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Biomedical subjects

M Uchida

Publications and source records attributed to M Uchida.

At least 451 records · Page 25Linked to original sources

Purification of a membrane-bound neutral endopeptidase from rat kidney and its activation by polyamines.

An endopeptidase which cleaves succinyl trialanine p-nitroanilide (Suc(Ala)3-pNA) into succinyl dialanine and alanine p-nitroanilide (Ala-pNA) was solubilized from a microsomal membrane fraction of rat kidney with Nonidet P-40 following treatment with 1 M KCl and Brij 35. The solubilized enzyme was purified to homogeneity by DEAE-Sephadex chromatography, Sepharose CL-6B gel filtration and sucrose gradient centrifugation. The final enzyme preparation had a specific activity of 1.69 mumol/min/mg protein, representing about 140-fold purification over the starting membrane. The enzyme hydrolyzes Suc(Ala)3-pNA with a Km value of 0.28 mM and a Vmax value of 1.3 mumol/min. The molecular weight of the undenatured enzyme was estimated to be 360,000 by gel filtration on a Sepharose CL-6B column and that of the denatured enzyme to be 92,000 by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, revealing the presence of a single polypeptide chain. The enzyme was markedly activated by polyamines, producing increases in the values of both Km and Vmax. Comparatively less activation was found in the presence of some monovalent cations and Ca2+. The activation by polyamines was inversely proportional to the concentration of monovalent cations, but Ca2+ and polyamines seemed to stimulate additively.

Aminopeptidases↗

Mammalian signal peptidase: partial purification and general characterization of the signal peptidase from microsomal membranes of porcine pancreas.

Signal peptidase has been enriched extensively from microsomal membranes of porcine pancreas. Microsomal membranes were washed with 1 M KCl and Brij 35, and then solubilized with 1% Nonidet P-40. The solubilized signal peptidase was purified by DEAE-cellulose chromatography and Sepharose CL-6B filtration. Cleavage of pre-human placental lactogen with the partially purified enzyme gave the mature form, whose NH2-terminus was identified as valine. The signal peptidase is heat-labile and approximately 90% of the enzymatic activity was lost at 60 degrees C within 1 min. The pH optimum of the activity was 7 to 8. Chymostatin and o-phenanthroline at concentrations of 2.5 mM inhibited the signal peptidase activity by 62% and 30%, respectively.

Amino Acid Sequence↗

Gate mechanism in breathlessness caused by chest wall vibration in humans.

The effects of bilateral alternating out-of-phase vibrations were studied in 10 normal healthy subjects and five asthmatic patients. The second or third intercostal spaces were vibrated during expiration, and the seventh to ninth intercostal spaces were vibrated during inspiration. Most subjects sensed breathlessness during such vibrations, and 100 Hz was most effective. The degree of breathlessness correlated positively with increased respiratory rate. Respiratory rate increased from 14.1 +/- 3.78 (mean +/- SD) to 22.3 +/- 7.14 breaths/min (P less than 0.05) during relatively severe breathlessness and to 20.39 +/- 5.66 breaths/min (P less than 0.05) during less uncomfortable sensation. Slight or negligible breathlessness induced no significant increase in rate (15.33 +/- 4.19 breaths/min). All asthma patients described the sensations during vibration as similar to those during asthma attacks, and their respiratory rates increased 20.7 +/- 11.03% during 100 Hz vibration (P less than 0.01). It is suggested that the uncomfortable sensation of breathlessness may be induced by muscle spindles in the intercostal muscles being activated out of phase with the respiratory cycle. The central mechanism that receives the intercostal afferents may have a certain gate that operates in relation to the sensation of breathlessness.

Adult↗

[A study of the incidental rate of the radiation-induced cancer in the head and neck region].

In a review of 2710 patients with head and neck disease treated with irradiation at the Cancer Institute Hospital, Tokyo, between 1946 and 1955, second primary malignancies occurred in 35 of 2223 patients who were treated by reason of malignant tumors. The incidental rate of these second primary malignancies was significantly different from the population based rates. In 10 of 292 patients who were treated by irradiation for reason of benign disease such as cervical tuberculosis and hemangioma, primary cancers were developed under the long period of observation. These primary cancers were proved to be radiation-induced malignancies.

Adolescent↗

Effect of bestatin on syngeneic tumors in mice.

