The significance of physical breaches of the trophoblastic layer of the placenta in transmission of HIV from mother to infant was evaluated in 17 HIV-infected pregnant women. Samples of peripheral blood were obtained from the women during pregnancy and at delivery, at which time a small piece of placental tissue was obtained from a random site and immediately placed into fixative. Blood samples were obtained from infants at or shortly after birth and thereafter at approximately 3-month intervals, until the age of 18 months, in order to determine their HIV infection status. HIV RNA and p24 antigen were quantified in maternal plasma and CD4 cells enumerated. Paediatric diagnosis was conducted using polymerase chain reaction, virus isolation, detection of p24 antigen, and measurement of class-specific antibodies. Placental damage was quantified and evaluated using transmission electron microscopy. Maternal viral load was low, with a mean RNA copy number of 8,237 per millilitre of plasma (range 230-37,233 copies/ml). Only two women were p24-antigenaemic, and CD4 numbers ranged from 0.09 to 2.8 x 10(9)/l. There was evidence of breaks in the trophoblastic surface to the depth of the basement membrane in all 17 placentas, and perivillous fibrinoid deposits were also observed to a varying degree in all samples. However, none of the 13 infants available for follow-up had evidence of infection with HIV. Superficial damage to the trophoblastic surface of the placenta, with exposure of the basement membrane and potential exposure of CD4-expressing cells, does not appear to be a significant factor in the transmission of HIV from mother to infant during pregnancy.

Female↗

PubMed1996

Abnormal umbilical artery Doppler waveforms and cord blood corticotropin-releasing hormone.

OBJECTIVE: To determine whether placental secretion of corticotropin-releasing hormone into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. METHODS: Twenty women with abnormal Doppler umbilical artery flow velocity waveforms and six women with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms had cord blood concentrations of corticotropin-releasing hormone, ACTH, cortisol, and beta-hCG estimated. RESULTS: The mean cord blood corticotropin-releasing hormone concentration was significantly higher in pregnancies with abnormal umbilical artery flow velocity waveforms than in normal pregnancies (108 +/- 27 versus 24 +/- 8 pg/mL, P = .019). Elevated cord blood corticotropin-releasing hormone levels were seen in the abnormal group regardless of the presence or absence of preeclampsia or fetal growth restriction. There were no significant differences in cord blood cortisol, ACTH, or beta-hCG concentrations. CONCLUSION: The concentration of corticotropin-releasing hormone in the fetal circulation is significantly increased in pregnancies complicated by abnormal umbilical artery flow velocity waveforms. This may represent a stress-responsive compensatory mechanism in the human placenta.

Adult↗

PubMed1996

Effect of cross-linking agents on the dynamic mechanical properties of hydrogel blends of poly(acrylic acid)-poly(vinyl alcohol-vinyl acetate).

A range of hydrogels were prepared by blending aqueous solutions of poly(vinyl alcohol-vinyl acetate) with poly(acrylic acid) in various proportions. The effects of two cross-linking agents (glyoxal and glutaraldehyde) and subsequent thermal treatment on the properties of the blends are discussed. Dynamic mechanical analysis (DMA) of the xerogels indicated complete miscibility of the various blends which was evident from the appearance of a single glass transition temperature (Tg) in the presence of either glyoxal or glutaraldehyde at all thermal treatments studied. A 50/50% wt/wt blend was found to have the highest storage modulus and was thus selected for further study. Hydrogels prepared with glutaraldehyde without subsequent thermal treatment exhibited higher storage modulus values than those prepared using glyoxal when tested isothermally at 20 degrees C in a water bath. A further increase in the storage modulus was observed when these hydrogels were thermally treated at 120 or 150 degrees C. In a non-isothermal study on the cross-linked hydrogels, no variation in storage modulus was observed. Broad peaks were observed in tan delta plots, these peaks shifting towards higher frequencies as the degree of cross-linking increased in the hydrogel.

Acrylates↗

PubMed1996

Three-dimensional kinematics of the rearfoot during the stance phase of walking in normal young adult males.

Three-dimensional video analysis was used to quantify three-dimensional motion of the rearfoot in 14 normal young adult males during the stance phase of walking. A stringent calibration procedure enabled standardization of the neutral position of the rearfoot. Surface markers were placed on the calcaneus and lower tibia, and a joint coordinate system was used to determine the relative displacement between the calcaneus and lower leg as representative of rearfoot motion. Confirmation was made of the assumption of a mechanical coupling between the rearfoot displacements of abduction/adduction and eversion/inversion. However, there were several findings which contrasted with commonly held assumptions. For example, the rearfoot was found to evert gradually, rather than rapidly, from heel contact to just prior to heel rise. Also the conventional descriptions of the composite movements of pronation and supination were not applicable to rearfoot movement in this study, and it was therefore concluded that pronation and supination are not valid descriptors of three-dimensional rearfoot motion during the stance phase of walking.

Journal Article↗

PubMed1996

Perioperative care in the elderly urologic patient.

