Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 307 records · Page 17Linked to original sources

PubMed1999

Role of complement regulatory membrane proteins in ischaemia-reperfusion injury of rat gastric mucosa.

BACKGROUND: The role of complement in ischaemia-reperfusion injury has not been well investigated. 5I2 is a monoclonal antibody (mAb) directed against a rat membrane inhibitor of the C3 convertase step, which is the rat counterpart of mouse Crry/p65. 6D1 is a mAb against rat CD59 which inhibits the formation of membrane attack complexes. METHODS: We visualized the tissue distribution of these membrane inhibitors in rat gastrointestinal tract by immunohistochemical staining with the appropriate mAb. Then, we tested the hypothesis that complement regulatory proteins protect rat gastric mucosa against ischaemia-reperfusion stress by using these mAbs. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51Cr]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. RESULTS: Rat 6D1 and 5I2 antigens were both widely distributed and predominantly expressed on smooth muscle and endothelial cells in gastrointestinal tracts. Blockade of complement regulatory proteins with 5I2 and 6D1 mAbs resulted in a significant increase in [51Cr]-EDTA clearance after reperfusion. CONCLUSIONS: These findings support the hypothesis that endogenous complement regulatory proteins may act as important protective factors against ischaemia-reperfusion stress in rat gastric mucosa.

Animals↗

PubMed1999

The early induction of cyclooxygenase 2 associated with neurofibrillary degeneration in brains of patients with Fukuyama-type congenital muscular dystrophy.

Brains of thirteen patients with Fukuyama-type congenital muscular dystrophy (FCMD) were evaluated regarding the expression of cyclooxygenase 2 (COX2), an enzyme involved in the synthetic pathway of prostaglandins and thromboxanes, as well as neurofibrillary tangles (NFT). The neuronal induction of COX2 was demonstrated with immunohistochemistry and Western blotting confirmed the up-regulation. Preceded by COX2 immunoreactivity, NFT-containing neurons appeared in the majority of FCMD patients without beta-amyloid deposition or senile plaques. The hippocampus did not demonstrate neurodegeneration, while, in other areas, neurons with NFT spread in a similar manner to Alzheimer's disease. NFT-bearing neurons were concomitantly shown to be immunoreactive to COX2. The precedent induction of COX2, therefore, may be related to the formation of NFT in this genetic disorder.

Adolescent↗

PubMed1999

Increased urinary phosphate excretion in pseudohypoparathyroidism type II with long-term treatment with phosphodiesterase inhibitor.

A 58-year-old woman was diagnosed to have pseudohypoparathyroidism (PHP) type II because of the absence of an increase of urinary phosphate secretion, despite a marked increase in urinary cAMP excretion on the Ellsworth-Howard test. We treated the patient with a cyclic-nucleotide phosphodiesterase inhibitor, theophylline, resulting in increased urinary phosphate and cAMP excretions. Dibutyl cAMP administration induced the increase in the urinary phosphate excretion. In this case, the unresponsiveness of the urinary phosphate secretion to cAMP was recovered by a high dose of cAMP or long-term administration of a phosphodiesterase inhibitor. These data imply that cAMP responsiveness to renal tubular phosphate reabsorption should be more strictly elucidated in the patient with PHP type II.

Bucladesine↗

PubMed1999

S values are not a signature for a significant contribution of neutrons to the radiation dose received by atomic-bomb survivors.

PURPOSE: It has been proposed previously that the ratio of complete to incomplete translocations as seen by fluorescence in situ hybridization (FISH), the S value, can be a cytogenetic fingerprint of exposure to radiation of different qualities. Results from a previous study suggested that the S value is approximately 10 for sparsely ionizing radiations such as X- and gamma-rays, and 2 for densely ionizing radiations. Based on FISH data of atomic-bomb (A-bomb) survivors, which showed an S value of 3.25, a significant neutron component to A-bomb radiation was suggested. To examine the possibility, the present in vitro study was conducted using X-rays. MATERIALS AND METHODS: Human blood lymphocytes were exposed to X-rays and first metaphases were examined with FISH using DNA probes for chromosomes 1, 2 and 4. RESULTS: The S value was 3.16 for X-rays, which differs from approximately 10 as reported previously, and not larger than the 3.25 obtained from the blood lymphocytes of A-bomb survivors. CONCLUSIONS: S values seem to vary among laboratories even after exposure of cells to sparsely ionizing radiations. Data from this study show that S values are not a signature for a significant contribution of neutrons to the radiation dose received by A-bomb survivors in Hiroshima.

