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Biomedical subjects

S Kawano

Publications and source records attributed to S Kawano.

At least 145 records · Page 8Linked to original sources

Germline mutations of the MEN1 gene in Japanese kindred with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial cancer syndrome. The responsible gene MEN1 has recently been isolated, and its germline mutations have been identified in affected individuals in the United States, Canada and Europe. We screened for MEN1 mutations by direct nucleotide sequencing of all protein-coding regions, and identified five distinct germline mutations in five among six Japanese kindreds with familial MEN1 or familial hyperparathyroidism. The mutations were dispersed across the gene. These findings suggest that, because of the absence of an obvious founder effect, the entire MEN1 gene region should be examined for germline mutations in the probands of MEN1 and related syndromes in Japanese families.

DNA, Neoplasm↗

Relationship between interleukin-8 levels and myeloperoxidase activity in human gastric mucosa.

Although interleukin (IL)-8 is well known as a chemotactic agent for neutrophil migration in vitro, the relationship between IL-8 activity and the degree of neutrophil infiltration in gastric mucosa is still unclear. In the present study, we investigated IL-8 and myeloperoxidase activity, a marker of neutrophil infiltration, in gastric antral mucosa using biopsy samples in 23 patients with no gastric lesions. The results indicate that there is a good correlation between IL-8 and myeloperoxidase activity (y = 0.173x + 13.9; r = 0.49, P < 0.01). Furthermore, IL-8 and myeloperoxidase activity are significantly higher in Helicobacter pylori-positive patients than in H. pylori-negative patients. In conclusion, an increase of IL-8 activity in the gastric mucosa causes increased neutrophil infiltration in human gastric mucosa and H. pylori infection accelerates these reactions in the mucosa.

Aged↗

Purification, characterization, and localization of a novel trypsin-like protease found in the human airway.

A novel trypsin-like protease was purified to homogeneity from the sputum of patients with chronic airway diseases, by sequential chromatographic procedures. The enzyme migrated on SDS-polyacrylamide gel electrophoresis to a position corresponding to a molecular weight of 28 kDa under both reducing and non-reducing conditions, and showed an apparent molecular weight of 27 kDa by gel filtration, indicating that it exists as a monomer. It had an NH2-terminal sequence of Ile-Leu-Gly-Gly-Thr-Glu-Ala-Glu-Glu-Gly-Ser-Trp-Pro-Trp-Gln-Val-Ser-Leu- Arg-Leu, which differed from that of any known protease. Studies with model peptide substrates showed that the enzyme preferentially cleaves the COOH-terminal side of arginine residues at the P1 position of certain peptides, cleaving Boc-Phe-Ser-Arg-4-methylcoumaryl-7-amide most efficiently and having an optimum pH of 8.6 with this substrate. The enzyme was strongly inhibited by diisopropyl fluorophosphate, leupeptin, antipain, aprotinin, and soybean trypsin inhibitor, but hardly inhibited by secretory leukocyte protease inhibitor at 10 microM. An immunohistochemical study indicated that the enzyme is located in the cells of the submucosal serous glands of the bronchi and trachea. These results suggest that the enzyme is secreted from submucosal serous glands onto the mucous membrane in patients with chronic airway diseases.

Amino Acid Sequence↗

Fruiting-inducing activity and antifungal properties of lipid components in members of Annelida.

Fruiting-inducing activity and antifungal properties of lipid components in the phylum Annelida were examined. Some amphoteric cerebrosides carrying a phosphocholine group showed fruiting-inducing activity on Schizophyllum commune, and one of them possessed activity comparable to that of Sch II, the most potent substance known. Furthermore, alkyl lysophosphatidylcholines were found to have an inhibitory effect on the growth of phytopathogenic fungi, Alternaria kikuchiana and Phomopsis mali. The relationship between structure and biological activities is discussed.

Alternaria↗

Effect of estrogen on the development of disuse atrophy of bone and muscle induced by tail-supension in rats.

