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Novel therapies are urgently needed to combat the global threat of multidrug-resistant pathogens. Complement forms an important arm of innate defenses against infections. In physiological conditions, complement activation is tightly controlled by soluble and membrane-associated complement inhibitors, but must be selectively activated on invading pathogens to facilitate microbial clearance. Many pathogens, including Neisseria gonorrhoeae and N. meningitidis, express glycans, including N-acetylneuraminic acid (Neu5Ac), that mimic host structures to evade host immunity. Neu5Ac is a negatively charged 9-cabon sugar that inhibits complement, in part by enhancing binding of the complement inhibitor factor H (FH) through C-terminal domains (19 and 20) on FH. Other microbes also bind FH, in most instances through FH domains 6 and 7 or 18-20. Here we describe two strategies to target complement activation on Neisseriae. First, microbial binding domains of FH were fused to IgG Fc to create FH18-20/Fc (binds gonococci) and FH6,7/Fc (binds meningococci). A point mutation in FH domain 19 eliminated hemolysis caused by unmodified FH18-20, but retained binding to gonococci. FH18-20/Fc and FH6,7/Fc mediated complement-dependent killing in vitro and showed efficacy in animal models of gonorrhea and meningococcal bacteremia, respectively. The second strategy utilized CMP-nonulosonate (CMP-NulO) analogs of sialic acid that were incorporated into LOS and prevented complement inhibition by physiologic CMP-Neu5Ac and resulted in attenuated gonococcal infection in mice. While studies to establish the safety of these agents are needed, enhancing complement activation on microbes may represent a promising strategy to treat antimicrobial resistant organisms.

We used a combination of sampling and statistical approaches to investigate the relative influence of metals, soil acidity, and organic matter on a suite of analogous plant and microbial community parameters in floodplain soils contaminated by mine wastes in the early twentieth century. We compared the sensitivity of plant and microbial communities to environmental variables and to one another using constrained ordination analyses. Environmental factors accounted for a larger percentage of the total variance in microbial communities (56.2%) than plant communities (22.0%). We also investigated biological and geochemical changes that occurred along a short transect (64 cm) that spanned a transition from productive grassland to an area of barren wasteland representing a total functional collapse of the grassland/soil ecosystem. Along this small-scale transect we quantified geochemical parameters and biological parameters in two soil layers, an upper layer (0–10 cm) and a lower layer (10–20 cm). Results from the short transect indicated that soil respiration was not a strong indicator of underlying metal concentrations, but soil acidity was correlated in the upper and lower layers. PLFA profiles changed with distance along the gradient in the upper, but not the lower layer. Implications for remediation of contaminated floodplain soils are discussed.

Human factor H (HufH), a key inhibitor of the alternative pathway of complement, binds to Neisseria gonorrhoeae and constitutes an important mechanism of human-specific complement evasion. The C-terminal domain 20 of HufH contains the binding site for sialylated gonococci. We exploited differences in amino acid sequences between human and non-binding chimpanzee fH domain 20 to create cross-species mutations to define amino acids important for binding to sialylated gonococci. We used fH/Fc fusion constructs that contained contiguous fH domains 18–20 fused to Fc fragments of murine IgG2a. The Fc region was used both as a tag for detection of each fusion molecule on the bacterial surface and as an indicator for complement-dependent killing. Arg-1203 was critical for binding to both porin (Por) B.1A and PorB.1B strains. Modeling of the R1203N human-to-chimpanzee mutation using the crystal structure of HufH19–20 as a template showed a loss of positive charge that protrudes at the C terminus of domain 20. We tested the functional importance of Arg-1203 by incubating sialylated gonococci with normal human serum, in the presence of wild-type HufH18–20/Fc or its R1203A mutant. Gonococci bound and were killed by wild-type HufH18–20/Fc but not by the R1203A mutant. A recombinant fH/Fc molecule that contained chimpanzee domain 20, humanized only at amino acid 1203 (N1203R) also bound to sialylated gonococci and restored killing. These findings provide further insights into the species specificity of gonococcal infections and proof-of-concept of a novel therapeutic approach against gonorrhea, a disease rapidly becoming resistant to conventional antibiotics.

