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Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 721 records · Page 40Linked to original sources

A 1-h topical therapy for the treatment of Helicobacter pylori infection.

OBJECTIVE: A novel topical therapeutic methodology for the treatment of Helicobacter pylori infection was developed and studied in 25 patients with H. pylori to evaluate safety and efficacy. METHODS: The patients had been given lansoprazole (30 mg, hs) orally and pronase (18,000 tyrosine units, b.i.d.) for the 2 days before topical therapy. One hundred milliliters of solution with 80 ml of 7% sodium bicarbonate and 20 ml of contrast medium meglumine sodium amidotrizoate containing bismuth subnitrate (1 g), amoxicillin (2 g), metronidazole (1 g), and pronase (36,000 tyrosine units) were instilled into the stomach through a nasally introduced 16-Fr intestinal tube with a balloon at its radiopaque tip, which was inflated with approximately 25 ml of air and lodged postbulbarly at the superior duodenal angle under fluoroscopy, thus preventing leakage of the solution distally into the jejunum. The solution was kept in the stomach for 1 h, and the patient's position was changed every 15 min from the sitting to the supine, prone, and right lateral position to expose the entire gastric mucosa. The solution was suctioned at the end of the procedure. RESULTS: H. pylori infection was successfully cured in 24 (96%) patients, confirmed 4 wk after the therapeutic procedure by negative smear, culture, and histology of the antral and corpus biopsy specimens. No side effects were observed except for loose stools in one case. CONCLUSION: This 1-h topical therapy is a safe, effective, and well tolerated procedure for the treatment of H. pylori infection. With further improvements and modifications of the method itself, as well as of the drug regimens, this method may become a highly efficient modality for anti-H. pylori therapy.

Adult↗

[A case of bilateral multiple lung metastases from breast cancer successfully treated with carboplatin].

A 57-year-old female was admitted for right breast tumor. Modified radical mastectomy (Kodama method) was carried out. A prophylactic postoperative radiation was undertaken because of large tumor (T4b) and histologic metastasis to a Rotter's lymph node. At the end of irradiation, bilateral lung metastases were found on chest CT gram. The combination endocrine chemotherapy using MPA 600 mg and UFT 3 capsules p.o. daily and ADM 10 or 20 mg i.v. every two weeks was performed on an outpatient basis. As the lung metastases were increased four months later, carboplatin 150 mg i.v. was replaced with ADM. Four months later, the metastases almost disappeared on CT gram. These results suggested the possibility of one of the therapeutic options for metastatic breast cancer.

Adenocarcinoma↗

[Improvement of pulmonary eosinophilic granuloma after smoking cessation in two patients].

We encountered two cases in which pulmonary eosinophilic granuloma improved after cessation of smoking. The patient in case 1 was a 39-year-old woman. She smoked 10-15 cigarettes a day for 20 years. The patient in case 2 was a 19-year-old man. He smoked a pack of cigarettes a day for 5 years. CT revealed cystic lesions and small nodular lesions predominantly in the upper and middle lung fields. Diagnosis was made by thoracoscopic lung biopsy in case 1 and by transbronchial lung biopsy in case 2. After smoking cessation, symptoms, CT findings, and vital capacity of both patients improved remarkably. Smoking cessation may have been related to the improvement in these patients.

Adult↗

Double-blind comparative study of sulfasalazine and controlled-release mesalazine tablets in the treatment of active ulcerative colitis.

To evaluate the effect of a controlled-release mesalazine tablet, in patients with ulcerative colitis (UC), a multicenter double-blind study was carried out, using sulfasalazine (500 mg tablet) as the control drug. The mesalazine tablet contained 250 mg of ethyl cellulose-coated mesalazine granules. The patients were assigned to two groups, one to receive mesalazine tablets (1500 mg/day) and a sulfasalazine placebo (group M) and the other to receive sulfasalazine tablets (3000 mg/day) and a mesalazine placebo (group S). The test medications were administered orally for 4 consecutive weeks. The study subjects were selected from among patients with mild to moderate active UC, and 118 patients were enrolled. Concomitant use of steroids and immunosuppressors was prohibited during the study period. Of the 118 patients, 9 dropped out. A total of 109 complete records were thus obtained, 52 in group M and 57 in group S. There was no difference in the improvement of clinical symptoms and endoscopic findings between the two groups. The overall safety, based on adverse reactions and laboratory data, was higher, at 86.5%, for group M (n = 52), compared to 66.7% for group S (n = 57). The general usefulness, based on the improvement and safety, was higher, at 65.3%, for group M (n = 49), compared to 45.6% for group S (n = 57). The controlled-release mesalazine tablet thus appears to be useful in the treatment of mild to moderate active UC.

