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Biomedical subjects

H Wang

Publications and source records attributed to H Wang.

At least 649 records · Page 36Linked to original sources
PubMed2000

Differentiation-independent retinoid induction of folate receptor type beta, a potential tumor target in myeloid leukemia.

Folate receptor (FR) type beta is expressed in the myelomonocytic lineage, predominantly during neutrophil maturation and in myeloid leukemias. FR-beta expression was elevated up to 20-fold by all-trans retinoic acid (ATRA) in KG-1 myeloid leukemia cells in a dose-dependent and reversible manner in the absence of terminal differentiation or cell growth inhibition. ATRA also increased FR-beta expression in vitro in myeloid leukemia cells from patient marrow. FR-beta was not up-regulated in KG-1 cells treated with phorbol ester, dexamethasone, 1,25-dihydroxy vitamin D(3), or transforming growth factor beta. ATRA did not induce FR-beta expression in receptor negative cells of diverse origin. The ATRA-induced increase in FR-beta expression in KG-1 cells occurred at the level of messenger RNA synthesis, and in 293 cells containing a stably integrated FR-beta promoter-luciferase reporter construct, ATRA induced expression of the reporter. From experiments using retinoid agonists and antagonists and from cotransfection studies using the FR-beta promoter and expression plasmids for the nuclear receptors retinoic acid receptor (RAR)alpha, RARbeta, or RARgamma, it appears that the retinoid effect on FR-beta expression could be mediated by ligand binding to RARs alpha, beta, or gamma, but not to retinoid X receptors. Furthermore, there was apparent cross-talk between RARalpha and RARgamma selective agonists or antagonists, suggesting a common downstream target for RAR isoforms in inducing FR-beta expression. Thus, blocks in the RARalpha-specific pathway of retinoid-induced differentiation may be bypassed during retinoid induction of FR-beta expression. The results suggest that to facilitate FR-targeted therapies, retinoids may be used to modulate FR-beta expression in myeloid leukemia cells refractory to retinoid differentiation therapy.

Antineoplastic Agents↗
PubMed2000

[A pilot project with mammography--results from the first screening round].

BACKGROUND: Organised mammography screening can reduce mortality from breast cancer. A pilot project for organised mammography screening was started in four Norwegian counties in 1995/1996. This paper evaluates the results from the first screening round with focus on early indicators predicting future mortality reduction. MATERIALS AND METHODS: All women aged 50-69 were offered two-view mammography biennially. The screening examinations were performed in dedicated screening units, and the mammograms were read at breast diagnostic centres located in university hospitals. All test results and information about diagnostic procedures and treatment were reported to The Cancer Registry of Norway and registered in a central screening database. This database was essential in order to monitor and evaluate the pilot project. RESULTS: 79.5% of the invited women accepted and about 127,000 women were examined. The detection rate was 6.7 cancers per 1,000 women screened. 53.1% of the invasive tumours were less than 15 mm; about one fifth of the patients had axillary lymph node metastasis. INTERPRETATION: The obtained results met the predefined aims. Thus a future mortality reduction of at least 30% is expected. The parliamentary decision on expanding the pilot project to a nationwide programme seems well founded.

Aged↗
PubMed2000

A potential role of nuclear matrix-associated protein kinase CK2 in protection against drug-induced apoptosis in cancer cells.

Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. Its activity is generally elevated in rapidly proliferating tissues, and nuclear matrix (NM) is an important subnuclear locale of its functional signaling. In the prostate, nuclear CK2 is rapidly lost commensurate with induction of receptor-mediated apoptosis after growth stimulus withdrawal. By contrast, chemical-induced apoptosis in prostate cancer and other cells (by etoposide and diethylstilbestrol) evokes an enhancement in CK2 associated with the NM that appears to be because of translocation of CK2 from the cytoplasmic to the nuclear compartment. This shuttling of CK2 to the NM may reflect a protective response to chemical-mediated apoptosis. Supporting evidence for this was obtained by employing cells that were transiently transfected with various expression plasmids of CK2 (thereby expressing additional CK2) prior to treatment with etoposide or diethylstilbestrol. Cells transfected with the CK2alpha or CK2alphabeta showed significant resistance to chemical-mediated apoptosis commensurate with the corresponding elevation in CK2 in the NM. Transfection with CK2beta did not demonstrate this effect. These results suggest, for the first time, that besides the commonly appreciated function of CK2 in cell growth, it may also have a role in protecting cells against apoptosis.

