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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 775 records · Page 43Linked to original sources

Intestinal metaplasia of the stomach confined to the fundic gland area. Report of two cases.

Two patients with intestinal metaplasia of the stomach, whose distribution was exclusively confined to the fundic gland area, are presented herein. The first, a 51-year-old male, had been treated for pernicious anemia for 14 years when he was found to have gastric cancer. His serum gastrin level was quite high, whereas his gastric acid output was markedly low. The polypoid cancer in the fornix of the stomach, which had been removed endoscopically, revealed tubular adenocarcinoma with its invasion limited to the mucosa. The resected stomach showed no residual carcinoma but had numerous minute foci of intestinal metaplasia, diffusely distributed but exclusively confined to the fundic gland area, by macroscopic observation using the leucine aminopeptidase-alkaline phosphatase double staining method. The intestinal metaplasias were all of the complete type, and the parietal and chief cells were almost completely lost. The second patient, a 76-year-old male without pernicious anemia, underwent total gastrectomy for two polypoid cancers in the body of the stomach. The resected specimens, in addition to two hyperplastic polyps in the transitional area, showed the same distribution of intestinal metaplasia as seen in the first patient.

Adenocarcinoma↗

Possible involvement of an impaired baroreflex mechanism but not the renin-angiotensin system and vasopressin in the enhanced pressor responsiveness to physostigmine in spontaneously hypertensive rats.

Effects of physostigmine on heart rate, mean arterial pressure (MAP), plasma renin concentration (PRC) and vasopressin (AVP) release were investigated in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Physostigmine (100 micrograms/kg, i.a.) produced a greater and prolonged hypertensive response in the SHR than in the WKY. Heart rate was increased by physostigmine in SHR rats while it was unchanged in the WKY. PRC was unchanged or even slightly decreased in these animals when MAP was increased by physostigmine. An AVP pressor antagonist did not attenuate the pressor and cardiac effects of physostigmine in these animals. These data indicate that an impaired baroreflex mechanism or a different mode of sympathetic neuronal activation by physostigmine through the central mechanism appears to be contributory, at least in part, to the enhanced pressor responsiveness in the SHR. The renin-angiotensin system and AVP do not appear to be involved in the enhanced pressor responsiveness to physostigmine in SHR rats.

Animals↗

Expression of human lysozyme in an insoluble form in yeast.

A high level of expression in yeast of a chemically synthesized human lysozyme (hL) gene was achieved by introducing an A-rich DNA fragment just upstream from the ATG start codon. The synthesized recombinant human lysozyme (r-hL) was insoluble and biologically inactive. It was solubilized with 7 M urea (pH 9) from yeast cells and its lytic activity was efficiently regenerated by oxidative renaturation. This renaturation experiment and Western blotting analysis under reducing and non-reducing conditions indicate that the insoluble form might be caused by the formation of incorrect intra- or intermolecular disulfide bonds. The N-terminal amino acid sequence of the purified r-hL was identical with that of authentic hL.

Amino Acid Sequence↗

Antihypertensive action of melatonin in the spontaneously hypertensive rat.

The effects of melatonin on blood pressure and heart rate were studied in 23-week-old male spontaneously hypertensive rats. Melatonin infused i.p. at a dose of 6 mg/rat per day for 5 days using an osmotic minipump produced a significant reduction of blood pressure and a slight but significant decrease of heart rate in the conscious and unrestrained state. These cardiovascular effects of melatonin developed gradually. Plasma renin concentration tended to decrease after melatonin treatment. These results demonstrate that melatonin has an antihypertensive action. The mechanism of the antihypertensive action of melatonin requires further study.

Animals↗

Studies on orally active cephalosporin esters.

The synthesis and the biological properties of orally active cephalosporin esters are described. 3-Methoxymethyl cephem derivatives having a 2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamide function at C-7 (1) showed good activity against a wide variety of bacteria including some beta-lactamase producing species. The prodrug type esters of 1 exhibited a good urinary recovery after oral administration to mice and 1-(isopropoxycarbonyloxy)ethyl ester (2a, CS-807) has been pre-clinically tested as an orally active cephem prodrug.

Administration, Oral↗

Comparison of antigenicity of serum immunoglobulin G among human, cynomolgus monkey, African green monkey and squirrel monkey.

