Biomedical subjects
Publications and source records attributed to M Ueno.
The aggregation form of mixtures of phosphatidylcholine and MDP derivatives was studied. The mixed vesicles containing less than 40% of B30-MDP were unilamellar, and over 40% B30-MDP aggregates of mixed vesicles or oligolammellar vesicles appeared. The mixed vesicles containing less than 20% of DV-7401 were unilamellar, and over 20% of it fibriform structures appeared.
In order to control the release rate of slightly water soluble medicine by using the solid dispersion (SD) method, the SD was prepared with a water soluble polymer and the slightly soluble medicine, and the medicine release from the solid dispersion granules was studied. The SD granules were prepared by the evaporation of ethanol after dissolving into ethanol a slightly water soluble medicine (flurbiprofen (FP)) and soluble polymers (hydroxypropyl cellulose (HPC)). HPC has four grades of molecular weight. The release rate of FP from SD was measured by the rotating basket method (JP XII). The release rate of FP from the SD granules was markedly larger than that from FP powder, and it was larger with a lower HPC molecular weight. It is speculated that these results were mainly based on the molecular dispersion state of FP and HPC in SD.
Epidermal growth factor (EGF) in the milk fat globule membrane (MFGM) emulsion enhanced the absorption of this factor from the intestine, especially to the intestinal lymph. Most of the radioactive EGF administered was degraded to small molecular weight materials. These degraded materials were absorbed and appeared in both the intestinal lymph and portal vein blood. However, a certain portion of EGF, although small, appeared in the lymph maintaining the original molecular mass. The MFGM emulsion used enhanced the lymphatic absorption of intact EGF, suggesting that this dosage form increased the absorption of EGF, protected the degradation of EGF in the intestine or promoted the absorption of intact EGF. The enhancing effect on the absorbed dose percentage of EGF recovered using MFGM emulsion was also observed in the portal vein plasma. However, the effect on the absorption of intact EGF was much larger in the lymph than in the portal vein.
A 67-year-old male presented with a left temporal convexity vacuolated meningioma associated with acute subdural hematoma manifesting as sudden headache, nausea, and vomiting without neurological deficit. Magnetic resonance imaging disclosed an extra-axial mass as mixed low- and high-signal intensities and a crescent high-intensity area in the left convexity. Histological examination diagnosed meningotheliomatous meningioma with vacuolated components and hemorrhagic foci. The tumor and hematoma were removed without postoperative complications.
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Delaminomycins A, B, C and their derivatives were prepared and investigated biological activities of them. Among these compounds, spiro compounds (A2, B2 and C2) showed stronger inhibitory activity than natural products (A1, B1 and C1) on B16 melanoma cells adhesion assay and Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, A1, B1 and C1 showed more potent inhibitory activity than spiro compounds (A2, B2 and C2). On the other hand, as to C-5' substituents of pyrrolidine ring, the order of inhibitory activity was R = OH > R = OCH3 > R = H on Con A-induced proliferation of murine splenic lymphocytes assay. In MLCR and antimicrobial assay, however, the order of inhibitory activities were R = H > R = OCH3 > R = OH. Inhibitory activities of A4 which was lacked pyrrolidine ring were reduced on B16 melanoma cells adhesion assay and on cytotoxicity against tumor cells in vitro in comparison with those of A1.
The biosynthesis of delaminomycin A, produced by Streptomyces albulus MJ202-72F3, was investigated by feeding 13C-labeled compounds followed by 13C NMR analyses. The results indicate that delaminomycin A is derived from six acetate units, five propionate units and one glycine unit.
In our search for inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin, laminin and collagen type IV, we succeeded in finding a novel cyclic hexadepsipeptide antibiotic, named IC101, which was isolated from cultured mycelium of Streptomyces albulus MJ202-72F3. It was purified by centrifugal partition chromatography, preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder. IC101 strongly inhibited cell adhesion to ECM components, suppressed immune responses in vitro and in vivo, and exhibited antimicrobial activity on Gram-positive bacteria.