Adenocarcinoma↗
PubMed2000

DNA sequence of the insertional hot spot of Tn916 in the Clostridium difficile genome and discovery of a Tn916-like element in an environmental isolate integrated in the same hot spot.

Tn916 is a broad host range tetracycline resistance conjugative transposon. In most bacteria, this element enters the bacterial genome at multiple sites. However, in Clostridium difficile, the element has a strong hot spot when introduced by filter mating from Bacillus subtilis. In this work, the DNA sequence of the preferred insertion site (att916) was obtained. An environmental isolate of C. difficile was also discovered which contained an element indistinguishable from Tn916, Tn916CD. Tn916CD was found integrated at att916.

Bacillus subtilis↗
PubMed2000

Antitumor-promoting effects of cyclic diarylheptanoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

Eleven cyclic diarylheptanoids were screened as potential antitumor promoters by examining the ability of the compounds to inhibit Epstein-Barr virus early antigen activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. 13-Oxomyricanol and myricanone showed the highest activity and also exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These data suggest that certain diarylheptanoids might be valuable antitumor promoters and/or chemopreventors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

First demonstration of an inhibitory activity of milk proteins against human immunodeficiency virus-1 reverse transcriptase and the effect of succinylation.

A variety of milk proteins including lactoferrin, angiogenin-1, alpha-lactalbumin, beta-lactoglobulin, lactoperoxidase, casein and the novel whey proteins lactogenin and glycolactin were tested for inhibitory activity toward human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT), alpha-glucosidase, beta-glucosidase and beta-glucuronidase. Lactoferrin exerted the most potent inhibitory action with an IC50 of about 6 microM. Lactoperoxidase, lactogenin, angiogenin-1 and glycolactin inhibited HIV-1 RT activity with decreasing potencies. Beta-lactoglobulin, alpha-lactalbumin and casein displayed little or no inhibitory effect. Succinylation with succinic anhydride augmented the inhibitory effect of glycolactin, beta-lactoglobulin, alpha-lactalbumin, casein and human lactoferrin. The inhibitory effect of the various milk proteins on the activities of alpha-glucosidase, beta-glucosidase and beta-glucuronidase was meager. Succinylation tended to increase the alpha-glucosidase-inhibitory effect of milk proteins but neither their beta-glucosidase-inhibitory nor beta-glucuronidase-inhibitory effect was affected.

Animals↗
PubMed2000

Development of Th1-type immune responses requires the type I cytokine receptor TCCR.

On antigen challenge, T-helper cells differentiate into two functionally distinct subsets, Th1 and Th2, characterized by the different effector cytokines that they secrete. Th1 cells produce interleukin (IL)-2, interferon-gamma (IFN-gamma) and lymphotoxin-beta, which mediate pro-inflammatory functions critical for the development of cell-mediated immune responses, whereas Th2 cells secrete cytokines such as IL-4, IL-5 and IL-10 that enhance humoral immunity. This process of T-helper cell differentiation is tightly regulated by cytokines. Here we report a new member of the type I cytokine receptor family, designated T-cell cytokine receptor (TCCR). When challenged in vivo with protein antigen, TCCR-deficient mice had impaired Th1 response as measured by IFN-gamma production. TCCR-deficient mice also had increased susceptibility to infection with an intracellular pathogen, Listeria monocytogenes. In addition, levels of antigen-specific immunoglobulin-gamma2a, which are dependent on Th1 cells, were markedly reduced in these mice. Our results demonstrate the existence of a new cytokine receptor involved in regulating the adaptive immune response and critical to the generation of a Th1 response.

