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Biomedical subjects

Y Komuro

Publications and source records attributed to Y Komuro.

At least 19 recordsLinked to original sources

Influence of L-365,260, a CCK-B/gastrin receptor antagonist, on tetragastrin-stimulated mucin metabolism in rat gastric mucosa.

The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 microg/kg s.c. )-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 microg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70-80% of tetragastrin) and the mucus gel (45-70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1-10 micromol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 microg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.

Animals

Mesalazine-induced eosinophilic pneumonia.

A 35-year-old woman with a 6-month history of ulcerative colitis and treatment with oral mesalazine (5-aminosalicylic acid) developed dry cough, low-grade fever and bilaterally wandering pulmonary infiltrates. Improvement in clinical symptoms and radiological abnormalities occurred spontaneously after discontinuation of mesalazine. The transbronchial lung biopsy demonstrated the organizing stage of eosinophilic pneumonia. Drug lymphocyte stimulation test was positive for mesalazine and negative for sulfasalazine and sulfapyridine. The present case indicates that although mesalazine-induced eosinophilic pneumonia is an extremely rare entity, its possibility should be fully considered in patients developing unexplained respiratory symptoms while on mesalazine therapy.

Adult

Distinct effects of tetragastrin in rat gastroduodenal mucosa on mucin content and mucosal protective action against histamine-induced injury.

We examined the effects of tetragastrin on mucin (mucus glycoprotein) content and mucosal damage in the rat stomach and duodenum. Following an injection of tetragastrin (12, 120, or 400 microg/kg subcutaneously), no macroscopic damage was found to the gastric mucosa but an increase in corpus mucin content was noted, whereas mucosal lesions appeared and the mucin content decreased in the duodenum in a dose-related manner. In the groups with histamine (0.8, 8, or 80 mg/kg intraperitoneally) administration, the extent of mucosal damage and the decrease in mucin content were dose-related in both these regions. For assessment of the effect of tetragastrin on the protective action in gastroduodenal mucosa, changes in mucin content and mucosal damage with histamine (80 mg/kg) -induced injury were examined. Coadministration of tetragastrin prevented the gastric mucosal damage and inhibited the decrease in corpus mucin content. In the duodenum, tetragastrin aggravated the histamine-induced mucosal damage and did not inhibit the reduction of the mucin content. From the present results, the increase in gastric mucins induced by tetragastrin might be related to the protective effect of gastric mucosa against injury. Tetragastrin did not protect the duodenal mucosa, and histamine-induced injury occurring in this region would be aggravated by the increase in HCl secretion and the decrease in mucin content induced by tetragastrin.

Animals

Blood coagulation activity during microsurgery.

The authors investigated blood coagulation activity in patients who underwent microsurgery. Hemostatic parameters were measured in 9 patients (10 operations) who were undergoing free tissue transfers. These parameters included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinopeptide A (FPA), prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT). The flap totally necrosed owing to vasospasm in 1 patient with osteomyelitis of the heel, and the FPA, F1 + 2, and TAT values significantly increased. Reexploration was required because of flap cyanosis in 1 patient with a hemangioma on the wrist, and the F1 + 2 and TAT values increased during the salvage procedure. These molecular markers could be important in indicating hypercoagulable state sensitivity, and they serve as a warning of possible vascular compromise to a surgeon.

Adult

Vertical symphyseal osteotomy.

For the treatment of mild crossbite with increased bigonial distance, the authors performed a vertical symphyseal osteotomy on six patients in the last 3 years. Three of these patients had cleft lip deformities and the others had operations for orthodontic or aesthetic reasons. After exposing the mandible through the buccal mucosal incision, both premolars were extracted with or without conventional segmental osteotomy. The two vertical symphyseal osteotomies were performed with approximately 1 cm between them, and the central part of the mandibular bone was discarded. The bilateral segments of the mandibular body were fixed in the midline using titanium miniplates. Satisfactory results were obtained with a reduction in the size of the mandibular arch, which produced better three-dimensional proportions in the bimaxillary area. No patients had temporomandibular joint problems, however postoperative orthodontics were essential for this type of operation.

Adult

Acute acalculous cholecystitis with a decrease in CD4/CD8 ratio.

Acute acalculous cholecystitis (AAC) usually occurs in the elderly and in those with severe pre-existing pathological conditions. However, there have recently been reports of AAC in relatively young immunosuppressed patients, such as those with acquired immunodeficiency syndrome (AIDS). We report here a 27-year-old woman with AAC who received an emergent cholecystectomy. Although anti-human immunodeficiency virus antibody (anti-HIV) was not detected, a decrease in the CD4/CD8 ratio in sera was found. This rare case of AAC in a patient with decreased CD4/CD8 ratio who showed no other related diseases suggests that surgeons should keep in mind the possible presence of immunosuppression in this condition.

