Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 91 records · Page 5Linked to original sources

PubMed1999

A novel case of a sporadic desmoid tumour with mutation of the beta catenin gene.

A 42 year old man without familial adenomatous polyposis had recurrent desmoid tumours in the left subclavicular site. Histological examination showed a typical desmoid tumour. Molecular analysis was performed in genomic DNA from this tumour, using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing methods. No mutation could be detected in the entire coding sequence of the APC gene, nor in H-ras, K-ras, N-ras, or p53 genes. On seeking a mutation of the beta catenin gene (CTNNB1), an activating mutation from ACC (Thr) to GCC (Ala) at codon 41 was found. Immunohistochemical staining showed that accumulated beta catenin protein was predominantly localised in the nuclei of desmoid cells. This is the first example of a sporadic desmoid tumour in which a mutation of the beta catenin gene was revealed.

Adult↗

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

Development of X-ray TV M-mode and reconstructed ultrasound M-mode methods for investigating tongue movement during swallowing in humans.

There were two purposes of this study. The first purpose was to introduce the "X-ray TV M-mode waveform" which is reconstructed from sequential X-ray TV images and the "reconstructed ultrasound M-mode waveform" which is delivered from ultrasound B-mode images. The second purpose was to evaluate the usefulness of these two types of waveforms in the investigation of tongue movement during swallowing. The instrument system employed in this study consisted of ultrasound and X-ray TV synchronized by a time marker. After the X-ray images and ultrasound B-mode images were recorded on an optical disk, X-ray TV M-mode waveform and ultrasound M-mode waveform were reconstructed using an MC 68030/OS-9 computer. No significant differences in quality of images were observed between the X-ray TV M-mode waveform and the reconstructed ultrasound M-mode waveform. Therefore, both waveforms of the X-ray TV M-mode and the reconstructed ultrasound M-mode are equally useful in measuring tongue movement.

Adult↗

PubMed1999

Structure-activity relationships of carbapenems to the antagonism of the antipseudomonal activity of other beta-lactam agents and to the beta-lactamase inducibility in Pseudomonas aeruginosa: effects of 1beta-methyl group and C-2 side chain.

The antagonism of the antipseudomonal activity of ceftazidime by meropenem (1a) was much less than those by imipenem (2a) and panipenem (2b). To reveal the major structural features of carbapenem compounds responsible for the antagonism, we investigated the structure-activity relationships of carbapenems to their antagonism of the antipseudomonal activity of ceftazidime and to their beta-lactamase-inducibility in P. aeruginosa. The antagonistic effect of 1a was less than that of desmethyl-meropenem (1b). Two other meropenem-analogues (3, 4), with the highly basic C-2 side chain, showed greater antagonistic effects than that of 1a, which has a weakly basic C-2 side chain. The beta-lactamase-inducibility of 1a in P. aeruginosa was lower than those of 2a, 1b and 4. These results indicated that the antagonism of the antipseudomonal activity of ceftazidime by carbapenems was due to the induction of beta-lactamase in P. aeruginosa. As a result of the study on the structure-activity relationships, we clarified that the introduction of a 1beta-methyl group and/or the reduction of the basicity (cationic character) of the C-2 side chain in carbapenem skeleton decreased the antagonistic effect of carbapenems on the antipseudomonal activity of ceftazidime resulted mainly from the decreasing the beta-lactamase inducibility.

Carbapenems↗

PubMed1999

Microsatellite instability and loss of heterozygosity in primary and secondary proliferative lesions of the parathyroid gland.

