Biomedical subjects
Publications and source records attributed to T Shindo.
Separation of a lipophilic extract of a soft coral, Sinularia sp., assayed by enhancement of glucose transport in rat adipocytes, gave farnesyl 4-O-beta-D-arabinopyranosyl-beta-D-arabinopyranoside-2,2',3- triacetate (1a) whose structure was determined by spectroscopy. Enhancers of glucose transport may be useful for the prevention and treatment of diabetic disorders.
We have developed an efficient system for obtaining myeloma mutants defective in trans-acting factors required for immunoglobulin (Ig) gene expression. The system consists of a myeloma cell line designed for this purpose and an efficient method for selecting mutants from it. The cell line is X63.653 transfected with the mu gene, whose tailpiece sequence was replaced with the transmembrane sequence of human EGF receptor to hold mu on the cell surface and whose CH1 sequence was removed to prevent mu from being retained in the endoplasmic reticulum. It efficiently and stably expressed mu chains of IgM on the cell surface (mu m+) without light chains. To obtain mutants lacking mu m (mu m-) from the mu m+ cell line by selectively killing mu m+ cells, a method with ricin A-conjugated anti-mu antibody was more reliable than complement lysis mediated by anti-mu antibody. Applying the system, we obtained a variety of mu m- mutants.
Coronary artery spasm plays an important role in acute ischemic events, and it has a close relationship with coronary atherosclerosis. Thus we attempted to determine the most significant risk factor for coronary artery spasm. Among 3000 consecutive patients who underwent coronary cineangiography with ergonovine maleate testing, 330 with typical angina pectoris (group 1) and 294 with old myocardial infarction (group 2) were studied. We divided each group into three or four subgroups according to the presence of fixed organic stenosis (FOS+) or a positive reaction to ergonovine maleate (coronary artery spasm [CAS]+). We examined the relationship between coronary artery spasm and eight coronary risk factors: age, sex, hypertension, diabetes mellitus, smoking, and serum cholesterol, uric acid, and high-density lipoprotein cholesterol levels. The proportion of smokers in the subgroups with CAS(+) was significantly higher than in the subgroups with CAS(-)(p less than 0.01). There was no correlation between smoking and fixed organic stenosis. According to the results of multiple regression analysis, there was a positive correlation between smoking and CAS(+) and between serum high-density lipoprotein cholesterol levels and CAS(+)(p less than 0.01). Thus we concluded that smoking is the most significant risk factor in discriminating between patients with and without coronary artery spasm.
The irritable bowel syndrome (IBS) is characterized by alteration in bowel habits (i.e., constipation and/or diarrhea) and abdominal pain, and is most common gastrointestinal disorder in adults. The recurrent abdominal pain (RAP) in children is similar to IBS in adults except bowel habits, but there is no settled conception of IBS in children. In our department, diagnosis of pediatric IBS will be made if the child has; #1 functional gastrointestinal disorders without organic diseases, #2 abdominal pain and other gastrointestinal symptoms continuing more than 3 weeks, #3 psychogenic background factors. We experienced 63 cases of IBS (23.5% in all 268 cases) from April 1990 to March 1992 at our pediatric digestive outpatient clinic. They ranged from 4 to 15 years old and about 60% of them were elder than 13 years old. Psychogenic factors were usually related to environment of school life and home. Careful history taking and routine examination were most important for the diagnostic approach. Management of this disease included counseling and drug therapy. Almost all cases reached much better condition 1 to 6 weeks after the therapy started. The combination therapy with psychologist was required in a few cases.
Fourteen patients underwent pneumonectomy for destroyed lung or tuberculous empyema at the Shimada Municipal Hospital from September 1980 to December 1985. Mean age was 61 and ten patients were males. Cough and sputum (in 12 cases) and hemosputum or hemoptysis (in 8 cases) were common complaints. Three patients had complications in the immediate postoperative period: hemorrhagic shock, pulmonary embolism and contralateral pneumothorax. They were treated conservatively. The postoperative course was uneventful in the other patients and all complaints were reduced or disappeared. And lung function improved in 3 cases with chronic empyema compressing the mediastinum. In conclusion, pneumonectomy is one of the radical operation for destroyed lung or chronic tuberculous empyema with low pulmonary function and complaints. And the critical level are 40% of %VC and 25% of FEV1.0/pr. %VC in preoperative pulmonary function.
Three cases of suspected variant thrombasthenia patients (out of 10 cases of Glanzmann's thrombasthenia), who had significant amounts of platelet GPIIbIIIa, underwent flow cytometry to analyse the binding capacity of monoclonal antibodies against GPIIbIIIa to platelets. The monoclonal antibodies used in this study were as follows: PLT-1 and AP-2 recognizing the IIbIIIa complex; TP 80, P2 and AP-4 recognizing IIb:;AP-5 recognizing IIIa;OP-G2, which binds an epitope near the RGD binding site and 3F11. OP-G2 also recognizes conformational changes of activated platelets by increased binding. Case 1 platelets showed a binding capacity of 28-63% of that of normal platelets for TP80, AP-2, AP-4, and 3F11, but no binding to OP-G2. Case 2 platelets also showed 16-44% binding with TP80, AP-2, AP-4, AP-5, and 3F11, but no binding to OP-G2. These findings indicated the presence of structural abnormalities of the functional site of platelet GPIIbIIIa in cases 1 and 2. Case 3 platelets bound with all monoclonal antibodies normally, but normal increase in the binding of OP-G2 to platelets activated by thrombin or ADP was not seen, indicating a lack of activation of the fibrinogen binding site of platelet GPIIbIIIa.
