Biomedical subjects

N Itoh

Publications and source records attributed to N Itoh.

At least 217 records · Page 12Linked to original sources

PubMed1997

Colchicine-induced elevation of tissue metallothionein contents is mediated by inflammation-independent serum factor.

Subcutaneous injection of colchicine caused dose-dependent and time-dependent induction of hepatic MT in mice. Other than colchicine, similar MT induction was observed in vincristine- or vinblastine-injected mice, but not in beta-lumicolchicine-injected mice. MT contents were also elevated in the kidney, spleen, lung and heart by colchicine injection. Isoforms of colchicine-induced MT in the liver were identified to be MT-I and II by immunoblot analysis. Unlike turpentine-induced MT synthesis, dexamethasone, an anti-inflammatory agent, could not block the MT-inducing activity of colchicine. Therefore, the MT-inducing activity of colchicine does not appear to be due to inflammation. Mouse serum, obtained at 4-24 h after colchicine treatment, stimulated MT induction in rat hepatoma H4IIEC3 cells. The MT-inducing activity in the serum from colchicine-treated mice was determined to be highest at 12 h after colchicine injection. The MT-inducing activity from sera of colchicine-treated mice was completely blocked by glucocorticoid antagonist, RU38486, similar to such activity in the serum from lipopolysaccharide-treated mice. The ability of sera to induce MT was abolished by heat treatment (56 degrees C, 30 min). The molecular weight of the MT-inducing factor estimated by gel filtration was approximately 20 000 Da. Thus, colchicine-induced stimulation of MT production is mediated by some humoral factor. The production of the MT-inducing factor was not blocked by dexamethasone. We conclude that the mediator is not an inflammatory cytokine or a glucocorticoid and suspect that the disruption of microtubule triggers production or release of such humoral mediator which stimulates MT induction.

Animals↗

PubMed1997

Squamous cell carcinoma arising from thyroglossal duct remnants: report of a case and results of immunohistochemical studies.

We report on the case of a 57-year-old male found to have squamous cell carcinoma (SCC) arising from thyroglossal duct remnants. The patient presented with an asymptomatic tumor in his anterior neck which was immovable on palpation. Aspiration biopsy cytology revealed class V malignancy with many atypical clusters and marked keratinization. After preoperative radiation, a radical operation employing Sistrunk's procedure with bilateral neck dissection was performed. Histopathological examination confirmed a diagnosis of moderately differentiated SCC, but revealed ciliated columnar epithelium in the walls of the cyst without a normal layer of squamous cells. Furthermore, immunohistochemical studies demonstrated the tumor to be negative for thyroglobulin staining, but positive for cytokeratin and carcinoembryonic antigen. These histopathological findings proved attributable to squamous metaplasia occurring in the ciliated columnar epithelium of the thyroglossal duct. Thus, SCC might originate in the metaplastic portion of the thyroglossal duct remnants. Although the prognosis associated with SCC in the thyroglossal duct is not as optimistic as that associated with papillary carcinoma, no evidence of recurrence has been observed in this patient in the 7 years since his operation. This suggests the effectiveness of our therapeutic approach for this unusual disease.

Carcinoma, Squamous Cell↗

PubMed1997

Postoperative outcome of insufficient surgery for small differentiated thyroid carcinoma.

We performed conservative surgery for small differentiated thyroid carcinoma, but also inadvertently carried out minimal insufficient surgery, such as enucleation (Ex) or partial lobectomy (pLx) without regional node dissection for malignant thyroid nodules. In this study, the long-term postoperative outcome after such insufficient surgical treatment was evaluated. Of 348 patients with differentiated thyroid carcinoma who underwent initial surgery between 1953 and 1976, 84 underwent either Ex or pLx and their records are herein reviewed. The frequency of recurrence from the remnant gland or regional lymph nodes was examined in relation to the tumor diameter (< or = 1.0 cm, tis; 1.0 cm-2.0 cm, t1; > 2.0 cm, t2). After Ex/pLx, the recurrence rate in the tis group was 13.3% and not significantly different from that (13.6%) in the t1 group. The recurrence rate was notably increased in the t2 group. Moreover, there was no significant difference between the recurrence rate in the tis and t1 groups after Ex/pLx and that after lobectomy with nodal dissection. These results suggest that a reoperative procedure with a more extensive thyroidectomy and neck dissection might not necessarily be required immediately after minimal insufficient surgery is inadvertently carried out in patients with small differentiated thyroid carcinoma measuring 2.0 cm in diameter or less.

