Placental Transfer of Lactate, Glucose and 2-deoxyglucose in Control and Diabetic Wistar Rats

Placental transfer of lactate, glucose and 2-deoxyglucose was examined employing the in situ perfused placenta. Control and streptozotocin induced diabetic Wistar rats were infused with [U14C]-glucose and [3H]-2-deoxyglucose (2DG). The fetal side of the placenta was perfuseci with a cell free medium and glucose uptake was calculated in the adjacent fetuses. Despite the 5-fold higher maternal plasma glucose concentration in the diabetic dams the calculated fetal glucose metabolic index was not significantly different between the 2 groups. Placental blood flow was reduced in the diabetic animals compared with controls but reduction of transfer of [U14C]-glucose and [3H]-2-deoxyglucose and endogenously derived [14C]-Lactate to the fetal compartment, could not be accounted for by reduced placental blood flow alone. There was no significant net production or uptake of lactate into the perfusion medium that had perfused the fetal side of the placenta in either group. The plasma lactate levels in the fetuses adjacent to the perfused placenta were found to be higher than in the maternal plasma and significantly higher in the fetuses of the diabetic group compared with control group. In this model the in situ perfused placenta does not secrete significant quantities of lactate into the fetal compartment in either the control or diabetic group

Pair densities at contact in the quantum electron gas

The value of the pair distribution function g(r) at contact (r = 0) in a quantum electron gas is determined by the scattering events between pairs of electrons with antiparallel spins. The theoretical results for g(0) as a function of the coupling strength r_s in the paramagnetic electron gas in dimensionality D=2 and 3, that have been obtained from the solution of the two-body scattering problem with a variety of effective scattering potentials embodying many-body effects, are compared with the results of many-body calculations in the ladder approximation and with quantum Monte Carlo data.Comment: 7 pages, 2 figure

Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users

Nasal colonization plays an important role in the pathogenesis of Staphylococcus aureus infections. To identify characteristics associated with colonization, we studied a cross-section of a well-described cohort of HIV-seropositive and -seronegative active and former drug users considered at risk for staphylococcal infections. Sixty percent of the 217 subjects were Hispanic, 36% were women, 25% actively used injection drugs, 23% actively used inhalational drugs, 23% received antibiotics, and 35% were HIV-seropositive. Forty-one percent of subjects had positive nasal cultures for S. aureus. The antibiotic susceptibility patterns were similar to the local hospital's outpatient isolates and no dominant strain was identified by arbitrarily primed polymerase chain reaction (AB-PCR). Variables significantly and independently associated with colonization included antibiotic use (odds ratio [OR] = 0.37; confidence interval [CI] = 0.18-0.77), active inhalational drug use within the HIV-seropositive population (OR = 2.36; CI = 1.10-5.10) and female gender (OR = 1.97; CI = 1.09-3.57). Characteristics not independently associated included injection drug use, HIV status, and CD4 count. The association with active inhalational drug use, a novel finding, may reflect alterations in the integrity of the nasal mucosa. The lack of association between HIV infection and S. aureus colonization, which is contrary to most previous studies, could be explained by our rigorous control for confounding variables or by a limited statistical power due to the sample sizes

Recognition of skin malignancy by general practitioners: observational study using data from a population-based randomised controlled trial

Skin malignancy is an important cause of mortality in the United Kingdom and is rising in incidence every year. Most skin cancer presents in primary care, and an important determinant of outcome is initial recognition and management of the lesion. Here we present an observational study of interobserver agreement using data from a population-based randomised controlled trial of minor surgery. Trial participants comprised patients presenting in primary care and needing minor surgery in whom recruiting doctors felt to be able to offer treatment themselves or to be able to refer to a colleague in primary care. They are thus relatively unselected. The skin procedures undertaken in the randomised controlled trial generated 491 lesions with a traceable histology report: 36 lesions (7%) from 33 individuals were malignant or pre-malignant. Chance-corrected agreement (κ) between general practitioner (GP) diagnosis of malignancy and histology was 0.45 (0.36–0.54) for lesions and 0.41 (0.32–0.51) for individuals affected with malignancy. Sensitivity of GPs for the detection of malignant lesions was 66.7% (95% confidence interval (CI), 50.3–79.8) for lesions and 63.6% (95% CI, 46.7–77.8) for individuals affected with malignancy. The safety of patients is of paramount importance and it is unsafe to leave the diagnosis and treatment of potential skin malignancy in the hands of doctors who have limited training and experience. However, the capacity to undertake all of the minor surgical demand works demanded in hospitals does not exist. If the capacity to undertake it is present in primary care, then the increased costs associated with enhanced training for general medical practitioners (GPs) must be borne