Amino Acid Sequence↗
PubMed2000

Resuscitative effects of polynitroxylated alphaalpha-cross-linked hemoglobin following severe hemorrhage in the rat.

alphaalpha-Cross-linked hemoglobin (alphaalphaHb) is an example of a hemoglobin-based oxygen carrier (HBOC) with significant cardiovascular activity. This may compromise the safety and efficacy of this HBOC by causing systemic hypertension and reducing blood flow to some organs. The present work is based on the hypothesis that incorporating antioxidant activity into an HBOC in the form of a covalently attached nitroxide may prevent these effects. We have tested this hypothesis by adding antioxidant activity to alphaalphaHb with 2,2,6,6-tetramethyl-piperidinyl-1-oxyl (Tempo) to create polynitroxylated alphaalphaHb (PN-alphaalphaHb). The new compound PN-alphaalphaHb acts as an antioxidant in our in vitro and in vivo assays. In this study urethane-anesthetized rats were hemorrhaged to a mean arterial pressure (MAP) of 35-40 mmHg and maintained for 30 min. Animals were resuscitated with solutions of (1) 10% PN-alphaalphaHb (43 mmHg), (2) 10% alphaalphaHb (43 mmHg), (3) 7.5% albumin (43 mmHg), (4) 300% Ringers lactate (RL), and (5) 0. 9% normal saline equal to the shed blood volume (SBV). Hemodynamics and regional blood circulation was measured at baseline, following hemorrhage, and at 30 and 60 min postresuscitation using a radioactive microsphere technique. Base deficit (BD) was measured at baseline, following hemorrhage, and at 60 min following resuscitative fluid infusion. Finally survival was determined as the time following resuscitation until secession of heart rhythm. Saline and 300% RL resuscitation did not improve BD, systemic hemodynamics, or regional blood circulation. PN-alphaalphaHb, alphaalphaHb, and albumin significantly improved these parameters, however, only PN-alphaalphaHb and alphaalphaHb improved survival. PN-alphaalphaHb was found to be less hypertensive than alphaalphaHb due to blunted increases in both cardiac output and systemic vascular resistance. This study demonstrates that, by using alphaalphaHb as a scaffold for polynitroxylation, improvement in vasoactivity and resuscitative efficacy may be possible. In conclusion, the addition of antioxidant activity in the form of polynitroxylation of a low molecular weight Hb (alphaalphaHb) may create a safe and efficacious resuscitative fluid.

Animals↗
PubMed2000

The gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics.

A microtubule-associated protein, gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein (GABARAP), was previously identified as binding to the intracellular domain of GABA(A) receptors by using the yeast two-hybrid screen. In the present work, immunofluorescent staining and green fluorescent protein-tagged receptor subunits showed that GABARAP is associated with and promotes the clustering of GABA(A) receptors in QT-6 quail fibroblasts. The tubulin-binding motif of GABARAP and the gamma2 subunit of the receptor are required. Disruption of microtubules prevents the clustering in a time-dependent manner. When green fluorescent protein-tagged alpha1 or gamma2 subunit coexpressed with beta2, gamma2L, and GABARAP was used, recordings from visually identified cells revealed that clustered GABA(A) receptor had an EC(50) of about 20 microM, vs. 5.7 microM for the diffuse receptor. Clustered receptors deactivated faster and desensitized slower than the diffuse receptors, because of decrease in the apparent affinity of GABA binding. Different properties for clustered receptors relative to unclustered receptors in heterologous cells suggest that homologous differences between extrasynaptic and synaptic clustered receptors in neurons may be due to the organization of the postsynaptic machinery.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Observation of a continuum-continuum interference hole in ultrafast dissociating core-excited molecules.

The femtosecond dissociation of HCl after core excitation has been studied through the resonant Auger decay. The spectra contain contributions from decay occurring at both "molecular" and "atomic" internuclear distances. We have observed a new interference mechanism in these spectra: An atomic spectral line develops into a negative spectral contribution, a "hole," when detuning the excitation energy from the maximum of the Cl2p(-1)sigma(*) resonance. Resonant x-ray scattering theory quantitatively explains this behavior as due to a novel destructive continuum-continuum interference between molecular and atomic contributions to the Auger decay.

Journal Article↗
PubMed2000

A zebrafish vitellogenin gene (vg3) encodes a novel vitellogenin without a phosvitin domain and may represent a primitive vertebrate vitellogenin gene.

