Search PubMed⌕ Search

Biomedical subjects

Y Itoh

Publications and source records attributed to Y Itoh.

At least 361 records · Page 20Linked to original sources
PubMed1997

Permeability of a neuroprotective compound NS-7 into brain: comparison between normal and middle cerebral artery-occluded rats.

The pharmacokinetics of 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride (NS-7), a novel neuroprotective compound, in brains of normal and ischemic rats were investigated. In normal rats, the concentrations of NS-7 in the cerebral cortex and striatum were more than 10-folds higher than those in plasma during 5 min and 12 h after intravenous injection. The time course changes in plasma concentration of NS-7 were fitted to the two-compartment open model, in which elimination half-life (t(1/2)beta) was 6.0 h and distribution volume (V1) was 4.4. The estimated striatal interstitial concentration of NS-7 measured by microdialysis was unexpectedly low and almost constant after intravenous injection. Subsequently, the level of NS-7 in brain was compared between sham-operated and middle cerebral artery (MCA)-occluded rats. In MCA-occluded rats, the concentrations of NS-7 in the ischemic cerebral cortex and striatum were 64-71% of those in sham-operated group at 1 h after injection, although the initial concentrations (at 2-5 min) were much lower (about 20%) in MCA-occluded rats. The t(max) was observed at 1 h after injection, which was later than that (5 min) determined in sham-operated rats. Moreover, its elimination half-life was longer in MCA-occluded rats than in sham-operated animals. From these results it is suggested that peripherally administered NS-7 readily penetrates into brain, in which it exists for the most part in parenchymal fraction. In addition, substantial amount of NS-7 may distribute to the ischemic brain regions when it was injected after MCA occlusion.

Animals↗
PubMed1997

Immunohistochemical distribution of rabbit polyclonal antiurinary protein 1 antibody in the female (Skene's gland) and male prostate: new marker for neuroendocrine cells?

Using rabbit polyclonal antiurinary protein 1 antibody to study the female prostate (Skene's gland) and the male prostate, characteristic localizations patterns appeared in single cells and groups of cells. The majority correspond to cells positive for neuroendocrine markers. In the cytoplasm, cells positive for protein 1 were most frequently found in the epithelial lining of the female urethra, in the pars prostatica of the male urethra, and in the ducts of the female and male prostate where the lining consisted of pseudostratified columnar epithelium. Their occurrence rate was far lower among secretory and basal cells of the male and female prostate glands. The cells with protein 1 corresponded to those displaying positivity for chromogranin A, silver staining by the Grimelius and less by the Sevier-Munger method, and by neuron specific enolase. Using the Masson-Hamperl argentaffin method, positive cells were only exceptionally found. The cells positive for protein 1, and particularly chromogranin A, and characterized by Grimelius positivity, contained different amounts of neuroendocrine granules and varied in size and shape. The majority of these cells had contact with the lumen of male and female prostatic ducts (open type of neuroendocrine cells). In some cases of the male and female urethra and of the great paraurethral ducts, a remarkably high number of cells containing protein 1 corresponded to cells only containing neuron-specific enolase but not chromogranin A and other neuroendocrine markers. These cells can be considered stem cells responsible for the renewal of the uroepithelium of the urethra and prostatic ducts. Protein 1 may thus be a further, though presumably not specific marker for the identification of cells of the neuroendocrine system in the prostate of the male and female. This marker could well be used to study uroepithelium maturation. The corresponding immunohistochemical distribution of human protein 1 in neuroendocrine and other cells of the male and the female prostate provides another analogous functional and morphological parameter of prostatic tissue in both sexes and further evidence supporting the non-vestigial concept of the prostate in the female.

Adolescent↗
PubMed1997

Effects of recombinant human interleukin-3 on maturation of megakaryocytic cell line, CMK.

