Biomedical subjects
Publications and source records attributed to Y He.
The phosphoramidites of 8-aza-7-deaza-2'-deoxyisoguanosine (1a) and its bromo derivative 1b as well as of 6-aza-2'-deoxyisocytidine and its 5-methyl derivative (3a,b) were synthesized. Parallel-stranded duplexes containing the nucleosides 1a,b show a significantly enhanced duplex stability compared to those containing 2'-deoxyisoguanosine.
It is believed that the major mechanisms by which hydroxymethylglutaryl coenzyme A reductase inhibitors lower plasma cholesterol levels are by inducing hepatic low-density lipoprotein (LDL) receptor activity and by decreasing apolipoprotein B (apoB) secretion by the liver. However, the intestine is also an important cholesterogenic organ and the possibility that this class of drugs may alter lipoprotein secretion by the intestine has not been fully studied. The purpose of the present study was to examine the possible role of cholesterol in regulating apoB secretion by the intestine by testing if the suppression of cholesterol synthesis by the reductase inhibitor lovastatin affected the secretion of apoB by CaCo-2 human intestinal cells. Differentiated post-confluent CaCo-2 cells were incubated for 24-72 h in serum-free medium in the presence or absence of 5 microM lovastatin, and the secretion rate of lipids, as well as apoB and apolipoprotein AI (apoAI) into the medium, was measured. Lovastatin markedly inhibited the incorporation of [1-14C]acetate into cholesterol for at least 48 h, lowered the content of esterified cholesterol in cells, and reduced their rate of cholesterol secretion. However, under basal conditions lovastatin had no effect on the secretion rate of apoB. After stimulation of apoB secretion by addition of 0.8 mM oleic acid to the medium, lovastatin did not alter apoB secretion in the first 2 days of incubation, but reduced the content of apoB in media from the 3rd day by 30%. This could not be explained by an increase in the rate of LDL degradation. Furthermore, supplementation with mevalonic acid only reversed about one-half of the effect of lovastatin, suggesting that this effect was at least parly nonspecific or unrelated to inhibition of cholesterol biosynthesis. There was also no specific effect of lovastatin on apoAI secretion. When cells were cultured with [1-14C]acetate for 24 or 72 h, the specific activity of cholesterol in medium at the end of the incubation was the same as in cells, suggesting that cholesterol used for lipoprotein secretion was in equilibrium with bulk cellular cholesterol and was not from a segregated compartment derived from newly synthesized cholesterol. This may explain why apoB secretion by CaCo-2 cells was unaffected by inhibition of cholesterol synthesis with lovastatin.
In this paper, a field study was carried out to examine the effect of flue gas desulfurization (FGD) by-product on water quality at an underground coal mine in central-eastern Ohio. Flue gas desulfurizalion by-product was injected into the down-dip portions of the Robert-Dawson mine in an attempt to seal major seeps exiting the mine and to coat exposed pyritic surfaces. Immediately following grout injection, significant increases in acidity, iron, aluminum, sulfur, and calcium were observed at most surface and ground water locations near where grouting was carried out. Following this initial flush of elements, concentrations of most constituents have decreased to near pre-grouting levels. Data from the site and geochemical modeling suggest that an increase in water level or rerouting of drainage flow resulted in the dissolution of iron and aluminum sulfate salts and ferrihydrite. Dissolution of the FGD grout material resulted in increases in calcium and sulfate concentrations in the drainage waters. Water within the mine voids was saturated with respect to calcium sulfate and gypsum immediately following grout injection. Based on an analysis of core samples obtained from the site, acid mine drainage (AMD) was in contact with at least some portions of the grout and this resulted in grout weathering. Subsequent transport of calcium and sulfate to the underclay, perhaps by fracture flow, has resulted in the deposition of gypsum and calcium sulfate solids.
The gene for the sperm adhesion molecule 1 (PH-20), SPAM1, has been known to be testis-specific and exclusively haploid expressed. We show that in mice, the 2 common isoforms of the protein (Spam1) observed in sperm are also present in the caput, corpus, and cauda epididymides. Both qualitative and quantitative variation of expression of the protein were observed in epididymis with the highest expression detected in the corpus. The endogenous production of enzymatically active (via hyaluronidase) Spam1 by epididymal cells is supported by the detection of steady-state Spam1 epididymal messenger RNA in both wild type and germ cell-deficient mice. In situ transcript hybridization shows the transcript to be localized to the principal cells of the epithelium. The protein was similarly immunolocalized to these cells, predominantly in vesicles near the apical region. The results suggest a mechanism for transportation of Spam1 from the epididymal epithelium to sperm during their transit and storage in the cauda. None of the current categories of spermatogenic-expressed genes shows the dual transcription pattern (haploid testicular/diploid epididymal) observed for Spam1. The work also confirms and extends the finding that Spam1 is expressed in the kidney.
For the studies of bioactive peptides, our laboratories have been employed an integrated approach including synthesis, bioassays, and conformational analysis. To obtain highly potent, selective and metabolically stable analogs, peptidomimetics such as peptide backbone modifications (retro-inverso structures), constrained amino acids, and cyclic structures have been incorporated into many bioactive peptide sequences. The conformational studies of the resulting analogs have led to topochemical models for the bioactivities of those peptides. This lecture will be focused on the results of such studies on opioids and somatostatin. We have synthesized numerous opioid analogs with various peptidomimetics based on three classes: enkephalins, dermorphin-deltorphins, and morphiceptins. Many of these analogs exhibit high potency, selectivity, and metabolic stability. Conformational studies of these analogs have enabled us to define the structural characteristics necessary for bioactivities of morphiceptins, dermorphins, enkephalins, and deltorphins. From these results, we can propose conformational models responsible for bioactivities at the mu- and delta-receptors. Our studies of cyclic somatostatin analogs are based on the highly active Merck analog c(-Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11-) (where the superscripts denote position in native somatostatin). To investigate the topochemical preference of backbone and side chains, unusual amino acids, including beta-methylphenylalanine7 or 11, beta-methyltryptophan8, as well as backbone modifications such as retro-inverso structures have been incorporated. The bioactivity profiles of these peptidomimetic molecules provide much information on the effects of backbone and side chain constraints on bioactivity.
A total of 159 Y. pestis strains isolated in different geographical regions of China have been studied. Y. pestis isolated in the majority of natural foci of plague in China carry plasmids with molecular weights of 6, 13, 15 and 63 MD. One isolated strain has been found to carry plasmid with a molecular weight of 36 MD. Only a few strains have no plasmids with molecular weights of 6 and 45 MD. In certain geographical zones strains carrying large plasmids of 52 and 92 MD have been detected.