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Biomedical subjects

Y Haraguchi

Publications and source records attributed to Y Haraguchi.

At least 55 records · Page 3Linked to original sources

The incidence of chromogranin A defined endocrine cells decreases with tumour progression in gastric adenocarcinoma.

The immunohistochemical expression of chromogranin A (CGA) was investigated in 60 normal mucosas, 95 primary tumours and 38 metastatic lymph nodes. CGA was expressed in 100% of the normal mucosas, 61% of the primary tumours that were restricted within the submucosal layer, 21% of the primary tumours that invaded beyond the submucosal layer, and 11% of the metastatic lymph nodes. The 5-year survival rates in patients with negative and positive expression of CGA in primary tumours were 60.4% and 74.6%, respectively. These results indicate that endocrine cells occupy an integral part of gastric adenocarcinoma with regard to tumour progression.

Adenocarcinoma↗

Immunohistochemical expression of tenascin in normal stomach tissue, gastric carcinomas and gastric carcinoma in lymph nodes.

The immunohistochemical expression of tenascin was examined in the normal adult mucosa of the stomach, primary tumours and lymph node metastases of gastric cancer patients. In normal gastric tissue tenascin was expressed in the muscularis mucosae, muscularis propria and vessel walls, however it was not expressed in either the mucosal connective tissue or the stromal tissue in the submucosal layer. In gastric cancer, tenascin was expressed in 35 of 85 primary tumours, and in 8 of 25 metastases in lymph nodes. Tenascin was located in the fibrous stroma surrounding foci of cancer. The expression of tenascin in the primary tumour did not correlate with the depth of invasion, lymph node metastasis or prognosis. Tenascin appears during the process of either malignant transformation or tumour progression in gastric cancer, and the positive expression of tenascin may be useful as a stromal marker for the early detection of gastric cancer.

Adult↗

Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types.

Age Factors↗

Effect of lansoprazole on peptic ulcers.

Lansoprazole is the first proton pump inhibitor developed in Japan. We studied the clinical efficacy of lansoprazole 30 mg q.d. on peptic ulcers and the subsequent relapse rates. The endoscopic healing rate of gastric ulcers (n = 86) after 8 weeks of treatment and duodenal ulcers (n = 52) after 6 weeks of treatment were 94.2 and 96.2%, respectively. The endoscopic S2-stage shift rates in gastric and duodenal ulcers were 45.5 and 65.4%, respectively. Factors affecting healing rates of gastric ulcers included colonization by Helicobacter pylori, the size and depth of the ulcers, pretreatment stage, and ulcer history, whereas those factors did not influence healing in duodenal ulcers. The clearance rates of H. pylori after lansoprazole treatment were 54.5% in patients with gastric ulcer and 66.7% in those with duodenal ulcer. The cumulative relapse rates after 1 year with standard maintenance therapy of H2-receptor antagonists (ranitidine, famotidine, and cimetidine) were 15.8% for gastric ulcer and 21.2% for duodenal ulcer. In conclusion, lansoprazole is highly effective in peptic ulcer disease and there are few relapses after treatment. Furthermore, it is suggested that lansoprazole is efficacious against H. pylori at usual clinical doses.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Detection of neutralizing antibodies against human T-cell leukemia virus type 1 using a cell-free infection system and polymerase chain reaction.

We have developed a cell-free infection system to titrate neutralizing antibodies against human T-cell leukemia virus type 1 (HTLV-1) using the polymerase chain reaction (PCR). S+L-CCC (8C) feline kidney or U-251 MG human glioma cells were infected with a cell-free culture supernatant derived from HTLV-1-infected c77 feline cells. DNA was extracted from 8C or U-251 MG cells after incubation for 24 hr and amplified by PCR. The c77 cell supernatant gave discrete bands, whereas those of HTLV-1-positive T cells did not. When the inocula were treated with HTLV-1 antibody-positive human sera or the monoclonal or polyclonal antibody against the peptide 190-199 of HTLV-1 envelope protein gp46, the subsequent formation of HTLV-1 proviral DNA was inhibited. We determined the titers of neutralizing antibodies by densitometrically scanning the intensity of the PCR bands. These titers correlated well with those determined by the plaque assay using a pseudotype of vesicular stomatitis virus bearing the envelope antigens of HTLV-1. At high serum concentrations, many seronegative samples markedly inhibited the plating of the HTLV-1 pseudotype whereas they barely affected results obtained by PCR. Thus, the c77-PCR system can detect neutralizing antibodies against HTLV-1 even at low titers.

