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Biomedical subjects

M Page

Publications and source records attributed to M Page.

At least 73 records · Page 4Linked to original sources
PubMed1995

A method for simultaneous physiological and radiographic recordings from sleeping neonatal piglets.

A healthy neonatal piglet model was developed to investigate the effects of simulated gastro-esophageal reflux (GER) on airway protective mechanisms in different sleep states. Piglets were chosen for the model because there are similarities in esophageal morphology, development of the cardiorespiratory system and sleep-wakefulness cycle between the piglet and the human infant. Unanesthetized piglets were instrumented and trained to sleep in a radiolucent, temperature-controlled box. Physiologic recordings of sleep (electroencephalogram, 'ear-o-gram', behavioral observations), cardiorespiratory function (end-tidal CO2, O2 saturation, heart rate, respiratory movements), swallowing (pharyngeal or esophageal pressures) and GER (signaled by a fall in esophageal pH) were displayed and stored on a computer. An image intensifier was used for radiographic observations. The outputs from the computer and image intensifier were synchronized and recorded on videotape. The method enabled simultaneous physiologic and radiographic observations to be made during the simulation of GER by the injection of normal NaCl, distilled water or HCl (pH 2 and 3) into either the pharynx or different sites in the esophagus. The piglet model appears to accurately reflect the normal physiologic responses of the healthy sleeping neonate.

Airway Obstruction↗
PubMed1995

Tailoring nursing models to clients' needs. Using the Roper, Logan and Tierney model after discharge.

1. The use of nursing models and the nursing process in any setting must be justified by their value for clients. 2. If no empirical evidence confirms the worth of a particular model, it is the responsibility of nurses to determine the value of the model used in their own setting. 3. Models should be adapted to the patient setting, and seen as a tool rather than applied ritualistically.

Health Services Needs and Demand↗
PubMed1995

[IgG subclass distribution in intravenous immunoglobulin products: determination of reproducibility of a method of IgG subclass determination. Ring Study of the "Plasma Blood Components" Section of the German Society of Transfusion Medicine and Immunohematology].

BACKGROUND: The working group "Blood Plasma Constituents" of the DGTI has carried out a multicenter study with human immunoglobulins for intravenous administration (IVIG) and a NIBSC serum, with the designation 67/98C, since the European Pharmacopoeia IVIG monograph gives no information for the IgG subclass determination. Aim of the ring study was 1) the determination of the IgG subclass distribution with a standardized method and 2) the determination of the IgG subclass distribution in the NIBSC serum 67/98C and to test if the NIBSC serum coded 67/98C is suited as a reference serum for the IgG subclass determination. MATERIAL AND METHODS: Ten laboratories from Europe participated in the ring study. The IgG subclasses were determined by radial immunodiffusion (RID). RESULTS: The results showed good consistency between the participating laboratories and showed distinct differences in the IgG subclass composition of the tested IVIGs. The reproducibility of the method showed coefficients of variation of approximately 10%. CONCLUSION: The NIBSC serum 67/98C is suitable as reference serum for the IgG subclass determination in sera and IVIGs.

Germany↗
PubMed1994

Structural and kinetic characterization of a beta-lactamase-inhibitor protein.

The past decade has seen an alarming worldwide increase in resistance to beta-lactam antibiotics among many pathogenic bacteria, which is due mainly to plasmid- or chromosomally encoded beta-lactamases that specifically cleave penicillin and cephalosporins, rendering them inactive. There is therefore a need to develop new strategies in the design of effective inhibitors of beta-lactamase. All the small-molecule inhibitors in clinical use are not very effective and are rapidly degraded. Furthermore, newly characterized mutants of the plasmid-mediated beta-lactamase TEM-1 are highly resistant to these small-molecule inhibitors, including clavulanic acid and tazobactam. It has been shown that Streptomyces clavuligerus produces an exocellular beta-lactamase inhibitory protein (BLIP; M(r) 17.5 K). Here we present data defining BLIP as the most effective known inhibitor of a variety of beta-lactamases, with Ki values in the subnanomolar to picomolar range. To identify those features in BLIP that make it such a potent inhibitor, we have determined its molecular structure at 2.1 A resolution. BLIP is a relatively flat molecule with a unique fold, comprising a tandem repeat of a 76-amino-acid domain. Each domain consists of a helix-loop-helix motif that packs against a four-stranded antiparallel beta-sheet (Fig. 1a). To our knowledge, BLIP is the first example of a protein inhibitor having two similarly folded domains that interact with and inhibit a single target enzyme.

