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Biomedical subjects

M Iida

Publications and source records attributed to M Iida.

At least 253 records · Page 14Linked to original sources

Total synthesis of glycononaosyl ceramide with a sialyl dimeric Le(x)-sequence.

The first total synthesis of glycononaosyl ceramide with a sialyl dimeric Le(x) sequence 1 is described. Regio- and stereo-selective glycosylations of sialyl donors 6,7,8 with the suitably protected Le(x) trisaccharide acceptors 9,10 beta were performed to give the expected tetrasaccharides 15 and 21, which were converted into the corresponding donors 20 and 22. Boron trifluoride etherate-promoted glycosylation of 20 with pentasaccharide acceptor 11 afforded regioselectively the expected nonasaccharide 23. After replacing benzyl groups of 23 by acetyl groups, the anomeric acetate was transformed into the alpha-trichloroacetimidate 27. The crucial coupling between 27 and (2S, 3R, 4E-3-O-benzoyl-2-N-tetracosanoylsphingenine 3 was executed to afford completely protected beta-glycoside 28. Finally, selective cleavage of the methyl ester and N,O-deprotection of 28 gave the target ganglioside 1.

Carbohydrate Sequence↗

Brain ischemia and gastric mucosal damage in spontaneously hypertensive rats: the role of arterial vagal adrenoceptors.

Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through alpha1-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.

Adrenergic Agents↗

Role of endotoxin-like contaminants in the apparent anti-inflammatory activity of bovine superoxide dismutase.

Bovine CuZn superoxide dismutase (SOD: 1, 3 and 10 mg/kg) dose-dependently reduced carrageenan-induced paw edema in rats when administered intravenously 30 min before irritant injection. However, heat-treated SOD (10 mg/kg) was as effective as native SOD (10 mg/kg) although the enzymic activity was reduced to 9.7%. Examination of the contaminants of the native SOD revealed a fairly large amount of endotoxin-like activity, 47 ng as Escherichia coli endotoxin per mg, and 59.6% of this activity remained after heat treatment. Bovine CuZn SOD (1, 3 and 10 mg/kg), which contained negligible endotoxin-like materials and 1.5 times more enzyme units, had no effect on edema under the same conditions. Furthermore, Escherichia coli endotoxin (10, 100 and 1000 ng/kg) reduced edema dose-dependently. These results suggest that contamination by endotoxin-like materials is responsible for the anti-inflammatory action of the SOD preparation we observed. Hence, the anti-inflammatory action of contaminating endotoxin-like materials may lead to misinterpretation as a protective effect of SOD unless stringent precautions are taken against endotoxin-like contaminants in the SOD under examination.

Animals↗

Esophageal Candida infection and adherence mechanisms in the nonimmunocompromised rabbit.

Candida infection of the esophagus has been reported not only in immunocompromised hosts but also in healthy individuals. However, its mechanisms of action in healthy individuals have not been clarified. Our previous study suggested that physical contact was an important factor for the adherence of Candida albicans. The aim of the present study was to test our hypothesis and clarify the adherence mechanisms. Suspensions of Candida albicans cells were given to rabbits in drinking water without the use of immunosuppressive drugs and/or antibiotics, and the esophagus was examined. Candidial lesions were observed in 14 of 15 rabbits given the suspensions held in water with and without 30% sucrose for 13 days. The number of Candida albicans cells adhering to the esophagus per square millimeter by subepithelial cell insertion was significantly larger than that adhering by attachment. These results indicate that adherence of Candida albicans to the esophagus occurs by sustained physical contact alone under a nonimmunosuppressive state, and that subepithelial cell insertion results in greater attachment on adherence. Our findings provide a clue that may help clarify the mechanism of Candida infection in healthy individuals.

Animals↗

Relationship between structure and inhibitory effect of arginine analogues on neuronal nitric oxide synthase activity.

Since nitric oxide (NO) is synthesized by nitric oxide synthase (NOS) from L-arginine (Arg) which has an amidino group in its molecule, we examined the effect of 29 kinds of Arg analogues on neuronal NOS (nNOS) activity in the rat brain. None of the Arg analogues acted as a substrate for nNOS. Diamidinocystamine, hirudonine, and guanethidine inhibited nNOS activity to 67.3%, 64.2% and 74.1%, respectively, but their inhibitory efficiency was lower than NG-monomethyl-L-arginine (to 36.5%) which is a well known NOS inhibitor. Dimethylguanidine and N-benzoylguanidine also significantly inhibited nNOS activity to 88.0% and 90.7%, respectively. Whereas almost all of the NOS inhibitors previously reported were synthesized by substituting the amidino nitrogen of Arg, none of these new inhibitors were substituted at this position. Furthermore, hirudonine, which is a naturally occurring compound, was thought to act as an agonist at polyamine binding site of the N-methyl-D-aspartate type of glutamate receptor complex. It is also interesting that guanethidine, an antihypertensive agent, inhibit nNOS activity. These new drugs are useful for the investigation not only of the chemical nature of nNOS but also of the physiologic function of NO.

Animals↗

The requirement for and mobilization of calcium during induction by sodium ascorbate and by hydrogen peroxide of cell death.

