Total synthesis of sulfated Le(a) pentaosyl ceramide.
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Biomedical subjects
Publications and source records attributed to M Iida.
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Recent studies have shown that eosinophils are capable of generating and releasing cytokines, providing a novel biologic aspect of eosinophils for regulating allergic inflammation by an autocrine or paracrine mechanism. Eosinophils synthesize various cytokines; however, the physiologic stimuli that trigger eosinophils to generate cytokines have not been fully elucidated. We examined the effect of chemotactic agonists on eosinophil cytokine generation by employing the determination of IL-8 as the main parameter. Both C5a and FMLP stimulated eosinophils to release IL-8, whereas platelet-activating factor and C-C chemokines did not exert any significant effects. On a molar basis, C5a was two orders of magnitude more potent than FMLP. The generation of IL-8 by chemoattractants was absolutely dependent on the presence of cytochalasin B. Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production, indicating the involvement of pertussis toxin-sensitive G-proteins in the signal-transduction process leading to these responses. Experiments of in situ hybridization and PCR amplification revealed that both C5a and FMLP promoted eosinophil IL-8 production through transcriptional gene activation. Pyrrolidine dithiocarbamate completely abrogated chemoattractant-induced IL-8 production, indicating the involvement of NF-kappa B in the cytoplasmic/nuclear signal-transduction process. Furthermore, chemoattractant-induced cytokine production was not limited to IL-8; C5a and FMLP but not platelet-activating factor induced significant secretion of granulocyte-macrophage-CSF from eosinophils. These results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokines, which could be an important mechanism in the regulation of allergic inflammation.
Clinical and endoscopic manifestations of 18 gastric inflammatory fibroid polyps (IFP) in 16 patients who underwent endoscopic or surgical removal were retrospectively analyzed. All of the lesions were located within the pyloric antrum, and the sizes varied from 0.8 to 7.0 cm. On endoscopy, six polyps which measured 1.0 cm or less uniformly seemed to be sessile or intramural tumors, whereas four of the nine polyps between 1.1 and 2.0 cm in size were additionally accompanied by a central depression. The remaining three, which measured more than 2.0 cm, showed characteristic polypoid growth with ulcerations. Three polyps more than 1.0 cm in size occasionally prolapsed into the duodenal bulb. Three patients with these prolapsing polyps and two with polyps accompanied by ulcerations experienced abdominal pain, nausea, or severe anemia. Two polyps (11%) were precisely diagnosed as IFP by means of conventional forceps biopsy. Histological examinations revealed that all of the polyps proliferated within the submucosa. Therefore, this type of polyp may be subject to endoscopic removal to enable a precise diagnosis and treatment.
A total of 263 gastric hyperplastic polyps, which had been removed endoscopically from 202 patients, were clinicopathologically analyzed. Among these polyps, there were nine polyps with neoplastic components (3.4%), corresponding to adenoma in five lesions and mucosal adenocarcinoma in four lesions. Comparing the neoplastic transformed polyps with the pure hyperplastic polyps, there was no significant difference according to age, gender, location, gross appearance, or size. However, the transformed polyps which were located in the lower third of the stomach were larger in size (mean, 20.8 mm) and were more likely to be found among older patients (mean, 75.8 years) than were the pure hyperplastic polyps (mean size and age: 14.5 mm and 61.8 years). These results may indicate the possibility of a different carcinogenesis belonging to gastric hyperplastic polyps by location, and this finding seems to be significant in the application of endoscopic polypectomy.
A case of familial adenomatosis coli with villous adenoma of the third portion of the duodenum, which falls in the category of a Gardner's syndrome, is described. The patient, who had complained of an abdominal mass which had been diagnosed as a desmoid tumor after surgical resection, had numerous adenomatous polyps throughout the colon confirmed by colonoscopy with biopsy. Endoscopic examination of the upper gastrointestinal tract revealed fundic gland polyposis in the stomach and numerous small adenomas in the duodenum. In addition, there was a pedunculated polyp in the third portion of his duodenum, measuring 30 mm in diameter, the surface of which had a cauliflowerlike appearance. The polyp was removed with the electrocautery snare and was histologically diagnosed as villous adenoma. Our case report supports the concept that villous adenoma, which possesses a high malignant potential, may occur in the upper gastrointestinal tract in patients with familial adenomatosis coli, and careful examination of the upper gastrointestinal tract including the distal duodenum seems to be necessary in the follow-up patients with this disease.
