Research on the correlation between activating transcription factor 3 expression in the human coronary artery and atherosclerotic plaque stability.

BACKGROUND: Activating transcription factor 3 (ATF3) is an early response gene that is activated in response to atherosclerotic stimulation and may be an important factor in inhibiting the progression of atherosclerosis. In this study, we directly measured the expression of ATF3 and inflammatory factors in human coronary atherosclerotic plaques to examine the relationship between ATF3 expression, inflammation and structural stability in human coronary atherosclerotic plaques. METHODS: A total of 68 coronary artery specimens were collected from the autopsy group, including 36 cases of sudden death from coronary heart disease (SCD group) and 32 cases of acute death caused by mechanical injury with coronary atherosclerosis (CHD group). Twenty-two patients who had no coronary heart disease were collected as the control group (Con group). The histological structure of the coronary artery was observed under a light microscope after routine HE staining, and the intimal and lesion thicknesses, thickness of the fibrous cap, thickness of necrosis core, degree of lumen stenosis were assessed by image analysis software. Western blotting and immunohistochemistry were used to measure the expression and distribution of ATF3, inflammatory factors (CD45, IL-1ß, TNF-α) and matrix metalloproteinase-9 (MMP-9) and vascular cell adhesion molecule 1 (VCAM1) in the coronary artery. The Pearson correlation coefficient was used to analyse the correlation between ATF3 protein expression and inflammatory factors and between ATF3 protein expression and structure-related indexes in the lesion group. RESULTS: Compared with those in the control group, the intima and necrotic core in the coronary artery were thickened, the fibrous cap became thin and the degree of vascular stenosis was increased in the lesion group, while the intima and necrotic core became thicker and the fibrous cap became thinner in the SCD group than in the CHD group (P < 0.05). There was no or low expression of ATF3, inflammatory factors, VCAM1 and MMP-9 in the control group, and the expression of inflammatory factors, VCAM1 and MMP-9 in the SCD group was higher than that in CHD group, while the expression of ATF3 in the SCD group was significantly lower than that in CHD group (P < 0.05). In the lesion group, the expression of ATF3 was negatively correlated with intimal and necrotic focus thickness, positively correlated with fibrous cap thickness (P < 0.01), and negatively correlated with inflammatory factors, VCAM1 and MMP-9 (P < 0.01). CONCLUSIONS: The expression of ATF3 may be related to the progression and stability of atherosclerotic plaques, and may affect the structural stability of atherosclerotic plaques by regulating the inflammatory response, thus participating in the regulation of atherosclerotic progression.

Age-Related Changes of Material Mechanics and Bone Material Parameters of Rat Skulls.

ABSTRACT: Objective To study the relationship between material mechanics and bone material parameters of rat skulls and their correlation with age by examination of the parameters. Methods Forty-eight healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52 and 104 week groups according to their age. Each group had six rats. The right cranium was compressed by KD Ⅱ-0.2 microcomputer controlled electronic universal testing machine, and material mechanics parameters （ultimate load, compression strength and compression modulus） were measured, then the skull slices were cut off and scanned by Micro-CT system to detect bone material parameters （skull thickness, bone mineral density, bone volume, and trabecular thickness）. Results The differences in ultimate load, compression strength and compression modulus among all groups had statistical significance （P<0.05）, and were positively correlated with age within 26 weeks （P<0.05）. The differences in skull thickness, bone mineral density, bone volume and trabecular thickness among all groups had statistical significance （P<0.05）, and were positively correlated with age within 52 weeks （P<0.05）. All material mechanics parameters were positively correlated with bone material parameters （P<0.05）. Conclusion There is a positive correlation between bone material parameters （skull thickness, bone mineral density, bone volume, trabecular thickness）, material mechanics parameter （skull ultimate load, compression strength, compression modulus） and age in a certain range, which can be used to infer age.

Application of Sequential Changes of Dural Thickness and Biomechanical Parameters in Postmortem Interval Estimation.

