Biomedical subjects

K Itoh

Publications and source records attributed to K Itoh.

At least 343 records · Page 19Linked to original sources

PubMed1999

Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFalpha gene and HLA genes.

OBJECTIVE: To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor alpha (TNFalpha) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). METHODS: One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFalpha, HLA-A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. RESULTS: The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFalpha gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFalpha -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). CONCLUSION: The -1,031C/-863A allele and the -857T allele of the TNFalpha gene, both of which are related to high production of tumor necrosis factor alpha, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.

Arthritis, Juvenile↗

PubMed1999

Trypsin-catalyzed peptide synthesis with m-guanidinophenyl and m-(guanidinomethyl)phenyl esters as acyl donor component.

Two series of inverse substrates, m-guanidinophenyl and m-(guanidinomethyl)phenyl esters derived from N-(tert-butyloxycarbonyl)-amino acid, were prepared as an acyl donor component for trypsin-catalyzed peptide synthesis. The kinetic behavior of these esters toward tryptic hydrolysis was analyzed. They were found to couple with an acyl acceptor such as L-alanine p-nitroanilide to produce dipeptide in the presence of trypsin. Streptomyces griseus trypsin was a more efficient catalyst than the bovine trypsin. Within the enzymatic peptide coupling methods, this approach was shown to be advantageous, since the resulting peptides are resistant to the enzymatic hydrolysis.

Animals↗

PubMed1999

Validity of 99mTc-DMSA renal uptake by planar posterior-view method in children.

Renal uptake of 99mTc-DMSA has been quantified by various methods. The aim of this study is to obtain a normal value for 99mTc-DMSA renal uptake calculated by the posterior view method and age variation, and to assess its clinical validity. Scintigrams of 238 children (0-12 years) with 99mTc-DMSA were reviewed. All the children had a clinical history of primary vesicoureteral reflux and/or neurogenic bladder, ureteral or urethral anomalies. Their kidneys were divided into two groups, "normal" and "abnormal" according to their scintigraphic findings and split renal functions. Percent renal uptake per injected dose (% RU) was quantitated from planar images at 2 hours after injection of an age-adjusted dose (26-95 MBq) of 99mTc-DMSA. Calculated total % RU, individual % RU of the right and left kidneys (mean +/- sd) in patients with normal kidneys were 40.7 +/- 5.0%, 20.2 +/- 3.0%, 20.4 +/- 2.7%, respectively. There was no significant correlation between % RU and age (r = 0.231). Longitudinal variation in the % RU in 9 patients ranged from 1.2% to 18%. Our conventional method for quantifyng % RU is simple, practical and feasible in routine clinical practice, especially for children under follow up.

Adolescent↗

PubMed1999

Reappraisal of Tc-99m DMSA scintigraphy for follow up in children with vesicoureteral reflux.

We reviewed Tc-99m DMSA scintigraphy in children with vesicoureteral reflux (VUR) in order to assess whether repeated Tc-99m DMSA scans are necessary for the follow up of these patients. Ninety-seven children who were followed up for more than one year (1-7.4 years, average 2.8 years) after the first DMSA scan were included in the study. Fifty-one patients had been diagnosed as primary VUR and 46 as secondary VUR. Age at the first examination ranged from 0 to 14 years (average 5.1 years). Planar images were taken 2 hours after injection. The % renal uptake per injected dose (%RU) was calculated from posterior images. Kidneys in 11 patients (11.3%) changed morphologically during the follow up. Of these, new photon deficient areas (PD) were detected in only 4 patients (4.1%). All of these 4 patients had neurogenic bladder and were managed with self-catheterization. Of the remaining 7 patients, cortical thinning progressed in 5 patients (5.2%) and PDs resolved in 3 patients (3.1%). In one of these 7 patients, PD resolved in one kidney and cortical thinning progressed in the contralateral kidney. Of 97 patients reviewed, % RU decreased more than 20% during the follow up in 6 patients (6.2%). All were diagnosed as secondary VUR due to neurogenic bladder. %RU decreased only in the contracted kidneys at the initial scan. Two of them underwent renal transplantation because of severe renal failure. In conclusion, new PD rarely developed and % RU decreased in only a few patients during the follow up of children with VUR. Repeated Tc-99m DMSA scintigraphy therefore seems to have little benefit in the follow up of children with VUR. It should be performed in selected patients with high risk of urinary tract infection or renal failure.

