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Biomedical subjects

P L Wang

Publications and source records attributed to P L Wang.

At least 19 recordsLinked to original sources
PubMed1997

Pharmacokinetics and cardiovascular effects of ma-huang (Ephedra sinica) in normotensive adults.

The purpose of this study was to evaluate heart rate and blood pressure responses to a commercially available source of ma-haung, a natural source of the sympathomimetic substance, ephedrine, and to evaluate the pharmacokinetic properties of the product in normotensive, healthy adults. On day 1, twelve study participants were monitored with an ambulatory blood pressure device between hours 7 and 20. On day 2, they ingested four capsules of powdered ma-huang at hours 8 and 17 while again wearing the monitor between hours 7 and 20. Serial plasma samples were obtained and concentrations of ephedrine were analyzed by high-performance liquid chromatography. Pharmacokinetic parameters of ephedrine were determined from plasma concentration-time profiles. The ephedrine alkaloid content of each capsule was also determined by high-performance liquid chromatography. Six participants experienced a statistically significant increase in heart rate, but the effects on blood pressure were variable. The half-life, volume of distribution, clearance, and maximum concentration in plasma of ephedrine in the ma-huang product were similar to values previously reported for a 20 mg, immediate-release ephedrine tablet. Values for the absorption rate were considerably lower and time to reach maximum concentration was longer for the capsules, compared with the standard tablet. Variability in alkaloid content of ephedrine was low and yielded a mean dose of ephedrine at 19.4 mg; pseudoephedrine at 4.9 mg; and methylephedrine at 1.2 mg for a four-capsule dose. In summary, ma-haung had variable effects on blood pressure and increased heart rate in healthy, normotensive adults. Pharmacokinetic parameters for ephedrine were in agreement with those previously reported; however, the absorption rate was much slower after ingestion of ma-huang.

Adult↗
PubMed1996

Molecular model of the solution structure for the paramagnetic four-iron ferredoxin from the hyperthermophilic archaeon Thermococcus litoralis.

A molecular model for the three-dimensional solution structure of the paramagnetic, four-iron ferredoxin (Fd) from the hyperthermophilic archaeon Thermococcus litoralis (Tl) has been constructed on the basis of the reported 1H NMR spectral parameters [Donaire, A. (1996) J. Biomol. NMR 7, 35-47]. The conventional use of long mixing time NOESY cross-peak intensity, backbone angles, and hydrogenbonding constraints for building the structure was augmented by short mixing time NOESY, steady-state NOE, paramagnetic relaxation constraints, and the angular dependence of the ligated Cys H beta contact shifts. Distance geometry was used to generate various initial structures, and these structures were refined with the simulated annealing protocol. The family of structures with inconsequential violations exhibited low RMS deviations for the backbone except for a few residues in the immediate cluster vicinity and traces out a secondary structure very similar to those of the structurally characterized single cubane cluster Fds. The ability to describe the cluster environment depended on the use of numerous paramagnetic relaxation constraints which resulted in even the cluster loop residues exhibiting well-defined orientations, with the exception of one residue (Ilel1) whose 1H signals have not been located. Comparison of the structure of Tl Fd to those of mesophilic ferredoxins reveals that Tl Fd possesses the same secondary structural elements, two beta-sheets, two helices, and four turns, with the exception that the beta-sheet involving the termini incorporates a third strand in Tl Fd. Several minor structural adjustments in Tl Fd relative to other Fds, in addition to the third strand for beta-sheet, include the incorporation of the termini into the beta-sheet, a likely salt bridge from the side chain of the third beta-strand to the N-terminus, and a more hydrophobic and compact interaction between the large beta-sheet and the long helix. It is likely that each of these modifications, among others not yet well-defined (i.e., surface salt bridges), contributes to the extraordinary thermostability of Tl Fd.

Amino Acid Sequence↗
PubMed1995

Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type 1 diabetes mellitus.

