PubMed Health⌕ Search

Biomedical subjects

P A Rice

Publications and source records attributed to P A Rice.

At least 19 recordsLinked to original sources
PubMed1992

Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor.

A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66-kilodalton subunit has a large cleft analogous to that of the Klenow fragment of Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of identical sequence has no such cleft because the four subdomains of the pol domain occupy completely different relative positions. Two of the four pol subdomains appear to be structurally related to subdomains of the Klenow fragment, including one containing the catalytic site. The subdomain that appears likely to bind the template strand at the pol active site has a different structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built into the cleft that runs between the ribonuclease H and pol active sites. Nevirapine is almost completely buried in a pocket near but not overlapping with the pol active site. Residues whose mutation results in drug resistance have been approximately located.

Azepines↗
PubMed1992

Seroprevalence of human immunodeficiency virus in parturients at Boston City Hospital: implications for public health and obstetric practice.

OBJECTIVE: We measured the seroprevalence of human immunodeficiency virus in women seeking reproductive services. STUDY DESIGN: Demographic and risk behavior data from women were linked anonymously to human immunodeficiency virus antibody results. RESULTS: The overall human immunodeficiency virus seropositivity rate of cord blood was 22 per 1000. Crude seroprevalence rates were higher for black women versus white women (25/1000 vs 22/1000) but lower for black Americans versus white Americans (21/1000 vs 29/1000). Human immunodeficiency virus infection was significantly higher for those women who acknowledge intravenous drug use (odds ratio 12.9, 95% confidence interval 7.3 to 22.7), were born in Haiti (odds ratio 2.6, 95% confidence interval 1.6 to 4.1), lacked prenatal care (odds ratio 2.2, 95% confidence interval 1.1 to 4.2), or received prenatal care at the hospital clinic versus a neighborhood health center (odds ratio 3.0, 95% confidence interval 1.7 to 5.3). The seroprevalence rates were 18/1000 for women seeking abortion and 16/1000 for women seeking family-planning services. CONCLUSION: Intravenous drug use and country of origin are major risk factors for human immunodeficiency virus infection in women, which may explain differences in seroprevalence rates in various racial or ethnic groups. Hospital-specific data on human immunodeficiency virus infection may be useful for monitoring the epidemic and allocating resources for education, counseling, testing, and prevention.

Abortion, Induced↗
PubMed1992

Human vaccination with Escherichia coli J5 mutant induces cross-reactive bactericidal antibody against Neisseria gonorrhoeae lipooligosaccharide.

The lipopolysaccharides of enteric gram-negative bacteria and the lipooligosaccharides (LOS) of Neisseria gonorrhoeae may share antigenic determinants that are targets of bactericidal antibody. Natural (disseminated) infection with a serum-resistant gonococcal strain and immunization with Escherichia coli J5 stimulated bactericidal IgG anti-LOS antibodies that recognize different serum-resistant gonococcal LOS epitopes. In bactericidal assays, convalescent serum from disseminated infection killed only the homologous strain while post-J5 vaccination serum killed 6 of 9 additional strains. Both convalescent and post-J5 vaccination sera mediated marker (51Cr) release from liposomes sensitized with serum-resistant gonococcal LOS (homologous strain), linking acquired killing activity to cross-reacting anti-LOS antibody. Post-J5 IgG mediated 51Cr release more effectively than did convalescent IgG. Thus, bactericidal antibody elicited by J5 vaccination is more efficacious and broadly cross-reactive against serum-resistant gonococci than is antibody elicited by natural infection. Moreover, multiple LOS epitopes may serve as bactericidal targets on serum-resistant gonococci.

Antibodies, Bacterial↗
PubMed1992

Early complement components enhance neutralization of Chlamydia trachomatis infectivity by human sera.

Immunoglobulin G in human serum neutralizes chlamydial infectivity in vitro. Complement-intact, C5-depleted, and C8-depleted human serum all have significantly more neutralizing activity than serum heated to inactivate early components of complement. Cobra venom factor, an analog of human C3b, enhances neutralization of antichlamydial immunoglobulin G in the absence of early complement components.