Animals↗

Increased incidence of undifferentiated type of gastric cancer with tumor progression in 912 patients with early gastric cancer and 1245 with advanced gastric cancer.

BACKGROUND: There is little information concerning alteration in histologic differentiation with progression of gastric cancers. METHODS: The authors analyzed data of 912 patients with early gastric cancer and 1245 with advanced gastric cancer. All patients underwent gastric resection. Special focus was placed on the grade of histologic differentiation. RESULTS: The undifferentiated type was found in 38% of early gastric cancers and 58% of advanced gastric cancers (P < 0.01). The undifferentiated type was found in 37% of gastric cancers limited to the mucosal layer, and increased with tumor progression into the deep layer to account for 65% of the cancers that invaded the gastric serosa. With regard to tumor location, the undifferentiated type in the gastric body or other locations was more common in patients with advanced gastric cancer (P < 0.01). CONCLUSIONS: One explanation for the histologic predominance of the undifferentiated type in advanced gastric cancer is that in some gastric cancers, the predominant histologic type may be altered from the differentiated to the undifferentiated type with progression of the tumor.

Cell Transformation, Neoplastic↗

OXBOX and REBOX, overlapping promoter elements of the mitochondrial F0F1-ATP synthase beta subunit gene. OXBOX/REBOX in the ATPsyn beta promoter.

Three positive (PR1-3) and one negative (NR1) transcriptional control domain have been tentatively mapped in the promoter of the human F0F1-ATP synthase beta subunit gene (ATPsyn beta) in the context of expression in myogenic cells. Lipofection of promoter-chloramphenicol acetyltransferase fusion constructs into C2C12 myogenic cells revealed that two of the three positive domains (PR1 and PR2) function in both myoblasts and myotubes, whereas the third positive domain (PR3) and the sole negative domain (NR1) seem to function only in myotubes. PR1 contains a cluster of four CCAAT cis-elements, PR2 is a small 44-base pair region containing an SP1-like motif, and PR3 is a region previously shown to be recognized by both OXBOX- and REBOX-binding factors. By site-directed polymerase chain reaction linker mutations, the activity of the OXBOX/REBOX cis-element in myoblasts is shown to be masked by flanking sequences in PR3. The negative domain, NR1, is located between 300 and 1,000 base pairs upstream from the OXBOX/REBOX elements in a region containing multiple Alu repeats. Mobility gel shift analysis of DNA-protein complexes using competitor DNAs verified the involvement of both OXBOX- and REBOX-binding factors in PR3. Similar experiments show SP1-specific binding at PR2. These data with observations of OXBOX and REBOX-specific binding of an OXBOX/REBOX-like region within the conserved sequence block C of the human mitochondrial DNA D-loop sequence are consistent with the idea that OXBOX- and REBOX DNA-binding factors coordinate the expression of mitochondrial energy genes in highly oxidative tissues by working with well characterized general transcription factors such as SP1 and CCAAT DNA-binding proteins, which exist in the nucleus, and MTF, which exists in the mitochondrion.

Animals↗

Inhibition of adsorption of human T-cell-leukemia virus type 1 by a plant lectin, wheat-germ agglutinin.