The salivary glands of mammals synthesize and secrete a number of peptide growth factors that play important roles in cell/tissue homeostasis and embryonic development. Using a radioimmunoassay, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) were detected in saliva from mice. Unlike epidermal growth factor (EGF), there was no sexual dimorphism in the concentrations of the insulin growth factor family. Immunohistochemical localization of IGF-I and IGF-II was confined to the duct cells of both the parotid and the submandibular glands. Reverse transcriptase-polymerase chain reaction amplification of total RNA from parotid and submandibular glands confirmed the presence of all three hormone/growth factor mRNAs in both glands. The levels of insulin and IGF-I were higher in saliva from an animal model for autoimmune type 1 diabetes, the non-obese diabetic (NOD) mouse, than in a second inbred strain, BALB/c. In contrast, the IGF-II levels were decreased relative to the BALB/c strain. With the onset of diabetes in NOD mice, insulin levels declined, while IGF-I and IGF-II levels showed trends toward lower levels of these growth factors when compared with non-diabetic animals. These changes were reflected in the concentrations from parotid and submandibular gland cell lysates.

Animals↗
PubMed1994

Limited modulation of the mitogen-activated protein kinase pathway by cyclic AMP in rat parotid acinar cells.

Treatment of rat parotid acinar cells, in vitro, with agents that elevate intracellular cAMP had only limited impact on the ability of EGF to subsequently stimulate MAP-kinase activity or phosphorylation. A time course of cAMP accumulation following in vivo administration of isoproterenol showed the greatest level of cAMP 15 min following the primary injection. Over a 72 hr injection regimen, agonist-stimulated cAMP levels were gradually reduced to control levels while cAMP-dependent protein kinase A (PKA) activity in immunoprecipitates of Raf-1 or MAP-kinase remained elevated. Raf-1 did not undergo phosphorylation following incubation with the catalytic subunit of PKA, suggesting that in normal rat acinar cells proliferation induced by isoproterenol or EGF involves the p21ras-Raf-MAP-kinase signaling cascade despite the presence of cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Effect of chronic insulin administration on mouse parotid and submandibular gland function.

Chronic (six-day) injection of insulin (im, 50 microM/animal) into BALB/c mice resulted in changes in secretory function, hypertrophy and hyperplasia of the parotid and submandibular glands. There were no significant changes in the flow rate or concentrations of proline-rich proteins, TGF alpha, or amylase in saliva when measured against constant protein levels. However, amylase enzyme activity and total saliva protein content were reduced when measured against constant saliva volume. In contrast, EGF synthesis and secretion from the submandibular gland was increased. Both the parotid and submandibular gland showed evidence of gland hypertrophy and increased rates of DNA synthesis as indicated by [3H]-thymidine incorporation in response to insulin treatment. Chronic injection of insulin did not effect the level of receptor in the plasma membrane of either gland.

Animals↗
PubMed1994

Activation of SH2-containing proteins by insulin in proliferating mouse parotid gland acinar cells.

Chronic treatment of mice with insulin results in hypertrophy and hyperplasia of the parotid and submandibular glands (Wang et al.: 1994, Proc Soc Exp Biol Med 205:353-361). Hyperplasia of the parotid gland is mediated by the elevation of tyrosine phosphorylation of phospholipase C gamma, p21ras-GTPase activating protein (p21ras-GAP) and phosphatidylinositol 3-kinase. These proteins were found to be associated with the insulin receptor substrate-1 most likely through src homology (SH2) domains of these proteins. There was also a transient increase in intracellular cAMP and protein kinase A during the first day of treatment which declined by Day 3 to near control values. Protein kinase C activity, on the other hand, remained elevated for the 3-day injection regimen. Thus, acinar cell proliferation induced by insulin requires activation of many of the same signaling components as other tyrosine kinase possessing growth factor receptors.

Animals↗
PubMed1994

Structure-activity relationship of memory enhancing peptide ZNC (C) PR analogs.

