Evaluation of morphological changes of the atherosclerotic aorta by enhanced computed tomography.

Enhanced and non-enhanced computed tomography (CT) were performed in 405 subjects (222 men; 183 women; mean age 57 years). Intimal atherosclerotic changes of the aorta were quantified by enhanced CT, revealing the atheromatous intima to be projecting and thick-walled, while non-enhanced CT demonstrated aortic calcification. We measured the degree of aortic intimal changes at various segments of the aorta. In 224 cases, CT was performed from the aortic root to the bifurcation of the abdominal aorta. Intimal changes were found predominantly at the aortic arch, the middle descending thoracic and the infrarenal abdominal aorta. As for the intimal changes, aortic calcification and aortic pulse wave velocity were significant atherosclerotic characteristics. The aortic diameter did not show a significant association with intimal change. Among the various atherosclerotic risk factors, intimal change was significantly associated with age, systolic blood pressure, serum total cholesterol and diabetes mellitus, whereas gender, diastolic blood pressure, relative weight and cigarette use were not significantly related. For coronary artery disease and arteriosclerosis obliterans, aortic intimal changes constituted a significant atherosclerotic feature. In cerebrovascular disease, however, aortic intimal change did not play a significant role.

Expansion rate of thoracic aortic aneurysms and influencing factors.

The risk of rupture of an aortic aneurysm increases with size and rapid expansion rate. We studied the expansion rate of thoracic aortic aneurysms and the factors influencing expansion rate, and compared the results with those of abdominal aortic aneurysms. Forty thoracic aortic aneurysms and 25 abdominal aortic aneurysms were serially examined with enhanced and nonenhanced computed tomography. The mean expansion rate of thoracic aortic aneurysms was 1.3 +/- 1.2 mm/yr and was significantly lower than 3.9 +/- 3.2 mm/yr of abdominal aortic aneurysms. The factors increasing expansion rate of thoracic aortic aneurysms were initial size of aneurysms, diastolic blood pressure, and presence of renal failure by univariate analysis. Multivariate analysis concerning the entire aortic aneurysms also revealed that the large size of the aneurysm and the presence of the aortic aneurysm in the abdomen increased expansion rate of aneurysms.

Generation of free radical and hydrogen peroxide from 2-hydroxyemodin, a direct-acting mutagen, and DNA strand breaks by active oxygen.

Among several hydroxylated metabolites of emodin, a fungal anthraquinone and constituent of rhubarb, 2-hydroxyemodin was a direct-acting mutagen showing a large electron-spin resonance (ESR) signal in the presence of DNA, especially at alkaline pH. Coupled with generation of free radical, hydrogen peroxide but not superoxide was formed. The active oxygen produced from 2-hydroxyemodin induced strand breaks in phi X 174 replicative form I DNA (supercoiled covalently closed circular duplex DNA). These results suggest a possible role of active oxygen in the process of mutagenesis.

Metabolic activation of emodin in the reconstituted cytochrome P-450 system of the hepatic microsomes of rats.

Studies were undertaken to elucidate further the mechanism by which emodin, an anthraquinoid mycotoxin and constituent of rhubarb, was converted into a direct-acting mutagen to Salmonella typhimurium TA1537 by the hepatic microsomes and the reconstituted cytochrome P-450 system. Emodin was activated into a mutagenic principle(s) in the reconstituted cytochrome P-450 system, and its mutagenicity was significantly higher with the fraction II (P-448 type) than the fraction I (P-450 type) derived from the hepatic microsomes of PCB-induced rats. Thin-layer chromatographic analysis revealed that the purified cytochrome II-a (maximal CO-differential spectrum at 448.0 nm and high-spin form) activity converted emodin into 2-hydroxy-emodin, a direct-acting mutagen.

2-Hydroxyemodin, an active metabolite of emodin in the hepatic microsomes of rats.

The hepatic microsomes derived from rats transformed emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), an anthraquinone present in fungal metabolites and constituent of rhubarb, into at least 10 anthraquinoid metabolites. Metabolite d proved to be mutagenic to Salmonella typhimurium TA1537 in the absence of activation system. MS, NMR, UV and mutagenicity test analysis revealed that metabolite d was 2-hydroxyemodin (1,2,3,8-tetrahydroxy-6-methyl-anthraquinone) and exhibited mutagenicity in doses of 2-20 micrograms/plate. In addition to this active metabolite, TLC analysis revealed the formation of 4-hydroxyemodin (metabolite a), 5-hydroxyemodin (metabolite b), 7-hydroxyemodin (metabolite d') and others. No mutagenicity of these monohydroxyemodins was demonstrated in the absence of activation system.

omega-Hydroxyemodin, a major hepatic metabolite of emodin in various animals and its mutagenic activity.

