Biological activity of damavaricin derivatives.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Onodera.
Explore the source record for details and available documents.
The effects of histidine treatment on histamine levels in brain regions and the muricidal suppression in thiamine deficient rats were examined. Intraperitoneal administration of L-histidine significantly increased the histamine levels in several regions of normal and thiamine deficient rats. A dose of 200 mg/kg of histidine suppressed muricide induced by thiamine deficiency. The histamine levels of those thiamine-deficient killer-rats, whose muricide was suppressed by histidine treatment, were significantly higher in the amygdala, striatum and hypothalamus than of those whose muricide was not suppressed. It is suggested that the activation of central histaminergic neuron systems, especially in the amygdala, may underlie the mechanism of muricidal suppression by histidine treatment in thiamine deficient rats.
Viability of rat 3Y1 fibroblasts transformed by adenovirus type 12 (Ad12) was markedly impaired by the administration of dilinoleoylglycerol (DLG) to the culture medium. To identify the gene(s) of Ad12 responsible for the high sensitivity to DLG, we established several transformed sublines of 3Y1 induced by the viral E1A gene or by the mutants of Ad12 which have mutations in the E1A region. All of the transformed sublines of 3Y1 expressing either the 12S or the 13S message from the E1A region were highly sensitive to the cytotoxicity of DLG. We propose that the high sensitivity of Ad12-transformed cells to the DLG mediated cytotoxicity is attributable to the common function of E1A-12S and E1A-13S mRNA products.
Tuberous sclerosis is a dominant hereditary disease characterized by the appearance of angiofibromas on the face, epileptic attacks, and mental retardation. Attention has been paid to the atypical cells observed histologically in the stroma of the angiofibroma as they may play an important role in forming lesions. We have established a cell line from an angiofibroma to clarify the nature of these cells at the cellular and biochemical levels. The cultured cells have been stably maintained for four years and show an abnormal morphology resembling that of neuronal cells. In culture, these cells divide into daughter cells, which consist of both normal cells and abnormal ones whose nuclei disintegrate and cannot divide further. The cells resemble normal fibroblasts in their pattern of staining with antibodies against tubulin, actin, vimentin, and fibronectin. However, they also stain with an antibody against the glia-specific acidic protein, which is thought to be a specific marker protein for glial cells. The gel profile of cyclic-AMP binding proteins was not fibroblastic, but rather of the neuron cell type. These results indicate the gene expression of these cells is also abnormal. They are a useful tool for understanding this specific genetic disease.
A CD4+ human monocytoid cell line, U937, was transfected with a constructed plasmid which has the envelope gene of human immunodeficiency virus under the transcriptional control of the human metallothionein IIA promoter and was cloned thereafter. These cloned cell lines (EH and EL cells) expressed the viral gp160 in the cytoplasm. The expression of surface CD4 antigen examined by Leu3a and OKT4 monoclonal antibodies, however, disappeared completely in EH cells, which produce a larger amount of gp160, while diminishing only partly in EL cells, which produce a smaller amount of gp160. These results indicate that the level of expression of surface CD4 antigen correlates inversely with the amount of intracellular gp160. Moreover, immunoprecipitation studies using lysate from EH cells showed that OKT4 monoclonal antibody precipitated a significant number of CD4 molecules even after surface CD4 disappeared. However, Leu3a monoclonal antibody, which recognizes the binding site for envelope protein, could not precipitate any CD4 molecules in the same cell lysate. Taken together, these results suggested that CD4 molecules are still synthesized normally after the augmented production of gp160 in the cells but form a complex with the envelope protein in the cytoplasm and become unable to be transported to the cell surface, resulting in the observed depletion of surface CD4 antigen. This mechanism may explain the decrease or absence of surface CD4 antigens in human lymphocytes infected with human immunodeficiency virus.
