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Biomedical subjects

T Yasugi

Publications and source records attributed to T Yasugi.

At least 73 records · Page 4Linked to original sources

Independent association of antibodies against human papillomavirus type 16 E1/E4 and E7 proteins with cervical cancer.

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an E1/E4 fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac-E1/E4 and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti-E1/E4 antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti-E1/E4 and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.

Adenocarcinoma↗

In vitro hydrolysis of methyl acetate, a limitation in application of head-space gas-chromatography in biological monitoring of exposure.

Stoichiometric conversion of methyl acetate to methanol in vitro was detected when methyl acetate was incubated with blood for 2 to 8 h. The velocity of the reaction was so fast that almost all of methyl acetate disappeared in 8 h. The methanol formation was further confirmed by means of gas-chromatography-mass spectrometry. The capacity to hydrolyze methyl acetate was evenly distributed in cellular and noncellular fractions of blood, but not in urine. The significance of the observation is discussed in relation to biological monitoring of exposure to industrial ester solvents by means of head-space gas-chromatography of blood samples.

Acetates↗

Curvi-linear relation between acetone in breathing zone air and acetone in urine among workers exposed to acetone vapor.

An occupational health study was conducted on 45 acetone-exposed male workers in combination with 343 non-exposed men to examine the quantitative relationship between the intensity of acetone vapor exposure and the concentration of acetone in urine. The time-weighted average acetone concentrations were measured by means of diffusive samplers with water as absorbent, whereas urine samples were collected at the end of the shift as well as before the shift on the next morning. Acetone concentration in shift-end urine did not increase when the workers were exposed to acetone up to approx. 15 ppm, and this was followed by a gradual increase at a higher atmospheric acetone concentration, in a manner dependent to acetone vapor concentration. The comparison in acetone concentrations between the urine samples collected at the shift-end and those before the shift of the next morning showed that the levels in two sets of samples were the same among those exposed to 15 or less ppm acetone, whereas acetone in the shift-end samples was significantly higher than the counterpart levels in the pre-shift samples among those exposed to acetone at more than 15 ppm.

Acetone↗

Urinalysis vs. blood analysis, as a tool for biological monitoring of solvent exposure.

Blood and urine samples were collected at the end of an 8-h workshift from 30 male workers exposed to a mixture of n-hexane, ethyl acetate and toluene (each being about 2 ppm as geometric means) and also from 20 nonexposed male workers. Blood samples were analyzed for n-hexane and toluene, and urine samples were analyzed for n-hexane, toluene, 2,5-hexanedione (both with and without hydrolysis) and hippuric acid. Based on the correlation between biological exposure indicators and solvent concentrations in air, sensitivity as an exposure indicator was compared between solvents in blood and solvents or metabolites in urine in terms of the lowest solvent concentration at which the exposed subjects can be statistically separated from the nonexposed. Both n-hexane and toluene in blood were sensitive enough to detect the exposure at 6.1 ppm and 1.4 ppm, respectively. n-Hexane exposure below 2 ppm was detectable also by urinalysis for 2,5-hexadione without hydrolysis. Urinary hippuric acid, however, failed to detect low toluene exposure under the conditions studied. Of additional interest is the fact that toluene in urine correlated significantly with toluene in air, which apparently deserves further study for confirmation.

Acetates↗

Significance of C3 nephritic factor (C3NeF) in non-hypocomplementaemic serum with membranoproliferative glomerulonephritis (MPGN).

