Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 631 records · Page 35Linked to original sources

PubMed1997

Mucosal ulcerogenic action of monochloramine in rat stomachs: effects of polaprezinc and sucralfate.

Effects of a novel zinc compound polaprezinc [N-(3-aminopropionyl)-L-histidinatozinc] and sucralfate on the mucosal ulcerogenic responses induced by monochloramine (NH2Cl) were examined in rat stomachs. Oral administration of NH2Cl (>60 mM) produced severe lesions in unanesthetized rat stomachs, with concomitant increase of lipid peroxidation. These lesions were aggravated by sensory deafferentation but not affected by pretreatment with indomethacin or L-NAME. The mucosal ulcerogenic response to NH2Cl was significantly inhibited by oral pretreatment with either dmPGE2 (10 microg/kg), capsaicin (30 mg/kg), or NOR-3 (3 mg/kg), the NO donor. Gastric lesions induced by NH2Cl were also inhibited by prior oral administration of polaprezinc (3-30 mg/kg) as well as sucralfate (30 and 100 mg/kg). The protective effect of polaprezinc was not affected by any pretreatments such as indomethacin, L-NAME, or sensory deafferentation, while that of sucralfate was significantly mitigated in the presence of either indomethacin or L-NAME. On the other hand, mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery, followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were also attenuated by prior application of polaprezinc, while dmPGE2 and sucralfate prevented such lesions without affecting the reduced PD response. These results suggest that: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa, (2) both polaprezinc and sucralfate protect the stomach against injury caused by NH2Cl, and (3) the mechanisms underlying the protective action of sucralfate may be partly mediated by both endogenous PGs and NO but may be different from those of polaprezinc.

16,16-Dimethylprostaglandin E2↗

PubMed1997

Mechanism of acid secretory changes in rat stomach after damage by taurocholate: role of nitric oxide, histamine, and sensory neurons.

The present study was performed to investigate the mechanism underlying the acid stimulatory response in the stomach after damage under the inhibition of nitric oxide (NO) production by N(G)-nitro-L-arginine methyl ester (L-NAME). A rat stomach was mounted in an ex vivo chamber, perfused with saline, and the potential difference (PD) and acid secretion were measured before and after the application of 20 mM taurocholate (TC) for 30 min. Exposure of the stomach to TC caused a PD reduction and a decrease of acid secretion. Pretreatment with L-NAME did not affect basal acid secretion but significantly enhanced the acid secretion in the stomach after damage with TC, without any effect on the PD response. This effect of L-NAME was antagonized by simultaneous administration of L-arginine but not D-arginine. The luminal appearance of NO was significantly increased in the stomach after exposure to TC, and this change was completely blocked in the presence of L-NAME or when EGTA was applied together with TC. The enhanced acid secretory response to TC in the presence of L-NAME was inhibited by pretreatment with cimetidine, FPL-52694 (a mast cell stabilizer), or spantide (a substance P antagonist) or by chemical ablation of capsaicin-sensitive sensory neurons. Mucosal exposure to TC increased histamine output in the lumen and decreased the number of metachromatically staining cells in the stomach, and these changes were also significantly prevented by FPL-52694, spantide, or sensory deafferentation. These results suggest that 1) damage in the stomach may activate the acid stimulatory pathway in addition to the NO-dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion, 2) the acid stimulation in the damaged stomach may be mediated by histamine released from the mucosal mast cell which may interact with capsaicin-sensitive sensory nerves, and 3) L-NAME unmasks the acid stimulatory response by suppressing the inhibitory mechanism.

Animals↗

PubMed1997

Gastric motility and mucosal ulcerogenic responses induced by prokinetic drugs in rats under prostaglandin-deficient conditions.

