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Biomedical subjects

R Pierce

Publications and source records attributed to R Pierce.

At least 37 records · Page 2Linked to original sources

Development of a vaccine strategy against human and bovine schistosomiasis. Background and update.

Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have now been confirmed in human populations. Following the molecular cloning and expression of a 28 kDa protein of Schistosoma mansoni and its identification as a glutathione-S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appropriate monoclonal antibody probes made it possible to demonstrate that the inhibition of parasite fecundity following immunization was related to the inhibition of enzymatic activity of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Sleep related breathing disorders.

Sleep disorders encompass a broad group of conditions. In this article the sleep related breathing disorders are considered from the initial presentation through diagnosis and investigations to management.

Humans

[Detection of Toxoplasma gondii by "Polymerase Chain Reaction" (PCR) technique in AIDS infected patients using the repetitive sequence TGR1E].

A repetitive original DNA sequence, TGR1E, was cloned and sequenced, then used to develop a polymerase chain reaction (PCR) test for detecting Toxoplasma gondii. Preliminary studies were performed using purified T. gondii DNA or a lysate of purified T. gondii cells [7], with or without a leukocyte lysate. A negative correlation was evidenced between sensitivity of the test and the amount of cellular debris contaminating the DNA to be amplified. Nevertheless, the method was tested on 100 clinical specimens subjected to lysis using the same method. Among the 88 specimens from AIDS patients, four were positive by conventional diagnostic tests and by PCR. Among the 12 specimens tested as part of evaluations for the prevention of congenital toxoplasmosis, PCR failed to detect the positive results yielded by conventional tests on two amniotic fluid specimens. No false positive result was seen with the PCR method.

Acquired Immunodeficiency Syndrome

Efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in US children aged 18-59 months. Haemophilus Influenzae Vaccine Efficacy Study Group.

Vaccines prepared from the polyribosylribitol phosphate (PRP) capsule of Haemophilus influenzae b (Hib) have not consistently shown good efficacy in protecting children aged over 18 months from invasive Hib disease. To evaluate the efficacy of conjugate-PRP vaccines in this age-group, and to compare their effect with that of PRP vaccines, a post-marketing case-control study was conducted among 10,400,000 persons. Between Oct 1, 1988, and Feb 28, 1990, 75 patients with Hib disease and 161 control children between 18 and 60 months of age were enrolled. To minimise potentially confounding socioeconomic variables, controls were selected either from among patients' classmates at their day-care centre or from among family acquaintances. 9 of the 75 patients had received the diphtheria toxoid conjugate Hib vaccine more than 2 weeks before onset of illness. After adjusting for age and household crowding, the efficacy of PRP Hib vaccine was 64% (95% Cl = -20,89) and efficacy of the diphtheria toxoid conjugate Hib vaccine was 74% (95% Cl = 30,90). The study shows that the protective efficacy of this conjugate vaccine is less than ideal and highlights the need for additional post-licensing studies to confirm and expand understanding of the efficacy of these new products.

Analysis of Variance

Immunological crossreactivity between the human immunodeficiency virus type 1 virion infectivity factor and a 170-kD surface antigen of Schistosoma mansoni.

A monoclonal antibody (mAb) directed against a synthetic peptide derived from the sequence of the human immunodeficiency virus type 1 (HIV-1) regulatory protein virion infectivity factor (vif) labeled the surface of Schistosoma mansoni schistosomula by indirect immunofluorescence. Western blotting showed that two S. mansoni proteins of 170 and 65 kD were recognized by the mAb. Sera from 20% of S. mansoni-infected HIV-seronegative individuals tested recognized the PS4 peptide in an ELISA as did sera from S. mansoni-infected rats. Sera from individuals seropositive for HIV-1, but without schistosomiasis, that reacted with the vif peptide also recognized a 170-kD S. mansoni protein. This crossreactive S. mansoni antigen appears to be a target of immunity in vivo since passive transfer of the mAb VIF-CD3 to naive rats had a protective effect against a challenge infection with S. mansoni cercariae.

Amino Acid Sequence

Florida red-tide toxins (brevetoxins) produce depolarization of airway smooth muscle.

Crude preparations of brevetoxin (PBTX) produce airway contraction; however, it is not known if this toxin-induced mechanical response is coupled to changes in airway smooth muscle membrane potential. Membrane potentials and contractility of in vitro canine trachealis smooth muscle preparations were simultaneously measured with a microelectrode and microforce transducer before and during exposure to either the crude toxin (0.01-1.2 micrograms/ml), or the purified fractions PBTX-2 or PBTX-3 (0.01-0.07 micrograms/ml). Membrane potentials in cultured airway smooth muscle-reaggregate preparations were similarly studied. Toxins produced concentration-dependent depolarizations and contractions in in vitro preparations. These responses were not obtained in the presence of either the muscarinic blocking agent atropine, the sodium channel blocker tetrodotoxin (TTX), 0 mM extracellular Ca2+, or the Ca2+ channel blocker verapamil. The toxins were without effect in cultured cells, whereas acetylcholine produced depolarizations which were blocked in the presence of atropine, but not TTX. This suggested the presence of functional cholinergic receptors in cultured cells, and the PBTX-induced release of endogenous acetylcholine from peripheral nerve endings in the in vitro airway smooth muscle response.