Adolescent↗

PubMed1997

Rapid diagnosis of adenoviral conjunctivitis on conjunctival swabs by 10-minute immunochromatography.

PURPOSE: Several methods are available for the diagnosis of acute conjunctivitis, all of which are time-consuming or require the use of a well-equipped laboratory. A new method, immunochromatography (IC), for detecting the presence of adenovirus (Ad) has been developed. Two direct rapid tests to detect Ad antigen, IC and enzyme immunoassay (EIA), were compared with regard to sensitivity, specificity, and technical complexity. METHODS: The study materials consisted of 130 swabs from patients with conjunctivitis (95 samples of adenoviral conjunctivitis proven by positive virus DNA on polymerase chain reaction [PCR], 35 samples of nonadenoviral conjunctivitis proven by PCR). IC is a one-step procedure that detects the presence of adenoviral antigen by sandwich EIA on a paper disc. RESULTS: In 95 adenoviral DNA-positive samples by PCR, the sensitivity and specificity of IC were 54.7% and 97.1%, respectively, whereas those of EIA were 50.5% and 100%, respectively. By IC, PCR-positive Ad type 3 was recognized in 31%; Ad4 in 100%; Ad7 in 60%; Ad8 in 67%; and Ad37 in 59%, showing similar positivity rates for different serotypes (except Ad7) to those using EIA. Visual determination of the presence of Ad took an average of 10 minutes by IC compared with 70 minutes by EIA. CONCLUSIONS: These results indicate that IC is a more rapid and easier test compared with EIA, and it has high specificity. Detection of Ad antigen by this simple and rapid method will serve physicians as a useful tool for early diagnosis and prevention of adenoviral conjunctivitis.

Adenoviridae↗

PubMed1997

Spatially restricted expression of fibroblast growth factor-10 mRNA in the rat brain.

Fibroblast growth factor (FGF)-10 is a novel member of the FGF family. Although FGF-10 mRNA was preferentially expressed in the lung, the mRNA was also expressed, although at low levels, in the brain. We examined the localization of FGF-10 mRNA along with FGF-7 mRNA in the rat brain by in situ hybridization. FGF-10 mRNA showed spatially restricted expression in some regions of the brain, including the hippocampus, thalamus, midbrain and brainstem, although FGF-7 mRNA was not expressed in any of the brain regions examined. FGF-10 mRNA was strongly expressed in several restricted nuclei, especially in motor nuclei, including the oculomotor nucleus, dorsal motor nucleus of vagus, motor trigeminal nucleus, facial nucleus and hypoglossal nucleus. This localization pattern was distinct from those of aFGF, bFGF FGF-5 and FGF-9 mRNAs reported previously. The cellular localization of FGF-10 mRNA showed that the mRNA in the brain was preferentially expressed in neurons but not in glial cells. The present findings indicate that FGF-10, an additional member of the FGF family expressed in the brain, has a distinct role in the brain.

Animals↗

PubMed1997

Transient expression of FGF-5 mRNA in the rat cerebellar cortex during post-natal development.

Previously, we showed that fibroblast growth factor (FGF) receptor-4 mRNA was transiently expressed in proliferative granule cells of the external granule layer of the rat cerebellar cortex during early post-natal development (A. Miyake et al., Mol. Brain Res., 31 (1995) 95-100). In this study, we examined the expression of FGF-5 mRNA in the rat brain during post-natal development by in situ hybridization. FGF-5 mRNA was transiently expressed in granule cells of the internal granule layer of the cerebellar cortex during early post-natal development. The temporal sequence of FGF-5 mRNA expression was similar to that of FGFR-4 mRNA expression. As the proliferation of granule cells in the external granule layer and their migration through the molecular layer into the internal granule layer actively occur during these periods, the present findings suggest that FGF-5 as well as FGFR-4 might play important roles in the proliferation and/or migration of granule cells during the post-natal development of the cerebellar cortex.

Animals↗

PubMed1997

Metallothionein-independent hepatoprotection by zinc and sakuraso-saponin.

