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Biomedical subjects

M Hidaka

Publications and source records attributed to M Hidaka.

At least 19 recordsLinked to original sources
PubMed2005

Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

Adolescent↗
PubMed2004

Differential susceptibility to oxidative stress of two scleractinian corals: antioxidant functioning of mycosporine-glycine.

This study examined the importance of mycosporine-glycine (Myc-Gly) as a functional antioxidant in the thermal-stress susceptibility of two scleractinian corals, Platygyra ryukyuensis and Stylophora pistillata. Photochemical efficiency of PSII (F(v)/F(m)), activity of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), and composition and abundance of mycosporine-like amino acids (MAAs) in the coral tissue and in symbiotic zooxanthellae were analyzed during 12-h exposure to high temperature (33 degrees C). After 6- and 12-h exposures at 33 degrees C, S. pistillata showed a significantly more pronounced decline in F(v)/F(m) compared to P. ryukyuensis. A 6-h exposure at 33 degrees C induced a significant increase in the activities of SOD and CAT in both host and zooxanthellae components of S. pistillata while in P. ryukyuensis a significant increase was observed only in the CAT activity of zooxanthellae. After 12-h exposure, the SOD activity of P. ryukyuensis was unaffected in the coral tissue but slightly increased in zooxanthellae, whereas the CAT activity in the coral tissue showed a 2.5-fold increase. The total activity of antioxidant enzymes was significantly higher in S. pistillata than in P. ryukyuensis, suggesting that P. ryukyuensis is less sensitive to oxidative stress than S. pistillata. This differential susceptibility of the corals is consistent with a 20-fold higher initial concentration of Myc-Gly in P. ryukyuensis compared to S. pistillata. In the coral tissue and zooxanthellae of both species investigated, the first 6 h of exposure to thermal stress induced a pronounced reduction in the abundance of Myc-Gly but not in other MAAs. When exposure was prolonged to 12 h, the Myc-Gly pool continued to decrease in P. ryukyuensis and was completely depleted in S. pistillata. The delay in the onset of oxidative stress in P. ryukyuensis and the dramatic increase in the activities of the antioxidant enzymes in S. pistillata, which contains low concentrations of Myc-Gly suggest that Myc-Gly provides rapid protection against oxidative stress before the antioxidant enzymes are induced. These findings strongly suggest that Myc-Gly is functioning as a biological antioxidant in the coral tissue and zooxanthellae and demonstrate its importance in the survival of reef-building corals under thermal stress.

Amino Acids↗
PubMed2001

NGF, NT-3 and Trk C mRNAs, but not TrkA mRNA, are upregulated in the paraventricular structures in experimental hydrocephalus.

OBJECTS: This study was designed to detect possible alterations in the expression of neurotrophins and trks in kaolin-induced hydrocephalus by in situ hybridization. METHODS AND RESULTS: Sixteen rats were treated by injection of 25 mg kaolin suspended in 0.1 ml of physiological saline into the cisterna magna. Four rats were injected with saline and served as controls. The kaolin-treated rats were divided into two groups studied 1 and 4 weeks after treatment. Rats were anesthetized and killed, and their brains were rapidly dissected and frozen. DNA oligonucleotide probes for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and trkA, trkB, and C were labeled with [(35)S]dATP using terminal deoxyribonucleotidyl transferase for in situ hybridization. Hydrocephalic brains were also classified according to the degree of ventricular enlargement. The results observed were as follows. (1) The medial septal and striatal NGF mRNA levels increased with severity in animals. (2) Hippocampal trkB and BDNF mRNA levels increased with time in animals with moderate ventricular enlargement. (3) Expression of hippocampal trkB, trkC, and NT-3 mRNA increased in animals with moderate ventricular enlargement, while it apparently decreased in the large ventricular enlargement group reaching normal ranges. (4) In the corpus callosum there was an apparent increase in NGF, NT-3 and trkC mRNA, but not in trkA, in hydrocephalic animals. NT-3 EIA confirmed the presence of NT-3 protein increases in corpus callosum. It is therefore possible that simultaneous NGF, NT-3, and trkC receptor upregulation occurred in glial elements of the white matter. CONCLUSIONS: These results demonstrate that neurotrophins and their receptors are overexpressed in many damaged structures of the severely hydrocephalic brain. There were discrepancies in the distribution of NGF and trkA mRNA, and we hypothesize that NGF mRNA in the damaged white matter structure might be due to the reduced availability of other receptors, such as the low-affinity NGF receptors.