Acetylcholine

Brief upper airway (laryngeal) dysfunction.

We describe in six men, recurrent episodes recurring over months or years, of sudden, brief complete obstruction to respiration followed by dyspnoea with loud inspiratory stridor lasting two to five minutes. Attacks occurred during wakefulness and/or sleep. In one patient an episode was witnessed endoscopically: the initial obstruction was seen to be caused by complete laryngeal closure. The false vocal cords then opened, but the vocal cords remained adducted and caused inspiratory stridor. The similarity of the attacks described by the other patients suggests that they were all caused by laryngeal closure. Furthermore, they could simulate the episodes by voluntarily adducting their vocal cords. The symptoms were usually preceded by a sensation of throat irritation and in four cases symptoms of upper respiratory infection were present. Associated features present in some of the patients included post-nasal discharge, snoring, sleep apnoea and gastro-oesophageal reflux. None was hypocalcaemic. Although stimulation of laryngeal receptors is known to produce reflex laryngeal closure, cough is the usual response during wakefulness. Treatment aimed at reducing upper airway irritation and voluntary inhibition of coughing appeared successful in reducing the incidence and severity of the episodes. Recognition of the condition is important as it may be confused with other causes of acute dyspnoea and it appears to respond to specific management.

Adult

Increased release of the N-terminus of the atrial natriuretic factor prohormone with increasing absolute atmospheres of pressure in a hyperbaric chamber and reversal with oxygen therapy.

Increasing atmospheres of absolute pressure (ATA) on the cardiopulmonary system results in a marked diuresis. The present investigation was designed to determine if the diuresis observed with increasing ATA is associated with increased release of the N-terminus of the atrial natriuretic factor (ANF) prohormone that contains two potent diuresis-producing hormones consisting of amino acids (aa) 1-30 (pro ANF 1-30; long-acting sodium stimulator) and aa 31-67 (pro ANF 31-67; vessel dilator) of this 126 aa prohormone. Seven healthy volunteers (mean age, 31 years) had the circulating concentration of the N-terminus of the ANF prohormone evaluated at 1, 2, and 3 ATA in a monoplace hyperbaric chamber by two specific and sensitive radioimmunoassays that immunologically recognize (1) the whole 98 aa N-terminus and (2) the midportion of the N-terminus consistent with aa 31-67 (pro ANF 31-67). With increasing ATA from 1 (sea level) to 2 (equivalent to 33 feet of sea water), the circulating concentrations of both the whole N-terminus and pro ANF 31-67 increased threefold. At 3 ATA (66 feet of sea water), their circulating concentrations increased sixfold over their concentrations, at 1 ATA. With the addition of 100 percent O2 while at 3 and 2 ATA, the circulating concentrations of both the whole N-terminus and pro ANF 31-67 immediately decreased to their prehyperbaric ATA levels and remained there with further decompression to 1 ATA and removal of O2 supplementation. The increased circulating concentration of the N-terminus of the ANF prohormone containing two peptides with potent diuretic effects during increasing atmospheres of absolute pressure may help to explain the diuresis that has been observed with increasing ATA.

Adult

Serum levels of beta-carotene, vitamin A, and zinc in male lung cancer cases and controls.

The mean serum levels of beta-carotene and vitamin A in a multivariate analysis of data from 64 histologically confirmed male lung cancer cases were statistically significantly lower than those from 63 randomly selected male hospital controls, who were admitted for small surgical operations (p values for both beta-carotene and vitamin A less than 0.001). The mean serum levels of zinc were not statistically significantly different between cases and controls (p = 0.10). The levels of beta-carotene, vitamin A, or zinc were not statistically significantly influenced by either the extent of the cancer (p = 0.45) or the cancer cell type (p = 0.06). The possible biological significance of these findings is discussed briefly.

Adenocarcinoma

Release of atrial natriuretic factor with increasing absolute atmospheres of pressure in a hyperbaric chamber and reversal with oxygen therapy.

Diving is associated with a marked diuresis which can be accurately reproduced in a hyperbaric chamber where the pressure of a specific depth can be precisely controlled. The present investigation was designed to determine if the diuresis observed with diving is associated with increased release of a new diuresis-producing hormone, atrial natriuretic factor (ANF). Seven experienced divers (3 men and 4 women; average age of 31 years) had their circulating concentration of atrial natriuretic factor measured at 1, 2 and 3 atmospheres of absolute pressure (ATA) in a monoplace hyperbaric chamber while breathing air. With the simulated dive to 33 feet (2 ATA), the circulating concentration of ANF increased 3-fold and at a depth of 66 feet (3 ATA) ANF increased 6-fold over the concentration at 1 ATA. With the addition of 100% oxygen while at depths of 33 and 66 feet, the concentration of ANF immediately decreased to its pre-dive concentration and remained there with further decompression to surface air and removal of oxygen supplementation. Thus, the increased release of ANF with depth may help to explain the diuresis observed with diving.

Adult