Biomedical subjects

K Saigenji

Publications and source records attributed to K Saigenji.

At least 55 records · Page 3Linked to original sources

PubMed1998

CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer.

The pathophysiological significance of tumor infiltrating lymphocytes remains controversial. To clarify their role, we performed clinicopathological analysis of CD8+ T cells in 131 cases of human colorectal cancer. CD8+ T cells were classified into three groups by their localization: (a) those infiltrated within cancer cell nests; (b) those distributed in the cancer stroma; and (c) those present along the invasive margin (tumor-host interface). Of these, CD8+ T cells within cancer cell nests were most significantly associated with a better survival of patients by both mono- and multivariate analyses. The impact on survival was similar to that of Dukes' staging. Granzyme B+ cytoplasmic granules were detected in lymphocytes within cancer cell nests, confirming their activated, cytotoxic phenotype. CD8 and Ki-67 double immunohistochemistry confirmed higher proliferative activity of CD8+ T cells within cancer cell nests. Our data suggested that human colorectal cancer tissue was infiltrated by various numbers of T cells that had cytotoxic phenotype, contributing to a better survival of patients. This infiltration of colorectal cancer cell nests by CD8+ T cells could be a novel prognostic factor.

Analysis of Variance↗

PubMed1998

Lafutidine-induced stimulation of mucin biosynthesis mediated by nitric oxide is limited to the surface mucous cells of rat gastric oxyntic mucosa.

Although the new histamine H2 receptor antagonist, lafutidine (FRG-8813), N-[4-[4-(piperidinylmethyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2-(fur furylsulfinyl)acetamide accelerates mucin metabolism of rat gastric mucosa, the physiological mechanisms by which this drug stimulates the biosynthesis remain unclear. In this paper, we report the effect of lafutidine on mucin biosynthesis in distinct sites and layers of rat gastric mucosa, including the possible participation of nitric oxide (NO). Lafutidine enhanced [3H]glucosamine incorporation into the mucin in the full thickness corpus mucosa, but not in the antrum. This stimulation on mucin biosynthesis disappeared by the removal treatment of surface mucosal cells. The lafutidine-induced increase of [3H]-labeled mucin in the corpus was completely blocked by either NG-nitro-L-arginine (10[-5] M) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolne-1-oxyl-3-oxide (10[-5] M). The inhibitory action of NG-nitro-L-arginine was totally reversed by L-arginine (5 x 10[-3] M). These results suggest that the lafutidine-induced stimulation of mucin biosynthesis mediated by NO is limited to the surface mucous cells of rat gastric oxyntic mucosa.

Acetamides↗

PubMed1998

Hepatitis G virus infection from needle-stick injuries in hospital employees.

A new RNA virus, hepatitis G virus (HGV) is known to be transmissible by blood transfusion. The aim of this study was to assess whether HGV is an occupational risk to hospital employees as a result of exposure to needle-stick injuries. Among 220 cases of needle-stick injuries, 21 employees were contaminated with HGV. Initially none of the 21 recipients were HGV positive. Fourteen of the 21 recipients were followed up and further tested for HGV RNA and serum anti-envelope (E2) specific antibody. None of the 21 recipients exposed to HGV developed liver function abnormalities, but one of the 14 recipients became positive for HGV RNA after the injury. Anti-E2 was negative in all recipients tested. These findings suggests a low clinical risk of occupational exposure to HGV in hospital employees. Nevertheless HGV is transmissible by needle-stick injury.

Acute Disease↗

PubMed1998

Distinct effects of tetragastrin in rat gastroduodenal mucosa on mucin content and mucosal protective action against histamine-induced injury.