Clonality and genetic abnormalities were evaluated to characterize proliferative lesions of the parathyroid gland. Fourteen lesions from patients with single-gland proliferation (adenomas [PA]), 6 lesions from patients with multiple-gland proliferation (primary hyperparathyroidism [PHPT]), and 47 lesions from 16 patients with secondary hyperparathyroidism (SHPT) were examined. Based on the X chromatin inactivation pattern, which was revealed by a HUMARA assay of lesions from female patients (n = 34; 24 informative cases), monoclonality was demonstrated in 6 of 10 PA (60%), 2 of 5 PHPT (40%), and 6 of 9 SHPT lesions (14 of 27 lesions, 52%). By PCR analysis using 17 microsatellite markers on eight chromosomes (chromosomes 1, 2, 3, 5, 6, 11, 13, and 17), loss of heterozygosity was sporadically observed in 4 of 14 PA, 3 of 6 PHPT, and 7 of 47 SHPT lesions, in most cases on a single locus of chromosome 11. On the other hand, microsatellite instability was observed more frequently: ie, in six PA, five PHPT, and nine SHPT lesions. The profile of microsatellite instability depended on the type of proliferation: microsatellite instability (MI) seemed to cluster in the region of chromosome 11 in PA. Microsatellite instability on TP53 was observed in 3 of 6 PHPT lesions and in 2 of 47 SHPT lesions but in no PA lesions. Microsatellite instability on Mfd47 was observed in only some cases of SHPT. Although no significant correlation was identified among histologic features, clonality, and genetic abnormalities in cases of primary proliferation, genetic abnormalities were more frequently observed in SHPT lesions that lacked fat tissues. Thus, genetic instability might be important in proliferative disorders of the parathyroid gland, either with or without uremia. However, genetic instability seems to be induced by different mechanisms in the three types of proliferation studied. In SHPT, the absence of fat tissues may indicate that the proliferation is accompanied by genetic changes.

Adenoma↗

PubMed1998

Telomerase activity in gastrointestinal stromal tumors.

BACKGROUND: Telomerase activity has been observed in 80-90% of carcinomas derived from various organs. However, to the authors' knowledge this report is the first assessment of telomerase activity in gastrointestinal stromal tumors (GISTs). METHODS: Telomerase activity was analyzed by the telomerase repeat amplification protocol assay in 29 tumors from 26 patients (23 primary tumors from 22 patients, 1 pair of primary and metastatic tumors from 1 patient, and 4 metastatic tumors from 3 patients). Phenotypes, tumor cell proliferation, and overexpression of p53 protein were evaluated immunohistochemically. RESULTS: Seven of 24 primary tumors (29%) and 5 of 5 metastatic tumors (100%) showed telomerase activity. Telomerase activity positive (+) GISTs were significantly larger (P < 0.05) and showed a significantly higher rate of proliferation than telomerase activity negative (-) tumors (P < 0.0001). All telomerase activity (+) GISTs were classified histologically as high risk tumors. Conversely, 15 of the 17 telomerase (-) GISTs were classified histologically as low risk tumors (P < 0.0001). With regard to p53 immunoreactivity, two and seven telomerase activity (+) tumors showed diffuse and sporadic positivity, respectively, whereas only five telomerase activity (-) tumors showed only focal or sporadic positivity. Telomerase activity was correlated significantly with poor prognosis (P < 0.05) in the patients in whom the primary GISTs were evaluated (n = 23). CONCLUSIONS: Telomerase activity may be a useful marker for evaluating the malignant potential of GIST. A distinct subgroup of GISTs is a target for therapy with a telomerase inhibitor.

Adult↗

PubMed1998

Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease.

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.

Adult↗

PubMed1998

Catabolic fate of dietary trilinoleoylglycerol hydroperoxides in rat gastrointestines.

To elucidate whether dietary lipid peroxides are absorbed in the body, the catabolic fate of trilinoleoylglycerol hydroperoxides (TL-OOH), in the gastrointestines of rats was examined. Oxidized trilinoleoylglycerol with a peroxide value of 1000 meq/kg, 0.5 or 20 mg, was dosed intragastrically to rat together with 59.5 or 40 mg unoxidized trilinoleoylglycerol, respectively. The fate of TL-OOH in gastric and intestinal lumina was determined by high-performance liquid chromatography periodically until 240 min after treatment. At low dose, TL-OOH was soon broken down to linoleic acid hydroperoxides (LA-OOH) and hydroxyls, probably through gastric lipases, whereas at high dose, TL-OOH was retained in the stomach. In both cases, TL-OOH did not reach the intestines, though the unoxidized lipids moved to the intestines. When LA-OOH was given intragastrically, the lipids decomposed in the stomach, and linoleic acid hydroxyls, hexanal, 9-oxononanoic acid, and two novel compounds were detected 30 min after treatment. The novel compounds were identified to be epoxyketones, 11-oxo-12,13-epoxy-9- and 11-oxo-9,10-epoxy-12-octadecenoic acids. Thus, dietary TL-OOH was broken down in the stomach releasing, LA-OOH which decomposed further, and did not reach the intestines.

Animals↗

PubMed1998

Dietary hydroperoxides of linoleic acid decompose to aldehydes in stomach before being absorbed into the body.