Adult↗

Adverse effects of sulfasalazine and treatment of ulcerative colitis with mesalazine.

We investigated the adverse effects of sulfasalazine in the treatment of inflammatory bowel disease in Japan. In our first survey, adverse effects were observed in 52 out of 751 patients with ulcerative colitis (6.9%) and in 8 out of 221 patients with Crohn's disease (3.6%); i.e., such effects were observed in 60 out of 972 patients with inflammatory bowel disease. In our second survey, we examined 94 adverse reactions in 64 patients with ulcerative colitis. The main adverse reactions were exanthema, fever, nausea and vomiting, angioedema, and liver damage, in decreasing order of frequency; these reactions accounted for about 80% of the adverse reactions. Most of the reactions (62%) occurred within 1 month after the beginning of sulfasalazine intake. Mesalazine is thought to effectively release the 5-ASA molecule in the colon and has already proven of value in patients with mild active ulcerative colitis. We evaluated the effect of mesalazine in patients intolerant to sulfasalazine. Effectiveness was observed in 14 out of 18 patients with active ulcerative colitis (78%) and in 3 out of 3 patients in the quiescent state. These results suggest that mesalazine is effective for the treatment of patients with ulcerative colitis who are intolerant to sulfasalazine; this drug could be a gleam of hope to those patients.

Adverse Drug Reaction Reporting Systems↗

The role of proinflammatory and immunoregulatory cytokines in the pathogenesis of ulcerative colitis.

We investigated the production of proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) and immunoregulatory cytokines (IL-2, IFN-gamma, and IL-10) in the colonic mucosa of patients with active ulcerative colitis (UC), inactive UC, and non-inflammatory bowel disease (IBD) colitis by organ culture. The production of proinflammatory cytokines was significantly increased in all the studied groups compared with controls. In active UC, levels of these cytokines, except for IL-1 beta, were markedly increased compared with non-IBD colitis, and the levels were positively correlated with the degree of inflammation. Patients with non-refractory active UC receiving steroids showed levels of IL-1 beta and TNF-beta production similar to those in controls. IL-10 production was also significantly increased in all the studied groups, the value of being the highest in active UC. In contrast, IL-2- and IFN-gamma production was significantly decreased in both active and inactive UC compared with controls, and the values in active UC were inversely correlated with the degree of inflammation. In non-IBD colitis, decreased IL-2 production was observed, but IFN-gamma production did not differ from that in controls. In an experimental study, each of the proinflammatory cytokines was injected into the colonic mucosa of rats. All of these proinflammatory cytokines, except for IL-1 beta induced colonic mucosal damage that showed some histologic features similar to those of UC. These results suggest that the increased production of proinflammatory cytokines, particularly of IL-6 and IL-8, and the decreased production of IL-2- and IFN-gamma, probably downregulated by the enhanced production of IL-10, play an important role in the pathogenesis of UC.

Animals↗

Dual therapy with lansoprazole and clarithromycin for eradication of Helicobacter pylori.

AIM: To evaluate the eradication of Helicobacter pylori by therapy with a combination of 60 mg lansoprazole and 800 mg clarithromycin. PATIENTS AND METHODS: In an open therapeutic trial, 30 H. pylori-positive patients with active ulcer disease took 30 mg lansoprazole twice a day and 400 mg clarithromycin twice a day for the first 2 weeks, followed by 30 mg lansoprazole once a day for 4-6 weeks. Endoscopy was performed both before and at the end of therapy, and 4 weeks after the end of the therapy. H. pylori was detected by using a combination of smear, culture and tissue sections. RESULTS: Complete pain relief occurred within 3 days in all patients and all ulcers were healed by the end of the therapy. The H. pylori clearance rate was 83.3% and the eradication rate was 73.3%. A minor side effect (metallic taste) was reported by only one patient (3.3%). CONCLUSIONS: Therapy with a combination of 60 mg lansoprazole and 800 mg clarithromycin is efficacious in the eradication of H. pylori and has the advantage of a low incidence of side effects and quick pain relief for patients with active ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Helicobacter pylori detected deep in gastric glands: an ultrastructural quantitative study.

