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Biomedical subjects

L Miao

Publications and source records attributed to L Miao.

At least 55 records · Page 3Linked to original sources

[Epidemiological studies on 321 children with congenital diaphragmatic hernia in China].

Perinatal babies delivered in hospitals with gestation of 28 weeks to seven days after birth were monitored by National Birth Defects Monitoring Network from September 1986 to December 1993 to study the prevalence of congenital diaphragmatic hernia in China and the risk factors contributing to their prognosis. Results showed that 321 cases of congenital diaphragmatic hernia in 4,777,220 perinatal babies were detected with an incidence of 0.7 per ten thousand, a case-fatality ratio of 84.1 percent and, fetal death and stillbirth accounting for 28.1 percent of the total perinatal deaths. There was significant difference in birth weight between perinatal deaths and survival perinatal. And, 54.4 percent of the cases complicated with other congenital deformities and severe deformities in heart, lung and central nervous system accounted for the most proportion of them, which were the most important factors contributing to death. A case-fatality ratio of cases with single malformation was 74.7 percent and that of those with multiple malformation 92 percent, with a statistically significant difference. The cases diagnosed antenatally accounted for 11.3 percent of the total, and multiple malformation accounted for a large proportion of them. It indicated that proportion of antenatal diagnosis for congenital diaphragmatic hernia deformity was lower, and their perinatal case-fatality ratio was higher and their prognosis worse.

Abnormalities, Multiple↗

[Experimental study of coral implantation in repair of skull bone defect in rabbit: histomorphometry of bone].

In order to evaluate coral as a bone graft substitute in repair of bone defect, particulates of coral were implanted into skull bone defect of rabbit, 1.5 cm in diameter. Hydroxyapatite and blank were taken as controls. The rabbits were sacrificed at the second, fourth, eighth and twelveth weeks after the operation. The specimens were taken and performed histological examination and histomorphometry observation. Results were as follows: at the second week many multinucleus giant cells infiltrated. As time elapsed, the coral were progressively degenerated and new bone was formed to fill the defect. Up to the twelveth week, the coral degenerated completely and new bone formed in the center of the defect. Percentage of new bone was in defect was 36.9%. Compared with the controls, there were significant differences (P < 0.01). It was suggested that coral had good osteoconductility. Howevel, coral underwent rapid degeneration, it might result in inconplete repair of bone defect.

Animals↗

Model of a sub-main transition in phospholipid bilayers.

A recently discovered submain phase transition in multi-lamellar bilayers of long-chain saturated diacyl phosphatidylcholines (Jørgensen, K. (1995) Biochim. Biophys. Acta 1240, 111-114) is discussed in terms of a theoretical molecular interaction model using computer simulation techniques. The model interprets the transition to be due to a decoupling of the acyl-chain melting from the melting of the pseudo-two-dimensional crystalline lattice of the P beta' phase. A two-stage melting process is predicted by the calculations suggesting that the sub-main transition involves a lattice melting whereas the acyl-chain melting takes place at a higher temperature at the main transition. The calculated heat contents of the two transitions as well as the chain-length dependence compare favorably with experimental data for multi-lamellar phosphatidylcholine lipid bilayers.

Calorimetry↗

Common sequence variants of lipoprotein lipase: standardized studies of in vitro expression and catalytic function.

We have assessed the functional activity of three common sequence variants of human lipoprotein lipase (LPL). Two of these, Asn291Ser and Asp9Asn arise from missense mutations while the third, Ser447Ter, derives from a nonsense mutation, truncating LPL by two residues. As previous in vitro studies have produced conflicting results, we have re-analyzed the catalytic function of these variants using the COS cell transfection system, under optimized and standardized experimental protocols. We found the Asn291Ser variant to manifest with a decrease in catalytic activity (57% of normal) due to a reduction in secretion and stability of the active homodimeric form. The Asp9Asn variant also showed a significant decrease in catalytic activity (85% of normal), but this was found to be due to a decreased rate of secretion only, as the homodimeric form was stable. The findings for these mutants contrasted with those of the Ser447Ter truncation variant which proved to be catalytically normal; this variant also manifested normal homodimer stability. The truncated variant did however, present with a higher total secreted mass level (131%) than control LPL. This was most likely due to enhanced secretion of the monomeric form. None of these mutations exhibited defects in binding affinity to cell surface proteoglycans. Each of these variants deviated significantly from normal as regards to their secreted activity or mass levels in the COS cell transfection system.

