Biomedical subjects

N Konishi

Publications and source records attributed to N Konishi.

At least 55 records · Page 3Linked to original sources

PubMed1999

Carcinogenic effects of N-ethyl-N-hydroxyethylnitrosamine and its metabolites in rats and mice.

N-ethyl-N-hydroxyethylnitrosamine (EHEN), a member of the nitrosamine class of carcinogens induces renal cancer. However, since very little is known about the metabolic products of EHEN and their effects, these were investigated in rats and mice. EHEN, N-ethyl-N-formylmethylnitrosamine (EFMN) and N-ethyl-N-carboxymethyl-nitrosamine (ECMN) were administered in the drinking water for 2 weeks and the animals were then maintained until sacrifice at week 32. The urine of the rats was collected over the 2-week exposure period and analyzed by HPLC. The results showed that EHEN but not EFMN or ECMN induces tumors in the kidneys of rats. In mice the lungs were targeted not only by the parent compound but also by both metabolites. The findings suggest that the kidney is the most susceptible organ to EHEN effects in the rat while the lung is the most susceptible organ in mice. These results are consistent with inter-species variation in the metabolism of xenobiotics.

Animals↗

PubMed1999

A novel sperm-specific hypomethylation sequence is a demethylation hotspot in human hepatocellular carcinomas.

Certain human DNA regions are strikingly undermethylated at CpG sites in sperm compared to adult somatic tissues. These sperm-specific hypomethylation sequences are thought to function early in embryogenesis or gametogenesis. By using the restriction landmark genomic scanning (RLGS) cloning method, we have isolated a novel sperm-specific hypomethylation sequence, the status of which changes during spermatogenesis, embryonal growth and differentiation. This sequence is a part of a new 'NotI repeat' consisting of a 1.4 kb repetitive unit sequence named DE-1. The sequence is GC-rich and has high homology to a CpG DNA clone that was isolated by a methyl CpG protein binding column, indicating that it was normally highly methylated. We investigated the methylation status of this sequence. In the normal genome the sequence was methylated, but in the human hepatocellular carcinoma (HCC) genome, the target sequence was demethylated at the cytosine residue of the CpG dinucleotides with high frequency (75% in the previous study). These data suggest that this regional DNA hypomethylation may play a role in both cell differentiation and hepatocarcinogenesis.

Animals↗

PubMed1999

Isolation of NotI clusters hypomethylated in HBV-integrated hepatocellular carcinomas by two-dimensional electrophoresis.

To examine genetic and epigenetic alterations associated with HBV integration in hepatocarcinogenesis, we compared genomic DNA profiles of primary hepatocellular carcinomas (HCCs) and cell lines that either contained or did not contain integrated HBV. To accomplish this, we carried out Restriction Landmark Genomic Scanning (RLGS), a two-dimensional system that displays 2000-3000 Not I landmark sites in a single gel electrophoresis experiment. We identified one Not I landmark spot that showed high signal intensity in HBV-integrated cell lines or in primary HCCs, but not in HCCs or tumor-cell lines free of HBV integration. Cloning of this spot revealed that it consisted of a Not I cluster sequence enriched with CpG dinucleotides. This sequence, hypomethylated in association with HBV integration, was found in the peri-centromeric region of human acrochromosomes. The results demonstrate that epigenetic changes at specific sequences in the genome occur in association with HBV integration during the process of hepatocarcinogenesis.

Base Sequence↗

PubMed1999

Effect of polyphenon-60 on the development of renal cell tumors in rats treated with N-ethyl-N hydroxyethylnitrosamine.

Green tea consumed as a beverage in Asia contains polyphenols, which contain about a 15% mixture of catechins. The present paper reports the effect of polyphenon-60 (60% pure catechin) on the development of renal cell neoplasms in Wistar rats pretreated with N-ethyl-N-hydroxyethylnitrosamine (EHEN): 0.1% polyphenon-60 in block diet was given over a period of 30 weeks while EHEN was given in drinking water for 2 weeks. The results appears to show a tendency for green tea catechins (GTC) to decrease the incidence of renal cell tumors greater than 3 mm in diameter in Wistar rats but not tumors that are less than 3 mm in diameter. Polyphenon-60 did not affect EHEN initiation in the kidneys of rats. It is postulated that free radicals induced by EHEN may be suppressed by GTC, resulting in a lowering of the tendency for tumor growth.