Dehydroepiandrosterone (DHEA), a precursor sex steroid, circulates in sulphated form (DHEAS). Serum DHEAS concentrations are inversely correlated with metabolic syndrome components and in vivo/in vitro studies suggest a role in modulating adipose mass. To investigate further, we assessed the in vitro biological effect of DHEA in white (3T3-L1) and brown (PAZ6) preadipocyte cell lines and human primary preadipocytes. DHEA (from 10(-8)M) caused concentration-dependent proliferation inhibition of 3T3-L1 and PAZ6 preadipocytes. Cell cycle analysis demonstrated unaltered apoptosis but indicated blockade at G1/S or G2/M in 3T3-L1 and PAZ6, respectively. Preadipocyte cell-line adipogenesis was not affected. In human primary subcutaneous and omental preadipocytes, DHEA significantly inhibited proliferation from 10(-8)M. DHEA 10(-7)M had opposing effects on adipogenesis in the two fat depots. Subcutaneous preadipocyte differentiation was unaffected or increased whereas omental preadipocytes showed significantly reduced adipogenesis. We conclude that DHEA exerts fat depot-specific differences which modulate body composition by limiting omental fat production.

Purpose: To examine associations between depressive symptoms and dyad-level sexual risk behavior in young heterosexual dyads with sexually transmitted infection (STI). Methods: Chlamydia-positive 14-24-year-old, heterosexually active outpatients and their opposite-sex partners completed an assessment that included demographics, past and recent STI risk behaviors, and the Beck Depression Inventory (BDI). Participants in the top 25% of BDI scores within gender were categorized as depressed. Variables were created to identify dyads in which the female or male partner was depressed, as well as a measure of concordance of depression between partners. Dyad-level STI risk variables were created from the STI risk characteristics reported by each dyad member, and associations between these and the depression variables were analyzed. Results: The 130 dyads were comprised of young men and women at high STI risk. One-third of dyads had at least one depressed partner. Dyads in which the female partner was depressed had greater partner age difference, greater total number of lifetime partners, and one or more partners reporting substance use within 2 hours before sex, compared with dyads in which the female partner was not depressed. Dyads in which the male partner was depressed were more likely than the nondepressed-male dyads to report substance use before sex. All dyads in which both partners were depressed reported substance use before sex. Conclusions: In young, chlamydia-infected, heterosexual dyads, depressive symptoms, especially in women, is related to increased dyad-level STI risk, including greater partner age difference, more partners, and substance use before sex.

Tocopheryl Polyethylene Glycol Succinate 1000 (TPGS 1000) can inhibit P-glycoprotein (P-gp); TPGS 1000 was not originally designed to inhibit an efflux pump. Recent work from our laboratories demonstrated that TPGS activity has a rational PEG chain length dependency. In other recent work, inhibition mechanism was investigated and appears to be specific to the ATPase providing P-gp energy. Based on these observations, we commenced rational surface-active design. The current work summarizes new materials tested in a validated Caco-2 cell monolayer model; rhodamine 123 (10microM) was used as the P-gp substrate. These results demonstrate that one may logically construct non-ionic surfactants with enhanced propensity to inhibit in vitro efflux. One new surfactant based inhibitor, Tocopheryl Polypropylene Glycol Succinate 1000 (TPPG 1000), approached cyclosporine (CsA) in its in vitro efflux inhibitory potency. Subsequently, TPPG 1000 was tested for its ability to enhance the bioavailability of raloxifene - an established P-gp substrate -in fasted male rats. Animals dosed with raloxifene and TPPG 1000 experienced an increase in raloxifene oral bioavailability versus a control group which received no inhibitor. These preliminary results demonstrate that one may prepare TPGS analogs that possess enhanced inhibitory potency in vitro and in vivo.

Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease restricted to humans. Complement forms a key arm of the innate immune system that combats gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por) molecules to bind complement clown-regulatory proteins, C4b-binding protein (C4BP) and factor H (M), to evade killing by human complement. In addition, sialylation of gonococcal lipooligosaccharide (LOS) also enables N. gonorrhoeae to bind fH. Strains of N. gonorrhoeae that resist killing by human serum complement are killed by serum from rodent, lagomorph and primate species, which cannot be readily infected experimentally with this organism and whose C4BP and/or fH molecules do not bind to N. gonorrhoeae. Serum resistance of gonococci is restored in these sera by human C4BP and/or fH Direct binding specificity of human and chimpanzee C4BP and human fH to gonococci may explain, in part, species-specific restriction of natural gonococcal infection and address why Por1B, but not Por1A containing gonococcal strains, have been successful in experimental chimpanzee infection. Our findings may help to improve animal models for gonorrhea while also having implications in the choice of complement sources to evaluate neisserial vaccine candidates. (C) 2008 Elsevier Ltd. All rights reserved.

