PubMed HealthSearch

Biomedical subjects

T Shimoyama

Publications and source records attributed to T Shimoyama.

At least 19 recordsLinked to original sources

Inhibition assay for the binding of biotinylated von Willebrand factor to platelet-bound microtiter wells in the presence of ristocetin or botrocetin.

We developed a solid-phase inhibition assay for the binding of biotinylated von Willebrand factor (vWF) to platelet glycoprotein (GP)Ib based on an enzyme-linked immunosorbent assay (ELISA) with platelet-bound microtiter wells. Washed platelets were immobilized onto the microplates via the anti-GPIIb/IIIa monoclonal antibody (mAb) VNR-5. In the presence of an antibiotic ristocetin (1 mg/ml, final) or the snake venom botrocetin (2 micrograms/ml, final), biotinylated vWF bound to the affixed platelets with half-maximal binding occurring at a vWF concentration of approximately 2 micrograms/ml. Several specific inhibitors of the binding of vWF to GPIb abolished the interaction of biotinylated vWF with GPIb in a dose-dependent fashion, with comparable protein concentrations to those seen in the liquid-phase inhibition assay using 125I-vWF. These inhibitors included mAb against vWF (NMC-4), mAb against GPIb (AP-1), and two vWF fragments containing vWF's putative GPIb-binding domain, namely a 39/34-kDa dispase-digested vWF fragment and a recombinant vWF fragment. Thus, this new assay is a convenient alternative to the conventional inhibition assay using 125I-vWF.

Anti-Bacterial Agents

Validity of various diagnostic tests to evaluate cure of Helicobacter pylori infection.

Many diagnostic methods have been developed and used for detecting Helicobacter pylori to evaluate the success of treatment of H. pylori infection. We investigated and compared the suitability of the rapid urease test (RUT), polymerase chain reaction (PCR), 13C-urea breath test (13C-UBT), and serology with culture for evaluating cure of H. pylori infection. Forty-seven H. pylori-positive gastric ulcer patients received dual therapy of lansoprazole (30 mg u.i.d.) and clarithromycin (200 mg b.i.d.). Four weeks after the completion of treatment, RUT, PCR, 13C-UBT, and culture were performed and the negative rates of these tests were compared. Anti-H. pylori IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA) before and 4 weeks after completion of the treatment to evaluate changes of titers during the treatment. The negative rate of RUT (55%) was significantly greater than that of culture (27%). Significant declines in titers were seen in the patients who had negative culture results, while the decline in the titer was not significant in the patients who had positive results. PCR assay and 13C-UBT were suitable for the evaluation of H. pylori eradication, but RUT was not suitable, because of its sensitivity. By monitoring anti-H. pylori IgG antibody titers, therapeutic failure can be detected early after completion of treatment.

2-Pyridinylmethylsulfinylbenzimidazoles

Genotypes and multiple infections with hepatitis C virus in patients with haemophilia A in Japan.

Hepatitis C virus (HCV) RNA was tested for, and HCV genotypes determined, in 96 patients with haemophilia A in Japan. Of 88 patients aged > or = 10 years, 74 (84%) were positive for HCV RNA at a frequency higher than that in patients aged less than 10 years (one of eight, 13%, P < 0.001). Genotype I/1a was detected in 30(40%), II/1b in 12 (16%), III/2a in eight (11%), IV/2b in five (7%) and V/3a in 12 (16%); mixed infection with HCV of two different genotypes was identified in the remaining nine (12%). This distribution was markedly different from that in 767 Japanese HCV carriers without haemophilia, in whom II/1b accounted for the majority (68.7%), I/1a was rare (0.5%), V/3a was absent, and mixed infection was observed rarely (1.3%). Mixed infection was transient in all of the seven haemophilic patients who were followed for 1 to 7 years. One of them was infected with genotype II/1b and an unclassifiable genotype, which showed nucleotide sequence similarity to genotype 4c from Zaire (82% homology in the E1 gene) and to 4a from Egypt (91% homology in a part of the NS5b region). In this patient, HCV of genotype II/1b disappeared while that of group 4 survived during a 4-year observation period. These results indicate different epidemiology of HCV genotypes in Japanese haemophiliacs, attributable to HCV contaminating factor VIII imported in the past, and an increased opportunity in haemophiliacs for mixed infection with HCV of different genotypes.

Adolescent

Polypoid carcinoma of the tongue.

An unusual case of polypoid carcinoma in a 72-year-old woman is reported. The tumor showed a pedunculated growth on the lateral border of the tongue and was composed of a malignant basaloid component in intimate association with definable foci of epithelial dysplasia of the surface mucosa. It was considered that histologic features of the present case corresponded with those of basaloid squamous carcinoma.

Aged

Glandular odontogenic cyst with hyaline bodies: an unusual dentigerous presentation.

We present an unusual case of glandular odontogenic cyst (GOC) enclosing the crown of an impacted canine that developed in the anterior mandible in a 54-year-old woman. Microscopically, it contained numerous glandular structures and hyaline bodies in the epithelial lining. The present rare case is sufficiently distinctive to be considered a dentigerous variant of GOC.