The hepatic microsomes derived from various animal species transformed emodin (1,3,8-trihydroxy-6-methylanthraquinone), an anthraquinoid pigment present in fungal metabolites and a constituent of plant medicines, into an unidentified anthraquinone h, along with 2-hydroxy-, 4-hydroxy- and 7-hydroxyemodins. TLC, UV, MS and NMR clarified this unidentified major metabolite as omega-hydroxy-emodin (1,3,8-trihydroxy-6-hydroxymethylanthraquinone). Among 7 animal species, the highest activity to produce this omega-hydroxyemodin was observed in the hepatic microsomes of guinea pig and rat, followed by mouse and rabbit. The microsomal activity to convert emodin into omega-hydroxyemodin was accelerated by the pretreatment of animals with phenobarbital, and inhibited by SKF 525A. The microsomal hydroxylation reactions of the methyl residue and the anthraquinoid nucleus of emodin were presumed to be catalyzed regiospecifically by multiple forms of cytochrome P-450. omega-Hydroxyemodin was not mutagenic to Salmonella typhimurium in the absence of S9, but exhibited mutagenicity in the presence of an activating system. This genotoxic potential was comparable to 2-hydroxyemodin, a direct-acting mutagen.

Unoperated thoracic aortic aneurysms: survival rates of the patients and determinants of prognosis.

The purpose of this study was to evaluate the long-term prognosis of unoperated thoracic aortic aneurysms, and to detect the risk factors which determine the prognosis of unoperated patients. The subjects were 52 unoperated patients with 58 thoracic aortic aneurysms (22 of the ascending aorta, 36 of the descending aorta or the aortic arch) and 38 with abdominal aortic aneurysms. The survival rates of the patients with ascending aortic aneurysms at 3 years and 5 years and those of the patients with descending aortic aneurysms at 5 years were significantly higher than those of the patients with abdominal aortic aneurysms. The risk factors for rupture of thoracic aortic aneurysms were the large size of aneurysms and non-management by the cardiologist and the risk factors for death unrelated to the aneurysms were patient age, male gender and non-management by the cardiologist.

Coronary artery calcification detected by CT: clinical significance and angiographic correlates.

Cardiac computed tomography (CT) to detect coronary calcification was performed on 161 patients undergoing coronary angiography for proven or suspected coronary artery disease. Among 108 patients in whom coronary calcifications was identified, 90% had significant coronary stenosis angiographically (greater than 75% stenosis), and 80% of 121 patients with significant coronary stenosis showed calcification by CT. The relationship between the calcification site and the significance in stenosis of each vessel was determined. Calcification was present in 133 arteries among 205 stenotic coronary arteries (sensitivity = 65%) as compared with 59 of 439 entire arteries with normal coronary angiograms (specificity = 87%). In the younger age group the sensitivity of calcification for stenosis of each coronary artery was lower and the specificity and predictive value were generally higher than those in the elderly group. These results demonstrate that CT is a valuable procedure for detecting coronary arterial disease, since this examination is easy to conduct, noninvasive, and widely applicable for screening a large population.

Clinical importance of coronary calcification detected by CT.

Coronary calcifications appear in advanced atheromatous lesions therefore fluoroscopy is useful for the detection of the atherosclerotic coronary artery disease (Aldrich et al., 1979). However, the detection of coronary calcification by fluoroscopy is difficult in the case of obesity or thick chest wall and also impaired by the background structures including bone and other intrathoracic calcifications. X-ray CT is more advantageous than fluoroscopy in the detection of coronary calcification. It can eliminate the interference from background structures and clearly demonstrates calcified sites of the coronary artery. Therefore, we investigated the clinical usefulness in the detection of coronary calcification with X-ray CT.

Biological modification of trichothecene mycotoxins: acetylation and deacetylation of deoxynivalenols by Fusarium spp.

Attempts were made to elucidate the acetyl transformation of novel trichothecene mycotoxins, 3a,7a,15-trihydroxy-12,13-epoxytrichothec-9-en-8-one (deoxynivalenol) and its derivatives, by trichothecene-producing strains of Fusarium nivale, F. roseum, and F. solani. In the peptone-supplemented Czapek-Dox medium, F. roseum converted 3a-acetoxy-7a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (3-acetyldeoxynivalenol) to deoxynivalenol. 3-Acetyldeoxynivalenol was also deacetylated by intact mycelia of the three strains in sugar-free Czapek-Dox medium. The growing F. nivale acetylated deoxynivalenol to afford a small amount of 3-acetyldeoxynivalenol. 3a,7a,15-Triacetoxy-12,13-epoxytrichothec-9-en-8-one (7,15-diacetyl-deoxynivalenol), which was then deacetylated to give 7a-acetoxy-3a,15-dihydroxy-12,13-epoxytrichothec-9-en-8-one (7-acetyldeoxynivalenol). It was noted that the ester at C-7 was not hydrolyzed by the fungal mycelium.