The requirement for and mobilization of Ca2+ ions during induction of cell death by sodium ascorbate were compared with those during induction of cell death by hydrogen peroxide. When HL-60 cells were incubated with sodium ascorbate, a rapid increase in the intracellular concentration of Ca2+ ions and subsequent apoptotic cell death, characterized by cell shrinkage, nuclear fragmentation and cleavage of internucleosomal DNA to yield fragments that were multiples of 180-200 base pairs, were induced. However, these effects of sodium ascorbate were significantly reduced in Ca2+-depleted medium. By contrast, hydrogen peroxide induced similar apoptosis associated phenomena in the presence and in the absence of extracellular Ca2+ ions. The intracellular concentration of the reduced form of glutathione was not significantly affected and glutathione disulfide was undetectable during the early stages of apoptosis. These data suggest that sodium ascorbate and hydrogen peroxide initiate cell death by different mechanisms.

Apoptosis↗

The significance of colonic mucosal lymphoid hyperplasia and aphthoid ulcers in Crohn's disease.

OBJECTIVE: To access concordance between radiological severity of aphthae and the more advanced features of Crohn's disease. PATIENTS AND METHODS: In 75 patients with an established diagnosis of Crohn's disease, we evaluated the radiological severity of colonic aphthae by meticulous double-contrast radiography. The degree of aphthae was defined as follows: AE0 = no lesions; AE1 = small nodules without barium flecks (lymphoid hyperplasia); AE2 = minute barium flecks < or = 1 mm in size with a translucent halo (umbilical or eroded lymphoid hyperplasia); AE3 = barium flecks varying from 2 mm to 5 mm in size (typical aphthoid ulcerations). We compared the degree of the lesions to the disease activity, and reviewed these sequential changes during a mean interval of 10 months. RESULTS: AE3 lesions were more prevalent than AE1 or AE2 lesions in patients with active colitis. AE1 or AE2 lesions were found regardless of the involved bowel sites or the disease activity. Of 44 patients receiving a nutritional diet, 26 patients showed regression of the lesions although most of the patients still exhibited AE1 or AE2 lesions. In two of eight patients without the treatment, the lesions progressed. CONCLUSION: In Crohn's disease, development of aphthoid ulcers is associated with disease activity; lymphoid hyperplasia may exist independently of disease activity.

Adolescent↗

Nonpolypoid adenomas of the duodenum in patients with familial adenomatous polyposis (Gardner's syndrome).

BACKGROUND: Although duodenal adenomas are very common in familial adenomatous polyposis, we wished to emphasize our experience with finding nonpolypoid adenomas in the duodenum of patients with this disease. METHODS: Duodenoscopy was performed in 23 patients with an established diagnosis of familial adenomatous polyposis or Gardner's syndrome. RESULTS: Endoscopy revealed single or multiple nonpolypoid adenomas of the duodenum in 7 patients (30%). The lesions were smaller than 5 mm and were endoscopically recognized as flat or depressed reddish lesions; one lesion was completely flat and the remaining lesions were flat-topped elevations with a central depression. All of the lesions were histologically diagnosed as tubular adenoma with moderate epithelial atypia. CONCLUSION: These findings suggest that duodenal nonpolypoid adenomas are common in familial adenomatous polyposis or Gardner's syndrome and that careful surveillance endoscopy seems necessary in patients with this disease.

Adenoma↗

Time course of coproantigen excretion in Echinococcus multilocularis infections in foxes and an alternative definitive host, golden hamsters.

Coproantigen excretion during experimental infections of Echinococcus multilocularis in foxes and an alternative definitive host, golden hamsters, was evaluated by a sandwich ELISA using a monoclonal antibody. A sigmoidal increase of antigen excretion from the developing parasites was observed in in vitro incubation of the parasites collected on different days during the first 21 days post-infection (DPI). In hamsters, the ELISA O.D. value of faeces became positive at 4 DPI. Thereafter, the O.D. value increased in semi-sigmoidal fashion in the first 42 DPI, probably reflecting the development of the parasites. In foxes, the O.D. value became positive at 6 DPI. However, contrary to that in hamsters, after the initial steep rise, the O.D. value suddenly decreased to 1/2 the level during 15-17 DPI, indicating that a large number of worms might have been expelled. The parasite eggs were detected by the sugar centrifugal-flotation technique (Ito, Yagi & Ishige, 1989) from 29 to 84 DPI but not thereafter to 125 DPI, although mature parasites were detected at 125 DPI. In contrast, positive O.D. values were obtained almost constantly until 125 DPI, indicating that the coproantigen detection assay was more sensitive than the egg detection assay. The detection limit of the coproantigen assay was roughly estimated to be around 100 worms. These observations, along with the fact that the assay was designed to detect a heat-resistant coproantigen in heat-sterilized fecal samples, indicate that the coproantigen detection assay is a safe and useful method, not only for diagnosis in the definitive host of E. multilocularis, but also for monitoring parasite development and change in parasite burden during an experimental infection.

Animals↗

Hyperleptinemia in chronic renal failure.

