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J Ding

Publications and source records attributed to J Ding.

At least 217 records · Page 12Linked to original sources
PubMed1995

Proton nuclear magnetic resonance studies on huwentoxin-I from the venom of the spider Selenocosmia huwena: 1. Sequence-specific 1H-NMR assignments.

The complete sequence-specific assignments of resonances in the 1H-NMR spectrum of huwentoxin-I from the Chinese bird spider, Selencocosmia huwena, is described. A combination of two-dimensional NMR experiments including 2D-COSY, 2D-NOESY, and 2D-TOCSY has been employed on samples of the toxin dissolved in D2O and in H2O for assignment purposes. Protons belonging to spin systems for each of the 33 amino acids were identified. The sequence-specific assignments were facilitated by the identification of d alpha N connectivities on the fingerprint regions of the COSY and NOESY spectra and were supported by the identification of dNN and d alpha N connectivities in the TOCSY and NOESY spectra. These studies provide a basis for the determination of the solution-phase conformation of this toxin.

Amino Acid Sequence↗
PubMed1995

Structures of DNA and RNA polymerases and their interactions with nucleic acid substrates.

DNA and RNA polymerases are enzymes that are primarily responsible for copying genetic material in all living systems. The four polymerases whose structures have been determined by X-ray crystallographic methods have significant similarities at the polymerase active site that are indicative of common requirements for polynucleotide synthesis. Structural studies of complexes of the Klenow fragment of Escherichia coli DNA polymerase I, HIV type 1 reverse transcriptase, and rat DNA polymerase beta with DNA are leading to generalized models for catalysis.

Animals↗
PubMed1995

International variation in intervention rates. What are the implications for patient selection?

While international variations in intervention rates are well recognized, little is known about their implications for patient selection. This paper describes an exploratory study in which the probability of undergoing an elective intervention (surgery for benign prostatic hyperplasia) in an area in the United Kingdom was compared with an area in the United States. It found that the area with high intervention rates was associated with higher levels of surgery in men with low levels of need who are unlikely to gain much benefit.

Aged↗
PubMed1995

Transforming growth factor-beta 3 is required for secondary palate fusion.

Mice lacking TGF-beta 3 exhibit an incompletely penetrant failure of the palatal shelves to fuse leading to cleft palate. The defect appears to result from impaired adhesion of the apposing medial edge epithelia of the palatal shelves and subsequent elimination of the mid-line epithelial seam. No craniofacial abnormalities were observed. This result demonstrates that TGF-beta 3 affects palatal shelf fusion by an intrinsic, primary mechanism rather than by effects secondary to craniofacial defects.

Animals↗
PubMed1995

Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors.

We report the structure of HIV-1 reverse transcriptase (RT) complexed with the nonnucleoside inhibitor TIBO R 86183 at 3.0 A resolution. Comparing this structure with those of complexes of HIV-1 RT/alpha-APA R 95845 and HIV-1 RT/nevirapine provides a basis for understanding the nature of nonnucleoside inhibitor binding, the structure of the binding site and the interactions between the bound inhibitors and surrounding amino acid residues as well as for understanding mechanisms of inhibition by and resistance to nonnucleoside inhibitors. All three inhibitors considered assume a similar butterfly-like shape and bind to HIV-1 RT in a very similar way. Important differences occur in the conformation of amino acid residues that form the binding pocket.

Acetamides↗
PubMed1995

Cloning and sequence analysis of a protective M-like protein gene from Streptococcus equi subsp. zooepidemicus.