By analysis of zebrafish EST (expressed sequence tag) clones from an adult cDNA library, we have identified 44 clones, about 11% of the adult EST clones, encoding vitellogenins. These vitellogenin EST clones have been derived from at least seven distinct vitellogenin genes. One of the largest vitellogenin cDNA clones, vg3, and its 5' extended clone isolated by 5' RACE (rapid amplification of cDNA ends)-PCR, have been sequenced completely. The deduced complete sequence includes a predicted mature vitellogenin of 1233 amino acids and a truncated signal peptide of 18 amino acids. Interestingly, the predicted vitellogenin has no polyserine phosvitin domain. The lack of the phosvitin domain was confirmed by isolation and sequencing of the vg3 genomic region. Phylogenetic analysis indicates that the phosvitinless vitellogenin is an intermediate between invertebrate vitellogenins and all known vertebrate vitellogenins, and thus may represent a primitive vertebrate vitellogenin. Like other vitellogenins in vertebrates, the phosvitinless vitellogenin is also synthesized mainly in the liver and weakly in the intestine.

Amino Acid Sequence↗
PubMed2000

Parallel analyses of nociceptive neurones in rat superior colliculus by using c-fos immunohistochemistry and electrophysiology under different conditions of anaesthesia.

Multiple sensory inputs to the superior colliculus (SC) play an important role in guiding head and eye movements toward or away from biologically significant stimuli. Much is now known about the visual, auditory, and somatosensory response properties of SC neurones that mediate these behavioural reactions. Rather less is known about the responses of SC neurones to noxious stimuli, and thus far, most of this information has been obtained in anaesthetised animals. Therefore, the purpose of the present study was to use the c-fos immunohistochemical technique and standard extracellular electrophysiology as parallel measures of nociceptive activity in the SC under different conditions of anaesthesia. In unanaesthetised animals, experimental and control treatments induced a qualitatively similar pattern of Fos-like immunoreactivity (FLI) in the SC, which was quantitatively related to the severity or biologic salience of the treatment; thus, baseline control < control injections of saline < a nonpainful stressor (immobilisation) < noxious injections of formalin. Compared with baseline levels, urethane and avertin anaesthesia induced FLI expression in the SC intermediate layers, although the FLI response to both noxious stimulation and control conditions was differentially suppressed in different layers of the SC by anaesthesia. Parallel electrophysiologic recordings found that anaesthesia was associated with high levels of spontaneous activity in the SC intermediate layers, often in neurones which were also nociceptive. High rates of background spike activity were also induced in the SC intermediate layers by noxious stimulation in chronically recorded awake animals. Although these results point to some differences between the nociceptive responses of SC neurones in anaesthetised and unanaesthetised animals, both data sets support the view that there are different populations of nociceptive neurones in the rodent SC that may be related to different adaptive functions of pain.

Anesthesia↗
PubMed2000

Volumetric properties for the monosaccharide (D-xylose, D-arabinose, D-glucose, D-galactose)-NaCl-water systems at 298.15 K.

Densities have been measured for monosaccharide (D-xylose, D-arabinose, D-glucose and D-galactose)-NaCl-water solutions at 298.15 K. These data have been used to determine the apparent molar volumes of these saccharides and NaCl in the studied solutions. Infinite-dilution apparent molar volumes for the saccharides (V0(phi,S)) in aqueous NaCl and those for NaCl (V0(phi,E)) in aqueous saccharide solutions have been evaluated, together with the standard transfer volumes of the saccharides (delta(t) V0S) from water to aqueous NaCl and of NaCl (delta(t) V0E) from water to aqueous saccharide solutions. It is shown that the delta(t) V0S and delta (t) V0E values are positive and increase with increasing co-solute molalities. Volumetric parameters indicating the interactions of NaCl with saccharides in water have been obtained, respectively, by using transfer volumes of the saccharides and NaCl, and the resulting values are in good agreement with each other within experimental error. The interactions between saccharides and NaCl are discussed in terms of the structural interaction model and the stereochemistry of the saccharide molecules in water.