Acute Disease

Effects of histamine on mucin biosynthesis in rat gastric mucosa.

Mucin biosynthesis is stimulated by gastrin during the process of glycosylation in the corpus mucosa of the rat stomach. The purpose of this study was to clarify, using an organ culture technique, whether biosynthetic responses to histamine in the rat gastric mucin are the same as that to gastrin. Radiolabeled mucin was obtained from the corpus and antral mucosa of the rat stomach after in vitro incubation for 5 h with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate. Addition of histamine (10(-7)-10(-5) M) to the culture medium increased [3H]GlcN-labeled mucin in the corpus tissue in a concentration-dependent manner. In the antrum, there was no significant change in the biosynthetic activity of mucin in response to histamine. Histamine at 10(-5) M also increased the incorporation of both [35S]sulfate and [14C]Thr into the corpus mucin. These results indicate that histamine stimulates the biosynthesis of the mucin peptide, as well as the glycosylation step in the corpus, and suggest that the effect of histamine on mucin synthesis is distinct from that of gastrin.

Animals

Correction of pectus excavatum and pectus carinatum assisted by the endoscope.

Six patients with pectus excavatum and two patients with pectus carinatum had their conditions corrected by a partial costal cartilage resection with a sternal osteotomy through a 2.5-cm to 4-cm skin incision located just above the xyphoid process assisted by an endoscope. In addition to the incision, stab wounds of less than 3 mm in diameter were also made, in some cases, for insertion of the surgical instruments to facilitate the operation. The ribs and rib cartilages were exposed beyond the affected area through a prexyphoid incision under endoscopic control. The mobility of the skin incision site was thus enhanced, and it was possible to perform most of the subperichondrial partial costal cartilage resection under direct visualization. The pleura was freed from the sternum under endoscopic visualization. The advantages of this technique include minimal operative scars and the ability to free the pleura from the sternum under endoscopically magnified visualization, which prevents rupturing of the pleura in the retrosternal area.

Adolescent

Stimulation of mucin metabolism in rat gastric mucosa by histamine.

We examined the effects of histamine on mucin localized in the different regions and layers of rat gastric mucosa by determining the changes in the content as well as the biosynthetic activity of the mucin. In vivo administration of 0.8 mg/kg of histamine, which could not induce a concomitant gastric acid secretion, caused a significant increase in the mucin content in the corpus mucosa, but not in the antral mucosa. This increase was due to a significant accumulation of the mucin in the mucus gel and surface mucosa of the corpus region, whereas that in the deep mucosa did not significantly change. In the in vitro incubation system of rat gastric mucosa, histamine and dibutyryl cyclic AMP significantly increased [3H]-labeled mucin in the corpus. The histamine-induced acceleration of mucin biosynthesis was suppressed by ranitidine, but not pyrilamine. In the antrum, the biosynthetic activity showed no significant change by histamine. These results suggest that histamine promotes mucin metabolism via histamine H2 receptors in the surface mucosal layer of the corpus.

Animals

Synthesis of chiral aminophosphines via nucleophilic aromatic substitution and their application to palladium-catalyzed enantioselective allylic substitution.

Novel chiral aminophosphines, N,N-disubstituted diphenyl(1-amino-2-naphthyl)phosphines 4 were synthesized via nucleophilic aromatic substitution reaction on 1-methoxy-2-(diphenylphosphinoyl)naphthalene (1) by chiral lithium amides 2, followed by reduction of the phosphinoyl function. The new ligands were tested for their efficiency in the palladium-catalyzed allylic substitution of dimethyl malonate with 1,3-diphenyl-2-propenyl acetate and high asymmetric inductions up to 80%ee were observed.

Allyl Compounds

Effect of topical application of a stable prostacyclin analogue, SM-10902 on wound healing in diabetic mice.

