Biomedical subjects

H Wang

Publications and source records attributed to H Wang.

At least 721 records · Page 40Linked to original sources

PubMed2000

Participation of endogenously produced interferon gamma in interleukin 4-mediated tumor rejection.

To elucidate the molecular mechanism underlying IL-4-induced tumor rejection, we challenged mice with a mouse adenocarcinoma cell line, colon 26, genetically engineered to express constitutively IL-4 gene (colon 26/IL-4). Immunocompetent BALB/c mice rejected colon 26/IL-4 cells but not parental cells or cells transduced with a control gene (colon 26/control). Moreover, on rechallenge, parental cells and colon 26/control cells were rejected by normal BALB/c mice that had previously rejected colon 26/IL-4. However, both nude and severe combined immunodeficiency (SCID) mice failed to reject colon 26/IL-4 as well as parental or colon 26/control cells. In contrast, nude mice did reject colon 26/IL-4 after transfer of lymphocytes obtained from the draining lymph nodes of BALB/c mice injected with colon 26/IL-4. These results indicate that challenging mice with colon 26/IL-4 tumor cells resulted in the generation of memory cytotoxic T lymphocytes in the draining lymph nodes. At 3 days after the challenge, IFN-gamma, IL-12 p35, and p40 mRNA expression was selectively enhanced in the draining lymph nodes of mice bearing colon 26/IL-4 cells. Finally, mice deficient in the IFN-gamma gene did not reject colon 26/IL-4 cells. These results suggest that IL-4-induced memory cytotoxic T lymphocyte generation requires IFN-gamma production in the draining lymph nodes, in order to generate a protective immune response.

Adenocarcinoma↗

PubMed2000

Interaction of von Willebrand factor domain A1 with platelet glycoprotein Ibalpha-(1-289). Slow intrinsic binding kinetics mediate rapid platelet adhesion.

We investigated the crucial hemostatic interaction between von Willebrand factor (VWF) and platelet glycoprotein (GP) Ibalpha. Recombinant VWF A1 domain (residues Glu(497)-Pro(705) of VWF) bound stoichiometrically to a GPIbalpha-calmodulin fusion protein (residues His(1)-Val(289) of GPIbalpha; GPIbalpha-CaM) immobilized on W-7-agarose with a K(d) of 3.3 microM. The variant VWF A1(R545A) bound to GPIbalpha-CaM 20-fold more tightly, mainly because the association rate constant k(on) increased from 1,100 to 8,800 M(-1) s(-1). The GPIbalpha mutations G233V and M239V cause platelet-type pseudo-von Willebrand disease, and VWF A1 bound to GPIbalpha(G233V)-CaM and GPIbalpha(M239V)-CaM with a K(d) of 1.0 and 0.63 microM, respectively. The increased affinity of VWF A1 for GPIbalpha(M239V)-CaM was explained by an increase in k(on) to 4,500 M(-1) s(-1). GPIbalpha-CaM bound with similar affinity to recombinant VWF A1, to multimeric plasma VWF, and to a fragment of dispase-digested plasma VWF (residues Leu(480)/Val(481)-Gly(718)). VWF A1 and A1(R545A) bound to platelets with affinities and rate constants similar to those for binding to GPIbalpha-CaM, and botrocetin had the expected positively cooperative effect on the binding of VWF A1 to GPIbalpha-CaM. Therefore, allosteric regulation by botrocetin of VWF A1 binding to GPIbalpha, and the increased binding affinity caused by mutations in VWF or GPIbalpha, are reproduced by isolated structural domains. The substantial increase in k(on) caused by mutations in either A1 or GPIbalpha suggests that productive interaction requires rate-limiting conformational changes in both binding sites. The exceptionally slow k(on) and k(off) provide important new constraints on models for rapid platelet tethering at high wall shear rates.

Antibodies, Monoclonal↗

PubMed2000

Presence of NMDA-type glutamate receptors in cingulate corticostriatal terminals and their postsynaptic targets.

