Biomedical subjects

F Kojima

Publications and source records attributed to F Kojima.

At least 73 records · Page 4Linked to original sources

PubMed1984

Role of intramuscular enzymatic changes in the development of muscular weakness in rats with experimental allergic neuritis.

We investigated the role of intramuscular enzymatic changes in the development of muscular weakness in rats suffering from experimental allergic neuritis. At an initial stage without apparent clinical symptoms, enzymatic changes of similar types occurred in the muscles of the forelimbs and hind limbs. At a later stage when the weakness appeared in the hind limb but not in the forelimb, dissociation of the pattern of the enzymatic changes occurred between the two limbs. Comparison of the intramuscular enzymatic changes between the two stages and between the two limbs suggested that the increased activities of aminopeptidases and endopeptidases play some important roles in the development of muscular weakness in this experimental model. Low molecular weight protease inhibitors may thus be worthy of a trial in this disease condition.

Aging↗

PubMed1984

Difference in enzyme networks between mouse and hamster models of muscular dystrophy.

The present study was undertaken to compare the peculiarity of enzymatic changes in dystrophic hamsters and mice. Various enzymatic activities in muscle, bone, heart, spleen, liver and kidney were measured. The enzymes tested include 7 aminopeptidases, 5 endopeptidases, 3 glycosidases, creatine kinase, phosphatase and esterase. In dystrophic mice, the enzymatic changes were chiefly confined to muscle and bone. In dystrophic hamsters, on the other hand, extensive and pronounced changes in enzymatic activities were seen not only in skeletal muscle but also in bone, heart muscle, spleen, liver and kidney. Furthermore, resemblance of pattern of enzymatic changes was seen among several organs including skeletal muscle, heart muscle, bone and spleen in the hamster model. Comparing the enzymatic changes in these two models, dystrophic mouse may be regarded as more specific a model for musculoskeletal diseases. Dystrophic hamster may be related more to multiorgan diseases possibly associated with immunological or other systemic diseases. These models may represent two different disease categories, respectively.

Aminopeptidases↗

PubMed1984

Similar effects of various low-molecular-weight enzyme inhibitors on enzyme networks in dystrophic mice.

We compared the therapeutic effects of various low-molecular-weight enzyme inhibitors on dystrophic mice. Leupeptin, bestatin, forphenicinol and forphenicine significantly affected the enzymatic activities in the dystrophic muscles. The pattern of enzymatic changes in the muscles of forelimb and hindlimb caused by these inhibitors were similar in spite of the variety of their inhibitory spectra in vitro. However, comparing the pattern of enzymatic changes in spleen, forphenicinol differed from the other inhibitors tested. This may be related to the peculiar effects of this inhibitor on immunologically responsive cells.

Alkaline Phosphatase↗

PubMed1984

Oscillation of enzyme networks in spleen triggered by an immunopotentiator, bestatin.

In order to understand the effects of an immunomodulator in vivo, we performed time series analysis on mice given an aminopeptidase inhibitor, bestatin. This agent, which is known to be an immunopotentiator, caused peculiar oscillation of the activities of various hydrolytic enzymes in spleen. Autocorrelation curves obtained from serial data of each enzymatic activity revealed that sine curve-type oscillations are brought about in enzyme networks by this inhibitor. Judging from the pattern of the variations of enzymatic activities, it seems that metabolic homeostasis is strongly affected by this agent. The inhibitor probably initiated the homeostatic movements directly and secondarily caused extensive changes in the enzyme networks in vivo. This effect of bestatin may be useful in altering the pathological homeostasis (such as the one in autoimmune diseases) by affecting the dynamic equilibrium among the various components in the immunological system.

Adjuvants, Immunologic↗

PubMed1984

Abnormalities of splenic enzyme networks in nude mice.

The activities of various hydrolytic enzymes in splenic tissues of nude mice were compared with those of their controls of the same age. Since all of the enzymatic activities varied with age in both nude mice and in the controls, the difference between the two groups were difficult to define clearly. Principal component analysis enabled us to clearly categorize the enzymatic variations of both groups into two main components. One was related to the maturation process of the animals and the other to the pathological processes in the nude mice. The enzymes related especially to the latter component were formyl-methionine aminopeptidase (fMet-AP), mannosidase, and beta-N-acetyl-D-glucosaminidase (GlcNAc-ase). These enzymes may represent the abnormality of the surface of lymphocytes in the nude mice.

Aging↗

PubMed1984

Different enzymatic oscillations in vivo caused by the stereoisomers of an aminopeptidase inhibitor, bestatin.

The present study was undertaken to compare the enzymatic oscillations induced in three major organs, spleen, kidney, and liver, of mice by the active and inactive forms of an aminopeptidase inhibitor, bestatin. Although bestatin caused sine curve-type oscillations of enzymatic activities in spleen and kidney, its isomer, possessing no enzyme-inhibiting actions and no biological actions, did not show any typical enzymatic changes. Such typical oscillations were not elicited by either one of those two agents in liver, in spite of the apparent difference in the type of oscillations induced by them in this organ. These observations were taken to indicate that the enzymatic oscillations in vivo caused by bestatin are closely related to its aminopeptidase-inhibiting actions seen in vitro and that the immunomodifying actions of this agent are based on its effects on enzymes sensitive to it, possibly involving immunoresponsive cells.

