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Biomedical subjects

K Ashida

Publications and source records attributed to K Ashida.

At least 55 records · Page 3Linked to original sources

[Age-related changes of IgE-mediated allergic reaction in patients with late onset asthma--relationship between IgE-mediated allergy and age at onset].

We examined age-related changes in the IgE-mediated allergic reaction in patients with late onset asthma, whose asthma first occurred at over 40 years. 1. The number of patients with a high serum IgE level (over 300 IU/ml) was larger in patients with an age of onset between 40 and (40-49 years group) and in patients older than 60 at age of onset (60-year group) than in patients with an age of onset between 50 and 59 (50-59 year group). 2. A positive RAST score to house dust mite (HDm) allergen was more frequently found in the 40-49 year group and in the 60- year group than in the 50-59 year group. Frequency of positive RAST score to HDm in the 50-59 year group was significantly lower (p < 0.01) than in early-onset asthma patients (age at onset less than 39 years). 3 Frequency of family history of asthma in the 50-59 years group was high, being equal to that of early-onset asthma patients. 4 In the 50-59 year group, the frequency of severe asthma was comparatively higher than that of the other groups. The frequency of IgE-mediated allergic reaction changed in regard to age of onset of asthma, and allergic reactions in late-onset asthma partially resembled those of early-onset asthma. These results suggest that an atopic constitution is related to the onset of bronchial asthma in the elderly.

Adolescent↗

Aberrant p16INK4 expression related to clinical stage and prognosis in patients with pancreatic cancer.

The p16 tumor suppressor gene is thought to play an important role in cell cycle regulation by encoding for protein products that can inhibit the progression from G1 to S phase in the cell cycle. Recently, the p16 gene has been found to be mutated or deleted in a variety of different types of primary human malignant tumors and human-derived malignant tumor cell lines. In this study, primary ductal pancreatic adenocarcinomas from 32 human patients were analyzed immunohistochemically for expression of p16 protein, with emphasis on the role of abberant p16 protein expression as a prognostic indicator. In addition, the same tumors were also assessed for p53 protein expression, AgNOR counts, and DNA ploidy. Nineteen out of the 32 cases (59%) showed positive immunoreactivity for p16 protein in their tumors and a significant association was found between lack of p16 protein expression, and both advancing clinical stage classification of disease, and poorer survival (p<0.05). The rate of positive immunoreactivity for p53 protein expression was 59%, however, no clear association was found between p53 protein expression, and either clinical stage of disease, or survival. These findings suggest that alteration of the p53 gene may be a relatively early event in pancreatic tumorigenesis, whereas alteration of the p16 gene is more likely to be correlated with tumor progression in pancreatic malignancies. Further survival analysis revealed that all five of the 32 cases that survived for three years or longer had positive immunostaining for p16 protein, and a relatively low level of AgNOR counts. In four out of five of these patients, the tumors also exhibited negative immunostaining for p53 protein and DNA diploidy. These findings suggest that molecular analysis of patient tumor sections may yield potentially useful prognostic indicators for patients undergoing surgical resection for pancreatic cancer.

Aged↗

Cell proliferative activity in intraductal papillary-mucinous neoplasms and invasive ductal adenocarcinomas of the pancreas: an immunohistochemical study.

OBJECTIVE: To evaluate cell proliferative activity and expression of cytokeratins (CKs) and epithelial membrane antigen (EMA) in intraductal papillary-mucinous neoplasm of the pancreas (IPNP). METHODS: We examined cell proliferative activity in normal pancreatic ducts, IPNP, and invasive ductal adenocarcinoma of the pancreas by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and Ki67 antigen. Expression of CKs and EMA was also examined immunohistochemically. RESULTS: In normal pancreas (n = 5), PCNA- or Ki67-positive ductal epithelia were not found. Cytokeratins (polyclonal, CAM5.2, CK-7, CK-8, CK-18, and CK-19) were expressed in the ducts and ductules but not in the acinus, and EMA expression was noted in the acinus but rarely in the ducts. In IPNP (n = 9) and invasive ductal adenocarcinoma (n = 6) of the pancreas, the overall PCNA-labeling index (PCNA-LI) was 3.2 +/- 4.1 and 16.0 +/- 7.2, respectively, and overall Ki67-LI was 2.2 +/- 2.6 and 14.5 +/- 6.3, respectively. In IPNP, the PCNA-LI and Ki67-LI were low in adenoma areas (PCNA-LI = 0.9 +/- 0.7), intermediate in dysplastic areas (PCNA-LI = 3.7 +/- 2.4), and rather high in carcinoma in situ areas (PCNA-LI = 11.5 +/- 8.4). Both CKs and EMA were noted in tumor cells. CONCLUSIONS: The data suggest that cell proliferative activity is low in IPNP compared to invasive ductal adenocarcinoma, that cell proliferative activity increases with the grade of cell atypia in IPNP, and that CK expression is not changed during the neoplastic change, but EMA is newly expressed or overexpressed during the neoplastic change.