Hepatoprotective activities of zinc and sakuraso-saponin against toxicity of carbon tetrachloride were investigated in metallothionein (MT)-deficient mice. Pretreatment of control 129/Sv mice with zinc or sakuraso-saponin blocked carbon tetrachloride-induced elevation of plasma transaminase activities. Quantitatively equivalent protection against carbon tetrachloride-induced hepatic damage was also observed in MT-deficient mice. Zinc and sakuraso-saponin caused elevation of hepatic MT levels in control 129/Sv mice, whereas hepatic MT was undetectable in MT-deficient mice. To examine the possibility that sakuraso-saponin-induced hepatoprotection is mediated by endogenous zinc, the hepatic concentration of zinc was analyzed. Hepatic zinc concentration in MT-deficient mice was not changed by the treatment of sakuraso-saponin. Injection of sakuraso-saponin caused a decrease of activity of aniline hydroxylation. The suppression of cytochrome P450 appears to be a mechanism by which sakuraso-saponin protects mice from the hepatotoxic effects of carbon tetrachloride. These findings indicate that the hepatoprotective activity of zinc or sakuraso-saponin is not dependent on their MT-inducing activity.

Animals↗

PubMed1997

Localization of insulin receptor-related receptor in the rat kidney.

Insulin receptor-related receptor (IRR), a member of the insulin receptor family, is most abundantly expressed in the kidney. However, its endogenous ligand and physiological roles are still unknown. To elucidate the physiological role of IRR, an orphan receptor, in the kidney, we examined the localization of IRR mRNA and its immunoreactivity in the rat kidney by in situ hybridization and immunohistochemistry, respectively. IRR mRNA was found to be exclusively localized in the cortical collecting duct. The localization of IRR immunoreactivity was consistent with that of IRR mRNA. Furthermore, IRR immunoreactivity was found to be localized on the basolateral plasma membrane of the epithelial cells that were a minor cell subpopulation (20 to 30%) of the duct. The present findings indicated that IRR in the kidney was exclusively localized on the basolateral plasma membrane of type B intercalated cells of the cortical collecting duct.

Animals↗

PubMed1997

Effects of sigma ligands on the nociceptin/orphanin FQ receptor co-expressed with the G-protein-activated K+ channel in Xenopus oocytes.

Taking advantage of the functional coupling of the nociceptin/orphanin FQ receptor with the G-protein-activated inwardly rectifying K+ (GIRK) channel, we investigated the effects of various sigma ligands on the nociceptin/orphanin FQ receptor in Xenopus oocytes co-injected with the cloned nociceptin/orphanin FQ receptor and GIRK1 mRNAs. Carbetapentane and rimcazole, which induced no current response at 100 microM, reversibly suppressed the inward K+ current responses induced by nociceptin in a concentration-dependent manner, and the IC50 values (microM) for these compounds were 9.0 and 12.6, respectively. (+/-)-N-allylnormetazocine. (+)-cyclazocine, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine and 1,3-di-(2-tolyl)guanidine, at 100 microM, had no effect on the receptor. These results suggest that carbetapentane and rimcazole act as antagonists at the nociceptin/orphanin FQ receptor and may be involved in pain regulation.

Animals↗

PubMed1997

Induction and inhibition of cytochrome P450 isoforms by imazalil, a food contaminant, in mouse small intestine and liver.

1. The effects of imazalil, a food contaminant used as a fungicide, were investigated on the expression and activity of cytochrome P450 in the small intestinal mucosa and liver of mice. Imazalil was orally administered to mice daily at 1 or 10 mg/kg for 3 days. 2. Imazalil enhanced cytochrome P450-catalysed ethoxyresorufin O-deethylase and pentoxyresorufin O-depentylase (PROD) activities in both tissue microsomes at the 10 mg/kg/day dose level, indicating the induction of cytochrome P450 subfamilies CYP1A and CYP2B. In addition, immunochemical analyses also demonstrated an enhanced expression of CYP2B, CYP2C and CYP3A subfamilies in both tissues. 3. Imazalil was a potent inhibitor of cytochrome P450-dependent monooxygenase activities (PROD, aminopyrine N-demethylase and erythromycin demethylase) in in vitro assays using both small intestinal and liver microsomes. 4. From these findings, imazalil has been demonstrated to have not only a potent inhibitory activity but also a significant inducing ability of P450 isoforms in the small intestine. Prolonged ingestion of such a food contaminant may modulate the xenobiotic-metabolizing enzyme system at the site of a primary portal of xenobiotic entry to the systemic circulation.

Animals↗

PubMed1997

A high prevalence of functional inactivation by methylation modification of p16INK4A/CDKN2/MTS1 gene in primary urothelial cancers.