Chromosome Breakage↗

PubMed1999

Internal absorbed dose estimation by a TLD method for 18F-FDG and comparison with the dose estimates from whole body PET.

The thermoluminescent dosimeter (TLD) method has been proposed as a useful tool for estimating internal radiation absorbed dose in nuclear medicine. An efficient approach to verify the accuracy of the TLD method has been performed in this study. Under the standard protocol for 2-[F-18]fluoro-2-deoxy-D-glucose (18F-FDG), whole body PET experiments and simultaneous body surface dose measurements by TLDs were performed on six normal volunteers. By using the body surface dose measured with TLDs, the cumulated activities of nine source organs were estimated with a mathematical unfolding technique for three different initial guesses. The accuracy of the results obtained by the TLD method was investigated by comparison with the actual cumulated activity of the same source organs measured by whole body PET. The cumulated activities of the source organs obtained by the TLD method and whole body PET show a significant correlation (correlation coefficient, r > 0.98, level of confidence, p < 0.001) with each other. The mean effective doses in this study are 3.2 x 10(-2) mSv MBq(-1) obtained from the TLD method and 2.9 x 10(-2) mSv MBq(-1) obtained from the whole body PET. Good agreement between the results of the TLD method and whole body PET was observed.

Adult↗

PubMed1999

Prevention of the death of the rat axotomized hypoglossal nerve and promotion of its regeneration by bovine brain gangliosides.

We have examined the time course of the neuronal death and regeneration of rat axotomized hypoglossal nerve with various conditions of the nerve resection, and established a useful system to measure neurotrophic activities of bioactive substances. In this system, neuronal death can be evaluated by counting surviving neurons in the nucleus of hypoglossal neuron at the brain stem, and the degree of the regeneration can be measured by counting horseradish peroxidase-positive cells at the same region after injection of horseradish peroxidase into tongue. Using this system, the effects of brain gangliosides on rat hypoglossal nerve regeneration following 5 mm transection were examined. The addition of a ganglioside mixture from bovine brain as well as the autograft strongly prevented the death of neurons and promoted the regeneration of the lesioned nerve at 10 weeks after the operation. Further analyses on the dose effects and injection sites of gangliosides were performed. Although the mechanisms of the neurotrophic effects of the gangliosides are unknown, the therapeutic application of gangliosides for neuronal degeneration is a promising approach.

Animals↗

PubMed1999

Sclerosing mediastinitis: findings on fluorine-18 fluorodeoxyglucose positron emission tomography.

Whole-body serial positron emission tomography scanning was done using fluorine-18 fluorodeoxyglucose (F-18 FDG) in a patient with a mediastinal mass. Uptake correlated well with the clinical symptoms and aggressiveness of the disease. Based on the F-18 FDG findings, a biopsy specimen was taken from the active region of the mass, which confirmed the diagnosis of sclerosing mediastinitis.

Biopsy↗

PubMed1999

Decreased pancreatic exocrine function in the mutant Eisai hyperbilirubinemic rat (EHBR).

The Eisai hyperbilirubinemic rat (EHBR) is a Sprague-Dawley rat (SDR) mutant with conjugated hyperbilirubinemia as an autosomal recessive trait. EHBRs manifest jaundice from birth, which is permanent except for a transient decrease at 6-8 weeks of age. To investigate whether the hyperbilirubinemia affects pancreatic exocrine function and acinar cell growth, EHBRs at 6 (without jaundice) and 12 weeks (with jaundice) of age were compared, along with SDRs as controls. Pancreatic wet weights did not significantly differ, but amylase content of acini was lower in EHBRs than SDRs. No correlation was found between pancreatic wet weight and serum bilirubin levels in EHBRs. In vitro amylase release in response to 1-100 pM cholecystokinin octapeptide (CCK-8), 1 microM 12-O-tetradecanoylphorbol 13-acetate, and 2.5 microM calcium ionophore A23187, and in vivo pancreatic secretion stimulated by CCK-8 (0.08 microg/kg body weight/h) were significantly lower in the EHBR cases than in the SDRs. At the electron microscopic level, many acinar cell nuclei were pyknotic, most elements of their Golgi complexes were atrophied, some mitochondria demonstrated fusion, and the rough-surfaced endoplasmic reticulum (RER) was dilated in EHBRs. These findings are indicative of a hypofunctional state. However, no differences between EHBRs at 6 and 12 weeks of age were evident, suggesting that the hyperbilirubinemia does not exert any pronounced influence on acinar cell growth or pancreatic exocrine function.