The glutamatergic projection from the anterior cingulate cortex to the medial caudate-putamen nucleus (CPN) has been implicated in motor and cognitive functions, many of which are potently modulated by activation of N-methyl-D-aspartate subtype of glutamate receptors (NMDARs). To determine the functional sites for NMDAR activation within this circuitry, we combined anterograde transport of biotinylated dextran amine (BDA) from deep layers of the rat anterior cingulate cortex with immunogold labeling of NMDAR subunit, NMDAR1, in the dorsomedial CPN. BDA-containing axons were seen in patch-like clusters in a neuropil that showed more uniform immunogold-silver labeling for NMDAR1. Electron microscopy of these regions showed that BDA-labeling was present exclusively in axons and terminals, 23% (98 of 421) of which also contained NMDAR1-immunoreactivity (IR). BDA-labeled terminals often apposed NMDAR1-immunoreactive neuronal and glial profiles. These terminals also formed asymmetric excitatory-type synapses with dendritic spines. Of 155 anterogradely labeled axon terminals forming asymmetric synapses, 34% were with NMDAR1-labeled, and 66% with unlabeled dendritic spines. These results provide ultrastructural evidence for the involvement of NMDARs in presynaptic regulation of glutamate transmission, and in postsynaptic modulation of the excitability of spiny neurons in patch-like compartments of the dorsomedial CPN. These dual NMDAR-mediated actions are likely to play a major role in the acquisition of new behaviors and reward-related processes that have been associated with cortical input to the striatal patch compartments.

Animals↗

PubMed2000

Electric-octupole and pure-electric-quadrupole effects in soft-X-Ray photoemission

Second-order [ O(k(2)), k = omega/c] nondipole effects in soft-x-ray photoemission are demonstrated via an experimental and a theoretical study of angular distributions of neon valence photoelectrons in the 100-1200 eV photon-energy range. A newly derived theoretical expression for nondipolar angular distributions characterizes the second-order effects using four new parameters with primary contributions from pure-quadrupole and octupole-dipole interference terms. Independent-particle calculations of these parameters account for a significant portion of the existing discrepancy between experiment and theory for Ne 2p first-order nondipole parameters.

Journal Article↗

PubMed2000

Cre-mediated cerebellum- and hippocampus-restricted gene mutation in mouse brain.

Using the phage P1-derived Cre/loxP recombination system, we have created a line of cre-transgenic mice in which the Cre-mediated gene deletion is restricted to granule cells of cerebellum and dentate gyrus of hippocampus. Low levels of deletion were also present in pyramidal cells of hippocampal CA1 and CA3 fields. The Cre/loxP recombination occurred prenatally. The recombination efficiencies in the granular layer of the cerebellum, the granular layer of the dentate gyrus, and the CA1 and CA3 pyramidal cells of the hippocampus were 34.0%, 23.1%, 3.0%, and 9.8%, respectively. This line of cre-transgenic mice should be conducive to studies of the effect of a gene mutation upon brain development and plasticity.

Animals↗

PubMed2000

Current aspects in pharmacology of modified hemoglobins.

Blood substitutes are products that are designed to replace whole blood (or) red blood cells in the field of transfusion medicine. There are two major classes that belong to this new therapeutics: (i) modified hemoglobins and (ii) perfluorocarbons. Modified hemoglobins have made tremendous progress in the past decade and are being considered for a wide variety of conditions like trauma, elective surgery, oxygenation of tumors to make them more sensitive to radiation therapy, stroke etc. Although, these agents are primarily used for oxygen delivery, their pharmacological actions have been significantly important. Several mechanisms are being explored to explain these pharmacological effects. Modified hemoglobins suffer several drawbacks including hypertension, renal toxicity, and pulmonary hypertension that restrict their development. This review deals with the clinical status and pharmacological actions of modified hemoglobins presently in advanced stages of development and some of the newer generation hemoglobin based therapeutics are also discussed.

Animals↗

PubMed2000

Stage-specific isoforms of Ascaris suum complex. II: The fumarate reductase of the parasitic adult and the succinate dehydrogenase of free-living larvae share a common iron-sulfur subunit.