Aged↗

Clinical significance of serum P53 antibody in patients with gastric cancer.

The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.

Adenoma↗

Lipopolysaccharide-induced increase in plasma nitrotyrosine concentrations in rats.

Since the production of peroxynitrite may contribute to the pathophysiology of endotoxemia or sepsis, the quantities of the produced peroxynitrite were evaluated in rats after lipopolysaccharide (LPS) treatment by measuring plasma nitrotyrosine concentrations with a new method. The intraperitoneal administration of LPS caused a persistent increase in plasma nitrotyrosine concentrations, which reached a maximum with 6-fold level of the base line (105 pmol ml-1) at 24 h and gradually declined to 3-fold level of the base line at 7 days. However, plasma concentrations of nitrite and nitrate peaked at 18 h, returning to base line within 48 h. The effect of LPS on the increase in plasma concentration of nitrotyrosine was dose-dependent and consistent with that of nitrite and nitrate concentrations. On the other hand, intravenous injection of nitrotyrosine revealed a rapid clearance with a plasma half-life of 1.67 h. These results indicate that the elevation of plasma nitrotyrosine concentrations may persist for more than a week after LPS treatment, and that the determination of plasma nitrotyrosine concentrations may be useful to detect the previous peroxynitrite-dependent oxidative damages.

4-Chloro-7-nitrobenzofurazan↗

Abolition of Torsade de Pointes after radiofrequency catheter ablation at right ventricular outflow tract.

Radiofrequency (RF) catheter ablation was tried to treat a patient with syncope, perhaps due to polymorphic ventricular tachycardia (VT) of Torsade de Pointes (TdP) type which was documented by Holter monitoring. Electrophysiological study showed that the isolated ventricular extrasystoles (VEs) that initiated TdP were exactly replicated by pace mapping at the septal site of the right ventricular outflow tract. Performance of RF ablation at this site abolished the TdP and episodes of syncope with no requirement for antiarrhythmic agents for 3 years, whereas isolated VEs persisted. Although it is difficult to mention whether RF ablation was successful or not in this case, this procedure should be considered as a potentially curative approach to the TdP, when the arrhythmogenic focus can be fixed and identified as in this case.

Adolescent↗

Loss of heterozygosity of the retinoblastoma gene in liver cirrhosis accompanying hepatocellular carcinoma.

Carcinogenesis is a multistep process. Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not known well. The present study was conducted to evaluate aberration of the retinoblastoma (RB) gene in HCC and adjacent non-tumorous liver using 22 patients with chronic liver damage accompanying HCC. The specimens obtained by microdissection from paraffin-embedded tissues were analyzed using an assay based on the polymerase chain reaction for highly polymorphic nucleotide sequences of microsatellites in the RB gene. Out of 22 cases, 15 showed constitutional heterozygosity for the microsatellite markers. In 11 (73.3%) of these 15 informative cases, the primary HCC foci showed loss of heterozygosity (LOH). In 8 of these 11 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 20 (64.5%) of 31 microdissected non-tumorous foci. All of the non-tumorous foci showing RB loss were cirrhotic lesions but there were no foci of chronic hepatitis. The remaining 4 cases without LOH in HCC foci showed no LOH in non-tumorous lesions. In our study, LOH of the RB gene was frequently observed in liver cirrhosis surrounding tumor.

Aged↗

Endocrine cells in intraductal papillary-mucinous neoplasms of the pancreas. A histochemical and immunohistochemical study.

