[A case of various cardiac disorders due to interferon-alpha].
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Publications and source records attributed to K Okada.
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Plasmin is a serine protease with trypsin-like specificity and is activated from plasminogen by several plasminogen activators. Since plasmin has lysine binding site in its heavy chain, lysine derivatives react with plasmin and then modify its activity. The effects of lysine derivatives such as epsilon-aminocaproic acid (EACA) and tranexamic acid on bovine plasmin activity were investigated. In the absence of lysine derivatives, the bovine plasmin activity which was evaluated as the amidolytic activity was reduced in a time- or temperature-dependent manner. However, the bovine plasmin activity became stable upon adding EACA or tranexamic acid. When plasmin was incubated at 4 degrees C for 1, 3 or 5 days without lysine derivatives, the plasmin activity decreased to 43.9%, 19.9% and 11.9% of the initial activity, respectively. On the other hand, when plasmin was incubated at 37 degrees C for 1, 3 or 5 days with tranexamic acid, its activity remained at 110%, 95.6% and 85.9%, respectively. After bovine plasmin had been incubated for 5 days at 4 degrees C in the absence of tranexamic acid, the plasmin activity declined to less than 20%. However, when bovine plasmin had been incubated for 5 days at 37 degrees C in the presence of tranexamic acid, the residual plasmin activity was more than 80%. A similar effect of EACA on bovine plasmin was observed, but it was weaker than that of tranexamic acid. Reversed-phase HPLC followed by SDS-PAGE demonstrated that bovine plasmin was degraded into several fragments. Amino acid sequencing of these fragments revealed that the Lys77-Arg78 or Arg78-Ile79, Arg342-Met343 and Arg557-Ile558 peptide bonds in the bovine plasmin molecule were cleft, respectively. Only the fragment consisting of the amino acid region from Met343 to the C-terminal amino acid, Asn786, exhibited amidolytic activity. In proportion to inactivation of the bovine plasmin, this fragment disappeared. The above findings suggest that lysine derivatives react with bovine plasmin and then stabilize the activity of plasmin by preventing the degradation of active fragment (Met343-Asn786).
Fas Ag is a cell surface molecule that transduces the signal for apoptosis. Since mesangial cells (MC) play important roles in regulating glomerulonephritis, we investigated regulatory mechanisms of Fas system in MC. Fas Ag was expressed on MC from normal mice. This Fas Ag expression was down-regulated by inducing proliferation with platelet-derived growth factor or 18% fetal bovine serum, but was reversed when cycloheximide was added to the culture. Anti-Fas Ab alone did not induce apoptosis in MC, but MC became susceptible to apoptosis induced by anti-Fas Ab is actinomycin D or cycloheximide was added. Noteworthy findings are that mRNA of Fas ligand was expressed in MC. Taken together, MC appears to control the proliferation by regulating Fas system-mediated apoptosis, at least in part, through an autoregulatory mechanism with Fas Ag Fas ligand expressed on their own MC.
OBJECTIVE: To investigate whether ultrasound (US) guidance improves the sensitivity of fine-needle aspiration biopsy (FNAB) in patients with palpable breast tumors. DESIGN: A retrospective study. SETTING: A university hospital. PATIENTS: A total of 107 patients with breast tumors (114 lesions) underwent US-guided FNAB and 138 patients (143 lesions) underwent FNAB guided by palpation (standard FNAB). MAIN OUTCOME MEASURES: The diagnoses obtained by FNAB were compared with the surgical findings and the diagnostic value of US-guided FNAB was evaluated. RESULTS: The sensitivity of US-guided FNAB was 89.3%, the specificity was 82.9%, and the accuracy was 86.9%. In contrast, the sensitivity of standard FNAB was 61.1%, the specificity was 73.3%, and the accuracy was 65.0%. For breast tumors 2.0 cm or less in diameter, the sensitivity and accuracy of US-guided FNAB were significantly higher than those of standard FNAB. CONCLUSION: Ultrasound-guided FNAB can improve the preoperative diagnosis of breast cancer, especially in patients with tumors that are 2 cm or less in diameter.
