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Biomedical subjects

F Kojima

Publications and source records attributed to F Kojima.

At least 55 records · Page 3Linked to original sources
PubMed1989

Possible relationship between poly(ADP-ribose)synthetase and formation of antibody against acetylcholine receptors in patients with myasthenia gravis.

We examined the relationship of the serum levels of antibody against acetylcholine receptors to the serum levels of 13 enzymes, including various hydrolytic enzymes, poly(ADP-ribose)synthetase (Poly(ADP-ribose)Syn), and sialyltransferase (NANA-trans), in patients with myasthenia gravis. The patients were divided into two groups, depending on the presence or absence of thymoma. In spite of the absence of significant difference in the absolute levels of individual enzymatic activities between the two groups, the network relationships of such enzymes were quite different between the two groups. Of the 13 enzymes examined, only Poly(ADP-ribose)Syn showed a weak but significant correlation with the level of the antibody in the patients without thymoma. A multivariate study more clearly suggested the relationship between the antibody formation and Poly(ADP-ribose)Syn in the patients without thymoma. Such observations were not found in the patients with thymoma.

Autoantibodies↗
PubMed1989

Suppression of the activities of T-lymphocyte-related enzymes in spleen by administration of an immunosuppressant, 15-deoxyspergualin.

We investigated the effects of both (-) and (+)-enantiomers of 15-deoxyspergualin (DSG), an immunosuppressant, on enzyme networks in spleens of ICR mice. Of the 14 hydrolytic enzymes tested, the activity of dipeptidyl aminopeptidase IV (DAP-IV) was found to be significantly suppressed by the administration of (-)-DSG but not by that of (+)-DSG. In contrast, the activity of N-acetyl-beta-D-glucosaminidase (GlcNAc-ase) was suppressed by the administration of both enantiomers of DSG. Judging from the previous reports of ours and others which suggested specific relations of these enzymes to T-lymphocytes, the above findings may warrant further studies of these enzymes in relation to immunologic functions of the body.

Acetylglucosaminidase↗
PubMed1989

Multiple enzymes related to differentiation of lymphocyte subpopulations in man.

We studied the relation of various enzymes to subpopulations of lymphocytes in man. T cell-rich fractions were separated with a nylon column from mononuclear cells in the buffy coat. Comparing the enzymatic profiles of the two fractions, we found that the difference between the two groups came from the dominancy of B cells and/or macrophages in the former fraction, and from that of T cells in the latter. The enzymes characterizing T cells included N-Ac-beta-D-glucosaminidase (GlcNAc-ase), prolyl endopeptidase (Post-Pro-Enz), and dipeptidyl aminopeptidase IV (DAP-IV), whereas those characterizing B cells and/or macrophages include poly(ADP-ribose) synthetase, leucine aminopeptidase (Leu-AP), AP-B, cathepsin B, sialidase, and AP-A. Inhibitors of these enzymes may lead to modification of the function of T and B cells.

B-Lymphocytes↗
PubMed1988

Synthesis of histargin and related compounds and their inhibition of enzymes.

A novel method for the synthesis of histargin and its analogs is described. It includes two kinds of N-alkylation reactions that prevent the formation of side products. The inhibition of enzymes by these compounds was also measured. Some of the compounds strongly inhibited carboxypeptidase B, carboxypeptidase A, carboxypeptidase N (kininase I), and angiotensin converting enzyme.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Feedback analysis of the behavior of the renin-angiotensin system under inhibition of angiotensin-converting enzyme.

It was previously shown that autoregressive modeling can be used for feedback analysis in the body. We used this method to investigate the dynamic changes in and around the renin-angiotensin system in vivo induced by angiotensin-converting enzyme (ACE) inhibition. Long-term studies were performed on rabbits, which were given a daily injection of one of the following ACE inhibitors: captopril, foroxymithine, or histargin. For comparison, other rabbits received injections of saline or the renin inhibitor pepstatin. Autoregressive coefficients were computed from the raw data thus observed and were used to simulate the impulse-response function proper to each animal. The response of each animal estimated in this way exposed the effects of ACE inhibitors in vivo which were obscured by the feedback regulation of the renin-angiotensin system. Also, it was suggested that histargin has a peculiar action, blocking the negative feedback that would be elicited by the usual ACE inhibition. Feedback analysis seems to be essential to elucidate the in vivo effects of enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Relative deficiency of serine proteinase activities in spleens of aged mice.