The endocrine cells in intraductal papillary-mucinous neoplasms (IPN) of the pancreas have rarely been investigated. In the normal pancreatic ducts of normal pancreases (n = 5) there were a few endocrine cells: argyrophil in 5 (100%), chromogranin A in (100%), pancreatic polypeptide (PP) in 3 (60%), and insulin in 7 (20%). These endocrine cells were scattered, and located in the basal portions of pancreatic ducts. In IPN of the pancreas (n = 9), there were many endocrine cells: argyrophil in 7 (78%), argentaffin in 8 (89%), chromogranin A in 8 (89%), PP in 7 (78%), serotonin in 7 (78%), insulin in 4 (44%), and gastrin in 5 (56%). In invasive ductal adenocarcinoma of the pancreas (n = 6), many endocrine cells were also detected: argyrophil cells in (67%), chromogranin A in 3 (50%), insulin in 3 (50%), glucagon in 4 (67%), and somatostatin in 3 (50%). In positive cases, endocrine cells were situated under or among the neoplastic cells and the proportion of endocrine cells in IPN was less than 5% of the total neoplastic cell population. These data show that normal pancreatic ducts contain endocrine cells and that IPN frequently contain argyrophil, argentaffin, chromogranin A, and hormone-containing endocrine cells. These data also suggest that endocrine differentiation occurs during neoplastic transformation and progression of IPN of the pancreas.

Adenocarcinoma, Mucinous↗

Expression of pancreatic digestive enzymes in normal and pathologic epithelial cells of the human gastrointestinal system.

Pancreatic digestive enzymes have rarely been reported in human nonpancreatic organs. We examined their expression in the epithelial cells of the nonpancreatic gastrointestinal organs, looking for pancreatic alpha-amylase, trypsin, chymotrypsin and pancreatic lipase. Western blotting, enzyme assay and pancreatic alpha-amylase mRNA were also used in selected specimens. In normal tissues, immunoreactivity of one or more of these enzymes was frequently noted in cells of the salivary glands, stomach, duodenum, large pancreatic ducts, extrahepatic bile ducts and gall bladder. The epithelium of the normal oesophagus, small intestine and colon were consistently negative for these enzymes. In pathologic tissues, immunoreactivity for one or more enzymes was present in epithelial cells of pleomorphic adenomas of the salivary glands, oesophageal squamous cell carcinoma, gastric adenoma and adenocarcinoma, pancreatic adenocarcinoma, cholecystitis, adenocarcinoma of the gall bladder and extrahepatic bile duct, and colon adenoma and adenocarcinoma. Western blotting showed a specific band of each enzyme in some specimens of normal stomach. In situ hybridization for pancreatic alpha-amylase mRNA showed specific signals in the normal stomach, but not in the normal colon. Reverse transcriptase polymerase chain reaction analysis for pancreatic alpha-amylase mRNA revealed specific signals in the normal stomach. Enzyme assay revealed that the stomach and gall bladder showed these activities. The data suggest that pancreatic digestive enzymes are produced by several epithelial cell types of the nonpancreatic gastrointestinal organs, that the organs positive for pancreatic enzyme have a common cell lineage, and that neoplasms continue to express or neoexpress these enzymes after neoplastic transformation.

Adult↗

Quantitative analysis of cyclooxygenase-2 gene expression on acute gastric injury induced by ischemia-reperfusion in rats.

The rat model of acute gastric damage induced by ischemia-reperfusion (I-R) has been used to evaluate the protective effect of various drugs on gastric injury. However, the quantitative expression state of cyclooxygenase-2 (COX-2), a protein which induces cytoprotective prostaglandins during inflammation, is still unknown in acute gastric injury induced by I-R. Therefore, we have quantitatively investigated the level of expression of COX-2 mRNA in injured gastric tissue of this model using the reverse transcription-competitive polymerase chain reaction method. The mRNA for COX-2 was expressed at low or undetectable levels in the normal gastric tissues in control rats, which were fasted for 18 hrs without I-R. The mRNA levels of COX-2 in injured gastric tissues were higher than those of control tissues between 6 hrs and 48 hrs after I-R. The maximum expression of COX-2 mRNA was recorded at 24 hrs (approximately a 200-fold increase). The expression state of COX-2, which has been ascertained in this study, should be useful in evaluating the effect of various drugs on the expression of COX-2 in acute gastric damage.

Actins↗

Inhibition by cigarette smoke of lipid peroxidation-induced neurotransmitter release.