Amino Acid Sequence↗
PubMed1994

Passive immunization of cynomolgus macaques with immune sera or a pool of neutralizing monoclonal antibodies failed to protect against challenge with SIVmac251.

In the first of two passive transfer experiments, three groups of four macaques were injected intraperitoneally with a normal serum pool, an immune serum pool (pool 1) collected 132-172 weeks postinfection with the 11/88 pool of SIVmac251, or with a pool of four neutralizing monoclonal antibodies (KK9, 17, 54, and 56) raised against gp120 of the 11/88 pool. Sera were given at a dose of 13 ml/kg whereas the MAb pool was given at 30 ml/kg. In a second experiment, a further four macaques were injected with an immune serum pool (pool 2) collected 12 weeks postinfection with simian-grown SIVmac251 at a dose of 19 ml/kg. Animals in both experiments were challenged with SIVmac251 grown in simian peripheral blood lymphocytes. Despite high levels of circulating antibodies in the serum of animals that received either the immune serum pools or the MAbs, all macaques became infected following challenge. The results described are in contrast to a previous report in which passive transfer of sera from animals infected with SIVsm successfully protected against challenge with the homologous virus grown in human PBMCs. Challenge with SIVmac251 grown in simian PBMCs may be the reason for these conflicting results. Nevertheless, the results suggest that in this model the presence of circulating neutralizing antibodies alone does not necessarily confer protection against challenge with SIVmac251 grown in simian cells.

Animals↗
PubMed1994

Autoantibodies to myelin basic protein are not present in the serum and CSF of MS patients.

Myelin basic protein (MBP) is one of the main constituents of the CNS myelin sheaths, and an autoimmune response directed against MBP may be crucial in the demyelination process in patients with multiple sclerosis (MS). In this study sera and cerebrospinal fluid (CSF) from 25 MS patients, 25 patients with other neurological diseases and 16 healthy controls were examined for antibodies against MBP by using radio immunoblot, western blot, radio immunoassay and enzyme-linked immunosorbent assay. No evidence for the presence of antibodies to MBP was found in sera or CSFs in either the MS patients, or in the control groups tested.

Adult↗
PubMed1994

Serum antibodies from MS patients do not recognize HTLV-I, HIV-1, HIV-2 and SIV.

A retroviral aetiology has been proposed for multiple sclerosis (MS). Although there is as yet no definitive evidence of viral involvement, there have been preliminary reports of antiretroviral antibody detection in sera from MS patients. Such sera have, for example, been found to react with HTLV-I. We here describe investigations involving various immunological techniques which attempt to confirm the virus-specific nature of these antibodies against a range of human and macaque retroviruses. Sera from 25 MS patients, 25 patients with non-associated neurological diseases and 16 patients with non-neurological conditions were tested by immunoblotting methods using lysates of HIV-1-, HIV-2-, HTLV-I- and SIV-infected cells as antigens. None of the sera reacted against any of these retroviral antigens but each serum demonstrated a distinctive and reproducible reaction pattern against cellular components of the cells in which the viruses were propagated. Further examination of the sera was carried out by ELISA using synthetic oligopeptides covering the HIV-1 Gag p24 protein as antigens. None of the sera reacted with the peptides. Our results suggest that in some MS patients the repeated seropositivity to HTLV-I may be due to the reaction with host cell proteins.

Adult↗
PubMed1993

Cloning and expression of a rat neuronal nitric oxide synthase coding sequence in a baculovirus/insect cell system.

A DNA sequence encoding rat neuronal NO synthase (nNOS) was isolated and cloned into the baculovirus expression vector pVL1393 to generate pVLRBNOS. Transfection of Spodoptera frugiperda Sf-21 cells with the construct pVLRBNOS resulted in the synthesis of high levels of neuronal NO synthase. Analysis of the expression pattern revealed soluble, enzymatically active NO synthase in the cytoplasm of cell extracts. Active enzyme could also be purified from culture supernatants using 2'-5' ADP sepharose affinity chromatography. This enzyme was recognised by antibodies to the native nNOS and showed a similar degree of inhibition by arginine analogs as the native nNOS. The majority of the NOS synthesised had accumulated as insoluble "inclusion-body" material. The purification of recombinant nNOS from insect cells should facilitate characterisation of neuronal NO synthase.

Amino Acid Oxidoreductases↗
PubMed1993

An appraisal of a selection of products currently available to older consumers.