Carrageenan Is a Potent Inhibitor of Papillomavirus Infection

Certain sexually transmitted human papillomavirus (HPV) types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate–independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs

Variant calling on the GRCh38 assembly with the data from phase three of the 1000 Genomes Project

We present biallelic SNVs called from 2,548 samples across 26 populationsfrom the 1000 Genomes Project, called directly on GRCh38. We believethis will be a useful reference resource for those using GRCh38,representing an improvement over the “lift-overs” of the 1000 GenomesProject data that have been available to date and providing a resourcenecessary for the full adoption of GRCh38 by the community. Here, wedescribe how the call set was created and provide benchmarking datadescribing how our call set compares to that produced by the final phase ofthe 1000 Genomes Project on GRCh37

Many-body aspects of positron annihilation in the electron gas

We investigate positron annihilation in electron liquid as a case study for many-body theory, in particular the optimized Fermi Hypernetted Chain (FHNC-EL) method. We examine several approximation schemes and show that one has to go up to the most sophisticated implementation of the theory available at the moment in order to get annihilation rates that agree reasonably well with experimental data. Even though there is basically just one number to look at, the electron-positron pair distribution function at zero distance, it is exactly this number that dictates how the full pair distribution behaves: In most cases, it falls off monotonously towards unity as the distance increases. Cases where the electron-positron pair distribution exhibits a dip are precursors to the formation of bound electron--positron pairs. The formation of electron-positron pairs is indicated by a divergence of the FHNC-EL equations, from this we can estimate the density regime where positrons must be localized. This occurs in our calculations in the range 9.4 <= r_s <=10, where r_s is the dimensionless density parameter of the electron liquid.Comment: To appear in Phys. Rev. B (2003

Cross-neutralization of cutaneous and mucosal Papillomavirus types with anti-sera to the amino terminus of L2

AbstractVaccination with papillomavirus L2 has been shown to induce neutralizing antibodies that protect against homologous type infection and cross-neutralize a limited number of genital HPVs. Surprisingly, we found that antibodies to bovine papillomavirus (BPV1) L2 amino acids 1–88 induced similar titers of neutralizing antibodies against Human papillomavirus (HPV)16 and 18 and BPV1 pseudoviruses and also neutralized HPV11 native virions. These antibodies also neutralized each of the other pseudovirus types tested, HPV31, HPV6 and Cottontail rabbit papillomavirus (CRPV) pseudoviruses, albeit with lower titers. HPV16, HPV18, HPV31, HPV6 and CRPV L2 anti-sera also displayed some cross-neutralization, but the titers were lower and did not encompass all pseudoviruses tested. This study demonstrates the presence of broadly cross-neutralizing epitopes at the N-terminus of L2 that are shared by cutaneous and mucosal types and by types that infect divergent species. BPV1 L2 was exceptionally effective at inducing cross-neutralizing antibodies to these shared epitopes

Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin A or toxin B in cell-based in vitro neutralization assays. Three anti-toxin A HuMAbs (3H2, CDA1, and 1B11) could all inhibit the enterotoxicity of toxin A in mouse intestinal loops and the in vivo toxicity in a systemic mouse model. Four anti-toxin B HuMAbs (MDX-1388, 103-174, 1G10, and 2A11) could neutralize cytotoxicity in vitro, although systemic toxicity in the mouse could not be neutralized. Anti-toxin A HuMAb CDA1 and anti-toxin B HuMAb MDX-1388 were tested in the well-established hamster model of C. difficile disease. CDA1 alone resulted in a statistically significant reduction of mortality in hamsters; however, the combination treatment offered enhanced protection. Compared to controls, combination therapy reduced mortality from 100% to 45% (P\u3c0.0001) in the primary disease hamster model and from 78% to 32% (P\u3c0.0001) in the less stringent relapse model