Catalysis↗

Effects of formic acid hydrolysis on the quantitative analysis of radiation-induced DNA base damage products assayed by gas chromatography/mass spectrometry.

Gas chromatography/mass spectrometry (GC/MS-SIM) is an excellent technique for performing both qualitative and quantitative analysis of DNA base damage products that are formed by exposure to ionizing radiation or by the interaction of intracellular DNA with activated oxygen species. This technique commonly uses a hot formic acid hydrolysis step to degrade the DNA to individual free bases. However, due to the harsh nature of this degradation procedure, the quantitation of DNA base damage products may be adversely affected. Consequently, we examined the effects of various formic acid hydrolysis procedures on the quantitation of a number of DNA base damage products and identified several factors that can influence this quantitation. These factors included (1) the inherent acid stabilities of both the lesions and the internal standards; (2) the hydrolysis temperature; (3) the source and grade of the formic acid; and (4) the sample mass during hydrolysis. Our data also suggested that the N,O-bis (trimethylsilyl)trifluoroacetamide (BSTFA) derivatization efficiency can be adversely affected, presumably by trace contaminants either in the formic acid or from the acid activated surface of the glass derivatization vials. Where adverse effects were noted, modifications were explored in an attempt to improve the quantitation of these DNA lesions. Although experimental steps could be taken to minimize the influence of these factors on the quantitation of some base damage products, no single procedure solved the quantitation problem for all base lesions. However, a significant improvement in the quantitation was achieved if the relative molecular response factor (RMRF) values for these lesions were generated with authentic DNA base damage products that had been treated exactly like the experimental samples.

DNA Damage↗

Increased renal tubular expression of transforming growth factor beta in human allografts correlates with cyclosporine toxicity.

Cyclosporine A (CsA) is a potent immunosuppressive drug that inhibits the transcription of several proinflammatory cytokines including interleukin-2. In contrast, CsA stimulates transcription of the pleuripotent cytokine, transforming growth factor-beta (TGF beta). Since the effect of CsA in transplant recipients is unpredictable, we examined whether tissue levels of TGF beta protein in renal allografts correlate with in vivo CsA responsiveness. Intra-allograft TGF beta protein content was assessed in renal biopsies by immunohistochemical means using the mouse anti-TGF beta monoclonal antibody (Mab), 1D11. We studied 68 specimens: 21 with acute CsA toxicity (ACT), 11 with acute tubular necrosis (ATN) and 36 with acute cellular rejection (ACR). Intensity of TGF beta immunostaining was evaluated in a blinded fashion using a scale from 0 to 3+. In biopsies with histological evidence of CsA toxicity, 77% demonstrated intense (2 to 3+) TGF beta immunostaining. TGF beta protein was detected in both proximal and distal tubules but was either absent or present in low levels within glomeruli and interstitium. In contrast, only one of the 11 biopsies with ATN had minimal staining (1+) for TGF beta. The remaining 10 biopsies with ATN were negative for TGF beta immunostaining. In biopsies with ACR, the levels of renal TGF beta were more variable with 36% showing intense (2 to 3+) staining and 64% having minimal or no (0 to 1+) tubular TGF beta. Within the first 18 months post-transplantation, patients with intense TGF beta staining and ACR underwent an average of 4.1 +/- 1.8 allograft biopsies and suffered 33% graft losses. During the same period of time, the patients with ACR and absent or low (0 to 1+) TGF beta levels underwent only 2.1 +/- 1.2 biopsies, maintained better late renal function and suffered 4% graft losses. In conclusion, we demonstrate that TGF beta protein levels in renal allografts correlate with CsA effect and differentiate ACT from ATN. In CsA treated patients who develop ACR, TGF beta levels predict the subsequent clinical course and graft function. Therefore, evaluating tissue levels of TGF beta may offer unique diagnostic and prognostic benefits in the care of patients receiving CsA based immunosuppression.

Adult↗

Cocaine-induced microvascular vasoconstriction but differential systemic haemodynamic responses in Yucatan versus Yorkshire varieties of swine.