We describe a very rare case in which macroamylasemia was associated with ulcerative colitis of total colitis type. The patient's serum amylase isozyme pattern by electrophoresis showed a broad abnormal peak toward the side of the positive pole compared with regular salivary and pancreatic fractions. Sephadex G-200 column chromatography showed a sedimentation coefficient of 6.6 S. Amylase activity was bound to IgG. Double diffusion experiments demonstrated that amylase activity could be precipitated in gel by an antibody to the lambda chain. Although inflammatory bowel disease is occasionally associated with hyperamylasemia due to pancreatitis, we emphasize that, when hyperamylasemia is recognized in patients with inflammatory bowel disease, macroamylasemia also should be considered.
This case report describes a patient with a rare form of ectopic sebaceous glands. The patient was a 53-year-old woman complaining of prolapse of a polyp through the anus who was admitted for polypectomy of the rectal polyp. After polypectomy, esophagogastroduodenoscopy was performed to detect other lesions. Although she had no symptoms from an upper gastrointestinal series, such as dysphagia, heartburn, or epigastric pain, multiple yellow rounded elevated lesions arranged in rows, 0.5 mm in diameter and more than 100 in number were observed in the middle and lower esophagus. Histological examination of the biopsied specimens taken from the lesions endoscopically revealed a structure with the characteristics of a sebaceous gland including an excretory duct.
We investigated the endoscopic and histologic features of 74 nonpolypoid neoplasias of the colorectum measuring 15 mm or less in diameter. Colonoscopically, they were characterized by flat growth, being either slightly elevated with a central depression or else completely flat against the surrounding mucosa. Of the 54 lesions measuring 5 mm or less in diameter, 3 (7%) were diagnosed as cancer, whereas the remaining 51 (93%) were diagnosed as adenomas with moderate epithelial atypia. The lesions measuring more than 5 mm were fewer in number (20), and they were more frequently given the histologic diagnosis of severe epithelial atypia (20%) and cancer (70%). Whereas the endoscopic features of the cases of adenoma with moderate atypia included both complete flatness and flat-topped elevation with a central depression, the lesions diagnosed as adenoma with severe atypia were endoscopically recognized as flat or slightly depressed lesions, and a deep central depression or prominent elevation was noted in the lesions diagnosed as cancer. These findings suggest that some minute nonpolypoid neoplasias may transform to nonpolypoid cancers and invade the submucosa, whereas others do not manifest rapid growth.
The clinicopathologic and endoscopic features of 15 patients with small flat cancer of the rectum were investigated. Whereas 4 patients had hematochezia, the remaining 11 patients were asymptomatic, and stool positive for occult blood was the only remarkable clinical feature in 8 of them. Endoscopic features were slight elevation with central depression in 8 lesions, flat-topped elevation in 4, and shallow depression with irregular margin in 3. The surface of the tumor was often faint red in color and frequently characterized by mucosal friability. Five flat rectal cancers were missed during initial endoscopy, and they were found by repeated endoscopic examination. Three flat cancers were not identified in the distal rectum until retroflexed colonoscopic observation was performed. Although all tumors were smaller than 2 cm in diameter and 6 of them were under 1 cm, 9 lesions had deeply invaded the submucosal layer and 7 tumors showed lymphovascular permeation. Two lesions of 1 cm or greater had metastasized to perirectal lymph nodes. These results suggest that careful observation during endoscopy is necessary to detect flat rectal cancers, and a U-turn to examine the anorectal junction should be routinely done in the appropriate age group.