Streptococcus equi subsp. zooepidemicus, a Lancefield group C streptococcus, is a frequently isolated opportunist pathogen from a variety of animal hosts, including the horse. Previous studies have indicated that equine strains carry antigens with characteristics of the antiphagocytic M proteins on the Lancefield groups A and G streptococci. We have cloned a protective M-like protein gene (SzPW60) of an equine strain of S. equi subsp. zooepidemicus W60 and determined its sequence. This gene encodes a protein with a molecular weight of 40,123 which protects mice against subsp. zooepidemicus but not subsp. equi, stimulates antibodies which opsonize subsp. zooepidemicus but not equi, and reacts with antiserum to the protein of the parent strain. The predicted amino acid structure shows significant homology with the carboxy termini of groups A and G M proteins but no other homology. The M-like protein, although showing an extensive region of alpha helix, lacks the A, B, and C repeats found in group A M proteins and has a shorter signal sequence. A proline-rich region upstream from the LPSTGE motif contains 20 repeats of the tetrapeptide PEPK. The presence of this repeat region may account for the slow migration of the M-like protein in sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Amino Acid Sequence↗
PubMed1995

Alterations in intestinal bacterial flora modulate the systemic cytokine response to hemorrhagic shock.

To test the hypothesis that the resident gut flora plays an active role in modulating the cytokine response to hemorrhagic shock, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured from the following three groups of rats before, immediately after, and 3, 8, or 24 h post-hemorrhagic shock (90 min at 30 mmHg)/sham shock: 1) rats with a normal gut flora (NF), 2) rats whose gut flora had been decontaminated with oral antibiotics (AD), and 3) rats with intestinal overgrowth with E. coli. In all three groups, portal and systemic TNF and IL-6 levels were 2- to 10-fold higher in the shock than the sham-shock rats (P < 0.05), with the highest TNF and IL-6 levels observed in the rats that were colonized with Escherichia coli (P < 0.05 vs. AD and NF). TNF levels were higher in the NF than the AD groups at 3 and 8 h postshock. The present study suggests that changes in the gut microflora modulate the systemic cytokine response to hemorrhagic shock with intestinal bacterial overgrowth leading to the greatest increase in plasma IL-6 and TNF levels.

Animals↗
PubMed1995

Autosomal recessive Alport syndrome: mutation in the COL4A3 gene in a woman with Alport syndrome and posttransplant antiglomerular basement membrane nephritis.

Autosomal recessive Alport syndrome can arise from a mutation in either of the genes COL4A3 and COL4A4 on chromosome 2, which encode, respectively, the alpha 3 and alpha 4 chains of Type IV collagen. This report describes a mutation in COL4A3 in a girl who presented at age 5 with hematuria and proteinuria, lacking any family history of renal disease. Renal biopsy at age 8 showed immunoglobulin A nephropathy and Alport syndrome. Sensorineural deafness developed during adolescence, and the patient's renal disease progressed to terminal renal failure by age 20. She received a living related donor renal allograft at age 20 and developed antiglomerular basement membrane nephritis of the allograft 8 months after transplantation. Amplification and sequencing of exon 5 of COL4A3 (counting from the 3' end of the gene) revealed a 7-base-pair deletion, producing a shift of the reading frame and the creation of a premature stop codon. Each parent was heterozygous for the normal and mutant exon 5 sequences. This mutation in COL4A3 would result in the loss of 222 amino acids from the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The mutant chain would be unable to form trimers with other Type IV collagen alpha chains. In addition, the mutant chain would lack the Goodpasture epitope, which resides in the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The absence of this epitope may underly the subsequent development of anti-glomerular basement membrane nephritis in the allograft.

Adult↗
PubMed1995

Comparison of plasma cytokine levels in rats subjected to superior mesenteric artery occlusion or hemorrhagic shock.

The overall goal of this study was to compare the effects of systemic hypotension (hemorrhagic shock) versus local gut ischemia (superior mesenteric artery (SMA) occlusion) on cytokine production and bacteria/endotoxin translocation. Sham or actual SMA occlusion led to an increase in tumor necrosis factor (TNF), which was greatest at the end of the occlusion period, while the IL-6 response peaked 3 h post-SMA occlusion. The TNF and IL-6 response after hemorrhagic shock differed from that observed after SMA occlusion in that the peak response occurred later and was of lower magnitude (p < .05). Although the animals subjected to SMA occlusion had a significantly increased incidence of bacterial translocation to both the mesenteric lymph nodes and systemic organs compared to rats subjected to hemorrhagic shock, in neither group was the blood level of endotoxin elevated and there was no association between bacterial translocation and cytokine levels. These results suggest that different models of intestinal ischemia have different cytokine profiles and that the early TNF response associated with SMA occlusion model is primarily due to the laparotomy.