Antigenicity of IgG was compared among human, the cynomolgus monkey, the African green monkey and the squirrel monkey by the quantitative precipitation test using purified IgG of and rabbit anti-IgG serum to each species. Clear cross-antigenicity was observed between the cynomolgus monkey and the African green monkey and less clear cross-antigenicity between human and the cynomolgus monkey or the African green monkey. The cross-antigenicity observed between the squirrel monkey and the other three species examined was evidently weak.

Animals↗

Role of the glucopyranose ring in the elicitation of feeding.

To relate the structural characteristics of the glucose pyranose ring to feeding elicitation, biochemically and structurally similar glucose analogues were investigated to determine if they could elicit short- or long-term effects on food intake in rats. Testing solutions were infused once into unrestrained and unanesthetised rats through a chronically indwelling cannula in the third ventricle. D-Glucose markedly decreased meal size in doses from 6 to 24 mumol, but it's epimers, D-mannose, D-allose and D-galactose, did not affect food intake. Among the glucose analogues modified at C-2, rats treated with 12 mumol D-glucosamine ate a much larger size of meal than those with 12 mumol halogenglucoses or 24 mumol 2-deoxy-D-glucose, while 2-fluoro-2-deoxy-D-glucose with 2-chloro-2-deoxy-D-glucose induced a more potent feeding than 2-deoxyglucose. Glucosamine also induced hyperglycaemia, but did not affect plasma insulin. Activity of glucose, sensitive neurons in the lateral hypothalamus was increased by electro-osmotic application of 2-deoxyglucose or glucosamine, and the reciprocity was observed on neurons of the ventromedial hypothalamus. One-aminoglucose (beta-D-glucopyranosylamine), which is an aminoglucose analogue modified on C-1, increased meal size and more potently prolonged the duration of the meal compared to 1-deoxyglucose (1,5-anhydroglucitol). Together with the behavioural and structural characteristics of glucose analogues, a hydroxyl group on C-1 or C-2 is involved in feeding elicitation. The magnitude of the effect can be partly explained by the chemical concept of 'inductive effect'.

Animals↗

[A case of Ewing's sarcoma treated successfully by combination chemotherapy consisting of high-dose methotrexate, aclacinomycin-A and vindesine].

A 22-year-old man was admitted to Kyushu University Hospital because of high fever, and pain in the right foot and back. An X-ray examination revealed an osteolytic lesion on the 5th metatarsal bone of the right foot. Paraplegia and disturbance of bladder function occurred and compression of the spinal cord between T3 and L5 was found by myelography. An extradural tumor was removed by emergent laminectomy, and a histological examination of the tumor showed aggregations of small round cells, which suggested Ewing's sarcoma. Although T-9 protocol was started with initial effect, the tumor recurred during the therapy. The patient was then treated with HD-MTX, ACR and VDS, which induced a clinical improvement for 4 months without maintenance therapy. This result showed that HD-MTX, ACR and VDS warrant further consideration for the treatment of refractory Ewing's sarcoma.

Aclarubicin↗

Distribution of cefodizime to exudate in the croton oil-induced rat granuloma pouch and its therapeutic effects on experimental infections in the pouch.

Cefodizime was compared with cefotaxime (CTX) in regard to its distribution to an inflammatory site (exudate in croton oil-induced granuloma pouch) of rats and its therapeutic effects on experimental infections in such pouches after intravenous injection. Cefodizime levels in rat serum and pouch exudate were higher than those of CTX, and the former compound disappeared from the serum and pouch exudate far more slowly than the latter. In the tests for therapeutic effects, cefodizime showed almost the same degree of inhibitory activity as CTX against growth in pouch exudate of Escherichia coli Ec-7, Proteus mirabilis Pm-428, and Serratia marcescens Sm-390 for which the minimum inhibitory concentrations (MICs) of cefodizime were equal to or greater than the CTX values, and such activity of cefodizime lasted for a longer period than that of CTX. These results suggest that the above pharmacokinetic features of cefodizime compensate for its MICs against organisms displaying lower values for CTX.

Animals↗

In vitro antimicrobial activity of cefpirome, a new cephalosporin with a broad antimicrobial spectrum.

