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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 1,063 records · Page 59Linked to original sources

Hormonal effects on the development changes of mouse small intestinal glycolipids.

The composition of intestinal glycosphingolipids during normal and hormone-perturbed development was investigated. The concentrations of glycosphingolipids of mouse small intestine were affected by the injection of thyroxine or cortisone during suckling and weaning periods. GDla was reduced by the hormonal treatment among major gangliosides, GM3, GM1 and GD1a, of mouse small intestine during the suckling period. In contrast, asialo GM1 was precociously produced by the treatment, which scarcely found in control suckling mouse small intestine. The results showed that these hormones were related to developmental alteration of small-intestinal glycolipids.

Aging↗

Keratoconus with pellucid marginal corneal degeneration.

Examination of 1,625 Japanese patients with keratoconus and 20 patients with pellucid marginal corneal degeneration showed that 17 patients with pellucid degeneration also had keratoconus in the central portion of the cornea. Three patients with pellucid degeneration without keratoconus showed bilateral involvement. Among the 17 cases of pellucid degeneration with keratoconus, eight patients showed bilateral involvement and the others showed unilateral involvement. Pellucid marginal corneal degeneration with or without keratoconus may be a variant of keratoconus or a different manifestation of the same etiologic factor.

Adult↗

Dosage form design for improvement of bioavailability of levodopa VI: formulation of effervescent enteric-coated tablets.

A new dosage form of levodopa, which has the characteristics of loading high concentrations of levodopa at the upper part of the intestine, has been developed to improve its bioavailability. It is shown that an effervescent tablet formulation, coated with hydroxypropyl methylcellulose phthalate (carboxybenzoyl radical content: 20-24%) as the enteric material, is suitable for the purpose of dissolution. This was confirmed from animal experiments, which showed that tablets of this composition disintegrate instantly on reaching the upper part of the intestine. This tablet was considered appropriate for the bioavailability tests described in this paper.

Animals↗

Ibuprofen inhibition of postsurgical adhesion formation: a time and dose response biochemical evaluation in rabbits.

Recently, a reduction in postoperative adhesion formation in rabbits which received high-dose ibuprofen (280 mg/kg/day) treatment in the perioperative interval was reported. Because these results could have resulted from a nonspecific effect of ibuprofen, the effects of ibuprofen on peritoneal injury in a time and dose response fashion was evaluated. Seventy rabbits were assigned to seven groups. All rabbits received a dose of ibuprofen 1 hr prior to surgery. The time of the second dose was either 8 or 12 hr after the surgical procedure; 8 hr for groups A, C, and E; 12 hr for groups B, D, and F (A, B: 70 mg/kg; C, D: 35 mg/kg; E, F: 17.5 mg/kg, respectively). Thereafter, rabbits received further dosing every 6 hr to complete a total 10-dose regimen. Group G served as a nontreatment control. Surgical injury was induced by either abrasion or ischemia of the right uterine horn. Immediately after closing the incision, 10 muCi of 14C-labeled glucosamine and 10 muCi of 14C-labeled proline were injected into each rabbit. All rabbits underwent a second laparotomy on the fifth postoperative day for evaluation of adhesion formation. Uterine tissue adjacent to the site of uterine healing was excised for determination of glycosaminoglycan and collagen concentration. In the nontreatment control group G, 5 of the 10 rabbits had severe grade 2 adhesions at the time of second laparotomy, 3 had grade 1 filmy adhesions, and 2 had no adhesions. This is in marked contrast (P less than 0.025) to the group that received ibuprofen at 70 mg/kg/day with the first postoperative dose 8 hr after surgery (group A). In this group, no rabbits had severe grade 2 adhesions, 3 rabbits had filmy grade 1 adhesions, and 7 rabbits were free of pelvic adhesions. A gradual tendency towards more adhesions and more severe adhesions was apparent in groups B-F as the dose of ibuprofen was decreased and the time of first postoperative injection was prolonged. The recovery of 14C-labeled glucosamine from the glycosaminoglycan extraction demonstrated a positive correlation between the cpm recovered and the severity of adhesions formed. Groups A and B had, overall, the lowest ratios of glucosamine (1.47 +/- 0.08 and 1.56 +/- 0.09, respectively) which were statistically different from the nontreatment control group G (1.76 +/- 0.11, P less than 0.05). There was also a positive correlation between the formation of severe adhesions and the ratio of 14C-labeled proline recovered by collagen extraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Immunological activity of chitin and its derivatives.