It is well known that interleukin-3 (IL-3) stimulates the proliferation of megakaryocyte colonies. On the other hand, it remains unclear whether IL-3 also promotes the maturation of megakaryocytes. In this report, we investigated the effects of IL-3 on megakaryocyte maturation in vitro using the human megakaryocytic cell line, CMK, which excludes the influence of bone marrow accessory cells. CMK cells were incubated both with and without 2-50 U/ml of recombinant human IL-3 (rhIL-3) and then analyzed for the effects on proliferation, cell size, DNA ploidy and the expression of platelet glycoproteins. We initially confirmed that CMK cells express IL-3 receptors (IL-3R) on the surface, and rhIL-3 stimulates the proliferation of CMK cells, showing their IL-3R function normally. With addition of rhIL-3 to the CMK cell culture system, increments in cell size, a significant shift toward high ploidy classes, and an increased expression of platelet glycoproteins CD29, CD41, CD42a, CD42b and CDw49f were newly observed. These findings suggest that rhIL-3 acts directly on human megakaryocytes and has the ability to directly promote both proliferation and maturation of megakaryocytes, without the help of accessory cells. Furthermore, rhIL-3 induced/enhanced the expression of mRNA for granulocyte-macrophage colony stimulating factor (GM-CSF) and leukemia inhibitory factor (LIF) in CMK cells. Therefore, the effects of rhIL-3 on the maturation of megakaryocytic cell lines demonstrated in this study may be partly mediated by the action of cytokines such as LIF and GM-CSF, which are induced by IL-3 in the megakaryocytic cell line.

Cell Division↗
PubMed1997

The effects of prednisolone and interferons on serum macrophage colony stimulating factor concentrations in chronic hepatitis B.

BACKGROUNDS/AIMS: Serum concentrations of macrophage-colony stimulating factor (M-CSF) are increased in parallel with hepatic inflammation. The aim of this study was to assess the immunologic significance of elevated M-CSF in patients with chronic hepatitis B virus infection. METHODS: The subjects included 20 asymptomatic HBV carriers and 45 patients with chronic hepatitis B, including 8 undergoing prednisolone treatment, 10 experiencing an acute exacerbation, and 12 undergoing daily administration of interferons. RESULTS: Serum concentrations of M-CSF significantly decreased during prednisolone administration, but significantly increased following prednisolone withdrawal, similar to the increase during acute exacerbation. Changes in the lipopolysaccharide-stimulated production of interleukin-1-beta and tumor necrosis factor-alpha by peripheral whole blood, or of interferon-gamma by peripheral blood mononuclear cells showed a similar pattern. Serum concentrations of M-CSF did not correlate with the titers of HBV-DNA or HBV-DNA polymerase activity. However, serum M-CSF peaked preceding seroconversion to HBe antibody in three HBe antigen positive patients. Exogenous interferon-alpha, -beta, or -gamma induced significant elevation in serum M-CSF concentrations, irrespective of changes in the serum alanine aminotransferase levels. CONCLUSIONS: Increased serum M-CSF is closely associated with increased serum interferons and/ or proinflammatory cytokines produced by peripheral blood cells during hepatic inflammation in chronic hepatitis B. This may be a consequence of the altered cytokine cascade resulting from the host immune response against hepatitis B virus.

Adolescent↗
PubMed1997

Surgical management of eosinophilic fasciitis of the upper extremity.

Eosinophilic fasciitis is a rare inflammatory disease associated with peripheral eosinophilia, hyper-gammaglobulinaemia and contractures of any joint in the upper extremity. Although conservative treatments are generally advocated, this study reports the results of surgical intervention. Four patients aged from 20 to 48 years underwent fasciectomy followed by oral administration of prednisolone. All presented with contractures of digits, wrist, or elbow due to eosinophilic fasciitis in the upper extremities. Despite one case that required a second operation for recurrence, all patients regained the range of motion of the affected joints a few weeks after surgery. The recovery was much sooner than in previously reported cases treated conservatively, suggesting that surgical management of eosinophilic fasciitis is effective in alleviating symptoms quickly and allows patients to resume activities of daily living sooner.

