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Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 1,495 records · Page 83Linked to original sources

Advanced ovarian carcinoma: molecular evidence of unifocal origin.

The clonal origin has sometimes been disputed in advanced epithelial cancers when multiple sites of peritoneal tumors were present because of the developmental similarity of the surface epithelium of the ovary and the peritoneal mesothelium. We have taken two independent approaches to study the clonality of advanced epithelial carcinoma. Tumor samples of both ovaries, and/or omentum, and/or peritoneum from nine patients were examined. The analysis of loss of heterozygosity (LOH) at 86 polymorphic chromosomal loci distributed on every chromosome revealed the loss of the same allele in every tumor of each patient when LOH was detected. In addition, we used a restriction-fragment-length polymorphism in an X-linked sequence (DXS255) to examine the pattern of X-chromosome inactivation based on the differential methylation of DXS255 in active and inactive X chromosomes. Inactivation of the same X chromosome in various tumors from the same patient was observed in each of the five informative patients. Our results strongly suggest that the advanced epithelial cancers are monoclonal in origin.

Adult↗

Frictional transition of pesticides from protective clothing.

Frictional transition of pesticides, the transition of the dried pesticide due to rubbing, from protective clothing was investigated by using an AATCC standard crockmeter. One insecticide (carbaryl) and two herbicides (atrazine and metolachlor) were studied, together with three protective clothing materials [cotton, polyester, and polyester/cotton (65/35) blend] and three crock fabrics (cotton, nylon, and silk). The effects of the properties of pesticide, fabrics, water, and perspiration on the frictional transition are discussed. The experiment showed that up to 12% of the pesticide could transfer from contaminated protective clothing to the skin through rubbing. Choosing the right materials for protective clothing and underwear would greatly decrease the frictional transition of the pesticide.

Laundering↗

Controlled release low dose medroxyprogesterone acetate (MPA) inhibits the development of mammary tumors induced by dimethyl-benz(a) anthracene in the rat.

Medroxyprogesterone acetate (MPA) is well recognized to have beneficial effects for the treatment of advanced breast cancer which are comparable to those achieved with other forms of endocrine therapy. Using mammary tumors induced in the rat by dimethylbenz(a)anthracene (DMBA) as a model, we have studied the possibility that low dose MPA could prevent the development of these tumors. Single subcutaneous injection of Depo-Provera (crystalline suspension of MPA) or MPA encapsulated in biodegradable microspheres of 50:50 poly[DL-lactide-co-glycolide] was given 7 days before oral DMBA. While 63% of intact animals developed palpable mammary tumors within 85 days after DMBA administration, tumor incidence decreased to 28% and 23% in animals who had received 30 mg and 100 mg of Depo-Provera, respectively. The same amounts of MPA delivered in microspheres caused a further decrease in tumor incidence to respective values of 7% and 6%. Average tumor area, on the other hand, decreased from 4.89 cm2 in intact rats to about 0.75 (0.57-0.88) cm2 and approximately 0.20 (0.14-0.22) cm2 in the Depo-Provera and microsphere-treated groups, respectively. Using the 50:50 formulation of poly[DL-lactide-co-glycolide] designed to release MPA at a constant rate for a 4-month period, the serum MPA concentration at 3 months was measured at 4.99 +/- 0.43 ng/ml. Such data suggest that administration of a low dose controlled-release formulation of MPA in 50:50 poly[DL-lactide-co-glycolide] microspheres could well be an efficient and well tolerated approach for the prevention of breast cancer in women.

9,10-Dimethyl-1,2-benzanthracene↗

Dependence of the bilayer phase transition temperatures on the structural parameters of phosphatidylcholines.

Most saturated diacyl phosphatidylcholines C(X):C(Y)PC (saturated 1,2-diacyl-sn-glycero-3-phosphocholine with X carbons in the sn-1 acyl chain and Y carbons in the sn-2 acyl chain), in excess water, can self-assemble into lamellae which, upon heating, may undergo multiple thermotropic phase transitions at well-defined, discrete temperatures. The transition temperature corresponding to the main or the gel to liquid-crystalline phase transition (Tm) is known for many bilayers of fully hydrated phosphatidylcholines. In this study, we have analyzed the Tm values of 44 molecular species of phosphatidylcholines in terms of their structural and packing characteristics in the gel-state bilayer. Two general equations are thus derived: Tm = 162.26-3651.71 (1/N) - 88.42 (delta C/N) for C(X):C(Y)PC with X > or = Y, and Tm = 157.68-3525.44 (1/N) - 93.28 (delta C/N) for C(X):C(Y)PC with X < Y. Here, N is the minimal hydrophobic thickness of the dimeric C(X):C(Y)PC in the gel-state bilayer and delta C is the effective chain length difference between the sn-1 and sn-2 acyl chains for the monomeric C(X):C(Y)PC in the gel-state bilayer. The advantage of these two equations in predicting the Tm values for phosphatidylcholines with delta C/CL values in the range of 0.07 to 0.40 is their simplicity. A figure containing a total of 173 calculated Tm values is also presented.