Blood Bactericidal Activity↗
PubMed1991

Pathogenesis of pelvic inflammatory disease. What are the questions?

Pelvic inflammatory disease is usually caused by Chlamydia trachomatis or Neisseria gonorrhoeae. Chlamydiae and gonococci are primary pathogens of the cervix and often ascend. Resultant damage to the cervix may permit organisms to move upward, but this mechanism of action is not well understood. Puberty and hormones, particularly oral contraceptives, may enhance chlamydial infection, but the mechanisms and likelihood of spread to the upper tract are ill defined. Upper tract infection with C trachomatis involves an acute phase, characterized by an influx of polymorphonuclear leukocytes and a chronic or persistent phase characterized by the presence of mononuclear cells (delayed hypersensitivity). Gonococci invade nonciliated epithelial cells, but are toxic to ciliated cells, due to elaborated lipooligosaccharides and peptidoglycan. Certain gonococci stimulate chemotaxis of polymorphonuclear leukocytes whose release of toxic metabolites may damage tissue. The immunologic mechanisms that permit specific host responses to these two organisms are now being elucidated and should receive more attention by researchers.

Chlamydia Infections↗
PubMed1990

The crystal structure of the catalytic domain of the site-specific recombination enzyme gamma delta resolvase at 2.7 A resolution.

The crystal structure of the catalytic domain of the site-specific recombination enzyme gamma delta resolvase has been determined at 2.7 A resolution. Its first 120 amino acids form a central five-stranded, beta-pleated sheet surrounded by five alpha helices. In one of the four dyad-related dimers, the two active site Ser-10 residues are 19 A apart, perhaps close enough to contact and become covalently linked to the DNA at the recombination site. This dimer also forms the only closely packed tetramer found in the crystal. The subunit interface at a second dyad-related dimer is more extensive and more highly conserved among the homologous recombinases; however, its active site Ser-10 residues are more than 30 A apart. Side chains, identified by mutations that eliminate catalysis but not DNA binding, are located on the subunit surface near the active site serine and at the interface between a third dyad-related pair of subunits of the tetramer.

Binding Sites↗
PubMed1990

A helix-turn-strand structural motif common in alpha-beta proteins.

By exhaustive structural comparisons, we have found that about one-third of the alpha-helix-turn-beta-strand polypeptides in alpha-beta barrel domains share a common structural motif. The chief characteristics of this motif are that first, the geometry of the turn between the alpha-helix and the beta-strand is somewhat constrained, and second, the beta-strand contains a hydrophobic patch that fits into a hydrophobic pocket on the alpha-helix. The geometry of the turn does not seem to be a major determinant of the alpha-beta unit, because the turns vary in length from four to six residues. However, the motif does not occur when there are few constraints on the geometry of the turn-for instance, when the turns between the alpha-helix and the beta-strands are very long. It also occurs much less frequently in flat-sheet alpha-beta proteins, where the topology is much less regular and the amount of twist on the sheet varies considerably more than in the barrel proteins. The motif may be one of the basic building blocks from which alpha-beta barrels are constructed.

Alcohol Dehydrogenase↗
PubMed1990

Modification by sialic acid of Neisseria gonorrhoeae lipooligosaccharide epitope expression in human urethral exudates: an immunoelectron microscopic analysis.

Expression of lipooligosaccharide (LOS) antigenic determinants during human gonococcal infection was studied in secretions from seven men with gonococcal urethritis. Five monoclonal antibodies with distinct gonococcal LOS specificities and an H.8 lipoprotein monoclonal antibody were used in combination with immunogold electron microscopic analysis. The LOS epitope defined by antibody 6B7 was present on all seven strains in secretions and after in vitro growth. Gonococci from six of seven patients, when grown in vitro, expressed the 6B4 LOS epitope. The 6B4 epitope is a Gal beta 1-4-GlcNAc residue, which is immunochemically similar to the precursor of the human erythrocyte i antigen. This epitope was found unmodified on gonococcal LOS in urethral secretions from two patients. The unmodified epitope could not be demonstrated on organisms in five secretions. Neuraminidase digestion exposed the 6B4 epitope on organisms in these secretions and increased the 6B4 epitope density in the two secretions, which contained the unmodified epitope. These studies indicate that in vivo modification by sialylation of gonococcal LOS Gal beta 1-4-GlcNAc residue occurs during human infection.