Age Factors↗

PubMed1999

The NS5A protein of hepatitis C virus partially inhibits the antiviral activity of interferon.

The non-structural protein 5A (NS5A) of some hepatitis C virus (HCV) isolates has been implicated in the inhibition of the antiviral activity of interferon (IFN). In the present study, the possible inhibitory effects of NS5A from two isolates of HCV subtype 1b, HCV-1bJk and M094AJk, and their chimeric form on the antiviral activity of IFN were examined. HCV-1bJk and M094AJk are categorized as IFN resistant and IFN sensitive, respectively, based on the sequences of the IFN-sensitivity determining region (ISDR). When encephalomyocarditis virus was used as a challenge virus, NS5A was shown to eliminate the antiviral activity of IFN, with inhibition being more prominent with HCV-1bJk NS5A than with M094AJk NS5A. Moreover, the inhibition was significantly weaker in cells expressing a chimeric NS5A that had a short stretch of 49 amino acids (aa 2209-2257), including the ISDR sequence, from M094AJk in the backbone of the HCV-1bJk sequence than in cells expressing the original NS5A from HCV-1bJk. These results suggest an important role for the 49 aa sequence, including the ISDR, in the inhibition of IFN-mediated antiviral activity. On the other hand, only a slight reduction of IFN antiviral activity by HCV-1bJk NS5A was observed when vesicular stomatitis virus was used as a challenge virus, and barely any reduction was observed when Japanese encephalitis virus was used. These results may reflect differential importance of each of the IFN-mediated signalling pathways in conferring resistance against different viruses.

3T3 Cells↗

PubMed1999

REM sleep components predict the response to initial treatment of infantile spasms.

PURPOSE: The phasic inhibition index (PII) is the rate of the simultaneous occurrence of rapid eye movement bursts (RBs) and phasic chin muscle activity (PCMA) during rapid eye movement sleep (REMS). PII is low insofar as physiologically occurring REM-related phasic inhibition acts on chin muscles. Previously we found that PII was significantly higher in patients with infantile spasms (ISs) who had a recurrence of convulsions than in patients with ISs who exhibited no recurrence. We aimed to predict the response of patients with ISs to conventional anticonvulsants (AEDs) by means of REMS components including PII, expecting to facilitate avoidance of potentially hazardous hormonal therapy. METHODS: REMS, recorded before the beginning of any medication, was retrospectively examined in 15 patients with ISs. The patients were classified into two groups according to the response to initial treatment with conventional AEDs. Conventional AEDs were enough to control the spasms in six good responders (GRs), whereas further hormonal therapy was required in nine poor responders (PRs) to control the spasms. RESULTS: The amount of REMS was significantly lower in patients with ISs than in controls. GRs had less REMS than did PRs, although no significant difference was observed. Although the frequencies of RB and PCMA showed no significant differences among GRs, PRs, and controls, the average PII value in PRs (12.6+/-3.4; mean+/-SD) was significantly (p < 0.001) higher than that in GRs (6.1+/-1.7). CONCLUSIONS: PII is a useful parameter for differentiating GRs from PRs.

Anticonvulsants↗

PubMed1999

Standards for selecting percutaneous ethanol injection therapy or percutaneous microwave coagulation therapy for solitary small hepatocellular carcinoma: consideration of local recurrence.

OBJECTIVE: Percutaneous ethanol injection therapy (PEIT) and percutaneous microwave coagulation therapy (PMCT) are effective treatments for small hepatocellular carcinoma (HCC). There are no clear standards, however, for the selection of PEIT or PMCT. We determined standards based on local recurrence. METHODS: The subjects were 88 patients with solitary HCC measuring < or = 30 mm in diameter, who were treated by PEIT (n = 45) or PMCT (n = 43) and judged to be cured using computerized tomography (CT) with contrast medium after treatment. Patient characteristics, including age, gender, viral markers, Child-Pugh classification, tumor size, tumor cell differentiation, and serum alpha-fetoprotein (AFP) concentration we analyzed, and the factors influencing the local recurrence in the PEIT and PMCT groups were determined, using univariate and multivariate analysis. RESULTS: Univariate analysis indicated that tumor cell differentiation and serum AFP concentration influenced local recurrence in the PEIT group, and tumor size did so in the PMCT group. Multivariate analysis revealed that tumor cell differentiation influenced local recurrence in the PEIT group, and tumor size did so in the PMCT group. PEIT was effective for treating well-differentiated HCC, and PMCT was effective for treating HCC measuring < or = 15 mm in diameter. PMCT was superior to PEIT for treating patients with HCC measuring < or = 15 mm in diameter. In such cases with well-differentiated HCC, PEIT was as effective as PMCT. CONCLUSIONS: The selection of PEIT or PMCT to treat patients with HCC should be based on tumor size and cell differentiation.