Animals↗

PubMed1999

Posttraumatic intestinal stenosis presenting as a perforation: report of a case.

A 78-year-old woman was admitted to the hospital after falling into a ditch approximately 1 m deep and sustaining a blunt abdominal trauma with a left femur fracture. On the tenth day after admission, symptoms of a small bowel obstruction occurred. A nasogastric tube was inserted, and the symptoms thus improved. She sometimes complained of abdominal pain during the 12 months after the fall, but recovered with conservative management. The next year, she was readmitted to the hospital for a pin extraction of the left femur bone. During this admission, 15 months since her admission after her fall, she again complained of abdominal pain. Abdominal pain increased with a muscular defense, and abdominal X-rays revealed free air. She was referred to our hospital with a diagnosis of perforative peritonitis, and emergency surgery was performed. Upon laparotomy, circumferential stenoses of the small bowel were recognized in the proximal segments about 40cm, 80cm, and 100cm from the ileocecal region. In addition, a perforation and prominent dilatation of the bowel segment was observed just proximal to the stenosis about 100cm from the ileocecal region. She underwent a small intestinal resection at two sites. There were no findings of an intestinal specific ulcer, such as Crohn's disease, intestinal tuberculosis, or malignancy, based on the results of a histopathological examination.

Abdominal Injuries↗

PubMed1999

A highly sensitive enzyme-linked immunoassay for serum free prostate specific antigen (f-PSA).

Monoclonal antibodies (MAbs) were generated against human prostate specific antigen (PSA) to allow development of a sensitive free-PSA (f-PSA) assay. Of a total of 211, 12 could detect only f-PSA, the other 199 MAbs binding to both f-PSA and complex-PSA. In the present study, one MAb (no. 5C6) specific for f-PSA and another (no. 79) reacting with both forms were used to develop an enzyme-linked immunoassay (ELISA) for serum f-PSA. The detection limit was established as 0.008 microg/l (n = 20, mean of zero standard + 3 S.D.) and the average recovery of f-PSA was 93-102%. The within-run and between-day coefficient of variation (CV) varied from 5.4-7.4% and 4.8-6.5%, respectively. The cross-reactivity of the assay to PSA-alpha1-antichymotrypsin complex was determined to be < 0.4%.

Animals↗

PubMed1999

Association of 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa.

It is well documented that gastric mucosa can increase its resistance to mucosal damage caused by aspirin during repeated long-term administration of aspirin. However, the underlying mechanism of this adaptation is not well established. In the present study, we investigated the effect of long-term (chronic) administration of aspirin on expression of heat shock proteins (HSPs), which are known as endogenous cytoprotectants, in rat gastric mucosa. Rats were administered aspirin (100 mg/kg) daily for up to 20 days. After various periods of aspirin administration, a high dose of aspirin (250 mg/kg) was administered, and the mucosal damage was assessed. Expression of heat shock proteins (HSPs) in gastric mucosa was evaluated by Western blot. Intracellular localization of each HSP was studied immunohistochemically. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels were also investigated. Long-term aspirin administration resulted in development of resistance to aspirin-induced mucosal damage, and the increase of HSP72 expression correlated with mucosal resistance to aspirin. No significant increase was observed in HSP60 and HSP90 levels. Immunohistochemical study showed an increase of HSP72 in the cytoplasm of mucosal surface cells. The PGE2 level was suppressed and no change in the level of LTB4 was observed. It is possible that HSP72 could play important roles in gastric mucosal adaptation when the PGE2 level is suppressed by NSAIDs.

Adaptation, Physiological↗

PubMed1999

E-cadherin and alpha-, beta- and gamma-catenin expression in prostate cancers: correlation with tumour invasion.

