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Biomedical subjects

N Higuchi

Publications and source records attributed to N Higuchi.

At least 55 records · Page 3Linked to original sources

Synthesis and inhibitory activity of acyl-peptidyl-prolinalderivatives toward post-proline cleaving enzyme as nootropic agents.

Several prolinal derivatives were synthesized and examined for their inhibitory activity on post-proline cleaving enzymes from Flavobacterium meningosepticum and bovine brain and their possible properties as nootropic agents. Almost all the compounds tested inhibited the activity of both enzymes at low IC50 values of the order of nM, but a specificity difference was observed with alkylacyl-prolinal derivatives which strongly inhibited only the bacterial enzyme. Prolyl-prolinal derivatives were the most effective inhibitors for both enzymes. In the passive avoidance test using amnesic rats experimentally induced with scopolamine, the prolinal derivatives that have potent inhibitory activity toward post-proline cleaving enzymes showed also strong anti-amnesic activities at dose of 10-1000 micrograms/kg, i.p. Some of the compounds showed a bell-shape dose dependency. These results suggest that the post-proline cleaving enzymes play an important role in the regulation of learning and memory consolidation in the brain and inhibitors of these enzymes are suggested as possible candidates for nootropic agents, particularly for an anti-amnesic drug.

Amino Acid Sequence↗

Inhibitory effect of di- and tripeptidyl aldehydes on calpains and cathepsins.

Eight different di- and tripeptidyl aldehyde derivatives, each having at its C-terminus an aldehyde analog of L-norleucine, L-methionine, or L-phenylalanine with a preceding L-leucine residue, were synthesized and tested for their inhibitory effects on several serine and cysteine endopeptidases. These compounds showed almost no inhibition of trypsin, and only weak inhibition of alpha-chymotrypsin and cathepsin H, while they exhibited marked inhibition of cathepsin B less than calpain II congruent to calpain I less than cathepsin L, being stronger in this order. The mode of inhibition of these cysteine proteinases was competitive for the peptide substrate used and inhibitor constants (Ki) were calculated from the Dixon plot. The best inhibitors found were: 4-phenyl-butyryl-Leu-Met-H for calpain I (Ki, 36 nM) and calpain II (Ki, 50 nM); acetyl-Leu-Leu-nLeu-H for cathepsin L (Ki, 0.5 nM); acetyl-Leu-Leu-Met-H for cathepsin B (Ki, 100 nM).

Aldehydes↗

Response to and control of destructive energy by magnetic resonance.

Magnetic resonance imaging techniques can be used to control and monitor the deposition of destructive energy. The authors evaluated the feasibility of phosphorus-31 magnetic resonance spectroscopy for the control, monitoring, and prediction of the three-dimensional extent of tissue destruction during interstitial laser surgery. Characteristic metabolic changes were demonstrated within the lesion and in the adjacent normal tissue during the deposition of thermal energy.

Adenosine Triphosphate↗

[Effect of androgen on the onset of diabetes in the KK mice treated with monosodium aspartate].

Obese diabetes was induced by monosodium aspartate (MSA) administration in KK male mice and the diabetic KK mice were divided into two groups, younger (12-week-old) and older (35-week-old). The diabetic KK mice were castrated and administered with androgen and effect of androgen on glycosuria appearance was investigated. Androgen dependent tear proteins (Mtp-M) were detected by the method of polyacrylamide gel electrophoresis. Blood androgen level was estimated by observation of change of the pattern of Mtp-M. In the younger mice group, glycosuria disappeared temporarily after castration and then appeared naturally again. The Mtp-M declined with castration, but did not disappear in this experimental period. In the older mice group, glycosuria and Mtp-M disappeared completely and blood glucose level decreased considerably after castration. However, in the castrated older mice, the glycosuria and the Mtp-M appeared again after the administration of dehydroepiandrosterone (DHEA), and the increasing of blood glucose level was observed. These results strongly suggested that androgen had an important role in the onset of diabetes in the KK mice treated with MSA.

Age Factors↗

[Study on the feeding function and feeding behavior of children. 1. Biting pressure and masticatory efficiency for 3, 4 and 5 years old children].

The purpose of this study was to investigate the biting pressure and masticatory efficiency of 3, 4 and 5 year old children. Some of them had trouble regarding their feeding behavior, either saying that they were not able to bite hard food or that they didn't want to bite hard food. A new method using A.T.P. (Adenosine Triphosphate) granules introduced with rubber finger protectors was used for measurement of the masticatory efficiency. 69 healthy 3, 4 and 5 year old children who had normal occlusion and were caries free were the subject. The results obtained were as follows. 1) The mean of the biting pressure for the 2nd primary molars for 69 children was 21.7 Kg. As for the data of the biting pressure for each age group, it was shown to increase with age (3 to 5 year old). 2) The mean of the masticatory efficiency for 69 children was 0.201 abs. As for the data of the masticatory efficiency for each age, it were shown to increase with age (3 to 5 year old). 3) The coefficient of the correlation of the biting pressure and the masticatory efficiency for 69 children was 0.410 which was considered statistically significant. (P less than 0.05) The coefficient of the correlation of the biting pressure and the masticatory efficiency for 3 year old children was 0.461, the coefficient of the correlation for the same items for 4 year old children was 0.395 and the coefficient of the correlation for 5 year old children was 0.353. All of these were considered statistically significant. (P less than 0.05)

Bite Force↗

[Clinical analysis of postoperative recurrent nerve palsy in patients undergoing operation of carcinoma of the thoracic esophagus].