Adolescent↗

PubMed1999

Two cases of inflammatory bowel disease with multiple myeloma.

A significant increase has been reported in reticuloendothelial neoplasms in patients with inflammatory bowel diseases. We present two rare cases of multiple myeloma in patients with inflammatory bowel diseases. One was in a 58-year-old woman with ulcerative colitis, and the other was in a 59-year old woman with Crohn's disease. In both patients, multiple myeloma occurred during long-term observation of inflammatory bowel disease and during the inactive stage of intestinal inflammation. The multiple myeloma appeared to have resulted from monoclonal gammopathy of undertermined significance in both patients, and was diagnosed by characteristic serum and bone marrow findings. Our findings suggested that multiple myeloma should be particularly considered in women of middle or advanced age with ulcerative colitis or Crohn's colitis and serum monoclonal gammopathy.

Female↗

PubMed1999

Transformation of bile acids and sterols by clostridia (fusiform bacteria) in Wistar rats.

The effects on bile acid and sterol transformation of clostridia (fusiform bacteria), the dominant intestinal bacteria in rodents (ca. 10(10) counts per g wet feces) were examined in Wistar rats. After inoculation of clostridia into germ-free rats and into rats previously inoculated solely with Escherichia coli, most of the endogenous bile acids were deconjugated, and cholic acid and chenodeoxycholic acid were 7alpha-dehydroxylated to deoxycholic acid and lithocholic acid, respectively. Tauro-beta-muricholic acid, another major bile acid in rats, was deconjugated, but only part of it (ca. 30%) was transformed into hyodeoxycholic acid. Cholesterol and sitosterol were also reduced to coprostanol and sitostanol, respectively. Escherichia coli transformed neither bile acids nor sterols. These data suggest that clostridia play an important role in the formation of secondary bile acids and coprostanol in rats.

Animals↗

PubMed1999

Consensus report on quality control of quantitative measurements of renal function obtained from the renogram: International Consensus Committee from the Scientific Committee of Radionuclides in Nephrourology.

Among all the physiological indices that can be quantified using renography, measurement of renal function is the most basic. These measurements are used to make critical clinical management decisions and, as such, their reliability needs to be quality assured. This article seeks to address each aspect of the renography procedure, with particular emphasis on the effect on measurement of relative renal function. Estimation of individual kidney function is mentioned, but only briefly. A consensus approach was adopted, overseen, and directed by a chairman appointed by the Scientific Committee of the International Radionuclides in Nephro-Urology Group. The chairman selected the panel of experts from eight different countries based on their practical experience in the field. Where evidence exists to support the various recommendations it is given. Otherwise, the stated guidance represents the considered opinion of a body of experts, based on long experience and unpublished data. Some necessary compromises were made to account for the fact that renography is seldom performed solely with the purpose of measuring relative renal function. The technicalities of renography have always been a source of debate in nuclear medicine, which is reflected by the fact that a consensus could simply not be reached on a small number of issues. The structure of the report ensures that these are clearly indicated. This should serve to highlight gaps in our current knowledge, thus helping to direct future research. It is envisaged that the recommendations will be revised on a 2-year cycle to ensure that they remain up to date. An "open" process will be used to encourage participation and ownership. It is hoped that promotion of these guidelines, suitably complemented by audit processes, will raise standards in the practice of gamma camera renography.

Adult↗

PubMed1999

Urinary excretion of the vitronectin receptor (integrin alpha V beta 3) in patients with Fabry disease.

A renal disorder is one of the important manifestations of Fabry disease, but the details of the pathogenesis have not been clarified yet. We examined the possibility that the vitronectin receptor (VNR, integrin alpha V beta 3), one of the integrins, is involved in the progression of the renal injury in Fabry disease. We measured the urinary excretion of beta 3 originating from VNR in Fabry patients by immunoblotting analysis and enzyme-linked immunosorbent assay (ELISA). Immunofluorescent microscopic analyses for VNR and globotriaosylceramide were performed on urinary sediments from Fabry patients. Furthermore, beta 3 and vitronectin in kidney tissues were analyzed immunohistochemically. Immunoblotting analysis and ELISA showed that the urinary excretion of beta 3 originating from VNR was significantly increased in the Fabry group compared with both the pathological and healthy control groups. Immunofluorescent microscopy revealed the expression of VNR and accumulation of globotriaosylceramide in urinary sediments from the Fabry patients. Increased expression of beta 3 was observed in glomerular epithelial cells, and in Bowman's capsular epithelial layer and tubular cells, and the amount of vitronectin was moderately increased in the kidney tissues from the Fabry patients. The urinary excretion of VNR was increased, and the expression of VNR was observed in Fabry kidney tissues. The expression of VNR may be involved in the progression of the renal injury in this disease.