We examined the effects of tetragastrin on mucin (mucus glycoprotein) content and mucosal damage in the rat stomach and duodenum. Following an injection of tetragastrin (12, 120, or 400 microg/kg subcutaneously), no macroscopic damage was found to the gastric mucosa but an increase in corpus mucin content was noted, whereas mucosal lesions appeared and the mucin content decreased in the duodenum in a dose-related manner. In the groups with histamine (0.8, 8, or 80 mg/kg intraperitoneally) administration, the extent of mucosal damage and the decrease in mucin content were dose-related in both these regions. For assessment of the effect of tetragastrin on the protective action in gastroduodenal mucosa, changes in mucin content and mucosal damage with histamine (80 mg/kg) -induced injury were examined. Coadministration of tetragastrin prevented the gastric mucosal damage and inhibited the decrease in corpus mucin content. In the duodenum, tetragastrin aggravated the histamine-induced mucosal damage and did not inhibit the reduction of the mucin content. From the present results, the increase in gastric mucins induced by tetragastrin might be related to the protective effect of gastric mucosa against injury. Tetragastrin did not protect the duodenal mucosa, and histamine-induced injury occurring in this region would be aggravated by the increase in HCl secretion and the decrease in mucin content induced by tetragastrin.

Animals↗

PubMed1998

Staging of gastric cancer with endoscopic ultrasonography and endoscopic mucosal resection.

Since it was found that the gastrointestinal wall is visualized as a five-layered structure corresponding to the histological layers of the wall, endoscopic ultrasonography (EUS) has become recognized clinically as the most accurate method for diagnosing and assessing the local staging of gastric cancer. However, some problems have remained, including how to differentiate between cancer invasion and ulcer fibrosis, how to detect microinvasion, and how to recognize malignant lymph nodes. Using the pattern analysis for depressed-type gastric cancer, it is usually possible to distinguish between cancer invasion and ulcer fibrosis, except in cases of microinvasion into ulcer fibrosis or inadequate scanning. However, the sensitivity of EUS for evaluating metastatic lymph nodes is still problematic. Endoscopic mucosal resection (EMR) for early gastric cancer has been widely accepted as a standard treatment in Japan due to its minimal invasiveness. According to our data, the overall rate of radical resection was 68.3% (168 of 246), and 31.7% of the remaining patients additionally received laser treatment, surgery, or heater-probe treatment. There were no deaths owing to gastric cancer. Some lesions in which there was microinvasion of the submucosa were incorrectly diagnosed by EUS. It may be possible to solve this problem using three-dimensional EUS (3D-EUS) in the near future.

Endoscopy↗

PubMed1998

Prevalence of hepatitis G virus RNA and anti-E2 in a Japanese haemodialysis population.

BACKGROUND: Patients on maintenance haemodialysis (HD) are at greater risk of parenterally transmitted infection with not only A-E hepatitis virus but also with hepatitis G virus (HGV) that has been recovered from patients with non A-E hepatitis. The prevalence of HGV infection in HD patients, which is based on the detection of HGV RNA using reverse transcription-polymerase chain reaction techniques, differs widely between countries. Recently, a new assay has been developed that detects an antibody to the envelope protein (E2) of HGV (anti-E2) that appears to be associated with the loss of HGV RNA from the serum and which may be a useful marker for previous HGV infection. METHODS: To determine the actual prevalence of HGV infection in maintenance HD patients, we examined both HGV RNA and anti-E2 antibody in sera from 200 patients undergoing maintenance HD. RESULTS: Thirty patients (15%) tested positive for HGV RNA, and 14 (7%) tested positive for E2 antibody. Of these, two individuals tested positive for both markers. Overall, 21% of these HD patients had been exposed to HGV. A logistic regression analysis failed to show any clinical feature associated with the detection of HGV RNA. The duration of HD and the presence of HCV RNA were associated with anti-E2. Male gender and HCV RNA were risk factors for the elevation of serum ALT activities. HGV RNA sequences of the patients were not identical to each other. CONCLUSIONS: Our data indicate that HGV infection is prevalent in patients undergoing HD but that liver abnormalities are rare. The nosocomial transmission of HGV in the HD unit was not confirmed.

