Molecular recognition of modified adenine nucleotides by the P2Y(1)-receptor. 1. A synthetic, biochemical, and NMR approach.

The remarkably high potencies of 2-thioether-adenine nucleotides regarding the activation of the P2Y(1)-receptor (P2Y(1)-R) in turkey erythrocyte membranes represent some of the largest substitution-promoted increases in potencies over that of a natural receptor ligand. This paper describes the investigation regarding the origin of the high potency of these P2Y(1)-R ligands over that of ATP. For this study, an integrated approach was employed combining the synthesis of new ATP analogues, their biochemical evaluation, and their SAR analysis involving NMR experiments and theoretical calculations.

Odorants presented to the rat nasal cavity increase cortical blood flow.

Complaints about unpleasant environmental odorants, both outdoor and indoor, are increasingly being reported. The main complaints of health symptoms from environmental odorants are eye, nose and throat irritation, headache and drowsiness. Complaints may arise from the stimulation of olfactory receptors or trigeminal chemoreceptors.

Potential of polymeric lamellar substrate particles (PLSP) as adjuvants for vaccines.

In recent years microspheres or microparticles produced from biodegradable polymers such as poly(D,L-lactide) (PLA) and poly(D, L-lactide-co-glycolide) (PLGA) containing encapsulated vaccine antigens have been investigated for administration via parenteral, oral, and intranasal routes. These microparticles allow the controlled release of vaccines with an aim to reduce the number of doses for primary immunisation or to develop single dose vaccines. The polymer materials have been widely regarded as being of minimal toxicity.

Primary hypoparathyroidism in two horses.

Two Thoroughbred horses were presented with various clinical signs which included sweating, agitation, muscle twitching and synchronous diaphragmatic flutter. These signs were associated with profound hypocalcaemia. A diagnosis of primary hypoparathyroidism was made on the basis of low serum ionised calcium concentration, hyperphosphataemia and markedly reduced serum immunoreactive parathyroid hormone concentrations in the presence of normal renal function.

Characterization of "mini-nucleotides" as P2X receptor agonists in rat cardiomyocyte cultures. An integrated synthetic, biochemical, and theoretical study.

The design and synthesis of "mini-nucleotides", based on a xanthine-alkyl phosphate scaffold, are described. The physiological effects of the new compounds were evaluated in rat cardiac cell culture regarding Ca(2+) elevation and contractility. The results indicate biochemical and physiological profiles similar to those of ATP, although at higher concentrations.

Improved pulmonary function after surgical reduction of congenital diaphragmatic hernia in lambs.

Background/purpose: Modern trends are toward delayed surgical reduction of congenital diaphragmatic hernia. This study was conducted to verify the hypothesis that the "ease" of ventilation found in the authors' postoperative experience in infants with congenital diaphragmatic hernia (CDH) is associated with postsurgical improvement in pulmonary mechanics.

Methods: Very severe CDH was surgically induced in utero at 90 days' gestation in 31 lambs.

Retinol status of newborn infants with congenital diaphragmatic hernia.

The etiology of congenital diaphragmatic hernia (CDH) is not yet known. Studies in the literature from 1941 have reported that nutritional deficiency of vitamin A during pregnancy could lead to CDH, associated or not with other malformations in young rats. More recently, possible correlations between expression patterns of cellular retinoid-binding protein and retinoic-acid receptors and morphologic effects of vitamin A deficiency have been suggested.

Resorbable lamellar particles of polylactide as adjuvants for influenza virus vaccines.

Lamellar particles and microspheres were produced by precipitation from solutions of resorbable, biocompatible, semi-crystalline poly(L-lactide)[PLA] and amorphous poly(DL lactide co-glycolide)[PLG] copolymer, respectively, to investigate their adjuvanticity towards adsorbed influenza virus. Both types of substrate were capable of adsorbing large quantities of virus (> 15% w/w) and retaining virus (> 60% of the initial load) over an 8 week time scale in-vitro. Potent immune responses were obtained in mice after the intra-muscular injection of adsorbed vaccine systems.

Life-long dietary restriction attenuates age-related increases in hippocampal glial fibrillary acidic protein mRNA.