The mechanism of wound healing induced by topical application of an ointment containing a new stable prostacyclin analogue, SM-10902 ((+)-methyl[2-[(2R,3aS,4R,5R, 6aS)-octahydro-5-hydroxy-4-[(E)-(3S,5S)-3-hydroxy-5-methyl-1- nonenyl]-2-pentalenyl] ethoxy] acetate), was investigated in the full-thickness wounds of genetically diabetic mice (db/db mice). The db/db mice treated with SM-10902 ointment (1, 10 and 100 micrograms/g) showed greater decrease in wound lesion area not covered with epidermis and fewer complete healing days than those treated with ointment base, and the effects of this prostacyclin analogue were greater than those of lysozyme chloride ointment (50 mg/g, Reflap ointment). SM-10902 ointment increased skin blood flow in the central site of the wound with development of wound healing. Histological evaluation of wounds revealed that SM-10902 ointment increased the capillary number during the early stage of the wound-healing process. These results suggest that SM-10902 ointment promotes wound healing through the stimulation of angiogenesis and the improvement of blood flow in neovascularization of repairing wound and may be useful in the treatment of skin ulcers caused by peripheral circulatory insufficiency.

Administration, Topical

Effects of prostaglandins and cyclic AMP on cytokine production in rat leukocytes.

Prostaglandins E1, prostaglandin E2, 3-oxa-methano-prostaglandin I1 (SM-10906), a stable prostaglandin I2 analog, and dibutyryl cyclic AMP suppressed the production of tumor necrosis factor and interleukin-1 in lipopolysaccharide-stimulated rat pleural resident monocytic cells, whereas they enhanced the production of interleukin-6 and cytokine-induced neutrophil chemoattractant (CINC), a rat interleukin-8-like chemokine, in these cells. SM-10906 also inhibited the in vivo production of tumor necrosis factor and interleukin-1 in pleural exudates, when injected into the rat pleural cavity concomitantly with carrageenin. The cyclic AMP (cAMP) level in the lipopolysaccharide-stimulated resident cells was increased when the cells were incubated in the presence of prostaglandin E1, prostaglandin E2 or SM-10906. Prostaglandin I2 showed only slight effects. The addition of pentoxifylline, a phosphodiesterase inhibitor, to the incubation mixture increased the cAMP level and also enhanced the effect of prostaglandins, indicating that these regulating actions of prostaglandins may be exerted partly through a mechanism involving an increased intracellular cAMP level.

Alprostadil

Antiplatelet functions of a stable prostacyclin analog, SM-10906 are exerted by its inhibitory effect on inositol 1,4,5-trisphosphate production and cytosolic Ca++ increase in rat platelets stimulated by thrombin.

The mechanism of the antiplatelet functions of SM-10906, the active form of the 3-oxa-methano-prostaglandin (PG) I1 analog SM-10902, was examined in rat platelets. SM-10906 activated adenylate cyclase in crude membrane fractions, and inhibited platelet aggregation and release of adenine nucleotides stimulated by thrombin. SM-10906 also inhibited malondialdehyde production induced by thrombin, but not that induced by arachidonic acid. This may account for its inhibitory effects on phospholipase A2. SM-10906 prevented thrombin-induced inositol 1,4,5-trisphosphate production, Ca++ mobilization from intracellular Ca storage and 45Ca++ influx into platelets, which were all reversed by pretreatment with the adenylate cyclase inhibitor 2',5'-dideoxyadenosine. PGI2 and PGE1 have the same antiplatelet profiles in the order of PGI2 > or = SM-10906 > PGE1. These results indicate that SM-10906 as well as PGI2 and PGE1 may exert antiplatelet activities by stimulating adenylate cyclase to prevent thrombin-induced phospholipase C and A2 activations and increase in cytosolic Ca++ level.

Adenylyl Cyclases

Proliferating trichilemmal tumor on the dorsum of the hand.

A patient with a proliferating trichilemmal tumor on the dorsum of a hand is described. A surgical excision was performed, and the skin defect was covered with a distally based posterior interosseous island flap. In the operation, an iron fragment was found beneath the mass, and this was thought to have triggered development of the tumor.

Aged

Effects of lansoprazole on gastric ulcer healing and mucin content.

The effect of lansoprazole, a new benzimidazole proton pump inhibitor, on the relationship between ulcer healing and changes in mucin content was studied in gastric ulcer patients. Twenty-one outpatients with active gastric ulcers received lansoprazole 30 mg once daily given in the morning for 8 weeks. The gastric mucin content was examined by HPLC analysis of hexosamines in gastric biopsy specimens obtained from the lesser curvature of the pylorus and the greater curvature of the upper body. The ulcer healing rate for lansoprazole was 85.7% at 8 weeks. The mucin content of both mucosal regions significantly decreased to approximately 70% (pylorus 70.9%; upper body 74.7%) of the value before drug treatment. The results of this study demonstrate that 30 mg lansoprazole once daily is remarkably effective in healing gastric ulcers because of its potent acid suppression. It appears that acid inhibition is the primary factor in initial treatment. However, maintaining an altered gastric mucosal defense mechanism may have implications for the long-term treatment of gastric ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles