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Biomedical subjects

S Z Wang

Publications and source records attributed to S Z Wang.

At least 19 recordsLinked to original sources
PubMed2001

neurogenin2 elicits the genesis of retinal neurons from cultures of nonneural cells.

neurogenin2 (ngn2) encodes a basic helix-loop-helix transcription factor and plays an important role in neurogenesis from migratory neural crest cells. Its role in retinal development is poorly understood. We observed that in the developing chick retina, ngn2 was expressed in a subpopulation of proliferating progenitor cells. Ectopic expression of ngn2 in nonneural, retinal pigment epithelial cell culture triggered de novo generation of cells that expressed neural-specific markers and exhibited neuronal morphologies. Further molecular and morphological analyses showed that the main products of the induced neurogenesis were cells resembling young photoreceptor cells and cells resembling retinal ganglion cells. The generation of multiple cell types suggests that ngn2 induces various retinal pathways. Thus, unlike in the peripheral nervous system where ngn2 specifies one type of sensory neuron, ngn2 in the retina is likely involved in a common step leading to different cellular pathways. Our finding that ngn2 can instruct nonneural retinal pigment epithelial cells to differentiate toward retinal neurons demonstrates one possible way to induce de novo retinal neurogenesis.

Animals↗
PubMed2001

Embryonic abnormalities from misexpression of cNSCL1.

cNSCL1 encodes a bHLH transcription factor and is specifically expressed in the developing nervous system. We used a replication-competent retrovirus to drive misexpression of cNSCL1 in chick embryos. We found that cNSCL1 misexpression was embryonic lethal and the embryos exhibited gross abnormalities. Many skeletal bones were abnormal and some were completely absent. Expression of BMP4 was reduced. The abnormalities were due to cNSCL1 misexpression in the systemic region, since microinjection of cNSCL1 retrovirus at one hindlimb primordium severely retarded its development, while other limbs on the same animal appeared normal. Similar misexpression of cNSCL2, a closely related bHLH gene, did not produce these phenotypes. Thus, the detrimental effects on embryonic development were specific to cNSCL1. These data indicate that cNSCL1 expression must be tightly regulated during development.

Animals↗
PubMed2001

Leucocyte populations in respiratory syncytial virus-induced bronchiolitis.

OBJECTIVES: To enumerate the cellular composition of the airways in infants with acute bronchiolitis. METHODOLOGY: Cells were obtained by airway lavage from the upper and lower airway and the peripheral blood of infants with respiratory syncytial virus (RSV)+ bronchiolitis, RSV- bronchiolitis and age-matched controls. RESULTS: Neutrophils are the predominant cells present in the upper and lower airway. Neutrophils are present at a higher number/unit volume in the airway than in the peripheral blood. CONCLUSIONS: Neutrophils, being the dominant cellular infiltrate into the airway, are likely to contribute to the pathophysiology of bronchiolitis. Therapies targeted at limiting neutrophil influx or neutrophil-mediated damage in the airway may have a therapeutic role.

Bronchiolitis, Viral↗
PubMed2001

CCSP modulates airway dysfunction and host responses in an Ova-challenged mouse model.

Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar cells in the lung and modulates lung inflammation to infection. To determine the role of CCSP in the host response to allergic airway disease, CCSP-deficient [(-/-)] mice were immunized twice with ovalbumin (Ova) and challenged by Ova (2 or 5 mg/m(3)) aerosol. After 2, 3, and 5 days of Ova aerosol challenge (6 h/day), airway reactivity was increased in CCSP(-/-) mice compared with wild-type [CCSP(+/+)] mice. Neutrophils were markedly increased in the bronchoalveolar lavage fluid of CCSP(-/-) Ova mice, coinciding with increased myeloperoxidase activity and macrophage inflammatory protein-2 levels. Lung histopathology and inflammation were increased in CCSP(-/-) compared with wild-type mice after Ova challenge. Mucus production, as assessed by histological staining, was increased in the airway epithelium of CCSP(-/-) Ova mice compared with that in CCSP(+/+) Ova mice. These data suggest a role for CCSP in airway reactivity and the host response to allergic airway inflammation and provide further evidence for the role of the airway epithelium in regulating airway responses in allergic disease.