Adolescent↗

PubMed1999

Hyperechoic renal papillae as a physiological finding in neonates.

AIM: The increased echogenicity of medullary pyramids in neonates and children is poorly understood. Hence we conducted a prospective ultrasound study of the kidneys of neonates and fetuses. Hence we conducted a prospective ultrasound study of the kidneys of neonates and fetuses. PATIENTS AND METHODS: Ultrasound images of kidneys in neonates and fetuses in late pregnancy were analysed. RESULTS: Thirteen percent of the studied neonates showed hyperechogenicity in the renal papillae that disappeared spontaneously within 1 week, although no hyperechoic papillae were seen in any of the fetuses. Urine volume of the neonates with hyperechogenicity was significantly less than that of those without it. CONCLUSION: The fact that no hyperechoic findings appeared before the 34th week of gestation suggests that maturation of renal tubules and ability to concentrate urinary substances were contributing factors. Because only the tips of the pyramids were hyperechogenic, however, the term hyperechoic papillae would seem more appropriate than hyperechoic pyramids, the term generally used today.

Birth Weight↗

PubMed1999

Expression of protective protein in human tissue.

The authors investigated by immunohistochemistry the distribution of protective protein in human tissues. Immunoreactivity was observed in the cytoplasm, revealing a granular pattern and cell type specificity. The most intense staining was observed in the large neurons of brain, distal and collecting tubular cells of kidney, epithelial cells of bronchus, and Leydig cells of testis. In a patient with galactosialidosis type IIa, all these stains were absent. The neurons that were most strongly stained in the control group, such as the Betz cells, neurons in the basal forebrain, motor neurons in the cranial nerve nuclei, and ventral horn cells of the spinal cord, were markedly ballooned in the patient with galactosialidosis.

Adolescent↗

PubMed1999

NADPH-diaphorase and cytosolic urea cycle enzymes in the rat accessory olfactory bulb.

The nitric oxide cycle consists of nitric oxide synthase, argininosuccinate synthetase and argininosuccinate lyase to form nitric oxide. We have examined the colocalization of nitric oxide synthase and the cytosolic urea cycle enzymes (argininosuccinate synthetase, argininosuccinate lyase and arginase) in the accessory olfactory bulb of the rat by using a double labeling procedure combining reduced-nicotinamide-adenine-dinucleotide-phosphate-diaphorase (NADPH-d) reaction with fluorescent immunocytochemistry. Each glomerulus showed a different NADPH-d activity, and those with the strongest NADPH-d activities were assembled in the caudomedial part of the accessory olfactory bulb. Argininosuccinate synthetase-like immunoreactive glomeruli were distributed in the caudomedial part of the accessory olfactory bulb, and most of them were also strongly NADPH-d positive. The mitral or tufted cells were argininosuccinate synthetase-, argininosuccinate lyase- and arginase-like immunoreactive, but were not NADPH-d positive. The granule cells were NADPH-d positive or argininosuccinate lyase-like immunoreactive, but were not argininosuccinate synthetase- or arginase-like immunoreactive. Some granule cells were both NADPH-d positive and argininosuccinate lyase-like immunoreactive. The results indicate the heterogeneity of glomeruli of the accessory olfactory bulb with respect to the distribution of these enzymes. The granule cells have nitric oxide synthase and argininosuccinate lyase, and thus may efficiently produce nitric oxide.

Animals↗

PubMed1999

Effects of ischemia and H2O2 on the cold stress protein CIRP expression in rat neuronal cells.