Aged↗

PubMed1998

An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer.

The purpose of this study was to evaluate the feasibility and efficacy of 3-hour infusional paclitaxel for the treatment of advanced gastric cancer with measurable metastatic diseases. Eligibility criteria included no more than one regimen of prior chemotherapy. Paclitaxel was administered as an intravenous infusion over 3 hours at a dose of 210 mg/m2 every 3 weeks. Premedication of dexamethazone, ranitidine, and diphenhydramine were given to all patients. Sixteen patients were registered in the study. One patient did not receive paclitaxel because of gastrointestinal bleeding before the initiation of drug's administration. Thirteen of the 15 patients had a prior history of chemotherapy. Although 10 patients (67%) developed grade 4 neutropenia, no serious infections occurred during the study. Nonhematologic toxicities were generally mild. Three (20%) patients who showed evidences of resistance to the previous intensive regimen achieved a partial response. In conclusion, a 3-hour infusion of paclitaxel is a safe and promising treatment for advanced gastric cancer. Paclitaxel appears to be non-cross resistant to other agents that are commonly used for gastric cancer. A large-scale phase II study is now underway.

Adult↗

PubMed1998

A prospective randomized study of amoxycillin and omeprazole with and without metronidazole in the eradication treatment of Helicobacter pylori.

A combination of amoxycillin and omeprazole is often used to treat Helicobacter pylori infection. A three-drug regimen comprising metronidazole, amoxycillin and omeprazole has been proposed as an alternative therapy. In a prospective, randomized, comparative study, we evaluated these two regimens with respect to safety and efficacy in patients with H. pylori infection. Sixty patients with peptic ulcer (gastric, 32 patients; duodenal, 28 patients) who had a history of ulcer recurrence were randomly assigned to dual therapy with amoxycillin (500 mg three times daily for 2 weeks) and omeprazole (20 mg once daily for 8 weeks) or to triple therapy with metronidazole (500 mg twice daily for 2 weeks) plus amoxycillin and omeprazole, given in the same dosages as dual therapy. Forty-eight patients completed the protocol; treatment was discontinued because of side effects in nine patients, and three patients dropped out of the study. On the basis of all patients treated, the rate of H. pylori eradication was significantly higher for triple therapy 20/23 cases, 87.0%; 95% confidence interval (CI), 0.664-0.972) than for dual therapy 13/25, 52.0%; 0.313-0.722; P < 0.05). On an intention-to-treat basis, the difference between the groups in the rate of H. pylori eradication was marginally significant (P = 0.06 [0.028-0.512]). Side effects were reported by five patients receiving triple therapy (skin rash, one; nausea, two; headache, one; abdominal pain, one), and four patients receiving dual therapy (skin rash, two; abdominal pain, one; diarrhoea, one). All side effects resolved spontaneously after termination of treatment. There was no significant difference in safety between the two regimens. Triple therapy with metronidazole, amoxycillin, and omeprazole was significantly more effective for the eradication of H. pylori than dual therapy with amoxycillin and omeprazole alone. The safety of these regimens was similar, and triple therapy was found to be clinically acceptable.

Adult↗

PubMed1998

Distinct effects of tetragastrin, histamine, and CCh on rat gastric mucin synthesis and contribution of NO.