Aminopeptidases↗

PubMed1983

Two different modes of enzymatic changes in serum with progression of Duchenne muscular dystrophy.

Nineteen serum enzymes from patients with Duchenne muscular dystrophy and asthma, and normal subjects were studied. These enzymes include aminopeptidases, cathepsin C, angiotensin-converting enzyme, serine proteinase, sulphatase, phosphatase, esterases and ribonuclease. The enzymatic changes in dystrophic patients were related to two parameters: severity of the disease as judged from symptomatology, and duration of the disease. Most of the enzyme levels tested were increased in milder cases, but they tended to decrease with severity of the disease. On the other hand, there was a group of enzymes showing just opposite tendencies: serine proteinase, cathepsin C and ribonuclease. Even when viewed from the relationship to duration of the disease, the above mentioned grouping of enzymes was generally valid. Most of the enzyme levels, including those routinely applied as clinical parameters, tended to decrease, logarithmically, with an increase in duration of the disease. On the contrary, some others, including serine proteinase, cathepsin C and ribonuclease, tended to increase toward their control levels. Such tendencies were not found in the patients with asthma. The discrepancy between the above two groups of enzymes may have some implications for the process of protein degradation in dystrophic patients.

Adolescent↗

PubMed1983

Relation between in vivo effects and in vitro effects of serine and thiol proteinase inhibitors.

In the present study we investigated the relationship between the in vivo effects and the in vitro effects of serine and thiol proteinase inhibitors. Each one of the inhibitors, leupeptin, dansyl-L-leucyl-L-argininal (Dan-Leu-Argal), pyroglutamyl-L-leucyl-L-argininal (Pyr-Leu-Argal), E-64C or EP-459 was given intraperitoneally to mice for 8 consecutive days and various enzymatic activities were tested in 6 organs: forelimb muscle, hindlimb muscle, heart, spleen, liver and kidney. A multivariate analysis clearly differentiated the effects of leupeptin from those of its two analogues (Dan-Leu-Argal and Pyr-Leu-Argal), while the two analogues showed close relations with each other as to their in vivo effects. E-64C and EP-459 also showed resemblance of in vivo effects between them, but the effects of these two agents were clearly differentiated from those of leupeptin and its two analogues. This kind of study seems important to assess the in vivo effects of physiologically active substances including enzyme inhibitors.

Animals↗

PubMed1983

Systemic enzymatic changes in guinea pigs suffering from experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is one of the experimental models of human demyelinating diseases and recently is regarded also as a useful model for studying cell-mediated autoimmune diseases. Because of the possibility of induction of systemic changes in this model, we investigated enzymatic changes in serum and main organs of the diseases animals, including brain, spinal cord, limb muscle, heart muscle, spleen, liver and kidney. The enzymes measured consisted of 7 aminopeptidases, 5 endopeptidases, 3 glycosidases, creatine kinase, phosphatase and esterase. Significant changes of many enzymatic activities occurred in all the organs tested in 1 to 2 weeks after the administration of EAE antigen, myelin basic protein (MBP). Interesting correlations of the pattern of enzymatic changes were seen among most of the organs tested. Those patterns changed in the course of the 2 weeks and there remained marked changes characteristic for each organ. This model may represent some type of systemic autoimmune diseases.

Animals↗

PubMed1983

Enzymatic changes in various organs of guinea pigs caused by the administration of Freund's complete adjuvant.

Although our previous studies demonstrated marked changes in the activities of hydrolytic enzymes in guinea pigs afflicted with experimental allergic encephalomyelitis (EAE), it is possible that at least some parts of them were due to the effects of Freund's complete adjuvant (FCA) per se used for immunization. Thus we tried to find the property of the enzymatic changes in the tissues of limb muscle, heart muscle, spleen, liver, kidney, brain, spinal cord and serum induced by the administration of FCA alone to the guinea pigs. FCA caused rather intensive enzymatic changes in every organ tested. When the patterns of these enzymatic changes were compared with those of the animals afflicted with EAE, a significant correlation was seen only in forelimb muscle at 1 week after the injection of the agents, whereas at 2 weeks significant correlations were seen in heart and liver. Although these results indicate that in some organs there are some similarities between the two experimental conditions, the degree of determination for this phenomenon was not high, being 28% at the highest. This means that most of the enzymatic changes seen in the animals afflicted with EAE could not be explained by the effects of FCA. It was concluded that FCA causes unique and systemic enzymatic changes when administered to the animals.

Animals↗

PubMed1983

Abnormalities of various serum enzyme activities in patients with congenital adrenal hyperplasia.