Animals↗
PubMed1995

[Multivariable analysis of survival in patients with transitional cell bladder carcinoma].

In 82 transitional cell bladder cancer patients with adequate follow-up, the prognostic value of histological grade, depth of invasion, size, site, appearance, number of primary tumours, surgical treatment and ages of patients were assessed. Univariable analysis showed the statistically significant relation of histological grade, depth of invasion, size, site, appearance and number of tumours to survival. Survival analysis with Cox's regression model indicated that the histological grade is the most important prognostic factor, followed by site of tumours and depth of invasion. The results suggest that the information of site should not be omitted.

Adult↗
PubMed1995

[Prevention and treatment of surgical complications of tracheobronchoplastic procedures. An analysis of 22 cases].

This paper reported the surgical complications of various tracheobronchoplastic procedures in 22 cases between May 1979 to March 1994. The incidence of postoperative complication was 14.5%. The mortality rate was 1.3%. Among them, complications of the respiratory system occurred in 9 cases (41%), cardiovascular system in 4(18%), digestive system in 2(9%), chest incision infection and early recurrence of carcinoma in 1 each (5%) and those due to surgical skill in 5(23%) respectively. Tracheostomy should be done with ventilatory support should be given if early respiratory failure occurred. Particular attention should be paid to prevent fatal complications from detachment of embolus in the pulmonary vein or bronchus. Because of the surgical complications, indications of tracheobronchoplastic procedures for lung cancer should be strictly handled.

Adult↗
PubMed1994

Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase. Implications for mechanisms of drug inhibition and resistance.

The locations of HIV-1 RT nucleoside and non-nucleoside inhibitor-binding sites and inhibitor-resistance mutations are analyzed in the context of the three-dimensional structure of the enzyme and implications for mechanisms of drug inhibition and resistance are discussed. In order to help identify residues that may play a role in inhibitor binding, solvent accessibilities of amino acids that comprise the inhibitor-binding sites in the structure of HIV-1 RT complexed with a dsDNA template-primer are analyzed. While some mutations that cause resistance to nucleoside analogs, such as AZT, ddI, and ddC, are located near enough to the dNTP-binding site to directly interfere with binding of nucleoside analogs, many are located away from the dNTP-binding site and more likely confer resistance by other mechanisms. Many of the latter mutations are located on the surface of the DNA-binding cleft and may lead to altered template-primer positioning or conformation, causing a distortion of the geometry of the polymerase active site and consequent discrimination between normal and altered dNTP substrates. Other nucleoside analog-resistance mutations located on the periphery of the dNTP-binding site may exert their effects via altered interactions with dNTP-binding site residues. The structure of the hydrophobic region in HIV-1 RT that binds non-nucleoside inhibitors, for example, nevirapine and TIBO, has been analyzed in the absence of bound ligand. The pocket that is present when non-nucleoside inhibitors are bound is not observed in the inhibitor-free structure of HIV-1 RT with dsDNA. In particular it is filled by Tyr181 and Tyr188, suggesting that the pocket is formed primarily by rotation of these large aromatic side-chains. Existing biochemical data, taken together with the three-dimensional structure of HIV-1 RT, makes it possible to propose potential mechanisms of inhibition by non-nucleoside inhibitors. One such mechanism is local distortion of HIV-1 RT structural elements thought to participate in catalysis: the beta 9-beta 10 hairpin (which contains polymerase active site residues) and the beta 12-beta 13 hairpin ("primer grip"). An alternative possibility is restricted mobility of the p66 thumb subdomain, which is supported by the observation that structural elements of the non-nucleoside inhibitor-binding pocket may act as a "hinge" for the thumb.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1994

Wortmannin and 1-butanol block activation of a novel family of protein kinases in neutrophils.