In order to develop a new class of immunomodulator we have searched for a low molecular weight inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin (FN), laminin (LM) and collagen type IV (CL), and succeeded to find a group of novel antibiotics, named delaminomycins. Delaminomycins were isolated from the mycelium and cultured broth of Streptomyces albulus MJ202-72F3. It was purified by use of centrifugal partition chromatography (CPC), preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder. Delaminomycins with inhibitory activity for cell adhesion to ECM components suppressed immune responses in vitro and in vivo and exhibited antimicrobial activity on Gram-positive bacteria.
Delaminomycins, novel extracellular matrix receptor antagonists, have been isolated from a culture broth of Streptomyces albulus MJ202-72F3. The structure of delaminomycin A was determined to be 3-[[2-[(3E,5E)-2,8-dihydroxy-7-methyl-3,5-decadienyl]- 1,6,8- trimethyl-1,2,4a,5,6,7,8,8a-octahydro-1-naphthyl]carbonyl]-5- hydroxypyrrolidine-2,4-dione by analyses of spectral properties and chemical studies.
To elucidate the relationship between glomerular deposition of plasmin-alpha 2-plasmin inhibitor complexes (PIC) and renal lesions or dysfunction, 25 patients with various glomerulopathies and various degrees of renal injuries were examined. Glomerular PIC deposition was found in eight patients (group A), and other 17 patients showed no deposition (group B). PIC was found mainly in the mesangium and along the capillary loops. Group A showed significantly more severe hematuria (p < 0.05) than group B. Group A showed a significant decrease in glomerular filtration rate (GFR; p < 0.05): the mean values being 60.8 +/- 39 in group A and 94.5 +/- 32 ml/min in group B. Group A showed a significant decrease in the phenolsulfonphthalein excretion test (p < 0.05). There was no significant difference in the mean values of plasma PIC, D-dimer, and thrombin-antithrombin III complexes (TAT) between two groups. Histologically, group A showed a significantly high incidence of adhesion (p < 0.05), crescentic formation (p < 0.05), endothelial swelling and/or detachment (p < 0.01), tubulointerstitial changes (p < 0.01), and glomerular deposition of platelet factor 4 (p < 0.01). The present study demonstrates that glomerular PIC deposition reflects the existence of activation of coagulation and fibrinolysis within the glomeruli and suggests that glomerular PIC deposition plays a part in the progression of renal injuries in various glomerulopathies.
The purpose of this study was to investigate the immunosuppressive effect of Cyclosporine A (CsA), FK506 (FK) and 15-Deoxyspergualin (DSG) on pancreatic islet xenotransplantation (hamster to rat). Mean graft survival time of control was 2.9 +/- 0.6 days. CsA of 20mg/kg/day, FK of 0.5mg/kg/day and DSG of 1mg/kg/day prolonged graft survival to 6.2 +/- 2.0, 6.4 +/- 1.6 and 5.2 +/- 1.9 days, respectively. In combination of CsA with FK, graft survival time was 12.9 +/- 6.3 days, DSG combined with CsA, and DSG combined with FK could significantly prolong graft survival in synergistic fashion to 31.4 +/- 13.2 days and 30.7 +/- 6.5 days, respectively. Triple combination of these three drugs could not prolong graft survival more than double combination. Lymphocytotoxic antibody titer rose after grafting in single use of CsA, FK and DSG, but any combination therapy completely suppressed production of lymphocytotoxic antibody. Histologically, CsA combined with FK eliminated medullary thymocytes, but not cortical thymocytes. On the other hand, DSG combined with CsA or FK eliminated both of medullary and cortical thymocytes. In conclusion, CsA and FK may have similar immunosuppressive mode of action different from that of DSG. Combination therapy of DSG with CsA or FK could significantly prolong islet xenograft survival.