Animals↗
PubMed2001

Atrophy of Müller glia and photoreceptor cells in chick retina misexpressing cNSCL2.

PURPOSE: To investigate whether and how the basic helix-loop-helix (bHLH) gene cNSCL2 is involved in retinal development. METHODS: cNSCL2, the chick homologue of human NSCL2, was isolated and sequenced. In situ hybridization was used to examine its spatial and temporal expression pattern in the retina. Replication-competent retrovirus RCAS was used to drive cNSCL2 misexpression in the developing chick retina, and the effect of the misexpression was analyzed. RESULTS: Expression of cNSCL2 in the retina was restricted. Its mRNA was detected in amacrine and horizontal cells, but not in photoreceptor, bipolar, or ganglion cells. Retroviral-driven misexpression of cNSCL2 in the developing chick retina resulted in missing photoreceptor cells and gross deficits in the outer nuclear layer (ONL). These deficits were probably not because of decreased photoreceptor production, in that the ONL appeared normal in early developmental stages. TUNEL+ cells were detected in the ONL, indicating that photoreceptor cells underwent apoptosis in retinas misexpressing cNSCL2. Müller glial cells were far fewer in the experimental retina than in the control, indicating that cNSCL2 also caused Müller glia atrophy. The onset of Müller glia disappearance preceded that of photoreceptor degeneration. CONCLUSIONS: Expression of cNSCL2 in the chick retina was restricted to amacrine and horizontal cells. Misexpression of cNSCL2 caused severe retinal degeneration, and photoreceptor cells and Müller glia were particularly affected.

Animals↗
PubMed2001

[The development of cerebral circulation analyzer].

In this paper a new cerebral circulation analyzer is introduced, inducing the main structure, the operating principle, the software program and its clinical applications. We can get the cerebrovascular hemodynamics indexes such as resistance, compensatorg blood flow etc., from the blood velocity, pressure waveform, and arterial diameter detected in carotid and vertebral arteries.

Algorithms↗
PubMed2000

Expression of an array of photoreceptor genes in chick embryonic retinal pigment epithelium cell cultures under the induction of neuroD.

Coaxing plastic, non-neuronal cells to transdifferentiate into a particular type of neurons might have clinical applications. Previously we reported that neuroD induces transdifferentiation of retinal pigment epithelium (RPE) cells derived from day-6 chick embryos into cells that resemble young photoreceptor cells. These cells also express visinin, a gene expressed early during cone photoreceptor differentiation. Further characterization showed that the transdifferentiated cells express a number of photoreceptor genes, including interphotoreceptor retinoid binding protein, the alpha-subunit of phosphodiesterase, and opsin genes encoding rhodopsin, the red, the green, and the blue visual pigments. Our data demonstrate that neuroD can reprogram RPE to become photoreceptor cells with substantial differentiation, and suggest the possibility of generating photoreceptor cells from RPE using neuroD as a molecular trigger.

Animals↗
PubMed2000

Adhesion molecule expression on epithelial cells infected with respiratory syncytial virus.

Respiratory epithelium is both a target and an effector of airway inflammation. Adhesion molecules on epithelium play an important role in a variety of airway diseases. Respiratory syncytial virus (RSV) is the most important pathogen for airway diseases in infants. The expression of adhesion molecules on epithelium in RSV infection, however, is unclear. The expression of selected adhesion molecules and major histocompatibility complex (MHC) class I and II antigens on a human alveolar type II epithelial cell line (A549) infected with RSV was investigated by means of flow cytometry and immunocytochemistry. The results showed that intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were expressed on A549 cells at a low level. E-cadherin and MHC class I antigen were constitutively expressed on the cells. RSV infection of A549 cells significantly upregulated the expression of ICAM-1, VCAM-1 and MHC class I and II antigens on these cells. RSV infection also altered the expression of E-cadherin on A549 cells. Immunostaining showed that E-cadherin was mainly upregulated around or in RSV-induced giant cells. These data suggest that respiratory syncytial virus infection of respiratory epithelial cells enhances the expression of adhesion molecules and major histocompatibility complex antigens. These changes may play an important role in the pathophysiology of respiratory syncytial virus disease.