Neutrophils contain four uncharacterized protein kinases with molecular masses of ca. 69, 63, 49 and 40 kDa that are rapidly activated upon stimulation of these cells with the chemoattractant fMet-Leu-Phe [Ding, J. and Badwey, J.A. (1993) J. Biol. Chem. 268, 17326-17333]. We now report that wortmannin and 1-butanol block activation of all four of these kinases. These reagents are known to inhibit superoxide generation in neutrophils stimulated with this agonist. Wortmannin inhibits phosphatidylinositol 3-kinase and blocks activation of phospholipase D, whereas 1-butanol can reduce the generation of phosphatidate in cells by serving as a substrate for phospholipase D. These data suggest that phosphatidylinositol 3-kinase and phospholipase D may be involved in the activation of several novel protein kinases in neutrophils and that one or more of these kinases is/are involved in superoxide release.

1-Butanol↗
PubMed1994

Farnesyl-L-cysteine analogs can inhibit or initiate superoxide release by human neutrophils.

A series of farnesylcysteine analogs was studied with respect to their abilities to interfere with fMet-Leu-Phe (fMLP)-stimulated superoxide (O2-.) release by human neutrophils. Simple acyl derivatives of farnesyl-L-cysteine, such as the N-acetyl (L-AFC) and N-isobutyryl derivatives (L-iBFC), which are substrates for the isoprenylated protein methyltransferase, can block O2-. release. The N-butyryl analog (L-BFC), which is an isomer of L-iBFC and also a substrate for the methyltransferase, does not inhibit O2-. release but actually stimulates it in the absence of fMLP. Other analogs, including the N-pivaloyl derivative, which has been found to be neither a substrate nor an inhibitor of methyltransferase, also stimulate very large quantities of O2-. production. The stimulatory effects of these derivatives are saturable and exquisitively sensitive to small structural changes in the analogs. The signal transduction pathway(s) utilized by pivaloyl derivatives for triggering O2-. generation is very similar to that employed by fMLP. These data make it clear that farnesyl-L-cysteine analogs do not produce their pharmacological effects in neutrophils via methyltransferase blockade. This could be further demonstrated by showing that sinefungin and S-adenosylhomocysteine, both powerful and general methyltransferase inhibitors which bind at the S-adenosylmethionine site, had no effect in preventing the increased oxygen consumption associated with O2-. production in permeabilized neutrophils. These studies reveal that farnesyl-L-cysteine analogs interact with a hitherto undefined target in neutrophils that may be exploited for inhibiting or stimulating the inflammatory or antimicrobial responses of these cells.

Chromatography, High Pressure Liquid↗
PubMed1994

Sensitivity of wild-type human immunodeficiency virus type 1 reverse transcriptase to dideoxynucleotides depends on template length; the sensitivity of drug-resistant mutants does not.

Analysis of the three-dimensional structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) complexed with double-stranded DNA indicates that while many nucleoside-resistance mutations are not at the putative dNTP binding site, several are in positions to interact with the template-primer. Wild-type HIV-1 RT and two nucleoside-resistant variants, Leu74-->Val and Glu89-->Gly, have been analyzed to determine the basis of resistance. The ability of the wild-type enzyme to incorporate, or reject, a 2',3'-dideoxynucleoside triphosphate (ddNTP) is strongly affected by interactions that take place between the enzyme and the extended template strand 3-6 nt beyond the polymerase active site. Inspection of a model of the enzyme with an extended template suggests that this interaction involves the fingers subdomain of the p66 subunit in the vicinity of Leu74. These data provide direct evidence that the fingers subdomain of the p66 subunit of HIV-1 RT interacts with the template strand. The wild-type enzyme is resistant to ddITP if the template extension is 3 nt or less and becomes sensitive only when the template extends more than 3 or 4 nt beyond the end of the primer strand. However, the mutant enzymes are resistant with both short and long template extensions. Taken together with the three-dimensional structure of HIV-1 RT in complex with double-stranded DNA, these data suggest that resistance to the dideoxynucleotide inhibitors results from a repositioning or change in the conformation of the template-primer that alters the ability of the enzyme to select or reject an incoming dNTP.