C3NeF is an autoantibody of C3 convertase (C3bBb) and is often detected in the serum of hypocomplementaemic MPGN patients. Serum samples from 104 non-hypocomplementaemic MPGN patients (C3NeF) were studied. C3NeF, which cannot activate the alternative pathway, was found in the sera of 6 patients. We examined the C3NeF in purified IgG from five of the non-hypocomplementaemic serum samples (non-hypo C3NeF) and four hypocomplementaemic serum samples (hypocomplementaemic C3NeF) to determine why C3NeF does not induce C3 splitting and hypocomplementaemia. Purified IgG from non-hypo C3NeF stabilized EAC4b3bBb cells in a manner similar to IgG from hypocomplementaemic C3NeF in EDTA gelatin veronal buffer. However, the non-hypo C3NeF IgG did not stabilize C3 convertase (EAC4b3bBb cells) in the presence of control proteins (factors H and I), whereas the hypocomplementaemic C3NeF IgG did. The C3NeF in the hypocomplementaemic serum displayed two characteristics: (i) inhibition of intrinsic decay of Ce convertase (C3bBb); and (ii) inhibition of extrinsic decay by factors H and I. Although the C3NeF in the non-hypocomplementaemic sera did inhibit the intrinsic decay in a manner similar to the hypocomplementaemic C3NeF IgG, it did not inhibit the extrinsic decay. Due to the different characteristics of hypocomplementaemic C3NeF and non-hypo C3NeF in the serum samples, the non-hypo C3NeF did not activate C3. Therefore, we conclude that C3NeF exhibits a heterogeneity which is very important in relation to the pathogenesis of MPGN.

Complement C3 Nephritic Factor↗

Lipoprotein(a) levels in the nephrotic syndrome.

We investigated serum lipoprotein(a) [Lp(a)] levels in 20 patients with the nephrotic syndrome. Lp(a) levels in the nephrotic syndrome patients were significantly higher than those in a control group (30.4 +/- 22.5 vs 10.4 +/- 17.7 mg/dl). Overall, the serum Lp(a) and lipid levels showed no relationship, but on an individual basis the serum Lp(a) level varied with the serum levels of total cholesterol and low density lipoprotein cholesterol in the nephrotic syndrome patients. Our findings suggest that a decrease in serum albumin led to increased hepatic Lp(a) synthesis. It is well known that thrombotic disease supervenes on hypercoagulability in the nephrotic syndrome, so the determination of Lp(a) levels in these patients may provide information which is useful for preventing thrombotic complications.

Adolescent↗

The effect of manidipine on renal hemodynamics in essential hypertensive patients: responses to acute stress.

The effects of the calcium antagonist manidipine 20 mg/day on changes in blood pressure and renal hemodynamics in response to acute stress by the mental arithmetic test (MAT) and the cold pressor test (CPT) were investigated in 14 patients with essential hypertension (median age: 50 +/- 2, WHO stage I-II). During the drug-free period, acute stress by both MAT and CPT caused an increase in the renal vascular resistance index (RVRI) [% change in RVRI, 17% for MAT (p < 0.05) and 26% for CPT (p < 0.01)] and an increase in blood pressure [% change in mean blood pressure (MBP): 17% for MAT (p < 0.001) and 16% for CPT (p < 0.001)]. CPT stress resulted in a reduction in RAFV (% change in RAFV: -12%, p < 0.05). Oral administration of manidipine resulted in hypotensive effects at rest [MBP: from 116 to 99 mmHg, p < 0.001], no change in RAFV (31.3 to 32.9 cm/sec, p = ns), and reduced RVRI (from 3.9 to 3.2 mmHg.sec/cm, p < 0.02). Manidipine inhibited the hypertensive response to acute stress by both MAT and CPT [% change in MBP: from 17% to 11% for MAT (p < 0.02) and from 16% to 11% for CPT (p < 0.01)] and also inhibited the increase in RVRI [% change in RVRI: from 17% to -1% for MAT (p < 0.05) and from 26% to 8% for CPT (p < 0.01)]. Manidipine has beneficial effects on blood pressure and renal hemodynamics at rest in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[A case of nonobstructive hypertrophic cardiomyopathy associated with ventricular tachycardia and sick sinus syndrome].