ABSTRACT: Objective To study the relations of the dural thickness and the biomechanical parameters with postmortem interval （PMI） of human cadavers, and to explore the feasibility of the two indexes used for PMI estimation. Methods Dural samples were collected at different postmortem intervals of 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 48 h, 60 h, 72 h, 84 h and 96 h, then fabricated into 4.0 cm×1.0 cm A and B test specimens. The thickness of the A test specimen was measured, and the biomechanical parameters, such as ultimate load, maximum force deformation, tensile strength, elastic modulus and fracture force, were measured. The regression equations of thickness, biomechanical parameters and PMI were fitted respectively, and the difference between the predicted value and actual measured value of PMI was verified by the verification group. The B test specimen was fixed with 10% neutral formaldehyde solution, then tissue sections were prepared to observe its morphological changes. Results From 6 h to 96 h after death, the dural thickness decreased gradually, the collagen fibers gradually changed from clear arrangement to mutual fusion, and the number of nuclei decreased gradually. The dural thickness, ultimate load, tensile strength, elastic modulus and fracture force decreased sequentially, among which the dural thickness, ultimate load, elastic modulus and fracture force had a correlation with PMI （P<0.05）. In the return test, the difference between the predicted value and actual measured value of PMI in the verification group had no statistical significance （P>0.05）. Conclusion The dural thickness, ultimate load, elastic modulus and fracture force change sequentially from 6 h to 96 h after death. The regression equation established by the relationship between the changes and PMI can be used for PMI estimation.

Apparent diffusion coefficient in differentiation between malignant and benign breast masses: does size matter?

AIM: To determine whether lesion size affects the diagnostic performance of apparent diffusion coefficient (ADC) in the evaluation of breast masses. MATERIALS AND METHODS: Consecutive breast lesions detected at magnetic resonance imaging (MRI) from June 2010 to July 2013 were retrospectively reviewed. Differences in the ADCs of benign and malignant mass lesions were compared. Receiver operating characteristics analysis was performed to evaluate diagnostic performance of ADC regarding lesion size (≤ 1 cm or >1 cm) and their T2W signal intensities. RESULTS: Seventy-four malignant lesions (77.9%) and 21 (22.1%) benign lesions were included. Twenty-two of the 95 (23.2%) masses measured ≤ 1 cm (mean 0.73 ± 0.4; range 0.51-0.8 cm) and 73/95 (76.9%) masses measured >1 cm (mean 2.11 ± 0.1; range 1.1-3.3 cm). The mean ADC was significantly lower for malignant than for benign lesions (mean for malignant lesion, 0.89 ± 0.29 × 10(-3) mm(2)/s; mean for benign lesions, 1.27 ± 0.42 × 10(-3) mm(2)/s; p<0.01). The optimal ADC cut-off for differentiating benign and malignant lesion was 1.088 × 10(-3) mm(2)/s with a sensitivity of 85.9% and specificity of 77% for lesions >1 cm. The sensitivity and specificity were lowered to 60% and 50%, respectively, for lesions of size ≤ 1. Maximal sensitivity and specificity were reached when the ADC value was used to evaluate T2-dark lesions. CONCLUSION: Diffusion-weighted MRI is useful for characterizing masses that are hypointense on T2-weighted images. Lower sensitivity and specificity were found for breast lesions ≤ 1 cm.

Deoxycytidine kinase and cytosine nucleoside deaminase activities in synchronized cultures of normal rat kidney cells.

Previous work has suggested that 1-beta-D-arabinofuranosylcytosine 5'-triphosphate is the active metabolite of 1-beta-D-arabinofuranosylcytosine. The amount of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate formed in tissues has been shown to be influenced by the relative levels of deoxycytidine kinase and cytosine deaminase. In this study we have measured the intracellular levels of deoxycytidine kinase and cytosine deaminase activities in synchronized cultures of normal rat kidney cells. The deoxycytidine kinase activity was found to be cell cycle related with a minor peak of activity in early G1 phase and a major peak of activity in middle and late S phase. The cytosine deaminase activity was also found to be cycle dependent with a peak of activity at G1 phase and another at S phase of the cell cycle. Similar results were obtained when cytosine deaminase activities were measured with cytidine, deoxycytidine, or 1-beta-D-arabinofuranosylcytosine as substrate. Present studies also confirmed earlier studies by other workers that the main effect of 1-beta-D-arabinofuranosylcytosine is in the late S phase of the cell cycle.

Effect of tetrahydrouridine on the action of 1-beta-D-arabinofuranosylcytosine in synchronized cultures of normal rat kidney cells.