Base Sequence↗
PubMed1994

Binding sites for cholesterol on Ca(2+)-ATPase studied by using a cholesterol-containing phospholipid.

Phosphatidylcholines have been synthesized containing a cholesterol moiety at the 2-position of the glycerol backbone. Fluorescence quenching studies show that cholesterol-containing phosphatidylcholines can bind at the lipid-protein interface of the Ca(2+)-ATPase from skeletal muscle sarcoplasmic reticulum, with an affinity half that of dioleoylphosphatidylcholine. The ATPase activity measured for the ATPase reconstituted with the cholesterol-containing phosphatidylcholine containing an oleoyl fatty acyl chain, (C18:1, CHS)PC, is less than that measured for the ATPase reconstituted with dioleoylphosphatidylcholine. The activity measured for the ATPase reconstituted with the cholesterol-containing phosphatidylcholine containing a myristoleoyl fatty acyl chain, (C14:1, CHS)PC, is less than that measured in (C18:1,CHS)PC and is comparable to that measured in dimyristoleoylphosphatidylcholine (di(C14: 1)PC. The stoichiometry of Ca2+ binding to the ATPase is two Ca2+ ions bound per ATPase molecule in the native membrane or in (C18:1,CHS)PC, but one bound per ATPase molecule in di(C14:1)PC or (C14: 1,CHS)PC. Addition of cholesterol to the ATPase in di(C14:1)PC or (C14:1,CHS)PC increases the Ca2+ binding stoichiometry to the usual 2:1, but the binding stoichiometry remains 1:1 in mixtures of di(C14: 1)PC and (C14:1,CHS)PC. Removal of Ca2+ from the Ca(2+)-bound ATPase results in a decrease in tryptophan fluorescence intensity for the ATPase in the native membrane, but an increase in fluorescence intensity for the ATPase in di(C14:1)PC or (C14:1,CHS)PC. Addition of cholesterol to the ATPase in di(C14:1)PC or (C14:1,CHS)PC reverses this change. It is concluded that cholesterol linked to a phospholipid molecule can interact with the ATPase only at the lipid-protein interface.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1994

Reciprocal interactions between protein kinase C and components of the NADPH oxidase complex may regulate superoxide production by neutrophils stimulated with a phorbol ester.

The 47-kDa subunit of the NADPH oxidase system (p47-phox) of neutrophils undergoes an association with proteins in the Triton X-100-insoluble fraction upon stimulation of the cells with 4 beta-phorbol 12-myristate 13-acetate. This fraction contains the assembled oxidase that catalyzes the generation of superoxide by stimulated cells. In this paper, we report that the addition of an inhibitor of protein kinases (1-(5-isoquinolinylsulfonyl-2-methylpiperazine) to neutrophils that are already stimulated results in the dissociation of p47-phox from this fraction. Antagonists of type 1 and 2A protein phosphatases (calyculin A, okadaic acid) prevented this phenomenon. In contrast, norokadanone, an inactive analog of okadaic acid, did not affect this response. These observations are correlated with previous studies on the phosphorylation of p47-phox and superoxide release. In addition, we show that protein kinase C (PKC) also undergoes an extensive redistribution to the Triton X-100-insoluble fraction in 4 beta-phorbol 12-myristate 13-acetate-stimulated cells, the extent of which is diminished significantly in neutrophils from chronic granulomatous disease patients who lack either p47-phox or cytochrome b558. These studies strongly indicate that PKC and type 1 and/or 2A protein phosphatases are involved in a continuous phosphorylation reaction that maintains the oxidase in the assembled/active state. Moreover, components of the oxidase may target and facilitate the translocation of PKC to a cellular site in close apposition to the oxidase.

Amino Acid Sequence↗