A blind performance test was conducted to evaluate dose-calibrator measurements at nuclear pharmacies in the United States (US). Two test-sample geometries were chosen to represent those used for measurements of 90Y-ibritumomab tiuxetan (ZEVALIN). The radioactivity concentration of test-samples was verified by the US National Institute of Standards and Technology. Forty-five results were reported by 10 participants. Eighty percent of reported values were within the US Pharmacopoeia content standard (+/-10%) for 90Y-ZEVALIN. All results were within US Nuclear Regulatory Commission conformance limits (+/-20%) for defining therapeutic misadministrations.

The 2C7 epitope is a conserved oligosaccharide structure, a part of lipooligosaccharide (LOS) on Neisseria gonorrhoeae, present in 95% of clinical gonococcal isolates. 2C7 may represent a potential candidate for an anti-gonococcal vaccine. To circumvent the limitations of saccharide immunogens in producing long lived immune responses, we identified a peptide that mimics the 2C7 epitope using a random peptide library, characterizing linear and cyclic forms and formulating a multiple antigenic peptide. The multiple antigenic peptide Octa-MAP1 was used for immunization, and elicited >or=4-fold increase in cross-reactive anti-LOS antibodies in 26 of 30 mice (87%). IgG anti-LOS antibody elicited by Octa-MAP1 immunization possessed dose-responsive direct complement (C)-dependent bactericidal activity against gonococcal strains that expressed the 2C7 epitope. These data indicate that a peptide can mimic an oligosaccharide epitope and may form the basis for the development of a vaccine candidate for human immunization against N. gonorrhoeae.

Septic arthritis caused by N gonorrhoeae is monoarticular or pauciarticular, and is more commonly associated with positive synovial fluid cultures and negative blood cultures. Gonococcal bacteremia is more likely to be associated with polyarthralgias and skin lesions. The diagnosis of gonococcal arthritis or DGI is also secure if a mucosal gonococcal infection is documented in the presence of a typical clinical syndrome that responds promptly to appropriate antimicrobial therapy. Hospitalization is indicated in patients with suppurative arthritis or when the diagnosis is in doubt. Initial treatment with ceftriaxone or another advanced-generation cephalosporin is warranted until signs and symptoms have improved; continuation of treatment for a total period of therapy of 1 week can be accomplished with a fluoroquinolone.

Glucans are fungal cell wall glucose polymers that are released into the blood of infected patients. The role of glucans in infection is unknown. We examined serum glucan and cytokine levels in intensive care unit (ICU) patients with infections. There was an inverse correlation (p0.001) between serum glucan levels and interleukin (IL)-2), IL-4, tumor necrosis factoralpha (TNFalpha) and granulocyte macrophage-colony stimulating factor (GM-CSF) levels in infected ICU patients. The correlation between serum cytokines and serum glucan was only observed at glucan concentrations40 pg/ml. No change was observed at serum glucan levels of40 pg/ml. There was no correlation between serum glucan levels and systemic levels of IL-1beta, IL-5, IL-6, IL-8, IL-10 or IFNgamma. Interestingly, blood borne glucans did not suppress systemic cytokine levels in infected ICU patients, instead they were maintained at control levels. We conclude that circulating glucans may prevent cytokine upregulation in response to infection. This may represent an adaptive response to septic injury.