Thirty-six lectins that recognize various sugar chains were examined for inhibitory activities against infection with human T-cell leukemia virus type I (HTLV-I). Wheat-germ agglutinin (WGA) was the most inhibitory among them: plating of the pseudotype of vesicular-stomatitis virus (VSV) bearing envelope antigens of HTLV-I was markedly inhibited by treatment of indicator cells with WGA just before adsorption, but not by treatment after virus adsorption. Treatment with WGA before adsorption, however, could not inhibit the plating of VSV, VSV pseudotypes of bovine leukemia virus, Moloney murine leukemia virus and human immunodeficiency virus type I. Syncytium formation induced by HTLV-I was also inhibited by WGA upon co-cultivation of U-251 MG human glioma cells or MOLT-4 human T-cells with HTLV-I-producing C91/PL cells. Formation of proviral DNA detected one day after infection was also inhibited when indicator cells had been treated with WGA before adsorption of HTLV-I, but not after its adsorption. These findings indicated that WGA specifically inhibits plating of HTLV-I when added to culture just before adsorption and suggested that a substance(s) containing sugar chains recognized by WGA might be involved in an adsorption step of HTLV-I.

Adsorption↗

The delayed glucocorticoid-responsive and hepatoma cell-selective enhancer of the rat arginase gene is located around intron 7.

Liver-selective transcription of the gene for rat arginase, an ornithine cycle (urea cycle) enzyme, is induced by glucocorticoids in a delayed secondary manner; the mRNA induction by the hormones requires de novo protein synthesis, and is preceded by a time lag of several hours. We searched for a DNA element mediating the glucocorticoid induction of the arginase gene with a transient transfection system using hepatoma cell lines. Within the 233-base pair region that is located 11 kilobases downstream from the transcription start site and that spans the junction of intron 7 and exon 8, we detected an enhancer element that is glucocorticoid-responsive and hepatoma cell-selective. The time course of the glucocorticoid induction through this enhancer element was delayed compared to that through the primary glucocorticoid-responsive mouse mammary tumor virus promoter. Footprint analysis revealed four protein-binding sites in this enhancer region. In gel retardation analysis, each site exhibited a complicated profile characterized by a number of shifted bands, some of which were tissue-selective and others ubiquitous. Gel shift competition and antibody supershift/inhibition analysis demonstrated that two of the four sites are recognized by members of the CCAAT/enhancer binding protein (C/EBP) family, some of which are liver-enriched.

Animals↗

Colonic submucosal tumors: comparison of endoscopic US and target air-enema CT with barium enema study and colonoscopy.

PURPOSE: To compare the imaging characteristics of colonic submucosal tumors at endoscopic ultrasound (US) and target air-enema computed tomography (TACT) with those at conventional double-contrast barium enema study and colonoscopy. MATERIALS AND METHODS: Twenty consecutive patients with suspected colonic submucosal tumors at barium enema study and colonoscopy underwent endoscopic US, TACT, or both. Morphologic features and posture-related change in shape of tumor were evaluated with barium enema study, color and consistency of tumor with colonoscopy, internal echogenicity of tumor and layer of origin in normal colonic wall with endoscopic US, and CT attenuation number with TACT. RESULTS: Eight lipomas, seven carcinoids, three leiomyomas, four lymphangiomas, and one hemangioma were found at histologic examination. Lipomas and lymphangiomas had characteristic findings at endoscopic US and TACT. The differential diagnosis of the other submucosal tumors was facilitated by using endoscopic US. CONCLUSION: Endoscopic US and TACT may play a valuable role in the evaluation of colonic submucosal tumors.

Adult↗

[A case of ischemic colitis due to polyarteritis nodosa].

A 78-year-old female was admitted to our hospital with acute abdomen (abdominal pain and bloody stool). Abdominal examination revealed mild rebound tenderness on the right side. The laboratory data revealed severe inflammation (WBC: 33100/microliters, CRP:35.5 mg/dl). Panperitonitis was suspected because of diffuse and severe abdominal pain and rebound tenderness on the next day. X-ray examination by gastrografin showed mucosal irregularity and tubular narrowing of the tubular narrowing of the ascending colon which indicated ischemic colitis, and an emergency operation was performed. Histological examination of the pathologic specimens revealed fibrinoid necrosis and destruction of the internal lamina in small and medium-size arteries. We report a case diagnosed as ischemic colitis due to polyarteritis nodosa by the findings of its pathologic specimens.