1. Systemic and coronary haemodynamics were measured in 6 Yorkshire swine and 6 Yucatan miniature swine under isoflurane anaesthesia to investigate the influence of cocaine following its intravenous administration at 1, 3 and 7 mg kg-1. 2. Cocaine in Yorkshire swine decreased mean arterial pressure and rate pressure product (systolic pressure x heart rate), suggesting a cardiac depressant effect, whereas cocaine in Yucatan miniature swine increased these parameters, consistent with a hyperadrenergic state. 3. Cocaine in both Yorkshire swine and Yucatan miniature swine decreased coronary blood flow and coronary flow reserve, and increased coronary vascular resistance. 4. A modest generalized epicardial coronary artery constriction was observed by angiography, without evidence of focal spasm. 5. Our results confirm a marked vasoconstrictor effect of cocaine on the coronary arterial circulation, predominantly distal to the epicardial coronary arteries, but also indicate important differences in the systemic cardiovascular responses to the drug between two closely related strains of animals within the same species. Due to the similarities between the swine and human coronary arterial vasculature, we suggest that vasoconstriction in the coronary microcirculation may produce cardiac toxicity in man.

Angiocardiography↗

Cholinergic stimulation modulates negative inotropic effect of cocaine on ferret ventricular myocardium.

We tested the hypothesis that the negative inotropic effect (NIE) of cocaine is mediated, at least in part, by cholinergic stimulation and can be correlated with the degree of adenosine 3',5'-cyclic monophosphate (cAMP) dependency of the inotropic state. Cardiac myocytes were isolated from left ventricles of ferrets and loaded with the fluorescent Ca2+ indicator indo 1. Cells were placed in physiological solution containing 2.0 mM Ca2+ and stimulated at 0.5 Hz and 30 degrees C. Cocaine decreased peak cell shortening and peak intracellular Ca2+ in a concentration-dependent manner (10(-8)-10(-4) M). The concentration-response curve of cocaine was shifted significantly downward compared with those of lidocaine and procaine in the same range of concentrations. Atropine (10(-6) M) shifted the concentration-response curve of cocaine, but not those of lidocaine and procaine, rightward, with a pA2 value (7.66) similar to that obtained with carbachol (7.99). With prior addition of isoproterenol (ISO, 10(-8) M) or increased Ca2+ (4.0 mM) to increase cell shortening to the same degree (approximately 60%), cocaine and carbachol decreased contractility to a significantly greater extent in ISO-stimulated myocytes. To clarify whether these treatments changed responsiveness of the contractile elements to Ca2+, the effect of 2,3-butanedione monoxime, an agent that interferes with the interaction of myosin and actin, was tested with previous addition of ISO or increased Ca2+, and no differential effect occurred. Therefore, we postulate that 1) the NIE of cocaine on myocytes is caused by decreased Ca2+ availability; 2) this effect is due to specific stimulation of cholinergic receptors in addition to other direct myocardial (probably local anesthetic) effects; and 3) the NIE correlates with the level of cAMP dependence of the inotropic state.

Animals↗

A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) results in altered postprandial chylomicron triglyceride and retinyl palmitate response in normolipidemic carriers.

An Asn291Ser mutation in exon 6 of the lipoprotein lipase gene (LPL) frequently occurs in Caucasians (2-4%) and results in a partial catalytic defect. Although this mutation may be associated with low HDL cholesterol and elevated triglyceride levels, some carriers are normolipidemic and may have LPL activity in the normal range in the fasting state. To assess in vivo the influence of dietary stress on the function of this mutation, we have performed oral fat load studies on three unrelated normolipidemic Asn291Ser carriers and compared these results to five healthy controls and to a subject with a clear 50% reduction in LPL activity compared with controls. The Asn291Ser carriers exhibited a more pronounced postprandial response compared with non-carriers as evidenced by higher chylomicron triglyceride (TG) and chylomicron retinyl palmitate peaks (P = 0.03 and P = 0.02, respectively). Significantly higher area under response curves were also seen for both chylomicron triglycerides (P = 0.02) and chylomicron retinyl palmitate (P = 0.01) when compared with non-carriers. These results provide further in vivo evidence for the functional effects of this common mutation despite normal fasting lipid levels. These data suggest that even though subjects with this mutation may be normolipidemic in the fasting state, environmental stress such as an oral fat load may unmask the catalytic defect and result in significant disturbances in postprandial chylomicron metabolism.

Adult↗

[Analysis of 106,272 cases of postterm pregnancy in China].