We identified Neisseria meningitidis lipooligosaccharide (LOS) as an acceptor for complement component C4b (C4b). Phosphoethanolamine (PEA) residues on the second heptose (HepII) residue in the LOS core structure formed amide linkages with C4b. PEA at the 6-position of HepII (6-PEA) was more efficient than 3-PEA in binding C4b. Strains bearing 6-PEA bound more C4b than strains with 3-PEA and were more susceptible to complement-mediated killing in serum bactericidal assays. Deleting 3-PEA from a strain that expressed both 3- and 6-PEA simultaneously on HepII did not decrease C4b binding. Glycose chain extension of the first heptose residue (HepI) influenced the nature of the C4b-LOS linkage. Predominantly ester C4b-LOS bonds were seen when lacto-N-neotetraose formed the terminus of the glycose chain extension of HepI with 3-PEA on HepII in the LOS core. Related LOS species with more truncated chain extensions from HepI bound C4b via amide linkages to 3-PEA on HepII. However, 6-PEA in the LOS core bound C4b even when the glycose chain from HepI bore lacto-N-neotetraose at the terminus. The C4A isoform exclusively formed amide linkages, whereas C4B bound meningococci preferentially via ester linkages. These data may serve to explain the preponderance of 3-PEA-bearing meningococci among clinical isolates, because 6-PEA enhances C4b binding that may facilitate clearance of 6-PEA-bearing strains resulting from enhanced serum killing by the classical pathway of complement.

Glucans are fungal cell wall polysaccharides which stimulate innate immune responses. We determined the minimum unit ligand that would bind to glucan receptors on human U937 cells using laminarin-derived pentaose, hexaose, and heptaose glucan polymers. When U937 membranes were pretreated with the oligosaccharides and passed over a glucan surface, only the heptasaccharide inhibited the interaction of glucan with membrane receptors at a Kd of 31 µM (95% CI 20-48 µM) and 100% inhibition. However, the glucan heptasaccharide did not stimulate U937 monocyte NFjB signaling, nor did it increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger and more complex glucan polymer (M w = 7 700 g/mol), only partially inhibited binding (61 ± 4%) at a K d of 2.6 µM (99% CI 1.7-4.2 µM) with characteristics of a single binding site. These results indicate that a heptasaccharide is the smallest unit ligand recognized by macrophage glucan receptors. The data also indicate the presence of at least two glucan-binding sites on U937 cells and that the binding sites on human monocyte/macrophages can discriminate between glucan polymers. The heptasaccharide and laminarin were receptor antagonists, but they were not receptor agonists with respect to activation of NFjB-dependent signaling pathways or protection against experimental sepsis. © 2001 Editions scientifiques et medicales Elsevier SAS glucan / receptors / heptasaccharide / NFjB / macrophage / monocyte / sepsis

Screening of 29 strains of Neisseria gonorrhoeae revealed that 16/21 serum resistant strains and 0/8 serum sensitive strains bound C4bp, suggesting that C4bp binding to gonococci could contribute to serum resistance. C4bp bound to gonococci retained cofactor (C4b-degrading) function. Using allelic exchange to construct strains with hybrid Por1A/B molecules, we demonstrate that the N-terminal loop (loop 1) of Por1A is required for C4bp binding. Serum resistant Por1B gonococcal strains also bind C4bp via their Por molecule. Using allelic exchange and site-directed mutagenesis, we have shown that loops 5 and 7 together form a negatively charged C4bp binding domain. C4bp-Por1B interactions are ionic in nature (inhibited by high salt as well as by heparin), while the C4bp-Por1A bond is hydrophobic. mAbs directed against SCR1 of the alpha-chain of C4bp inhibit C4bp binding to both Por1A and Por1B. Furthermore, only recombinant C4bp mutant molecules that contain alpha-chain SCR1 bind both Por1A and Por1B gonococci, confirming that SCR1 contains Por binding sites. C4bp alpha-chain monomers do not bind strains with either Por molecule, suggesting that the polymeric form of C4bp is required for binding to gonococci. Inhibition of C4bp binding to serum resistant Por1A and Por1B strains in a serum bactericidal assay using fAb fragments against C4bp SCR1 results in complete killing at 30 min of otherwise fully serum resistant strains in only 10% normal serum, underscoring the role of C4bp in mediating gonococcal serum resistance.