We examined, a 64 year old man with hypertrophic nonobstructive cardiomyopathy (HNCM) accompanied with dizziness. Twenty-four hour ECG monitoring showed sinus bradycardia and sinoatrial block. Electrophysiologic study demonstrated inducible sustained ventricular tachycardia (VT) by continuous rapid high right atrum pacing during which systolic blood pressure fell to 40 mmHg. Induced VT degenerated into ventricular fibrillation in ten seconds. We implanted a DDD pacemaker for sick sinus syndrome (SSS) and administrated 90mg/day of diltiazem for VT. Treadmill exercise test was carried out while the patient was taking diltiazem and no arrhythmia was induced. This case of HNCM is rare in that he presented both sick sinus syndrome and sustained VT.

Aged↗

Complement receptors in atherosclerotic lesions.

Accumulation of cholesterol in the tunica intima of arteries is a feature of atherosclerotic development. Recently, the demonstration of oxidized LDL in atherosclerotic lesions considerably strengthened the possibility of its role in the atherogenesis in vivo. However, the mechanism of lipid accumulation in monocyte-derived macrophages has not yet been clarified. It has been reported that the complement system may be related to atherosclerosis. In this report, complement receptors in the atherosclerotic lesions obtained from autopsy sample were investigated. Initially C3b receptors were detected using sheep erythrocytes bearing human C3b (EAC1423b cells). EAC1423b cells adherent to only aortic sections showing intimal thickening, but not to intact artery. Second, immunostaining of consecutive aortic sections was performed. Apo B and C5b-9 complex were stained using the indirect immunoperoxidase method, and macrophage, C3b receptor (CR1) and C3bi receptor (CR3) were stained using monoclonal antibody in the alkaliphosphatase anti-alkaliphosphatase method. In the intact artery of 3 month old patient, antigen- specific staining were not observed. In intimal thickening and atheroma of older patients, consecutive sections suggested that complement receptor-expressing cells were macrophages. Staining for apo B antigen existed at extracellular site in the intima, and C5b-9 complex was observed in intima and partially in the media. The above data showed that macrophage complement receptors were expressed in the atherosclerotic lesions when the complement system was activated. We conclude that these data suggest that the complement system and complement receptors may be related to the uptake of LDL by macrophages.

Adolescent↗

[Property of electrocardiogram gated single photon emission tomography by 99mTc-methoxy isobutyl isonitrile].

99mTc-methoxy isobutyl isonitrile (MIBI) is a new developed myocardial perfusion imaging agent. Because this compound has higher photon energy than thallium (Tl), electrocardiogram gated single photon emission tomography (SPECT): end-diastolic (ED) and end-systolic (ES) short axis (SA) images could be taken. To investigate property of gated MIBI SPECT, MIBI myocardial scintigraphy, Tl scintigraphy (TMS) and analysis of left ventricular wall motion were performed in 6 patients with myocardial infarction. Left ventricle was divided into 8 segments. Perfusion defect (PD) was scored: "0" (normal), "1" (hypo-perfusion), "2" (defect). Wall motion abnormality (WMA) was also scored: "0" (normokinesis), "1" (hypo-kinesis), "2" (a-, dys-kinesis). Severity and extent of PD and WMA were calculated. Severity of WMA was 3.0 +/- 2.0 (M +/- SD), severity of PD was 3.3 +/- 1.7 in TMS, 3.7 +/- 1.3 in no-gated MIBI, 5.0 +/- 0.6 in ES-MIBI, 7.3 +/- 2.0 in ED-MIBI. Extent of WMA was 2.3 +/- 1.0. Extent of PD was 2.5 +/- 1.3 in TMS, 3.0 +/- 1.6 in no-gated MIBI, 3.5 +/- 0.8 in ES-MIBI, 4.8 +/- 1.0 in ED-MIBI. Compared with wall motion abnormality, severity and extent of PD in ED-MIBI was larger. From our data, it is concluded that perfusion defect in ED-MIBI was overestimated significantly. When we evaluate gated MIBI image, we must consider this property.

Aged↗

Chemical stimulation of the locus coeruleus: inhibitory effects on hemodynamics and renal sympathetic nerve activity.

