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Biomedical subjects

R Pierce

Publications and source records attributed to R Pierce.

At least 19 recordsLinked to original sources

Ligand binding was acquired during evolution of nuclear receptors.

The nuclear receptor (NR) superfamily comprises, in addition to ligand-activated transcription factors, members for which no ligand has been identified to date. We demonstrate that orphan receptors are randomly distributed in the evolutionary tree and that there is no relationship between the position of a given liganded receptor in the tree and the chemical nature of its ligand. NRs are specific to metazoans, as revealed by a screen of NR-related sequences in early- and non-metazoan organisms. The analysis of the NR gene duplication pattern during the evolution of metazoans shows that the present NR diversity arose from two waves of gene duplications. Strikingly, our results suggest that the ancestral NR was an orphan receptor that acquired ligand-binding ability during subsequent evolution.

Amino Acid Sequence

Local transient induction of inflammatory cytokines after intranasal administration of recombinant Bordetella pertussis.

Inflammatory cytokines have been described to play a critical role in the orientation and amplification of the IgA immune response. In this study, we show that the intranasal administration of a Bordetella pertussis strain expressing the protective antigen glutathione-S-transferase of Schistosoma mansoni (Sm28GST) induced an inflammatory response in the lungs of mice, characterized by the production of inflammatory cytokines, such as Tumor Necrosis Factor alpha, Interleukin-6 and Transforming-Growth Factor beta. The production and the secretion of these cytokines in lung tissues were early and transient. Their presence was observed only during the first week after administration despite the persistence of the bacteria for 1 month. Two weeks after inoculation, Interleukin-10 secretion was detected in the lungs, which could explain the decrease in the production of inflammatory cytokines. These inflammation-regulating cytokines, induced in the lungs by the presence of the bacterial vector, could be part of the process generating the local immune response, in particular the anti-Sm28GST IgA response.

Administration, Intranasal

Developmental skills of children with spastic diplegia: functional and qualitative changes after selective dorsal rhizotomy.

OBJECTIVE: This study examined changes in muscle tone, passive range of motion, stability, and mobility in developmental skills at 6 months and 1 year after selective dorsal rhizotomy (SDR). DESIGN: Prospective outcome study of a consecutive sample. SETTING: Private children's hospital. PATIENTS: Twenty-six children with spastic diplegia: 13 independent and 13 dependent ambulators (assistive devices). RESULTS: A decrease in spasticity was seen at 6 months after SDR, with no further decrease at 1 year. Increases in passive range of motion of the hip and ankle were seen at 6 months after SDR. The ability to assume and maintain developmental positions with improved alignment and stability was seen more frequently at 6 months after SDR, whereas an improvement in the ability to perform transitional movements was seen more frequently at 1 year after SDR. CONCLUSION: SDR decreases spasticity and increases lower extremity range of motion in children with spastic diplegia and appears to be associated with the ability to assume a greater variety of developmental positions with improved alignment, thus greater stability. Improvements in the ability to perform difficult transitional movements at 1 year after SDR are most likely the result of the combined effect of maturation, SDR, and intensive therapeutic intervention.

Activities of Daily Living

The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition.

A peptide recognized by two cytotoxic T cell clones specific for the human minor histocompatibility antigen H-Y and restricted by HLA-A*0201 was identified. This peptide originates from SMCY, as do two other H-Y epitopes, supporting the importance of this protein as a major source of H-Y determinants in mice and humans. In naturally processed peptides, T cells only recognize posttranslationally altered forms of this peptide that have undergone modification of a cysteine residue in the seventh position. One of these modifications involves attachment of a second cysteine residue via a disulfide bond. This modification has profound effects on T cell recognition and also occurs in other class I MHC-associated peptides, supporting its general importance as an immunological determinant.

Animals

Product of the Schistosoma mansoni glutathione peroxidase gene is a selenium containing phospholipid hydroperoxide glutathione peroxidase (PHGPx) sharing molecular weight and substrate specificity with its mammalian counterpart.

In the blood fluke Schistosoma mansoni a functionally active, monomeric, phospholipid hydroperoxide glutathione peroxidase (PHGPx) has been purified and characterized. This enzyme contains a catalytically active selenocysteine. The protein has been shown to be the product of a cloned gene, previously referred to as a glutathione peroxidase gene. S. mansoni PHGPx has been found 5 times more abundant in female than in male worm extract. As in vertebrate PHGPx, homology alignment indicates that the residues involved in the glutathione binding by the tetrametric cellular glutathione peroxidase are mutated in the S. mansoni enzyme. Thus, this aspect appears a landmark of the PHGPx-type of glutathione peroxidases, which might be of functional relevance.

Amino Acid Sequence

A selenium-containing phospholipid-hydroperoxide glutathione peroxidase in Schistosoma mansoni.