Serum secretory IgA was measured to elucidate the significance of secretory IgA in patients with IgA nephropathy. The levels of serum secretory IgA and IgA were, respectively, 6.8 +/- 3.5 micrograms/ml and 231.0 +/- 69.2 mg/dl in the controls and 11.8 +/- 3.2 micrograms/ml and 385.3 +/- 78.7 mg/dl in the patients. The levels of serum secretory IgA and IgA in the patients were significantly higher than those in controls (p less than 0.01). Elevated serum secretory IgA may reflect the excessive state of the IgA-secreting system in IgA nephropathy patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
n-Pentyl ether of damavaricin Fc (n-pentyl DvFc) preferentially killed human T-cell lymphotropic virus type I (HTLV-I)-transformed cell lines. The mechanism of action of the drug was investigated using MT-4 cells. Cytotoxic action was diminished by the removal of n-pentyl DvFc from the culture or by the addition of sulfhydryl compounds such as 2-mercaptoethanol and dithiothreitol. The killing activity of n-pentyl DvFc was also diminished by membrane-acting agents including quinidine and diphenylhydantoin. Influx and subsequent efflux of Ca2+ were observed when either HTLV-I infected (MT-4 cells) or uninfected cells were treated with n-pentyl DvFc. An efflux of K+ was observed in HTLV-I infected MT-4 cells immediately after the exposure of the cells to n-pentyl DvFc. The K+ efflux, however, was not observed in the uninfected T cells. n-Pentyl DvFc seems to act primarily on the cell surface of MT-4 cells, leading to the perturbation of membrane function. The restoration of cell growth, however, is critically dependent on the presence of dithiothreitol and 2-mercaptoethanol, implying a role for a free sulfhydryl group in the killing activity.
Recently reports of congenital coronary-pulmonary fistula have been increasing with the wide-spread use of coronary angiography. However, the cause of the angina sometimes seen as a chief complaint in coronary fistula has not been well demonstrated although it has been suggested that coronary steal phenomenon accounts for it. This report documented coronary hemodynamics in a patient who came to develop anterior chest pain in the middle age owing to congenital coronary-pulmonary fistula, measuring coronary flow before and after the fistula-closure operation. A 35-year-old woman suffered from a sudden onset of severe anterior chest pain in April, 1986. She was referred to our hospital on suspicion of ruptured aneurysm of Valsalva. Auscultation disclosed continuous murmur at 3 LSB, but no evidence of ruptured aneurysm of Valsalva was detected by echocardiography nor aortography. Coronary angiography showed both left and right coronary fistula into the stem of pulmonary artery and otherwise normal angiogram. Great cardiac vein flow (GCVF) measured with regional thermodilution method was 25 ml/min at rest (70 bpm) and 30 ml/min during rapid atrial pacing (150 bpm) before the operation, and 30 ml/min (78 bpm) and 58 ml/min (150 bpm) after the operation, respectively. Before the surgery, anterior coronary resistance (CRant) was higher than that in normal subjects at rest and remained almost steady during atrial pacing. After the surgery, CRant was still higher at rest but remarkably reduced during pacing of 150 bpm. These findings suggest that the gradual increase in peripheral coronary resistance for a long time may lead to the inducement of coronary steal in the middle-later age in patients with coronary fistula.
A case of acute myocardial infarction due to the lesion in the left main coronary artery was reported. A 50-year male was referred to our department for suspected acute myocardial infarction. Physical examination on admission revealed slight cyanosis with cold sweating due to severe chest pain. Pulse was irregular and heart rate was 78 beats/min. Blood pressure was 100/80 mmHg. A series of electrocardiograms (ECG) and laboratory data provided the diagnosis of wide-ranged anterolateral infarction in the left ventricle. Emergency coronary angiograms taken without delay showed a subtotal occlusion (99% stenosis) of the left main coronary trunk (LMT) before the initiation of intracoronary thrombolysis (PTCR). Following the intracoronary infusion of urokinase of 1,200,000 units, symptoms and ECG changes transiently improved but worsened later, and LMT stenotic lesion and delayed filling of myocardium were similar with before PTCR. Emergency coronary-aorto bypass graft (CABG) was undertaken without a significant delay to both the left anterior descending artery (LAD) and left circumflex coronary artery (LCX). With these treatments, the patient could survive despite the wide area of infarction due to LMT lesion. Coronary angiograms performed 37 days after the CABG showed that the graft to LAD was completely occluded and the LCX graft was patent with partial stenosis. Treadmill test at this time induced an anginal episode with ischemic ECG changes on moderate exercise, indicating the presence of significant area of ischemic myocardium. For salvage of the ischemic myocardium, percutaneous transluminal coronary angioplasty (PTCA) was successfully performed for the LMT stenosis, resulting in no episode of angina nor ischemic ECG changes during exercise loading.(ABSTRACT TRUNCATED AT 250 WORDS)
Chemical pleurodesis induced with fibrin glue (fibrinogen 1.0 g, thrombin 500 mu, 2% CaCl2 10 ml, tranexamic acid 10 ml) was performed in 6 cases with spontaneous pneumothorax in whom surgery was not indicated because of various reasons, such as low pulmonary function or old age. These cases were complicated with left pneumonectomy, bilateral emphysema, pulmonary tuberculosis and interstitial pneumonia. In all cases, favorable results were obtained and there was no recurrence. As side effects, only transient low grade fever and slight chest pain were observed with no liver damage or pleural thickening. These results suggest that chemical pleurodesis induced with fibrin glue is very useful in the treatment of inoperable spontaneous pneumothorax.