ZNC(C)PR has been found to be a new neuropeptide in rat brain as a significant enhancer of learning and memory. In this work, the structure-activity relationship of ZNC(C)PR was studied. First, the roles of every residue in ZNC(C)PR were investigated theoretically and analogs were designed according to the predicted conformational properties. Five analogs were synthesized following the design. Passive avoidance behavior tests in rats showed that NIPR, NVPR, and NAPR have positive effects to facilitate memory, while NSPR has no effect, and DLPR has somewhat inhibitory effect. As the experimental results are in good agreement with that of theoretical calculations, it is suggested that further research may help us to understand more details on the structure-activity relationship of ZNC(C)PR and provides a way for further design of potent agonist, antagonist and possible nonpeptide mimetics of ZNC(C)PR.

Animals↗
PubMed1993

Epidermal growth factor and isoproterenol stimulation of the Ras-guanine nucleotide exchange factor in proliferating rat parotid gland acinar cells.

Chronic treatment of rat parotid gland acinar cells with either epidermal growth factor (EGF) or the beta-adrenergic receptor agonist isoproterenol leads to cell proliferation through activation of the tyrosine kinase second messenger signalling pathway. Activation of p21ras activity in acinar cells was evaluated by measuring the levels of protein bound GTP and GDP. Both EGF and isoproterenol increased the amount of p21ras-GTP complex during active proliferation. The increase in bound GTP appears to be the result of an increased activity for the Ras-guanine nucleotide exchange factor.

Animals↗
PubMed1993

Characterization of antinuclear autoantibodies present in the serum from nonobese diabetic (NOD) mice.

The nonobese diabetic (NOD) mouse develops insulin-dependent type 1 diabetes in response to autoantibodies and T-cell attack directed against pancreatic islet cell antigens. Sera obtained from nondiabetic and diabetic female mice demonstrated a 1.4-fold increase in IgG levels when compared to BALB/c control animals. Nondiabetic and diabetic male mice had a 2.1- and 3-fold increase, respectively, in serum IgG levels over that of control mice. Seven of 11 non-diabetic and 7/10 diabetic sera from female NOD mice contained antibody to cytoplasmic or nuclear components of HEp-2 cells. Cytoplasmic staining revealed reaction against cytoskeletal and midbody structures. Punctate nuclear staining patterns with HEp-2 cells showed antibody reaction to the centriole, mitotic chromosomes, and nuclear rim. On the other hand, sera from BALB/c mice were negative for antibody staining of HEp-2 cells. Confirmation of the autoantibody nature of the NOD sera was obtained by antibody staining of nuclear structures from the mouse 3T3 fibroblast cell line, and by staining of salivary gland tissue sections. The nuclear and cytoplasmic staining patterns of diabetic NOD sera were reminiscent of the autoantibody staining patterns observed in Sjögren's syndrome and other inflammatory autoimmune connective tissue diseases.

Animals↗
PubMed1993

Effects of surgical ovariectomy on rat salivary gland function.

Studies sought to determine whether there are specific changes in salivary gland protein synthesis and secretion in response to hormone deficiency caused by ovariectomy of female rats. After 50 days, the wet weights of the parotid and submandibular glands did not change with hormone loss while that of the sublingual gland increased by 26% when compared to sham-operated controls. Amylase activity in the parotid declined, as did the level of enzyme activity present in saliva. The amount of the acidic proline-rich protein in the parotid was not altered after ovariectomy when compared to control sham-operated animals, using constant quantities of lysate protein. The total of secreted protein per unit volume did not change with ovariectomy. However, sodium dodecylsulphate-polyacrylamide gel electrophoresis of whole saliva showed the loss of a substantial number of proteins, including amylase and the acidic proline-rich proteins, from the experimental group. Epidermal growth factor concentrations were not significantly altered in the submandibular gland, while again showing a decrease in the concentration from saliva in ovariectomized rats.

Amylases↗
PubMed1992

Alterations in the subcellular distribution of p21ras-GTPase activating protein in proliferating rat acinar cells.

Rat parotid acinar cells undergo transient proliferation in response to chronic administration of the beta-adrenergic agonist isoproterenol or epidermal growth factor (EGF). Treatment with these agents caused an increase in tyrosine phosphorylation of p21ras-GTPase activating protein (GAP). This phosphorylation event was accompanied by a redistribution of the protein from the plasma membrane to internal membrane compartments. Separation of subcellular membranes revealed increased GAP associated with a low density population of vesicles concomitant with growth stimulation as well as to the nuclear membrane, but not the nucleoplasm. Upon cessation of hyperplasia induced by isoproterenol, phosphorylated GAP present in the plasma membrane returned to control cell levels.