The present study was performed to examine whether gastric prokinetic drugs may induce damage in the rat stomach under normal and prostaglandin (PG)-deficient conditions. Male SD rats fasted for 18 hr were administered subcutaneously with three different prokinetic drugs such as metoclopramide (3-60 mg/kg), ondansetron (0.3-3 mg/kg), and cisapride (3-30 mg/kg). Half the number of these animals were pretreated with indomethacin (5 mg/kg) subcutaneously for induction of PG deficiency in the stomach. Administration of these drugs increased gastric motor activity in a dose-dependent manner and expedited gastric emptying at lower doses than those affecting gastric motility; the potency of the hypermotility effect was in the following order: metoclopramide = ondansetron > cisapride. None of these drugs alone caused gross damage in the stomach, although whitish rough areas were observed in the gastric mucosa along the folds. In the rats pretreated with indomethacin, however, both metoclopramide and ondansetron provoked multiple hemorrhagic lesions in the gastric mucosa. Indomethacin at this dose showed over 90% inhibition of cyclooxygenase activity without causing any damage in the stomach, and this PG-deficient effect was not affected by coadministration with the prokinetic drugs. The mucosal ulcerogenic responses induced by metoclopramide in the presence of indomethacin were significantly inhibited by prior administration of atropine (1 mg/kg) or PGE2 (300 micrograms/kg) at doses that inhibited gastric hypermotility induced by metoclopramide. These results suggest that: (1) gastric prokinetic drugs induce damage in rat stomachs under PG-deficient conditions at the doses that enhance gastric motility and emptying but not at the doses that expedite gastric emptying only, and (2) gastric hypermotility has the potential to cause gross damage in the stomach, supporting the importance of gastric motility as a pathogenic element of gastric lesions.

Animals↗

PubMed1997

Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.

1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.

Alopecia↗

PubMed1997

Cyclo-oxygenase isozymes in mucosal ulcergenic and functional responses following barrier disruption in rat stomachs.

1. We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses. 2. Rat stomachs mounted in ex vivo chambers were perfused with 50 mM HCl and transmucosal potential difference (p.d.), mucosal blood flow (GMBF), luminal acid loss and luminal levels of prostaglandin E2 (PGE2) were measured before, during and after exposure to 20 mM TC. 3. Mucosal application of TC in control rats caused a reduction in p.d., followed by an increase of luminal acid loss and GMBF, and produced only minimal damage in the mucosa 2 h later. Pretreatment with indomethacin (10 mg kg[-1], s.c.), a nonselective COX-1 and COX-2 inhibitor, attenuated the gastric hyperaemic response caused by TC without affecting p.d. and acid loss, resulting in haemorrhagic lesions in the mucosa. In contrast, selective COX-2 inhibitors, such as NS-398 and nimesulide (10 mg kg[-1], s.c.), had no effect on any of the responses induced by TC and did not cause gross damage in the mucosa. 4. Luminal PGE2 levels were markedly increased during and after exposure to TC and this response was significantly inhibited by indomethacin but not by either NS-398 or nimesulide. The expression of COX-1-mRNA was consistently detected in the gastric mucosa before and after TC treatment, while a faint expression of COX-2-mRNA was detected only 2 h after TC treatment. 5. Both NS-398 and nimesulide significantly suppressed carrageenan-induced rat paw oedema, similar to indomethacin. 6. These results confirmed a mediator role for prostaglandins in the gastric hyperaemic response following TC-induced barrier disruption, and suggest that COX-1 but not COX-2 is a key enzyme in maintaining 'housekeeping' functions in the gastric mucosa under both normal and adverse conditions.

Animals↗

PubMed1997

Fatal interstitial pulmonary disease in a patient with dyskeratosis congenita after allogeneic bone marrow transplantation.

Chronic restrictive lung disease in a 9-year-old boy with dyskeratosis congenita (DC) 7 years after allogeneic bone marrow transplantation (BMT) is described. When he was 1 year and 10 months old, severe aplastic anemia developed. He received a marrow transplant from his HLA serologically identical, but HLA-DP mismatched brother. He developed grade II acute graft-versus-host disease (GVHD) and thereafter chronic GVHD of progressive type, and was treated with both prednisolone and azathioprine resulting in clinical improvement. Thereafter he complained of dyspnea, and bilateral noncircumscribed interstitial shadows on chest CT scan were present. His pulmonary function showed restrictive changes. Prednisolone was not effective and he died of respiratory failure. Post-mortem examination confirmed interstitial fibrosis, lymphocytic infiltration of the bronchioles and alveoli with luminal fibrosis. There was no evidence of chronic GVHD in the skin and the liver. These findings raise the possibility that this pulmonary complication was associated with DC itself.