Tetrahydrouridine (THU) is a reduced pyrimidine nucleoside and has been found to be a potent cytidine deaminase inhibitor. We have examined the effect of THU on the action of 1-beta-D-arabinofuranosylcytosine (ara-C) on DNA synthesis and its cytotoxic effect on normal rat kidney (NRK) cells. The results indicated that THU, when present alone, has no effect on the DNA synthesis or viability of the NRK cells. The addition of THU can, however, further increase the cytotoxic effect of sublethal doses of ara-C and can enhance its ability to inhibit DNA synthesis. Studies on the duration of exposure of the NRK cells to ara-C and on the effect of ara-C on synchronized cultures of NRK cells also support the earlier reports that ara C, through its active compound 1-beta-D-arabinofuranosylcytosine 5'-triphosphate, is capable of blocking cells from progression from G1 into S phase of the cell cycle. Furthermore, we have shown that this inhibition is reversible after the drug has been removed. The addition of THU in the presence of noninhibiting levels of ara-C can also result in the blocking of cells from progression into S phase of the cell cycle. Similar to the effect of ara-C, this inhibition is also reversible. These studies suggest that the addition of THU enhances the cytotoxicity of sublethal doses of ara-C and its ability to inhibit DNA synthesis.

Different epidermal growth factor growth responses and receptor levels in human colon carcinoma cell lines.

The growth response to epidermal growth factor (EGF) and the numbers and types of EGF receptors were studied in three human colon tumor cell lines from each of two groups of cell lines that differ markedly in their growth properties and extent of differentiation. Aggressively growing and poorly differentiated colon cells (group I) did not respond to EGF alone, while less aggressively growing and more differentiated cells (group III) responded with increased growth when EGF was added to their chemically defined, serum-free medium. The average number of EGF receptors (EGF-R) measured at the surface of group III cell lines by radioligand binding assays, was eight-fold higher than that measured for group I cell lines. These observations provide evidence for possible autocrine mechanisms that maintain available EGF-R levels in more differentiated group III colon tumor cells and down-regulate EGF-R levels in group I colon tumor cells.

Transferrin and insulin enhance human colon tumor cell growth by differentiation class specific mechanisms.

Human colon tumor cell lines that were adapted to grow in chemically defined medium were tested for their growth sensitivity to exogenous transferrin, insulin, and epidermal growth factor (EGF). Less differentiated cell lines, C and HCT116, were able to grow in the presence of a single peptide supplement, to respond synergistically to transferrin and insulin in combination, and to be insensitive to supplementation with exogenous EGF. The more differentiated cell lines, CBS and GEO, were found to respond to exogenous EGF in a concentration-dependent manner, to require at least two peptide factor supplements to support growth, and to respond synergistically when EGF was added to chemically defined medium that already contained transferrin and insulin. To investigate whether changes in the number or the affinity-classes of the EGF-receptor might be involved in any of these growth responses, changes in EGF-receptor number and dissociation constant were determined as a function of cell growth condition. The poorly differentiated HCT cell line HCT116 was found to undergo 28 to 64% increases in [125I]EGF-binding when its medium was supplemented with transferrin, insulin, or transferrin plus insulin. The more differentiated CBS cell line responded to all peptide supplements with decreases in [125I]EGF-binding ranging from 12 to 73%. These findings indicate that the actions of transferrin and insulin are fundamental to the growth regulatory mechanisms of these two differentiation classes of human colon tumor cell lines, but that their mechanisms are different.

The residual effect of chronic neuroleptic treatment on the neuroleptic binding assay in rats.

Chronic chlorpromazine administration to rats (25 mg/Kg/day) for 30 days followed by a washout period of 10 days resulted in an increase in both the measured maximum number of binding sites, Bmax, and the apparent dissociation constant, Kd, for the binding of 3H-spiroperidol to neural membranes of the brain. When membrane suspensions were progressively diluted before the binding assay, it was found that the apparent Bmax did not change with dilution, remaining higher in membranes of chlorpromazine-treated rats than in controls. The apparent increase in Kd, on the other hand, was found to be an artifact of the assay. Thus extrapolation of the measured or apparent Kd value to infinite dilution resulted in identical value for Kd regardless of the treatment.

Fetal loss from umbilical cord abnormalities--a difficult case for prevention.