Expression of CIRP (cold-inducible RNA-binding protein) is inducible at 32 degrees C in cultured fibroblasts. Because ischemia is known to induce expression of heat shock proteins, its effect on the CIRP expression was examined using the rat transient forebrain ischemia model. The isolated rat CIRP cDNA encoded amino acids 100% identical in its sequence to mouse CIRP. Northern blot analysis revealed that the CIRP transcripts were ubiquitously expressed in various tissues. In situ hybridization histochemistry of normal rat brain revealed the expression of CIRP in neurons in the hippocampus and the cerebral cortex among others. In the hippocampus of postischemic rats, CIRP mRNA level decreased from 3-6 h after the onset of reperfusion, while it did not change in the cerebral cortex. When PC12 pheochromocytoma cells were cultured at 32 degrees C, the CIRP mRNA level was increased. The presence of H2O2 in the culture media inhibited dose dependently this induction as well as constitutive expression, suggesting that the effect of brain ischemia on CIRP expression is related to generation of reactive oxygen species. Further studies are necessary to clarify the roles played by cold shock proteins in the hypothermic therapy of brain damages.

Amino Acid Sequence↗

PubMed1999

Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand.

We previously reported that osteoblasts/stromal cells are essentially involved in the activation as well as differentiation of osteoclasts through a mechanism involving cell-to-cell contact between osteoblasts/stromal cells and osteoclast precursors/osteoclasts. Osteoclast differentiation factor (ODF, also called RANKL/OPGL/TRANCE) and macrophage colony-stimulating factor (M-CSF, also called CSF-1) are two essential factors produced by osteoblasts/stromal cells for osteoclastogenesis. In other words, osteoblasts/stromal cells were not necessary to generate osteoclasts from spleen cells in the presence of both ODF/RANKL and M-CSF. In the present study, we examined the precise roles of ODF/RANKL and M-CSF in the activation of osteoclasts induced by calvarial osteoblasts. Osteoclasts were formed in mouse bone marrow cultures on collagen gel-coated dishes in response to a soluble form of ODF/RANKL (sODF/sRANKL) and M-CSF, and recovered by collagenase digestion. When recovered osteoclasts were further cultured on plastic dishes, most of the osteoclasts spontaneously died within 24 h. Osteoclasts cultured for 24 h on dentine slices could not form resorption pits. Addition of sODF/sRANKL to the recovered osteoclasts markedly enhanced their survival and pit-forming activity. M-CSF similarly stimulated the survival of osteoclasts, but did not induce their pit-forming activity. When primary mouse osteoblasts were added to the recovered osteoclasts, resorption pits were formed on dentine slices. Bone-resorbing factors such as 1alpha,25-dihydroxyvitamin D3, parathyroid hormone, or prostaglandin E2 enhanced pit-forming activity of osteoclasts only in the presence of osteoblasts. M-CSF-deficient osteoblasts prepared from op/op mice similarly enhanced pit-forming activity of osteoclasts. The pit-forming activity of osteoclasts induced by sODF/sRANKL or osteoblasts was completely inhibited by simultaneous addition of osteoprotegerin/osteoclastogenesis inhibitory factor, a decoy receptor of ODF/RANKL. Primary osteoblasts constitutively expressed ODF/RANKL mRNA, and its level was upregulated by treatment with 1alpha,25-dihydroxyvitamin D3, parathyroid hormone, and prostaglandin E2. These results, obtained by using an assay system that unequivocally assesses osteoclast activation, suggest that ODF/RANKL but not M-CSF mediates osteoblast-induced pit-forming activity of osteoclasts, and that bone-resorbing factors stimulate osteoclast activation through upregulation of ODF/RANKL by osteoblasts/stromal cells.

Animals↗

PubMed1999

Adrenal adenoma with foci of oncocytes in a patient with pre-Cushing's syndrome.

A case of unilateral adrenal adenoma with foci of oncocytes in a 64-year-old woman is reported. The tumour manifested clinically pre-Cushing's syndrome with autonomous steroidogenesis which was insufficient to cause typical features of Cushing's syndrome. Whether the pathogenesis of oncocytes and adenoma cells, which were thought to have some metabolic deficiency in the present tumour, are linked remains to be determined.

Adenoma↗

PubMed1999

The prognosis of stage A patients treated with the antiandrogen chlormadinone acetate.

To determine the efficacy of the antiandrogen chlormadinone acetate as a treatment option for stage A prostate cancer, a retrospective analysis of 111 patients who received chlormadinone acetate was done. Of 55 stage A1 patients, progression was seen in one patient (1.8%) 8 years after the diagnosis. Six out of 56 stage A2 patients (10.7%) showed disease progression at 1-7 years (mean 68 months) after the diagnosis. Progression rates associated with antiandrogen therapy for stage A1 and stage A2 patients were lower than those without treatment reported in the literature. It could be assumed that antiandrogen treatment with chlormadinone acetate inhibited the progression.