Anemia, Aplastic↗

PubMed1997

Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes.

To assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, six CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were 13.5 +/- 13.7 months and 17.4 +/- 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 months after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early (<6 months) relapse, early (<12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioning did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 developed chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is warranted.

Adolescent↗

PubMed1997

Demonstration of the intralobular lymphatics in the guinea pig pancreas by an enzyme-histochemical method.

Intralobular lymphatics in the guinea pig pancreas were demonstrated enzyme-histochemically showing the extent, distribution and fine structure by combined light and transmission electron microscopy. 5'-nucleotidase(5'-Nase)-positive lymphatic vessels were present throughout the pancreas. Intralobular lymphatics among the acini were comparatively rare and generally independent of the blood capillaries, pancreatic ducts and acini. These lymphatics revealed the usual structural features, such as typical intercellular junctions and very tenuous vascular walls without continuous basal laminae. Fine precipitates of the cerium-based reaction product for 5'-Nase activity were found to be associated with cell membranes of the lymphatic endothelium and pinocytotic vesicles. Lymphatics were not closely related to the endocrine islets, although alkaline phosphatase(ALPase)-positive blood capillaries were well developed. Collecting lymphatic vessels with valves with weaker 5'-Nase activity were also detected in the interlobular connective tissue. ALPase activity, absent in the lymphatics, was positive in the blood capillaries, suggesting that it is also a useful way demonstrating, histochemically, the blood capillaries in the guinea pig pancreas.

5'-Nucleotidase↗

PubMed1997

Roles of prostaglandin E-receptor subtypes in gastric and duodenal bicarbonate secretion in rats.

BACKGROUND & AIMS: Receptors activated by prostaglandin (PG) E2 are pharmacologically subdivided into four subtypes (EP1-EP4). The EP-receptor subtype(s) involved in stimulation of gastroduodenal HCO3- secretion in rats were investigated. METHODS: Under urethane anesthesia, a stomach mounted in an ex vivo chamber or a proximal duodenal loop was perfused with saline, and HCO3- secretion was measured using a pH-stat method. RESULTS: Intravenous PGE2 increased HCO3- secretion by the gastroduodenal mucosa; this action was verapamil sensitive and, only in the duodenum, potentiated by isobutylmethyl xanthine (IBMX). Duodenal HCO3- secretion was stimulated by enprostil, sulprostone (EP1/EP3 agonist), misoprostol (EP2/EP3 agonist), and ONO-NT012 (EP3 agonist) but was not affected by butaprost (EP2 agonist) or 17-phenyl-PGE2 (EP1 agonist). Gastric HCO3- secretion was stimulated by sulprostone, enprostil, and 17-phenyl-PGE2 but not by misoprostol, butaprost, or ONO-NT012. SC-51089 (EP1 antagonist) inhibited the HCO3--stimulatory action of sulprostone only in the stomach. IBMX potentiated the HCO3- response to sulprostone in the duodenum, whereas verapamil reduced the response in both the stomach and duodenum. CONCLUSIONS: PGE stimulates HCO3- secretion via different EP-receptor subtypes in the stomach and duodenum: in the stomach, EP1 receptors are linked to Ca2+; in the duodenum, EP3 receptors are coupled with both adenosine 3', 5'-cyclic monophosphate and Ca2+.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Oxidative stress-mediated apoptosis of hepatocytes exposed to acute ethanol intoxication.