The antitumor effect of bestatin against syngeneic tumors such as colon adenocarcinoma 26 (colon 26) and myeloid leukemia C1498 ( C1498 ) was investigated. Bestatin effectively inhibited the growth of both tumors in vivo. The inhibition observed for colon 26 was the largest when bestatin was administered on days 1 to 5 after transplantation of the tumor. The inhibition of C1498 was the largest when bestatin was administered on days 7 to 11. In contrast to these results, bestatin was not at all inhibitory to either tumor line in vitro. Thus, the effect of bestatin administration on the functions of the spleen cells of mice bearing tumors was examined. Spleen cells taken from mice bearing colon 26 and C1498 did not neutralize the corresponding tumor. However, when bestatin was administered to these mice, spleen cells from the administered mice did neutralize the corresponding tumor. Bestatin enhanced antibody-dependent cell-mediated cytotoxicity and natural killer cell activity of the spleen cells of colon 26-bearing mice. Further, bestatin did not inhibit the growth of colon 26 in BALB/c nu/nu mice. It was concluded that bestatin exhibits its antitumor effect against colon 26 and C1498 indirectly by immunomodulation via spleen cells and possibly via T cells.

Adenocarcinoma↗

[Experimental studies on gastric ulcer (6). Endoscopical evaluation of healing processes of acetic acid ulcer in rats (2): Healing, recurrence and relapse of ulcer].

The progress of acetic acid-induced gastric ulcers in rats were sequentially observed with an endoscope for 365 days, and the influences of the ulcer-induced site, age and sex on the healing, recurrence and relapse of these ulcers were investigated. Submucosal injections of 20% acetic acid at the region between the fundus and the pylorus on the anterior wall of the stomach (site A) in 7 weeks old male rats produced active round-shaped ulcers with blood coagulation and debris on the 3rd day after ulcer induction. The ulcers diminished in size with the progress of time (10--50 days), and 50% of the ulcerated rats healed with convergences of mucosal folds (35--154 days). On and after the 50th day, some diminished or healed ulcers showed signs of relapse (37% of used rats) or recurrence (40% of healed rats, 21% of used rats), with the cumulative relapse and recurrence percentage (CR%) reaching 59% on the 365th day. Ulcers in the glandular portion on the greater curvature (site B) healed significantly faster than those in site A. All of the ulcers in site B healed within 133 days and did not recur or relapse. The cumulative healing percentage (CH%) and the CR% of the ulcers in site A in 25 weeks old male rats were 33% and 67%, respectively, and those of the ulcers in site A in 7 weeks old female rats were 60% and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

[A bacteriological study on urinary calculi associated with infections].

There are difficult problems in the management of urinary calculi associated with infections. Stones associated with infections are not only infection stones such as struvite stones, but also other kinds of stones such as calcium oxalate. Therefore, from practical view points, bacteriological studies should be carried out on urinary calculi associated with infections as a whole. We investigated 120 cases of urinary calculi associated with infections with special reference to bacteria on the stone surface, within the stone, compositions of the stone and permeation of an antibiotic into the stone. Proteus was isolated most frequently from the urine, followed by E. coli and Pseudomonas. These bacteria were isolated from the stone surface, although the incidence of Proteus mirabilis was higher than that in the urine. Bacteria were isolated in 25 of the 33 specimens of the inside parts and in 12 of the 12 stones of MAP and MAP plus other components. Proteus mirabilis was found in 7 of the 12 stones. Bacteria were isolated from the inside of 9 of the 16 stones of CaP and CaP plus other components and Proteus mirabilis was found in 6 of these 9 cases. Pseudomonas was isolated in 2 out of the 7 stones of CaP plus CaOX and its growth was seen in 5 specimens. The incorporation of an antibiotic, Cefmetazole, into the stone differed greatly with each stone. There were some cases in which the concentration of Cefmetazole in the inside was less than 5% of that in the outside. Stones may function as a sanctuary for organisms and may protect these organisms.

Adult↗

Desensitization to histamine in the absence of external Ca++ in the guinea-pig taenia caecum.

Short-term desensitization of the contractile response of the guinea-pig taenia caecum to histamine was tested in the absence of Ca++. Desensitization was monitored both by the fall of histamine response and by the decrease of irreversible blockade by phenoxybenzamine. In Ca++-free solution with 0.2 mM EGTA, desensitization occurred as in normal physiological solution containing Ca++.

Animals↗

Enhancement of phenoxybenzamine-induced irreversible blockade by organic Ca antagonists.