The E-cadherin-catenin complex plays an important role in establishing and maintaining intercellular connections and morphogenesis and reduced expression of its constituent molecules is associated with invasion and metastasis. In the present study, we examined E-cadherin and alpha-, beta- and gamma-catenin levels in tumour tissues obtained by radical prostatectomy in order to investigate the relationship with histopathological tumour invasion. Immunohistochemical findings for 45 prostate cancer specimens demonstrated aberrant expression of each molecule to be associated with dedifferentiation and, in addition, alteration of staining patterns for the three types of catenin was significantly correlated with capsular but not lymphatic or vascular invasion. The data thus suggest that three types of catenin may be useful predictive markers for biological aggressiveness of prostate cancer.

Aged↗

PubMed1999

Expression of pepsinogen II with androgen and estrogen receptors in human prostate carcinoma.

The expression of pepsinogen II (PG II), an aspartyl proteinase usually involved in the digestion of proteins in the stomach, was immunohistochemically investigated in conjunction with androgen (AR) and estrogen receptor (ER) status in prostate adenocarcinomas. Of a total of 38 samples obtained from radical prostatectomies, 23 tumors (60.5%) were positive for PG II and there was a significant positive correlation to the expression of AR but not to ER. Cells positive for PG II were localized mainly to the peripheral zones of tumorous glands which, in normal prostate, are negative, and in areas also expressing AR. In addition, a significant correlation between AR and ER was detected in the prostate carcinomas examined, which suggests a hormone-dependent status. On the basis of these results, PG II expression might be closely related to hormonal alterations associated with the development of prostate tumors.

Adenocarcinoma↗

PubMed1999

Structure and enzymatic properties of genetically truncated forms of the water-insoluble glucan-synthesizing glucosyltransferase from Streptococcus sobrinus.

Glucosyltransferase-I (GTF-I: 175 kDa) of a cariogenic bacterium, Streptococcus sobrinus 6715, mediates the conversion of water-soluble dextran (alpha-1,6-glucan) into a water-insoluble form by making numerous alpha-1,3-glucan branches along the dextran chains with sucrose as the glucosyl donor. The structures and catalytic properties were compared for two GTF-I fragments, GTF-I' (138 kDa) and GS (110 kDa). Both lack the N-terminal 84 residues of GTF-I. While GTF-I' still contains four of the six C-terminal repeats characteristic of streptococcal glucosyltransferases, GS lacks all of them. Electron microscopy of negatively stained samples indicated a double-domain structure for GTF-I', consisting of a spherical head with a smaller spherical tail, which was occasionally seen as a long extension. GS was seen just as the head portion of GTF-I'. In the absence of dextran, both fragments simply hydrolyzed sucrose with similar K(m) and k(cat) values at low concentrations (<5 mM). At higher sucrose concentrations (>10 mM), however, GTF-I' exhibited glucosyl transfer activity to form insoluble alpha-1, 3-glucans. So did GS, but less efficiently. Dextran increased the rate and efficiency of the glucosyl transfer by GTF-I'. On removal of the C-terminal repeats of GTF-I' by mild trypsin treatment, this dextran-stimulated transfer was completely lost and the dextran-independent transfer became less efficient. These results indicate that the N-terminal two-thirds of the GTF-I sequence are organized as a structurally and functionally independent domain to catalyze not only sucrose hydrolysis but also glucosyl transfer to form alpha-1,3-glucan chains, although not efficiently; the C-terminal repeat increases the efficiency of the intrinsic glucosyl transfer by the N-terminal domain as well as rendering the whole molecule primer-dependent for far more efficient insoluble glucan synthesis.

Bacterial Proteins↗

PubMed1999

PTEN/MMAC1 mutations in hepatocellular carcinomas: somatic inactivation of both alleles in tumors.

Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1-bp insertion at codon 83-84 in exon 4 and two 4-bp deletions, both at codon 318-319 in exon 8; two C-to-G transversion mutation, both at -9 bp from the initiation codon in the 5' non-coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors.