Cell Adhesion Molecules↗
PubMed2000

The interaction of neutrophils with respiratory epithelial cells in viral infection.

Viral respiratory infection is very common. Respiratory syncytial virus (RSV) infects almost all children during the first 2 years of life. Respiratory syncytial virus is the most frequent cause of bronchiolitis, which is strongly linked with asthma. However, the pathophysiology of RSV bronchiolitis is unclear. Neutrophils are the predominant airway leucocytes in RSV bronchiolitis and other viral infections. Neutrophils and their products are likely to play an important role in viral infection. Current evidence indicates that: (i) viral infection of epithelial cells increases the production of neutrophil chemoattractants or chemokines, which induce neutrophil migration into the inflammatory sites; (ii) the expression of adhesion molecules on neutrophils and epithelial cells is up-regulated in viral infection, and neutrophil-epithelial adhesion is increased; (iii) neutrophils augment epithelial damage and detachment induced by viral infection and contribute to the pathophysiology of viral disease; (iv) neutrophil apoptosis is up-regulated in RSV infection, which may be an in vivo mechanism to limit neutrophil-induced epithelial damage; (v) inhibitors of chemokines, adhesion molecules or neutrophil proteases may be useful in prevention of neutrophil-induced epithelial damage. In conclusion, neutrophils play an important role in viral infection, and intervention to prevent neutrophil-induced epithelial damage may be a potential clinical therapy.

Animals↗
PubMed2000

Differences in lymphocyte-regulatory activity among variants of ovine IFN-tau.

Interferon-tau (IFN-tau) is secreted from trophectoderm of the ruminant preimplantation conceptus and functions during pregnancy to prevent luteolysis. In addition, IFN-tau can inhibit proliferation of peripheral blood lymphocytes (PBL) and other cells. Several distinct ovine IFN-tau (OvIFN-tau) gene variants exist; three of these (IFN-tau4, IFN-tau6d, IFN-tau11) differ in their ability to prevent luteolysis (IFN-tau4 > IFN-tau6d > IFN-tau11), inhibit growth of Daudi cells (IFN-tau4 > IFN-tau6d > IFN-tau11), and induce an antiviral state (IFN-tau4 > IFN-tau6d = IFN-tau11). The present objective was to compare variants for differences in ability to inhibit proliferation of phytohemagglutinin-stimulated PBL. At equal concentrations, IFN-tau4 was more inhibitory than IFN-tau6d, IFN-tau11, or an IFN-omega control. Similar differences in potency were seen when IFN-tau variants were tested at equal antiviral concentrations. Thus, the sheep trophectoderm secretes variants of IFN-tau that differ in ability to regulate lymphocyte function. The nature of the effect of the trophectoderm on endometrial lymphocytes may depend on the relative amount of each variant produced.

Animals↗
PubMed2000

Ultrasonographic study of carotid artery structural changes with natural longevity.

The changes in carotid artery structure during the natural longevity of the Uighurs people were compared with other ethnic groups. The 419 subjects were divided into (1) longevity and (2) older groups as follows: Uighurs longevity group in Hotan (ULH); and Uighurs, Hans and Kazaks older groups in Hotan or Balikun (UOH, HOH, HOB and KOB). The wall thickness of the common carotid artery (CCA) was measured by ultrasonography. Risk factors were evaluated by measuring total cholesterol (T-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and fasting glucose, and by 24-h ambulatory blood pressure monitoring. Wall thickness and blood pressure were greater in the Balikun groups than in the Hotan groups. The CCA wall was thicker in Uighurs and Kazaks than in Hans, in the ULH than in the UOH. There was no significant difference in blood pressure among the Hotan groups. LDL-C and glucose were higher and HDL-C was lower in the Hotan groups than in the Balikun groups. T-C, LDL-C, TG and glucose were higher in the HOH than in the ULH and UOH. Systolic blood pressure and LDL-C were higher and TG was lower in the KOB than in the HOB. These results suggest that an increased CCA wall thickness can be attributed to age in Hotan, and to a higher blood pressure level in Balikun, and that the higher blood pressure affected the Balikun groups more than the Hotan groups.