Animals↗
PubMed2001

Enhanced homologous recombination caused by the non-transcribed spacer of the rDNA in Arabidopsis.

The problem of the low frequency of homologous recombination observed in higher plants has been approached in several ways. Here, we report a new strategy to enhance homologous recombination in Arabidopsis. In Escherichia coli and Saccharomyces cerevisiae, hotspots that enhance homologous recombination nearby have been identified in regions close to sites associated with the blocking of DNA replication forks or with intensive transcriptional activity. In yeast, a recombination hotspot (HOT1) was found in a region spanning two non-transcribed spacers (NTS) between ribosomal RNA genes (rDNA), which contains both a replication fork barrier ( RFB) and the promoter for transcription of the 35S rRNA gene. Since rDNA has a common structure among eukaryotes, we analyzed the effect of the endogenous NTS on homologous mitotic recombination in a higher plant. We constructed transgenic lines of Arabidopsis containing this NTS and a recombination substrate, in which two 3'- and 5'-deleted uidA (beta-glucuronidase) genes with partially overlapping sequences are separated by a Hyg(r) gene. Reconstitution of functional uidA genes by homologous recombination was monitored by histochemical GUS staining. We found that recombination occurred more frequently in all organs tested in F (Fork block) lines transgenic for the NTS than in C (Control) lines without the NTS. The average number of GUS+ spots on leaves in F lines was more than nine-fold higher than in C lines. Furthermore, by genomic Southern analysis, post-recombinational molecules were detected in a transgenic line, F43, which had an extremely high number of GUS+ blue spots. These results strongly suggest that NTS-dependent enhancement of homologous recombination may be a common feature of higher plants as well as yeast.

Arabidopsis↗
PubMed2001

Cryoprecipitate of patients with cryoglobulinemic glomerulonephritis contains molecules of the lectin complement pathway.

Serological and histological studies were carried out to explore the role of the lectin complement pathway in the pathogenesis of cryoglobulinemic glomerulonephritis. Sixteen patients with mixed cryoglobulinemia type II with glomerulonephritis (GN) were enrolled. All cases had hepatitis C virus (HCV) infection. The serum concentration of mannose-binding lectin (MBL) was significantly higher in the GN patients than in the normal controls according to ELISA (P < 0.01). IgG, IgM, C1q, C4d, HCV envelope antigen, MBL, and MBL-associated serine protease-1 (MASP-1) could be visualized in the cryoprecipitate of the 16 patients by Dot blot assay. Renal biopsy specimens obtained from 3 patients were examined by immunohistochemistry, and the glomeruli strongly stained for IgG, IgM, MBL, MASP-1, C4d, C3c, and C3d in a fringe-like pattern. The pattern of HCV constituent deposition was partially fringe-like. The complement profiles of the 16 cases were distinctive; briefly, the serum levels of C1q, C2, and C3 were reduced, although the levels of circulating regulatory proteins (C1-inhibitor, factor H, and factor I) were in the normal range. The serum C4 level was significantly reduced. These results indicate that immune complex formation involves molecules of the lectin pathway and leads to organ damage in cryoglobulinemic glomerulonephritis.

Adolescent↗
PubMed2001

Dynamic measurement of the flow rate in cerebrospinal fluid shunts in hydrocephalic patients.

We compared clinical outcomes in hydrocephalic patients and observed variation in the rate of flow in ventriculoperitoneal shunts with changes in posture in 231 separate examinations of shunt flow in 148 patients. A small cadmium telluride detector was placed over the shunt reservoir, and clearance of radioisotope injected into the reservoir was recorded as a measure of flow. Flow rate tended to increase during head elevation. Four patterns of radioisotope clearance were seen: type I, no flow; type II, adequate flow with moderate opening pressure; type III, adequate flow with low opening pressure; and type IV, excessive flow. This categorisation reflected clinical shunt function. Our method effectively assesses flow rate with the patient in a variety of postures or during movement, yielding useful information for adjustment of shunt valve pressure.