Aged↗

PubMed1999

Spontaneous accumulation of eosinophils and macrophages throughout the stroma of the epididymis and vas deferens in alymphoplasia (aly) mutant mice: I. A histological study.

PROBLEM: The alymphoplasia (aly) mutation of mice causes the systemic absence of lymph nodes and Peyer's patches. Histopathological analysis has revealed that lymphocytes accumulate in some organs such as the salivary glands, lungs, kidneys, liver, and pancreas of homozygotes (aly/aly) but not heterozygotes (aly/ + ). However, the presence of lymphocytic accumulation in male reproductive tissues of aly/aly mice has not been reported. METHOD OF STUDY: The male reproductive organs of homozygous aly/aly, heterozygous aly/ +, and other immunodeficient mice bred in a specific pathogen-free state were histologically investigated. RESULTS: Testes, ductuli efferentes, prostates, coagulating glands, and seminal vesicles of homozygous aly/aly mice were free from any pathological accumulation of leukocytes. However, their epididymides and vasa deferentia exhibited massive infiltration by leukocytes, which were composed of eosinophils and macrophages. In all homozygotes examined, both eosinophils and macrophages were extensively observed throughout the stroma of the epididymis and vas deferens, but never within the epithelium or lumen of the ducts, with no parenchymal tissue damage. The accumulation of eosinophils was never found in nonreproductive organs. In aly/ + heterozygous mice and other immunodeficient mice, no pathological accumulation of leukocytes were noted. CONCLUSIONS: The accumulation of eosinophils and macrophages is specific to the epididymides and vasa deferentia of immunodeficient aly/aly homozygotes, although the pathogenesis remains unknown.

Animals↗

PubMed1999

F4/80-positive cells rapidly accumulate around tubuli recti and rete testis between 3 and 4 weeks of age in the mouse: an immunohistochemical study.

PROBLEM: Previous studies demonstrated that F4/80 antigen (murine macrophage-specific antigen)-positive cells in testes of normal adult mice accumulate particularly in the interstitium adjacent to the tubuli recti and rete testis (i.e., the central region). However, it remains unknown whether this accumulation is a congenital or acquired phenomenon. METHOD OF STUDY: The distribution of F4/80-positive cells on frozen sections of testes obtained from various aged mice was immunohistochemically examined to determine when the positive cells specifically accumulate in the central region. RESULTS: F4/80-positive cells were homogeneously distributed throughout the testicular interstitium with no specific accumulation until 2 weeks of age. However, at 3 weeks of age, the density of positive cells in the central region became slightly, but significantly, higher than that in the interstitium between the seminiferous tubules. Between 3 and 4 weeks of age, the cell density in the central region increased rapidly, the density at 4 weeks of age reaching the level of the mature testes of 8-week-old mice. CONCLUSION: These results demonstrate that the specific accumulation of F4/80-positive cells in the central region is an acquired phenomenon, which starts and ends before puberty.

Animals↗

PubMed1999

[An outbreak of parainfluenza 3 virus infection in the elderly in a ward].

In the D ward of Nagoyashi-Koseiin geriatric hospital (36-beds), upper respiratory illnesses were recognized in all the inpatients between July and August in 1995, and we studied 7 elderly subjects with parainfluenza 3 infection diagnosed by serology and viral culture. The outbreak of upper respiratory illnesses occurred in the ward during the 17 days from July 21 through August 6, 1996. Fifteen of the 18 elderly persons with upper respiratory illnesses were tested by serology; parainfluenza 3 infection was identified in 7. One of the 7 patients, parainfluenza 3 virus was isolated. Seven elderly subjects with parainfluenza 3 infection were 2 males and 5 females and five of them (71.4%) were bedridden. The most common complaint was fever and coughing in 7/7 (100%), followed by sputum in 5/7 (71.4%), wheezing in 4/7 (42.9%). The pyrexial period in the parainfluenza-infected group ranged from 1 to 4 days (average 3.1 days), and was significantly shorter than that of the influenza group. The maximum recorded temperature in the parainfluenza-infected group ranged from 37.0 to 39.2 degrees C (average 38.1 degrees C), and was significantly lower than that of the influenza group. Two of the 7 patients with parainfluenza 3 virus infection had pneumonia, but nobody died, and all 7 patients recovered without sequele. It is possible that parainfluenza 3 virus infection among elderly subjects cause secondary bacterial infection, so we think that prevention of nosocomial parainfluenza infection should be a high priority in the case of outbreak of such an infection in a ward.