The effect of chitin and its derivatives on the activation of peritoneal macrophages in vivo, on the suppression of tumour growth in syngeneic mice and on the protection of the host against bacterial infection was examined. Thirty percent deacetylated chitin (30% DA-chitin), 70% DA-chitin and carboxymethyl-chitin (CM-chitin) induced cytotoxic macrophages most effectively. Chitosan, hydroxyethyl-chitin, dihydroxypropyl-chitin (DHP-chitin) and DHP-chitosan had moderate activities. Phosphorylated-, sulphonated- or acetyl-chitin, however, were less effective. Both 70% DA-chitin and DHP-chitosan were most active on the suppression of Meth-A tumour growth in BALB/c mice, and 30% DA-chitin had a moderate effect. For the stimulation of non-specific host resistance against Escherichia coli infection, 30% and 70% DA-chitin were effective.

Adjuvants, Immunologic↗

Vascular angiotensin-converting enzyme activity in man and other species.

Angiotensin-converting enzyme (ACE) activity in blood vessels of different species was determined. ACE was solubilized by Nonidet P-40, and assayed by reversible phase high performance liquid chromatography. Approximately 98% ACE was recovered in the liquid phase by the use of the detergent. The ACE activity varied with chloride ion (Cl-) concentrations; the maximum activities in dog, human, monkey and rabbit tissues were obtained at the concentrations of 800, 600, 600 and 300 mmol/l respectively. The optimal Cl- concentration was quite similar in different tissues and plasma obtained from the same species. The ACE activity in the cerebral, mesenteric, pulmonary and renal arteries was in a range between 1.01 and 1.60 m-units/mg of protein in dogs and between 0.43 and 0.94 m-unit/mg of protein in monkeys. The activity in dog aortae was 0.20 +/- 0.02 m-unit/mg of protein, and the activity in aortic endothelial cells was 2.61 +/- 0.65 m-units/mg of protein. ACE activities in the dog lung, kidney cortex and cerebral cortex were 28.6 +/- 2.6, 15.7 +/- 3.0 and 3.5 +/- 0.6 m-units/mg of protein respectively. SA-446, a captopril-like ACE inhibitor, reduced the ACE activity in arteries in a dose-dependent manner. Vascular ACE appears to be concentrated in the endothelium and may contribute to regulate vascular muscle tone and local blood flow by a conversion of angiotensin I into II.

3-Mercaptopropionic Acid↗

Induction by butylated hydroxyanisole of specific molecular forms of glutathione S-transferase and UDP-glucuronyltransferase and inhibition of development of gamma-glutamyl transpeptidase-positive foci in rat liver.

Effects of an antioxidant, butylated (3-tert-butyl-4-) hydroxyanisole (BHA) on the induction of specific molecular forms of glutathione S-transferase (GST), UDP-glucuronyltransferase (UDP-GT) and other glutathione-related enzymes in rat liver were investigated. The development of gamma-glutamyl transpeptidase (gamma-GTP)-positive foci and hyperplastic nodules induced by diethylnitrosamine, 200 mg/kg i.p., followed by 0.02% N-2-fluorenylacetamide (FAA) in diet plus partial hepatectomy was inhibited by the administration of 0.75% BHA in the FAA-containing diet. Inhibition was reflected in decreased area of gamma-GTP-positive foci which correlated with a decrease in gamma-GTP activity measured biochemically. Under the present experimental conditions, total activities of GSTs, especially that of GST-A form, and of UDP-GTs, especially that of the late fetal form (o-GT), were markedly increased, together with glutathione levels in the whole liver, within one week after BHA administration. Without BHA administration the activities of GST-A and o-GT, as well as glutathione levels, were also increased by FAA treatment, primarily localized within gamma-GTP-positive foci. These results suggest that the induction of specific molecular forms of detoxicating enzymes either in enzyme-altered foci or in the whole liver may play an important role in determining the extent of development of preneoplastic nodules from initiated foci under the short term induction conditions used.

Animals↗

Responses of isolated dog arteries to amrinone.