The case was a 33-year-old woman with hypertension and hypokalemia, who presented depression of renin activity and the abnormal elevation of plasma deoxycorticosterone (DOC) and 11-deoxycortisol on laboratory tests. After admission, abdominal CT scan, 131I-adosterol scintigram and adrenal venogram revealed a tumor in the left adrenal, which histologically seemed to be benign. When the tumor was resected, blood pressure and all the biochemical data returned to normal range. DOC and 11-deoxycortisol levels in the tumor were abnormally elevated as compared with those in the normal adrenal tissue. These findings suggested that the abnormal elevation of hormone levels resulted from depression of 11 beta-hydroxylase. Though numerous adrenal tumors have been documented, we rarely encounter an apparently benign adrenal tumor that produces 2 kinds of hormones. This seemed to be the first case of benign adrenal tumor in which both DOC and 11-deoxycortisol were elevated.
A 53-year woman, who had been under observation for combined valvular heart disease, was admitted to our hospital for further examination of embolic episodes to brain and kidney. Echocardiographic examination showed the evidence of free-moving ball thrombus in the left atrium, and emergent cardiac catheterization following the echocardiography confirmed the diagnosis of it as well as mitral stenosis, aortic regurgitation with stenosis, and tricuspid regurgitation. In addition, coronary angiography disclosed the anomalous coronary venous run. With these findings, the cause of embolic episodes was found to be due to the thrombus in the left atrium. In the surgery performed a ball thrombus of 40 x 35 x 36 mm and a mural thrombus of 15 x 35 x 20 mm in size in the left atrium were detected and removed, and both mitral and aortic valves were replaced to artificial ones. She had a good hospital course after the surgery and discharged without any complication. In this report, we discussed a case of left atrial thrombus observed in a combined valvular heart disease, with 29 literatures reported in our country.
Explore the source record for details and available documents.
We describe a family case of IgA nephropathy and Henoch-Schönlein purpura nephritis. This is the first report involving IgA nephropathy in a child and Henoch-Schönlein purpura nephritis in a parent. It is suggested that the two were related etiologically as well as clinicopathologically.
A case of an electrocution is reported, involving a 37-year-old man who while engaged in an electrical work, received an electric shock by touching an electric wire of 11,000 volts. Both of his arms had to be amputated. A piece of muscle tissue was removed from the amputated arm to be examined by light and electron microscopy. Under light microscopy, the muscle tissue, after myoglobin staining, showed a particular pattern that closely resembled the pattern on the skin of a python. Thus the author has named the pattern seen in this case as the "Python-pattern". The electron microscopy inspection revealed on myoglobin staining excessive stretching and fragmentation of the myofibrils where the myoglobin staining was negative in the slide.
The colony-forming ability of rat 3Y1 fibroblasts transformed by adenovirus type 12 (Ad12) was drastically reduced when the cells were cultivated for 18 h in medium augmented with 300 micrograms/ml of liposomes composed of either phosphatidylcholine (PC) or phosphatidylinositol. In contrast, those of untransformed 3Y1 cells and simian virus 40-transformed and polyomavirus-transformed 3Y1 cells were not. The cytotoxicity of PC liposomes was also observed in 3Y1 cells transformed by plasmid DNA containing Ad12-E1A gene but not in those transformed by adenovirus type 2, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene. The extensive killing of Ad12-transformed and E1A-transformed 3Y1 cells occurred in liposomes of dioleoyl-PC and of dilinoleoyl PC but not those of dipalmitoyl PC, distearoyl-PC, or diarachidonyl PC, suggesting that the acyl groups of phospholipids play an important role in cytotoxicity. Dilinoleoylglycerol, 60 micrograms/ml, was also cytotoxic selectively to Ad12-transformed and E1A-transformed 3Y1 cells, although the toxicity of lysophosphatidylcholine or linoleic acid was not specific to these transformants. These results suggest that cell transformation by Ad12 is characterized by a high sensitivity to exogenously administered phospholipids and diacylglycerol that contain oleoyl or linoleoyl acyl groups and that the sensitivity is attributable to the expression of E1A gene of Ad12.