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Biomedical subjects

E Kaneko

Publications and source records attributed to E Kaneko.

At least 19 recordsLinked to original sources
PubMed1997

Percentage changes in serum pepsinogens are useful as indices of eradication of Helicobacter pylori.

OBJECTIVE: Eradication of Helicobacter pylori has been gaining significance for the treatment of gastroduodenal diseases. Establishment of a precise diagnostic method for H. pylori is of great value. The aim of this study was to establish a new method for precisely judging the eradication of this bacteria. METHODS: We measured serum pepsinogen I (PG I) and pepsinogen II (PG II) levels in 105 cases of peptic ulcer with H. pylori infection before and after anti-H. pylori treatment, determined percentage changes in serum PG I:PG II ratios before and 1 month after the treatment, and established cut-off values for them to distinguish success from failure of H. pylori eradication. Cut-off values for percentage changes in serum PG I:PG II ratios were tentatively set as +40%, +25%, and +10% when the serum PG I:PG II ratios before treatment were less than 3.0, not less than 3.0 but less than 5.0, and not less than 5.0, respectively. RESULTS: With these cut-off values, the sensitivity, specificity, and validity for determination of eradication of H. pylori-on the basis of culture, histology, the rapid urease test, and a polymerase chain reaction method-were 100.0%, 93.1%, and 96.2%, respectively. These cut-off values could be applied to both gastric ulcer and duodenal ulcer. CONCLUSION: Our findings suggest that percentage changes in serum PG I:PG II ratios are useful as indices for distinguishing success from failure in eradication therapy for H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Induction of hepatic heme oxygenase and changes in cytochrome P-450s in response to oxidative stress produced by stilbenes and stilbene oxides in rats.

Both trans- and cis-stilbene oxide (TSO and CSO) markedly induced heme oxygenase-1 (HO-1) at the transcriptional level in rat liver. HO-1 induction by TSO and CSO was preceded by glutathione (GSH) depletion in the liver. Pretreatment of rats with buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis, enhanced GSH depletion evoked by either TSO or CSO and augmented the increase in HO-1 mRNA. In contrast, pretreatment with perfluorodecanoic acid (PFDA), which reduced hepatic GSH S-transferase activity, prevented TSO- and CSO-mediated GSH depletion and abolished HO-1 induction. In addition, TSO and CSO enhanced c-jun but not c-fos mRNA, which is in parallel with the HO-1 mRNA change. These findings indicate that the oxidative stress evoked by GSH depletion after the treatment of rats with stilbene oxides could stimulate both HO-1 and c-jun gene expression. Pretreatment with either BSO or PFDA also affected the induction of CYP2B1/2 mRNA and apoprotein by TSO or CSO, suggesting that not only the change of heme pool size but also some other unknown factor or factors may be involved in the regulation of the CYP2B1/2 and HO-1 gene expression. cis-Stilbene (CS), a parent compound of CSO, also induced HO-1 mRNA, together with hepatic GSH depletion, but trans-stilbene (TS) failed to elevate HO-1 mRNA under the experimental conditions. In addition, CS increased CYP2B1/2 mRNA, whereas TS did not. These results suggest that CS could be rapidly oxidized by cytochrome P-450 (P-450) to CSO, leading to GSH depletion in the liver. Such differences in the hepatic metabolic pathways of CS and TS are attributable to the differential effects on HO and P-450 induction by these compounds. Like other phenobarbital-type P-450 inducers, TSO and CSO also induced CYP2C6 and 3A2 apoproteins in rat liver. Stilbene oxide reduced CYP2E1 mRNA and apoproteins for CYP2E1 and 2C11. All of these findings indicate that stilbene compounds have unique effects on hepatic HO-1 and P-450 regulation in rats.

Animals↗
PubMed1996

Effects of aging on the microclimate pH of the rat jejunum.

The acidic microclimate layer in the vicinity of the cell surface of mammalian jejunum is important for absorption of some nutrients, such as small peptides and folate. The present study was undertaken to investigate the effect of aging on the cell surface pH (microclimate pH) of the jejunum of rats. The microclimate pH was measured in vitro in superfused preparations using single-barreled pH-sensitive microelectrodes filled with a liquid ion exchanger. The thickness of the microclimate layer was estimated by reading the distance of microelectrode advancements. The existence of a microclimate pH in the jejunum was confirmed in the senescent rats, but the value of the microclimate pH was significantly higher in the senescent (24 mo) rats (6.52 +/- 0.02) than in the young-adult (6 mo) rats (6.09 +/- 0.01) (P < 0.01). Na+ removal from the perfusate or the addition of amiloride elevated the pH in the senescent rats as well as in the young-adult rats. The microclimate layer was slightly thinner in the senescent rats than in the young-adult rats. The acidity of the microclimate layer of intestinal surface is lower in senescent animals than in the young-adult ones. One of reasons for this is the thinner mucus layer in senescent animals.