Complex II of adult Ascaris suum muscle exhibits high fumarate reductase (FRD) activity and plays a key role in anaerobic electron-transport during adaptation to their microaerobic habitat. In contrast, larval (L2) complex II shows a much lower FRD activity than the adult enzyme, and functions as succinate dehydrogenase (SDH) in aerobic respiration. We have reported the stage-specific isoforms of complex II in A. suum mitochondria, and showed that at least the flavoprotein subunit (Fp) and the small subunit of cytochrome b (cybS) of the larval complex II differ from those of adult. In the present study, complete cDNAs for the iron-sulfur subunit (Ip) of complex II, which with Fp forms the catalytic portion of complex II, have been cloned and sequenced from anaerobic adult A. suum, and the free-living nematode, Caenorhabditis elegans. The amino acid sequences of the Ip subunits of these two nematodes are similar, particularly around the three cysteine-rich regions that are thought to comprise the iron-sulfur clusters of the enzyme. The Ip from A. suum larvae was also characterized because Northern hybridization showed that the adult Ip is also expressed in L2. The Ip of larval complex II was recognized by the antibody against adult Ip, and was indistinguishable from the adult Ip by peptide mapping. The N-terminal 42 amino acid sequence of Ip in the larval complex II purified by DEAE-cellulofine column chromatography was identical to that of the mature form of the adult Ip. Furthermore, the amino acid composition of larval Ip determined by micro-analysis on a PVDF membrane is almost the same as that of adult Ip. These results, together with the fact, that homology probing by RT-PCR, using degenerated primers, failed to find a larval-specific Ip, suggest that the two different stage-specific forms of the A. suum complex II share a common Ip subunit, even though the adult enzyme functions as a FRD, while larval enzyme acts as an SDH.

Amino Acid Sequence↗

PubMed2000

Total synthesis of the fumiquinazoline alkaloids: solution-phase studies.

Biomimetic total syntheses of glyantrypine, fumiquinazoline F, fumiquinazoline G, and fiscalin B were achieved in four steps from tryptophan methyl ester. In the key step, the anthranilamide residue in a linear tripeptide is dehydrated to a benzoxazine by reaction with triphenylphosphine, iodine, and a tertiary amine. The benzoxazines subsequently undergo rearrangement to the natural products via an amidine intermediate. This dehydrative oxazine to quinazoline route is applicable to a broad range of N-acylanthranilamides, including sterically hindered cases.

Alkaloids↗

PubMed2000

White matter volumes and periventricular white matter hyperintensities in aging and dementia.

OBJECTIVE: To determine the relationship between MRI periventricular white matter hyperintensities, cerebral white matter volumes, neuropathologic findings, and cognitive status in aged individuals. BACKGROUND: The significance of periventricular white matter hyperintensities seen on MR images in aged individuals remains controversial. The Nun Study is a longitudinal cohort aging study in which all 678 initially enrolled participants agreed to autopsy neuropathologic examination. METHODS: We used MRI to measure white matter volumes of the cerebral hemispheres in 52 formaldehyde-fixed brains for correlation with white matter and neocortical pathology, postmortem MRI observations, and cognitive measures. RESULTS: Reduced white matter volume is associated with dementia, but periventricular white matter hyperintensities were not related to white matter volume, stroke, or dementia. CONCLUSIONS: Our results do not support the hypothesis that periventricular hyperintensities seen on MR images have deleterious consequences in these aged individuals.

Aged↗

PubMed2000

Fractionation and analysis of Artemisia capillaris Thunb. by affinity chromatography with human serum albumin as stationary phase.

A method for the screening and analysis of biologically active compounds in traditional Chinese medicine is proposed. Affinity chromatography using a human serum albumin (HSA) stationary phase was applied to separate and analyze the bioactive compounds from Artemisia capillaris Thunb. Five major peaks and several minor peaks were resolved based on their affinity to HSA, two of them were identified as scoparone (SCO, 6,7-dimethoxycoumarin) and capillarisin (CAP). CAP shows a much higher affinity to HSA than SCO. The effects of acetonitrile concentration, eluent pH, phosphate concentration and temperature on the retention behaviors of several major active components were also investigated, and it was found that hydrophobicity and eluent pH play major roles in changing retention values. The results demonstrate that the affinity chromatography with a HSA stationary phase is an effective way for analyzing and screening biologically active compounds in traditional Chinese medicine.

Acetonitriles↗

PubMed2000

Simian virus 40 large T antigen binds a novel Bcl-2 homology domain 3-containing proapoptosis protein in the cytoplasm.

A 193-kDa SV40 large T antigen (T-Ag)-binding protein, designated p193, was identified and cloned. Inspection of the deduced amino acid sequence revealed the presence of a short motif similar to the Bcl-2 homology (BH) domain 3, suggesting that p193 may be a member of a family of apoptosis promoting proteins containing only BH3 motifs. In support of this, p193 expression promoted apoptosis in NIH-3T3 cells. Deletion of the BH3 motif abolished p193 apoptosis activity. p193-induced apoptosis was antagonized by co-expression of Bcl-X(L). Immune cytologic analysis indicated that p193 is localized to the cytoplasm of transfected cells. p193-induced apoptosis was also antagonized by co-expression of T-Ag, which resulted in the cytoplasmic localization of both proteins. The p193 binding site was mapped to an N-terminal region of T-Ag previously implicated in transforming activity. These results suggest that T-Ag possesses an antiapoptosis activity, independent of p53 sequestration, which is actuated by T-Ag/p193 binding in the cytoplasm.