Computer Simulation↗

Vasal sterilization in China.

Vasal sterilization has become the most popular method of contraception in many countries since the 1960's. In China, an estimated 30 million men have undergone voluntary sterilization. There have been two major developments in vasectomy technique, the no-scalpel method and the percutaneous chemical vas occlusion. These methods have significantly increased the acceptability of male sterilization in some cultures since no incisions in the skin are required. The effective rate is over 98% for both methods. The clients experience less pain, fewer complications and more rapid recovery. Epidemiological studies of large numbers of volunteers receiving no-scalpel or chemical vas occlusion procedures have resulted in a clearer picture of their safety, effectiveness, simplicity and economy. Meanwhile, some promising reversible vasal sterilization techniques have also been studied.

China↗

Etofibrate increases binding of low and high density lipoprotein to human platelets of patients with type II hyperlipoproteinemia.

Previous work suggested an influence of etofibrate, a diester of nicotinic acid and clofibric acid, on lipoprotein receptors. Besides its beneficial effects on plasma lipoprotein levels of decrease in total cholesterol, LDL-cholesterol and triglycerides and increase in HDL-cholesterol, etofibrate was shown to inhibit platelet function. In order to further evaluate platelet-lipoprotein interactions, the effects of etofibrate on plasma lipids and lipoproteins on the specific binding of normal [111In]LDL and [111In]HDL onto platelets as well as its effect on platelet function were evaluated in 8 patients affected by Type II hyperlipoproteinemia (HLP). In all patients binding was saturable and indicated high affinity binding sites capable of binding 927 +/- 233 ng protein of [111In]LDL/10(9) platelets (Kd 12 +/- 3 micrograms protein/ml) and 1496 +/- 435 ng protein of [111In]HDL/10(9) platelets (Kd 14 +/- 3 micrograms protein/ml). The capacity of native LDL (HDL) to displace bound [111In]LDL ([111In]HDL) by half (IC50) amounted to 22 +/- 9 micrograms protein/ml (26 +/- 8 micrograms protein/ml). Following a 6-week treatment period with etofibrate (500 mg twice daily), decrease in plasma total cholesterol, LDL-cholesterol and apolipoprotein (apo) B and increase in HDL-cholesterol and apo AI was correlated to a significant (P < 0.01) increase in LDL- as well as HDL-receptor binding. The platelet binding capacity increased to 1085 +/- 212 ng protein/10(9) platelets (Kd 8 +/- 3 micrograms protein/ml) for [111In]LDL and to 1867 +/- 266 ng protein/10(9) platelets for [111In]HDL (Kd 11 +/- 3 micrograms protein/ml). Platelet function studies demonstrated significantly (P < 0.01) reduced platelet aggregation in response to ADP and thromboxane formation after 6 weeks of etofibrate therapy. These findings in patients with HPL Type II indicate in vivo upregulation of specific [111In]LDL as well as [111In]HDL binding sites on human platelets associated with reduced platelet activation following etofibrate therapy.

Adult↗

Measurement of mean velocity during pulsatile flow using time-averaged maximum frequency of Doppler ultrasound waveforms.

It has been suggested that mean velocity of flow could be estimated by the time-averaged maximum frequency over an integral number of cardiac cycles (Gill 1985). The present study verified this theory experimentally with a computer-controlled flow phantom. The effects of some parameters on the relationship between mean velocity and time-averaged maximum frequency were also studied. Parameters investigated included beam-vessel angle, diameter of tubing, pulsatility, flow rate and stenosis. The velocities measured by the Doppler system were compared with the actual velocities. A simple theoretical model was also developed to compare with the experimental results. The results showed that, in a long straight tube, the mean velocity can be estimated to within about 5% from the time-averaged maximum Doppler shift at various flow rates and pulsatilities. The error due to geometrical spectral broadening, especially for large beam-vessel angles, can be estimated to within 3% and therefore corrected.

Blood Flow Velocity↗

Nonlinear propagation in Doppler ultrasound.

The nonlinear propagation of ultrasound was demonstrated using Doppler transducers on two commercial duplex machines. The influence of nonlinear propagation on Doppler measurements was studied on both a flow phantom and a string phantom. It was found that although the pulse waveforms showed clearly different degrees of nonlinear distortion, no effect due to the nonlinearity could be detected on the received Doppler spectrum both in terms of the maximum frequency or underlying Doppler spectral profile.