Antibodies, Monoclonal↗
PubMed1989

Ribosomal protein L7/L12 has a helix-turn-helix motif similar to that found in DNA-binding regulatory proteins.

Inspection of the structure of the C-terminal domain of ribosomal protein L7/L12 (1) reveals a helix-turn-helix motif similar to the one found in many DNA-binding regulatory proteins (2-5). The 19 alpha-carbon atoms of the L7/L12 alpha-helices superimpose on the DNA binding helices of CAP and cro with root-mean-square distances between corresponding alpha carbons of 1.45 and 1.55 A, respectively. These helices in L7/L12 are within a patch of highly conserved residues on the surface of L7/L12 whose role is as yet uncertain. We raise the possibility that they may constitute a binding site for nucleic acids, most probably RNA. Consistent with this hypothesis are calculations of the electrostatic charge potential surrounding the protein, which show a region of positive potential centered on the first of these helices.

Bacterial Proteins↗
PubMed1989

Inhibition of human neutrophil NADPH oxidase by Chlamydia serovars E, K, and L2.

The effects of Chlamydia trachomatis (serovars E, K, and L2) on human neutrophil activation were examined with respect to the organisms both as primary agonists and as agents that modulate cell responses to a second stimulus. Unopsonized chlamydiae alone, at ratios of 1.5 to 100 organisms per cell, failed to elicit changes in intracellular calcium or membrane depolarization or to stimulate the respiratory burst or degranulation during 60 min of incubation. Each of these functions except the respiratory burst was also normally activated when chlamydia-infected neutrophils were subsequently stimulated with formylmethionyl leucine phenylalanine or phorbol myristate acetate; the respiratory burst was inhibited 30 to 65%. Inhibition was dependent on live organisms and was maximal within 5 min of incubation. The organisms had no effect on the superoxide (O2-) assay, and the site of chlamydial inhibition was determined at the level of the NADPH oxidase itself, not at an intermediate step in the activation cascade. The mechanism of enzyme inactivation could not be determined. These results show that unopsonized chlamydiae do not elicit responses from infected neutrophils and suggest that microbicidal mechanisms other than those dependent on elaboration of toxic oxygen-derived species are required to inactivate chlamydiae.

Calcium↗
PubMed1987

Mechanisms of stable serum resistance of Neisseria gonorrhoeae.

Neisseria gonorrhoeae that resist complement-dependent killing by normal human serum (NHS) are sometimes killed by immune convalescent sera from patients recovering from disseminated gonococcal infection (DGI). In these studies, killing by immune serum was prevented or blocked by immunoglobulin G (IgG) or F(ab')2 isolated from NHS. Purified human IgG antibodies directed against gonococcal protein III, contained most of the blocking activity in IgG. In addition, immune convalescent DGI serum, which did not exhibit bactericidal activity, was restored to killing by selective immunodepletion of protein III antibodies. Blocking IgG or F(ab')2 prepared from IgG, partially inhibited binding of bactericidal antibody to N. gonorrhoeae. Also, binding of a monoclonal antibody recognizing N. gonorrhoeae outer membrane protein PIII was almost completely inhibited by blocking F(ab')2. Presensitization of N. gonorrhoeae with increasing concentrations of blocking IgG or F(ab')2 before incubation with bactericidal antibody and an antibody free source of complement, increased consumption and deposition of the third component of human complement (C3) and the ninth component of complement (C9) but inhibited killing in dose-related fashion.

Antibodies, Bacterial↗
PubMed1987

Physical heterogeneity of neisserial lipooligosaccharides reflects oligosaccharides that differ in apparent molecular weight, chemical composition, and antigenic expression.