We examined the role of the locus coeruleus (LC) in the regulation of the hemodynamics and sympathetic nerve activity in anesthetized rats. Unilateral microinjection into the LC of the excitatory amino acid, L-glutamate (Glu), elicited dose-dependent decreases in arterial pressure (AP) and heart rate (HR). The bradycardic response was partially attenuated after intravenous injection of atropine sulfate, but the greater part of this response still remained. Interruption of the ascending projections of the LC by midbrain transection did not affect the depressor and bradycardic responses elicited by chemical stimulation. The renal sympathetic nerve activity showed transient but strong inhibition with this stimulation. Cardiac output was measured using an electromagnetic flowmeter implanted in the ascending aorta. The stroke volume and total peripheral resistance (TPR) were calculated. Microinjection of Glu elicited a significant decrease in TPR and slight decreases in cardiac output and stroke volume. Microinjection of the inhibitory amino acid, gamma-aminobutyric acid (GABA), or the alpha 2-adrenergic agonist, clonidine, exerted no effect on AP and HR. The present results therefore suggest that: (1) the LC neurons have an inhibitory influence on the sympathetic nervous system, and stimulation of these neurons can elicit depressor and bradycardic responses; (2) the depressor response was produced predominantly as a result of a decrease in vascular resistance, rather than a decrease in cardiac output; (3) these inhibitory responses may be provided not via the ascending projections of the LC; and (4) the LC neurons do not have a tonic influence on the cardiovascular system.

Animals↗

2-Acetylfuran, a confounder in urinalysis for 2,5-hexanedione as an n-hexane exposure indicator.

The apparent amount of 2,5-hexanedione, a biomarker of n-hexane expsoure in occupational health, in the urine of both exposed and non-exposed subjects varied not only as a function of the pH at which the urine sample was hydrolyzed but also depending on the capillary column used for gas chromatographic (GC) analysis of the urinary hydrolyzates after extraction with dichloromethane. The formation of a compound, identified by gas chromatography-mass spectrometry (GC-MS) as 2-acetylfuran, following acid hydrolysis was a major cause of confounding effects. This compound was hardly separated from 2.5-hexanedione on a capillary column such as DB-WAX, whereas separation could be achieved on a DB-1 capillary column. 2-Acetylfuran was formed when a urine sample was heated at a pH of less than 2 for hydrolysis, and the amount detected in urine did not differ between exposed and non-exposed subjects, indicating that the formation of 2-acetylfuran is independent of n-hexane exposure. When urinary hydrolysis is used, hydrolysis at a pH of less than 0.5, extraction with dichloromethane, and GC analysis on a non-polar capillary column are proposed to be the best analytical conditions for 2,5-hexanedione analysis in biological monitoring of exposure to n-hexane.

Confounding Factors, Epidemiologic↗

Methanol in urine as a biological indicator of occupational exposure to methanol vapor.

The exposure-excretion relationship and possible health effects of exposure to methanol vapor were studied in 33 exposed workers during the second half of 2 working weeks. Urinary methanol concentrations were also determined in 91 nonexposed subjects. The geometric mean value for methanol in urine samples from the latter was less than 2 mg/l (95% upper limit of normal, less than 5 mg/l) when log-normal distribution was assumed. Among the exposed workers, the methanol level in urine samples collected prior to the work shift exceeded the 95% upper limit of normal. The time-weighted average intensity of exposure to methanol vapor was measured using personal sampling devices (in which water severed as an absorbent) in 48 cases of methanol exposure (i.e., 2 of the 33 exposed workers failed to provide urine samples, whereas 17 subjects were examined twice). Methanol concentrations in urine were determined in samples collected at the end of the shift from the 48 exposed cases as well as from 30 nonexposed controls. There was a significant correlation between the exposure to methanol vapor at concentrations of up to 5,500 ppm and the levels of methanol measured in the shift-end urine samples. The calculation indicated that a mean level of 42 mg methanol/l urine (95% confidence range, 26-60 mg/kg) was excreted in the shift-end urine sample following 8 h exposure to methanol at 200 ppm (the current occupational exposure limit). Dimmed vision and nasal irritation were among the most frequent symptoms complained during work. Three cases showing clinical signs of borderline significance were identified.