Rat tail-suspension induces disuse atrophy of muscles and bones in hindlimbs. In the present investigation we studied how ovariectomy and estrogen substitution affect the development of the disuse atrophy induced by suspension. Five-week old female Wistar rats were ovariectomized and divided into two groups. One group received intramuscular injection of estradiol dipropionate once a week (OVX-E2 group), and the other received a vehicle injection (OVX group). After the third injection, each group was further divided into two groups, tail-suspended and non-suspended. After 7 days of tail-suspension, a significant decrease in the wet weight of femurs and their Ca and Pi content was observed in the OVX group. However, no significant change in those parameters was observed in the E2 group. In both E2 and OVX groups, a significant decrease in the wet weight of soleus and gastrocnemius muscles was demonstrated after the suspension. This demonstrated that estrogen administration to ovariectomized rats prevents the development of disuse bone atrophy but not that of muscle atrophy, suggesting that estrogen plays important roles in bone remodeling.

Animals↗

Effect of bisphosphonate administration on the excretion of stress hormones in tail-suspended rats.

We demonstrated that administration of a bisphosphonate, YH529, prevents the development of disuse atrophy of the hind limbs induced by tail-suspension in rats. Since tail suspension is accompanied by an increase in the secretion of stress hormones, we studied whether administration of bisphosphonate affects the secretion of stress hormones during that procedure. Tail suspension was carried out in a metabolic cage by connecting a wire inserted through tail bone to the ceiling of the cage. The control rat received the same treatment but was not suspended. YH529 or a vehicle (PBS=phosphate buffered saline) was administered daily starting 3 days before the commencement of tail suspension. Urine samples were collected before the wire was inserted (day 0), on the day of insertion (day 1) and 3, 5 and 7 days after. In the control rats receiving PBS, urinary excretion of corticosterone and epinephrine did not change throughout the 7-day experimental period. In the control rats receiving YH529, urinary excretion of corticosterone increased significantly on the day of tail-piercing and wiring but then returned to the prior level. This increase was not observed in the control group receiving PBS. In the tail suspended rats, excretion of corticosterone and epinephrine increased significantly in both PBS and YH529 groups, the highest level being observed on the first day of tail suspension. Although statistically not significant, corticosterone excretion on day 1 of tail suspension was higher in the YH529 groups than that in the PBS group. It is thus suggested that administration of YH529 causes an augmented response to stress load.

Animals↗

[Fibrinogenolytic activity of a novel trypsin-like enzyme found in human airways].

We previously reported finding a novel trypsin-like enzyme in sputum samples from patients with chronic airway diseases, and named it human airway tryptase (HAT). We also obtained data suggesting that HAT is secreted from submucosal serous glands onto the mucous membrane of the airway, and that fibrinogen is cleaved by HAT. We studied whether HAT can act as an anticoagulant in the airway by breaking down fibrinogen. The concentration of fibrinogen in sputum samples was measured by enzyme-linked immunosorbent assay. The concentration was higher in mucoid sputum from patients with bronchial asthma (6.3 +/- 5.5) than in mucoid sputum from patients with chronic bronchitis (1.9 +/- 1.1), and it was higher in purulent sputum from patients with bronchiectasis (18.8 +/- 8.8) than in mucoid sputum from patients with asthma. The trypsin-like activity in sputum (milliunit/ml) was 23.4 +/- 18.0 in mucoid sputum from patients with chronic bronchitis, 46.9 +/- 43.9 in mucoid sputum from patients with asthma, and 14.9 +/- 8.23 in purulent sputum from patients with bronchiectasis. The effect of HAT on human fibrinogen at concentrations from 4 to 2000 micrograms/ml was examined at pH 7.4 and 8.6, with purified HAT at concentrations from 0.5 to 10 milliunit/ml. SDS-polyacrylamide gel electrophoresis showed that HAT can cleave fibrinogen. especially the alpha-chain, at low concentrations (4 to 16 micrograms/ml) and at a high concentration (2000 micrograms/ml) of fibrinogen. Exposure of fibrinogen to HAT resulted in the loss of thrombin-induced clotting capacity; the strength of that effect depended on the duration of exposure to HAT and on the concentration of HAT. From these results we postulate that HAT acts at an anticoagulant in the airways, especially on the mucous membrane, by cleaving fibrinogen transported from blood.

Asthma↗

[Four cases of late infection following scleral buckling procedure].