This article summarizes the preoperative evaluation and postoperative care recommended for elderly patients undergoing urologic procedures. Most of the common issues faced during the perioperative period are discussed, but many other topics require reference to other sources or consultation with specialists. A thorough preoperative evaluation is needed, and meticulous attention to postoperative care is mandatory. The most important common problem is assessment of cardiovascular risk in patients and a general approach is suggested by the authors. Surgical risk in elderly patients is increased, but most of this excess risk is because of associated comorbid conditions. Effective pre- and postoperative assessment and care can minimize this risk and maximize the chances of a successful outcome.

Aged↗

PubMed1996

The World Wide Web as a graphical user interface to program macros for molecular graphics, molecular modeling, and structure-based drug design.

In this article we describe how the World Wide Web (WWW or Web) has been employed to provide access to computational chemistry software and protein structure data via program macros. We show how the combination of Web technology and macros can automate both the running of chemistry software and the execution of complex operations on protein structures. The current version of the system supports the molecular visualization packages GRASP, RASMOL, MOLVIEWER-OGL and INSIGHT95, and the ligand design tool GRID and includes more than 175 in-house protein-ligand complexes. The approach enables inexperienced users to confidently make full use of sophisticated modeling techniques by offering only sensible options, hiding parameter settings, and controlling program invocation and macro execution. Our interface provides both the expert and non-expert alike with powerful tools for protein structure visualization, molecular modeling, and rational drug design.

Computer Communication Networks↗

PubMed1996

Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel.

The effect of GABAA receptor activation varies from inhibition to excitation depending on the state of the transmembrane anionic concentration gradient (delta anion). delta anion was genetically altered in cultured dorsal root ganglion neurons via adenoviral vector-mediated expression of ClC-2, a Cl- channel postulated to regulate the Cl- concentration in neurons in which GABAA receptor activation is predominantly inhibitory. ClC-2 expression was verified by the presence of the appropriate mRNA, protein, and membrane conductance. CIC-2 expression resulted in a large negative shift in the Cl- equilibrium potential (ECl) that attenuated the GABA-mediated membrane depolarization and prevented GABAA receptor-mediated action potentials. These results establish that gene transfer of transmembrane ion channels to neurons can be used to demonstrate their physiological function, and that delta anion can be genetically manipulated to alter the function of neuronal GABAA receptors in situ.

Adenoviridae↗

PubMed1996

Interferon-gamma as a regulator of squamous differentiation.

Interferon-gamma (IFN-gamma) is a potent immunomodulatory molecule. Recent studies demonstrate that IFN-gamma can induce growth arrest and differentiation in epithelial cells. The signalling pathways controlling growth and differentiation in epithelial cells appears to be different to those regulating immune functions in non-epithelial cells and appear to impact on key cell cycle regulatory genes such as cdk1 and E2F1. In addition, studies with IFN-gamma have highlighted the complexity of the signalling pathways regulating the expression of differentiation markers in squamous differentiating epithelia. Given the actions of IFN-gamma upon epithelial cell growth and differentiation it should be considered a potential regulator of both immune and epithelial cell targets in various inflammatory pathologies such as psoriasis.

Adjuvants, Immunologic↗

PubMed1996

Introducing children to the accident and emergency department: the 999 club.

Explore the source record for details and available documents.

Child↗

PubMed1996

Scanning electron microscopy of teeth in osteogenesis imperfecta type I.

Opalescent teeth from five patients and nonopalescent teeth from six patients with osteogenesis imperfecta type I were examined with the scanning electron microscope and their appearances compared with those of teeth from normal persons. In opalescent teeth the main findings were a reduction in the number and variation in the size of the dentinal tubules that were irregularly embedded within the disturbed dentinal matrix and an abnormally smooth enamel-dentinal junction. Similar less marked dentinal abnormalities were found in the nonopalescent teeth from three patients. No abnormality was found in the enamel in any of the teeth examined. These findings suggest that in osteogenesis imperfecta teeth that appear normal may have defective dentine. This relevant to the current clinical classification of the disorder into subgroups according to the clinical presence or absence of affected teeth.

Adult↗

PubMed1996

Ionization states of the catalytic residues in HIV-1 protease.

Chemical synthesis was used to prepare the HIV-1 protease specifically 13C-labelled in the catalytically essential Asp 25 in each monomer. The NMR chemical shift of the 13C-enriched homodimeric enzyme was measured in the presence of the inhibitor pepstatin, a mimic of the tetrahedral intermediate formed in enzyme catalysis. In this complex, the catalytic carboxyls do not titrate in the pH range where the enzyme is active; throughout the range pH 2.5-6.5, one Asp 25 side chain is protonated and the other deprotonated. By contrast, in the absence of inhibitor the two Asp side chains are chemically equivalent and both deprotonated at pH6, the optimum for enzymatic activity. These direct observations of the chemical properties of the catalytic apparatus of the enzyme provide concrete information on which to base the design of improved HIV-1 protease inhibitors.

Aspartic Acid↗