The summaries of 12 pregnancies in which fetal distress and death were thought to be the result of umbilical cord abnormalities are presented. These included six cases of stricture and torsion of the cord, one case of umbilical vein aneurysm, one case of perivascular haemorrhage near the fetal end of the cord, one case of umbilical vein thrombosis, two cases of true knot of the cord and one case of very short cord. The perinatal mortality was 75% in the whole group (9 out of 12 fetuses), there being eight stillbirths and one neonatal death. Of the 12 fetuses, only three were small for dates at delivery. Nine patients volunteered the history of a decrease in fetal movements, and non-stress cardiotocography (NST) was abnormal in eight patients. It was noted, however, that fetal death tended to occur rapidly after an abnormal test. Observations in our series indicated that antepartum fetal deaths due to umbilical cord abnormalities are still difficult to prevent, as it is often impossible to detect fetal distress in time for appropriate intervention. Prompt action to deliver the baby after an abnormal NST appears to be a necessary step to prevent antepartum deaths due to such causes.

[Stereological studies on the brain development of fetuses in cretinism endemic region after supplement of iodized salt for 10 years].

Epidemiologic reports indicated that in the cretinism endemic regions the incidence of cretinism decreased obviously after supplement of iodized salt but there still existed many cretinoid cases accompanied with mild impairment of intelligence and retardation of somatic development. This suggests that some factors other than iodine deficiency might also play an important role in the pathogenesis of cretinism. 21 brains of therapeutically aborted fetuses from cretinism endemic region after a supplement of iodized salt for ten years were studied under both light and electron microscopes. Serum T3, T4 and TSH of the fetuses and their mothers were coincidentally assayed. The brain development of fetuses from the endemic region was noticed to be still retarded as compared with those from the non-endemic region, despite that the serum hormones of the fetuses and their mothers in the endemic region showed no more significant difference from those in the non-endemic region. The retardation of the brain development could be evidenced by the increase of cellular density, decrease of the average volume of neurocytes, increase of the volume ratio between nucleus and cytoplasma per neuron, as well as decrease in number and average surface area of the mitochondria, and all of these were obtained in the cerebral cortex, hippocampus and the layer of Purkinje's cells of the cerebellum.

Inhibition of murine sarcoma virus-induced foci formation by cytidine analogues and other drugs chemotherapeutically effective in human malignancies.

The present report describes an in vitro culture system using the Kirsten murine sarcoma virus transformation focus assay to evaluate the antiviral activities of 12 commonly used chemotherapeutically effective drugs. Since these drugs are cytotoxic, the plating efficiencies of the cells treated were monitored simultaneously. Using this procedure, Adriamycin, Daunorubicin, Bleomycin Camptothecin, Mithramycin, hydroxyurea, 5-fluorouracil, thioguanine, 9-beta-D-arabinofuranosyladenine, 1-beta-D-arabinofuranosylcytosine (ara-C), azacytidine and cyclocytidine were tested. Of all these compounds tested only the cytidine analogues - cyclocytidine, ara-C and, to a lesser extent, azacytidine - showed selective effect on inhibition of viral foci over cytotoxicity. Studies on the duration of exposure to ara-C indicated that an exposure time of 10-30 h produced the most pronounced effect on the inhibition of foci formation over that of cytotoxicity.

Atropisomerism of the C-1-C'-1 axis of 2,2',8,8'-unsubstituted 1,1'-binaphthyl derivatives.

The Suzuki coupling of optically active (S)-binaphthyl bromide 10 with (S)-binaphthyl boronic acid 11 produced a diastereomeric mixture of tetrahydroxyquaternaphthyls 4. The coupling products 4as well as their derivatives 5-7 can be considered as members of the family of 1,1'-binaphthyl-3,3'-diols. The C-1-C'-1 axis of all these compounds was found to have an unusually high rotational barrier. Generally, the barrier is higher for derivatives having more bulky substituents at the 3 and 3' positions.

Pregnancy hydronephrosis--a longitudinal ultrasonic evaluation.

The progression of physiological hydronephrosis through the 3 trimesters of pregnancy was assessed by ultrasonic measurement of calyceal diameters in 56 asymptomatic patients in a longitudinal study. A grading system basing on the maximum calyceal diameter was used; 89% of the patients showed at least mild dilatation before delivery. There was a preponderance of the right side being affected. In 6 patients (10.7%), severe dilatation was demonstrable and in all of them its onset appeared to be in the second trimester. The likelihood of progression to moderate or severe dilatation when only mild dilatation is demonstrated in the second trimester is low. Furthermore, it is not common for moderate dilatation in the second trimester to progress to severe dilatation in the third trimester. These findings appear to support the mechanical theory in the genesis of pregnancy hydronephrosis. Rapid regression of calyceal dilatation is not apparent in the first 5 days after delivery.

