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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 1,117 records · Page 62Linked to original sources

Unexplained elevated maternal serum alpha-fetoprotein levels and pregnancy outcome in twins.

OBJECTIVE: To evaluate whether elevated maternal serum alpha-fetoprotein (MSAFP) levels in uncomplicated twin gestations are associated with an increased risk for pregnancy complications and adverse outcomes. METHODS: A retrospective data-base analysis was conducted of 267 women with twin pregnancies delivered between January 1988 and October 1994, of whom 42 had elevated MSAFP levels and 225 had normal levels. We evaluated rates of preterm delivery (defined as gestational age less than 34 weeks at delivery), birth weight less than 1500 g, twin-to-twin birth weight discordance, small for gestational age (SGA) infants (defined as birth weight below the tenth percentile for gestational age), and fetal malformations. Also assessed were potentially confounding variables such as obstetric and medical histories as well as sociodemographic factors. RESULTS: Among nulliparous women, an unexplained elevation in MSAFP levels was associated with a statistically significant increased risk for preterm delivery. Among multiparous women, this association is suggested by the data, but not significantly so. An unexplained elevation in MSAFP level was also associated with a significantly increased risk for birth weight less than 1500 g, but this was related to the increased rate of preterm births. No appreciably increased risk was apparent for SGA infants, fetal malformations (other than neural tube defects and abdominal wall defects), or twin-to-twin birth weight discordance. CONCLUSION: In twin pregnancies, an unexplained elevation in MSAFP level may increase the risk for preterm delivery but not other adverse pregnancy outcomes.

Adult↗

Characterization of ventilatory responses to hypoxia in neonatal rats.

Newborn animals exhibit a biphasic response to hypoxia, with ventilation increasing and then declining. Our purpose was to define if this response could be supported by the pontile and medullary respiratory centers. Spontaneously breathing and paralyzed and ventilated decerebrate or anesthetized, vagotomized rats were studied from birth to 13 days thereafter. Peak integrated phrenic activity, or tidal volume, and frequency initially increased and then declined after inspired oxygen was reduced from hyperoxic to hypoxic levels; most animals became apneic in hypoxia. Apnea occurred in a greater proportion of animals and more quickly with more severe hypoxia. Following sectioning of the carotid sinus nerves, ventilatory activity declined with a change from hyperoxia to normoxia. We conclude that the biphasic ventilatory response to hypoxia represents a balance between synaptically-induced augmentations and reductions of brainstem neuronal activities. The carotid chemoreceptors play a fundamental role in the augmentations, and reductions appear dependent upon actions of hypoxia upon brainstem mechanisms.

Anesthesia↗

Managing osteopetrosis in children: a nutrition challenge.

Osteopetrosis, a rare condition caused by a failure of osteoclasts to resorb bone, results in dense and deformed bones, growth failure, anemia, hypoplastic dentition, chronic infection, blindness, and massive splenomegaly. Children with infantile osteopetrosis have disease-related complications that affect nutritional status. Altered calcium and phosphorus intake has been reported in these patients, but previous studies did not include an assessment of dietary adequacy or nutrition-related complications. A prospective study of six children with severe infantile osteopetrosis was conducted to identify specific nutrition-related problems and effective nutrition intervention strategies. Patients were monitored by a registered dietitian while they participated in a clinical research protocol at St Jude Children's Research Hospital. Dietary records for each patient were obtained at set intervals during the 4-month study period. Because most patients lacked adequate dentition, they had difficulty obtaining adequate nutrition through normal oral intake. Three children required nutrition supplementation (enteral feedings for one and oral supplements for two). We conclude that oral and enteral nutrition support can provide nutrients needed for improved growth and response to treatment in patients with osteopetrosis.

Adolescent↗

Lipid peroxidation in cord blood at birth.

OBJECTIVE: The purpose of this study was to determine oxygen free radical activity in the neonate at birth and relate it to umbilical cord blood acid-base status. STUDY DESIGN: A series of 110 singleton deliveries had determination of two lipoperoxides in umbilical cord blood: malondialdehyde and organic hydroperoxide. Umbilical pH, PO2, PCO2, bicarbonate, and base excess were also measured. RESULTS: There was a significant association between lipoperoxides and cord blood pH and base excess. A significant difference existed in the levels of umbilical artery lipoperoxides between nonacidemic and acidemic fetus, as defined by an umbilical arterial pH < 7.20. CONCLUSION: There is a positive association between lipoperoxide production and acid-base balance at delivery.

Acid-Base Equilibrium↗

Fatty acid unsaturation increases expression and capping of murine lymphocyte CD44 and CD45.