The present study was designed to investigate whether acute ethanol intoxication increases the production of active oxidants, and subsequently promotes apoptosis of hepatocytes. Hepatocytes were isolated from male Wistar rats, and cultured in the presence or absence of ethanol. The fluorescence in situ nick end labeling method and an enzyme-linked immunosorbent assay (ELISA) system to quantify fragmented DNA were used to estimate apoptotic change in hepatocytes. Nuclear morphological alterations and membrane barrier dysfunction of hepatocytes were assessed by staining with Hoechst 33342 and propidium iodide (PI). Intracellular glutathione level was determined as the fluorescence of monochlorobimane (MCLB), which forms conjugate with glutathione to become fluorescent. Ethanol (100 mmol/L) increased the amount of fragmented DNA and the number of apoptotic hepatocytes in vivo as well as in vitro. These ethanol-induced alterations in hepatocytes were attenuated by simultaneous incubation with either 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, or dimethylthiourea, an intracellular oxidant scavenger. Diethyl maleic acid (DMA), a glutathione depletor, enhanced the induction of apoptotic change, and decreased membrane barrier function in ethanol-treated hepatocytes, whereas ethanol per se did not increase the number of PI-positive hepatocytes. Furthermore, combination of ethanol and DMA but not ethanol alone decreased the hepatocyte MCLB fluorescence. Taken together, the present study suggests that active oxidants produced during ethanol metabolism mediate fragmentation of DNA in hepatocytes, and that intracellular antioxidants such as glutathione play a critical role in the cytoprotective mechanisms of hepatocyte against lethal cell death, ie, apoptosis, induced by ethanol.

Animals↗

PubMed1997

Fertilization of bovine oocytes grown in vitro.

Early antral follicles 0.5-0.7 mm in diameter were dissected from bovine ovaries, and oocyte-cumulus complexes with pieces of parietal granulosa (OCCGs) were then collected from the follicles. The OCCGs containing oocytes of 90-99 microm diameter (94.7+/-2.8 microm, n = 196) were selected and embedded in collagen gels and cultured for 14 days in TCM199 containing 10% fetal calf serum and 4 mM hypoxanthine. From cultured OCCGs, 144 surviving oocytes were recovered, of which 53 were granulosa cell-enclosed oocytes and 91 were denuded oocytes. The mean diameter of the surviving oocytes was 114.2+/-8.4 microm, significantly larger than that measured before culture (P < 0.05). The granulosa cell-enclosed oocytes and denuded oocytes were further cultured for maturation for 24 h. After culture, 72% (38/53) of the granulosa cell-enclosed oocytes and 59% (54/91) of the denuded oocytes showed normal morphology. These oocytes were then inseminated with bovine spermatozoa. After 29 h of insemination, all of the denuded oocytes had degenerated, while 32% (12/38) of the granulosa cell-enclosed oocytes showed normal morphology. Of the 12 oocytes, 5 were penetrated by spermatozoa, and 2 formed both male and female pronuclei. These results demonstrate for the first time that bovine oocytes grown in vitro acquire meiotic competence and can be penetrated by spermatozoa.

Animals↗

PubMed1997

Comparison of the accuracy of the lithium dilution technique with the thermodilution technique for measurement of cardiac output.

A new indicator dilution technique for measurement of cardiac output is described. Lithium chloride is injected via a central venous catheter and its dilution curve measured in arterial blood using a lithium-selective electrode. We assessed the lithium dilution cardiac output measurement (LiDCO) and a conventional thermodilution cardiac output measurement (ThDCO) by comparing the results of both with cardiac output determined by electromagnetic flowmetry (EMCO) under controlled laboratory conditions in 10 swine. They were monitored with a pulmonary artery catheter, femoral artery catheter and electromagnetic flowmeter placed around the ascending aorta. LiDCO, ThDCO and EMCO measurements were determined at baseline, in a hyperdynamic state produced by administration of dobutamine, at a second baseline and finally in a hypodynamic state induced by propranolol during deep anaesthesia. Data were analysed by linear regression analysis and the comparison method described by Bland and Altman; bias and precision of both LiDCO and ThDCO compared with EMCO were calculated by the method of Sheiner and Beal. The correlation coefficient between LiDCO and EMCO (0.95) was higher than that between ThDCO and EMCO (0.87). The precision value of LiDCO (0.04) was significantly less (i.e. better) than that of ThDCO (0.09). The results of this study indicated that LiDCO was more reliable compared with conventional ThDCO.

Animals↗

PubMed1997

HSDJ, a human homolog of DnaJ, is farnesylated and is involved in protein import into mitochondria.