We analyzed the genetic and epigenetic alterations of p16INK4A/CDKN2/MTS1 gene (MTS1 gene) in 38 primary urothelial cancers. Genetic alterations of the MTS1 gene consisted of one base substitution mutation in exon 2 (2.6%) and 6 homozygous deletions (16.2%). Hypermethylation of the 5' CpG island in exon 1 of the MTS1 gene was observed in 12 tumors (37.5%). Consequently, 19 of 38 tumors (50%) showed genetic alterations or epigenetic hypermethylation of the MTS1 gene. Retention of hypermethylated MTS1 gene(s) in 36% of the tumors showing loss of heterozygosity at the critical region indicates that the methylation modification could be an initial event followed by genomic rearrangements associated with total loss of MTS1 gene function. Immunohistochemical analysis of MTS1 expression revealed that all the tumors with genetic alterations of the MTS1 gene and 9 of 12 highly methylated tumors displayed an absence of MTS1 nuclear antigen. Genetic and epigenetic changes of the MTS1 gene were not correlated with the grade and stage of tumors, indicating that these alterations are early events in urothelial carcinogenesis, in which functional inactivation by hypermethylation is a predominant mechanism.

Cyclin-Dependent Kinase Inhibitor p16↗

PubMed1997

Concomitant presence of p16/cyclin-dependent kinase 4 and cyclin D/cyclin-dependent kinase 4 complexes in LNCaP prostatic cancer cell line.

The cyclin D/cyclin-dependent kinase (CDK)/CDK-inhibitory proteins/retinoblastoma protein (pRb) pathway is hypothesized to control the G1-S check point. The role of this pathway is reported to be different depending on the status of pRb. In the present study, we examined nine human urological tumor cell lines. Cells lacking functional pRb expressed p16, instead of forming cyclin D/ CDK4 complex. In the LNCaP prostatic cancer cell line, however, both p16/CDK4 and cyclin D/ CDK4 complexes were present independently, probably because of partial loss of pRb. In view of the concomitant presence of the incompatible complexes, LNCaP should provide us with a valuable model for the study of this pathway in cancer cells.

Carcinoma, Renal Cell↗

PubMed1997

Purification and characterization of phenylacetaldehyde reductase from a styrene-assimilating Corynebacterium strain, ST-10.

A novel phenylacetaldehyde reductase was purified about 50-fold to homogeneity from Corynebacterium sp. strain ST-10, which can assimilate gaseous styrene as the sole carbon and energy source. The enzyme was inductively synthesized when grown on gaseous styrene and had an important role in styrene metabolism in vivo. The enzyme had a molecular weight of 155,000 and was composed of four identical subunits (molecular weight, 42,000). The enzyme catalyzed the reduction of not only phenylacetaldehyde but also various aldehydes and ketones; however, it did not catalyze the reverse reaction, the dehydrogenation of 2-phenylethanol. The enzyme required NADH as a cofactor and showed no activity with NADPH; therefore, it was defined as an NADH-dependent phenylacetaldehyde reductase. The enzyme stereospecifically produced (S)-(-)-1-phenylethanol from acetophenone; therefore, it would be useful as a biocatalyst.

Acetaldehyde↗

PubMed1997

An early insulin intervention accelerates pancreatic beta-cell dysfunction in young Goto-Kakizaki rats, a model of naturally occurring noninsulin-dependent diabetes.

This study was designed to delineate the nature of beta-cell dysfunction in a model of genetically determined nonobese diabetes, the Goto-Kakizaki (GK) rat. Pancreatic beta-cell function was analyzed immediately after weaning and 5 weeks thereafter, comparing animals with or without insulin treatment during the interval. In 3.5-week-old GK rats, fasting plasma glucose was mildly elevated with normoinsulinemia, and the islet insulin content was reduced by 33%. When incubated with 3-30 mM glucose in vitro, the GK rat islets showed reduced glucose sensitivity, i.e. the EC50 values were 19.5 and 15.9 mM, and the Hill constants for the positive cooperativity 2.1 and 4.2 in the islets of GK and the control rats, respectively. On the other hand, the maximum response to glucose was not attenuated when reduced islet insulin content was considered. In 8.5-week-old GK rats hyperglycemia worsened and glucose-stimulated insulin release by the islets more severely impaired. A daily insulin injection from the 3.5-8.5 weeks of age significantly lowered plasma glucose in the GK rat, accompanied by a marked suppression of both basal (with 3 mM glucose) and glucose (6-30 mM)-stimulated insulin release by the islets. In the GK rat, beta-cell dysfunction develops by the age of 3.5 weeks, and insulin treatment during the subsequent 5 weeks accelerates its progression.

Animals↗

PubMed1997

The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor.