Adult↗
PubMed1997

Immunohistochemical detection of human natural killer cell like immunoreactivity in human pituitary adenomas, using monoclonal antibody NK-1.

Natural killer (NK) cells are specialized lymphocytes which are characterized as non-T and non-B cells, as they lack classic T and B cell surface markers. Recently, NK like immunoreactivity has been identified in endocrine and neuronal tissues as well as in the tumors derived from the neuroectoderm and neuroendocrine system. We examined the expression of NK-1 like immunoreactivity in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth hormone (GH) producing adenomas, 14 prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) producing adenomas, 5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioning adenomas) immunohistochemically. The expression of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which have been reported to secrete cytokines as immuno-endocrine modulators, were also examined. In normal pituitary glands, NK-1 was detected in all 6 tissues in the cytoplasm of about 5-10% of the anterior pituitary cells. By serial sectioning and double immunostaining, NK-1 immunopositivity was frequently found to be localized in ACTH cells. The colocalization with other anterior pituitary hormones such as GH. PRL, the beta-subunit of luteinizing hormone (LH beta), follicle stimulating hormone (FSH beta). TSH beta and alpha-subunit of glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells, which were scattered among hormone producing cells, were closely associated with NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present in all the types of pituitary tumors, and a total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivity in the individual adenoma types was; 14 of 16 GH producing adenomas (87.5%), 7 of 14 PRL producing adenomas (50%). 3 of 4 TSH producing adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfunctioning adenomas (31.3%). By double immunostaining, NK-1 was found to be frequently colocalized with ACTH in ACTH producing adenomas, and was colocalized with PRL in PRL producing adenomas, or with GH, PRL or the alpha-subunit in GH producing adenoma cells. NK-1 immunoreactive cells were observed in close association with S-100 immunopositive FS cells in the adenomas. Our results may indicate that NK-1 positive cells may have functions as a paracrine modulators of their neighboring cells, which includes S-100 positive FS cells.

Adenoma↗
PubMed1997

Immunohistochemical localization of human protein 1 in the female prostate (Skene's gland) and the male prostate.

Mouse monoclonal anti-urine protein 1 antibody and the biotin-streptavidin-peroxidase technique were used for the immunohistochemical demonstration of human protein 1 in prostatic tissue of both sexes. In the female prostate (Skene's gland), like the male prostate, high expression of human protein 1 was observed on the luminal surface and in the apical cytoplasm of secretory cells of prostatic glands, as well as on the luminal surface of the epithelium of the large ducts of the female prostate and urethra. Expression was also found in the membranes of secretory and basal cells of the glands, in membranes of the urethral uroepithelium and of the female prostate ducts, in the content of glands and ducts, as well as in vascular endothelium and smooth muscle. Human protein 1 (urine protein 1) expression in the secretory cells of the male and female prostate and its incorporation into the surface of cells lining the lumina of the female urethroprostatic complex is indicative not only of the secretory role of protein 1 but also of its potential protective properties operative in shielding the uroepithelium from the aggressive urinary environment. All genito-urinary tissue, and especially the female prostate, were found to be a potential source of urine protein 1 (human protein 1), refuting the notion held so far that it is exclusively the genito-urinary prostatic tissue of the male that participates in its production. The corresponding immunohistochemical distribution of human protein 1 in the same structures of the male and female prostate provides yet another analogous functional-morphological parameter of prostatic tissue in both sexes and further evidence supporting the non-vestigial concept of the prostate in the female.

Adolescent↗
PubMed1997

Generation and characterization of rat monoclonal antibodies against human serum amyloid A.