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We examined the combined effect of fosfomycin and ofloxacin against Pseudomonas aeruginosa in biofilms by using an in vitro experimental system with a modified Robbins device. Sessile cells in a mature or immature biofilm, developed on a silicon disk, were used, and an ATP bioluminescence assay was employed to assess antibacterial effects. A synergistic effect of fosfomycin and ofloxacin was clearly detected when concentrations at which each drug independently produced no detectable decrease in the bioactivity of sessile cells were used. Exposure of the cells in a mature biofilm to fosfomycin at concentrations of one-eighth of the MIC to 10 times the MIC (6.25 to 500 micrograms/ml) and ofloxacin at three or 10 times the MIC (18.75 or 62.5 micrograms/ml) resulted in reduction of the bioactivity to 1.5 to 4.5% after 72 h. Young sessile cells in an immature biofilm were more susceptible to this combination therapy. With a combination of fosfomycin at three times the MIC and ofloxacin at three times the MIC, complete eradication was confirmed by both ATP assay and scanning electron microscopy.
PURPOSE: To characterize posttraumatic intestinal stenosis clinically and radiographically. MATERIALS AND METHODS: The clinical records and radiographic and pathologic findings were reviewed in four patients with posttraumatic stenosis. RESULTS: The patients experienced abdominal symptoms from 1 to 18 weeks after the trauma. While the small intestine was affected in two patients with ileus, the colon was involved in the other two patients with rectal bleeding or diarrhea. Barium studies showed an irregular contour within the severely narrowed intestine in three patients, even 25 weeks after the trauma. In these three patients, pathologic examinations of the resected specimens revealed a circumferential, open ulcer, whereas a scarred ulcer was present in the other patient. CONCLUSION: Posttraumatic intestinal stenosis is clinically characterized by a delayed onset of symptoms that differ according to the site of involvement. This condition should be included in the differential diagnosis of intestinal stenosis.
Recent studies have shown that eosinophils are capable of generating and releasing cytokines, illustrating a novel biologic aspect of eosinophils in regulating allergic inflammation by either autocrine or paracrine mechanisms. The effect of chemotactic agonists on eosinophil cytokine generation was examined by determination of interleukin-8 (IL-8) as a main parameter. Both complement C5a and N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated eosinophils to release IL-8, but platelet activating factor (PAF) did not exert any significant effects. The generation of IL-8 by chemoattractants was absolutely dependent on the presence of cytochalasin B. Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production, indicating the involvement of pertussis toxin-sensitive G proteins in the signal transduction process. In situ hybridization showed that both C5a and FMLP promoted eosinophil IL-8 production via transcriptional gene activation. Furthermore, C5a and FMLP, but not PAF, induced significant secretion of granulocyte-macrophage colony-stimulating factor from eosinophils. These results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokines, which could be an important mechanism in the regulation of allergic inflammation.
BACKGROUND AND PURPOSE: Understanding the effects of alcohol intake on stroke and other cardiovascular diseases is an important issue for public health. METHODS: A 10.5-year prospective study of the relationship between alcohol intake and cardiovascular disease incidence was conducted in 2890 men, aged 40 to 69 years and free of a history of stroke and coronary heart disease, in three rural communities of Japan. RESULTS: One hundred seventy-eight strokes (40 intracerebral hemorrhages, 18 subarachnoid hemorrhages, 104 nonhemorrhagic strokes, and 16 unclassified strokes), 34 coronary heart disease events, and 19 sudden unclassified deaths occurred. Drinkers of > or = 70 g/d ethanol had an approximately 2.5 times higher age-adjusted risk of all stroke than never-drinkers; the excess risk was more evident for hemorrhagic stroke than nonhemorrhagic stroke. When hypertension category, serum total cholesterol level, cigarette smoking, and diabetes mellitus were taken into account, these excess risks were reduced but remained significant for all stroke (2.0; 95% confidence interval, 1.3 to 3.1) and hemorrhagic stroke (3.4; 95% confidence interval, 1.2 to 9.2). A J-shaped relationship was suggested between alcohol intake and risk of nonhemorrhagic stroke; drinkers of < 42 g/d ethanol had a slightly lower risk and heavy drinkers had a higher risk than never-drinkers. Current drinkers had a slightly lower risk of coronary heart disease than never-drinkers, although the risk difference was not statistically significant. The age-adjusted risk of sudden death was 10 times higher in heavy drinkers than never-drinkers, and the excess risk did not change when the covariates were controlled for. Total cardiovascular disease showed a similar pattern as did all stroke. CONCLUSIONS: Heavy drinking appeared to increase the risk of hemorrhagic stroke, in part due to hypertension, and to increase the risk of sudden death, which was probably due to drinking per se. Light or moderate alcohol consumption seemed to protect against nonhemorrhagic stroke and coronary heart disease.