We studied the effect of incubating murine lymphocytes with cis-unsaturated fatty acids on expression and capping of CD44 and CD45. Lymphocytes were incubated with stearic (18:0) or oleic (18:1 omega-9) acid bound to bovine serum albumin (BSA). After incubation with rat anti-CD44 or anti-CD45 monoclonal antibodies and then with fluorescent-labeled anti-rat antibody, mean fluorescence intensity (FI) was measured by using flow cytometry. Capping was measured after warning and fixation in paraformaldehyde. Steady-state fluorescence anisotropy (rs) was measured after the cells had been incubated with trimethylammoniumdiphenylhexatriene. Incubation with oleic acid, but not stearic acid or BSA alone, was associated with an increase in FI of CD44. Expression of CD45, however, was increased by both stearic and oleic acids to the same degree over BSA controls. CD44 and CD45 capping were both increased by incubation with oleic acid. Rs was decreased in cells incubated with oleic acid, suggesting an increase in membrane fluidity. We conclude that incubation with oleic acid increases expression of CD44 and increases capping of both CD44 and CD45. These findings were confirmed in feeding experiments, in which rs was reduced and CD44 capping increased by polyunsaturated fatty acid diets.

Animals↗

Msx3: a novel murine homologue of the Drosophila msh homeobox gene restricted to the dorsal embryonic central nervous system.

We have isolated Msx3, the third member of the murine Msx homeobox gene family which is homologous to the msh gene of Drosophila. The Msx3 cDNA encodes a protein of 204 amino acids which has striking regions of homology in addition to the homeodomain when compared to the other Msx family members. Msx3 maps to the distal end of mouse chromosome 7, thus it is unlinked to either Msx1 or Msx2. RNA in situ analysis of Msx3 gene expression during early development revealed that it is restricted to the dorsal portion of the neural tube with a rostral boundary in the rostral rhombencephalon. This sole expression domain for Msx3 overlaps with both Msx1 and Msx2 at early stages, but in older embryos, Msx3 expression becomes restricted to the ventricular zone of the dorsal neural tube, whereas Msx1 and Msx2 become localized to the non-neuronal roof plate region. The absence of detectable levels of Msx3 expression outside this restricted dorsal region of the developing central nervous system (CNS) is in marked contrast to Msx1 and Msx2, which have extensive expression domains in other embryonic tissues, particularly craniofacial structures and the limbs. By analogy with the expression of msh/Msx genes in other organisms, it is likely that one of the ancestral functions of the msh/Msx gene family is in patterning of the CNS.

Age Factors↗

Very early and transient vegetal-plate expression of SpKrox1, a Krüppel/Krox gene from Stronglyocentrotus purpuratus.

All endodermal and mesenchymal cells of the sea urchin embryo descend from the vegetal plate, a thickened epithelium of approximately 50 cells arising at the early blastula stage. Cell types that derive from the vegetal plate are specified conditionally by inductive interactions with underlying micromeres, but the molecular details of vegetal-plate specification remain unresolved. In a search for regulatory proteins that have roles in vegetal-plate specification, a screen was performed to clone Krüppel/Krox-related genes from a Strongylocentrotus purpuratus embryo cDNA library. One newly identified clone, named SpKrox1, contained four zinc fingers and a leucine zipper domain. SpKrox1 expression was low in unfertilized eggs, increased severalfold to the early blastula stage and decreased between the early gastrula and pluteus stages. SpKrox1 mRNA was first seen in macromeres of 16-cell stage embryos and was restricted to cells of the developing vegetal plate thereafter. Vegetal-plate expression corresponded to a ring of cells around the blastopore and overlapped the expression patterns of other genes with potential roles in vegetal plate-specification. As the vegetal-plate cells invaginated into the blastopore, SpKrox1 expression was lost, suggesting that its role was not in endoderm differentiation per se but rather in the initial establishment of the vegetal plate.

Amino Acid Sequence↗

A Listeria monocytogenes pentapeptide is presented to cytolytic T lymphocytes by the H2-M3 MHC class Ib molecule.

Polymorphism of MHC class Ia molecules severely constrains vaccine development against intracellular pathogens. Antigen presentation by MHC class Ib molecules, which are generally conserved between different individuals, may circumvent this obstacle. Herein, we use tandem mass spectrometry to identify a Listeria monocytogenes pentapeptide antigen that is presented to T lymphocytes by the H2-M3 MHC class Ib molecule. The peptide contains N-formyl methionine at the N terminus and exclusively hydrophobic amino acids. Mice of the H-2 d, H-2 b,and H-2 k haplotypes respond to this peptide upon infection with Listeria monocytogenes. Identification of antigens presented by MHC class Ib molecules is feasible and may provide opportunities for relatively unrestricted vaccine development.

Alleles↗

(Hydroxymethyl)acylfulvene: an illudin derivative with superior antitumor properties.