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Primary myelofibrosis (PMF) is regarded as a chronic myeloproliferative disorder. It is characterized by marrow fibrosis, leukoerythroblastosis, tear drop erythrocytes and extramedullary hematopoiesis. Most patients are in their late 50s when first diagnosed. Pediatric PMF is said to be quite rare. Here describe a female infant with PMF. The patient was born on Aug. 7, 1991. The pregnancy and delivery were uneventful. Hepatomegaly was noted soon after birth. Combined blood counts showed polycythemia and leukocytosis. It was thought to be extramedullary hematopoiesis due to intrauterine infection. She was followed up in another hospital, but since her condition was unchanged she was admitted to our hospital for further medical examinations at age 7 months. On the peripheral blood smear, there were tear drop erythrocytes, normoblasts and early myeloid elements. Repeated bone marrow aspirations were dry taps. This case presented the classical findings of fibrosis of the bone marrow on bone marrow biopsy. She is in good health without any therapy until now. A review of 7 cases of PMF, including our case, in Japanese children was made and discussed in comparison to adult cases.
Mediastinal lymph node metastasis associated with pulmonary metastasis is rarely seen in soft tissue sarcoma. A case is presented in which investigation of primary lung cancer (cT2N2M0) in a 78-year-old woman with a history of MFH of the left thigh revealed pulmonary metastasis of MFH accompanied by paratracheal (#2) and anterior mediastinal (#3a) lymph node metastases.
A case of epidural hematoma associated with cephalohematoma caused by a vacuum extraction was reported. Old liquefied hematoma was removed via a small burr hole in the parietal bone at the age of 23 days. No neurological deficits were recognized at the age of 6 months. As the dura mater does not easily detach from the overlying skull in the neonate, it is a very rare occurrence for this to happen as a complication of the use of forceps or in extractions. To our knowledge, only 4 cases of epidural hematoma after vacuum extraction have been reported. The mechanism of the development of an acute epidural hematoma during extraction is reported to be due to direct force to the dura mater and skull induced by negative pressure of a vacuum extraction. In the present case, it seems that negative pressure produced a detachment of the dura mater from the overlying skull. It suggests that examinations including plain craniogram and CT scan should be performed as soon as possible in the neonate with cephalohematoma when they have been delivered by a vacuum extraction.
Renal tissues from 171 patients with different glomerulopathies and 6 normal controls were examined by an immunofluorescent technique. Specimens were stained in particular with anti-Amyloid P (AP) antisera, and were also stained for immunoglobulins and complement. The intensity and distribution pattern of AP staining were studied. The AP staining revealed a faint/linear pattern in normal controls, and was granular and linear in pathological specimens. The distribution of AP was found to be mesangial, capillary and mesangiocapillary. According to the degree of AP intensity, the patients were divided into two groups: group I (56 patients) exhibiting a faint intensity as seen in the normal controls, and group II (115 patients) with a strong intensity. The histological findings and laboratory data were compared between the two groups as well as among patients with different diseases. The incidence of sclerotic lesions and the amount of proteinuria were significantly higher in group II than in group I. Increased amounts of AP deposition in different glomerular diseases thus appear to be related to a diminished renal function or glomerular damage.
We examined the effects of late reperfusion on infarct expansion and infarct healing process in conscious rats. Coronary occlusion and reperfusion were carried out in conscious rats 1 week after appropriate surgical preparations. The rats were randomized into the following four groups: sham operated, permanent occlusion, early reperfusion (i.e., reperfusion performed 1 hour after occlusion), and late reperfusion (i.e., reperfusion performed 6 hours after occlusion). Histological examination was performed 7 days after coronary occlusion. In the early reperfusion group, infarct size and expansion were reduced when compared to the permanent occlusion group. In rats subjected to late reperfusion, infarct size and expansion were not different from those in the permanent occlusion group. The extent of unresorbed necrotic myocardium in areas of infarcted scar was reduced in both early and late reperfusion groups. Infiltration by neutrophilic cells into areas of necrotic myocardium 16 hours after myocardial infarction was increased in both reperfusion groups. Infiltration by macrophages 3 days after infarction was also increased in both reperfusion groups. Late reperfusion, therefore, does not affect infarct expansion, but does contribute to the acceleration of the infarct healing process.