Monoclonal antibodies against human serum amyloid A (SAA) were generated in rat (which seems not to have mature SAA proteins) by immunizing intact human SAA. Thirteen clones selected by initial screening were analysed based on reactivity with synthetic peptides of SAA and with carboxyl-terminal truncated recombinant SAA. Antibodies were divided into four types, i.e. those recognizing the area around residue 18, 30, 90, and 100, respectively, of SAA. The antibody to the carboxyl terminus (around residue 100) of SAA, when subjected to immunohistochemistry for amyloid deposits in specimens from patients with reactive amyloidosis, always yielded negative reactivity, supporting the general concept that the carboxyl terminus of SAA is absent from human AA deposits.

Amino Acid Sequence↗
PubMed1997

Inhibition of ischemia-induced fodrin breakdown by a novel phenylpyrimidine derivative NS-7: an implication for its neuroprotective action in rats with middle cerebral artery occlusion.

The effect of a novel neuroprotective compound, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride], on ischemia-induced fodrin breakdown was examined both in vitro and in vivo. The fodrin breakdown was measured by western blot followed by a densitometric analysis. In slices of the rat cerebral cortex, a pronounced fodrin breakdown was observed under hypoxic and hypoglycemic conditions. The enhancement of fodrin breakdown was completely blocked by omission of extracellular Ca2+ and significantly inhibited by calpain inhibitors such as E-64 and calpain inhibitor-I, thereby suggesting that the fodrin breakdown induced by hypoxia/hypoglycemia is due to the activation of Ca2+-stimulated neutral protease calpain. NS-7 (1-30 microM) produced a concentration-dependent inhibition of hypoxia/hypoglycemia-induced fodrin breakdown. In rats with unilateral middle cerebral artery occlusion (MCAO), a pronounced fodrin breakdown was observed in the cerebral cortex and striatum, although the time course for the development of the fodrin breakdown was much slower in the cerebral cortex than in the striatum. NS-7 (0.5 mg/kg i.v.), when injected immediately after MCAO, suppressed not only the fodrin breakdown but also the infarction in the cerebral cortex. From these results it is suggested that inhibition of calpain activation is implicated in the neuroprotective action of NS-7.

Animals↗
PubMed1997

Intercellular adhesion molecule-1 and CD18 are involved in neutrophil adhesion and its cytotoxicity to cultured sinusoidal endothelial cells in rats.

The expression of several adhesion molecules is increased on the hepatic sinusoidal endothelial cells (SECs) in various liver diseases. The objective of this study is to assess the roles of intercellular adhesion molecule 1 (ICAM-1) and of CD18 in the interaction between the neutrophils (polymorphonuclear leukocytes [PMNs]) and SECs and in the injury to SECs mediated by PMNs. Rat PMNs was perfused on SECs stimulated with tumor necrosis factor alpha (TNF-alpha) using an in vitro flow system. The number of adhered PMNs to SECs and that of PMNs migrated under SECs was counted and the effects of anti-ICAM-1, anti-CD18, and dexamethasone were studied. We also define the effect of these antibodies on the SEC injury mediated by PMNs stimulated with phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP). TNF-alpha significantly increased the adhesion of PMNs to SECs (322 +/- 26 cells/mm2) compared with controls (194 +/- 22 cells/mm2). Anti-ICAM-1 and anti-CD18 significantly inhibited the adhesion of PMNs (131 +/- 10 and 51 +/- 30 cells/mm2, respectively). These antibodies also decreased the migration rate of PMNs (6.0% and 7.9%, respectively) compared with controls (migration rate, 21.2%). The SEC injury induced by PMA- and fMLP-activated PMNs was prevented by anti-ICAM-1 and anti-CD18. The adhesion of PMNs induced by TNF-alpha was inhibited by the treatment with dexamethasone (160 +/- 20 cells/mm2) via a down-regulation of ICAM-1 expression on SECs. The interactions between ICAM-1 and CD18 appeared to be important in the adhesion and the migration of PMNs to SECs. The injury to SECs was induced by the close interaction between the activated PMNs and SECs mediated via ICAM-1 and CD18.