Reaction of the fungal sesquiterpene illudin S with excess paraformaldehyde in dilute H2SO4 gives (hydroxymethyl)acylfulvene. The primary allylic hydroxyl thus formed can undergo very facile replacement by a variety of nucleophiles. (Hydroxymethyl)acylfulvene (MGI.114) was more toxic than a precursor, acylfulvene, but less toxic than the parent compound illudin S to HL 60 cells.

Animals↗

Potassium transport: from clearance to channels and pumps.

Potassium (K) homeostasis depends on the separate and interrelated regulation of K distribution between the intra- and extra-cellular fluid compartments and adequate renal excretion. This brief review focuses on the regulation of internal K distribution and the renal mechanisms of K handling. Based on clearance, micropuncture, and microperfusion studies, a large body of evidence supports the view that normally, renal secretion of K determines excretion and that the principal tubule cells in the initial and cortical collecting tubule secrete K, whereas K reabsorption may occur in intercalated cells. Studies of the electrochemical driving forces, of intracellular ion activities, the characterization of several ATPases, and patch clamp investigations have provided insight into the role of pumps and channels in those tubule cells that regulate K secretion and reabsorption.

Animals↗

Use of lattice square designs in bioassays.

The use of Lattice Square designs for estimating the relative potencies in a multiple bioassay is illustrated in this paper. The analysis is presented with and without recovery of inter-row and column information.

Biological Assay↗

Insulin unmasks a COOH-terminal Glut4 epitope and increases glucose transport across T-tubules in skeletal muscle.

An improved immunogold labeling procedure was used to examine the subcellular distribution of glucose transporters in Lowricryl HM20-embedded skeletal muscle from transgenic mice overexpressing either Glut1 or Glut4. In basal muscle, Glut4 was highly enriched in membranes of the transverse tubules and the terminal cisternae of the triadic junctions. Less than 10% of total muscle Glut4 was present in the vicinity of the sarcolemmal membrane. Insulin treatment increased the number of gold particles associated with the transverse tubules and the sarcolemma by three-fold. However, insulin also increased the total Glut4 immunogold reactivity in muscle ultrathin sections by up to 1.8-fold and dramatically increased the amount of Glut4 in muscle sections as observed by laser confocal immunofluorescence microscopy. The average diameter of transverse tubules observed in longitudinal sections increased by 50% after insulin treatment. Glut1 was highly enriched in the sarcolemma, both in the basal state and after insulin treatment. Disruption of transverse tubule morphology by in vitro glycerol shock completely abolished insulin-stimulated glucose transport in isolated rat epitrochlearis muscles. These data indicate that: (a) Glut1 and Glut4 are targeted to distinct plasma membrane domains in skeletal muscle; (b) Glut1 contributes to basal transport at the sarcolemma and the bulk of insulin-stimulated transport is mediated by Glut4 localized in the transverse tubules; (c) insulin increases the apparent surface area of transverse tubules in skeletal muscle; and (d) insulin causes the unmasking of a COOH-terminal antigenic epitope in skeletal muscle in much the same fashion as it does in rat adipocytes.

Animals↗

Effect of angiotensin II on the apical K+ channel in the thick ascending limb of the rat kidney.

We have used the patch-clamp technique to study the effect of angiotensin II (AII) on the activity of the apical 70 pS K+ channel and used Na(+)-sensitive fluorescent dye (SBFI) to investigate the effect of AII on intracellular Na+ concentration (Na+i) in the thick ascending limb (TAL) of the rat kidney. Addition of 50 pM AII reversibly reduced NPo, a product of channel open probability (Po) and channel number (N), to 40% of the control value and reduced the Na+i by 26%. The AII (50 pM)-induced decrease in channel activity defined by NPo was partially reversed by addition of 5 microM 17-octadecynoic acid (17-ODYA), an agent which blocks the cytochrome P450 monooxygenase. The notion that P450 metabolites of arachidonic acid (AA) may mediate the inhibitory effect of AII was further suggested by experiments in which addition of 10 nM of 20-hydroxyeicosatetraenoic acid (20-HETE) blocked the channel activity in cell-attached patches in the presence of 17-ODYA. We have used gas chromatography mass spectrometry (GC/MS) to measure the production of 20-HETE, a major AA metabolite of the P450-dependent pathway in the TAL of the rat. Addition of 50 pM AII increased the production of 20-HETE to 260% of the control value, indicating that 20-HETE may be involved in mediating the effect of AII (50 pM). In contrast to the inhibitory effect of 50 pM AII, addition of 50-100 nM AII increased the channel activity to 270% of the control value and elevated the Na+i by 45%. The effect of AII on the activity of the 70 pS K+ channel was also observed in the presence of 5 microM 17-ODYA and 5 microM calphostin C, an inhibitor of protein kinase C. However, addition of 100 microM NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, abolished completely the AII (50-100 nM)-induced increase in channel activity and addition of an exogenous nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine (SNAP), increased channel activity in the presence of L-NAME. These data suggest that the stimulatory effect of AII is mediated by NO. We conclude that AII has dual effects on the activity of the apical 70 pS K+ channel. The inhibitory effect of AII is mediated by P450-dependent metabolites whereas the stimulatory effect may be mediated via NO.