Recently, attentions are being aroused as to the enzymatic network abnormalities lying behind congenital enzyme deficiency syndromes. We investigated abnormalities in activities of various hydrolytic enzymes in serum of patients with congenital adrenal hyperplasia (CAH, 21-hydroxylase deficiency). Several enzyme activities including trypsin-like enzyme, cathepsin C and esterase were significantly decreased in patients' serum. Especially the esterase activity in patients' serum was reduced to one third of controls and this may have some relations to the abnormal steroid metabolism of these patients. A multivariate analysis showed unexpectedly extensive abnormalities in enzyme interrelationships. These results suggest that wide variety of abnormal metabolism may be related to an apparent enzyme deficiency.

Adolescent↗

PubMed1981

Various enzyme activities in muscle and other organs of dystrophic mice.

To elucidate the metabolic abnormality of musclar dystrophy, 27 kinds of enzyme activity in various organs of control and dystrophic mice were examined. The organs examined included muscle, bone, heart, testis, uterus, spleen, thymus, submaxillary gland, stomach, pancreas, liver, kidney, brain, and lung. The activities of 14 different aminopeptidases, 5 endopeptidases, 4 glycosidases, phosphatase, esterase, and ribonuclease were measured. Most of the enzyme activities were significantly elevated in muscles and bones of dystrophic mice. These organs were similar in their patterns of enzyme abnormality. Among the 14 kinds of aminopeptidase activity studied, the degree of increased activity was greater for the aminopeptidases (AP):Ala-AP, Leu-AP, Met-AP, Phe-AP, Trp-AP, Gly-Pro-Leu-AP. In addition to aminopeptidases, there were significant increases in activities of chymotrypsinlike enzyme, cathepsin C, cathepsin D, several glycosidases and neutral ribonuclease in the muscles of dystrophic mice. Similarly increased enzyme activity was also observed in organs other than muscle and bone. Furthermore, protein content in most organs was higher in dystrophic mice than in those of control mice. These abnormalities were seen in both males and females. The present results suggest that there are extensive abnormalities in the protein metabolism in dystrophic mice. It seems therefore that the therapeutic approach to muscular dystrophy should be studies not only from the well-known abnormality of intramuscular endopeptidases, but from other aspects as well.

Animals↗

PubMed1981

Intramuscular enzyme abnormalities of dystrophic chickens compared to those of dystrophic mice.

The present study was performed to investigate the enzymatic changes in dystrophic chickens compared to those of dystrophic mice. The activities of 14 kinds of aminopeptidases, 5 kinds of endopeptidase, 4 kinds of glycosidases, phosphatase, esterase, and ribonuclease were measured in muscles of control and dystrophic chickens. When the enzyme activities were expressed as specific activity per unit weight of organs, only some of them were found to be significantly elevated in dystrophic chickens; e.g., alanine aminopeptidase (Ala-AP), Gly-AP and cathepsin D. On the contrary, the activities of alpha-D-glycosidase, alpha-D-galactosidase and alpha-D-mannosidase were significantly decreased. Muscular protein contents of dystrophic chickens also tended to be lower than those of controls. These observations offer a striking contrast with the one obtained in the study on dystrophic mice. However, when expressed as specific activity per mg protein, many enzyme activities were found to be significantly elevated suggesting an extensive abnormality of metabolism in dystrophic chickens. Among 14 kinds of aminopeptidase activities, highly significant elevations were seen especially in AP-A, AP-B, Gly-AP, Ala-AP, Ser-AP, Pro-AP, Leu-AP, Met-AP and Trp-AP. Interestingly enough, a statistical approach suggested a significant correlation between the aminopeptidase changes of dystrophic chickens with those of dystrophic mice. In addition to aminopeptidases, there were highly significant increases in the activities of cathepsin D, alpha-D-glucosidase, beta-D-galactosidase, alpha-D-mannosidase, esterase and RNase. These results indicate that the intramuscular metabolic abnormality of dystrophic chickens are generally different from but partly resembled with those of dystrophic mice.

Aminopeptidases↗

PubMed1980

Purification by affinity chromatography using amastatin and properties of aminopeptidase A from pig kidney.

1. Amastatin, a specific inhibitor of aminopeptidase A (L-alpha-aspartyl(L-alpha-glutamyl)-peptide hydrolase, EC 3.4.11.7), was linked to an agarose matrix and by this affinity chromatography aminopeptidase A of pig kidneys was purified as a single protein shown by acrylamide gel electrophoresis. 2. Aminopeptidase A which was purified 710-fold, hydrolyzed only acidic amino acid beta-naphthylamide. The optimum pH and the optimum temperature was 7.5 and 45-50 degrees C, respectively. 3. The molecular weight was approx. 300 000 as determined by Sephadex G-200 gel filtration. 4. The activity of aminopeptidase A was not affected by sulfhydryl agents, S-S dissociating agents and serine proteinase inhibitor, but was inhibited strongly by metal chelating agents, and enhanced by alkaline earth metals. 5. Amastatin inhibited aminopeptidase A in a competitive manner with L-glutamic acid beta-naphthylamide, and the Ki value was calculated to be 2.5 x 10(-7) M. The inhibitory effect of amastatin on aminopeptidase A was not reversed by addition of Ca2+.

Aminopeptidases↗

PubMed1978