Aged↗
PubMed2000

24-hour blood pressure in Uygur, Kazakh and Han elderly subjects in China.

The Uygur in Hotan (Xinjiang, China) are reported to have a long life expectancy. The purpose of this study was to clarify the relationship between variations in blood pressure (BP) and longevity. Cross-sectional surveillance was carried out in both Hotan and Barkol. The subjects were divided into five groups: 1. Uygur longevity subjects in Hotan (103 subjects, age >90 yr); 2. Uygur elderly subjects in Hotan (107 subjects, age 65-70 yr); 3. Han elderly subjects in Hotan (41 subjects, age 65-70 yr); 4. Kazakh elderly subjects in Barkol (117 subjects, age 65-70 yr); 5. Han elderly subjects in Barkol (50 subjects, age 65-70 yr). BP was monitored and analyzed using the fourteen devices of ambulatory BP monitoring. The prevalence of hypertension was lowest in the Uygur (16.2% in Uygur elderly subjects in Hotan; 23.7% in Uygur longevity subjects in Hotan; 27.0% in Han elderly subjects in Hotan; 42.0% in Han elderly subjects in Barkol; 50.0% in Kazakh elderly subjects in Barkol). The ratio of dips in BP was largest in the Han (57% in Han elderly subjects in Barkol; 50% in Han elderly subjects in Hotan; 50% in Uygur longevity subjects in Hotan, 49% in Uygur elderly subjects in Hotan; 17% in Kazakh elderly subjects in Barkol). The 24-h mean systolic BP in Uygur longevity subjects in Hotan was not different from those in Uygur elderly subjects and Han elderly subjects in Hotan, nor did the 24-h mean diastolic BP differ from those in Uygur elderly subjects and Han elderly subjects in Hotan respectively. In conclusion, Uygur subjects seem to be less hypertensive, compared to Kazakh subjects. Uygur longevity subjects had more dipping in their BP variation than did the Kazakh subjects in Xinjiang, China.

Aged↗
PubMed1999

Misexpression of a bHLH gene, cNSCL1, results in abnormal brain development.

NSCL1 is a basic helix-loop-helix transcription factor involved in the development of the nervous system. To elucidate its role in neurogenesis, we cloned chick NSCL1 (cNSCL1) and examined its expression pattern and the effect of its misexpression on brain development. cNSCL1 was predominantly expressed during active neurogenesis. Double-labeling experiments showed that proliferating neuroblasts in the ventricular zone lacked cNSCL1 expression and cells expressing cNSCL1 were located just outside the ventricular zone. Retroviral misexpression of cNSCL1 in chick embryos produced a brain with abnormal structure. While the forebrain of the embryonic day-12 (E12) brain appeared normal, the tectum was enlarged. The enlargement was likely due to an increase in cell proliferation, since more radioactivity was detected in this region of the brain after [3H]thymidine labeling at E9. The cerebellum, on the other hand, was reduced in size. Fewer cells were labeled with BrdU in the external granule layer (a secondary germinal layer required for cerebellum development) in experimental embryos than in the controls, suggesting that misexpression of cNSCL1 might interfere with cell proliferation in the external granular layer. Our data indicate that regulated expression of cNSCL1 is required for normal brain development. They also imply that cNSCL1 might be involved in preventing some postmitotic cells from reentering the cell cycle during neurogenesis. Dev Dyn 1999;215:238-247.