106272 cases of postterm pregnancy in 945 hospitals in China during the period from Oct. 1986 to Sept. 1987 were surveyed, the overall incidence rate was 85.48/1000. Provincially, the highest two rates were 127.36/1000 and 120.92/1000 in Jilin and Shandong provinces respectively, and the lowest two rates 53.98/1000 and 61.38/1000 in Xizang and Qinghai provinces respectively. The perinatal mortality was 27.90/1000 (corrected 12.49/1000). The incidence of macrosomia (89.50/1000) in postterm pregnancy was twice as much as that in term delivery. Postterm pregnancy was more frequent in pregnant women of 20-34 years old,and of 42 weeks' gestation. The incidence malformations in postterm pregnancy was 154.13 per ten thousand, in which the frequency of malformations associated with low birth weight was three times that associated with macrosomia.

Adult↗

[Analysis of 822 infants with limb reduction defect in China].

This work is aimed at the basic condition of infants with limb reduction defect (LRD) in China. 822 cases of LRD occurring among 1,243,284 live and stillbirths of 28 or more gestation weeks in China from Oct. 1986 to Sept. 1987 were analysed. The overall prevalence of LRD was 6.6 per 10,000 ranging from 14.4 per 10,000 to 3.6 per 10,000. No sex difference was observed. The prevalence of LRD in infants with low birthweight was significantly higher than that in infants with normal birthweight (P < 0.001). Also the prevalence of LRD in rural area was higher than that in urban area (P < 0.001). Four-limb involvement was most common. The cases with only upper limb involvement (278/451, 61.6%) were significantly more prevalent than those with only lower limb involvement (173/451, 38.4%, P < 0.001), but no difference was found between the left LRD and right LRD (P > 0.05), nor was a significant difference noted between single LRD and multiple LRD. 75.8% of the infants with LRD had defects in other systems.

Abnormalities, Multiple↗

Potent inhibition of viral fusion by the lipophosphoglycan of Leishmania donovani.

Lipophosphoglycan (LPG) is an amphiphile produced by Leishmania. Its chemical structure consists of a hydrophilic flexible polymer of repeating PO4-6Gal beta 1-4Man alpha 1 units (on average 16 units) linked via a hexasaccharide core to a lyso-1-O-alkyl-P1 membrane anchor. In the study of viral fusion we report in this paper, we have introduced LPG into human erythrocyte ghost (HEG) membranes, with the purpose of understanding how the LPG-induced surface-structural changes may modulate the interactions between a viral envelope and the HEG membranes. We have found that LPG, when incorporated at very low concentrations into intact human erythrocyte membranes, strongly inhibits Sendai virus-induced hemolysis. When incorporated into HEGs, it reduces the binding of both Sendai and influenza viruses to HEGs; furthermore, it strongly inhibits the overall viral fusion to HEGs, being among the most potent known inhibitors. We have also shown that LPG stabilizes the bilayer structure of phosphatidylethanolamine against the formation of an inverted-hexagonal structure. We suggest that LPG may give rise to an effective "steric repulsion" between the viral and HEG membranes, thereby modulating some specific modes of interaction between viral-target membranes in the overall fusion process; LPG may also modulate the bending rigidity and the spontaneous curvature of the HEG membrane in the direction of making the destabilization and rearrangement of the underlying lipid bilayer more difficult.

Animals↗

A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia.

We performed denaturing gradient gel electrophoresis (DGGE) of exons 4, 5, 6 and their exon-intron boundaries of the LPL-gene in 169 unrelated male patients suffering from familial combined hyperlipidemia (FCH). Twenty patients were found to carry a nucleotide substitution in exon 6. Sequence and PCR/digestion analysis revealed one common mutation (Asn291Ser) in all these cases. This mutation was talso present in 215 male controls, albeit at a lower frequency than in FCH patients (10/215 = 4.6% vs. 20/169 = 11.8%; p < 0.02). Analysis of lipid, lipoprotein and apolipoprotein levels demonstrated an association between the presence of this Asn291Ser substitution and decreased HDL-cholesterol (0.94 +/- 0.31 vs. 1.12 +/- 0.26 mmol/l; p < 0.04) in our controls. FCH patients carrying this mutation showed decreased HDL-cholesterol (0.75 +/- 0.16 vs. 0.95 +/- 0.36 mmol/l; p = 0.05) and increased triglyceride levels (5.96 +/- 4.12 vs. 3.48 +/- 1.78 mmol/l; p < 0.005) compared to non-carriers. The high triglyceride and low HDL-cholesterol phenotype in carriers of this substitution was most obvious when BMI exceeded 27 kg/m2. Our study of male FCH patients revealed the presence of a common mutation in the LPL-gene that is associated with lipoprotein abnormalities, indicating that defective LPL is at least one of the factors contributing to the FCH-phenotype.