To determine the presence of Helicobacter pylori deep in the gastric glands and in the parietal cell canaliculi, biopsied specimens from 15 patients were observed by electron microscopy. In the specimens, 818 H. pylori and 1,846 parietal cells were detected. Most of the H. pylori (93.9%, 768/818) were present on the mucosal surface. However, a few organisms (50/818, 6.1%) were detected deep in the mucosa. The mean number of H. pylori per specimen was 2.13 (32/818, 3.9%) and 1.20 (18/818, 2.2%), deep in the gland and in the parietal cell canaliculi, respectively. All appeared morphologically intact. Although the combination of culture and histology from biopsy tissues is usually used for isolation of H. pylori in most laboratories, such organisms are considered difficult to detect with conventional methods and to dislodge with antimicrobial therapy. Therefore, H. pylori present deep in the mucosa are suggested to be one of the factors in recrudescence after eradication therapy. In addition, H. pylori in the parietal cell canaliculi may affect parietal cell function or alter gastric physiology.

Adult↗

Free radical-mediated oxidation of lipids induced by hemoglobin in aqueous dispersions.

In order to elucidate the effects of hemoglobin on the oxidative damage, the oxidations of soybean phosphatidylcholine (PC) liposomes and low density lipoprotein (LDL) in aqueous dispersions induced by ruptured erythrocytes (hemolysate) and methemoglobin were studied. The rate of oxidation of soybean PC liposomes induced by hemolysate was much faster than that induced by the same concentration of ferric sulfate or cupric chloride and increased with the increase in the amount of hemolysate. When soybean PC was treated beforehand with ebselen, which decomposes hydroperoxides but can not scavenge free radicals, the oxidation did not proceed. Furthermore, the oxidation was suppressed by the addition of pentamethylchromanol in liposomal membrane. The reaction of hemoglobin with methyl linoleate hydroperoxide in aqueous dispersions was also studied. It was found that hemolysate and methemoglobin decomposed the hydroperoxides much faster than cupric chloride and ferric sulfate. The electron spin resonance study strongly suggested that both hemolysate and methemoglobin decomposed hydroperoxides rapidly to form alkoxyl and peroxyl radicals. It was also found out by spectrophotometrical study and by using carbon monoxide and potassium cyanide that hemolysate was oxidized by organic hydroperoxide to form methemoglobin and ferrylhemoglobin. The rate of oxidation of LDL induced by hemolysate was much slower than that of soybean PC liposomes, while LDL was oxidized faster than soybean PC liposomes by cupric chloride under the same conditions. However, in the presence of tert-butyl hydroperoxide, the oxidation of LDL induced by hemolysate proceeded rapidly. These results were interpreted by both the chemical reactivity and the accessibility of metal catalyst to the lipid hydroperoxides in LDL and liposomes. It was suggested that hemoglobin released by hemorrhage might play a crucial role in the initiation of oxidative damage in vivo.

Erythrocytes↗

Selectivity of isoprenoid-containing imidazole antifungal compounds for sterol 14-demethylase P450 (P450(14)DM) and 7-ethoxycoumarin O-deethylase P450 of rat liver microsomes.