Arabinose↗
PubMed2000

Preparation and biological activity of amino acid and peptide conjugates of antitumor hydroxymethylacylfulvene.

The primary hydroxyl group in hydroxymethylacylfulvene, a potent antitumor drug, is readily replaced by thiols including cysteine, N-acetylcysteine, homocysteine, and glutathione. Best yields are obtained when reaction is carried out in the presence of dilute sulfuric acid. A variety of sulfur-containing analogues have been prepared, and their toxicity to tumor cells was examined.

Amino Acids↗
PubMed2000

Schizosaccharomyces pombe Rad9 contains a BH3-like region and interacts with the anti-apoptotic protein Bcl-2.

Here we report that the Schizosaccharomyces pombe Rad9 (SpRad9) protein contains a group of amino acids with similarity to the Bcl-2 homology 3 death domain, which is required for SpRad9 interaction with human Bcl-2 and apoptosis induction in human cells. Overexpression of Bcl-2 in S. pombe inhibits cell growth independently of rad9, but enhances resistance of rad9-null cells to methyl methanesulfonate, ultraviolet and ionizing radiation. These observations suggest that SpRad9 may represent the first member of the Bcl-2 protein family identified in yeast, though the cell death pathways in S. pombe may differ from those found in mammals.

Apoptosis↗
PubMed2000

Synthetic peptides which inhibit the interaction between C1q and immunoglobulin and prolong xenograft survival.

BACKGROUND: Acute vascular xenograft rejection (AVXR), also termed delayed xenograft rejection (DXR), occurs when hyperacute rejection (HAR) is prevented by strategies directed at xenoreactive natural antibodies and/or complement activation. We have hypothesized that AVXR/DXR is initiated in part by early components of the complement cascade, notably C1q. We have developed synthetic peptides (termed CBP2 and WY) that interfere with the interaction between C1q and antibody. METHODS: CBP2 and the WY-conjugates were used as inhibitors of immunoglobulin aggregate binding to solid phase C1q. Inhibition of complement activation by the peptides of the classical system was determined using lysis assays with sensitized sheep red blood cells or porcine aortic endothelial cells as targets and of the alternate complement pathway using guinea pig red blood cells as targets. Two transplant models were used to study the effects of administering peptides to recipients: rat heart transplant to presensitized mouse, and guinea heart transplant to PVG C6-deficient rats. RESULTS: CBP2 and WY-conjugates inhibited immunoglobulin aggregate binding to C1q. The peptides also inhibited human complement-mediated lysis of sensitized sheep red blood cells and porcine aortic endothelial cells in a dose-dependent manner and the WY-conjugates prevented activation of the alternate complement pathway as shown by inhibition of guinea pig red blood cells lysis with human serum. In addition, the use of the peptides and conjugates resulted in significant prolongation of xenograft survival. CONCLUSIONS: The CBP2 and WY peptides exhibit the functional activity of inhibition of complement activation. These peptides also prolong xenograft survival and thus provide reagents for the study of the importance of C1q and other complement components in transplant rejection mechanisms.

Animals↗
PubMed2000

HMG-1 as a mediator of acute lung inflammation.

Acute inflammatory lung injury is often a delayed complication of critical illness and is associated with increased mortality. High mobility group-1 (HMG-1) protein, in addition to its role as a transcriptional regulatory factor, has recently been identified as a late mediator of endotoxin lethality. In the present studies, HMG-1 given intratracheally produced acute inflammatory injury to the lungs, with neutrophil accumulation, the development of lung edema, and increased pulmonary production of IL-1beta, TNF-alpha, and macrophage-inflammatory protein-2. In endotoxin-induced acute lung inflammation, administration of anti-HMG-1 Abs either before or after endotoxin exposure decreased the migration of neutrophils to the lungs as well as lung edema. These protective effects of anti-HMG-1 were specific, because pulmonary levels of IL-1beta, TNF-alpha, or macrophage-inflammatory protein-2 were not decreased after therapy with anti-HMG-1. Together, these findings indicate that HMG-1 is a distal mediator of acute inflammatory lung injury.

Adjuvants, Immunologic↗