Adolescent↗
PubMed2001

A case of renal involvement in persistent immune activation caused by chlamydial salpingitis.

A 24-year-old woman presented with renal insufficiency, macrohematuria, and mild urinary protein. Polyclonal hypergamma-globulinemia, thrombocytosis, increased concentration of serum, and urinary interleukin (IL)-6 all indicated persistent immune activation caused by a Chlamydia trachomatis infection of the fallopian tube. Gynecological treatment with levofloxacin was effective both for the renal symptoms and other immunological parameters. First and second renal biopsy specimens showed an immune-complex glomerulopathy with extensive interstitial infiltration of many types of inflammatory cells, including plasma cells. Thus, we conclude that chlamydial salpingitis must be considered as one causative disease factor for renal involvement by means of its persistent immune activation effects.

Adult↗
PubMed2001

Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case.

We herein present a case of attenuated familial adenomatous polyposis (AFAP) with advanced rectal cancer in a 16-year-old boy. His mother and younger brother both had subcutaneous soft tissue tumors in the back and sparse-type colorectal polyposis. His mother also had dental anomalies and gastric fundic gland polyposis. The patient was admitted to our hospital for investigation of bloody stools. Barium enema and colonofiberscopy revealed advanced rectal cancer and sparse (<50) colorectal polyps. He also had dental anomalies, a subcutaneous soft tissue tumor in the back, and gastric fundic gland polyposis as extracolonic manifestations. A total proctocolectomy and ileoanal anastomosis were performed, and histological examination of the resected specimens confirmed moderately differentiated adenocarcinomas of the rectum with metastases to the regional lymph nodes. The other colorectal polyps were tubular adenomas with no evidence of malignancy. Germline mutations in the APC gene were observed in codons 486, 545, 1493, and 1556. This case serves to demonstrate that a total proctocolectomy with ileoanal anastomosis should be the procedure of choice for young patients found to have advanced rectal cancer associated with FAP.

Adenocarcinoma↗
PubMed2001

PGl2 analogue mitigates the progression rate of renal dysfunction improving renal blood flow without glomerular hyperfiltration in patients with chronic renal insufficiency.

Renal blood flow decreases with the progression of chronic glomerulonephritis (CGN). This disease induces medullary ischemia and further renal dysfunction in patients with chronic renal insufficiency (CRI). Prostacyclin (PGI2), with its vasodilative action, increases renal blood flow (RBF) without increasing glomerular filtration rate (GFR). We therefore examined the possibility that PGI2 would mitigate the progression of renal dysfunction by increasing RBF in patients with CRI. Sixteen patients with progressive renal insufficiency (serum creatinine: 2.14+/-0.89 mg/dl) due to CGN were prospectively chosen for this study. The blood pressure was already under control using calcium channel blockers before and during this study in nine hypertensive patients. In the first 6 months the patients received a low-protein (0.6 g/kg/day) and low-salt (5.0 g/day) diet. In the next 6 months they received 60 microg/day of PGI2 analogue (Beraprost sodium) orally. GFR was determined by 24-hour creatinine clearance, and effective renal plasma flow (ERPF) was determined by 99mTc-MAG3 scintigraphy. Glomerular capillary pressure, the resistance ratio of afferent and efferent arterioles (R(A)/R(E)), and the other hemodynamic parameters from Gomez's estimation equation were determined at the start of this study, just before the administration of Beraprost and at the end of the study. The levels of GFR and ERPF were 34.6+/-12.4 and 140.6+/-52.1 ml/min at the start of this study respectively, and decreased to 28.0+/- 12.0 and 115.6+/-45.3 ml/min after the first 6 months without Beraprost. The levels of GFR and ERPF stayed at 28.1+/-15.7 and 119.2+/-57.6 ml/min after the next 6 months with Beraprost in the same patients. R(A)/R(E) increased in the first 6 months from 7.9+/-3.6 to 10.8+/-8.6, but remained constant during 6 months of Beraprost administration, at 10.5+/-8.0. These data indicate that PGI2 analogue diminishes the vascular resistance of glomerular afferent and efferent arterioles regulating the decrease of renal blood flow without glomerular hyperfiltration, thus mitigating the progression rate of renal dysfunction.