Helically-cut strips of dog cerebral, coronary, mesenteric, renal and femoral arteries contracted with prostaglandin (PG) F2 alpha or K+ responded to amrinone (10(-5) to 10(-4) mol X litre-1) with relaxation, which was not influenced by treatment with propranolol, atropine, cimetidine, aminophylline or aspirin. The contractile response of mesenteric arteries to transmural electrical stimulation (2, 5 and 20 Hz) and noradrenaline was attenuated by amrinone (3 X 10(-5) and 10(-4) mol X litre-1); the attenuation of the response to nerve stimulation and noradrenaline did not significantly differ. Ca2+-induced contractions in mesenteric arteries exposed to Ca2+-free media and depolarised by excess K+ were inhibited by amrinone, and the inhibition could not be reversed by the addition of excess Ca2+. Treatment with amrinone potentiated the relaxant responses of mesenteric arteries to adenosine but did not alter the response to isoprenaline. Amrinone in concentrations sufficient to produce moderate and marked relaxation did not significantly alter the content of cyclic AMP in mesenteric arteries. Attenuation by amrinone of the contractile response to transmural stimulation, noradrenaline and Ca2+ and the relaxation of a variety of arteries induced by amrinone may not be due to interference with the transmembrane influx of Ca2+ and intracellular accumulation of cyclic AMP but to a nonspecific action on arterial smooth muscle. Amrinone appears to increase the metabolic vasodilatation by potentiating the vasodilator action of adenosine.

Adenosine↗

Identification of a porcine follicular fluid fraction which suppresses follicular response to gonadotropins.

To evaluate the role of nonsteroidal, follicular fluid proteins in folliculogenesis, the 10-55% saturated ammonium sulfate fraction of pooled porcine follicular fluid (PFF) was dialyzed against 0.025 M Tris/HCl, pH 7.5, using 10,000 molecular weight exclusion membranes, then passed through agarose-immobilized textile dye. Activity was determined by test fraction inhibition of human menopausal gonadotropin (hMG) [2 U human luteinizing hormone (LH)/follicle-stimulating hormone (FSH) per day] induced ovarian weight and serum estradiol increase in hypophysectomized, diethylstilbestrol (DES)-treated, 25-day-old female rats. Specific inhibition (84 +/- 7.4%) of ovarian weight increase was found in the material (5 ml) eluted from the orange A column with KCl (1.5 M, pH 6.8). Inhibitory activity of the orange A-bound material which eluted through a standardized Sephadex G-100 column corresponded to a molecular weight of 12,000-30,000. Isoelectric focusing (IEF) on a Sephadex G-15 support bed of orange A-bound material demonstrated inhibitory activity at pH 3.7-4.0. Serial dilutions of active material from IEF preparations demonstrated a dose-response relationship in the bioassay. No demonstrable activity was found in similar fractions eluted through a Concanavalin A-Sepharose 4B column with or without addition of alpha-methyl mannoside (2 M, pH 7). When active fractions were heated (56 degrees C, 1 h) or exposed to trypsin (10 mg%), activity was lost. When aliquots of the saturated ammonium sulfated precipitated, dialyzed, orange A-bound, Sephadex G-100 (Ve/Vo 1.3-1.7) eluent were separated by high-performance liquid chromatography (HPLC) using gel exclusion columns, activity in the bioassay was recovered in the 18,000-35,000 molecular weight range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Computed tomography of calcified gastric carcinoma.

The CT findings in a case of calcified gastric carcinoma of the mucin-producing type are described. These findings include localized thickening of the gastric wall and multiple tiny calcific nodules within it.

Adenocarcinoma, Mucinous↗

Influence of alpha- and beta-adrenergic blockade on systemic and pulmonary hemodynamics during intravenous administration of local anesthetics.

The effects of alpha- and beta-adrenergic blockade on the systemic and pulmonary circulation during i.v. bolus injection of sub-seizure doses of lidocaine and bupivacaine were studied in dogs anesthetized with nitrous oxide. Pretreatment with hexamethonium or propranolol produced a marked decrease in cardiac output (CO), although pretreatment with phenoxybenzamine inhibited the decrease in CO during i.v. administration of lidocaine. Pretreatment with hexamethonium or phenoxybenzamine attenuated the increase in total peripheral resistance (TPR) following lidocaine 10 mg/kg i.v. In contrast, the propranolol-treated dogs developed a marked increase in TPR. The increases in mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) following lidocaine 10 mg/kg i.v. were blocked by pretreatment with hexamethonium. Furthermore, PVR increased markedly with pretreatment with propranolol, although pretreatment with phenoxybenzamine prevented the large increase in PVR. These findings indicate that lidocaine has both a direct depressant effect and an indirect beta adrenergic stimulant effect on the heart. Systemic or pulmonary vasoconstriction following intravenous administration of lidocaine 10 mg/kg is associated primarily with an indirect stimulant effect mediated by alpha-adrenergic mechanisms. Bupivacaine, as well as lidocaine, has an indirect stimulant effect mediated by the autonomic nervous system.