Effects of water-soluble substance in cigarette smoke on neurotransmitter release were investigated using nerve terminals (synaptosomes) prepared from rat cerebral cortex. 2,2'-Azobis (2-amidinopropane) dihydrochloride (ABAP), a peroxyl radical-generator, enhanced the depolarization-evoked release of glutamate and aspartate from synaptosomes with concomitant increase in thiobarbituric acid-reactive substances (TBA-RS) levels in membrane lipids of synaptosomes. The trapped smoke-substance attenuated the lipid peroxidation-enhanced release of excitatory amino acids during the depolarization with reduction in TBA-RS, although it failed to affect the basal release of neurotransmitters. These data suggest that cigarette smoke may possess antioxidant properties to reduce oxidation-induced enhancement of transmitter release from nerve terminals.

Amidines↗

Substances in the aqueous fraction of cigarette smoke inhibit lipid peroxidation in synaptosomes of rat cerebral cortex.

The effects of water-soluble substances in cigarette smoke on lipid peroxidation were investigated using nerve terminals prepared from the rat cerebral cortex. The prepared smoke-substances significantly reduced the spontaneous increase in thiobarbituric acid-reactive substances in synaptosomes in a dilution factor-dependent manner. Furthermore, the aqueous extract also inhibited the elevation of lipid peroxidation induced by 2,2'-azobis (2-amidinopropane) dihydrochloride, a peroxyl radical generator. Smoke-substances scavenged superoxide radicals generated from stimulated human leukocytes and from the xanthine/xanthine oxidase system. These effects were not mimicked by nicotine. The antioxidant effects of smoke-substances were preserved for several days at 5 degrees or -80 degrees C. The results suggest that the smoke-substances may possess long half-lives and scavenge the radicals which cause lipid-peroxidation in synaptosome membranes.

Animals↗

Effect of plaunotol on gastric injury induced by ischaemia-reperfusion in rats.

Plaunatol, an anti-ulcer drug, increases prostaglandin content in gastric tissue but its effect on radical-mediated gastric damage or activity against reactive oxygen species is unknown. We examined the effects of oral administration of plaunotol (Kelnac) on the acute gastric mucosal lesion and its progression to ulcer lesion induced by ischaemia-reperfusion in rats. Plaunotol (30 and 100 mg kg-1, 15 min before ischaemia) significantly reduced the total erosion area observed immediately after ischaemia-reperfusion. When plaunotol (30 and 100 mg kg-1, once a day) was administrated orally 60 min after reperfusion, it prevented the progression from erosion to ulcer. At 72 h after ischaemia-reperfusion, the total area of ulcers lesions was significantly reduced compared with that without plaunotol administration. Furthermore, treatment with plaunotol (100 mg kg-1) significantly increased prostaglandin E2 content in gastric tissues of both acute gastric mucosal lesion and gastric ulcer lesion. In in-vitro experiments, plaunotol (1-3 mg mL-1) reduced the superoxide radicals generated by leucocytes, but not by xanthine oxidase. These results indicate that plaunotol has protective effects on both the onset of acute gastric mucosal injury and its progression to ulcer lesion induced by ischaemia-reperfusion. Both effects of plaunotol on increase in prostaglandin content in gastric tissues and inhibition of superoxide radical from leucocytes may play important roles on the protection against gastric mucosal injury.

Animals↗

High signal intensity on T2-weighted magnetic resonance imaging and cerebral hemodynamic reserve in carotid occlusive disease.

BACKGROUND AND PURPOSE: The importance of MR imaging in carotid artery disease is unclear. We evaluated the sensitivity and specificity of the high signal intensity changes on MR images for diagnosis of hemodynamically compromised unilateral internal carotid artery disease. METHODS: We evaluated the association of high signal intensities on T2-weighted MR images with changes in cerebral perfusion reserve measured using 99mTc-hexamethylpropyleneamine oxime single-photon emission CT and acetazolamide in 23 patients. RESULTS: Eleven patients had a type I response (normal flow and normal perfusion reserve), 8 patients had a type II response (normal flow and decreased perfusion reserve), and 4 patients had a type III response (decreased flow and decreased perfusion reserve). High signal intensities in the centrum semiovale (11/12) and/or posterior periventricular white matter (6/12) were frequently seen in the hemodynamically compromised groups. Extensive high signal intensities were associated with severely impaired cerebral circulation. MR imaging had high sensitivity (0.92) and specificity (1.0) in predicting hemodynamically compromised patients when we used the presence of T2 high intensity in the centrum semiovale as a criterion. CONCLUSIONS: The centrum semiovale T2 hyperintensities lateralized to the side of carotid occlusion are specific and sensitive for the presence and severity of hemodynamic compromise from carotid occlusive disease.

Acetazolamide↗