Our previous study (Biochim. Biophys. Acta 1393 (1998) 336-348, this issue) found that dietary hydroperoxides of trilinoleoylglycerol were broken down, releasing linoleic acid hydroperoxides (LA-OOH) in the stomach without reaching the intestines. The present paper describes the catabolic fate of LA-OOH in rat gastrointestines, in an attempt to elucidate those products which can be absorbed into the body. At an intragastric dose of 6.5 or 18 mumol, LA-OOH was not transported to the intestines as determined by HPLC. At large doses (200 or 800 mumol), much greater than that in the daily diet, there was partial leakage of LA-OOH to the intestines. The periodical fate was analyzed with 17.2 mumol [U-14C]LA-OOH chemically and radiochemically. Exemplifying the product composition at 30 min after treatment (as percentage of dosed amount), 27% unchanged LA-OOH, 9.7% epoxyketones, 3.5% hydroxyls (LA-OH), 2.4% decomposed aldehydes, and 13% unknown products were found in the gastric lumen. Another 25% was incorporated in the gastric tissue, and the other 6.4% occurred in the intestinal lumen and tissue as decomposed aldehyde. The LA-OH further decomposed to aldehydes with time in the stomach. When an aldehyde mixture was prepared and dosed, significant increases in hexanal and 4-hydroxynonenal were detected in the liver 15 h later. These results show that the dietary LA-OOH is decomposed to aldehydes in the stomach and that aldehydes are partly absorbed into the body.

Aldehydes↗

PubMed1998

Selective down-regulation of human papillomavirus transcription by 2-deoxyglucose.

The glycolytic pathway inhibitor 2-deoxyglucose (2-DG) is capable of suppressing the transcription of the human pathogenic papillomavirus type 18 (HPV 18) in cervical carcinoma cells and derived non-tumorigenic somatic cell hybrids at the level of transcription initiation. HPV down-regulation is selective, since other reference genes are not affected or even up-regulated under the same experimental conditions. Moreover, 2-DG appears to restore the normal half-life of the tumor suppressor gene product p53, because the protein is strongly up-regulated after HPV 18 E6/E7 suppression. The observed 2-DG-effect is not cytotoxic and is reversible after refeeding with fresh medium. HPV 18 suppression by 2-DG can be completely abrogated by simultaneous treatment with the intracellular Ca2+ antagonist TMB-8, indicating that Ca2+, a known intracellular "second messenger", is involved in this process. Elevated c-myc and p53 expression appears to be responsible for the time-dependent accumulation of apoptotic cells after prolonged 2-DG treatment. The finding that 2-DG acts selectively against the expression of a human pathogenic papillomavirus strongly suggests that an appropriate level of glycolysis is not only a peculiarity of growing tumors, but even may be an essential prerequisite for the maintenance of virus-specific E6/E7 gene expression. Our results may have substantial implications for the potential therapeutic application of 2-DG or other glucose derivatives in the treatment of precancerous and malignant HPV-associated lesions.

Adenosine Triphosphate↗

PubMed1998

Expression pattern of a novel death-promoting gene, DP5, in the developing murine nervous system.

We examined the expression patterns of the DP5 gene, which encodes a protein with apoptosis-inducing activity, in the developing nervous system of mice. This gene was primarily expressed in the spinal motor neurons and peripheral sensory ganglia of mouse embryos and transiently in the postnatal brain, particularly in the entorhinal cortex and hippocampus. These expression patterns suggest that the DP5 gene may be involved in the apoptosis, if not all, of the developing nervous system.

Amino Acid Sequence↗

PubMed1998

Polymorphism of the NADH/NADPH oxidase p22 phox gene in patients with coronary artery disease.

BACKGROUND: Oxidative stress in the vasculature has been implicated in the pathogenesis of coronary artery disease (CAD). NADH/NADPH oxidase is a key enzyme of superoxide production in the vasculature. p22 phox, an essential component of NADH/NADPH oxidase, has four types of polymorphism. The C242T polymorphism changes histidine-72 to tyrosine, located in the potential heme-binding sites, whereas A640G polymorphism is located in the 3' untranslated region. METHODS AND RESULTS: We investigated whether these polymorphisms were associated with risk of CAD by use of restriction fragment length polymorphism (RFLP). The prevalence of the TC + TT genotype of the C242T polymorphism was significantly more frequent in control subjects (n=201) than in the patients with CAD (n=201). The odds ratio of the TC + TT versus CC genotype of the C242T polymorphism between control subjects and case patients was 0.49 (95% CI, 0.28 to 0.87) (P=.015). The prevalence of the genotypes of the A640G polymorphism was not different between groups. The association of C242T polymorphism of the p22 phox gene with CAD was statistically significant and independent of other risk factors. CONCLUSIONS: The mutation of the potential heme-binding site of the p22 phox gene may reduce susceptibility to CAD. Our observations suggest that the C242T polymorphism of the p22 phox gene is a novel genetic marker that has a protective effect on coronary risk.