From January 1976 to April 1987, 325 cases of carcinoma of the thoracic esophagus were resected in our department. Among these cases, 25 cases were not included because of direct operative deaths or early hospital deaths, and 300 cases were selected for clinical analysis of postoperative recurrent nerve palsy, which occurred in 75 cases (25.0%). The rate of occurrence of this palsy in the last 6-year period was higher than that in the first 6-year period (34.0% and 15.3%, respectively). It was suggested that the extension of surgical procedures to the cervix and upper mediastinum had contributed to this increase in rate. The sides affected by palsy were as follows: left, 56.0%, right 12.0%, bilateral, 24.0%; unknown, 8.0%. The importance of gentle handling of the left recurrent nerve during operation should be emphasized. The rate of occurrence of palsy in the cases of "Iu" was higher than in cases of "Im" and "Ei" (53.3%, 31.6%, 26.8%, respectively). The rate of occurrence of this palsy was significantly higher in the cases in which cervical anastomosis was performed than in cases in which intrathoracic anastomosis was performed (31.9% and 2.8%, respectively; p less than 0.01). Of the cases complicated by this palsy (Group A), tracheostomy was done in 12.0% of the cases and long-term transnasal tracheal tube cannulation or tube reinsertion done in 29.3%. These rates were significantly higher than the rates for cases who did not develop this palsy (Group B). The rates of occurrence of postoperative pulmonary complications within one month after surgery in Group A and Group B were almost same (24.3% and 21.8%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High-performance affinity chromatography of human serum concanavalin A binding proteins.

A high-performance concanavalin A (Con A) affinity column Gelpack GL-L55C (Hitachi Kasei Industries) was successfully used for the fractionation of human serum Con A-binding proteins. Serum proteins that have strong affinity to Con A (ca. 11% of the recovered proteins) could be fractionated within 80 min. By analysing the eluates from the column by micro two-dimensional electrophoresis, followed by blotting and Con A staining, the specificity of the column was effectively visualized. Although the protein-binding capacity of the column gradually decreased during repeated loading of serum or tissue extracts, the specificity of the column to Con A-binding proteins did not change. Serum lipoproteins have been eluted from the column with 6 M urea, suggesting that the capacity decrease is caused by the binding of lipids or lipoproteins to the column.

Chromatography, High Pressure Liquid↗

Synthesis of a new cell penetrating calpain inhibitor (calpeptin).

N-terminal of Leu-norleucinal or Leu-methioninal was modified to obtain a cell penetrative peptide inhibitor against calpain. Benzyloxycarbonyl (Z) derivatives had less active against papain than phenylbutyryl derivatives and leupeptin. Z-Leu-nLeu-H (calpeptin) was more sensitive to calpain I than Z-Leu-Met-H and leupeptin. Calpeptin was most potent among synthesized inhibitors in terms of preventing the Ca2+-ionophore induced degradation of actin binding protein and P235 in intact platelets. After 30 min incubation with intact platelets, calpeptin completely abolished calpain activity in platelets but no effect was observed in case of leupeptin. Calpeptin also inhibited 20K phosphorylation in platelets stimulated by thrombin, ionomycin or collagen. Thus calpeptin was found to be a useful cell-penetrative calpain inhibitor.

Animals↗

Staining of serum concanavalin A-binding proteins after micro two-dimensional electrophoresis and blotting.

Human serum proteins separated by micro two-dimensional electrophoresis in the absence of denaturants were electrophoretically transferred to nitrocellulose sheets (blots), and glycoproteins on the blots were stained by sequential incubation with the lectin concanavalin A, the glycoprotein horseradish peroxidase and the substrates of peroxidase diaminobenzidine-hydrogen peroxide. The stained serum concanavalin A-binding glycoproteins were identified by referring to the "identification map" of human plasma proteins, which we have prepared by immunochemical staining of the proteins on the blots. The concanavalin A-peroxidase method applied for the blots after two-dimensional electrophoresis provided information on the location of serum concanavalin A-binding glycoproteins, and showed greater sensitivity than Coomassie Brilliant blue R-250 staining for several serum proteins.

Electrophoresis, Polyacrylamide Gel↗

Differentiation of mononucleosis from hepatitis by sonographic measurement of spleen size.

Spleen size in patients with infectious mononucleosis (IM) was measured using ultrasound, and the findings were compared with data obtained in cases of acute viral hepatitis (AVH). The size was expressed as the spleen index (SI) or the product of the longitudinal and transverse diameters, expressed in cm2, of the maximum cross-sectional area of the spleen. A normal value obtained from 28 healthy individuals was 15 +/- 7 cm2. The SI (mean +/- SD) of patients with AVH and IM were 38 +/- 7 cm2 and 88 +/- 26 cm2, respectively. When the SIs were divided into five groups--grade 0 (0-25), grade I (26-50), grade II (51-75), grade III (76-100), and grade IV (100+), 83.3% of the patients with AVH were graded as Grade 0 or I, whereas 88.9% patients with IM belonged to higher grades. Splenomegaly with a SI value over 75, grade III or IV, strongly suggests IM when IM and AVH are being considered in the absence of other potential causes of splenomegaly. Because the clinical features of IM sometimes resemble those of AVH, it is often difficult to differentiate the two entities. The measurement of spleen size could be a significant supplemental aid in the diagnosis of IM in primary medicine, before clinical data can be obtained.

Adult↗