The role of HSDJ, a human homolog of bacterial DnaJ and yeast YDJ1p/MAS5, in mitochondrial protein import was examined. Recombinant HSDJ was purified and an antibody was prepared. HSDJ mRNA was heat-induced in cultured cells. In pulse-labeling and chase experiments using COS-7 cells, the endogenous HSDJ homolog was prenylated. Transiently expressed HSDJ was also prenylated, whereas its mutant C394S in which cysteine of the "CaaX box" was mutated to serine, was not. HSDJ, but not C394S, synthesized in rabbit reticulocyte lysate was farnesylated. The HSDJ antibody inhibited import of ornithine transcarbamylase precursor (pOTC) into isolated mitochondria when added prior to pOTC synthesis, but not when added prior to import assay. In transient expression of pOTC in COS-7 cells, pOTC was synthesized and processed to the mature form with an apparent half-life of 2-3 min. Coexpression of HSDJ or C394S resulted in slight retardation of the pOTC processing. These results indicate that HSDJ is involved in an early step(s) of protein import into mitochondria.

Animals↗

PubMed1997

Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta.

Recently, we developed a simple method for detecting a secretory signal sequence encoded by a cDNA fragment. In this study, we used this method to select cDNA clones encoding secretory proteins from a human full-length cDNA library. Full-sequencing analysis of the candidate clones revealed that one clone encoded a novel TGF-beta superfamily protein. The clone encodes a protein of 308 amino acids of which the C-terminal region shows a characteristic feature of TGF-beta superfamily proteins: seven conserved cysteine residues at the C-terminal preceded by a putative processing site composed of a basic amino acid repeat. The corresponding transcripts are highly expressed in the placenta, so the novel protein may play an important role in reproduction.

Amino Acid Sequence↗

PubMed1997

Nitric oxide, histamine, and sensory nerves in the acid secretory response in rat stomach after damage.

The stomach normally responds to mucosa-damaging agents by decreasing acid secretion, but this acid response turn from "inhibition" into "stimulation" when the production of nitric oxide (NO) is inhibited by NG-nitro-L-arginine methyl ester (L-NAME). We investigated the mechanism underlying stimulation of acid secretion in the stomach after damage with taurocholate (TC) in the presence of L-NAME. A rat stomach was mounted in an ex vivo chamber and perfused with saline, and the potential difference (PD), luminal pH, and acid secretion were measured before and after application of 20 mM TC for 30 min. Exposure of the stomach to TC caused a reduction in PD, an increase in luminal pH, and a decrease in acid secretion. Pretreatment with L-NAME did not affect basal acid secretion but significantly increased secretion after damage with TC, without any effect on PD. This effect of L-NAME was antagonized by co-administration of L-arginine but not D-arginine. The luminal appearance of NO was also increased after exposure of the stomach to TC, a phenomenon completely blocked by L-NAME, or when EGTA was applied together with TC. The enhanced acid secretory response in the presence of L-NAME was inhibited by prior administration of cimetidine, FPL-52694 (a mast cell stabilizer), spantide (a substance P antagonist), or by chemical ablation of capsaicin-sensitive sensory neurons. Mucosal exposure to TC increased histamine output in the lumen and decreased the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 or sensory neuronal ablation. These results suggest that (a) damage in the stomach may activate acid stimulation in addition to an NO-dependent inhibitory mechanism but that the latter effect overcomes the former, resulting in a decrease in acid secretion, (b) acid stimulation in the damaged stomach may be mediated by histamine released from the mucosal mast cells, a process that may interact with capsaicin-sensitive sensory nerves, and (c) L-NAME unmasks the acid stimulatory response by suppressing the inhibitory mechanism.

Animals↗

PubMed1997

Mechanism of gastric hyperemic response during acid secretion in rats: relation to nitric oxide, prostaglandins, and sensory neurons.