Asparagine↗

[Analysis of factors contributing to low birth weight in Sichuan Province. Cooperating Group for Birth Defects Monitoring].

Data on low birth weight and some potential factors were obtained from an epidemiologic investigation of 111,676 births in Sichuan province during the period from Oct. 1986 to Sep. 1987. There were 8177 (73.22%) cases of low birth weight and 516 (79.89%) dead cases of low birth weight. The results suggest that the occurrence of low birth weight is affected by maternal age, fetal number and living level in rural areas. The incidence of low birth weight delivered by women aged 35 and over is 100.94%; it is 331.53% for twins and 265.96% for triplets. The incidence of low birth weight in rural areas (94.91%) is higher than that in urban areas (59.44%).

Adult↗

[Analyses of the prevalences for neural tube defects and cleft lip and palate in China from 1988 to 1991].

This paper reports the monitoring results of two main categories of birth defects-neural tube defects (NTD) and cleft of lip and palate (CLP) in China during the period of continuous monitoring (1988-1991). The method of hospital-based monitoring was adopted for data collection. From Jan. 1988 to Dec. 1991, a total of 2,750,588 births were monitored, and 28,168 cases of congenital malformations were identified. The prevalence of total birth defects was 102.4 per 10,000. 6885 cases of NTD were identified during this period, the prevalence of NTD being 25.0 per 10,000. The prevalence of NTD varied geographically; it declined gradually from the north to the south of China with the highest rate of NTD in the Taihang Mountain Regions. A total of 4548 cases of CLP were identified, and the provincial prevalence of CLP varied from 11.2 to 25.7 per 10000 with a mean of 16.5 per 10000. The prevalence of NTDs varied seasonally with the peak in winter (January). The sex ratio of NTD was 0.59, the prevalences in female births (32.1 per 10,000) being higher than that in male births (17.4 per 10,000) (P < 0.01). The sex ratio of CLP was 1.33. A significant difference was noted between the sex ratio of cleft palate (0.80) and that of the total cleft lip (1.46) (P < 0.01). The prevalence of NTD in rural areas (44.3 per 10,000) was 3 times as high as that in urban areas (14.4 per 10,000), but no difference in occurrence of CLP was observed between the urban and rural areas (P > 0.05).

China↗

Cardiogenic shock induced by cocaine in swine with normal coronary arteries.

OBJECTIVE: The aim was to test the hypothesis that acute intravenous cocaine administration can cause coronary microvascular constriction culminating in myocardial ischaemia and cardiogenic shock. METHODS: Systemic haemodynamic variables and coronary blood flow were measured in 14 Yorkshire swine at baseline and following intravenous administration of 1, 3, and 10 mg.kg-1 of cocaine. Epicardial coronary artery diameter was measured from coronary arteriograms and coronary flow velocity was recorded with a Doppler flow wire. RESULTS: Cocaine produced a decrease in mean arterial pressure (65%), cardiac output (80%), and stroke volume (80%), and an increase in pulmonary artery diastolic pressure (60%). Although coronary blood flow decreased by 70%, epicardial coronary cross sectional area decreased by only 37-45%. Pretreatment with prazosin did not abolish the decrease in coronary blood flow. After administration of 10 mg.kg-1 of cocaine, five of 14 animals developed myocardial ischaemia and cardiogenic shock, culminating in ventricular fibrillation and death. CONCLUSIONS: In anaesthetised Yorkshire swine, cumulative intravenous doses of cocaine caused a significant reduction in coronary blood flow resulting in myocardial ischaemia, which cannot be attributed to epicardial vasoconstriction alone. This suggest that cocaine-induced coronary ischaemia may result from microvascular constriction, which is only partially prevented by alpha 1 blockade. In addition, direct toxic effects of cocaine on the myocardium may also contribute to the development of cardiogenic shock.

Animals↗