[Clinical and epidemiologic study of pulmonary tuberculosis].
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Biomedical subjects
Publications and source records attributed to T Aoyagi.
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We examined the changes in the intracerebral activities, at the time of postmortem autopsy, in patients with Alzheimer's disease. When compared with the control group, the activity of kallikrein-like enzyme was significantly decreased, while prolyl endopeptidase activity increased, in the patients group. Aprotinin inhibited 50% of the activity of the former enzyme at 2 x 10(-7) M. Taken together with the results of a multivariate study, the above findings may indicate that intracerebral kallikrein deficiency plays an important role in the pathogenesis of Alzheimer's disease.
Changes in parameters of left ventricular (LV) diastolic filling flow obtained with Doppler echocardiography during the lower body positive and negative pressure method were analyzed in 15 patients (12 with coronary artery disease and 3 with dilated cardiomyopathy). Lower body pressure was altered at 5 steps (+20, +10, 0, -20 and -40 mm Hg vs atmospheric pressure). Pulmonary capillary wedge pressure measured with a balloon-tipped catheter was changed proportionally with lower body pressure during the procedures (p less than 0.01). Mean systemic arterial pressure was changed slightly during lower body positive pressure and negative pressure of -40 mm Hg. Heart rate was almost unchanged except at lower body pressure of -40 mm Hg. The peak velocity of LV early diastolic filling flow was changed with pulmonary capillary wedge pressure in an almost parallel fashion during the procedures (p less than 0.01). The peak velocity of LV late diastolic filling flow showed smaller changes than that of early diastolic filling flow. Changes in pulmonary capillary wedge pressure correlated positively with changes in the peak velocity of LV early diastolic filling flow (r = 0.759, p less than 0.01), but not with changes in the peak velocity of LV late diastolic filling flow (r = 0.039, not significant) during lower body negative pressure of -20 mm Hg. These data suggest that left atrial pressure is one of the important determinants of LV early diastolic filling flow in this acute clinical setting and that LV late diastolic filling flow is less sensitive to changes in left atrial pressure than LV early diastolic filling flow.
To study the relationship between plasma alpha-atrial natriuretic peptide (alpha-ANP) and cardiac function in patients with Duchenne's progressive muscular dystrophy (DMD), we measured plasma alpha-ANP levels in 51 patients with DMD and evaluated them according to the clinical severity of the disease and the echocardiographic left ventricular function. In many of the patients with DMD, plasma alpha-ANP levels were mildly elevated, but no clear correlation was observed between alpha-ANP levels and wall motion abnormalities of the left ventricle. The alpha-ANP level was moderately or markedly elevated (81 to 120 pg/ml) in 3 of the 16 patients with respiratory failure and extremely high (1208 pg/ml) in the one patient with congestive heart failure. Two patients with respiratory failure and one with congestive heart failure, in whom alpha-ANP levels were elevated, died within 2 months. Elevation of left atrial pressure as a result of left ventricular dysfunction caused by impairment of the myocardium and elevation of right atrial pressure as a result of pulmonary hypertension caused by impairment of the respiratory muscles are considered to be involved in the mechanism of increased plasma alpha-ANP levels in patients with DMD. It can be concluded that a moderate or marked elevation in plasma alpha-ANP levels in patients with terminal DMD is a sign of a poor prognosis and may be a useful index for the management of the disease.
The acute hemodynamic effects of nilvadipine, a newly synthesized calcium channel blocker, were studied in 12 patients with congestive heart failure. Hemodynamic measurements were made before and 15, 30, and 60 min after oral administration of 6 mg nilvadipine. Substantial reductions in systemic vascular resistance (-28.8 +/- 6.3%, p less than 0.01) and forearm vascular resistance (-52.0 +/- 6.2%, p less than 0.01) after nilvadipine administration were associated with increases in cardiac index (31.1 +/- 8.3%, p less than 0.01) and forearm blood flow (105.2 +/- 27.4%, p less than 0.01). Mean arterial and pulmonary arterial pressures were decreased by 12.2 +/- 3.0% (p less than 0.01) and 14.7 +/- 5.0% (p less than 0.05), respectively, after nilvadipine administration; however, heart rate remained unchanged. Decreases in mean arterial pressure correlated with the baseline arterial pressure (y = 0.58x - 41.6, r = 0.75, p less than 0.01). Pulmonary capillary wedge pressure decreased by 33.1 +/- 9.1% (p less than 0.01) after nilvadipine administration. However, right atrial pressure and the venous stiffness constant remained unchanged, and the venous pressure-volume curve was not shifted significantly. Therefore, the decrease in pulmonary capillary wedge pressure was attributed primarily to afterload reduction. Nilvadipine holds promise as a vasodilator for the therapy of congestive heart failure.