Cuspid

[LY188011 phase I study. Research Group of Gemcitabine (LY188011)].

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.

Adult

[Helicobacter pylori and gastric cancer].

H. pylori has been included as a definite biological carcinogen by WHO/ IARC. H. pylori is thought to play a role in the gastritis-metaplasia-carcinoma sequence by inducing atrophic gastritis. Clinical and epidemiological studies have shown a close association between H. pylori infection and gastric cancer. Yet, experimental evidence is equivocal. Epidemiological evidence also suggests that there are significant variable(s) other than H. pylori infection in gastric carcinogenesis. Clearly many questions regarding the role of H. pylori in gastric carcinogenesis have been left for further study. The authors have summarized these aspects together with their experimental results.

Animals

Helicobacter pylori in Japan.

Recent international consensus statements have concluded that Helicobacter pylori is a causal factor in peptic ulcer disease and a Group 1 carcinogen in humans, and that all patients with peptic ulcer associated with H. pylori infection should receive eradication therapy. There are marked differences in the presentation of peptic ulcer disease between Japanese patients and those from other countries, however, and thus a committee of the Japanese Society of Gastroenterology has been set up to develop guidelines for clinical trials in patients with gastric or duodenal ulcers associated with H. pylori. According to these guidelines, eradication therapy should normally consist of dual therapy with a proton pump inhibitor, such as omeprazole, and an antibiotic; a nitroimidazole can be added, however, if necessary. The diagnosis of H. pylori should be made on the basis of a positive culture of the organism or histological examination of gastric biopsies, together with a positive urease test or 13C-urea breath test. Eradication should be confirmed by the same means 4-6 weeks after treatment. Other research is investigating the relationship between H. pylori and gastric cancer, an important issue in view of the high incidence of this condition in Japan. There is evidence that the Mongolian gerbil may be a useful animal model to investigate this question.

Helicobacter Infections

The effects of dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice.

BACKGROUND: The increasing trend of colon cancer in Japan is attributed to changes in dietary habits, that is, increased amounts of fat and decreased amounts of fiber in the diet. The effects of Japanese dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice were examined. METHODS: Eighteen ICR mice in each group were fed with either a basal diet or a diet containing 5%, 10%, or 20% of yugao powder for 35 weeks. All the mice received a weekly intraperitoneal injection of 1,2-dimethylhydrazine (DMH), 10 mg/kg body weight for 10 weeks. The effects of yugao powder on the mucosal and luminal variables involved in colonic carcinogenesis were then compared with those of wheat bran in the mice without any carcinogen treatment. RESULTS: The incidence of colon tumors (adenocarcinomas) was lower in the yugao powder diet groups than in the basal diet group at week 35 (24% vs. 50%, P < 0.05). The bile acid concentration in the colon was reduced in all the fiber diet groups except for the 5% yugao powder diet group. The colonic luminal pH acidified as yugao powder contents also increased in the yugao powder diet groups. The findings on the colonic short chain fatty acids, microflora, and mucosal fatty acids and ornithine decarboxylase activity were all inconsistent with a tendency to either develop or to inhibit carcinogenesis in both the fiber diet groups. CONCLUSIONS: Dietary fiber from yugao-melon suppressed DMH-induced colonic carcinogenesis in mice by lowering the bile acid concentration and pH in the colon. The results of the luminal and mucosal variables examined also suggested that the mechanisms of action of yugao powder against colonic carcinogenesis differed from those of wheat brain.

Adenocarcinoma

Detection of immunoreactive antigen, with a monoclonal antibody to measles virus, in tissue from a patient with Crohn's disease.

Using immunofluorescence (IF), we investigated reactive antigens present in Crohn's disease patients with monoclonal antibodies derived from cells infected with measles virus, but not with the subacute sclerosing panencephalitis virus. During immunoblotting, one monoclonal antibody (mAb 86) reacted with a polypeptide with a molecular weight of 36,000 dalton (M; matrix protein) in measles virus-infected cells. This monoclonal antibody displayed a positive reaction only with tissues from patients with Crohn's disease by the IF test. It did not react with samples from patients with other chronic inflammatory bowel diseases, such as ulcerative colitis. Other monoclonal antibodies to the measles virus protein, and monoclonal antibodies to Herpes simplex virus type 1 did not react with the same tissue samples. The role of measles virus infection and/or a viral antigen (possibly the M protein) as a causative agent in Crohn's disease poses a challenging avenue for further research.

Antibodies, Monoclonal

Effect of leukotriene C4D4 antagonist on colonic damage induced by intracolonic administration of trinitrobenzene sulfonic acid in rats.