Animals↗
PubMed1997

Detachment activity but not cytotoxicity induced in a T-cell clone following antigen presentation in the presence of thymic epithelial cells.

The selective induction of effector functions of a T-cell clone (DB14), specific to pigeon cytochrome c 43-58 (p 43-58) and restricted to I-Ab, was analyzed using a professional antigen-presenting cell, B hybridoma (Th 2.58), and various non-professional antigen-presenting cells (APC), L cells transfected with I-Ab (I-Ab L cells), a medullary thymic epithelial cell line (m-TEC) and a cortical thymic epithelial cell line (c-TEC). The m-TEC, and c-TEC expressed I-Ab upon induction with interferon gamma (IFN-gamma). When stimulated with p 43-58 in the presence of I-Ab L cells as well as Th 2.58 cells, the DB14 cells showed marked proliferation and, after 18 hr of culturing, exhibited significant cytotoxicity against the APC. By contrast, in the presence of m, c-TEC, the DB14 cells showed neither proliferation nor cytotoxicity against these TEC but exhibited considerable detachment activity towards them. Furthermore, DB14 cells became expressed activation markers CD69 or CD44) following stimulation with p 43-58 plus m-TEC or c-TEC. The addition of rIL-2 to the culture of DC14 cells, p 43-58 and m-TEC or c-TEC, restored the proliferative responses. However, it was shown that anergy was not involved in the negligible proliferative responses of DB14 cells after stimulation with p 43-58 plus m, c-TEC. The present findings indicate that differences in APC functions are present among the non-professional APC and suggest that the selective induction of T-cell functions can be achieved using the appropriate non-professional APC. The characteristic activation of T cells by TEC may be related to their functional roles in situ.

Animals↗
PubMed1997

Amplification of rfbE and fliC genes by polymerase chain reaction for identification and detection of Salmonella serovar Enteritidis, Dublin and Gallinarum-Pullorum.

Polymerase chain reaction (PCR) primers for O9 antigen (rfbE) and phase 1 flagellin antigen (fliC) were designed for the rapid identification and detection of Salmonella serovar Enteritidis and Dublin. The rfbE primer pairs selectively amplified the rfbE region of group O9 Salmonella serovars. The fliC primer pairs amplified the DNAs of g,m and g,p-type flagellar antigen; Salmonella serovar Enteritidis, Dublin, and Essen. However, DNA from flagellar-negative Salmonella serovar Gallinarum-Pullorum was also amplified. The sensitivity of PCR primer pairs was 10(4) CFU/assay by boiled DNA preparation and 10(2) CFU/assay by proteinase K-treated DNA preparation.

Carbohydrate Epimerases↗
PubMed1997

Characterization of a Generalized Transducing Phage of Poly-(gamma)-Glutamic Acid-Producing Bacillus subtilis and Its Application for Analysis of Tn917-LTV1 Insertional Mutants Defective in Poly-(gamma)-Glutamic Acid Production.

A generalized transducing phage, (phi)BN100, was isolated from a Bacillus subtilis (natto) strain producing poly-(gamma)-glutamic acid ((gamma)PGA). Transduction frequencies for a given marker ranged from 3.8 x 10(sup-8) to 1.6 x 10(sup-6) per phage particle. The genome size of the phage was approximately 42 kb. (phi)BN100 was used successfully to identify bona fide Tn917-LTV1 transpositional mutants defective in (gamma)PGA production.

Journal Article↗
PubMed1997

Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa.