Angiotensin II↗

EITS changes following oleic acid induced lung water.

We present the results of using electrical impedance tomographic spectroscopy (EITS) to follow the changes in lung water induced by oleic acid. Measurements were made on three goats before and after the injection of oleic acid. In addition to the EITs measurements, lung water was also measured using a double-indicator technique. Large falls in lung electrical impedance were seen as a result of the increase in lung water but the size of the fall was a function of the frequency at which the measurements were made. These changes have been modelled using the Cole equation. Four-electrode measurements were also made on two extracted porcine lungs and Cole equation modelling carried out following the introduction of saline into the lungs. Results were similar in the two sets of animal experiments.

Animals↗

Cardiac-related changes in lung resistivity as a function of frequency and location obtained from EITS images.

ECG-gated electrical impedance tomographic spectroscopy (EITS) measurements of the lungs were taken on seven normal subjects in the frequency range 9.6 kHz to 614.4 kHz. The results show that in late systole the resistivity p' relative to the R-wave (i.e. p' = 1 at the R-wave) decreases consistently within the lung. In addition there arises an increase in p' in early systole towards the periphery of the lung. Frequency behaviour of p' changes with location. At all times after the R-wave, in the centre of the lung p' is higher at higher frequency f whereas in the periphery it is lower at higher f. The principal decrease in p' can be explained by increasing pulmonary blood volume due to cardiac contraction. The early systolic increase is presumably due to venous return to the left atrium locally leading blood output from the right ventricle which is delayed by the windkessel effect. Based on a model taking extracapillary and capillary blood volume increase into account, the change in frequency behaviour of p' is explained by regional variations in extracapillary blood vessel size determining the relative contributions of extracapillary blood volume and capillary blood volume change to p' at a certain frequency.

Adult↗

Modelling of cardiac-related changes in lung resistivity measured with EITS.

Resistivity data from 9.6 kHZ to 1.2 MHz were recorded from eight normal subjects using an electrical impedance tomographic spectroscopy (EITS) system and then averaged to a mean cardiac cycle using the ECG gating technique. The Cole-Cole model, that is, extracellular resistance R connected in parallel with intracellular resistance S and membrane capacitance C in series, with a distribution parameter a, was applied to model the frequency characteristics and to produce parametric images. During systole, SC and RC were found to decrease and FR increase. The changes in R/S were not consistent among the subjects. We estimated the peak changes in R, S and C to be -2.5%, -3.3% and -7.6% respectively. The results can be explained by considering the blood vessels as spheres of different sizes with blood inside them. The decrease in R during systole might be caused by the increased blood content in relatively large vessels, whereas that in S by the increased blood volume in relatively small vessels. The capacitance of blood is normally smaller than that of lung tissue, whereas FR blood is higher than that of lung tissue. Hence, as blood content increases, C should decrease and FR increase.

Blood Volume↗

A G/C-rich DNA-regulatory element controls positive expression of the sea urchin Lytechinus pictus aboral ectoderm-specific LpS1 gene.

The LpS1 beta gene of Lytechinus pictus is activated at the late cleavage stage about 12 hr after fertilization. LpS1 beta transcripts accumulate exclusively in aboral ectoderm lineages. LpS1 beta is thus a classic example of a gene whose expression is tightly controlled both temporally and spatially during early development. Previous studies on the LpS1 beta promoter identified two G-string DNA elements, one proximal and one distal to the LpS1 beta transcriptional start site, which bind to an ectoderm-enriched nuclear factor. In this report, we show that the ectoderm G-string factor binds to a G/C-rich region larger than the G-string itself and that the binding of the G-string factor requires sequences immediately downstream from the G-string. These downstream sequences are essential for full promoter activity. Two regions of 5'-flanking DNA are required for positive control of LpS1 beta, region I from base pairs -762 to -511, and region II, which includes the G/C-rich element, from base pairs -108 to -61. Region I also contains a mesenchyme cell repressor element. The results indicate that LpS1 beta expression is regulated positively in ectoderm cells and negatively in mesenchyme cells. Similar positive and negative control mechanisms regulate the expression of the related Spec genes of Strongylocentrotus purpuratus, but in this gene family the DNA elements are entirely different. We hypothesize that cis-regulatory elements are evolutionarily dynamic and that many different combinations of DNA elements are capable of given rise to aboral ectoderm-specific expression.

Animals↗