The effect of 15-deoxyspergualin (DSP), a newly developed immunosuppressive agent, on the development of spontaneously occurring lupus glomerulonephritis in MRL-lpr mice was examined. Administration of the drug was initiated at the age of 13 or 17 weeks, when polyclonal B cell activation and lupus nephropathy were apparent or became prominent. Treatment with DSP for up to 19 weeks of age at a dose of 2 mg/kg twice a day or 5 mg/kg daily strongly suppressed the increment of IgG-producing cell numbers in the spleen and serum levels of immune complexes and anti-DNA antibodies. Glomerular histological score estimated by light microscopy and IgG and C3 deposition in renal glomeruli were improved, compared with untreated control mice. Thus, DSP was shown to suppress the progression of polyclonal B cell activation and lupus nephropathy in MRL/lpr mice. These results suggest that DSP may be used as a therapeutic agent for systemic lupus erythematosus.
In order to search for more proximal factors in the pathogenesis of Alzheimer's disease, we studied the activities of various enzyme in the brains of patients, as well as control cases, by postmortem autopsy. In addition to the findings already known, such as the increase in prolyl endopeptidase (post-proline cleaving enzyme, PPCE) activity and the decrease in kallikrein activity, we found, anew, an increase in aminobutyrate aminotransferase (GABA-T) activity in the Alzheimer brain. This may be an important impetus for the reduction of gamma-aminobutyric acid (GABA) in the brain, one of the neurotransmitters. It has to be determined whether the former two abnormalities offer a background for such an abnormality of the neurotransmitter.
We previously reported an increase in aminobutyrate aminotransferase (GABA-T) activity in the cerebrum of Alzheimer patients. In the present study, we investigated whether such findings are common in the usual aging process as well. We examined the activity of various enzymes, which were examined in the previous study, in the cerebrum of Wistar-Kyoto rats and spontaneously hypertensive rats. In the two strains, we compared the enzyme activities between the two groups of animals, 5 weeks and 13 weeks of age. In both strains, the older animals had significantly higher activities of GABA-T and choline acetyltransferase (ChAc-T). In spite of other enzymatic changes coexisting, the above two enzymes were suggested by discriminant function analysis to be playing a major role in the multiple enzymatic changes in the cerebrum of the animals.
The concept of end-systolic myocardial stiffness permits the quantification of preload effects on fiber shortening and changes in the slope (max Eav) of the end-systolic stress-strain relation, which, if linear, reflect changes in the inotropic state. As an application of this new concept, the end-systolic stress-strain and shortening-afterload relations were evaluated on the basis of data from dogs studied during development of perinephritic hypertension. End-systolic stress-strain relations were linear before and 2 weeks after the induction of hypertension and the end-systolic pressure-diameter relations were not always linear. The shortening-afterload relations obtained directly from raw data points displayed enhanced contractility in the hypertensive state under beta-adrenergic receptor blockade. However, the preload-corrected shortening-afterload relations demonstrated that contractility was unchanged in hypertension. Hypertensive hearts operated at higher preload than normotensive hearts at any afterload levels. This discrepancy between the conventional method without preload-correction and the preload-corrected analysis indicates the importance of preload-correction on shortening-afterload relations in hypertension.
Probestin has been isolated as part of a program designed to find microorganism-produced inhibitors of aminopeptidase M from Streptomyces azureus MH663-2F6. It was purified by use of column chromatography of Amberlite XAD-4, silica gel, YMC-gel, Toyopearl HW-40, YMC D-ODS-5 (HPLC) and then isolated as colorless powders. Probestin is competitive with the substrate, and the inhibition constant (Ki) of it was 1.9 x 10(-8) M.