Organic Ca antagonists such as D600, diltiazem and nicardipine enhanced the irreversible blockade by phenoxybenzamine (POB) of the histamine response in guinea pig taenia caecum. The isotonic contractile response of the muscle was tested after incubation with POB (5 X 10(-6) M, 10 min) with or without an organic Ca antagonist. The blockade by POB was greater in muscle treated with an organic Ca antagonist and the effect lasted for more than 7 h.

Animals↗

Effects of calmodulin inhibitor on histamine release from rat peritoneal mast cells induced by concanavalin A and ionophore A23187.

The involvement of calmodulin in stimulus-secretion coupling of histamine release from rat mast cells was examined using a specific calmodulin inhibitor, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide]. W-7 at low concentrations inhibited histamine release induced by either concanavalin A or ionophore A23187 and at high concentrations enhanced the release. But its congener, W-5 [N-(6-aminohexyl)-1-naphthalenesulfonamide], which has virtually no calmodulin-inhibiting activity, did not affect the release. It is concluded that W-7 modulates histamine release by inhibiting some functions of calmodulin in the cells.

Animals↗

Agonist-induced contraction of rat myometrium in Ca-free solution containing Mn.

In Ca-free solution containing Mn, oxytocin caused the same extent of contraction of rat myometrium as in normal solution, whereas acetylcholine caused little contraction. The contraction caused by acetylcholine in medium containing Ca was inhibited by Mn dose-dependently, whereas that caused by oxytocin was not affected by Mn. The contraction caused by oxytocin in Ca-free solution containing Mn was inhibited dose-dependently by D-600. Mn ion had little effect on contractile protein, but the tissue level of Ca had an effect on oxytocin-induced contraction in Ca-free medium containing Mn.

Acetylcholine↗

Experimental studies on gastric ulcer. (4). Sequential observation and evaluation of gastric ulcers by endoscope in the rat.

In the present study, a sequential observation of the gastric lesions or ulcers in rats weighing from 100 g was made with an endoscope. It was found that bleeding, edema, hyperemia, fur of ulcer and convergences of the mucosal folds in the stomach could be observed in rats with a SES-1717S (phi = 1.7 mm) or SES-2217S (phi = 2.2 mm) endoscope. Furthermore, we have devised a method which we named the "sohmen method" for measuring ulcer-sizes with an endoscope. The ulcer-size was compared with 5 mm lengths of sohmen (Japanease vermicelli) which were inserted through the sheath of the endoscope into the stomach. Therefore, the ulcer-size could be accurately measured by this method. By this observation method, it is possible to observe repeatedly over a long term the changes in gastric lesions or ulcers, to measure changes in ulcer-sizes and to evaluate the relapse or recurrence of ulcers in the same rats.

Acetates↗

Studies on the antigenicity of glucagon.

In order to test the safety of glucagon (GG), the immunogenicity of GG was studied in rabbits and guinea pigs. Any sensitization, as revealed by anaphylactic shock, Arthus reaction, passive cutaneous anaphylaxis (PCA) or radioimmunoassay, was not demonstrated in animals immunized with GG alone. The anti-GG antibodies were detected by PCA and radioimmunoassay in two of the five animals immunized with GG mixed with Freund's complete adjuvant. Anti-GG IgE antibody production in mice was found in one of the ten mice given 570 micrograms and three of the six mice given 1,000 micrograms of GG with aluminum hydroxide gel (Alum), but other doses of GG with Alum produced no IgE antibody. These results indicate that the antigenicity of GG is very weak.

Anaphylaxis↗

[Combination chemotherapy (BEAM regimen) for head and neck cancer].

Twenty-eight patients with head and neck cancer were treated with a combination of bleomycin, cyclophosphamide, adriamycin, and methotrexate (BEAM regimen), consisting cyclophosphamide 600 mg/body and adriamycin 40 mg/body on day 1, bleomycin 15 mg/body and methotrexate 20 mg/body on days 1 and 5. Dose modifications were performed according to patient's conditions. Of 18 evaluable patients, 3 patients showed a complete response and 3 patients showed partial response with an overall response rate of 33.3%. In this study, the patients who had already been treated with surgery, radiotherapy, or chemotherapy produced good results. The median duration of response was 4.0 months in the complete responders, and 1.0 month in the partial responders. The median survival was 12.7 months in the complete responders 1.4 months in the partial responders, and 5.6 months in non-responders. The most frequent major toxic effects were leukopenia (66.7%), nausea (60%), and alopecia (57.3%) in the patients receiving the maximum dose of the drugs. Careful monitoring of patients is imperative during this treatment.

Adult↗