The expression of astrocyte-specific glial fibrillary acidic protein increases after experimental lesions and is elevated throughout the brain in aged rodents and primates. Clusterin (ApoJ) expression increases in astrocytes and microglia after lesions, but changes during aging have not been reported. Dietary restriction (DR) delays the onset and progression of many age-related physiological deficits in rodents.

Morphometrics of normal and hypoplastic lungs in preterm lambs with gas and partial liquid ventilation.

To test the hypothesis that perfluorochemical (PFC) instillation may reduce the pulmonary trauma commonly associated with conventional gas ventilation, we studied 12 lambs with normal lungs and 10 with pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH). We used mechanical ventilation for up to 3.5 h, with and without tracheal instillation of LiquiVent PFC liquid.

Morphometrics of normal and hypoplastic lungs in preterm lambs with gas and partial liquid ventilation.

To test the hypothesis that perfluorochemical (PFC) instillation may reduce the pulmonary trauma commonly associated with conventional gas ventilation, we studied 12 lambs with normal lungs and 10 with pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH). We used mechanical ventilation for up to 3.5 h, with and without tracheal instillation of LiquiVent PFC liquid.

A new stable pluronic F68 gel carrier for antibiotics in contaminated wound treatment.

Pluronic F68 was selected as the gel carrier for antimicrobial agents because of its extensive use as a wound cleanser in humans without discernable side effects. When the concentration of this surfactant is increased to 46%, it forms a water soluble gel that can serve as a carrier for antimicrobial agents. The stability of this gel can be enhanced by immediately cooling (-15 degrees C) the gel for 24 hours before storage and subsequent application.

Comparison between open and arthroscopic acromioplasties: evaluation of absenteeism.

Objective: To evaluate the rate of absenteeism from work in patients who had undergone open or arthroscopic acromioplasty.

Design: A retrospective case series.

Setting: A university hospital.

Cross-reaction but no avidity change of the serum antibody response after influenza vaccination.

Pre- and post-vaccination sera from 19 volunteers were analysed by the haemagglutination inhibition (HI) test, virus neutralization (VN) assay and avidity enzyme-linked immunosorbent assay (ELISA). The sera were tested against the three strains in a commercial inactivated influenza vaccine; A/Beijing/353/89(H3N2); A/Taiwan/1/86 (H1N1) and B/Yamagata/16/88. Additionally, a range of earlier strains and one newer isolate were assayed for HI- and VN-antibodies.

Combined gas ventilation and perfluorochemical tracheal instillation as an alternative treatment for lethal congenital diaphragmatic hernia in lambs.

Tracheal instillation of perfluorochemical liquid (PFC) lowers surface tension in the lung and thus might reduce barotrauma commonly associated with conventional gas ventilation (GV) in highly immature and hypoplastic lungs. It could be a promising alternative treatment for congenital diaphragmatic hernia (CDH) when GV alone is proving inefficient. The authors compared data for eight newborn lambs with surgically induced CDH.

Influence of Biobrane construction on adherence.

Biobrane (standard adherence) and Biobrane L (light adherence) were compared for their degree of adherence to donor site wounds on rabbits at 1, 4, 7, and 9 days. Biobrane, which has more nylon fabric exposed to the wound surface, had significantly greater adherence levels to the wound at all time periods when compared with Biobrane L, which has less nylon fabric exposed to the wound.

Pumpless respiratory assistance using a membrane oxygenator as an artificial placenta: a preliminary study in newborn and preterm lambs.

Newborns suffering from severe respiratory difficulties and not responding to conventional methods have been successfully treated by extracorporeal circulation with a membrane oxygenator (ECMO). However, the technique needs a highly specialized staff, excellent laboratory support, and continuous surveillance of the procedure to prevent complications. In a series of experiments on newborn and preterm lambs, we have investigated a relatively simpler technique of respiratory support that involves a pumpless arteriovenous bypass by cannulating both umbilical arteries and the umbilical vein.

Role of charge and hydration in effects of polysialic acid on molecular interactions on and between cell membranes.

Previous studies have shown that the polysialic acid (PSA) moiety associated with the neural cell adhesion molecule (NCAM) has strong antiadhesive properties that can influence a variety of cell-cell interactions. Based on the size and structure of this long linear homopolymer, we have proposed that the activity of PSA results from its physical properties. In the present study, the premise that the charge and hydration properties of PSA underlie its effects on membrane vesicle aggregation is investigated through the manipulation of ionic strength.

