer, and the effects depended on histologic differentiation and PSA level. Long-term follow-up data are needed to determine the effects on the patient prognosis.

Aged↗

Histologic characteristics of renal cell carcinomas with lymph node metastasis.

BACKGROUND: This study was conducted to determine if there are any specific histologic features that are associated with lymph node metastasis in renal cell carcinoma (RCC). METHODS: TNM classification, histologic grade, mean nuclear volume, cell type, and histologic architecture of the tumors were evaluated in 66 patients who had undergone nephrectomy and lymphadenectomy for RCC. In the 18 patients with positive lymph node metastasis, both primary lesions and metastatic lymph nodes were evaluated. RESULTS: Lymph node status was correlated with primary tumor stage, venous involvement, and distant metastasis. The tumor grade was higher, and the mean nuclear volume was larger, in both primary and metastatic lesions of RCCs with lymph node metastasis than in tumors with no metastasis. In primary lesions of RCCs with lymph node metastasis, clear cell, alveolar, or cystic patterns were observed less frequently, and granular or spindle/pleomorphic cells and papillary or solid patterns, were observed more frequently, as compared to those lesions without metastasis. Comparison between primary and metastatic lesions in individual patients revealed no significant difference in grade or mean nuclear volume. The development of new cell types or histologic architectures, which was not noted in the primary lesions, was also a rare event in the metastatic lesions. CONCLUSION: Several characteristic histologic features, which may reflect the increased metastatic potential of the tumor, were observed in both primary and metastatic lesions in cases of RCC with lymph node metastasis. No substantial difference in histologic features was observed between the primary or metastatic lesions of individual patients.

Adolescent↗

Significance of prostate-specific antigen after radical prostatectomy.

BACKGROUND: Serum prostate-specific antigen (PSA) is expected to be undetectable after radical prostatectomy unless there is residual disease or disease progression. The aim of this study was to confirm the usefulness of serum PSA measurements in monitoring patients after radical prostatectomy. METHODS: We conducted a study of 50 patients who underwent radical prostatectomy for clinical stage T1-2 or small T3 prostate cancer, analyzed serum PSA levels before and after surgery and compared the pathological findings and clinical outcome. RESULTS: Postoperative PSA elevation (PSA failure) was noted in 13% of patients with organ-confined disease (OCD), 43% with positive surgical margins and/or seminal vesicle involvement (PSM/SVI), and 60% with positive lymph nodes (N+). Postoperative clinical failure was noted in 8 patients, and all were preceded by PSA failures. The 3-year PSA failure-free rates were 86.5%, 32.1%, and 40.7% and the 3-year clinical failure-free rates were 100%, 67.5%, and 73.5% in patients with OCD, PSM/SVI and N+, respectively. CONCLUSION: An elevation of serum PSA levels after radical prostatectomy was a sensitive indicator of persistent disease after surgery, and preceded clinical manifestations of disease progression.

Aged↗