Comparative studies on microbial and chemical modifications of trichothecene mycotoxins.

The microbial modification of several trichothecene mycotoxins by trichothecene-producing strains of Fusarium nivale and F. solani was studied. These results were compared with the corresponding chemical modifications. The growing mycelia of Fusarium spp. did not convert 4beta-acetoxy-3alpha,7alpha, 15-trihydroxy-12, 13-epoxytrichothec-9-en-8-one (fusarenon) into 3alpha,4beta, 7alpha,15-tetrahydroxy-12,13-epoxy-trichothec-9-en-8-one (nivalenol), whereas 3alpha,4beta,7alpha,15-tetracetoxy-12,13-epoxytrichothec-9-en-8-one (tetraacetylnivalenol) was deacetylated to yield 3alpha-hydroxy-4beta,7alpha,15-triacetoxy-12,13-epoxytrichothec-9-en-8-one (4,7,15-triae-tylnivalenol), which was resistant to further deacetylation. T-2 toxin was transformed intoHT-2 toxin, and 8alpha-(3-methylbutyryloxy)-3alpha,4beta,-15-triacetoxy-12,13-epoxytrichothec-9-en-8-one (T-2 acetate) was transformed into HT-2 toxin via T-2 toxin. Chemical modification with ammonium hydroxide converted tetraacetylnivalenol into fusarenon via 4,7,15-triacetylnivalenol. 3alpha-7alpha,15-Triacetoxy-12,13-epoxytrichothec-9-en-8-one (triacetyldeoxynivalenol) gave deacetylation products lacking the C-7 or c-15 acetyl group in addition to 7alpha,15- diacetoxy-3alpha-hydroxy-12, 13-epoxytrichothec-9-en-8-one (7,15-diacetyldeoxynivalenol). These results demonstrate the regio-selectivity in microbial modification of trichothecenes. Based on the results and available knowledge concerning the transformation of trichothecenes, mechanisms for biological modifications of these mycotoxins are postulated.

Microbial acetyl conjugation of T-2 toxin and its derivatives.

The acetyl conjugation of T-2 toxin and its derivatives, the 12,13-epoxytrichothecene mycotoxins, was studied by using mycelia of trichothecene-producing strains of Fusarium graminearum, F. nivale, Calonectria nivalis, and F. sporotrichoides, T-2 toxin was efficiently converted into acetyl T-2 toxin by all strains except a T-2 toxin-producing strain of F. sporotrichoides, which hydrolyzed the substrate to HT-2-toxin and neosolaniol. HT-2 toxin was conjugated to 3-acetyl HT-2 toxin as an only product by mycelia of F. graminearum and C. nivalis, but was also resistant to conjugation by both F. nivale and F. sporotrichoides. Neosolaniol was also biotransformed selectively into 3-acetyl neosolaniol by F. graminearum. However, 3-acetyl HT-2 toxin was not acetylated by any of the strains under the conditions employed, but was hydrolyzed to HT-2 toxin by F. graminearum and F. nivale. This is the first report on the biological 3 alpha-O-acetyl conjugation of T-2 toxin and its derivatives.

Emetic and refusal activity of deoxynivalenol to swine.

The minimum emetic dose of deoxynivalenol to swine weighing 9 to 10 kg was 0.05 mg/kg of body weight intraperitoneally and 0.1 to 0.2 mg/kg orally. There was no emesis by undosed pigs consuming vomitus from pigs orally dosed with deoxynivalenol or penned with such pigs without access to vomitus. Analysis by gas-liquid chromatography of a sample of Gibberella zeae-infected corn containing about 25% visually damaged kernels indicated 12 ppm of deoxynivalenol. Deoxynivalenol added to feed reduced feed consumption of 20- to 45-kg pigs, ranging from a 20% decrease with 3.6 ppm to 90% reduction with 40 ppm. Loss in weight was associated with feed refusal. Feed refusal, however, was much greater for naturally infected corn samples than for feeds with equal concentrations of the pure compound added, indicating the involvement of an additional factor(s) in the swine refusal response.

Estimation of pulmonary water distribution and pulmonary congestion by computed tomography.

Computed tomography (CT) of the lung in normal subjects and patients with congestive heart failure was performed in the supine position with deep inspiration to obtain pulmonary CT values and images. The mean CT value in normal subjects was higher in the posterior than anterior lung field, presumably because blood vessels were more dilated in the former than the latter due to the effects of gravity. The mean pulmonary CT value in patients with congestive heart failure was significantly increased possibly due to an increase in blood flow per unit lung volume arising from either pulmonary congestion or pulmonary interstitial and alveolar edema. The mean pulmonary CT value increased parallel to the severity of pulmonary congestion, interstitial or alveolar edema and was well correlated with the pulmonary arterial wedge pressure, indicating that such a correlation was a valuable tool in assessing therapeutic effects. The results of the present study indicate that pulmonary CT is useful for the noninvasive estimation of intrapulmonary water content and its distribution, thereby providing an effective diagnostic clue to various conditions in congestive heart failure.