Computer-assisted evaluation of ultrasonic fetal weight prediction using multiple regression equations with and without the fetal femur length.

Ultrasonic fetal femur length (FL) measurement provides an accurate fetal length. Combined with cross-sectional dimensions such as the biparietal diameter (BPD) and abdominal circumference (AC), FL provides a three-dimensional profile of the fetus. The usefulness of incorporating FL measurements into weight-predicting regression equations containing the BPD and AC was assessed. Multiple regression equations containing these three parameters as a function of log10 birthweight were constructed from data obtained from 125 patients within 48 hours of delivery. The mean errors in fetal weight prediction derived from five of these equations were assessed in another 92 patients. The coefficients of multiple correlation were marginally better in those equations that contained FL. The mean differences were also slightly lower with these equations compared with those that did not contain FL. However, the mean differences derived from all the equations were not significantly different from each other (P greater than 0.05). Therefore, despite theoretical considerations, the results from this study do not justify the routine clinical use of these new equations containing FL to estimate intrauterine fetal weight, in replacement of existing charts based on BPD and AC.

Simple ultrasonic diagnosis of osteogenesis imperfecta type II in early second trimester.

Osteogenesis imperfecta (OI) Type II was diagnosed accurately in an at-risk fetus at 16 weeks gestation by real-time sonography. The most important findings were shortening, deformity and possibly fracture in the long bones particularly the femurs. Ultrasonic visualization of these signs in a fetus at risk will provide direct evidence in the diagnosis of OI Type II and any additional investigations are not indicated.

Transcutaneous bilirubinometer: its use in Chinese term infants and the effect of haematocrit and phototherapy on the TcB index.

The application of the transcutaneous bilirubinometer in screening for neonatal jaundice was evaluated in 259 full-term Chinese infants: 202 who had not received any treatment and 57 who were receiving phototherapy. The transcutaneous bilirubin index correlated well with the serum bilirubin level (SB) of the untreated infants and the coefficient of correlation was slightly higher for TcB readings obtained over the mid-sternal area (r = 0.91; P less than 0.001) than those over the forehead (r = 0.85; P less than 0.001). Transcutaneous bilirubinometry was unreliable in predicting the SB level in infants receiving phototherapy even if the SB readings were obtained over shaded skin. The haematocrit of the infants, though having a statistically significant effect on the TcB index, contributed only minimally to the regression line and correlation coefficient between the TcB index and SB level.

Abdominal circumference vs abdominal area--which is better?

The efficacies of ultrasonic abdominal circumference (AC) and abdominal area (AA) measurements in the evaluation of intrauterine fetal growth were compared. The intraobserver random and technical errors were found to be significantly higher with AA measurements. The correlation with intrauterine fetal weight was observed to be better with AC as compared with AA measurements, the fetal weights being expressed as either linear regressions or multiple regressions involving the two parameters. Between 32 and 38 weeks, a single AC measurement detects 74 per cent of small-for-date fetuses, while a single AA measurement detects only 58 per cent of such fetuses. The false-positive rates were similar for the two parameters. It is concluded that AA measurements are no more useful than AC measurements in the routine assessment of intrauterine fetal growth.

Is fetal femur length a better indicator of gestational age in the growth-retarded fetus as compared with biparietal diameter?

The accuracy of gestational age prediction in 30 growth-retarded fetuses as derived from the fetal femur length (FL) was compared with that derived from the biparietal diameter (BPD). The mean difference between the actual and predicted gestational age was smaller when FL was used, but the difference did not reach statistical significance when compared with that associated with the use of the BPD. No consistent pattern of head/limb growth retardation was obvious. The femur length and BPD were both reduced in varying proportions in the growth-retarded fetuses. The significance of such findings in the assessment of intrauterine growth retardation is discussed.

Zinc deficiency is not a cause for abortion, congenital abnormality and small-for-gestational age infant in Chinese women.

Zinc concentration in serum and hair was measured in a cross-sectional study of 437 Chinese women of whom 310 were normal controls studied at various stages of pregnancy and up to 12 months after delivery. The rest had spontaneous abortions, fetuses with a birthweight below the 10th centile for gestation or congenital abnormalities. Zinc concentration fell throughout normal pregnancy, the fall being greater in serum than in hair. There was no correlation between serum and hair levels. The infant birthweight had a positive correlation with serum level but a negative correlation with hair level. Abortion, low birthweight and congenital abnormality were not associated with low concentrations of zinc in plasma or hair.