To investigate the mechanism(s) of degradation of leptin, the protein product of ob (obese) gene, we measured serum leptin levels in 70 patients with chronic renal failure (CRF). The median of serum leptin concentrations of 36 male and 34 female patients with CRF were 7.3 ng/ml ranging from 0.5 to 39.0 ng/ml and 34.9 ng/ml from 1.1 to 76.1 ng/ml, respectively, while those of 29 male and 29 female healthy subjects were 5.8 ng/ml ranging from 0.5 to 37.7 ng/ml and 12.0 ng/ml from 2.0 to 45.2 ng/ml, respectively. The difference in male and female serum leptin concentrations between CRF group and the normal counterpart was statistically significant (p<0.005 and p<0.05, respectively). However, there was no significant correlation, either between serum creatinine or BUN, and serum leptin concentrations. These findings suggest that leptin is degraded and/or filtered in renal tissue.

Adult↗

Plasma fibrinogen and its correlates in urban Japanese men.

BACKGROUND: The intention of the study was to examine determinants of plasma fibrinogen concentrations in Japanese men. METHODS: A cross-sectional study was conducted in 1991 among 995 male employees aged 40-59 years in two urban companies. RESULTS: The overall mean value (standard deviation) of plasma fibrinogen concentration was 257 (57) mg/dl. There was a strong dose-response relationship between cigarette smoking and plasma fibrinogen concentration. Plasma fibrinogen was positively associated with age and serum total cholesterol, and inversely associated with ethanol intake, dietary intake of sea foods such as squid, octopus or shrimp. Intake of other major protein and lipid resources such as meat, eggs and milk, or intake of vegetables was not related to plasma fibrinogen. An effect of dietary intake of sea foods on plasma fibrinogen was small but significant after controlling for the other covariates; an 80 g/week larger intake of sea foods was associated with a 3.9 mg/dl (95% confidence interval: 0.5, 7.3) lower fibrinogen concentration. CONCLUSIONS: This study confirms the relation of known coronary risk factors to plasma fibrinogen in Japanese men, and suggests that dietary intake of sea foods affects plasma fibrinogen concentrations.

Adult↗

Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy.

Upper gastrointestinal endoscopy was performed in patients with rheumatoid arthritis (RA) during the period 1989-1991, and biopsy specimens were obtained from the stomach and from the duodenum for examining amyloid deposits. Among 407 patients, gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-two patients were regarded as having slight amyloid deposits, while 32 patients were categorized as having marked amyloid deposits. The incidence of clinical manifestations suggestive of systemic amyloidosis was more frequent in the marked deposits group than in the slight deposits group (47% vs 14%, P<0.05). Among the patients who died of manifestations associated with amyloidosis, the survival period following endoscopy was shorter in the marked deposits group than in the slight deposits group. These findings suggest that gastroduodenal biopsies may be useful for diagnosing secondary amyloidosis and that the degree of amyloid deposits seems to be correlated with the clinical manifestations of RA.

Amyloid↗

Jejunal angiodysplasia confirmed by intravascular injection technique in vitro. Report of a case and review of the literature.

Angiodysplasia of the small intestine is a rare but important cause of gastrointestinal bleeding. We present a 64-year-old man with repeated melena in whom the diagnosis of multiple angiodysplasia of the jejunum was suggested by angiography. The affected segment of the small intestine, in which reddish patches were detected by intraoperative endoscopy, was removed. The combined technique of injecting a dye and a water-soluble contrast medium into the resected specimen revealed areas of dilated vessels, which were diagnosed histologically as angiodysplasia. This case suggests that angiodysplasia of the small intestine can be recognized clinically before the operation and that the intravascular injection technique is useful in confirming the diagnosis in the resected specimen in vitro. We describe this case in detail and review other cases of small intestinal angiodysplasia reported in the English literature.

Angiodysplasia↗

Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry.

BACKGROUND: The mechanism of ulceration in Crohn's disease remains unknown. AIMS: To clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn's disease. METHODS: After identification of colonic lymphoid nodules and aphthoid lesions by magnifying colonoscopy, 76 biopsy specimens were obtained from 10 patients with Crohn's disease and three patients with colonic lymphoid hyperplasia. This study correlated magnifying colonoscopic, electron microscopic, and immunohistochemical findings of biopsy specimens. RESULTS: In Crohn's disease, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy, showed surface erosions 150-200 microns in size. These lymphoid nodules with red halos had small erosions either light microscopically or electron microscopically in 18 of 21 specimens (86%). Correlation of scanning and transmission electron microscopy showed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was limited in M cells of FAE in the patients with lymphoid hyperplasia without inflammatory bowel disease. In Crohn's disease patients in remission, however, HLA-DR antigen was strongly expressed over the entire FAE of lymphoid nodules with a red halo endoscopically, while the expression was weak and irregular in the mucosa surrounding the lymphoid nodules. HLA-DR was strongly expressed in the entire inflamed colonic mucosa in the active stage. CONCLUSION: The red halo appearance surrounding lymphoid follicles seems to precede visible aphthoid ulcers and suggests that ulcerations in Crohn's disease originate from FAE, possibly related to its physiological role as a portal of entry for potentially pathogenic agents.

Adolescent↗