Tremorgenic mycotoxin from Penicillium paraherquei.

A tremorgenic mycotoxin was isolated from Penicillium paraherquei Abe ex G. Smith and identified as verruculogen. It was produced at the rate of approximately 1 mg/g of the dried fungal mycelium cultured on peptone-enriched Czapek-Dox medium at 28 degrees C.

Noninvasive diagnosis of thrombus in the heart and large vessels--usefulness of two-dimensional echocardiography and X-ray CT.

The usefulness of two dimensional echocardiography (2-D echocardiography) and x-ray computed tomography (CT) for the diagnosis of thrombi in the cardiac cavity and large vessels was studied by comparing them with the findings of invasive methods. Among 56 subjects with mitral stenosis, left atrial thrombi were noted in 12 cases (16 regions) by CT and 8 cases (9 regions) by 2-D echocardiography. In 16 subjects who underwent operations, one false negative case by CT and 3 false negative and one false positive cases by 2-D echocardiography were found. In 80 subjects with myocardial infarction 2-D echocardiography, CT and left ventriculography (LVG) were performed at approximately the same time. Thrombi were detected in 10 subjects (12.5%) by 2-D echocardiography, in 15 (18.8%) by CT and in 14 (17.5%) by LVG. Although mural thrombi in abdominal aortic aneurysm were detected very easily, thin thrombi surrounding the false lumen of the dissecting aneurysm were not detected ultrasonographically. These thrombi were only detected by the enhanced CT. Our results show the usefulness of both methods for detecting thrombi in the heart and large vessels. CT can distinguish the thrombi more clearly than 2-D echocardiography, but 2-D echocardiography is performed more easily, safely and economically than CT.

The usefulness of x-ray computed tomography for the diagnosis of myocardial infarction.

Conventional and enhanced computed tomographic (CT) examinations were performed in 103 patients with myocardial infarction for evaluation of the diagnostic usefulness of CT. After intravenous bolus injection of contrast material, an initial filling defect and late enhancement of the infarcted myocardium appeared on the cardiac CT images. These two findings were direct evidence of myocardial infarction; the former was found mostly in the patient with recent myocardial infarctions, and the latter was recognized both in those with recent and those with "remote" infarctions. Wall thinning at the site of infarction was found by enhanced CT mostly in patients with anteroseptal or extensive anterior infarctions, and was rarely found in patients with inferoposterior infarctions. Left ventricular aneurysms and ventricular thrombi were found by enhanced CT in 39 and 23 of the 103 subjects, respectively, and the sensitivity of CT in detecting intracardiac thrombi was higher than that of two-dimensional echocardiography. Calcification of the myocardium and pericardial effusion associated with myocardial infarction were also detected by conventional nonenhanced CT. Thus, cardiac CT was found to be a useful test in evaluating patients with myocardial infarction.

[Magnetic resonance imaging of cardiovascular diseases: advantages of coronal and sagittal planes].

The usefulness of coronal and sagittal sections of the cardiovascular system by magnetic resonance imaging was evaluated. Coronal, sagittal and transverse spin echo scans using ECG-non-gating and gating during systole and diastole were performed for five normal volunteers, 91 with heart diseases (25 valvular disease, 28 ischemic heart disease, 14 cardiomyopathies, 14 congenital malformations, four pericardial diseases, and six others) and 32 patients with aortic abnormalities (17 aneurysms, 10 dissections and five others) using a 2.5 KGauss unit. Cardiac gating necessitated six to eight min per scan, but it was mandatory to obtain clear images of the details. On the other hand, in most of the aortic abnormalities, diagnostic images were obtained by the ECG-non-gating technique which required only about 2.5 min per scan. Coronal and sagittal sections were useful for estimating the entire shape and size of each cardiac chamber and intracardiac thrombi, the extent of postinfarctional wall thinning and cardiac aneurysms, and hypertrophy or narrowing of both the ventricular outflow tracts and apex. These planes were particularly useful, and more contributory than transverse planes for detecting inferior myocardial damage such as infarction. A few coronal and sagittal scans were sufficient to diagnose extensive lesions of the aorta, such as atherosclerosis, dissections and the aortitis syndrome. Local lesions such as coarctation, supravalvular aortic stenosis, annulo-aortic ectasia and aneurysm, especially those originating in the inferior wall of the aortic arch were easily discovered. Since the main arteries, such as the innominate, left common carotid, left subclavian and renal arteries, were clearly demonstrated by coronal images, coronal scans were considered more useful than transverse ones for observing the relationship between these arteries and dissections or aneurysms of the arch and of the abdominal aorta.