The arginine succinyltransferase (AST) pathway is the major arginine and ornithine utilization (aru) pathway under aerobic conditions in Pseudomonas aeruginosa. A 26-kb DNA fragment of the P. aeruginosa PAO1 chromosome carrying the regulatory argR gene and the aru structural gene cluster was cloned. Complementation tests and nucleotide sequence data established the locations of the argR, aruC, aruF, aruG, aruD, aruB, and aruE genes, in that order. The aruR, aruC, aruD, aruB, and aruE genes specify the ArgR regulatory protein, N2-succinylornithine 5-aminotransferase, N-succinylglutamate 5-semialdehyde dehydrogenase, N2-succinylarginine dihydrolase, and N-succinylglutamate desuccinylase, respectively, and the aruF and aruG genes encode the subunits (AruAI and AruAII) of arginine and ornithine N2-succinyltransferases. Furthermore, in vivo analysis of transcriptional aru fusions and of polar insertion mutations located at different sites in the aru cluster indicated the presence of three transcriptional units which are controlled by ArgR. The aruCFGDB genes appear to form an operon transcribed from a promoter upstream of aruC, whereas aruE has its own promoter. The argR gene, which is located upstream of the aruCFGDB operon, is a member of another (aot) operon coding for arginine transport genes. The deduced amino acid sequences of the AST enzymes were compared to those of homologous proteins of Escherichia coli specified by the ast genes lying in the chromosome region from 39.2 to 39.5 min (Kohara clone 327; GenBank/EMBL/DDJB accession no. D90818). The overall organization of the aru and ast genes in both organisms is similar, with the exception that E. coli appears to have a single AST gene.

Acyltransferases↗
PubMed1997

Laboratory investigation of enteroaggregative Escherichia coli O untypeable:H10 associated with a massive outbreak of gastrointestinal illness.

A massive outbreak of gastrointestinal illness occurred in Tajimi city, Gifu prefecture, in June of 1993 in which 2,697 children in elementary and junior high schools developed severe diarrhea. Stool specimens from 30 children with severe protracted diarrhea were studied. Twenty-seven strains of enteroaggregative Escherichia coli (EAggEC) isolated from 12 of 30 patients all belonged to the same serotype, O untypeable (OUT):H10, and showed the same biochemical characteristics and antibiotic susceptibility pattern. These strains were negative for the virulence factors of the four standard categories of diarrheagenic E. coli (enterotoxigenic, enteropathogenic, enteroinvasive, and enterohemorrhagic). However, the isolates showed an aggregative pattern of adherence to HEp-2 cells and had a 60-MDa plasmid and an astA gene, which encodes heat-stable enterotoxin-1 production. These data suggested that the EAggEC serotype OUT:H10 was associated with this massive outbreak of gastrointestinal illness.

Adolescent↗
PubMed1997

Panencephalopathic type of Creutzfeldt-Jakob disease associated with cadaveric dura mater graft.

A 52 year old man with Creutzfeldt-Jakob disease who received a cadaveric dura mater graft 99 months before the onset is reported. The prion protein gene was homozygous for methionine at the polymorphic codon 129. Neuropathological examination disclosed a panencephalopathic type of Creutzfeldt-Jakob disease which was characterised by severe involvement of the cerebral white matter and cerebellum, as well as of the cerebral cortical and deep grey matter. Thus the panencephalopathic type of Creutzfeldt-Jakob disease may occur in association with cadaveric dura mater grafts.

Cadaver↗
PubMed1997

Association of presenilin-1 polymorphism with cerebral amyloid angiopathy in the elderly.

BACKGROUND AND PURPOSE: An intronic polymorphism of presenilin-1 (PS-1), a gene responsible for early-onset familial Alzheimer's disease, has been reported to be associated with late-onset sporadic Alzheimer's disease. In a search for a genetic risk factor of sporadic cerebral amyloid angiopathy (CAA), we investigated the association of the polymorphism of PS-1 with CAA. METHODS: The association between the severity of CAA and genotypes of a polymorphism in intron 8 of PS-1 was investigated in 137 autopsy cases of the elderly. RESULTS: A significant decrease of PS-1 2/2 genotype frequency was associated with severe or moderate CAA. CONCLUSIONS: Our results suggest that PS-1 intronic polymorphism may be associated with the severity of CAA in the elderly.

Aged↗