Aging↗
PubMed1996

Magnetic resonance imaging to study lesions of atherosclerosis in the hyperlipidemic rabbit aorta.

We have developed a high resolution magnetic resonance (MR) imaging technique to serially assess lesions of atherosclerosis in a rabbit model. A volume phased array coil was designed and used to image the abdominal aortas of six atherosclerotic rabbits and two age-, sex-, and weight-matched controls. Lesions of atherosclerosis were induced by a combination of repeat balloon injury and a hyperlipidemic diet. All animals were imaged on at least two occasions 9-16 months after initiation of atherosclerosis. In addition, animals were imaged immediately after sacrifice. Anatomic dissection and histology were performed to verify the MR findings. The volume phased array coil improves the image signal-to-noise ratio over existing extremity coils and resulted in higher resolution images of the abdominal aorta. Proton density-weighted images acquired with 2D/3D fast spin-echo are the most useful sequence to outline the vessel wall and to differentiate wall from lumen and background. Progressive wall thickening and lumen stenosis were observed in the serial images of the diseased rabbits. Wall thickness and lumen area derived noninvasively from the in vivo MR images correlate with postmortem MR images and sections of aorta examined by dissection microscopy and histology. Spin-echo and fast spin-echo imaging with a phased array body coil can be used to accurately assess plaque dimensions, and potentially can be used to image intraplaque features and to monitor lesion progression or regression. It should also be possible to adapt these techniques to assess human disease, especially for peripheral vascular problems.

Animals↗
PubMed1996

Increased plasma lipid peroxidation in patients with aceruloplasminemia.

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism due to mutations in the ceruloplasmin gene. Although the presence of these mutations reveals an essential role for ceruloplasmin in human biology, the mechanisms of tissue injury in this disease are unknown. We report here on the identification of increased plasma lipid peroxidation in multiple affected family members with aceruloplasminemia. Consistent with the absence of serum ceruloplasmin, plasma ferroxidase activity was markedly reduced and serum ferritin was significantly increased. Plasma lipid peroxidation was determined as thiobarbituric acid-reactive products (TBA products) in plasma samples from control, heterozygote, and affected patients. Basal levels of lipid peroxides were three times control values in patients with aceruloplasminemia and were significantly increased in these patients in the presence of copper ions and hydrogen peroxide. In each case these increases were suppressed by the addition of exogenous ceruloplasmin. These data suggest that increased susceptibility to lipid peroxidation may contribute to the unique neuropathology observed in patients with aceruloplasminemia and imply a role for free radical-mediated tissue injury in degenerative disorders of the basal ganglia.

Adult↗
PubMed1996

Effects of aging on the regulation of intracellular pH in the rat jejunum.

Jejunal villus cells from young-adult (6 months) and senescent (24 months) male Wistar rats were studied to evaluate the effect of aging on intracellular pH (pHi) regulation. pHi was measured by quantitative fluorescence microscopy by using BCECF-AM [2',7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein acetoxy methylester] under basal conditions and after inducing cytoplasmic acidification with pulsed NH4Cl. In the senescent rats, the recovery rate from the acidified levels was significantly lower than that in the young-adult rats (.208 +/- .005 vs .255 +/- .004 pH units/min). The relationship between pHi recovery and external Na+ concentration followed Michaelis-Menten type kinetics, the maximum velocity (Vmax) of alkalinization being significantly lower in the senescent rats than in the young-adult rats (.227 +/- .033 vs .297 +/- .024 pH units/min). These results indicate that the recovery of pHi from an acidic level was slower in the senescent rats, due to the reduced activity of Na+/H+ exchange as revealed by the decreased Vmax value.

Aging↗
PubMed1996

Pyridoxal 5'-phosphate binding of a recombinant rat serine: pyruvate/alanine:glyoxylate aminotransferase.