Animals↗

Activation of prokallikrein in the rat kidney by proteases.

Prokallikrein was activated by trypsin and by alpha-chymotrypsin, but not by proteases, such as plasmin, thrombin, urokinase, carboxypeptidase B, papain, elastase, pepsin, and cathepsin D. Moreover, rat fresh serum did not activate prokallikrein. Maximum activation of prokallikrein by trypsin was obtained at the concentration of 10 micrograms to 1 mg per ml in PBS and that by alpha-chymotrypsin was at the concentration of 5 mg per ml. The enzymic properties of trypsin-activated and alpha-chymotrypsin-activated kallikreins were identical with those of active kallikrein in the kidney.

Animals↗

Relationship between regional myocardial blood flow and tissue ATP content in acute ischemia.

This study was undertaken to determine the relationships between myocardial mitochondrial function, regional myocardial blood flow (MBF), and tissue ATP content in acute ischemia. Fifty-one anesthetized dogs were used in the tests. MBF was measured by the H2 gas clearance method in order to define the ischemic area, during periods of coronary occlusion of 10, 20, 60, and 90 min. The correlation between MBF and myocardial ATP content in the ischemic area was positive and significant in each group (r = 0.54-0.82). The ATP content in the true ischemic area (where MBF was less than 20 ml/min/100 Gm) decreased significantly even after 10 min of occlusion, but mitochondrial function decreased only after 20 min of coronary occlusion when compared to the nonischemic area. Although ischemia induces mitochondrial dysfunction, a very short period of ischemia did not cause significant disturbance of mitochondrial function. Moreover, in the areas with MBF of 20-40 ml/min/100 Gm, the ATP content began to decrease 60 min after occlusion, whereas 10 or 20 min of occlusion did not reduce the ATP content. These results suggest that normal maintenance of ATP levels depends not only on MBF itself but also on the duration of ischemia plus the degree of damage to mitochondrial function, and that critical blood flow, defined as the minimum flow necessary to maintain the level of myocardial ATP, varies with the duration of ischemia.

Acute Disease↗

A family with a high serum aminopeptidase (microsomal) activity: properties of the enzyme from serum of the propositus.

We found a family with a high activity for hydrolyzing L-alanyl-beta-naphthylamide in their serum. This enzyme was confirmed to be aminopeptidase (microsomal) (EC 3.4.11.2) by means of immunological experiments involving anti-human kidney aminopeptidase (microsomal) antibody. We could not find the cause of the increased activity from the results of clinical and laboratory examinations. The enzyme from the propositus resembled that from the serum of normal subjects in molecular mass (240 000 Da), Km value (87 mumol/L), and degree of inhibition by antiserum to human kidney aminopeptidase (microsomal). It differed from the normal enzyme with respect to electrophoretic mobility (R1 value, 0.58; normal, 0.51), isoelectric point (pI, pH 3.4; normal, pH 3.8), and heat stability (more labile than normal). From information on this family and another one reported in the Japanese literature, we suggest that the mode of inheritance of a high activity of serum aminopeptidase (microsomal) may be autosomal dominant.

Adolescent↗

[Anti-tumor activity of peripheral lymphocytes of tumor-bearing rats by in vitro culture].

This basic study was performed to determine whether the anti-tumor effect of lymphocytes obtained from the peripheral blood of a tumor bearing host can be increased when cultured in vitro with Mitomycin C (MMC)-treated AH109A tumor cells, using interleukin-2 (IL-2). Donryu rats were used as tumor bearing hosts. The following results were obtained. Weak anti-tumor activity of lymphocytes was noted 7 days after lymphocytes were cultured in the medium to which only IL-2 was added. Anti-tumor activity was augmented by adding antigen (MMC treated tumor cells) to the above (1). Anti-tumor activity was further augmented by adding to (2) above antigen presenting cells such as intraperitoneal exudate macrophages or peripheral hole leukocytes. Anti-tumor activity of lymphocytes was detected when IL-2 and MMC treated antigen were added to the peripheral hole leukocytes containing the lymphocytes.

Animals↗