Case-Control Studies↗

PubMed1998

Clinicopathologic and genetic features of nonfamilial colorectal carcinomas with DNA replication errors.

BACKGROUND: DNA replication errors (RERs) are closely associated with hereditary nonpolyposis colorectal carcinoma (HNPCC). Recently, alterations in DNA mismatch repair genes, including hMSH2, hMLH1, and hPMS2, have been implicated in the pathogenesis of HNPCC: Several studies have demonstrated RER in 13-17% of nonfamilial colorectal carcinomas. It is unclear, however, as to whether or not these RER positive nonfamilial colorectal carcinomas are incomplete forms of HNPCC or are caused by incidental alterations of DNA mismatch repair genes. Consequently, the authors studied the characteristics of RER positive nonfamilial colorectal carcinomas, placing particular emphasis on hMSH2 and hMLH1 gene mutations. METHODS: Fresh or frozen samples of 103 nonfamilial colorectal carcinomas were examined for RERs using the polymerase chain reaction (PCR) and specific microsatellite primers. The authors also identified mutations of the hMSH2 and hMLH1 genes in RER positive samples by a PCR single strand conformational polymorphism analysis followed by direct nucleotide sequencing. RESULTS: The incidence of RER was 15.7% (17/103) in nonfamilial colorectal carcinomas, and only 1 case, which was found in the ascending colon, showed a somatic mutation at exon 12 in the hMSH2 gene. Neither germline nor somatic mutations of the hMSH2 or hMLH1 genes could be found in any of the remaining RER positive tumors. RER positive nonfamilial carcinomas tended to be located more frequently in the right colon. There was no increased prevalence in young patients, and the clinicopathologic characteristics of HNPCC were absent in the patients with RER positive nonfamilial colorectal carcinoma. CONCLUSIONS: Based on these findings, the carcinogenesis of RER positive nonfamilial colorectal carcinoma is considered different from that of HNPCC:

Adaptor Proteins, Signal Transducing↗

PubMed1998

Significance of microsatellite instability in different types of early-stage nonfamilial colorectal carcinomas.

PURPOSE: The aim of this study was to investigate the genetic alterations of early-stage nonfamilial colorectal carcinomas regarding microsatellite instability, with special reference to the shape of the tumors and the site of the lesions. METHODS: Formalin-fixed, paraffin-embedded specimens of 44 early-stage nonfamilial colorectal carcinomas were examined for microsatellite instability with use of polymerase chain reaction. RESULTS: The 44 carcinomas consisted of 16 flat carcinomas and 28 polypoid carcinomas. Nineteen carcinomas were located in the proximal colon (9 flat type and 10 polypoid type), whereas 25 were in the distal colon and rectum (7 flat type and 18 polypoid type). Ten (22.7 percent) of the 44 carcinomas had at least one positive locus, whereas five (11.4 percent) of them had two or more positive loci. In the proximal colon the percentage of flat carcinomas with at least one positive locus was significantly greater than that of the polypoid carcinomas (4/9 (44 percent) vs. 0/10; P = 0.04). Six patients had synchronous or metachronous colorectal carcinomas or both. They harbored microsatellite instability more frequently than patients with single colorectal carcinomas, and the differences were statistically significant (P < 0.02). CONCLUSIONS: These data suggest that in nonfamilial carcinomas in the proximal colon, the genetic pathway in flat carcinomas may be different from that in polypoid carcinomas.

Adult↗

PubMed1998

The therapeutic effect of hypertonic solutions on the changes in the effective circulating plasma volume in acute necrotizing pancreatitis in rats.