A woman had a karyotype of 46Xinv(X)(p21.2;q26.1) and mosaicism of dystrophin-negative muscle fibers. The X-chromosome inversion was transmitted to her daughter, who had an elevated serum CK. The genetic transmission as well as the probable random inactivation of the abnormal X chromosome in this mildly affected patient distinguish this case from those of dystrophinopathy with X;autosome translocations.
The bronchodilator and cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride) were evaluated. In anesthetized guinea pigs, i.v. bolus injections of NKH477 (1-100 micrograms/kg) inhibited the bronchoconstriction induced by inhaled leukotriene D4, increased the heart rate (HR) and decreased the diastolic arterial blood pressure (DBP) in a dose-dependent manner. The bronchodilator effect of NKH477 was 1500 times more potent than that of aminophylline and 17 times less potent than that of isoproterenol. The selectivity of NKH477 for bronchodilation vs an increase in HR was 15 times higher than that of isoproterenol and similar to that of aminophylline; and vs a decrease in DBP, the selectivity was 4 times higher than that of aminophylline and similar to that of isoproterenol. I.v. infusion of NKH477 (0.1-3 micrograms/kg/min) for 2 hr dose-dependently inhibited the bronchoconstriction induced by i.v. histamine. Isoproterenol (0.1 microgram/kg/min, i.v.) enhanced the bronchoconstriction after termination of the infusion, whereas NKH477 did not. In conscious guinea pigs, inhalation of NKH477 (0.1-5 mg/ml) concentration-dependently inhibited the bronchoconstriction induced by inhaled histamine, and a high concentration of NKH477 (35.4 mg/ml) increased the HR. The bronchodilator effect of inhaled NKH477 was 15 times less potent than that of isoproterenol. The selectivity of inhaled NKH477 was similar to that of isoproterenol. These results indicate that NKH477 may be useful as a bronchodilator.
To examine the prevalence of abnormalities in the insulin receptor structure gene in Japanese with non-insulin-dependent diabetes mellitus (NIDDM), a population of 51 patients with NIDDM was screened for mutations in this gene. Patient genomic DNAs of both alleles corresponding to 22 exons of the gene were amplified by polymerase chain reaction (PCR). The PCR products on pUC19 were sequenced. Three patients with heterozygous missense mutation Thr831-->Ala831 in exon 13 and one patient with heterozygous missense mutation Tyr1334-->Cys1334 in exon 22 of the beta-subunits were identified. Linkage analysis of one of the families plus statistical studies showed that the mutation Thr831-->Ala831 is possibly responsible for the onset of NIDDM. In COS cells transiently expressing both mutant receptor cDNAs and a cDNA of a M(r) 85,000 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase), the mutation Tyr1334-->Cys1334 impaired binding of the receptor with the M(r) 85,000 subunit of PI 3-kinase, but linkage analysis of the family showed that the mutation did not cosegregate with NIDDM in the pedigree. Therefore, one missense mutation (Thr831-->Ala831) in the insulin receptor, as found in three patients, is possibly involved in the etiology of a subset of the 51 NIDDM patients.