Staphylokinase obtains plasminogen activating activity by forming a complex with plasminogen. Although the enzymatic activity of staphylokinase is enhanced by fibrin, how fibrin enhances enzymatic activity has not been determined yet. The effects of fibrin, or fibrinogen fragments, on the activation of plasminogen by staphylokinase was investigated using CNBr-digested fibrinogen fragments (FCB-2 and FCB-5) and plasmin-degraded cross-linked fibrin fragments ((DD)E complex, DD fragments and E fragments). Kinetic analysis of the activity of staphylokinase revealed that its plasminogen activating activity, which was expressed as kcat/Km, was enhanced by FCB-2 (10-fold) and FCB-5 (5-fold). These fibrin fragments caused 38-, 30-, and 8.5-fold increases in activity for the DD fragment, (DD)E complex and E fragment, respectively. Although alpha2-antiplasmin inhibited the activation of plasminogen by staphylokinase, FCB-2 abolished its inhibitory effects, and the plasminogen activating activity of staphylokinase was restored. The inhibitory effects of alpha2-antiplasmin on the activation of mini-plasminogen by staphylokinase were less than for Glu- or Lys-plasminogen, and the inhibitory effect of alpha2-antiplasmin was not altered by fibrin or EACA. These findings indicate that the staphylokinase/plasmin(ogen) complex reacts with fibrin even in the presence of alpha2-antiplasmin, and efficient plasminogen activation takes place on the surface of fibrin.
Antitumor activities of liposomes containing adriamycin (L-ADM) and their distribution process into tumour cells were analysed. The lipid composition of the liposomes was dimyristoylphosphatidylglycerol (DMPG)/egg phosphatidylcholine/cholesterol/adriamycin (ADM) in a molar ratio of 11.4:2:12:1.3. Liver-metastasizing murine tumour models, M5076 and L5178Y-ML, were used. In vivo antitumour effect against these tumour models was assessed from increase in life span (ILS). The survival prolongation effect of L-ADM in mice with liver failure caused by M5076 was significantly higher than that of F-ADM. In contrast, significant enhancement of the effects by encapsulation in liposomes was not observed in L5178Y-ML-bearing mice. In vitro cytostatic activities of L-ADM against M5076 cells as well as against other tumour cell lines were lower than those of F-ADM. The in vitro kinetic study on the distribution of L-ADM to the tumour cells revealed that ADM in L-ADM was taken up into the tumour cells mainly after it was released from the liposomes rather than taken up as the liposomal form. Among the cell lines tested, M5076 cells had the highest phagocytic activity and therefore the highest uptake activity of ADM during incubation with L-ADM. These findings suggest that the augmented antitumour activity of L-ADM in M5076-bearing mice was the result of phagocytosis of L-ADM by M5076 cells as well as the reduction of toxicity, prolonged retention of ADM in systemic circulation, and liver accumulation of ADM after administration of L-ADM.
We examined eosinophil chemotactic activity (ECA) in bronchoalveolar lavage fluid (BALF) obtained from rats infected with Toxocara canis. For 4 weeks after infection, the number of eosinophils was determined in peripheral blood and BALF. ECA was assayed using a microchemotaxis chamber. Eosinophils in peripheral blood and BALF increased markedly after infection, peaking at 12 days and 2 weeks, respectively. ECA in BALF also increased significantly and peaked 2 weeks after infection. Partial characterization revealed that ECA was heat labile, lipid soluble, and resistant to trypsin digestion. Two ECA peaks were identified by molecular sieve column chromatography: one near the egg albumin marker (MW 45,000) and the other observed after elution with quinacrine (MW 472.9). Treatment with a specific leukotriene (LT) B4 receptor antagonist (ONO-4057), a platelet activating factor (PAF) receptor antagonist (TCV-309), and an anti-interleukin (IL)-5 monoclonal antibody (TB13) significantly reduced the ECA, suggesting that LTB4, PAF, and IL-5 contribute to the accumulation of eosinophils in the lungs of rats infected with T. canis.
The administration of bovine lactoferrin (LF) with 1 mg/g body weight before the murine cytomegalovirus (MCMV) infection completely protected the BALB/c mice from death due to the infection. In these LF-treated mice, a significant increase in the activity was found in the NK cells but not in the cytolytic T lymphocytes which recognized an MCMV-derived peptide. Moreover, the elimination of the NK cell activity by an injection with anti-asialo GM1 antibody abrogated such augmented resistance, thus supporting the hypothesis that the LF-mediated antiviral effect in vivo is performed through the augmentation of NK cell activity. No such LF-mediated antiviral effect in vivo with the increased NK cell activity was found in athymic nude mice, whereas it was restored completely by the transfer of splenic T cells from LF-treated donors. These findings therefore suggest that T lymphocytes induce both the augmentation of NK cell activity and the resultant antiviral effect in the LF-treated hosts.