Creatinine↗
PubMed2001

Regulation of in situ complement activation via the lectin pathway in patients with IgA nephropathy.

The lectin pathway, which is initiated by mannose-binding lectin (MBL) and MBL-associated serine protease (MASP), is one of the possible routes to activate the complement cascade in immunoglobulin A (IgA) nephropathy. The purpose of this study was to elucidate the regulatory mechanism of the pathway. Levels of complement activation products and regulatory proteins were measured in sera from 27 patients with IgA nephropathy, and generation of fluid-phase complement activation products in the presence of pooled normal human serum was quantified to evaluate activation in vitro. Although there were no significant differences in the serum levels and in vitro activation between the MBL-MASP positive (n = 14) and negative (n = 13) groups, there were positive correlations between complement activation products (Bb fragment and C4d fragment) and regulatory proteins (factor H, C4-binding protein, and C1 inhibitor) in the MBL-MASP-positive group. Furthermore, immunohistochemical studies demonstrated glomerular deposition of the regulatory protein (C4-binding protein, alpha2-macroglobulin, and factor H) in all patients in the MBL-MASP-positive group. These findings suggest that the regulatory proteins control in situ complement activation via the lectin pathway immediately, and continuous activation due to inadequate control will lead to the advanced glomerular injury.

Carrier Proteins↗
PubMed2000

Adrenomedullin increases phosphatidylcholine secretion in rat type II pneumocytes.

Adrenomedullin, a novel hypotensive peptide, has been reported to be produced in the lung as well as in the adrenal medulla. However, the effect of adrenomedullin on lung function is still poorly understood. In this study, we detected the expression of both adrenomedullin mRNA and putative adrenomedullin receptor mRNA in primary cultures of rat type II pneumocytes. Adrenomedullin increased the secretion of phosphatidylcholine, the predominant component of pulmonary surfactant, by type II pneumocytes. The increase was partly inhibited by pretreatment with the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37). Furthermore, the increased phosphatidylcholine secretion was significantly inhibited by several protein kinase C inhibitors, such as sphingosine, 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]3-(1H-indol-3-yl) maleimide (Gö6983), 3-[1-(3-amidinothio)-propyl-1H-indoyl-3-yl]3-(1-methyl-1H-++ +indoyl-3-yl ) maleimide methane sulfonate (Ro-31-8220), and staurosporine. Our results suggest that adrenomedullin can be considered a candidate autocrine modulator of surfactant secretion in type II pneumocytes.

Adrenomedullin↗
PubMed2000

L-152,804: orally active and selective neuropeptide Y Y5 receptor antagonist.

Neuropeptide Y (NPY) elicits food intake through the action of hypothalamic G-protein-coupled receptors. Previous publications indicate that the Y5 receptor may represent one of these postulated hypothalamic "feeding" receptors. Using a potent and orally available Y5 antagonist L-152,804, we evaluated the involvement of the Y5 receptor in feeding regulation. L-152,804 displaced [125I]peptide YY (PYY) binding to human and rat Y5 receptors with Ki values of 26 and 31 nM, respectively, and inhibited NPY (100 nM)-induced increase in intracellular calcium levels via human Y5 receptors (IC50 = 210 nM). L-152,804 did not show significant affinity for human Y1, Y2, and Y4 receptors at a dose of 10 microM. Intracerebroventricular (i.c.v.) (30 microg) or oral (10 mg/kg) administration of L-152,804 significantly inhibited food intake evoked by i.c.v.-injected bovine pancreatic peptide (bPP, 5 microg; a moderately selective Y4, Y5 agonist) in satiated SD rats. However L-152,804 did not significantly inhibit i.c.v. NPY (5 microg; a Y1, Y2, Y5 agonist)-induced food intake. These findings suggest that L-152,804 is a selective and potent non-peptide Y5 antagonist with oral bioavailability and brain penetrability. In addition, the anorexigenic effects of L-152,804 on bPP-induced feeding revealed participation of the Y5 receptor in feeding regulation, while i.c.v. administration of NPY does not appear to significantly contribute to Y5 stimulated food intake. We conclude that the potent and orally active Y5 antagonist, L-152,804, represents a useful tool to address the physiological role of the Y5 receptor.