Lipo-oligosaccharides (LOS) produced by Neisseria gonorrhoeae are important antigenic and immunogenic components of the outer membrane complex. Previously, we showed that murine monoclonal antibody (mAb) 2C7 did not cross-react with human glycosphingolipids but identified the LOS epitope that is widely expressed in vivo and in vitro (Gulati, S., McQuillen, D. P., Mandrell, R. E., Jani, D. B., and Rice, P. A. (1996) J. Infect. Dis. 174, 1223-1237). In the present study, we analyzed the structure of gonococcal strain WG LOS containing the 2C7 epitope and investigated the structural requirements for expression of the epitope. We determined that the WG LOS components are Hep[1]-elongated forms of 15253 LOS that have a lactose on both Hep[1] and Hep[2] (Yamasaki, R., Kerwood, D. E., Schneider, H., Quinn, K. P., Griffiss, J. M., and Mandrell, R. E. (1994) J. Biol. Chem. 269, 30345-30351). In addition, we found that expression of the 2C7 epitope within the LOS is blocked when the Hep[2]-lactose is elongated. Based on the structural data of these LOS and the results obtained from immunochemical analyses, we conclude the following: 1) mAb 2C7 requires both the 15253 OS minimum structure and the N-linked fatty acids in the lipoidal moiety for expression of the epitope; 2) mAb 2C7 binds to the LOS that elongates the lactose on Hep[1] of the 15253 OS, but not the one on Hep[2]; and 3) the 2C7 epitope is expressed on gonococcal LOS despite the presence of human carbohydrate epitopes such as a lactosamine or its N-acetylgalactosaminylated (globo) form. Our study shows that the conserved epitope defined by mAb 2C7 could potentially be used as a safe site for the development of a vaccine candidate.

Secretin and VIP stimulate cardiac adenylyl cyclase activity and exert a positive inotropic action in several mammalian species. This study examined positive inotropic activity and cAMP levels in rat papillary muscle. Isoproterenol and secretin increased contractions by 150+/-31% and 129+/-27%, respectively. VIP increased contraction by 30+/-21% only at 10 microM. Isoproterenol significantly increased cAMP levels by 82%, whereas increases by secretin (58%) and VIP (56%) were not significant. These results are consistent with reports that secretin and VIP stimulate cardiac adenylyl cyclase in the rat, but suggest that cAMP tissue levels cannot totally explain the positive inotropic responses to secretin and VIP.

An analytical framework is described to evaluate exotic weed control treatments applied to native vegetation for conservation purposes. The analyses were used to assess the following responses to herbicide applications for control of an exotic forb Centaurea maculosa in fescue grassland: (1) efficacy on the target weed species, (2) similarity to reference stands defining the potential natural communities, (3) resistance and resilience of the nontarget vegetation, and (4) community structure in terms of life form proportions. Vegetation data were collected from replicated plots one year before spraying and for the first three years after spraying at two sites in western Montana. Low rates of selected herbicides effectively suppressed the target weed for three years after treatment. Grasses responded positively to release from exotic forb competition, while total nontarget forb standing crops were similar between treated plots and untreated control plots three years after spraying. The site with lower pretreatment cover of exotic species and higher pretreatment composition of native species had the largest positive response to spraying in terms of similarity to the potential natural vegetation. Although some treatments caused depressions after one year, all treatments had the same or higher per cent of pretreatment species present compared to the untreated control plots in the third year after spraying. Herbicide-sensitive taxa were identified by multivariate analysis of canopy cover data. Implications of the results for conservation management of high priority grassland sites are discussed.

Monophosphoryl lipid A was prepared from the lipopolysaccharide of Chlamydia trachomatis, converted to the methyl ester, and fractionated by reverse-phase high-performance liquid chromatography. The peak fractions were collected and analyzed by mass spectrometry. Matrix-assisted laser desorption/ionization and liquid secondary ion mass spectrometry of the first of two major high-performance liquid chromatographic fractions showed multiple quasi-molecular ions of MNa+ at m/z 1780, 1794, 1808, 1822, and 1836. The positive-ion liquid secondary ion mass spectrometry spectrum also showed a minor series of peaks at m/z 1916, 1930, 1944, 1958, and 1971, consistent with the formation of matrix adducts with 3-nitrobenzyl alcohol. Oxonium ions representing the distal subunit were observed at m/z 1057, 1071, 1085, 1099, and 1113. The second fraction was similarly analyzed and found to contain structural homologs of the first fraction. Based on this study, the major lipid A component of chlamydial lipopolysaccharide is a glucosamine disaccharide that contains five fatty acids and a phosphate in the distal segment. Three fatty acyl groups are in the distal segment, and two are in the reducing end segment. The acyloxyacyl group is located in the distal segment in amide linkage. Two structural series, differing by 14 atomic mass units in the reducing subunit, were observed. Chlamydial lipid A is complex and consists of at least 20 homologous structural components. The relatively low potency of Chlamydia trachomatis lipopolysaccharide in activating lipopolysaccharide-responsive cells might be related to the unusual fatty acid composition of the lipid A moiety.