The 100000Xg supernatant parasite platyhelminth Schistosoma mansoni exhibits a glutathione peroxidase activity with the substrate phosphatidylcholine hydroperoxide. Purification yielded a protein of 20 kDa molecular mass both on gel filtration column chromatography and SDS/PAGE, thus suggesting that S. mansoni expresses a protein similar to the mammalian selenoenzynic phospholipid-hydroperoxide glutathione peroxidase. Kinetic analysis and substrate specificity corroborated this assumption, the second-order rate constants for the oxidation of the ground-state enzyme (k+1) being higher with phosphatidylcholine hydroperoxide than with other peroxide substrates, such as cumene liydroperoxide or H2O2, and quantitatively similar to those of mammalian phospholipid-hydroperoxide glutathione peroxidase. Partial sequencing of the protein and selenium measurement by neutron activation analysis established that the purified peroxidase corresponded to the product of the S. mansoni gene previously reported and supposed to encode a selenium-containing glutathione peroxidase [Roche, C., Williams, D. L., Khalife, J., LePresle, T., Capron, A. & Pierce, R. J. (1994) Cloning and characterization of gene encoding Schistosoma mansoni glutathione peroxidase, Gene 138, 149 - 152]. S. mansoni thus contains a scienoperoxidase sharing molecular mass, catalytic efficiency and substrate specificity with phospholipid-hydroperoxide glutathione peroxidase, dismantling the concept that those enzymes are unique to vertebrate organisms.

Amino Acid Sequence

Update on lung cancer.

Lung cancer is common, largely smoking related and thus preventable. Focal non small cell disease is surgically resectable but presentation with mediastinal and metastatic disease is common and has a poor prognosis. Small cell lung cancer is chemosensitive but has a very poor prognosis. Widespread screening programs are not currently considered cost-effective. New preventive and therapeutic approaches are the way forward and a multidisciplinary approach is clearly needed.

Humans

Temephos distribution and persistence in a southwest Florida salt marsh community.

The distribution and persistence of the mosquito larvicide temephos was monitored throughout an intertidal salt marsh community in southwest Florida following routine aerial applications of Abate 4-E (43% temephos) from 1988 through 1993. Temephos was found to be more highly concentrated in the surface water microlayer than in mid-depth water, exhibiting a mean of 330 micrograms/liter at the surface and 12 micrograms/liter at mid-depth from 1 fl. oz./acre applications and 120 micrograms/liter in the surface and 4.5 micrograms/liter in mid-depth water for 0.5 fl. oz./acre applications. Concentrations at both surface and mid-depth diminished rapidly within the first 24 hours. Mangrove leaves provided the most persistent reservoir for temephos, remaining more than 7 days. Temephos residues also were observed in select salt marsh organisms, including the sheepshead minnow (Cyprinodon variegatus), adult fiddler crabs (Uca rapax) and the ribbed mussel (Geukensia sp.).

Florida

Brief upper airway dysfunction.

We have analysed the clinical manifestations of nine patients with brief upper airway dysfunction (BUAD) who attended the thoracic department of a major teaching hospital between 1987 and 1991. Episodes of BUAD developed within 1-4 months of presentation in three patients but were undiagnosed for 2.5-12.5 years in six. The mean age at onset was 51 years ranging from 37 to 66 years. The episodes occurred at irregular intervals. They lasted approximately 1-5 min, were frightening and consisted of an initial phase of obstructive apneoa lasting a few seconds to 2 min and a second phase of respiratory distress with inspiratory stridor lasting 1-4 min. Daytime episodes occurred in all and at night in five, waking three of the patients from sleep. In most instances, throat irritability triggered the episodes which were often preceded by cough. Potential causes of throat irritability included respiratory tract infection, allergy, oesophageal reflux and obstructive sleep apnoea. After treatment of throat irritability BUAD has ceased for at least a year in six of the eight with adequate follow-up. In conclusion, BUAD has characteristics clinical features which should enable it to be recognized more frequently, ensuring successful management.

Adult

Characterization and localization of Schistosoma mansoni calreticulin Sm58.

Recombinant Schistosoma mansoni calreticulin (SmCaR) was expressed in Escherichia coli, using the glutathione S-transferase fusion protein, and its Ca(2+)-binding capacity was determined. Results obtained by a 45Ca2+ overlay technique showed that Ca(2+)-binding site(s) were present in the recombinant CaR indicating that proper folding of the protein was obtained using this system. An antiserum raised against the recombinant SmCaR showed that the native protein (Sm58) was expressed in all stages of the life-cycle from cercariae to the adult worm and in the egg. However, SmCaR seems to be a developmentally regulated protein whose expression can be used to study the post-transformational differentiation of the schistosomulum. Localization of SmCaR demonstrated that the majority of SmCaR was expressed in the epithelia of the digestive duct and in the genital organs. These results suggest that SmCaR, by regulating the Ca2+ concentration, may play an important role during cell proliferation. Finally the presence of SmCaR in miracidia and in the genital organs suggests that the antibody response directed against this protein could interfere in egg production.

Amino Acid Sequence

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