Acoustics↗

Energy-minimized structures and packing states of a homologous series of mixed-chain phosphatidylcholines: a molecular mechanics study on the diglyceride moieties.

Phosphatidylcholines or C(X):C(Y)PC, quantitatively the most abundant lipids in animal cell membranes, are structurally composed of two parts: a headgroup and a diglyceride. The diglyceride moiety consists of the glycerol backbone and two acyl chains. It is the wide diversity of the acyl chains, or the large variations in X and Y in C(X):C(Y)PC, that makes the family of phosphatidylcholines an extremely complex mixture of different molecular species. Since most of the physical properties of phospholipids with the same headgroup depend strongly on the structures of the lipid acyl chains, the energy-minimized structure and steric energy of each diglyceride moiety of a series of 14 molecular species of phosphatidylcholines with molecular weights identical to that of dimyristoylphosphatidylcholine without the headgroup are determined in this communication by molecular mechanics (MM) calculations. Results of two types of trans-bilayer dimer for each of the 14 molecular species of phosphatidylcholines are also presented; specifically, the dimeric structures are constructed initially based on the partially interdigitated and mixed interdigitated packing motifs followed subsequently by the energy-minimized refinement with MM calculations. Finally, tetramers with various structures to model the lateral lipid-lipid interactions in a lipid bilayer are considered. Results of laborious MM calculations show that saturated diacyl C(X):C(Y)PC with delta C/CL values greater than 0.41 prefer topologically to assemble into tetramers of the mixed interdigitated motif, and those with delta C/CL values less than 0.41 prefer to assemble into tetramers with a repertoire of the partially interdigitated motif. Here, delta C/CL, a lipid asymmetry parameter, is defined as the normalized acyl chain length difference between the sn-1 and sn-2 acyl chains for a C(X):C(Y)PC molecule; an increase in delta C/CL value is an indication of increasing asymmetry between the two lipid acyl chains. These computational results are in complete accord with the calorimetric data presented previously from this laboratory (H-n. Lin, Z-q. Wang, and C. Huang. 1991. Biochim. Biophys. Acta. 1067:17-28).

Animals↗

Chemical pathways of peptide degradation. V. Ascorbic acid promotes rather than inhibits the oxidation of methionine to methionine sulfoxide in small model peptides.

The effect of primary structure and external conditions on the oxidation of methionine to methionine sulfoxide by the ascorbate/Fe3+ system was studied in small model peptides. Degradation kinetics and yield of sulfoxide formation were dependent on the concentration of ascorbate and H+, with a maximum rate observed at pH 6-7. Phosphate buffer significantly accelerated the peptide degradation compared to Tris, HEPES, and MOPS buffers; however, the formation of sulfoxide was low. The oxidation could not be inhibited by the addition of EDTA. Other side products besides sulfoxide were observed, indicating the existence of various other pathways. The influence of methionine location at the C terminus, at the N terminus, and in the middle of the sequence was investigated. The presence of histidine in the sequence markedly increased the degradation rate as well as the sulfoxide production. The histidine catalysis of methionine oxidation occurred intramolecularly with a maximum enhancement of the oxidation rate and sulfoxide production when one residue was placed between the histidine and the methionine residue.

Amino Acid Sequence↗

What is the ideal treatment for early esophageal cancer?

A study was made of treatment policies for superficial cancer in 1,982 cases in Japan from 1966 to 1989, and on 45 cases experienced in our department. The majority of epithelial cancer and muscularis mucosal cancer was early cancer without lymph node metastasis, and the five-year survival rates, excluding other disease deaths, was approximately 90-95%. It was estimated that reduced surgery would be sufficient. In high risk cases, and for patients rejecting surgery, radiotherapy with chemotherapy was acceptable. In submucosal cancer, node metastasis existed in approximately 35% of cases, and the five-year survival rates, excluding other disease deaths, was approximately 60%. However, even though a case may be node negative, some develop recurrent disease and for this reason radical surgery, as applicable in advanced cancer cases, is desirable.

Combined Modality Therapy↗

Blood vessel diameter measurement by ultrasound.

Blood vessel diameter measurement is crucial to volume flow measurement in medical ultrasound. The accuracy of the measurement is examined in this study. Experiments were made on three kinds of tube using four transducers on three commercial duplex ultrasound scanners. The accuracy of the inner diameter measurement is affected by ultrasonic pulse length. By correcting this effect, it has been shown that the accuracy of the measurement can be increased significantly over a range of conditions.

Blood Vessels↗

Opioid regulation of gonadotropin-releasing hormone gene expression in the male rat brain as studied by in situ hybridization.