We examined the effects of eicosanoid antagonists on colonic damage induced by trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bowel model. TNB (30 mg) dissolved in 0.25 ml of 50% ethanol, was given intrarectally. The appropriate doses of ONO-1078 (a leukotriene C4D4 antagonist), ONO-4057 (a leukotriene B4 antagonist), and OKY-046 (a thromboxane A2 synthetase inhibitor) were given to obtain the same blood level, either 4 h before (pre-treatment model) or 24 h after (the post-treatment model) the administration of TNB (n = 8 in all groups). Drugs were given once daily for 6 days through a gastric feeding tube. Autopsy was performed on the 7th day. Colonic damage was assessed in terms of colonic damage scores, and myeloperoxidase (MPO) activity and eicosanoid concentrations in colonic tissues were measured. Compared with the group given TNB alone, the colonic damage score was reduced to 10% in the pre-treatment model with ONO-1078, but the score was not reduced in other groups, MPO activity was not changed in any group. The concentration of leukotriene C4 was reduced with ONO-1078 treatment, in both pre- and post-treatment models. These results demonstrated that a leukotriene C4D4 antagonist reduced colonic inflammation; however, its anti-inflammatory effect was limited in this colitis model.

Animals

Proton pump inhibitors for Helicobacter pylori eradication in patients with peptic ulcer.

We investigated the effects of omeprazole or lansoprazole on peptic ulcer healing, eradication of Helicobacter pylori (Hp) and abdominal symptoms. A prospective, randomized study was performed for the administration of omeprazole or lansoprazole. Hp-positive peptic ulcer patients (n = 86) were randomly assigned to two groups. Gastric ulcer patients received omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 8 weeks. Duodenal ulcer patients were given omeprazole 20 mg once daily or lansoprazole 30 mg once daily for 6 weeks. Endoscopy was performed at baseline, at the end of therapy, and 4 weeks after stopping therapy. The colony factor units (CFUs) of Hp in biopsy specimens were examined. The CFUs of Hp in gastric and duodenal ulcer were significantly decreased at 4 weeks after stopping lansoprazole therapy. We conclude that Hp eradication by combined use of lansoprazole with antibiotics appears to be a promising therapy.

2-Pyridinylmethylsulfinylbenzimidazoles

Eradication of Helicobacter pylori with lansoprazole and clarithromycin in gastric ulcer patients.

This study attempted to determine the efficacy of lansoprazole plus clarithromycin therapy in the eradication of Helicobacter pylori in gastric ulcer patients. The influence of H. pylori eradication on healing and relapse of ulcers was also studied. Thirty-nine patients received either lansoprazole 30 mg daily for 8 weeks (group 1) or clarithromycin 200 mg twice daily for 2 weeks and lansoprazole 30 mg daily for 8 weeks (group 2). Before treatment, H. pylori status was evaluated by a rapid urease test and histologic examination. H. pylori clearance and eradication were evaluated by a rapid urease test, polymerase chain reaction, and a [13C]urea breath test. Clearance of H. pylori was 0% in group 1 and was 33% in group 2. Eradication of H. pylori was 0% in group 1 and 21% in group 2. Although all five ulcers were healed in patients with H. pylori eradication, ulcers were not healed in the five patients without eradication. Relapse of ulcer was observed in three patients in whom eradication had failed. In this study, for H. pylori-positive gastric ulcer patients, better results were obtained when lansoprazole plus clarithromycin therapy was used, and H. pylori eradication was achieved.

2-Pyridinylmethylsulfinylbenzimidazoles

Combination therapies with a proton pump inhibitor for Helicobacter pylori-infected gastric ulcer patients.

We investigated the eradication and recurrence rate of Helicobacter pylori-infected gastric ulcer patients by combination therapies. Eighty-six H. pylori-positive gastric ulcer patients were assigned randomly to one of seven groups: I, omeprazole 20 mg (n = 9); II, lansoprazole (LPZ) 30 mg (n = 16); III, LPZ 30 mg plus plaunotol 480 mg (n = 13); IV, LPZ 30 mg plus ecabet sodium 2 g (n = 11); V, LPZ 30 mg plus clarithromycin 600 mg (the first 2 weeks; n = 11); VI, LPZ 30 mg plus plaunotol 480 mg plus clarithromycin 600 mg (the first 2 weeks; n = 13); and VII, LPZ 30 mg plus ecabet sodium 2 g plus amoxicillin 1,500 mg (the first 2 weeks; n = 13). All therapy was for 8 weeks except where otherwise noted. H. pylori eradication rates as diagnosed by culture, histology, urease test, and [13C]urea breath test 4 weeks after stopping therapy were 0, 0, 8, 45, 6, 46, and 62%, respectively, in groups I-VII. No patient achieving H. pylori eradication suffered recurrence. The combination therapies with proton pump inhibitors in addition to antibiotics and antiulcer agents are safe and effective in H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles

Occurrence of Graves' disease during retreatment with interferon-alpha 2a for chronic hepatitis C.

The present report describes a patient who developed Graves' disease 3 months after inception of retreatment with higher doses of interferon-alpha 2a for chronic hepatitis C, although the initial 6-month treatment caused no serious adverse reactions. Severe hyperthyroidism continued despite discontinuation of interferon-alpha 2a, and the patient was subsequently treated with 131I. This case suggests careful evaluation of the safety of retreatment to prevent manifestation of such a complication in the retreatment of chronic hepatitis C with interferon.

Adult