UNLABELLED: A 5-year-old Japanese girl was affected with acute nephritis. The patient had hypo-complementaemia and an elevation of anti-streptolysin O with positive throat culture of Group A streptococci. Four weeks after onset of the disease, serum complement level returned to normal, but proteinuria increased into the nephrotic range with a deterioration in renal function. Four weeks after onset, light microscopy of a renal biopsy showed diffuse endocapillary proliferation, and immunofluoroscopy revealed predominant IgA deposition in the mesangium. Electron microscopy showed electron dense deposits in the mesangial and subendothelial area, but subepithelial deposits were not found in the glomeruli. Histological diagnosis was IgA nephropathy, while her clinico-serological features were typical of acute post-streptococcal glomerulonephritis. CONCLUSION: These results suggest that in some patients, IgA nephropathy may be triggered by streptococcal infection and misdiagnosed as acute post-streptococcal glomerulonephritis if renal histological examinations are not done.
A case of ulcerative colitis complicated with gastric and duodenal lesions is reported. The patient was a 17-year-old male who was admitted with bloody diarrhea and abdominal pain. Based on the endoscopic and histological findings of the colon, a diagnosis of ulcerative colitis was made. Upper gastrointestinal endoscopy showed multiple erosions and granular changes in the antral greater curvature of the stomach and descending portion of the duodenum. Histological examination of the stomach and duodenum revealed marked inflammatory cell infiltration and crypt abscesses. Clinically, the gastric and duodenal lesions did not respond to antiulcer drugs, but were alleviated by steroid. It was concluded that the pathogenesis of the gastric and duodenal lesions in this patient was similar to that of the colonic lesions of ulcerative colitis.
OBJECTIVE: To clarify the clinicopathological features of periosteal ganglion. DESIGN: Three patients with periosteal ganglion were studied clinicopathologically. PATIENTS: One patient was selected from the files of our institute and two from a consultation file. RESULTS AND CONCLUSION: All three lesions were located over the medial aspect of the tibia. Plain radiographs showed cortical erosions of varying degrees and mild periosteal reaction of the medial side of the tibia. MR images demonstrated well-circumscribed lesions overlying the cortical bone of the tibia, shown as low-intensity areas on T1-weighted images. On T2-weighted images, lesions were homogeneous, lobulated, and showed a characteristic markedly increased signal intensity. These findings are helpful in making a diagnosis of periosteal ganglion. Each patient had an uneventful clinical course after an excision involving the wall of the ganglion, the adjoining periosteum, and the underlying sclerotic cortical bone.
We describe a single level intervertebral approach to decompress two adjacent involved nerve roots in cases of cervical spondylosis. The operation was undertaken in 4 patients. We carried out discectomy, partial excision of the vertebral body with removal of the anteromedial part of the pedicles, removal of osteophytes and excision of the posterior longitudinal ligament, followed by an anterior interbody fusion. Fusion was achieved with the spine in normal lordosis and without complications. Pain and motor weakness was relieved in every case. This procedure can maintain movement at one additional disc level and has a better fusion rate than multilevel inter-body fusion.
Mammary glands of pregnant, lactating and resting goats were studied by immunohistochemistry for lymphocyte subpopulations using a panel of monoclonal antibodies. All T lymphocyte subpopulations that may have a role in the immune response, CD2+, CD4+, CD8+ and gamma delta T cells and subsets, were present in the mammary gland and were noted to increase in number progressively during pregnancy, decrease significantly during lactation, and then moderately increase during the resting period. CD4+ cells, the predominant cell type in the mammary gland, were located mainly in the connective tissue, whereas CD2+, CD8+ and TcR1-N24+ cells were predominant in the intraepithelial areas. TcR1-N6+ cells were detected almost exclusively during pregnancy, being localized mainly in the connective tissue. Their proportion decreased markedly following parturition. Very few WC1-N3+ and -N4+ cells were detected in the mammary gland. It is suggested that the majority of gamma delta T lymphocytes in the mammary gland of the goat are CD2+ CD8+ WCl-, a distinctive subset from that of the WCl+ subset in peripheral blood.
Three monoclonal antibodies to IL-2R alpha (LCTB32, CACT116 and LCTB2) were used for immunohistologic staining of lymph nodes from normal young cattle and a calf suffering from phlegmon. In the normal cattle, a few IL-2R alpha positive cells were detected in the paracortex region. In the calf, IL-2R alpha was mostly expressed on follicle cells.