Sex and species differences in the effects of cohabitation on vasopressin messenger RNA expression in the bed nucleus of the stria terminalis in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus).

Three days of male and female cohabitation dramatically reduces the density of vasopressin-immunoreactive (AVP-ir) fibers in the lateral septum and lateral habenular nucleus of male, but not of female prairie voles. Here we tested whether this reduction is associated with changes in AVP messenger RNA (mRNA) expression in the bed nucleus of the stria terminalis (BST), the presumed source of these fibers, and with changes in testosterone levels, which may influence AVP biosynthesis in the BST. In addition, we tested whether similar changes can be found in meadow voles, which unlike prairie voles do not dramatically change their social behaviors after mating.

Codominant mixtures of viruses in reference strains of influenza virus due to host cell variation.

Influenza viruses grown in chicken eggs may comprise mixtures of variants, creating problems in establishing international reference strains and in preparing high growth reassortants. We therefore analyzed representative reference strains of H3N2 viruses from 1987 to 1989 by direct sequencing of HA1. Three of seven reference strains had different nucleotides at the same position in nucleotide gels, indicating the presence of codominant mixtures.

The role of amniotic passage in the egg-adaptation of human influenza virus is revealed by haemagglutinin sequence analyses.

Obtaining an isolate of a human influenza virus in the allantoic cavity of the embryonated hen's egg is more efficient if the clinical sample is initially passaged in the amniotic cavity. To investigate the extent to which the variants present after allantoic propagation are also selected by amniotic passage, clinical virus passaged once in the amnion has been subjected to extensive genetic and antigenic analyses. The data indicate that the natural virus can replicate unrestrictedly within the amnion.

Influence of host cell-mediated variation on the international surveillance of influenza A (H3N2) viruses.

Growth of clinical specimens of influenza viruses in eggs can result in the selection of antigenic variants distinct from corresponding viruses grown in mammalian tissue culture. To evaluate the contribution of host cell selection on the antigenic diversity of human influenza isolates, as seen in annual surveillance studies, viruses grown in embryonated eggs were compared by antigenic and genetic analyses with their mammalian tissue culture-grown counterparts. Clinical specimens were gathered from around the world from late 1987 to 1990 and the antigenicity of isolated viruses was assessed by hemagglutination-inhibition assays using immune ferret sera as is currently performed for routine surveillance and the selection of vaccine strains.

A new method of treatment for pulmonary hypertension in congenital diaphragmatic hernia: experimental study in cats.

This research proposes a new treatment for pulmonary hypertension secondary to perivascular emphysema, the so-called air-block syndrome. Vibrations applied on the thorax can fraction air bubbles around the vessels into smaller ones, facilitating their redistribution and reabsorption, thus reducing the extrinsic compression on pulmonary vasculature. In cats, pulmonary lesions were obtained by continuous insufflation of air at 40 cm H2O for 2 minutes in a lower lobe of the lung.

Estimation of lungs' hypoplasia on postoperative chest x-rays in congenital diaphragmatic hernia.

Since we stopped inserting ipsilateral underwater chest drains after surgical reduction of the herniated contents in congenital diaphragmatic hernia, both lungs are allowed to expand at their own pace, making it possible to estimate their degree of hypoplasia on postoperative chest x-rays. Thirty-nine consecutive series of postoperative chest x-rays were examined by an independent reviewer in a blind manner and classified into three groups: none to mild pulmonary hypoplasia (group I, 10 cases); moderate to severe (group II, 20 cases); and very severe hypoplasia (group III, 9 cases). Correlations were done among groups and available anatomical and clinical data.

Immune response of human volunteers and animals to vaccination with egg-grown influenza A (H1N1) virus is influenced by three amino acid substitutions in the haemagglutinin molecule.

Inactivated subunit vaccines were prepared from high-growth reassortants derived from two separate egg isolates from a single clinical specimen of influenza A (H1N1) virus. One of these reassortants, NIB-14, was antigenically indistinguishable from isolates made in tissue culture, while the other, NIB-17, was antigenically different and typical of egg isolates. The viruses differed by three amino acid residues in the haemagglutinin (HA) molecule and the anti-HA serological response induced was studied in animal models and human volunteers.