Although gastrin, histamine, and carbachol (CCh) accelerate gastric mucin metabolism, information about their target cells of mucin production is lacking. To clarify this, we examined the effects of these stimulants, including the possible participation of nitric oxide (NO), on mucin biosynthesis in distinct sites and layers of rat gastric mucosa. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing radioactive precursors and each stimulant, with or without NO synthase (NOS) inhibitor. Distribution of NOS was compared with that of the specific mucins by immunostaining using specific antiserum and monoclonal antibodies. In the full-thickness corpus mucosa, tetragastrin enhanced [3H]glucosamine incorporation into mucin but had no effect on [14C]threonine incorporation. Both histamine and CCh dose dependently increased 3H- and 14C-labeled corpus mucin. Only CCh stimulated antral mucin biosynthesis. CCh stimulation was noted in the corpus mucosa after removal of surface mucous cells, but stimulation by tetragastrin or histamine disappeared as a result of this pretreatment. Only tetragastrin-induced activation was completely blocked by the NOS inhibitor. NOS immunoreactivity was limited to surface mucous cells. Mucus-producing cells present in the different sites and layers of the gastric mucosa have distinct mechanisms for regulation of mucin biosynthesis. Gastrin-stimulated mucin biosynthesis mediated by NO is limited to surface mucous cells of rat gastric oxyntic mucosa.

Animals↗

PubMed1998

An autopsy case of troglitazone-induced fulminant hepatitis.

OBJECTIVE: To study an autopsy case of troglitazone-induced fulminant hepatitis. CASE REPORT: A 58-year-old man contracted severe hepatitis 2 months after administration of troglitazone for the treatment of type 2 diabetes. Liver damage progressed gradually, even after withdrawal of the agent. Despite intensive therapy, the hepatitis became fulminant and the patient died 8 weeks after the onset of liver damage. Autopsy revealed massive hepatic necrosis and cholestasis with inflammatory cell infiltration. The pathological findings and the positive result of the drug-induced lymphocyte stimulation test for troglitazone indicated that the liver damage was mediated by hypersensitivity to troglitazone. CONCLUSIONS: One report has attributed troglitazone-induced liver damage in less severe cases to idiosyncratic reactions. However, the present case indicates that troglitazone can induce hypersensitivity resulting in fulminant hepatitis. Careful monitoring of serum liver enzymes during troglitazone therapy is therefore essential.

Alanine Transaminase↗

PubMed1998

[A study of colonic mucins in two kinds of experimental colitis model in rat].

We investigated the quantitative changes in colonic mucins of rats with colitis. Male Wistar rats were treated with dextran sodium sulfate (DSS) or N-ethylmaleimide (NEM) to induce colitis. Both DSS and NEM caused depletion of goblet cells, infiltration of inflammatory cells and erosion at the colonic mucosa around the anus. Though the goblet cells decreased, colonic mucins increased in the distal colon. These phenomena may explain the clinical features of human ulcerative colitis, namely the goblet cell depletion and the mucous stool. The increase of colonic mucins may be a compensatory function of the colon tissue in response to the localized decrease of mucin production.

Animals↗

PubMed1998

[Mallory-Weiss syndrome].

Mallory-Weiss syndrome is one of the cause of upper gastrointestinal hemorrhage, which an abrupt rise in abdominal pressure due to nausea or vomiting induces a tear near the esophagogastric mucosal junction. Mallory-Weiss syndrome represents about 3-15% of all cases of upper gastrointestinal hemorrhage. Mallory-Weiss tear is mainly located on the cardia part of the stomach side and spanning across the esophagogastric mucosal junction, only in esophageal side is rarely seen. Hemorrhage frequently ceases spontaneously. When endoscopic findings reveal persistent hemorrhage, endoscopic hemostatic technique using heater probe thermocoagulation or hemoclipping is necessary. After endoscopic hemostasis, fasting and inhibitors of acid secretion (H2-receptor antagonists or proton pump inhibitors) are recommended.

Diagnosis, Differential↗

PubMed1998

[A randomized controlled study of total parenteral nutrition and enteral nutrition by elemental and polymeric diet as primary therapy in active phase of Crohn's disease].

