Role of HLA-DP antigen in xenogeneic iso-skin grafts using transgenic mice.
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Biomedical subjects
Publications and source records attributed to M Hagihara.
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We investigated the activity of peptidases in the serum of mice with experimental polyarthritis that was induced by the injection of type II collagen, an experimental model of human rheumatoid arthritis. The activity of dipeptidyl peptidase II (DPP II) was increased and that of dipeptidyl peptidase IV (DPP IV) was decreased resulting in the significant increase of the serum DPP II/DPP IV ratio in the polyarthritic mice compared with that of controls. These results indicate that the DPP II/DPP IV ratio is a novel index of disease activity in mice with collagen-induced polyarthritis and may be useful in assessing the activity of rheumatoid arthritis in humans.
The pretreatment characteristics of nine acute myelogenous leukemia (AML) patients with 8;21 translocation were evaluated to assess their value as prognostic indicators. All patients had AML-M2 according to French-American-British classification. The percentage of eosinophils in the bone marrow (EO/BM) correlated negatively with the percentage of blast cells in the peripheral blood (BL/PB) (p less than 0.05) and positively with complete remission duration (p less than 0.01). Three of the six patients with EO/BM under 5% showed aggressive clinical courses complicated with extra marrow lesions, while the patient with the highest EO/BM was the only one who survived for 5 years. These findings suggest that bone marrow eosinophilia could be useful as a prognostic indicator in AML patients with t(8;21).
We examined the activities of peptidases in the synovial membrane from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Dipeptidyl peptidase II (DPP II), prolyl endopeptidase (PEP), and collagenase-like peptidase (CLP) activities were higher in knee joint synovial membrane from patients with RA than in that from patients with OA. DPP II and PEP activities in knee joint synovial membrane of patients with RA increased in parallel with the increase in joint fluid volume, whereas DPP IV activity decreased in parallel with the increase in joint fluid volume. These results suggest that these peptidases in the synovial membrane may play some role in immunological disturbances in the joints of patients with RA. Measurement of these peptidases in synovial membrane may be useful in the diagnosis of the severity of local joint inflammation.
Nine acute myelogenous leukemia(AML) patients with a translocation 8;21, who were treated at Keio University Hospital between 1983 and August 1990, were reviewed. All of them were classified into AML-M2 subtype of the French-American-British classification. It formed 43% of all M2 cases. The patients' mean age was 47 years. Neutrophil alkaline phosphatase score was lower than normal and complete remission(CR) was achieved in all cases. In statistical analysis, patients with the t(8;21) showed a longer CR duration and a higher percentage of eosinophils than the other AML-M2 patients without this karyotype (p less than 0.05, p less than 0.01, respectively). As an additional chromosomal abberation, two patients showed a loss of Y chromosome at first diagnosis and another patient did a deletion of 12p at the 3rd relapse and an elongation of 20q in addition to the 12p- at the 4th relapse. Although patients with the t(8;21) are regarded as a favorable group in respect of survival, we found a subset of patients who had poor prognosis. Some of them were accompanied with solid tumor formation. Only one patient has lived longer than 5 years. These findings suggest that AML with the t(8;21) is clinically heterogenous.
Rats on calcium-deficient diets developed hypocalcemia, hyperparathyroidism and hypertension and showed an increase in plasma catecholamines. Adrenal gland catecholamines were decreased while tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were found to be increased, as compared to controls. In contrast, no significant differences were found between controls and parathyroidectomized rats in plasma catecholamines, and catecholamines, TH and DBH of the adrenal gland. These findings seem to indicate that the genesis of hypertension in rats on a low calcium diet is secondary to hyperparathyroidism caused by a low calcium diet. Furthermore, some relation between catecholamines and parathyroid hormone seems to exist in the regulation of blood pressure in rats.
The activity of DPP II was higher in gingiva from patients with periodontitis, but the activity of DPP IV, post-proline cleaving enzyme and collagenase-like peptidase was not significantly higher than that of the control group. As DPP II activity is known to be altered in immunological diseases, these findings may suggest some role for DPP II in the pathogenesis of chronic marginal periodontitis.
We have measured for the first time, using specific substrates and specific fluorometric analyses, activities of three pathophysiologically important peptidases, i.e., dipeptidyl peptidase II, dipeptidyl peptidase IV, and prolyl endopeptidase in effusions from 45 patients with chronic otitis media with effusion. In 20 patients, DPP II and DPP IV were assayed simultaneously in effusions and sera. Activity of PEP was also estimated in effusions and sera from 25 patients. The mean values (+/- SD) of DPP II and DPP IV (n = 45) and PEP (n = 25) in effusion from patients with OME were 0.020 +/- 0.007, 0.66 +/- 0.04, and 0.040 +/- 0.006 nmole/min/mg protein, and 0.21 +/- 0.01, 16.2 +/- 1.87, and 1.90 +/- 0.23 nmole/min/ml of effusion, respectively. The mean values (+/- SD) for DPP II, DPP IV, and PEP in sera were 2.82 +/- 0.18, 54.8 +/- 1.23, and 3.73 +/- 0.33 nmole/min/ml of serum, respectively, which were similar to our previously reported values. Activities of DPP II, DPP IV, and PEP of serous effusions were comparable to those in serum. However, there was no significant correlation between their activities in serum and effusion. This may suggest that the major source of these enzymes in effusions may not be serum but the cells in the middle ear.