We report four cases with late infection following a scleral buckling procedure. These cases were a 44-year-old male, a 52-year-old female, a 59-year-old male, and a 60-year-old male. All of these cases developed conjunctival injection, chemosis, and mucopurulent discharge 7 to 15 years after the procedure. The symptoms did not improve despite months of medical therapy, suggesting scleral buckle infection, and finally the buckling materials were removed. Solid silicone was used in 2 cases, and a sponge was used in 2 cases, with encircling elements in 1 case, and without encircling elements in 3 cases. Pus culture of the removal exoplant revealed fungaul infection in 2 cases. The others were negative, but bacterial infection was suspected from their clinical course and intraoperative findings. After removal of the buckles, the symptoms improved rapidly in all cases and there was no recurrence of retinal detachment. Scleral buckle infection should be suspected and removal of buckling materials should be considered, in cases with refractory conjunctival and scleral inflammation even years after scleral buckling procedure.

Adult↗

Endothelin-1 in the gastric mucosa in stress ulcers of critically ill patients.

OBJECTIVE: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators causing this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1), a potent vasoconstrictive peptide, in stress ulcers in critically ill patients. METHODS: Using sandwich enzyme immunoassay, we measured ET-1 content in plasma and the gastric mucosa of 16 critically ill patients with traumatic head injury on admission and of 11 healthy subjects. Gastric mucosal samples were obtained endoscopically. When gastric drainage contained occult blood, endoscopic examination was performed again, and ET-1 concentrations in injured and adjacent normal mucosa were compared. RESULTS: Plasma and mucosal ET-1 concentrations were significantly higher in critically ill patients on admission (6.1 +/- 0.6 pg/ml and 13.8 +/- 1.6 ng/g, respectively) compared with values in control subjects (2.7 +/- 0.4 pg/ml and 8.2 +/- 0.5 ng/g, respectively) (p < 0.01). The mucosal ET-1 concentration tended to be elevated in patients who had experienced hypoxia compared with those who had not (p = 0.07). In five patients who were again examined endoscopically, the ET-1 concentration in the injured mucosa was significantly higher than that in adjacent mucosa (19.2 +/- 3.2 and 10.1 +/- 1.6 ng/g, respectively; p < 0.05). CONCLUSIONS: These results suggest that endogenous ET-1 plays an important role in the local pathogenesis of stress ulcers, especially those caused by hypoxia.

Adult↗

Protection by Carolina rinse solution, acidotic pH, and glycine against lethal reperfusion injury to sinusoidal endothelial cells of rat livers stored for transplantation.

The critical injury causing graft failure after prolonged liver storage involves reperfusion-induced killing of sinusoidal endothelial cells and activation of Kupffer cells. Treatment of stored livers with Carolina rinse solution (CRS) prevents endothelial cell killing, reduces Kupffer cell activation, and improves graft survival. Accordingly, our aim was to evaluate the components of CRS and other agents for protection against reperfusion injury to rat livers stored 24 hr in University of Wisconsin solution. CRS virtually abolished endothelial cell killing, prevented denudation of the sinusoidal lining, and decreased structural changes in Kupffer cells indicative of activation. The only component of CRS preventing endothelial cell killing was acidic pH of 6.5. However, when pH was subsequently increased to 7.4, antioxidants (allopurinol, deferoxamine mesylate, and glutathione), vasodilators (adenosine and nicardipine), and possibly energy substrates (fructose, glucose, and insulin) partially blocked pH-dependent cell killing (pH paradox). Na+/H+ exchange inhibition, protease inhibition, and Ca(2+)-free buffer did not decrease reperfusion injury, but the amino acid glycine protected strongly. Strychnine, which binds to glycine receptors in the central nervous system, protected equally well. Protection by glycine and CRS was synergistic, virtually.

Animals↗

Helicobacter pylori extract stimulates inflammatory nitric oxide production.

This study examined whether an extract of Helicobacter pylori had the ability to stimulate an inflammatory synthesis of nitric oxide, a mutagen and precursor of nitrosocompounds. Macrophages and neutrophils were prepared from rat and incubated with the Helicobacter pylori extract. L-Arginine-dependent nitric oxide production in these cells was significantly stimulated by the co-incubation with the Helicobacter pylori extract. This ability of the extract was strongly attenuated by protease digestion or heating. These results indicate that Helicobacter pylori induces production of nitric oxide and participates in development of gastritis and gastric carcinogenesis.

Animals↗