The imidazole antifungal compound AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) has been shown to be a potent inhibitor for yeast lanosterol 14 alpha-demethylase (P450(14)DM), interacting specifically with the sterol side-chain recognition part of the substrate site through its geranyl moiety. AFK-108 acted as a potent inhibitor for rat liver P450(14)DM, while its farnesyl (AFK-110) and prenyl (AFK-122) homologues were weak inhibitors. This indicates that AFK-108 interacts with rat liver P450(14(DM in the same manner as with the yeast enzyme. However, the difference between the potency of AFK-108 and the homologues was greater in rat P450(14)DM than in the yeast enzyme. AFK-108 and its homologues partially inhibited 7-ethoxycoumarin O-deethylase activity of rat liver microsomes. The order of potency was AFK-122 > AFK-108 > AFK-110, indicating that some steric hindrance of the isoprenoid moiety might affect their potency. The inhibitory effect of AFK-108 for P450(14)DM was considerably higher than for 7-ethoxycoumarin O-deethylase P450, while the inhibition of AFK-110 and AFK-122 on these enzymes was of the same order of magnitude. These results suggest that azole compounds interacting with the side-chain recognition site of P450(14)DM may be good candidates as antifungal agents selective for fungal P450(14)DM.

7-Alkoxycoumarin O-Dealkylase↗

Archaebacterial lipid models: formation of stable vesicles from single isoprenoid chain-amphiphiles.

Surfactants, PhyN+(Me)3 (OH-/Br-), PhyPO4H- (H+/Na+), PhySO4- (H+/Na+) and Phy(CO2-) (H+/Na+), were prepared; Phy is a (3RS,7R,11R)-3,7,11,15-tetramethylhexadecyl group; phytanic acid or its sodium salt is expressed by Phy(CO2-) (H+/Na+). Equimolecular mixtures of the cationic surfactant and the anionic ones in aqueous media, upon sonication, gave rise to stable suspensions of multilamellar vesicles (MLVs). Unlike the molecular assemblies from cationic and anionic pairs of straight chain-surfactants, the MLVs could trap ionic and nonionic compounds such as 5(6)-carboxyfluorescein and glucose with the captured volume of 0.6-1.6 l/mol in water. The vesicles were tolerant to about 25 mM aqueous NaCl. The packing mode of the surfactants in the membranes are discussed in conjunction with the thickness (about 60 A) and the zeta-potential which was as large as 30-45 mV in water at 20 degrees C.

Archaea↗

Interaction of alpha-tocopherol with copper and its effect on lipid peroxidation.

The interaction between alpha-tocopherol and copper ion and its effect on the oxidations of methyl linoleate micelles and soybean phosphatidylcholine liposomes in aqueous dispersions have been studied. alpha-Tocopherol reacted with copper in methanol with a rate constant estimated as 0.56 M-1s-1 at 37 degrees C. Similarly, alpha-tocopherol incorporated into methyl linoleate and ethyl palmitate micelles and also phosphatidylcholine liposomal membranes interacted with copper at roughly the similar rate. In every case, the formation of alpha-tocopheroxyl radical and reduction of cupric ion to cuprous ion were observed. Under these circumstances, alpha-tocopherol acted as a prooxidant rather than antioxidant. This interaction was also observed between endogenous alpha-tocopherol in human low density lipoprotein and copper, and the rate was estimated to be higher than that in methanol, implying the facile interaction of the two at LDL surface. However, copper incorporated in ceruloplasmin or chelated with albumin did not interact with endogenous alpha-tocopherol in LDL. It was concluded that alpha-tocopherol reacts with free copper(II) ion to give more reactive copper(I) ion and may act as a prooxidant for lipid peroxidation in the presence of free copper ion. However, such a prooxidant effect of alpha-tocopherol may not be important in vivo, where substantially all the copper ion must be sequestered.

Cations, Divalent↗

Occurrence of a P450 showing high homology to yeast lanosterol 14-demethylase (P450(14DM)) in the rat liver.

The rat liver cDNA library in lambda gt11 was screened with the antisera against rat liver lanosterol 14 alpha-demethylase (P450(14DM)), and one clone (pRT-9) was isolated. The open reading frame of pRT-9 cDNA showed high homology to yeast P450(14DM) (48.9% in nucleotides and 37.7% in amino acids). Homology of the heme-binding region of pRT-9 protein to that of yeast P450(14DM) was 80%. Three additional regions showing more than 60% homology were identified and one of them was assignable as the distal helix. These findings suggest that pRT-9 protein is P450(14DM) and P450(14DMs) of rat and yeast may be orthologous. This is the first evidence suggesting the occurrence of orthologous P450 in widely diverged species.

Amino Acid Sequence↗