The concentrations of neopterin and biopterin in CSF of 18 younger and 10 older, control patients and of 18 patients with Parkinson's disease were measured by high-performance liquid chromatography with fluorescence detection. Both neopterin concentrations and the neopterin to biopterin ratios in CSF were lower in 50-year or younger group than in 51-year or older group. Biopterin concentrations were also decreased but not significantly in the older group. The concentrations of neopterin and biopterin in CSF of patients with Parkinson's disease were lower than those of the age-matched older control group. However, the neopterin/biopterin ratios tended to be lower but not change significantly as compared to the age-matched older control group.
Reported is the case of a 57-year-old male patient, who manifested tarry stool and who had undergone a subtotal gastrectomy at our hospital in 1983 for an early carcinoma, type IIc, which proved to be a well differentiated tubular adenocarcinoma. Three years later, he returned complaining of epigastralgia, although no evidence of a recurrence could be seen. An abdominal ultrasonogram and a CT scan, however, revealed a right renal tumor and he subsequently underwent an operation for the removal of a renal cell carcinoma, a clear cell type. In 1988, he again was readmitted to hospital, this time because he easily became fatigued. An upper GI series and gastroscopy located a polypoid lesion in the remnant stomach. Thus, a total gastric resection was performed, and the lesion was diagnosed as being a well differentiated tubular carcinoma, an early gastric cancer, type I. Triple carcinomas are very rare, and the details of this case are discussed.
One hundred and fifty five cases (237 eyes) of children with uveitis were clinically observed in the past 20 years. There was no fluctuation in the number of patients during the period. Concerning the age as the first visit, the smallest group was under 4 years of age and the numbers of patients increased at ages 14 and 15. Chief complaints usually corresponded to the age of the cases. Cases with anterior uveitis accounted for 25% of all cases, intermediate uveitis 12%, posterior uveitis 45% and panuveitis consisted of 17% of all cases, respectively. In the course of treatment, improvement of visual acuity was not statistically significant; the visual prognosis of cases affected under age 7 years was relatively poor. At the time of final observation, the visual acuity of cases, who had first visited during the past 10 years, were better than those who presented during the previous decade. Uveitis had healed or improved in 68% of cases treated in our clinic. As complications, band-shaped keratopathy was seen in 8% of the patients, cataract in 22% and glaucoma in 5%, respectively. Thirty two per cent of the cases received systemic steroid therapy and the average duration was 3.8 months. Fifty two operations were performed in 30 cases (19%), 37 eyes (16%); 16 were cataract operations and 24 were operations for glaucoma.
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Activities of peptidases were examined in tissues of male BXSB and male MRL/Mp-lpr/lpr (MRL/lpr) mice which are animal models of human systemic lupus erythematosus. Female BXSB and male MRL/+ + mice without histopathological changes were used as controls. Activity of DPP II in the spleen, kidney, and liver showed an increase at 13 and 20 weeks of age, while that of DPP IV was decreased at 20 weeks of age, as compared to control mice. The ratio of DPP II/DPP IV activities in the tissues was significantly increased and these findings agree with our previous results in the tissues of NZB mice and in the serum of patients with lupus erythematosus, underscoring the importance of hydrolytic enzymes in the pathogenesis of autoimmune diseases.
We examined the activities of peptidases in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Dipeptidyl peptidase IV (DPP IV) activity was lower in synovial fluid from patients with RA, in contrast to the increase of DPP II activity in synovial fluid, as compared with OA. The DPP II/DPP IV ratio for synovial fluid was significantly higher in patients with RA than in patients with OA. A significant correlation was observed between the DPP II/DPP IV ratio for synovial fluid from patients with RA and the amount of C-reactive protein reaction. These results may be useful in the diagnosis of joint effusion of unknown origin.
The activity of dipeptidyl peptidase IV (EC 3.4.14.5) in human sera from normal controls and osteoporotic patients was assayed with Gly-Pro-4-methylcoumaryl-7-amide (Gly-Pro-MCA) as substrate, at pH 8.7. The mean normal value for the activity in serum of 120 healthy subjects (ages 20-86 y) was 54.0 (SE 0.9, range 34.3-81.6) U/L at 37 degrees C and differed slightly but significantly between the younger group (less than 50 y old) and those older than 50 y. Values for the younger men were slightly but significantly higher than for the older men. Overall, however, the enzyme activities in serum were above normal in patients with osteoporosis. In contrast, the activity of post-proline cleaving enzyme (PPCE) was not increased in serum from patients with osteoporosis, as determined with succinyl-Gly-Pro-4-methylcoumaryl-7-amide (Suc-Gly-Pro-MCA) as substrate. These results suggest that high activities of dipeptidyl peptidase IV in serum of patients with osteoporosis are probably related to its severity.
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We found the presence of collagenase-like (CL) peptidase in synovial fluid by a highly sensitive fluorescence assay using (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methyl-coumaryl-7-amide (Suc-GPLGP-MCA) as a substrate. Suc-GPLGP-MCA is hydrolyzed at the Leu-Gly bond by CL-peptidase. The CL-peptidase activity in synovial fluid was significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA) and in arthropathy-free controls. No significant difference in CL-peptidase activity in synovial fluid was found between patients with OA and arthropathy-free controls.