Aged↗

Endoscopic ultrasonography using a 15/20 MHz probe in a direct contact technique: evaluation and application in esophageal and gastric varices.

Endoscopic ultrasonography (EUS) has been recently developed as a new diagnostic technique for portal hypertension. However, its conventional water-filled balloon technique is not suitable for the evaluation of esophageal varices, because the vessel lumen is compressed by the inflated balloon. Particularly for small varices, the vessel tends to collapse and is difficult to display. A miniature ultrasonic probe for use via the forceps channel in EUS has been developed and is expected to overcome this difficulty. Here we report the efficacy of this new probe in patients with esophago-gastric varices. Instead of using a water-filled balloon for an acoustic window, we displayed the EUS findings from the new probe in direct contact with gastrointestinal wall by removing air from the lumen under vacuum. Both conventional endoscopy and the new EUS were performed on 3 patients with esophageal varices. The transforceps-channel ultrasonic probe visualized grade 1 varices in addition to the larger varices, confirming this technique to be a useful method for assessing of esophageal varices. Moreover, this method does not require a specially designed endoscope for EUS, rather it can be employed in combination with conventional endoscopy. We conclude that this new technique is a preferred diagnostic technique, and it should become more widely accepted for routine clinical applications.

Aged↗

Laparoscopy-assisted colostomy.

The surgical modality of laparoscopic cholecystectomy is now widely accepted, and other intra-abdominal operations are also being done laparoscopically. This paper presents a case of laparoscopy-assisted colostomy in which a complete obstruction of the sigmoid colon associated with intraperitoneal dissemination and massive ascites in the end-stages of ovarian cancer was encountered. This procedure was found to be less invasive and thus should be considered the treatment of choice for an obstruction of the gastrointestinal tract in patients with a poor general status.

Aged↗

Genetic mapping of human heart-skeletal muscle adenine nucleotide translocator and its relationship to the facioscapulohumeral muscular dystrophy locus.

The mitochondrial heart-skeletal muscle adenine nucleotide translocator (ANT1) was regionally mapped to 4q35-qter using somatic cell hybrids containing deleted chromosome 4. The regional location was further refined through family studies using ANT1 intron and promoter nucleotide polymorphisms recognized by the restriction endonucleases MboII, NdeI, and HaeIII. Two alleles were found, each at a frequency of 0.5. The ANT1 locus was found to be closely linked to D4S139, D4S171, and the dominant skeletal muscle disease locus facioscapulohumeral muscular dystrophy (FSHD). A crossover that separated D4S171 and ANT1 from D4S139 was found. Since previous studies have established the chromosome 4 map order as centromere-D4S171-D4S139-FSHD, it was concluded that ANT1 is located on the side of D4S139, that is opposite from FSHD. This conclusion was confirmed by sequencing the exons and analyzing the transcripts of ANT1 from several FSHD patients and finding no evidence of aberration.

Alleles↗

Carbamyl phosphate synthetase I deficiency. One base substitution in an exon of the CPS I gene causes a 9-basepair deletion due to aberrant splicing.

Carbamyl phosphate synthetase I (CPS I; EC6,3,4,16) is an autosomal recessive disorder characterized by hyperammonemia. We studied the molecular bases of CPS I deficiency in a newborn Japanese girl with consanguineous parents. Northern and Western blots revealed a marked decrease in CPS I mRNA and enzyme protein but with a size similar to that of the control, respectively. Sequencing of the patient's cDNA revealed a nine-nucleotide deletion at position 832-840. Sequencing analysis of the genomic DNA revealed a G to C transversion at position 840, the last nucleotide of an exon in the splice donor site. This substitution altered the consensus sequence of the splice donor site and the newly cryptical donor site in the exon caused the 9-bp in-frame deletion. This report seems to be the first complete definition of CPS I deficiency, at the molecular level.

Amino Acid Sequence↗

Human colorectal carcinoma-specific glycoconjugates detected by pokeweed mitogen lectin.