Alleles↗

PubMed1999

DNA alterations in human oral squamous cell carcinomas detected by restriction landmark genomic scanning.

Genetic abnormalities in human oral squamous cell carcinomas (OSCC) were examined using restriction landmark genomic scanning (RLGS), a method of two-dimensional gel analysis allowing detection of amplifications and other aberrations in genomic DNA. DNAs from 11 oral tumours as well as from contiguous normal squamous epithelium, were cleaved with the restriction enzyme Not I, [32p] end-labeled and electrophoretically size-fractionated. Following a second digestion employing Hinf I, the further fragmented DNA was again electrophoretically separated. Five fragments/spots were found amplified in at least 64% (7/11) (chromosome nos. 4, 9-12 or 22) of carcinomas, with one of these spots amplified in 100% (chromosome no. 4) of tumour samples. In addition, six other spots were frequently reduced in at least 55% (chromosome nos. 15 or 9-12) of tumour tissues. Further characterization of these common changes is needed to determine if they represent important alterations in OSCC.

Carcinoma, Squamous Cell↗

PubMed1999

[Drug-resistance and definitive type 104 of Salmonella serovar typhimurium isolated from sporadic cases in Tokyo, 1980-1998].

A total of 674 Salmonella serovar Typhimurium (S. Typhimurium) strains consisting of 522 domestic strains and 152 imported strains isolated in Tokyo, 1980-1998, were examined regarding their drug-resistance and phage-type. Domestic strains accounted for 6.2% of all Salmonella (8,359 strains) isolated from domestic cases, and imported strains accounted for 3.7% of all Salmonella (4,083 strains) isolated from imported cases. A drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 245 strains (46.9%) of the domestic strains and 109 strains (71.7%) of the imported strains were resistant to some of the drugs, excluding FOM and NFLX. Drugs with a high resistance rate were TC, SM, ABPC, and CP for both groups. Drug-resistance patterns of the resistant strains varied among the 40 types. Among those, prevalent patterns recognized were CP.TC.SM.ABPC, CP.TC.SM.KM.ABPC, TC.SM, SM, and TC.KM in the domestic strains, and TC, CP.TC.SM.ABPC, CP.TC.SM.KM.ABPC, CP.TC.SM.KM.ABPC.ST and TC.KM in the imported strains. The results of the phage-typing test revealed that 31 strains of 52 domestic strains tested, and 13 strains of 46 imported strains tested were definitive type 104 (DT104). Those resistance patterns were CP.TC.SM.ABPC.SU (43 strains) and CP.TC.SM.KM.ABPC.SU (1 strain).

Anti-Bacterial Agents↗

PubMed1999

[Outbreak case caused by different colicin type of Shigella sonnei in a day nursery in Tokyo (1998)].

From October through December, 1998, person to person infection caused by Shigella sonnei had occurred in the day nursery in Hachioji-city Tokyo, and a total of 41 patients including 3 suspected cases and 3 carriers had been confirmed. Although one case was imported case which is one-year-old kindergarten child, the remaining was domestic case. Of patients, 33 cases (80.5%) were a three-year-old kindergarten children and their families, accounting for 20 and 13 cases, respectively. From the data of symptom onset of patients, epidemic could distinguish to the former part and the later part. The recur or reinfection, and re-detection case was observed in the later part. Clinical symptom of the patients was diarrhea (100%), fever (80%) and abdominal cramps (70%), and LVFX for adult or FOM for child was used for the therapy. In the colicin typing test and the antibiotic susceptibility test for 9 reagents, almost isolates in the former part were type 0 and susceptible, and MBC for FOM ranged from 6.25 to 100 micrograms/ml, whereas those in the later part was type 2 and resistant for the TC, and showed highly MBC for FOM with 50 or 100 micrograms/ml. However, both isolates showed same patterns in plasmid profiles and DNA fingerprints by RAPD analysis. On the other hand, the strain from imported case was also colicin 0, but it was different as regards resistant for ABPC and ST and two genetic analysis.