OBJECTIVE: Oral contraceptive use has been associated with a lower risk of symptomatic pelvic inflammatory disease but a higher risk of chlamydial cervicitis. To explain these seemingly contradictory findings, we asked whether oral contraceptive use was more common among women with unrecognized endometritis than among women with recognized endometritis. STUDY DESIGN: A multicenter case-control study was performed. Women without signs of pelvic inflammatory disease were ascertained through contact tracing of partners with sexually transmitted diseases or through presentation with cervicitis. Women with symptomatic pelvic inflammatory disease met a set of standard clinical criteria. We compared the 43 cases without signs of pelvic inflammatory disease but with endometritis ("unrecognized endometritis") with the 111 controls with recognized pelvic inflammatory disease and endometritis ("recognized endometritis"). RESULTS: Women with unrecognized endometritis were 4.3 times (95% confidence interval 1.6 to 11.7) more likely than women with recognized endometritis to use oral contraceptives. CONCLUSION: Future studies need to fully characterize the risks and benefits of oral contraceptives in relation to sexually transmitted diseases.(Am J Obstet Gynecol 1997;176:580-5.)

Although adenosine receptors have been implicated in the induction of preconditioning in a variety of experimental models, there is controversy concerning the specific adenosine receptor subtypes mediating this effect. Concentration-protection relationships for adenosine and adenosine agonists in rabbit cardiomyocytes were used to characterize the role of adenosine receptor subtypes in preconditioning. Isolated cells were ischemically preconditioned or pre-incubated for 10 min with increasing concentrations of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), APNEA (N6-2-(4-aminophenyl)ethyladenosine), or BNECA (N6-benzyl-5'-N-ethyl-carboxamidoadenosine) in the presence or absence of 1 or 10 microM of the selective A1-adenosine antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine). Following a 30-min post-incubation period, cells were pelleted, layered with oil and ischemically incubated for 180 min. Injury was assessed by osmotic swelling and trypan blue exclusion of sequential samples, and determination of the areas beneath the mortality curves. Adenosine produced a broad concentration-protection curve which was displaced to the right by DPCPX. The curve for A1-selective agonist CCPA was biphasic, with an initial response below 1 nM and a second above 1 microM. DPCPX abolished the early response leaving a steep monophasic curve between 0.1 and 10 microM CCPA. The APNEA curve appeared moriophasic, the major slope occurring between 1-100 nM; DPCPX (1 microM) shifted the concentration-response curve approximately 30-fold and decreased the slope. Adenosine receptor agonist BNECA produced preconditioning characterized by a shallow monophasic concentration-protection curve with a maximal effect of 49% and an EC50 of approximately 5 nM; DPCPX shifted the BNECA concentration-protection relationship approximately 40-fold with only a modest increase in slope. Analysis of the data suggests that induction of preconditioning results from interaction of agonists with the A1 receptor and a second adenosine receptor having properties consistent with the A3 receptor. Adenosine, CCPA, APNEA, BNECA and DPCPX each appear to be selective for the A1 adenosine receptor subtype in isolated rabbit cardiomyocytes.

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 acknowledged 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.

The role of protein kinase C (PKC) in mediating contractile responses in the rat vas deferens was studied. Phorbol-12,13-diacetate (PDA) in the presence of 20 mM K+ elicited a concentration-dependent response with an EC50 of 190 nM. The non-PKC activator 4 alpha-phorbol (2 microM) was unable to elicit contraction in 20 mM K+ buffer. Incubation of rat vas deferens with the PKC inhibitor iso-H7 (30 microM) attenuated the response to norepinephrine (NE) and neurokinin A, with maximal effects depressed to 42 and 39% of control, respectively. Responses to 60 mM K+ and 2 microM PDA (20 mM K+) was also significantly inhibited by iso-H7. In the presence of 2 microM PDA and 20 mM K+, the NE concentration-effect curve was shifted 3.6-fold to the right of the control curve in a parallel manner. 4 alpha-Phorbol (20 mM K+) at the same concentration did not produce this effect. These results suggest a significant role for PKC in the contractile response of the rat vas deferens.