Pokeweed mitogen (PWM) lectin, known to bind branched poly-N-acetyllactosamines, has a highly selective affinity for human colorectal carcinomas. We performed light microscopic (LM) histochemistry with PWM lectin on paraffin sections of human colorectal tissues. In histological sections, normal mucosae and adenomas with mild dysplasia exhibited negative reaction (0/10, 0/13, respectively) with or without neuraminidase pre-digestion, whereas adenomas with moderate dysplasia showed a small increase in PWM lectin reactivity after neuraminidase digestion (4/23). In contrast, we observed a high incidence of positive reactivity in colorectal carcinoma without neuraminidase pre-digestion (38/44). After digestion with neuraminidase, there was increased reactivity of colorectal carcinomas in situ (7/12) and invasive carcinomas (13/32). These results imply that human colorectal carcinomas consistently contain substantial amounts of PWM-reactive branched poly-N-acetyllactosamine glycoconjugates structures. We also compared the staining patterns of PWM lectin and monoclonal antibodies (MAb) directed to Lewis X (LeX) or Lewis Y (LeY) antigen. PWM lectin reactivity was largely confined to the apical membranes of carcinoma tissues. MAb-LeX or MAb-LeY immunoreactivity was seen on the apical membranes and in the cytoplasm of both adenomas and carcinomas. Therefore, histochemical studies with this lectin should be useful for identification of carcinoma tissues and analysis of glycoconjugates associated with colorectal carcinoma.

Adenoma↗

Transcriptional control of nuclear genes for the mitochondrial muscle ADP/ATP translocator and the ATP synthase beta subunit. Multiple factors interact with the OXBOX/REBOX promoter sequences.

The OXBOX promoter regions of the genes for the muscle-specific adenine nucleotide translocator (ANT1) and the beta subunit of the ATPsynthase (ATPsyn beta) have been implicated in the increased transcription of these nuclear-encoded oxidative phosphorylation (OXPHOS) genes in heart and skeletal muscle. DNA binding, electrophoretic mobility shift (gel-shift) assays now reveal that the OXBOX region has two unique but overlapping elements, the 13-base pair (bp) OXBOX and an 8-bp REBOX. The OXBOX binding factors are found only in myogenic cell lines, whereas the REBOX factors are ubiquitous. Methylation interference experiments have defined the boundaries of the OXBOX and REBOX elements, confirmed that the OXBOX factors are muscle-specific, and shown that the OXBOX and REBOX factors do not bind concurrently. The binding of the REBOX factors was found to be sensitive to NADH and thyroxine, suggesting that it may modulate OXPHOS gene expression in response to environmental and hormonal changes. Hence, the OXBOX/REBOX complex provides one mechanism by which mammalian energy metabolism can be adapted to developmental and environmental demands.

Animals↗

Intra-tumor DNA ploidy distribution pattern and its relation to histologic type in gastric carcinoma.

The pattern of intra-tumor DNA ploidy distribution was analyzed in stepwise sections in 64 cases of surgically resected gastric carcinoma. Five varying patterns were identified: Type A comprised only diploidy in all stepwise sections, Type B comprised only aneuploidy with the same DNA Index(DI), Type C comprised diploidy in the great majority of sections with aneuploidy in some parts, Type D comprised aneuploidy in the great majority of sections with diploidy in some parts and Type E comprised only aneuploidy, but with varying DI. These 5 patterns could be grouped into 2 categories; predominantly diploid (Types A and C) and predominantly aneuploid (Types B, D and E). The former category included 34 cases (12 differentiated carcinomas) while the latter included 30 cases (22 differentiated carcinomas). Thus, a statistically significant correlation was detected between the histologic type and the intra-tumor DNA ploidy distribution pattern; in the majority of cases, differentiated carcinoma exhibited predominantly aneuploidy, while undifferentiated carcinoma exhibited predominantly diploidy (p less than 0.01). This tendency was the same for all depths of invasion, except for submucosal carcinomas which exhibited predominantly diploidy.

Adenocarcinoma↗