Adult↗

Dose-dependent increase in 2,5-hexanedione in the urine of workers exposed to n-hexane.

The concentrations of 2,5-hexanedione (2,5-HD), an n-hexane metabolite, and 2-acetylfuran (2-AF) were measured in urine samples from 123 workers who had predominantly been exposed to n-hexane vapor and 53 workers who had experienced no exposure to solvents. The time-weighted average intensity of exposure to n-hexane vapor was determined by a diffusive sampling method. For biological monitoring of exposure, urine samples were collected late in the afternoon during the second half of a working week and were analyzed in the presence and absence of acid hydrolysis (at pH less than 0.5) for 2,5-HD and 2-AF by gas chromatography on a nonpolar capillary DB-1 column. The urinary 2,5-HD concentration increased as a linear function of the intensity of exposure to n-hexane, showing a correlation coefficient of 0.64-0.77 after acid hydrolysis and that of 0.73-0.83 in the absence of hydrolysis, depending on the correction for urinary density (P less than 0.01 in all cases, with no improvement in the coefficient occurring after the corrections). In contrast, 2-AF levels were independent of n-hexane exposure. The geometric mean 2,5-HD concentration in urine samples from 53 nonexposed men was 0.26 mg/l as observed (i.e., with no correction), 0.19 mg/l after correction for a urinary specific gravity of 1.016, and 0.23 mg/g creatinine after correction for creatinine concentration, and the geometric standard deviation was approximately 2.

Chromatography, Gas↗

Urinary methylhippuric acid isomer levels after occupational exposure to a xylene mixture.

The quantitative relationship between exposure to xylene vapor and urinary excretion of methylhippuric acid (MHA) isomers were studied in the second half of a working week. The participants in the study were 121 male workers engaged in dip-coating of metal parts who were predominantly exposed to three xylene isomers. The intensity of exposure measured by diffusive sampling during an 8-h shift was such that the geometric mean vapor concentration was 3.8 ppm for xylenes (0.8 ppm for o-xylene, 2.1 ppm for m-xylene, and 0.9 ppm for p-xylene), 0.8 ppm for toluene, and 0.9 ppm for ethylbenzene. Urine samples were collected at the end of the shift and analyzed for metabolities by HPLC. The statistical analysis showed that there is a linear relationship between the intensity of exposure to xylenes and the concentration of MHA in urine, that the regression line passes very close to the origin, and that the increment in observed (i.e., noncorrected) MHA concentrations as a function of increasing xylene concentration was 17.8 mg x l-1 ppm-1. Further examination on the basis on individual xylene isomers showed that the slopes of the regression lines for o- and m-isomers were similar (i.e., 17.1 and 16.6 mg l-1 ppm-1, respectively), whereas that for p-xylene was larger (21.3 mg l-1 ppm-1).

Air Pollutants, Occupational↗

The microvasculature of the 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumour. I. Vascular patterns as visualized by scanning electron microscopy of corrosion casts.

We examined the microvasculature of the 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumour by scanning electron microscopy of corrosion casts. An elaborate vascular envelope predominantly consisting of sinusoidal and venular vessels was formed around each tumour nodule. These vessels exhibited various abnormal features, whereas arterioles appeared normal. The abnormal vessels possessed many globular outpouches, possibly representing the site of angiogenesis. An additional capillary layer was seen in the marginal boundary between the tumour and host tissue. The lack of centrifugally extruding vessels in this layer may indicate a poor potency for vascular spread of tumour cells into the adjacent normal tissue. Loop-like or glomerular ingrowths were frequently found on the inner aspect of the vascular capsule, which eventually developed into a dense intranodular plexus. Intranodular vessels often showed focal narrowing, tapering and/or rupturing, possibly due to increased tissue pressure caused by proliferating tumour cells. Those surrounding necrotic portions were extremely dilated with occasional periodic varicosities. The features may be associated with the lessening of the tissue pressure resulting from tumour cell collapse.

9,10-Dimethyl-1,2-benzanthracene↗