Vertebrate limb formation has been known to be initiated by a factor(s) secreted from the lateral plate mesoderm. In this report, we provide evidence that a member of the fibroblast growth factor (FGF) family, FGF10, emanates from the prospective limb mesoderm to serve as an endogenous initiator for limb bud formation. Fgf10 expression in the prospective limb mesenchyme precedes Fgf8 expression in the nascent apical ectoderm. Ectopic application of FGF10 to the chick embryonic flank can induce Fgf8 expression in the adjacent ectoderm, resulting in the formation of an additional complete limb. Expression of Fgf10 persists in the mesenchyme of the established limb bud and appears to interact with Fgf8 in the apical ectoderm and Sonic hedgehog in the zone of polarizing activity. These results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs.

Amino Acid Sequence↗

PubMed1997

Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung.

During mouse lung morphogenesis, the distal mesenchyme regulates the growth and branching of adjacent endoderm. We report here that fibroblast growth factor 10 (Fgf10) is expressed dynamically in the mesenchyme adjacent to the distal buds from the earliest stages of lung development. The temporal and spatial pattern of gene expression suggests that Fgf10 plays a role in directional outgrowth and possibly induction of epithelial buds, and that positive and negative regulators of Fgf10 are produced by the endoderm. In transgenic lungs overexpressing Shh in the endoderm, Fgf10 transcription is reduced, suggesting that high levels of SHH downregulate Fgf10. Addition of FGF10 to embryonic day 11.5 lung tissue (endoderm plus mesenchyme) in Matrigel or collagen gel culture elicits a cyst-like expansion of the endoderm after 24 hours. In Matrigel, but not collagen, this is followed by extensive budding after 48-60 hours. This response involves an increase in the rate of endodermal cell proliferation. The activity of FGF1, FGF7 and FGF10 was also tested directly on isolated endoderm in Matrigel culture. Under these conditions, FGF1 elicits immediate endodermal budding, while FGF7 and FGF10 initially induce expansion of the endoderm. However, within 24 hours, samples treated with FGF10 give rise to multiple buds, while FGF7-treated endoderm never progresses to bud formation, at all concentrations of factor tested. Although exogenous FGF1, FGF7 and FGF10 have overlapping activities in vitro, their in vivo expression patterns are quite distinct in relation to early branching events. We conclude that, during early lung development, localized sources of FGF10 in the mesoderm regulate endoderm proliferation and bud outgrowth.

Animals↗

PubMed1997

Correlation between heart muscle damage and high-nutrient feed in broiler chickens.

One-day-old broiler chickens were given commercial chicken starters during first 4 weeks of growth. The chickens were then divided into two groups: one group was fed commercial intensive growers (control feed), and the other group was fed commercial broiler finishers (high-nutrient feed). Body weights were calculated weekly. At eight weeks old, blood samples were collected and heart tissues were examined histopathologically. Significant increases in body weight as well as pathological findings in the heart muscle and an elevation of serum creation kinase (CK) were observed in chickens fed with broiler finisher. Histopathological changes in heart fiber resembled that of sudden death syndrome, and this heart damage was thought to be related to the increase of CK levels.

Animal Feed↗

PubMed1997

Histopathologic study of the pancreas shows a characteristic lymphocytic infiltration in Japanese patients with IDDM.

We examined at autopsy 47 cases (22 males and 25 females) of insulin-dependent diabetes mellitus (IDDM) from 21 hospitals in Japan to clarify the pathological changes that occur in the pancreas vs. those in control patients. The mean age was 39.7 +/- 13.9 (mean +/- SD) years, and the duration of IDDM from clinical onset was 13.1 +/- 6.5 years. Causes of death included renal complications, infections, acute diabetic complications such as ketoacidosis or hyper- or hypoglycemic coma, and atherosclerotic disease. This study revealed noticeable decreases in the islet area and beta cell area, and a slight decreases in the alpha cell area and preservation of the number of islets. Insulitis was found in only 1 case, representing 25% of the cases with a duration of IDDM of one year or less. Lymphocytic infiltration of the exocrine gland was seen in 22 cases (46.8%). Predominant phenotypes of the lymphocytes were T lymphocytes and macrophages. Fibrosis, fatty change and atrophy were also found. Although this is not a strictly age- and sex-matched study, the high incidence of lymphocytic infiltration of the exocrine pancreas indicates that the exocrine tissue as well as beta cells is the target of immune reactions in Japanese patients with IDDM.

Adolescent↗