Serine: pyruvate/alanine: glyoxylate aminotransferase in the liver is a class IV amino-transferase. The present study was undertaken to characterize the pyridoxal 5'-phosphate (PLP) binding to a recombinant rat serine: pyruvate/alanine: glyoxylate aminotransferase (SPT10), which is a homodimer of 44.4 kDa subunits. Purified SPT10 exhibited absorption maxima at approximately 330 nm in addition to a 278 nm protein peak and a approximately 420 nm peak of PLP bound via Schiff base, and contained 0.56-0.69 mol of PLP per mol of subunit. Apo-SPT10 without measurable bound PLP did not exhibit the absorbance at approximately 420 nm, but still showed the approximately 330 nm peak. Upon reconstitution, 0.73-0.79 mol of PLP per mol of subunit was bound to apo-SPT10 with an apparent Kd of approximately 0.1 microM, resulting in a holo-SPT10 preparation whose specific activity and A approximately 420/A approximately 330 absorbance ratio were higher than those of the original SPT10. On SDS/PAGE of BrCN-cleavage peptides of NaBH4-reduced SPT10, 22-23 kDa fragments migrated as a pair of bands. On amino acid sequencing, the approximately 22 and approximately 23 kDa pair gave the same sequence, except that Lys was released only from the approximately 22 kDa band material in the cycle corresponding to Lys209. NaB3H4-treated SPT10 also migrated as a pair of 44-45 kDa bands and 3H was incorporated only into the approximately 45 kDa band. It appears that SPT10 has the capacity to bind 1 mol of PLP to Lys209 of every subunit, but usually binds less PLP in a Schiff base structure, probably due to the presence of a 330 nm-absorbing chromophore.

Alanine Transaminase↗
PubMed1996

A very large villous adenoma with an adjacent cancer of the rectum: an informative case for testing the proposed molecular basis of colorectal tumorigenesis.

It is currently accepted that colorectal tumorigenesis results from accumulation of multiple mutations in certain genes. This concept prompted us to search for possible mutations in the APC, k-ras, and p53 genes in an advanced cancer coexisting with a large villous adenoma of the rectum in a 54-year-old patient with no family history of colorectal cancer. Genomic DNA extracted from multiple subregions of the tumor and surrounding normal mucosa was studied by polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. Both the adenoma and carcinoma had abnormal PCR-SSCP for APC (exon 11) and k-ras, irrespective of the location within the tumors. However, p53 abnormality (exon 7) was detected only in samples taken from the carcinoma. Subsequent sequencing revealed a TTG to TAG mutation at codon 479 of APC, a GGT to GAT mutation at codon 12 of k-ras in both the adenoma and carcinoma, and a CGG to TGG mutation at codon 248 of p53 (exon 7) in the carcinoma. These findings were in accord with the current concept of colorectal tumor progression whereby genetic alteration of APC and k-ras occurs relatively early while that of p53 is rather late and is possibly a decisive event in relation to malignancy.

Adenoma, Villous↗
PubMed1996

Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR using synthetic DNA fragments.

Helicobacter pylori is closely related to upper gastrointestinal diseases, and the precise evaluation of H. pylori infection is necessary for the treatment of these diseases. The aim of the present study was to establish a method for the quantitative detection of H. pylori. We applied a competitive PCR method using various amounts of synthetic DNA fragments containing the same primer-binding and a subset of the same template sequences as the target competing for primer binding and amplification in order to quantify H. pylori in gastric mucus. The results obtained by this method were compared with the results of histological examination, the rapid urease test, bacterial culture, the [13C]urea breath test, and urea and ammonia measurements in gastric juice. As the quantity of H. pylori in gastric mucus increased, the rates of positivity of histological examination, the rapid urease test, and bacterial culture increased. The quantity of H. pylori in gastric mucus was also significantly correlated with the results of the [13C]urea breath test and was negatively correlated with the urea/ammonia ratio in gastric juice. The competitive PCR method provides an objective measure of the quantity of H. pylori and makes it possible to distinguish true negatives from false negatives due to incomplete PCR and true positives from false positives due to contamination. This method is very useful for the precise evaluation of gastric H. pylori infection.

Adult↗
PubMed1996

Late onset diabetes mellitus in patients with hereditary aceruloplasminemia.

Aceruloplasminemia is a systemic degenerative disorder characterized by mutations in the ceruloplasmin gene, the absence of serum ceruloplasmin, and iron accumulation in the brain, liver, and other tissues. Iron is an important catalyst of oxyradical-mediated cellular and tissue injury, and beta-cells in the pancreatic islets are susceptible to the cytotoxic effects of oxidative stress. We report three patients with aceruloplasminemia who have late-onset diabetes mellitus (DM) and impaired glucose tolerance (IGT) as well as neurologic symptoms. Their basal lipid peroxide levels, measured as thiobarbituric acid-reactive products, in plasma samples were three times the values for the controls. This increased susceptibility to lipid peroxidation in patients with aceruloplasminemia suggests that free-radical-mediated tissue injury plays a role in the occurrence of DM and IGT.

Brain↗
PubMed1996

[Reversed-phase high-performance liquid chromatograph--application to serum aluminium monitoring].