We examined the relation of hydrolytic enzymes in spleen to the aging process in mice over a period of 30 months. When the enzymatic activities were expressed as activities per milligrams protein, those of serine proteinases and dipeptidyl peptidase IV (Gly-Pro-AP) significantly decreased with age, whereas that of L-leucine aminopeptidase (Leu-AP) increased significantly. However, when expressed as total activities, the enzymatic activities in spleen generally tended to increase with age, except in the case of serine proteinases, because of the age-related increase in spleen weight. The results were taken to indicate that the activities of serine proteinases become relatively more deficient in the spleen as age increases. The results of a multivariate study maintained this peculiarity of serine proteinases in comparison with other enzymes. The relative deficiency of serine proteinases in spleen may be somehow related to immunodeficiency in aged animals, as judged from similar findings in animal models of systemic erythematodes.

Aging↗
PubMed1987

Dissociation between serine proteinases and proline related enzymes in spleen of MRL mouse as a model of systemic lupus erythematodes.

We investigated the changes in the activities of proteases and other hydrolytic enzymes in spleens of MRL mice as a model of systemic lupus erythematodes (SLE). Although there are various abnormalities in the activities of proteases in the spleens of such animals, a multivariate study helped to extract two important components. The first component, representing the activities of serine proteinases, tended to decrease with advancing age in MRL mice but not in control animals. The second component, representing Pro-IP and prolyl endopeptidase, tended to decrease with advancing age in control animals, but not in the MRL mice. The discrepancy between these two components may be related to the immunopathologic disturbances in this model.

Animals↗
PubMed1987

Decreased activities of serine proteinases in spleen of various murine models of systemic lupus erythematodes.

Previous studies indicated a relationship between immune deficiencies and abnormalities in the activities of various hydrolytic enzymes, including proteinases, in tissues. In the present study, we compared such activities in spleen among the three types of murine models of systemic lupus erythematodes (SLE) (i.e., New Zealand black/white mouse, MRL mouse, and BXSB mouse) and their controls. According to the results of multivariate analysis, it was shown that the most important enzymatic changes differentiating the pathologic animals from their controls were decreases in the activities of serine proteinases. Judging from the behavior of these enzymes in various immunological disturbances, it is likely that they play some important roles in pathophysiology of SLE.

Animals↗
PubMed1987

A multivariate study on enzymatic changes in limb muscles and heart muscle of dystrophic mice.

The present study was undertaken to elucidate further the enzymatic changes in dystrophic muscle using multivariate analysis. The activities of 14 kinds of enzymes, including 6 exopeptidases, 4 endopeptidases, beta-N-acetyl-D-glucosaminidase, phosphatase, esterase, and ribonuclease, were examined in forelimb and hindlimb muscles as well as in cardiac muscle of dystrophic mice and their controls. Two principal components identified from the enzymatic spectrum proved to be related especially to aminopeptidases and to serine proteinases, respectively. The enzymatic changes in forelimb muscle were very similar to those in hindlimb muscle when both were compared to those in cardiac muscle. The changes in aminopeptidases were unique to the limb muscles, whereas those of serine proteinases were unique to cardiac muscle of dystrophic mice. In the future, more attention should be focused on the role of exopeptidases in pathogenetic mechanisms of muscular dystrophy, because of the possibility that they play a major role in the initial stage of muscular dystrophy.

Animals↗
PubMed1986

The dissociation between the plasma levels of aminopeptidases A and B in spontaneously hypertensive rats.

We performed a longitudinal study for 20 weeks on spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKR) to determine the relationship between peptide metabolism and the age-dependent increase in blood pressure. In both SHR and WKR, the plasma level of aminopeptidase A (AP-A) clearly showed an age-dependent decrease. The plasma level of aminopeptidase B paralleled that of AP-A in WKR, but such an age-dependency was not observed in SHR, thus showing a dissociation between the two aminopeptidases. With age in both strains, the level of angiotensin-converting enzyme tended to decrease, while that of kallikrein activity tended to increase. In addition to these findings, a multivariate study testing the relationship of blood pressure to these enzyme activities, as well as to plasma levels of angiotensin I and renin activity, suggested abnormalities in the networks of proteolytic enzymes and in the peptide metabolism surrounding the renin-angiotensin system in SHR. These abnormalities may play some important roles in pathophysiological mechanisms of hypertension in SHR.

Aging↗
PubMed1986

Relation of hydrolytic enzymes in spleen to immunological dysregulation in mice.