3T3 Cells↗

PubMed2000

Crystal structure of a fibrillarin homologue from Methanococcus jannaschii, a hyperthermophile, at 1.6 A resolution.

Fibrillarin is a phylogenetically conserved protein essential for efficient processing of pre-rRNA through its association with a class of small nucleolar RNAs during ribosomal biogenesis. The protein is the antigen for the autoimmune disease scleroderma. Here we report the crystal structure of the fibrillarin homologue from Methanococcus jannaschii, a hyperthermophile, at 1.6 A resolution. The structure consists of two domains, with a novel fold in the N-terminal region and a methyltransferase-like domain in the C-terminal region. Mapping temperature-sensitive mutations found in yeast fibrillarin Nop1 to the Methanococcus homologue structure reveals that many of the mutations cluster in the core of the methyltransferase-like domain.

Amino Acid Sequence↗

PubMed2000

Congenital absence of permanent teeth in a six-generation Chinese kindred.

We report on rare, heritable, permanent tooth agenesis in a large Chinese kindred. The congenital absence of permanent teeth except the first and second accessory teeth was observed in 52 individuals through six successive generations in the kindred comprising 328 members. Clinical assessments were carried out, and inheritance mode and spousal influence of the anomaly on their offspring were analyzed. Consequently, the anomaly was transmitted in an autosomal dominant fashion with incomplete penetrance (P = 0.88), and no significant clinical manifestations other than the oligodontia were found. A geographical or environmental effect on the affected individuals was obviously eliminated, because any who are related to the kindred but live under the same conditions are fully healthy. The disorder we describe, therefore, differs from any previously reported oligodontia/anodontia syndromes. The oligodontia ranged from a few teeth to the whole set of teeth, and usually occurred at a period from age 7 or 8 years, the time when primary teeth are normally replaced by permanent teeth, to the forties. Roentgenography of the affected persons indicated that only the first and/or second accessory teeth with tooth buds developed as permanent teeth. In fact, the diphyodontic germination sometimes occurred in the oral cavity of the affected individuals.

China↗

PubMed2000

[Zinc modulates the Ca(2+)-ATPase activity of rat osteoblast membrane].

The effect and mechanism of zinc on Ca(2+)-ATPase and Na+, K(+)-ATPase activity of rat osteoblast membrane were studied. The activities were measured by colorimetric method. The effect of special inhibitors of protein kinase C or calmodulin on membrane Ca(2+)-ATPase and Na+, K(+)-ATPase activity which induced by zinc were also examined. The results showed that zinc could increase membrane Ca(2+)-ATPase activity, but no influence was observed on Na+, K(+)-ATPase activity. R24571, a special inhibitor of calmodulin, had no effect on membrane Ca(2+)-ATPase activity. Calmodulin also could not promote the basic Ca(2+)-ATPase activity of membrane. But trifluoperazine, a special inhibitor of protein kinase C, obviously reduced its activity. It was concluded that the modulation of zinc on membrane Ca(2+)-ATPase activity of rat osteoblast could be mediated by protein kinase C.

Animals↗

PubMed2000

Rapid antibody responses by low-dose, single-step, dendritic cell-targeted immunization.

We have compared the kinetics of antibody responses in conventional and dendritic cell-targeted immunization by using a model antigen in mice. Targeting was achieved by linking the reporter antigen (polyclonal goat anti-hamster antibody) to N418, a hamster mAb that binds to the CD11c molecule on the surface of murine dendritic cells. Intradermal injection of submicrogram quantities of goat anti-hamster antibody complexed to mAb N418 elicited goat antibody-specific serum IgG in mice. Antigen-specific IgG titers were detectable by day 5, with titers that ranged from 1:1000 to 1:100,000 by day 7. In contrast, when the goat antigen was injected alone or in the presence of a hamster antibody control to form nontargeted complexes, goat-specific serum IgG was undetectable at day 7. Additional control experiments showed that the interaction between the model antigen and mAb N418 is required for amplification of the serum antibody response. These studies demonstrate that a single-step, facilitated-delivery of small amounts of protein antigen to dendritic cells in vivo can give very rapid and high antibody responses. The approach may be particularly useful for vaccination immediately before or just after exposure to a pathogen and may enhance the utility of subunit antigens as immunogens.