High-Performance Liquid Chromatography (HPLC) with the reversed-phase partition mode separation (including ion-pair one) towards metal chelate compounds prepared in an off-line fashion (precolumn chelation) is most versatile in terms of high sensitivity with base-line flatness, unique selectivity and cost effectiveness. The extraordinary toughness to the complicated matrices encountered in clinical testing is exemplified by the successful application to the aluminium monitoring of human serum samples. The A1 chelate with 2,2'-dihydroxyazobenzene is efficiently chromatographed on a LiChroCART RP-18 column using an aqueous methanol eluent (63.6 wt%) containing tetrabutylammonium bromide as an ion-pair agent. The serum concentration level of A1 down to 6 micrograms dm-3 is readily monitored without influences from iron, chyle and haemolysis.

Aluminum↗
PubMed1996

Suppressed expression of phenobarbital-inducible hepatic cytochrome P-450s in Eisai-hyperbilirubinuria rats (EHBR/Eis).

The differential induction of hepatic cytochrome P-450 (P450) was studied in Eisai-hyperbilirubinuria rats (EHBR/Eis). This rat is a mutant that has as high a concentration of bilirubin in the urine as in the plasma. A single administration of trans-stilbene oxide (TSO, 2 mmol/kg), a phenobarbital (PB)-type P450 inducer, did not increase total P450, the CYP2B1/2 or the CYP2C6 in EHBR/Eis liver. TSO was able to induce delta-aminolevulinic acid synthetase and heme oxygenase, rate-limiting enzymes in heme biosynthesis and degradation, respectively, in both EHBR/Eis and Sprague-Dawley rat (SDR), the strain from which EHBR/Eis is derived. TSO also produced similar effects on glutathione depletion and on the activities of other drug-metabolizing enzymes in both strains. A 23-fold increase in CYP2B1/2 mRNA in the SDR liver was observed 24 hr after TSO treatment. In the EHBR/Eis strain, however, TSO increased CYP2B1/2 mRNA only 2-fold. In addition, repeated injection of TSO failed to induce P450 isozymes, CYP2B1/2, CYP2C6 or CYP3A2 in EHBR/Eis. On the other hand, there was essentially no difference in the induced levels of CYP1A1/2 apoprotein and mRNA between twins of SDR and EHBR/Eis livers treated with 3-methylcholanthrene or 1-benzylimidazole. The increased levels of both CYP2B1/2 apoprotein and mRNA from EHBR/Eis liver treated with TSO and 1-benzylimidazole were much smaller (2.5- and 5-fold increases, respectively) than from the SDR liver (17.5- and 15-fold increases, respectively). Although PB expressed CYP2B1/2 apoprotein and mRNA to a similar extent in both homozygous and heterozygous EHBR/Eis livers, CYP3A2 and CYP2C6 were less responsive to PB in homozygous EHBR/Eis. Repeated treatment with TSO induced these isozymes in heterozygote but not in homozygote. These findings suggest that the suppressed expression of PB-inducible P450 isozyme genes in the EHBR/Eis liver may be a general phenomenon associated with PB-type inducers. Therefore, EHBR/Eis may be experimentally useful for studying the mechanism of P450 induction by PB and PB-type inducers.

Animals↗
PubMed1996

Point mutation in the alpha-galactosidase A gene of atypical Fabry disease with only nephropathy.

A point mutation in exon 6 of the alpha-galactosidase A gene (alpha-GAL A) was found in a Japanese hemizygous male without typical manifestations of Fabry disease other than renal involvement. This 45-year-old man developed moderate proteinuria and was diagnosed with Fabry disease on the basis of renal histologic findings and prominent decreases in alpha-GAL A activity in his plasma, urine, leukocytes, and skin fibroblasts. Determination of the cDNA sequence of his alpha-GAL A gene revealed substitution of a G to A in codon 301, resulting in a glutamine rather than an arginine residue. Our case is unique in that this patient only demonstrated renal manifestations while all other reported patients with atypical Fabry disease, including a case with the identical point mutation, present with a cardiomyopathy. Direct DNA sequencing of exon 6 and measurement of alpha-GAL A activity among the patient's family confirmed that the mutation was transmitted from his mother.

Biopsy↗
PubMed1996

[Current topics and endoscopic characteristics of the diagnosis how to detect in early gastric or colon cancer].

It is now an era of diversity of treatment for early cancer. Endoscopic diagnosis for both early gastric and colon cancer have focused on the detection of small or minute cancers(smaller than 5 mm), which could be resected by endoscopically. It has been generally considered that endoscopic curative treatment for the small cancer (smaller than 10 mm) is useful from the data of lymph node metastasis in early gastric cancer, however, a high incidence of recurrence (7.5 approximately 22.9%) after endoscopic mucosal resectomy has been found. High cancer rates and high rates of sm invasion are recognized in the superficial type, especially IIc, IIc + IIa, IIa + IIc, of colon tumor. The degree of invasion should be defined and a criteria for indication of endoscopic treatment should be determined from the endoscopic findings.

Colonic Neoplasms↗