We studied the oligosaccharides (OS) of outer membrane lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis. OS from the LOS of an individual neisserial strain always eluted from Sephadex G-50S as multiple peaks; the polyacrylamide gel elution profiles were nearly identical to the polyacrylamide gel electrophoresis profiles of the sodium dodecyl sulfate-disaggregated native LOS from which the OS were derived. Neisserial OS coeluted with Dex14 to Dex27 dextran oligomers (Mr, 2,210 to 4,320). Monosaccharide composition varied among the several OS released from the LOS of a single strain. The two OS of a gonococcal strain sensitive to normal human serum (NHS) bacteriolysis (sers) varied in their ability to inhibit the binding of NHS immunoglobulin M to their parental LOS. The OS that was rich in hexosamines inhibited NHS immune lysis of its parent strain; the OS that was poor in hexosamines did not. We conclude that structural differences in their OS account for the Mr heterogeneity of the LOS of a strain.

Acetates↗
PubMed1987

Specificity of antibodies against Neisseria gonorrhoeae that stimulate neutrophil chemotaxis. Role of antibodies directed against lipooligosaccharides.

Five strains each of Neisseria gonorrhoeae sensitive or resistant to complement (C) dependent killing by normal human serum (NHS) were examined for their ability to stimulate chemotaxis of polymorphonuclear leukocytes (PMNs) after preincubation with NHS; or IgM or IgG derived from NHS. Serum-sensitive N. gonorrhoeae stimulated C-dependent chemotaxis when opsonized with IgM, but not IgG, however, serum-resistant strains, taken as a whole, failed to promote chemotaxis when opsonized with either isotype. IgM titers in NHS against lipooligosaccharide (LOS) antigens from individual serum-sensitive, but not serum-resistant strains, correlated with the magnitude of chemotaxis generated by the corresponding opsonized strains (r = 0.99). Western blots demonstrated that IgM and IgG from NHS recognized different antigenic determinants on LOS from serum-sensitive gonococci. IgM from NHS immunopurified against serum-sensitive LOS accounted for two-thirds of the chemotaxis promoting activity present in whole serum. IgG titers in NHS against LOS antigens from individual serum-resistant strains also correlated with magnitude of chemotaxis generated by the corresponding opsonized strains (r = 0.87), although most opsonized serum-resistant strains did not generate significantly higher magnitudes of chemotaxis than controls. In contrast, a serum-resistant isolate from a patient with disseminated gonococcal infection (DGI) stimulated chemotaxis when opsonized with IgG obtained from the patient's convalescent serum. By Western blot, convalescent IgG antibody recognized an additional determinant on serum-resistant LOS not seen by normal IgG.

Adult↗
PubMed1986

Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune serum.

Neisseria gonorrhoeae that resist complement-dependent killing by normal human serum (NHS) are sometimes killed by immune convalescent serum from patients recovering from disseminated gonococcal infection (DGI). In these studies, killing by immune serum was prevented or blocked by IgG isolated from NHS. Purified human IgG antibodies directed against gonococcal protein III, an antigenically conserved outer membrane protein, contained most of the blocking activity in IgG. Antibodies specific for gonococcal porin (protein I), the major outer membrane protein, displayed no blocking function. In separate experiments, immune convalescent DGI serum which did not exhibit bactericidal activity was restored to killing by selective depletion of protein III antibodies by immunoabsorption. These studies indicate that protein III antibodies in normal and immune human serum play a role in serum resistance of N. gonorrhoeae.

Antibodies, Bacterial↗
PubMed1986

The effect of ethanol on the production of lactate, triglycerides, phospholipids, and free fatty acids in the perfused human placenta.

Eighteen fresh term placentas from normal deliveries were perfused to determine the biochemical response of the human placenta in the absence and presence of ethanol. The production rates were generally increased by ethanol administration; lactate, 22%; triglycerides, 49%; sphingomyelin, 362%; lecithin, 67%; lipid phosphorus, 780%; free fatty acids, 897%. Only the changes in lipid phosphorus and free fatty acids were significantly different (p less than 0.05). Glucose utilization rates were 600 and 551 mg per hour per placenta for eight control and 10 ethanol runs, respectively. The ethanol utilization rate was 442 mg per hour per placenta. Little difference in ultrastructural appearance between control and ethanol groups was observed at the level of ethanol administered. The general behavior of ethanol metabolism in human placenta seems qualitatively similar to that in the liver.

Ethanol↗