In order to know the role of hydrolytic enzymes in various immunological disturbances, we compared the enzymatic changes in the spleens of nude mice and NZB/W mice relative to their respective controls. In spite of the different immunological features of these models, multivariate analysis demonstrated that there is some commonness in enzymatic changes between the two models. The enzymes related to such commonness included glycosidases, alkaline phosphatase, fMet-AP, and esterase. These enzymes may play some important roles in immunologic dysregulation , especially in relation to B-cell dominance in these disease models.

Animals↗
PubMed1986

Three modes of age-related changes of hydrolytic enzymes in murine brain.

We followed the time course of the activities of various hydrolytic enzymes in murine brain for 30 months to investigate their roles in the aging process. Although most of the 15 enzymatic activities tested tended to rise with the increase in age, by analyzing them by multivariate analysis their movements could be divided into three types, each having a particular mode of nonlinear regression: exponential, logarithmic, or parabolic. Several enzymatic activities, including those of angiotensin-converting enzyme, esterase, trypsin-like enzyme, post-proline-cleaving enzyme, and Gly-Pro-aminopeptidase, showed rhythmic oscillations with about one cycle per 3 months throughout the period of 30 months. The behavior of these enzymes probably represents some particular aspect of metabolism relatively independent from the aging process. These findings may provide a fundamental clue in association with the process of maturation and aging in the brain.

Aging↗
PubMed1985

Relation of blood glucose levels to the changes in plasma levels of various hydrolytic enzymes in diabetic patients.

Plasma levels of various hydrolytic enzymes in diabetic patients, as diagnosed by their blood glucose levels, were compared with those of control subjects. Most of the levels of the aminopeptidase activities examined were significantly increased, while those of angiotensin-converting enzyme (ACE) and esterase decreased, in diabetic patients. The results of multivariate analysis suggest that the increased aminopeptidase activities are related rather to secondary organ lesions than to the primary pancreatic lesion. It seems that the blood glucose level is not necessarily a good indicator of metabolic abnormalities underlying this pathological condition.

Acetylcholinesterase↗
PubMed1985

Influence of angiotensin-converting enzyme inhibitor, foroxymithine, on dynamic equilibrium around the renin-angiotensin system in vivo.

To understand the in vivo actions of angiotensin-converting enzyme (ACE) inhibitors, a prolonged study was performed in rabbits over a half year, using one of such inhibitors, foroxymithine. During the initial 2 months of the inhibitor administration, the serum level of ACE was suppressed. Thereafter, probably triggered by the consequent sharp rise in the plasma renin activity (PRA) level, the ACE level regained its initial value. Thus the close correlation between the levels of PRA and ACE seen in the control animal was entirely broken by this inhibitor. A multivariate study indicated that the inhibitor drastically changed the normal networks of peptide metabolism in vivo. These results are compatible with the notion that the ACE inhibitor blocks the regulatory mechanisms of the renin-angiotensin system in vivo.

Angiotensin I↗
PubMed1985

Systemic changes in hydrolytic enzyme activities in mice affected with murine leprosy.

In order to investigate the behavior of hydrolytic enzymes in chronic infections, the activities of 17 hydrolytic enzymes were tested in limb muscles, heart muscle, spleen, liver, and kidney of lepromatous mice infected with Mycobacterium lepraemurium (M. lepraemurium) and their controls. Typical increases in those enzymatic activities were seen in spleen and liver, where pathological changes were the most pronounced, especially at the 11th week after the inoculation of the bacilli. At the 16th week, the enzymatic changes became less remarkable probably because of the decreased viability of tissues in these organs. The enzymatic changes observed could not be explained as due to bacterial enzymes. These findings are compatible with the notion that the increases in hydrolytic enzyme activities are related to tissue damage caused by murine leprosy.

Animals↗
PubMed1985

Dissociation of creatine kinase activity from hydrolytic enzyme activities in muscle of dystrophic mice.

Time course studies were done to reexamine the age-dependency of intramuscular enzymatic changes in dystrophic mice. Most of the activities of hydrolytic enzymes in dystrophic mice were elevated in comparison to the controls throughout the span of 8 weeks which was examined. In contrast, the activity of creatine kinase remained depressed throughout the same period. This tendency was similarly seen in the muscles of forelimb and hindlimb but not in heart muscle. The observations are compatible with the notion that the increased activities of hydrolytic enzymes are causally related to the destruction of muscular tissue, leading to the malfunction of contractile machinery in the dystrophic muscles.

Animals↗