The importance of databases as a research tool in molecular biology is growing steadily, and a wide range of databases relevant to genome research is currently available. However, the design of current databases is inadequate for accurate representation and analysis of the results of large-scale genome mapping and sequencing projects. A new generation of databases is required to master the challenges of the future.

Biosensors provide analytical information about biochemical and biological systems. One such device is a light-addressable potentiometric sensor at the heart of an instrument called a microphysiometer. The instrument detects a signal that is closely related to the cellular metabolic rate. The use of this device is discussed.

Since Miller and Modigliani (1961), the issue of dividend payout policy on equity valuation has been largely ignored by the markets – the payment of dividends is generally regarded as irrelevant. Further, interest in dividend capture schemes in the market has to a large extent dried up as such strategies have fallen victim to tax laws which have attempted to wipe out their widespread use. Evidence presented in this paper suggests that investors should take another look at dividends and their value to equity holders. This paper examines stock prices of the 50 largest companies (by market capitalisation) listed on the Australian Stock Exchange, following the payment of dividends to determine the rate at which ex dividend stock price retraces back to the cum dividend price and the returns from this stock price movement. It finds evidence of significant retracing and as such questions whether shareholders are getting the value of dividends twice.

Neisseria gonorrhoeae can engage human complement receptor 3 (CR3) directly or through surface-bound iC3b. Factor H (fH) that binds to bacteria facilitates conversion of C3b to iC3b. fH also binds directly to CR3 on professional phagocytes. Certain nonprofessional phagocytes, such as primary cervical epithelial cells, also express CR3. We hypothesized that fH could bridge bacteria to CR3 and facilitate gonococcal association with host cells. Specificity of the fH-CR3 interaction was confirmed using human CR3-transfected Chinese hamster ovary (CHO-CR3) cells. Using recombinant proteins that comprised contiguous fH domains (fH contains 20 short consensus repeat [SCR] domains) fused to murine Fc, we observed strong binding through SCRs 18-20, whereas weaker binding occurred through SCRs 6-10. Both regions also bound to unsialylated porin (Por) B.1A-expressing N. gonorrhoeae. Accordingly, fH-related protein 1 (three of its five SCRs are highly homologous to fH SCRs 18-20) bound to CHO-CR3 and to unsialylated PorB.1A gonococci. An alternatively spliced variant of fH called fH-like protein-1 (contains fH SCRs 1-7) bound to gonococci but minimally to CHO-CR3. An fH SCRs 6-20 construct enhanced binding of unsialylated PorB.1A gonococci to CHO-CR3. However, a construct that contained only the apparently relevant SCRs (6, 7, and 18-20) bound to CHO-CR3 and to gonococci separately, but did not enhance bacteria-CR3 interactions, suggesting that the intervening SCRs (8-17) may impart a configurational and spatial requirement for fH to bridge gonococci to CR3. These results indicate adherence between fH-coated gonococci and CR3 and may provide a means for gonococci to gain sanctuary into nonprofessional phagocytes.

Symptomatic infection with Salmonella heidelberg developed in 55 children after their admission to the pediatric wards of two adjacent hospiatls in San Juan, Puerto Rico. Many of these children had been hospitalized for the treatment of diarrhea of unidentified etiology. In 25 of these patients, Salmonella bacteremia was documented. Five had clinically unsuspected and untreated bacteremia with no evidence of complications during the follow-up period of four and a half months. The remaining 30 had "standard" symptomatic infection due to S. heidelberg. Eight children died; four of these proved to be bacteremic. The index patient, who also introduced the infection into one of the hospitals, was identified. Person to person spread perpetuated the outbreak within and between the two hospitals for nearly four months. Although neonates with salmonellosis had a higher rate of bacteremia than other children, no other specific predisposing factors for Salmonella bacteremia were identified. Laboratory studies of the epidemic strain revealed neither invasive nor enterotoxic properties of the organisms, nor enhanced virulence in laboratory mice. Cohort nursing and isolation of patients with positive cultures halted the epidemic. Nontyphoid Salmonella bacteremia, sometimes clinically unsuspected and self-limited, should be recognized as a frequent accompaniment of Salmonella enteritis in young hospitalized children.