We performed randomized controlled study to compare the short-term therapeutic effect of total parenteral nutrition (TPN), elemental diet (ED) and polymeric diet (PD) given as primary therapy in active phase of Crohn's disease. In hospital for Crohn's disease, twenty-eight patients were given nutritional therapy: 9 patients by TPN, 10 by ED, and 9 by PD. Nutritional state, inflammatory reactions, disease activity and clinical remission rate were assessed two weeks and four weeks after treatment, and morphological findings were assessed before and after each nutritional therapy by radiographic and colonoscopic findings. Inflammatory reactions were more effectively controlled by TPN and ED than by PD, and early improvement achieved by TPN and ED was especially note-worthy. Clinical remission rate after treatment by TPN was highest in three types of nutritional approach, but no significant difference was seen at any point. In nutritional state, disease activity and morphological findings, comparable changes were effected without preference. These results suggest that nutritional therapy by total parenteral nutrition and elemental diet is superior to polymeric diet for treating active phase of Crohn's disease with marked inflammatory reactions.

Adolescent↗

PubMed1997

Intestinal Behçet's disease--pathognomonic changes in intramucosal lymphoid tissues and effect of a "rest cure" on intestinal lesions.

To clarify the pathognomonic changes of intestinal lesions of Behçet's disease and to determine effective therapeutic measures, we recruited 13 patients with the intestinal form of this disease for study. We performed pathology studies on the resected specimens of 7 patients and treated 5 of the other 6 patients with a low-residue diet. Pathology examination revealed that 6 of 7 had inflammatory ulcerations in the ileocecal region. The ileal ulcers were mainly on the antimesenteric side. We observed remnants of Peyer's patches at the margins of the major ulcerative lesions in 2 of 2 patients examined. There were aggregations of lymphocytes resembling destroyed lymph follicles in the superficial layer at the mouths of small fissuring lesions, and ulcer scars were also noted in Peyer's patches in 4 of 5 other patients. X-ray and endoscopic examinations revealed the disappearance of intestinal lesions in 5 patients within 1 month during, or following the low-residue diet treatment. We found the intestinal lesions of Behçet's disease at sites coinciding with intramucosal lymphoid tissue. The "rest cure" for the affected bowel was effective, i.e., there was significant alleviation of gastrointestinal symptoms and the intestinal lesions disappeared. We speculated that acute exudative inflammation, abscess formation, and consequent ulceration may occur in these tissues by the same mechanisms as those that operate in the positive needle-prick reactions seen in patients with Behçet's disease.

Adult↗

PubMed1997

Recovery of mucin content in surface layer of rat gastric mucosa after HCl-aspirin-induced mucosal damage.

Quantitative changes in mucin (mucus glycoprotein) in different layers of rat gastric mucosa after mucosal damage induced by acidified acetylsalicylic acid (HCl-aspirin; 0.15N HCl, 20-200 mg acetylsalicylic acid/kg body weight) were studied. More than 50 mg/kg HCl-aspirin led to a significant increase in macroscopic gastric injury (expressed as ulcer index) at 3 h, compared with control (no aspirin) and there was a significant recovery at 7 h. Three h after dosing with 50 mg/kg acidified aspirin, there was superficial mucosal damage and decreased mucin content in the surface mucosal layer. Mucin production recovered 7 h after the administration of 50 mg/kg acidified aspirin. Doses of acidified aspirin higher than 100 mg/kg decreased mucin content in the surface and deep corpus mucosal layers and no recovery was seen 7 h after the administration. Physiological damage after the administration of 50 mg/kg HCl-aspirin was limited mainly to surface epithelial mucus cells. An experimental model in which superficial erosion was induced in rat gastric mucosa was established with low-dose HCl-aspirin.

Animals↗

PubMed1997

Structural requirements for roxatidine in the stimulant effect of rat gastric mucin synthesis and the participation of nitric oxide in this mechanism.