It is well documented that gonadotropin-releasing hormone (GnRH) release is negatively regulated by opiates. In order to investigate the role of opiates in the regulation of GnRH gene expression in the rat brain, we studied the effects of chronic administration of the opioid drug morphine and an opiate receptor antagonist naloxone on GnRH mRNA levels as measured by in situ hybridization. Four-day treatment with morphine (40 mg kg day-2) produced a 44% decrease in the number of silver grains overlying GnRH neurones. Conversely, naloxone (4 mg kg day-2) also administered during 4 days increased by hybridization signal by 22%. The concomitant administration of morphine and naloxone completely prevented the effect of morphine on GnRH gene expression indicating the inhibitory influence of morphine is likely to be mediated by opioid receptors. The present data clearly indicate that opiates can inhibit not only the release of GnRH and consequently LH secretion but also the biosynthesis of the neuropeptide as evaluated by mRNA level measurements.

Animals↗

Effects of morphine and naloxone on prolactin and growth hormone gene expression in the male rat pituitary gland.

It is generally admitted that opioids can stimulate the release of both prolactin (PRL) and growth hormone (GH). In order to investigate the role of opioids in the regulation of PRL and GH gene expression in the rat pituitary, we studied the effects of chronic administration of the opioid drug morphine and an opiate receptor antagonist naloxone on both PRL and GH gene expression as measured by in situ hybridization. Four-day treatment with morphine (40 mg/kg/day) produced a 12% increase in PRL mRNA levels. Conversely, naloxone (4 mg/kg/day) decreased the autoradiographic reaction by 10%. The concomitant administration of morphine and naloxone induced no significant changes in PRL gene expression. On the other hand, treatment with morphine produced a 22% decrease in GH mRNA levels, an effect which was prevented by the concomitant administration naloxone. When injected alone, naloxone did not modify the hybridization signal. These results clearly indicate that opioids are involved not only in the regulation of GH and PRL release but also in the gene expression of the two hormones. The discordance observed between the acute effects of morphine on GH release and the effect of the opioid drug on mRNA levels remains to be clarified.

Animals↗

Chimeric influenza virus induces neutralizing antibodies and cytotoxic T cells against human immunodeficiency virus type 1.

Expression vectors based on DNA or plus-stranded RNA viruses are being developed as vaccine carriers directed against various pathogens. Less is known about the use of negative-stranded RNA viruses, whose genomes have been refractory to direct genetic manipulation. Using a recently described reverse genetics method, we investigated whether influenza virus is able to present antigenic structures from other infectious agents. We engineered a chimeric influenza virus which expresses a 12-amino-acid peptide derived from the V3 loop of gp120 of human immunodeficiency virus type 1 (HIV-1) MN. This peptide was inserted into the loop of antigenic site B of the influenza A/WSN/33 virus hemagglutinin (HA). The resulting chimeric virus was recognized by specific anti-V3 peptide antibodies and a human anti-gp120 monoclonal antibody in both hemagglutination inhibition and neutralization assays. Mice immunized with the chimeric influenza virus produced anti-HIV antibodies which were able to bind to synthetic V3 peptide, to precipitate gp120, and to neutralize MN virus in human T-cell culture system. In addition, the chimeric virus was also capable of inducing cytotoxic T cells which specifically recognize the HIV sequence. These results suggest that influenza virus can be used as an expression vector for inducing both B- and T-cell-mediated immunity against other infectious agents.

Amino Acid Sequence↗

Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus.

The neuraminidase (NA) gene of influenza A/WSN/33 (WSN) virus has previously been shown to be associated with neurovirulence in mice and growth in Madin-Darby bovine kidney (MDBK) cells. Nucleotide sequence analysis has indicated that the NA of WSN virus lacks a conserved glycosylation site at position 130 (corresponding to position 146 in the N2 subtype). To investigate the role of this carbohydrate in viral pathogenicity, we used reverse genetics methods to generate a Glyc+ mutant virus, in which the glycosylation site Asn-130 was introduced into the WSN virus NA. Unlike the wild-type WSN virus, the Glyc+ mutant virus did not undergo multicycle replication in MDBK cells in the absence of trypsin, presumably because of lack of cleavage activation of infectivity. In contrast, revertant viruses derived from the Glyc+ mutant were able to replicate in MDBK cells without exogenous protease. Nucleotide sequence analysis revealed that the NAs of the revertant viruses had lost the introduced glycosylation site. In contrast to wild-type and revertant viruses, the Glyc+ mutant virus was not able to multiply in mouse brain. These results suggest that the absence of a glycosylation site at position 130 of the NA plays a key role in the neurovirulence of WSN virus in mice.

Animals↗