Animals↗
PubMed1992

Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily.

We have identified and cloned cDNA for a novel cell-surface protein that we have named Tactile for T cell activation, increased late expression. It is expressed on normal T cell lines and clones, and some transformed T cells, but no other cultured cell lines tested. It is expressed at low levels on peripheral T cells and is strongly up-regulated after activation, peaking 6 to 9 days after the activating stimulus. It is also up-regulated on NK cells activated in allogeneic cultures. It is not found on peripheral B cells but is expressed at very low levels on activated B cells. Tactile-specific mAb immunoprecipitates a band of 160 kDa when reduced and bands of 240, 180, and 160 kDa nonreduced. Using an antiserum produced with affinity-purified Tactile protein to screen a lambda gt11 library, we have identified Tactile cDNA. Northern blot analysis shows an expression pattern similar to that of the protein and transfection of COS cells with the full-length 5.2-kb cDNA results in cell-surface expression. Comparison with the sequence databanks show that Tactile is a member of the immunoglobulin gene superfamily, with similarity to Drosophila amalgam, the melanoma Ag MUC-18, members of the carcinoembryonic Ag family, the poliovirus receptor, and the neural cell adhesion molecule. The deduced primary sequence encodes a protein with three Ig domains, a long serine/threonine/proline-rich region typical of an extensively O-glycosylated domain, a transmembrane domain, and a 45 residue cytoplasmic domain. These data suggest that Tactile may be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response.

Amino Acid Sequence↗
PubMed1991

A genetic study of human interferon-alpha-induced repair of DNA damage in hepatitis B patients.

In vitro treatment with human interferon-alpha (HuIFN-alpha) of hepatitis B virus-infected peripheral lymphocytes from 17 hepatitis B patients induced a decrease in the frequency of sister-chromatid exchanges (SCE). There was a significant difference in mean SCE frequencies between the HuIFN-alpha-treated patients and the control group, but not between acute and chronic hepatitis B patients treated with HuIFN-alpha.

Adult↗
PubMed1991

Preparation and anti-HIV activities of aurintricarboxylic acid fractions and analogues: direct correlation of antiviral potency with molecular weight.

Aurintricarboxylic acid (ATA) was fractionated by a combination of dialysis, ultrafiltration, and gel permeation chromatography. The number average and weight average molecular weights of the ATA fractions were determined by the universal calibration method. The sulfonic acid analogue of ATA was prepared and separated in high and low molecular weight fractions. The phosphonic acid analogue of ATA was also synthesized. All of the ATA fractions were tested for prevention of the cytopathic effect of HIV-1 and HIV-2 in MT-4 cell culture as well as against HIV-1 in CEM cell culture. The abilities of the fractions and analogues to inhibit syncytium formation between HIV-1- and HIV-2-infected HUT-78 cells and uninfected MOLT-4 cells were evaluated. In addition, the fractions and analogues were tested for cytotoxicity in mock-infected MT-4 cells, prevention of the binding of the OKT4A monoclonal antibody to the CD4 receptor, inhibition of the binding of anti-gp120 monoclonal antibody to gp120, inhibition of attachment of HIV-1 virions to MT-4 cells, and inhibition of HIV-1 reverse transcriptase. In all of these assays except cytotoxicity, there was a correlation of potency with molecular weight. The higher the molecular weight, the higher the activity. Several of the lower molecular weight fractions of ATA, which bound to gp120 but not to CD4, prevented HIV-1 and HIV-2 cytopathicity. A similar profile was observed for the phosphonic acid analogue of ATA and the lower molecular weight fraction of the sulfonic acid analogue. The results on the ATA fractions indicate that the binding of ATA to gp120 in the absence of CD4 binding is sufficient for anti-HIV activity. The active compounds bind more avidly to gp120 than to CD4. The anti-HIV activity of the ATA fractions is due to inhibition of virus binding due to an interference with the gp120-CD4 interaction.