A total of 239 patients undergoing serial coronary angiography with a concomitant ergonovine provocation test were studied between July 1974 and June 1987. The progression of coronary artery disease was evaluated in relation to risk factors, especially coronary artery spasm. Patients were classified into three groups: 1) new myocardial infarction group (39 patients); 2) progression without infarction group (90 patients); and 3) nonprogression group (110 patients). To assess how risk factors and coronary spasm are related to the occurrence of new myocardial infarction and progression without infarction, 11 variables in the three groups were examined: age, gender, the time interval between the studies, fasting blood sugar, systolic blood pressure, diastolic blood pressure, smoking, serum cholesterol, triglyceride, uric acid and a positive response to the ergonovine provocation test. Multiple regression analysis selected three independent predictors of progression without infarction: cholesterol (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). Multiple regression analysis also selected three independent predictors of the occurrence of new myocardial infarction: fasting blood sugar (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). A positive response to the ergonovine provocation test was the strongest factor for occurrence of both new myocardial infarction and progression without infarction. To evaluate segmental arterial changes, 3,275 coronary artery segments were analyzed in the 239 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
We analyzed pulmonary functions and rib cage-phrenic motions on 296 cases of chronic empyema patients who had surgical treatment. Pulmonary functions were better preserved in patients with a single step than in those with multi-step operations, and in those who had more than five operations the impairment was inevitable. Both %VC and rib cage-phrenic motions improved by decortication, and by air-plombage, but in those who developed multi-rib fractures after the latter procedure, ipsilateral chest wall motion almost disappeared. Since some restriction of rib cage-phrenic motion is inevitable after the surgery, we have developed a cuirass respirator which can synchronize with the respiration to assist the movement of the chest wall. The results attained so far are satisfactory.
From March 1986 through October 1987, elective diagnostic coronary angiography was performed in 1,542 consecutive patients. Among them, silent myocardial ischemia was investigated based on the histories in their medical questionnaires, the results of exercise stress tests and the presence of significant coronary artery stenosis. Exercise-induced silent myocardial ischemia was documented only in 3% in the non-infarction group, and in 2.1% of those with significant coronary stenosis. However, asymptomatic post-infarction patients comprised 33%. With regard to the extent of coronary artery disease in the non-infarction group, one-, two- and three-vessel disease accounted for 42%, 29% and 29%, respectively (NS). However, one-vessel disease was predominant among the asymptomatic post-infarction patients (p < 0.01). Among the non-infarction group, those with asymptomatic coronary stenosis had a relatively high incidence of diabetes mellitus (p < 0.01), but such a difference was not significant among the asymptomatic post-infarction patients. Among the post-infarction group, many of those who had chest pain during exercise showed redistribution on exercise thallium scintigraphy. Angioplasty was performed in most of the patients in the asymptomatic group, but its long-term effects are yet unknown.
Anticancer drug (AD), adriamycin (ADM) or cisplatinum (CDDP) were individually encapsulated into an insoluble fibrin clot (FC), using our own technique. FC-ADM or FC-CDDP was intraabdominally placed in AH 130-bearing rats, and ADM or CDDP solution was intraabdominally injected (IP) into other cancer-bearing rats. The survival time was recorded and related oncolytic mechanisms were investigated. Eleven of 14 rats treated with FC-CDDP, and four of eight rats given FC-ADM, survived for more than 200 days. In these animals, the ascites disappeared within 10 to 14 days after the treatment, and there was neither a recurrence of ascites nor metastases. Eight of these rats underwent challenge of AH 130 cells. All the challenged animals revealed no evidence of recurrence of the cancer and showed a killing activity against the AH 130 cancer cells. Survival time in the other cancer-bearing rats was shorter than three weeks, and the direct cause of death was cachexia. Our newly devised FC-AD showed high activity against implanted AH 130 tumors. These activities are attributed to both a sustained release of AD and immunoresponses induced with FC-AD.
A 48-year-old male was referred to our division, on the suspicion of lung cancer with bone metastasis. Chest radiography showed a mass shadow and bone scintigram demonstrated multiple scattered regions of increased uptake. However bronchial and bone biopsy specimens revealed granuloma with epithelial cells and giant cells. A diagnosis of tuberculous osteomyelitis was made, and antituberculous therapy was begun. Chest radiography and bone scintigrams one year later showed marked improvement.
Platelets from 10 patients with Glanzmann's thrombasthenia (7 patients with type I and 3 with type II) and their 18 family members (11 parents, 6 siblings and one daughter) were analyzed by flow cytometry using 3 different commercially available FITC-labeled monoclonal antibodies. The amount of platelet GPIIbIIIa was calculated by using the ratio of the fluorescence intensity of the mean channel in comparison to normal platelets. The amount of platelet GPIIbIIIa was lower than 19% in 6 patients with type I and one patient with type II thrombasthenia. One type I patient had a 46.5% GPIIbIIIa amount as assessed using the monoclonal antibody TP80 (Nichirei Corp. Japan) which recognized GPIIb, although the other 2 antibodies showed an amount of less than 5%. One type II patient showed the following results: 30.9% (TP80), 28.2% (P2 antibody, Immunotech, France), and 3.9% (PLT1, Coulter Immunology, USA). The remaining type II patient consistently showed a normal amount of platelet GPIIbIIIa using all antibodies, appeared to be a variant form of thrombasthenia. The parents of type I patients had a significantly lower amount of platelet GPIIbIIIa compared to normal and 2 siblings of type I patients were diagnosed as heterozygotes. These findings suggest that Glanzmann's thrombasthenia is more heterogeneous than we have previously suspected, and that flow cytometric analysis using different monoclonal antibodies is a useful tool for identifying those heterogeneities and for the detection of type I carriers.
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