Probestin, a new inhibitor of aminopeptidase M, has been isolated from the culture broth of Streptomyces azureus MH663-2F6. The 1H and 13C NMR studies and amino acid analysis confirmed the presence of one 3-amino-2-hydroxy-phenylbutanoic acid, leucine and two proline residues in the molecule. Stereochemistries of these amino acids were determined by HPLC analysis. The fragmentation pattern shown in the mass spectrum and the chemical analysis on probestin clarified the amino acid sequence. Thus the structure of probestin was defined as (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucyl-L-prolyl-L-pro line.
The relation of plasma renin activity (PRA) and plasma levels of angiotensin I (AI) and II (AII) to those of various proteases, including eight endopeptidases and four aminopeptidases, was investigated in 51 normal control subjects. The multivariate study using factor analysis showed that the plasma proteases can be classified into three main components: the aminopeptidase, the plasmin, and the kinin-kallikrein. PRA and AI were related almost exclusively to the aminopeptidase component, while the AII level was related not only to the same component but also to the kallikrein-kinin component. This kind of multivariate study may help in the elucidation of the role of proteases and bioactive peptides, such as angiotensin derivatives, in essential hypertension through a comparison of multivariate relationships in controls and patients.
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Clinical characteristics of the lung diseases due to M. avium and M. intracellulare classified by DNA probe test were investigated. Between M. avium and M. intracellulare, there was no significant differences in the samples' backgrounds and the clinical characteristics except for their prognoses. The prognosis of the lung diseases due to M. intracellulare was better than those due to M. avium, and M. avium was revealed to be highly susceptible to Cyclocerine than M. intracellulare. No remarkable difference was found in the susceptibility to other antituberculous drugs.
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We investigated, with use of a technique of feedback analysis, the dynamic changes in and around the renin-angiotensin system in vivo induced by ACE inhibition. Prolonged studies were performed over a half year on rabbits, which were treated by daily injections of saline or one of the inhibitors as follows: captopril, foroxymithine, histargin and pepstatin. In spite of the apparently bizarre movements of the raw data, the analysis with autoregressive modelling unveiled the different modes of feedback regulations of the renin-angiotensin system under the influence of the various inhibitors. In order to interpret the in vivo actions of enzyme inhibitors, it seems essential to take feedback regulations into consideration.
We investigated the effects of microbial protease inhibitors, in particular the aminopeptidase inhibitor bestatin, on DNA synthesis and cell division induced by epidermal growth factor (EGF) in hepatocytes. Although bestatin did not significantly affect binding of EGF to hepatocytes, it inhibited EGF-induced DNA synthesis and cell division. DNA synthesis in rat hepatocytes was maximal 24-26 h after EGF addition to the medium. The time required for maximal DNA synthesis was not affected if bestatin was removed less than 12 h after addition, but synthesis was partially inhibited if bestatin was added to the medium several hours after EGF addition, depending on the time of bestatin addition. Our results suggest that bestatin arrests the new cell cycle induced by EGF at about 12 h after the initiation. Considering also our results obtained by employing other protease inhibitors, we concluded that specific proteases play important roles in hepatocyte DNA synthesis and cell division induced by EGF.
Prominent sinusoidal dilatation of the liver, spleen, and adrenals has been observed in nude mice with transplanted human renal cell carcinoma (RCC). To confirm whether this is a paraneoplastic manifestations specific for patients with RCC, 145 human autopsy specimens of RCC, transitional cell carcinoma (TCC) and cerebral hemorrhage (CH) were studied histologically. Sinusoidal dilatation of the liver was found in nine of 45 RCC cases. That incidence rate was significantly high when compared with three of 50 TCC cases (P less than .05) and with none of 50 CH cases (P less than .005) in which sinusoidal dilatation of the liver was found. There were no significant differences among the RCC, TCC, and CH groups in the incidence of sinusoidal dilatation in the spleen and adrenals. The sinusoidal dilatation of the liver associated with RCC was unique in that it occurred focally in the mid-zone of the hepatic lobules without any findings related to passive congestion of the central vein, endothelial damage, or hepatocellular necrosis. This change was not necessarily accompanied by abnormal liver function, although sinusoidal dilatation has been reported as one of the histologic manifestations of the nonmetastatic liver dysfunction syndrome of RCC known as the Stauffer syndrome. Sinusoidal dilatation is thought to be one of the tumor-specific manifestations and the influence of some tumor products is suggested, although the exact etiology remains unclear.