Aged↗

PubMed1999

Polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in patients with rheumatoid arthritis.

Polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-a gene were examined to study the genetic background of rheumatoid arthritis (RA). Four variant alleles, -1,031C/ -863A, -1,031C/-238A, -857T and -308A, were identified and examined in 387 RA patients and 575 healthy Japanese controls. The frequency of the -857T allele in RA patients was significantly higher than that in the controls. However, the HLA-DRB1 analysis in the same subjects showed that the DRB1*0405 allele, which is in linkage disequilibrium with the -857T, was more strongly associated with the disease susceptibility than the -857T allele. These results suggest that the susceptible gene to RA is more closely linked to the HLA-DRB1 locus than to the TNF-alpha locus.

5' Untranslated Regions↗

PubMed1999

An essential part for Rho-associated kinase in the transcellular invasion of tumor cells.

Adhesion of tumor cells to host cell layers and subsequent transcellular migration are pivotal steps in cancer invasion and metastasis. The small GTPase Rho controls cell adhesion and motility through reorganization of the actin cytoskeleton and regulation of actomyosin contractility. Cultured rat MM1 hepatoma cells migrate through a mesothelial cell monolayer in vitro in a serum-dependent, Rho-mediated manners. Among several proteins isolated as putative target molecules of Rho, the ROCK (ROK) family of Rho-associated serine-threonine protein kinases are thought to participate in the induction of focal adhesions and stress fibers in cultured cells, and to mediate calcium sensitization of smooth muscle contraction by enhancing phosphorylation of the regulatory light chain of myosin. Transfection of MM1 cells with cDNA encoding a dominant active mutant of ROCK conferred invasive activity independently of serum and Rho. In contrast, expression of a dominant negative, kinase-defective ROCK mutant substantially attenuated the invasive phenotype. A specific ROCK inhibitor (Y-27632) blocked both Rho-mediated activation of actomyosin and invasive activity of these cells. Furthermore, continuous delivery of this inhibitor using osmotic pumps considerably reduced the dissemination of MM1 cells implanted into the peritoneal cavity of syngeneic rats. These results indicate that ROCK plays an essential part in tumor cell invasion, and demonstrate its potential as a therapeutic target for the prevention of cancer invasion and metastasis.

Amides↗

PubMed1999

CD34high+ CD38(low/-) cells generated in a xenogenic coculture system are capable of both long-term hematopoiesis and multiple differentiation.

CD34+ cells isolated from human umbilical cord blood (HUCB) are thought to have potential in clinical applications such as transplantation and gene therapy. Recently, we developed a xenogenic coculture system involving HUCB-CD34+ cells and murine bone marrow stromal cells, HESS-5 cells, in combination with human interleukin-3 and stem cell factor. Under these xenogenic coculture conditions, the numbers of CD34high+ cells and primitive progenitor cells, such as CD34high+ CD38(low/-) cells and high proliferative potential colony-forming cells (HPP-CFCs), increased dramatically by a factor of 102.1, 66.5 and 104.9, respectively. In the present study, we used a secondary culture of B progenitor cells and long-term culture (LTC)-initiating cells to characterize and compare the progenitor capability of re-isolated CD34high+ CD38(low/-) cells, which have been identified as one of the most primitive progenitor cells, with that of freshly isolated CD34high+ CD38(low/-) cells. Compared with freshly isolated CD34high+ CD38(low/-) cells, the re-isolated CD34high+ CD38(low/-) cells were equally as capable of proliferating and differentiating into myeloid and B progenitor cells. No significant differences were observed in the frequency of LTC-initiating cells in the re-isolated CD34high+ CD38(low/-) cells compared with that in freshly isolated CD34high+ CD38(low/-) cells. Furthermore, the re-isolated CD34high+ CD38(low/-) cells were capable of long-term reconstitution and multiple differentiation in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice). The results demonstrate that this xenogenic coculture system can be used for successful in vitro expansion of HUCB-progenitor cells that possess the capability for both long-term hematopoiesis as well as multipotent differentiation into myeloid and lymphoid cells both in vivo and in vitro.

ADP-ribosyl Cyclase↗