Adult↗

PubMed1999

[Incidence of Salmonella serovar Hadar from sporadic cases in Tokyo, and drug resistance of isolates].

A total of 780 Salmonella serovar Hadar (S. Hadar) strains consisting of 601 domestic strains and 179 imported strains isolated in Tokyo, 1980-1998, were examined regarding their incidence and drug-resistance. Domestic strains accounted for 7.2% of all Salmonella (8,359 strains) isolated from domestic cases, and imported strains accounted for 4.4% of all Salmonella (4,083 strains) isolated from imported cases. A drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOR, and NFLX) showed that 586 strains (97.6%) of the domestic strains and 175 strains (97.8%) of the imported strains were resistant to some of the drugs, excluding NFLX. Drugs with a high resistance rate were TC and SM for both groups. Drug-resistance patterns of the resistant strains varied among the 24 types. Among those, prevalent patterns recognized were TC.SM.KM (231 strains), TC.SM (205 strains), and TC.SM.KM.ABPC (65 strains) in the domestic strains, and TC.SM (135 strains) and TC (13 strains) in the imported strains.

Drug Resistance, Microbial↗

PubMed1999

[Strains of Shigella sonnei recently isolated in Tokyo].

A total of 341 Shigella sonnei strains consisting of 94 domestic strains and 247 imported strains isolated during 1990-1997 in Tokyo, were examined regarding their colicine-type, drug-resistance and ornithine-utilization. The colicine typing results showed that the domestic strains were classified into 7 types, and the imported strains were classified into 13 types. Among the colicine-types identified, 8-type, 0-type, 6-type and 12-type were predominant in the domestic strains, whereas 6-type, 0-type, 8-type, 9A-type and 12-type were predominant in the imported strains. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM and NFLX) showed that 89.4% of the domestic strains and 85.4% of the imported strains were resistant to some of the drugs except FOM and NFLX. Drugs with a high resistant rate were SM, TC and ST for both groups. Drug-resistance patterns of the resistant strains varied in 22 types. Among those, a triple drug-resistance type with TC.SM.ST was found in the most frequent pattern in both groups. The results of the ornithine-utilization test revealed that 28.7% of the domestic strains and 8.1% of the imported strains were negative. The ornithine-negative strains in the same source had a similar plasmid-profile, but generally there was no correlation between the different sources.

Drug Resistance, Microbial↗

PubMed1999

Immunohistochemical analysis of midkine expression in human prostate carcinoma.

Midkine (MK) is a growth/differentiation factor frequently expressed at high levels in some types of human malignancies. To investigate whether MK is a useful marker in prostate carcinogenesis, immunohistochemical analysis was performed on samples of both latent and clinical prostate cancers of various stages, as well as on specimens of normal gland and prostatic intraepithelial neoplasia (PIN). Of the 80 clinical cancers examined, 69 specimens (86.3%) were immunoreactive for MK, with metastatic lesions generally showing higher expression than the corresponding primaries; normal prostate tissues were negative or showed only weak staining. Midkine was also detected in 12 of 15 latent cancers (80%) and in 12 of 16 cases of PIN (75%). In sections of whole prostate, MK showed variable expression through tumorous sections, probably in reflection of heterogeneous cell populations. The results demonstrate the possible value of MK as a marker for early and latent disease, as well as for more advanced clinical stages of prostate cancer.

Aged↗

PubMed1999

Genomic alterations in human meningiomas detected by restriction landmark genomic scanning and immunohistochemical studies.

Using restriction landmark genomic scanning (RLGS) methods, 21 samples of human meningioma were analyzed. We found 3 alterations in the genomic DNAs of tumor samples located on chromosomes 5, 14 and 17 which appear to be common to the meningothelial subtype. Two other separate genetic abnormalities located on chromosomes 9-12 and 20 are apparently associated with atypical meningiomas. In addition, the neurofibromatosis type 2 gene is apparently involved in more than half of the tumor samples. There appear to be both common and type-specific genetic mutations associated with the formation and progression of human meningiomas.

Adult↗