Antiviral Agents↗
PubMed1990

31P NMR spectra of an oligodeoxyribonucleotide duplex lac operator-repressor headpiece complex.

The interaction of a symmetric lac operator duplex, d(TGTGAGCGCTCACA)2, with the N-terminal 56-residue headpiece fragment of the lac repressor protein was monitored by 31P NMR spectroscopy. The changes in the 31P chemical shifts upon addition of the headpiece demonstrated an end point of two headpiece fragments per symmetric 14-mer duplex with each headpiece binding to the T1pG2pT3pG4pA5 ends of the duplex. The specific phosphate 31P perturbations observed are consistent with those residues implicated in protein binding by previous NMR, molecular biological, and biochemical techniques. Upon complexation, the 31P signals of phosphates G2-A5 showed upfield or downfield shifts (less than 0.2 ppm) while most other residues were unperturbed. The interactions were dependent on ionic strength. The 31P NMR data provide direct evidence for predominant recognition of the 5' strand of the 5'-TGTGA/3'-ACACT binding site.

Bacteriophage lambda↗
PubMed1989

Choice of lasers for laser angioplasty.

Thrombi in test-tube, intraarterial thrombi and pig aorta wall were in vitro irradiated with continuous CO2 laser, short pulsal and ultrashort pulsal YAG laser (with pulse-width of 10 ns and 40 ps, respectively) and their double frequency laser and excimer laser with a wave-length of 308 nm and pulse-width of 20 ns. Their effect of vaporizing and ablating (photodecomposing) thrombi and their thermal injuring effect on adjacent tissues were compared and assessed in order to select optimal laser with little thermal injuring and more rapid vaporizing or ablating thrombi effect for laser angioplasty. The experimental results showed that excimer laser, ultrashort pulsal YAG laser and its double frequency laser, and double frequency laser of short pulsal YAG laser, with laser beam and blood vessel kept in a coaxial position, can effectively vaporize or ablate thrombi without thermal injury to vessel wall. So they may be used for laser angioplasty. Of them, especially, excimer laser and double frequency laser of ultrashort pulsal YAG laser have short wave-length and high peak power, and more effectively ablate thrombi than others, so they proved to be optimal lasers for laser angioplasty.

Angioplasty, Balloon↗
PubMed1989

Expression of human placental aromatase in Saccharomyces cerevisiae.

A full-length human placental aromatase cDNA clone, Aro 2, was isolated upon screening a human placental cDNA library with an aromatase cDNA probe and an oligonucleotide probe whose sequence was derived from a human aromatase genomic clone. Nucleotide sequence microheterogeneity was found in the 3'-untranslated region among Aro 2 and in two previously described human aromatase cDNA clones. Both the minor sequence differences and the expression of a single protein species in placental tissue suggest the presence of different alleles for aromatase. Northern blot analyses using one cDNA and two oligonucleotide probes are consistent with the two mRNA messages of 2.9 and 2.5 kilobases arising in human placenta as a consequence of differential processing. Several yeast expression plasmids containing the aromatase cDNA we cloned were constructed. The enzyme was expressed in Saccharomyces cerevisiae. The expressed activity was inhibited by the known aromatase inhibitor, 4-hydroxyandrostenedione. A level of 2 micrograms aromatase/mg partially purified yeast microsomes was estimated by analyses of carbon monoxide difference spectra on microsomal fractions from yeast carrying plasmid pHARK/VGAL. Using [1 beta, 2 beta-3H]androst-4-ene-3,17-dione as the substrate, an apparent Michaels-Menken constant (Km) of 34 nM and a maximum velocity (Vmax) of 23 pmol [3H]water formed per min/mg protein were obtained for the yeast synthesized aromatase by transformation with plasmid pHARK/VGAL. The kinetic results are similar to those determined for human placental aromatase, and suggest that the yeast synthesized aromatase will be useful for further structure-function studies.

Amino Acid Sequence↗