Animals↗

PubMed2000

Biphasic modulation of ryanodine binding to sarcoplasmic reticulum vesicles of skeletal muscle by Zn2+ ions.

With the use of a [(3)H]ryanodine binding assay, the modulation of skeletal muscle ryanodine receptor (RyR1) by Zn(2+) was investigated. In the presence of 100 microM free Ca(2+) concentration ([Ca(2+)](f)) as activator, the equilibrium [(3)H]ryanodine binding to heavy sarcoplasmic reticulum vesicles was biphasically modulated by Zn(2+). The binding was increased by a free Zn(2+) concentration ([Zn(2+)](f)) of less than 1 microM; a peak binding, approx. 140% of the control (without added Zn(2+)) was obtained at 0.3 microM [Zn(2+)](f). An inhibitory effect of Zn(2+) became obvious with a [Zn(2+)](f) of more than 1 microM; the [Zn(2+)](f) for producing half inhibition was 2.7+/-0.5 microM (mean+/-S.D.). Scatchard analysis indicated that the increase in the binding induced by low [Zn(2+)](f) was due to a decrease in K(d), whereas both an increase in K(d) and a possible decrease in B(max) were responsible for the decrease in binding induced by high [Zn(2+)](f). The binding in the presence of micromolar [Zn(2+)](f) showed a biphasic time course. In the presence of 3 microM [Zn(2+)](f), after reaching a peak with an increased rate of initial binding, the binding gradually declined. The decline phase could be prevented by decreasing [Zn(2+)](f) to 0.5 microM or by adding 2 mM dithiothreitol, a thiol-reducing agent. The [Ca(2+)](f) dependence of binding was changed significantly by Zn(2+), whereas Ca(2+) had no clear effect on the [Zn(2+)](f) dependence of binding. Moreover, some interactions were found in the effects between Zn(2+) and other RyR1 modulators. It is indicated that Zn(2+) can modulate the activation sites and inactivation sites for Ca(2+) on RyR1. The physiological significance of the effects of Zn(2+) on ryanodine binding is discussed.

Adenosine Monophosphate↗

PubMed2000

Synthesis of a silica-bonded bovine serum albumin s-triazine chiral stationary phase for high-performance liquid chromatographic resolution of enantiomers.

A novel method of synthesizing protein chiral stationary phase (protein-CSP) is proposed with 2,4,6-trichloro-1,3,5-triazine as the activator. The bovine serum albumin (BSA) based chiral columns (150 x 4.6 mm I.D.) were prepared successfully within 8 h. With tryptophan as the probe solute, it was observed that the BSA immobilized by this method had a better ability to distinguish enantiomers than that activated by glutaric dialdehyde. This may be due to the well-maintained BSA conformation and the larger amount of BSA immobilized on the silica gel. The BSA-CSP prepared by this method was relatively stable under experimental conditions, and the resolution of 13 chiral compounds was achieved. The coupling reaction in this method is mild, reliable and reproducible; it is also suitable for the immobilization of various biopolymers in the preparation of bioreactor, biosensor and affinity chromatography columns.

Chromatography, High Pressure Liquid↗

PubMed2000

Comparison of Transient Network Brightenings and Explosive Events in the Solar Transition Region.

The relation between transient network brightenings, known as blinkers, and explosive events is examined based on coordinated quiet Sun observations in the transition region line O v lambda630 recorded by the Coronal Diagnostic Spectrometer (CDS), in the transition region line Si iv lambda1402 recorded by the Solar Ultraviolet Measurements of Emitted Radiation (SUMER) instrument, and in photospheric magnetograms taken by the Big Bear Solar Observatory videomagnetograph. From these observations, we find that (1) explosive events, which are traditionally defined as features with very broad UV line profiles, tend to keep away from the centers of network brightenings and are mostly located at the edges of such brightenings, (2) CDS blinkers consist of many small-scale, short-lived SUMER "unit brightening events" with a size of a few arcseconds and a lifetime of a few minutes, and most importantly (3) each SUMER unit brightening event is characterized by a UV line profile that is not as broad as those of explosive events, but still has significantly enhanced wings. Our results imply that, like explosive events, individual unit brightening events involve high velocities, and, hence, blinkers may have the same physical origin as explosive events. It is likely that transient network brightenings and explosive events are both due to magnetic reconnection-but with different magnetic geometries.

Journal Article↗