Administration, Oral↗
PubMed2000

Acute alteration in bone mineral density and biochemical markers for bone metabolism in nephrotic patients receiving high-dose glucocorticoid and one-cycle etidronate therapy.

It is widely known that glucocorticoids induce and accelerate osteoporosis. High-dose glucocorticoids are administrated daily to patients in the acute phase of nephrotic syndrome. It could be inferred that high-dose glucocorticoids rapidly decrease patients' basal bone mineral density (BMD) and this accelerates the natural progress of osteoporosis associated with aging or menopause. Nine nephrotic patients (male/female: 5/4) without previous prednisolone administration were chosen to measure BMD and the level of the markers for bone turnover before and after treatment for 3 months (total prednisolone administration: 4.5 +/- 0.0 g). Twenty-three patients under remission with prednisolone administration (male/female: 14/9) were included in the long-term treatment group. Patients in this group whose %YAM in the lateral lumbar spine was less than 89% were classified into a low BMD group (n = 10, male/female: 3/7). They were administered etidronate disodium at 200 mg/day for 14 days. BMD and % of young adult mean (YAM) in the lumbar spine (L2-L4 in lateral objection) and other regions were measured by dual-energy X-ray absorptiometry. As markers of bone metabolism, the urinary level of deoxypyridinoline (Dpd) was determined to evaluate osteogenesis, and serum osteocalcin was measured to evaluate bone resorption. BMD of the lumbar spine significantly decreased in the 3-month treatment group (752 +/- 96 mg/cm(2), 7 +/- 4% reduction) compared with the pretreatment group (810 +/- 85 mg/cm(2)). BMD in the long-term treatment group decreased continuously (683 +/- 135 mg/cm(2)). No significant differences were noted in other measurement sites. BMD in the etidronate treatment group increased significantly (597 +/- 55 mg/cm(2)) compared with the pretreatment group (549 +/- 76 mg/cm(2)). Etidronate did not change BMD at the sites with a normal BMD. Among the biochemical markers (BM) examined, the urinary level of Dpd (nMol/liter. Cr) significantly increased in the 3-month treatment group (8.6 +/- 5.1 nMol/liter.Cr) compared with the pretreatment group (5.8 +/- 2.0 nMol/liter. Cr). No significant differences were seen in the BMs measured in the long-term treatment group. The urinary Dpd level of the etidronate treatment group decreased (3.9 +/- 1.4 nMol/liter. Cr) compared with the pretreatment group. These data indicate that etidronate could improve the accelerated bone resorption. In conclusion, high-dose glucocorticoid therapy causes rapid bone resorption and accelerates the natural progress of osteoporosis associated with aging or menopause. Etidronate administration prevents the progress of osteoporosis in nephrotic patients. Preventive treatment should be performed when the estimated BMD in 3 months falls below the baseline by more than 7 +/- 4%, reaching the therapeutic range.

Adolescent↗
PubMed2000

Gene trapping of two novel genes, Hzf and Hhl, expressed in hematopoietic cells.

Using an expression gene trapping strategy, we have identified and characterized two novel hematopoietic genes, Hzf and Hhl. Embryonic stem (ES) cells containing a gene trap vector insertion were cultured on OP9 stromal cells to induce hematopoietic differentiation and screened for lacZ reporter gene expression. Two ES clones displaying lacZ expression within hematopoietic cells in vitro were used to generate mice containing the gene trap integrations. Paralleling this in vitro expression pattern, both Hzf and Hhl were expressed in a tissue-specific manner during hematopoietic development in vivo. Hzf encodes a novel protein containing three C(2)H(2)-type zinc fingers predominantly expressed in megakaryocytes and CFU-GEMM. Hhl encodes a novel protein containing a putative phosphotyrosine binding (PTB) domain expressed in megakaryocytes, CFU-GEMM and BFU-E. These results demonstrate the utility of expression trapping to identify novel hematopoietic genes. Future studies of Hzf and Hhl should provide valuable information on the role these genes play during megakaryocytopoiesis.

Amino Acid Sequence↗