The in vitro activity of cefpirome (HR 810), a new cephalosporin antibiotic having a 2,3-cyclopentenopyridine group in the 3-position side chain, was compared with in vitro activities of 5 other cephalosporins. HR 810 showed a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria when tested using 71 standard strains and 876 clinical isolates. HR 810 inhibited 70% of the clinically isolated Staphylococcus aureus and Staphylococcus epidermidis strains when used at 0.59-0.84 microgram/ml, 2- to 25-fold lower than values of reference antibiotics, and the compound was also highly effective against Enterococcus faecalis which is relatively resistant to most of the existing cephem antibiotics. The activity of HR 810 against Enterobacteriaceae members (11 species), based on its minimal inhibitory concentrations inhibiting 90% of bacterial growth (MIC90S), was the highest among the cephalosporins used. Especially against Enterobacter species and Citrobacter freundii, the MIC90S of the compound were 4- to 64-fold lower than the values of the other antibiotics. Against Pseudomonas aeruginosa, HR 810 was as active as cefoperazone, an antipseudomonal agent. The minimal bactericidal concentrations (MBCs) of HR 810 were equal to or only 2-fold greater than the MICs for most of 12 standard strains tested. The compound markedly decreased viable bacterial counts at its MICs, thus showing strong bactericidal activities. The in vitro activity of HR 810 was not affected by pH or human serum content of agar media, but the activity against Gram-negative bacteria was lowered as the inoculum size increased.

Cephalosporins↗

Gastric K+-stimulated p-nitrophenylphosphatase cytochemistry.

A cytochemical study of gastric K+-stimulated p-nitrophenylphosphatase (K-NPPase) activity, corresponding to a K+-stimulated phosphoprotein phosphatase of H-K-ATPase system, has been made by a new cytochemical method. Sections of fixed guinea pig gastric mucosa in a mixture of 2% paraformaldehyde and 0.25% glutaraldehyde, were incubated with the incubation medium (1.0 M glycine-0.1 M KOH buffer, pH 9.0, 2.5 ml; 1.1 M KCl, 0.5 ml; 10 mM lead citrate dissolved in 50 mM KOH, 4 ml; levamisole, 6.0 mg; dimethyl sulfoxide, 2.0 ml; 0.1 M p-nitrophenylphosphate (Mg-salt), 1.0 ml; ouabain, 73.0 mg) for 30 min at room temperature. Under a light microscope the specific gastric K-NPPase reaction was distributed only in the parietal cells of the fundic glands. The electron microscopic cytochemistry showed that the gastric K-NPPase activity was localized on the membrane lining the apical surfaces, secretory canaliculi and tubulovesicles. On the other hand, ouabain-sensitive K-NPPase activity (Na-K-ATPase) was demonstrated to localize only in the basolateral membrane of parietal cells with Mayahara's method. These findings support the interrelationships between the apical surface membrane, secretory canalicular membrane and tubulovesicles, and the functional differentiation of the membrane between the secretory membrane and basolateral membrane.

4-Nitrophenylphosphatase↗

Hypophagia induced by endogenous or liposome-encapsulated 3,4-dihydroxybutanoic acid.

Hypophagia induced by 3,4-dihydroxybutanoic acid (2-deoxytetronic acid, 2-DTA), an endogenous short-chain polyhydroxymonocarboxylic acid, was investigated in rats. Intraperitoneal injection of 2500 mumol 2-DTA did not suppress feeding, but 2.5 mumol 2-DTA injected into the third cerebroventricle did. To efficiently transport exogenous 2-DTA into the brain, its encapsulation and delivery in specially made sulfatide liposomes was attempted. Feeding was suppressed dose-dependently by intraperitoneally injected 2-DTA in liposomes. Injection of 2500 mumol 2-DTA into the common carotid artery also suppressed feeding. Administration by either route prolonged postprandial intermeal interval with no change in meal size, as was observed after central administration of 2-DTA. Injection of 2.5 mumol 2-DTA into the third cerebroventricle elevated plasma glucose level, leaving insulin and free fatty acids unaffected. These findings, together with previous results, indicate that at least one site for the physiological action of 2-DTA is in the hypothalamic centers for food intake.

Animals↗

D-glucose suppression of eating after intra-third ventricle infusion in rat.

To clarify the hypophagic action of D-glucose, meal size, postprandial intermeal interval and eating rate were analyzed after infusion of glucose into the third cerebroventricle. The effects of glucose structure modification on feeding modulation were examined by comparing the effects of glucose to those of its epimers, D-mannose, D-allose and D-galactose. Glucose, infused in doses of 6 to 24 mumol, dose relatedly reduced meal size, but did not change other meal parameters. The minimum dose of glucose to induce feeding suppression was between three and 6 mumol. The epimers, at doses of 24 mumol, did not affect food intake or body weight. Drinking patterns and ambulatory activity were not changed by glucose infusion. These findings were consistent with neuronal activity observed in the ventromedial hypothalamic nucleus.

Animals↗