Amino Acid Sequence↗
PubMed1999

Misexpression of cNSCL1 disrupts retinal development.

cNSCL1 is the chick homologue of mammalian NSCL1, a basic helix-loop-helix gene transiently expressed during neurogenesis. To gain insight into its function, we studied the involvement of cNSCL1 in retinal neurogenesis. In situ hybridization showed dynamic, cell-type-specific expression of cNSCL1, first in developing ganglion cells and later in glial cells. This is drastically different from the expression of neuroD in young photoreceptor cells and their precursors, demonstrating that the proposed neurogenin --> neuroD --> NSCL1 cascade might not apply to retinal neurogenesis in the chick. Small eyes were produced when cNSCL1 was misexpressed in the retinal neuroepithelium through viral transduction. Pulse-labeling with BrdU and [(3)H]thymidine revealed a significant decrease in cell proliferation activity with cNSCL1 misexpression. Massive cell death occurred, but only after cell proliferation activity had subsided, resulting in major distortions of retinal structure. Our data demonstrate the importance of regulated expression of cNSCL1 during retinal development.

Animals↗
PubMed1999

Plasma surfactant protein-B is elevated in infants with respiratory syncytial virus-induced bronchiolitis.

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis. However the pathophysiology of bronchiolitis is unclear. Leukocytes, especially neutrophils, may play an important role in the pathogenesis of bronchiolitis. Whereas we have previously shown that neutrophils augment epithelial leakage and detachment in RSV infection in vitro, it is unknown whether epithelial damage occurs in vivo in infants with RSV bronchiolitis. We hypothesized that respiratory epithelial damage occurs in infants with RSV bronchiolitis and that surfactant proteins leak into the circulation. The plasma concentrations of surfactant protein-A and surfactant protein-B in infants with RSV bronchiolitis were measured by ELISA. Plasma immunoreactive surfactant protein-B in infants with RSV bronchiolitis was markedly higher than that in matching controls. Our study suggests that alveolocapillary permeability is increased in infants with RSV bronchiolitis in vivo and that surfactant protein-B may be a sensitive marker for lung injury in such infants.

Bronchiolitis, Viral↗
PubMed1998

neuroD induces photoreceptor cell overproduction in vivo and de novo generation in vitro.

The molecular mechanisms underlying the generation of the various types of cells in the vertebrate retina are largely unknown. We investigated the possibility that genes belonging to the basic helix-loop-helix (bHLH) family of transcriptional factors participate in cell-type specification during retinal neurogenesis. Chick neuroD was isolated from an embryonic cDNA library and its deduced amino acid sequence showed 75% identity with mouse neuroD. In situ hybridization showed that neuroD was expressed in cells located at the outer portion of the developing retinal neuroepithelium, the location where prospective photoreceptors reside. Misexpression of neuroD in retinal neuroepithelium through replication-competent, transformation-deficient retroviruses produced a retina with three, instead of two, layers of photoreceptor cells; the number of cells that express visinin, a marker for cone photoreceptors, increased over 50% compared to control embryos misexpressing the green fluorescent protein. No significant changes were observed in the number of other retinal neurons, including those that express RA4 (ganglion cells), pax6 (ganglion cells and amacrine cells), and chx10 (bipolar cells). Retroviral-driven misexpression of neuroD in monolayer cultures of retinal pigment epithelium yielded de novo production of photoreceptor cells with no other types of retinal neurons detected. We propose that neuroD is important for photoreceptor cell production in the vertebrate retina.

Amino Acid Sequence↗
PubMed1998

Silencing and activation of embryonic globin gene expression.

An understanding of the mechanisms that control developmental stage-specific transcription of globin genes offers the promise of successful therapeutic activation of fetal or embryonic beta-type genes in beta-thalassemia syndromes. A large body of evidence supports the notion of conservation of such mechanisms across vertebrate species and validates the use of pre-clinical studies of silencing and activation of fetal or embryonic globin genes in animals. Using globin gene transfections into primary avian erythroid cells and cultured murine erythroleukemia cells, we have studied mechanisms involved in stage-specific embryonic beta-type globin gene silencing and activation. These studies show that 1) methylation of the exact CpG nucleotides that are methylated in normal adult erythroid cells in vivo is capable of blocking transcription of a transfected embryonic globin gene promoter via binding of a methyl DNA binding protein in primary erythroid cells. 2) Activation of embryonic beta-type globin gene transcription in adult erythroid cells by short chain fatty acids is mediated through specific DNA sequences both in the promoter and downstream of the promoter.

Animals↗