The mechanism of gastric mucosal hyperemic response during pentagastrin-induced acid secretion was investigated in anesthetized rats in relation to prostaglandins (PGs), nitric oxide (NO), and sensory neurons. A rat stomach was mounted in an ex vivo chamber and perfused with saline or glycine (200 mM), and the mucosal blood flow (GMBF), determined by laser Doppler flowmetry, and acid secretion was measured simultaneously. Intravenous infusion with a submaximal dose of pentagastrin (60 micrograms/kg/h) caused a significant increase in GMBF as well as acid secretion. Such GMBF responses were totally attenuated when acid secretion was inhibited by omeprazole and cimetidine or when the luminal H+ was buffered by mucosal perfusion with glycine (200 mM). Tripelennamine, an H1 antagonist, did not have any affect on acid secretory and GMBF responses to pentagastrin. On the other hand, prior administration of NG-nitro-L-arginine methyl ester (L-NAME), the NO synthase inhibitor, significantly mitigated the increase of GMBF induced by pentagastrin without any influence on acid secretion, and this effect was antagonized by simultaneous administration of L-arginine. The gastric hyperemic response to pentagastrin was also significantly mitigated by indomethacin or sensory deafferentation after capsaicin pretreatment, with no effect on acid secretion, and was totally inhibited by combined treatments with indomethacin plus L-NAME in addition to sensory deafferentation. Pentagastrin infusion for 8 h did not by itself cause macroscopic damage in the stomach, but additional treatments with L-NAME and indomethacin plus sensory deafferentation provoked severe lesions in the gastric mucosa. These results suggest that the gastric hyperemic response to pentagastrin (submaximal dose) is totally dependent on H+ and that this process is mediated by endogenous NO and PGs as well as by capsaicin-sensitive sensory neurons and plays a pivotal role in maintaining mucosal integrity during acid secretion.

Animals↗

PubMed1997

Role of Helicobacter pylori infection in perforation of peptic ulcer: an age- and gender-matched case-control study.

Evidence showed a marked decrease in recurrence rate of peptic ulcer after eradication of Helicobacter pylori infection. However, whether H. pylori infection is etiologically related to perforation of peptic ulcer remains to be clarified. We therefore conducted an age- and gender-matched case-control study between perforated and nonsurgical peptic ulcers in H. pylori infection and examined differences in the cytotoxin genes cagA and vacA. Serum H. pylori IgG antibody (ELISA) was positive in 20/21 (95%) of perforated vs. 37/40 (93%) of nonsurgical duodenal ulcers and in 5/5 (100%) of perforated vs. 24/28 (86%) of nonsurgical gastric ulcer patients. Positivity of H. pylori DNA in gastric juice, which was amplified by PCR and identified by Southern blot hybridization, was 17/23 (74%) of perforated vs. 32/45 (71%) in the nonsurgical duodenal ulcer group. Positivity of the cytotoxin genes cagA and vacA in H. pylori DNA-positive gastric juice was as follows: perforated vs. nonsurgical duodenal ulcer, cagA 11/ 13 (85%) vs. 24/27 (89%); vacA1: 9/13 (69%) vs. 22/27 (82%); vacA2 8/13 (62%) vs. 21/27 (78%). There were no significant differences between the perforated and nonsurgical peptic ulcer groups for these H. pylori serum and gene markers. It is assumed that H. pylori infection is not etiologically related to perforation of peptic ulcer.

Antigens, Bacterial↗

PubMed1997

Induction of aberrant crypt foci and flat-type adenocarcinoma in the colons of dogs by N-ethyl-N'-nitro-nitrosoguanidine and their sequential changes.

Sequential endoscopic observation of dog colons was performed during colon carcinogenesis. Two beagle dogs were given suppositories containing N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) every day for five months. In month 3, aberrant crypt foci (ACF), a putative preneoplastic lesion, were found in the colons of both dogs, but not in an untreated dog. The frequency of ACF increased until month 10, and then decreased. In month 9, very small lesions, less than 1 mm in diameter, which were similar to human early flat tumors, were first noticed. One of these lesions grew to about 7 mm in size without a change in its shape for 10 months. There were more than ten flat-type tumors in the two dogs, but such lesions were not found in the untreated dog. By biopsy, two of the lesions were proved to be well-differentiated adenocarcinomas histologically. Four polypoid lesions were found in one of the carcinogen-treated dogs. Thus, flat-type adenocarcinomas were induced in the dog colon by ENNG, and their development was followed by magnifying endoscopy.

Adenocarcinoma↗