The total amount of main disaccharide units of skin glycosaminoglycans was compared between sun-exposed (n = 12) and sun-protected skin (n = 14) of aged people using high performance liquid chromatography after labeling with 1-phenyl-3-methyl-5-pyrazolone. The total amount of main disaccharide units in sun-exposed skin was comparable to sun-protected skin presumably due to the diversity of individuals. Consequently, we compared sun-exposed skin with sun-protected skin in identical individuals (n = 6). The total amount of main disaccharide units in sun-exposed skin was significantly greater than that in sun-protected skin (P < 0.05). In addition, the ratio of delta Di-HA (hyaluronic acid, HA)/delta Di-4S (dermatan sulfate, DS) in sun-exposed skin showed a decreasing trend as compared with sun-protected skin in four of six individuals. These results are in agreement with our previous results obtained in animal experiments of photoaging, i.e., hairless mouse skin exposed to repeated UV irradiation showed an increase in total amount of main disaccharide units and a decrease in the ratio of delta Di-HA(HA)/delta Di-4S(DS). We could confirm similar changes in skin glycosaminoglycans both in human and murine photoaging supporting the appropriate rationale for using the hairless mouse as an animal model for photoaging. Again, disaccharide analysis should provide a useful method to examine the biochemical changes of skin glycosaminoglycans in human photoaging.
Atherosclerotic aneurysm of the deep femoral artery is a rare peripheral aneurysm that is likely to have associated aortoiliac aneurysms. The case of a patient who had five atherosclerotic aneurysms located in the abdominal aorta, bilateral common iliac arteries, and the left common femoral and deep femoral arteries is reported. He underwent a semi-emergency operation for the aneurysm of the deep femoral artery, followed by a two-stage operation for the aortoiliac aneurysms. The aneurysm of the deep femoral artery was repaired, and reconstruction of the distal deep femoral artery successfully performed with direct anastomosis to the superficial artery. In this report, the clinical presentation of multiple atherosclerotic aneurysms and the details of surgical reconstruction are described.
BACKGROUND: A computerized 48-channel mapping system was used to investigate the characteristics of an atrial epicardial electrogram during chronic atrial fibrillation (AF) in patients with solitary mitral valve disease. We have devised a simple left atrial procedure to eliminate the chronic AF during a mitral valve operation. METHODS: Using this mapping system, we performed intraoperative atrial mapping in 11 patients with chronic AF associated with mitral valve disease. The AF duration ranged from 0.4 to 15 years (mean, 8.0 +/- 4.5 years). A simple surgical ablation of the AF on the left atrium only was performed during the mitral valve operations. RESULTS: The mean AF cycle length of the atria ranged from 129 to 169 milliseconds in the right atrium and from 114 to 139 milliseconds in the left atrium. The mean AF cycle length of the left atrium was shorter than that of the right atrium. Regular and repetitive activation was found in the left atria of 7 of 11 patients. The AF disappeared in all patients immediately after the operation, and 10 of these patients continued to have a sinus rhythm postoperatively (AF-free rate, 91%). CONCLUSIONS: Computerized intraoperative mapping revealed a shorter mean AF cycle length in the left atrium. A simple left atrial procedure was effective in eliminating chronic AF associated with solitary mitral valve disease.
A monoclonal antibody (MAb), c143, that recognizes a tumour-associated antigen that is "upregulated" on neoplastic B cells in cattle with enzootic bovine leukosis (EBL), was used as a marker to study disease progression. An immunohistochemical examination of neoplastic tissue and superficial cervical lymph nodes from 14 animals with EBL revealed three morphologically definable stages of change in the structure of lymph nodes, associated with the distribution of c143-positive cells: (1) the presence of c143-positive cells at the marginal sinus with no apparent changes in lymph node structure; (2) the presence of positive cells extending into and distorting the architecture of the lymph node, with clear evidence of proliferation before overt changes (enlargement of lymph nodes) were evident; and (3) the presence of positive cells throughout the lymph node with total disruption of lymph node structure when clinical signs of lymph node enlargement were evident. The results indicated that the bovine leukaemia virus-transformed lymphocytes or neoplastic cells in peripheral blood accumulate in the marginal sinus area at the earliest stages, and subsequently proliferate and infiltrate into follicles, leading to the development of clinical signs of lymphosarcoma.