1. The structural requirements of the histamine H2-receptor antagonist, roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide hydrochloride), for the stimulant effect on mucin biosynthesis and their relation to histamine H2-receptor antagonism were identified by considering the structural analogues of this drug using an organ culture system of the rat stomach and competition studies with [125I]iodoaminopotentidine ([125I]-APT) binding to membranes of the guinea pig striatum. 2. [3H]Glucosamine incorporation into mucin during 5 h incubation period was stimulated by roxatidine and its structural analogues A (2-hydroxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide) and B (N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl)acetamide). This effect was seen in mucosal cultures of the corpus, but not antrum, region. 3. Structural analogues, in which the length of the flexible chain between the benzene ring and the amide structure differs from that of roxatidine, failed to activate mucin synthesis. No significant change in mucus synthesis occurred with the addition of analogues in which the piperidine ring attached to the benzene ring via a methylene bridge was changed. 4. Specific [125I]-APT binding to the histamine H2 receptor of guinea pig brain membranes was inhibited by roxatidine and all structural analogues used in this study, except F (N-(3-[m-(N, N-dimethyl-aminomethyl)phenoxy]-propyl)acetamide). 5. Ranitidine at 10(-4) M did not suppress the roxatidine-induced increase in [3H]glucosamine incorporation into mucin. 6. Roxatidine-induced stimulation of [3H]glucosamine incorporation into mucin was completely blocked by the addition of either NG-nitro-L-arginine (10(-5) M) or 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide sodium salt (10(-5) M). The inhibitory action of NG-nitro-L-arginine was totally reversed by L-arginine (5 x 10(-3) M). 7. These results suggest that the cardinal chemical features of roxatidine for the activation of mucin biosynthesis in the corpus region of the rat stomach are the appropriate length of the flexible chain between the amide structure and the aromatic ring system bearing the methylpiperidinyl group at the meta position. The activity of roxatidine and its analogues to stimulate mucin synthesis is not related to their histamine H2 receptor antagonistic activity. Roxatidine-induced activation of mucin biosynthesis in the corpus tissue is mediated by nitric oxide.

Animals↗

PubMed1997

Effects of histamine on mucin biosynthesis in rat gastric mucosa.

Mucin biosynthesis is stimulated by gastrin during the process of glycosylation in the corpus mucosa of the rat stomach. The purpose of this study was to clarify, using an organ culture technique, whether biosynthetic responses to histamine in the rat gastric mucin are the same as that to gastrin. Radiolabeled mucin was obtained from the corpus and antral mucosa of the rat stomach after in vitro incubation for 5 h with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate. Addition of histamine (10(-7)-10(-5) M) to the culture medium increased [3H]GlcN-labeled mucin in the corpus tissue in a concentration-dependent manner. In the antrum, there was no significant change in the biosynthetic activity of mucin in response to histamine. Histamine at 10(-5) M also increased the incorporation of both [35S]sulfate and [14C]Thr into the corpus mucin. These results indicate that histamine stimulates the biosynthesis of the mucin peptide, as well as the glycosylation step in the corpus, and suggest that the effect of histamine on mucin synthesis is distinct from that of gastrin.

Animals↗

PubMed1997

Stimulation of mucin metabolism in rat gastric mucosa by histamine.

We examined the effects of histamine on mucin localized in the different regions and layers of rat gastric mucosa by determining the changes in the content as well as the biosynthetic activity of the mucin. In vivo administration of 0.8 mg/kg of histamine, which could not induce a concomitant gastric acid secretion, caused a significant increase in the mucin content in the corpus mucosa, but not in the antral mucosa. This increase was due to a significant accumulation of the mucin in the mucus gel and surface mucosa of the corpus region, whereas that in the deep mucosa did not significantly change. In the in vitro incubation system of rat gastric mucosa, histamine and dibutyryl cyclic AMP significantly increased [3H]-labeled mucin in the corpus. The histamine-induced acceleration of mucin biosynthesis was suppressed by ranitidine, but not pyrilamine. In the antrum, the biosynthetic activity showed no significant change by histamine. These results suggest that histamine promotes mucin metabolism via histamine H2 receptors in the surface mucosal layer of the corpus.

Animals↗