While hypovolemia or hypovolemic shock is dominant in the early stage of severe acute pancreatitis, there have been few studies on the effects of hypertonic solutions in the management of this disease. We conducted this study to evaluate the therapeutic effects of hypertonic saline solutions (HS) on the course of severe acute pancreatitis in rats. Pancreatitis was induced in male Wistar rats by injecting a 5% solution of sodium taurocholate into the biliopancreatic duct. The effective circulating plasma volume (ECPV) was measured using radioiodinated [125I]bovine serum albumin. Samples of blood and of ascitic fluid were obtained 3, 6, and 12 h after the onset of pancreatitis. Lactated Ringer's solution (LR) and HS were administered consecutively for 3 h beginning 3 h after the induction of pancreatitis. ECPV was measured 6 h after the onset of pancreatitis. The survival rates were investigated for up to 10 days. The mean ECPV decreased significantly from 24.9 +/- 1.1 ml/kg before disease onset to 11.5 +/- 1.3 ml/kg 6 h postoperatively. LR failed to achieve a normal value for ECPV even following a 150 ml/kg infusion. HS200 and HS300 restored the ECPV to the normal level, and with smaller volumes infused. All rats in the untreated group died within 3 days. LR and HS improved the survival rates, with the infusion of HS200, 100 ml/kg, thus attaining a 45% survival at 10 days.

Analysis of Variance↗

PubMed1998

Primary hyperparathyroidism and acute pancreatitis during pregnancy. Report of a case and a review of the English and Japanese literature.

The simultaneous occurrence of primary hyperparathyroidism (PHPT) and pancreatitis during pregnancy is very rare. We present a case of concurrent PHPT and pancreatitis in pregnancy and review 13 cases reported in the English and Japanese literature. Two maternal and three fetal deaths occurred. Mortality seemed to be related to delayed resection of the parathyroid tumor. Morphologically, severe pancreatitis was only seen in three cases, whereas even edematous or focal pancreatitis caused the same symptoms as clinically severe pancreatitis. Acute pancreatitis should be kept in mind in the differential diagnosis of unexplained nausea and abdominal pain during pregnancy, and hyper-or normocalcemia in the severe form of pancreatitis should be a clue to concurrent PHPT.

Acute Disease↗

PubMed1998

Hirschsprung's disease in an adult patient with familial occurrence: report of a case.

Hirschsprung's disease is almost always associated with newborns or infants; however, we report herein the unusual case of a 46-year-old woman in whom the symptoms of Hirschsprung's disease emerged late in adult life. The involved rectosigmoid region was successfully removed by performing Duhamel's operation with a diverting colostomy. After the colostomy was closed, she regained normal defecatory function. She had one male child affected by Hirschsprung's disease of the total colon type who was operated on as a 12-month-old baby. The genetic predisposition of Hirschsprung's disease has been reported, but its mode of inheritance has not yet been clarified. Moreover, most papers on the familial occurrence of this disease have reported that siblings were affected. Our patient was unique for the definite occurrence of the disease in successive generations. The features of Hirschsprung's disease in adults and the familial occurrence are discussed with a review of the literature.

Anastomosis, Surgical↗

PubMed1998

Important microsatellite markers in the investigation of replication errors (RER) in colorectal carcinomas.

BACKGROUND: DNA replication errors (RER) have been found in hereditary nonpolyposis colorectal carcinomas and in sporadic colorectal carcinomas. The incidence of RER depends on which and how many markers are examined. The main purpose of the present study was to determine the key markers for detecting RER most efficiently. METHODS: The RER status of 76 sporadic advanced colorectal carcinomas in the proximal colon were investigated. Seven microsatellite markers (D2S123, D3S1029, D3S1611, D2S72, TP53, Mfd26 and BAT26) were chosen to determine the RER status by PCR using the non-Rl method, because these seven markers have frequently been used in other studies and also detect RER. RESULTS: It was found that 44.7% of sporadic colorectal advanced carcinomas in the proximal colon (34 of 76) showed RER at one or more loci. Among these 34 cases, RER was present at three or more markers (severe RER) in 22. All 22 of these cases showed RER at BAT26 and TP53. The other 12 cases with RER showed RER at one or two markers (mild RER). Eleven of these 12 cases (91%) showed RER at Mfd26 and there were one or two cases with mild RER at each of the other loci. CONCLUSIONS: When one intends to analyze routinely a large number of cases, an analysis of two or three markers (Mfd26 and BAT26 or TP53) is considered to be sufficient for detecting mild and severe RER.

Aged↗