Aged↗

PubMed1999

Regulations of gonadotropin secretion by circulating inhibin, estradiol, and progesterone in cyclic hamsters.

The physiological importance of gonadal hormones in feedback control of gonadotropin secretion during the estrous cycle in golden hamsters was investigated with immunoneutralization methods. Anti-inhibin serum (inhibin-AS) treatment always induced a drastic increase in follicle-stimulating hormone (FSH) secretion and occasionally raised luteinizing hormone (LH) secretion. Anti-estradiol-17beta serum (estradiol-AS) treatment increased LH secretion typically. Although estradiol-AS elevated FSH secretion occasionally, the elevation was much less than that by inhibin-AS. Plasma FSH reached ovariectomized levels by a synergistic effect of both antisera. Elevated plasma LH with both antisera was much less pronounced than in ovariectomized animals. Plasma LH increased dramatically to the levels in the ovariectomized group when antibody against progesterone (progesterone-AB) was given together with inhibin-AS and estradiol-AS, although progesterone-monoclonal antibody alone did not alter plasma gonadotropin levels. These results indicate that in hamsters FSH secretion is mainly regulated by inhibin and LH secretion is regulated by estradiol-17beta and progesterone during the estrous cycle.

Animals↗

PubMed1999

The therapeutic effect of proton pump inhibitors on Helicobacter pylori-positive gastric ulcers.

The aim of the present study was to elucidate the risk factors that could delay gastric ulcer healing when either a proton pump inhibitor or an H2-receptor antagonist is used for gastric ulcer treatment. Endoscopically-diagnosed gastric ulcer patients (216 men and 96 women, mean age: 57+/-13 years) were investigated. All patients were consecutively recruited and randomly assigned to receive H2-receptor antagonist (n = 196) or proton pump inhibitor (n = 116) treatment for eight weeks. Chi-squared tests and multivariate analysis to determine factors influencing ulcer healing were used to analyse the patients profiles, endoscopic findings, and Helicobacter pylori-infection status. In the H2-receptor antagonist group, the most important risk factor was a large ulcer size (> 2 cm diam.), followed by a linear shape of the ulcer, undermining tendency of ulcer, previous history of gastric ulcer, and H. pylori infection. In the proton pump inhibitor group, linear shape of the ulcer was the only significant risk factor for slow ulcer healing; other factors, including H. pylori infection, were insignificant. These results indicate that ulcer morphology may be the most important information for predicting ulcer healing, and that H. pylori infection does not delay gastric ulcer healing when proton pump inhibitor treatment is used.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1999

Establishment of a method for mapping of N-linked oligosaccharides and its use to analyze industrially produced recombinant erythropoietin.

A rapid and convenient method for N-linked oligosaccharide structure analysis was developed and applied to the quality examination of commercially manufactured recombinant human erythropoietin (rEPO). Oligosaccharides released from rEPO expressed in Chinese hamster ovary cells were labeled with 2-aminobenzamide, and analyzed by a combination of diethylaminoethyl (DEAE) column HPLC and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). This newly developed method allowed us to analyze sialylated oligosaccharides directly. The results showed that these oligosaccharides are composed of neutral-mono-di-tri-tetrasialyl oligosaccharides in a ratio of <1:2:13:34:51%, and that the core structure was a mixture of complex type bi-, tri- and tetra-antennary forms with one to three polylactosaminyl chains. Further analysis showed clearly that the N-linked oligosaccharide structure of rEPO has not changed throughout the past ten years of manufacturing by our company. The analysis was carried out using a small quantity (1 nmol) of rEPO, demonstrating the efficacy of the newly developed method. Further, the N-linked oligosaccharides of rEPO manufactured by our company almost coincided with those of the erythropoietin European Pharmacopoeia Biological Reference Preparation (Eur.Ph.BRP), a standard product.

Animals↗

PubMed1999

Purification, properties and reactivity of the esterase from Micrococcus sp.

The esterase from Micrococcus sp., which hydrolyzes n-propyl-2-fluorocyclopropanecarboxylate (3) enantioselectively, was highly purified by three types of chromatography. The purified enzyme was inactivated by Hg and diisopropyl fluorophosphate (DFP). It was a monomer with a molecular weight of about 35000. The enzyme exhibits esterase activity towards many aliphatic propyl esters. The enantioselectivity for substrate (3) using purified enzyme did not differ from that of crude enzyme.

Esterases↗