ICE Ergonomics Ltd was commissioned to carry out an ergonomics appraisal of a selection of products for elderly people. The products chosen were 28 non-prescription items which were commercially available to the general public through retail outlets and marketed as aids to daily living for older members of the population. The survey included analysis of accident data from the Home Accident Surveillance System (HASS), and an expert appraisal of the products, taking into account safety, function and quality. The findings showed that many of these products were inappropriate or inadequate to perform the tasks for which they were intended. Some were of poor quality and could introduce hazards to a home environment. The paper highlights some of the products that were found to be unsuitable for older consumers. A list of references and ICE reports used during the study is given in the bibliography at the end of the paper.

Journal Article↗
PubMed1993

Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120.

A number of linear and conformation-dependent neutralizing monoclonal antibodies (MAbs) have been mapped to the first and second variable (V1 and V2) domains of human immunodeficiency virus type 1 (HIV-1) gp120. The majority of these MAbs are as effective at neutralizing HIV-1 infectivity as MAbs to the V3 domain and the CD4 binding site. The linear MAbs bind to amino acid residues 162 to 171, and changes at residues 183/184 (PI/SG) and 191/192/193 (YSL/GSS) within the V2 domain abrogate the binding of the two conformation-dependent MAbs, 11/68b and CRA-4, respectively. Surprisingly, a change at residue 435 (Y/H or Y/S), in a region of gp120 near the CD4 binding site (M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W. C. Goh, E. Terwilliger, A. Dayton, C. Rosen, W. Haseltine, and J. Sodroski, Science 237:1351-1355, 1987; L. A. Lasky, G. M. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. Capon, Cell 50:975-985, 1987; and U. Olshevsky, E. Helseth, C. Furman, J. Li, W. Haseltine, and J. Sodroski, J. Virol. 64:5701-5707, 1990), abrogated gp120 recognition by both of the conformation-dependent MAbs. However, both MAbs 11/68b and CRA-4 were able to bind to HIV-1 V1V2 chimeric fusion proteins expressing the V1V2 domains in the absence of C4, suggesting that residues in C4 are not components of the epitopes but that amino acid changes in C4 may affect the structure of the V1V2 domains. This is consistent with the ability of soluble CD4 to block 11/68b and CRA-4 binding to both native cell surface-expressed gp120 and recombinant gp120 and suggests that the binding of the neutralizing MAbs to the virus occurs prior to receptor interaction. Since the reciprocal inhibition, i.e., antibody inhibition of CD4-gp120 binding, was not observed, the mechanism of neutralization is probably not a blockade of virus-receptor interaction. Finally, we demonstrate that linear sequences from the V2 region are immunogenic in HIV-1-infected individuals, suggesting that the primary neutralizing response may be directed to both V2 and V3 epitopes.

Amino Acid Sequence↗
PubMed1992

Corticotropin-releasing factor innervation of the locus coeruleus region: distribution of fibers and sources of input.

Electrophysiologic studies support the hypothesis that corticotropin-releasing factor, the neurohormone that initiates adrenocorticotropin release during stress, also serves as a neurotransmitter in the pontine noradrenergic nucleus, the locus coeruleus. To elucidate the circuitry underlying proposed corticotropin-releasing factor neurotransmission in the locus coeruleus, the present study utilized immunohistochemical techniques to characterize corticotropin-releasing factor innervation of rat locus coeruleus and pericoerulear regions. Corticotropin-releasing factor-like immunoreactive fibers were identified in the locus coeruleus of colchicine- and non-colchicine-treated rats. However, corticotropin-releasing factor innervation of pericoerulear regions rostral and lateral to the locus coeruleus was more dense than that of the locus coeruleus proper. Double-labeling studies utilizing antisera directed against corticotropin-releasing factor and tyrosine hydroxylase indicated that corticotropin-releasing factor-like immunoreactive fibers overlap with tyrosine hydroxylase-like immunoreactive processes of locus coeruleus neurons, particularly in rostral medial and lateral regions. A group of corticotropin-releasing factor-like immunoreactive neurons was localized just lateral to the locus coeruleus and numerous corticotropin-releasing factor-like immunoreactive neurons were visualized just ventral to the rostral pole of the locus coeruleus in a region corresponding to Barrington's nucleus. None of these corticotropin-releasing factor-like immunoreactive neurons were tyrosine hydroxylase-positive. To determine the source of corticotropin-releasing factor-like immunoreactive fibers in the locus coeruleus, injections of the retrograde tracer [wheat germ agglutinin conjugated to inactivated (apo) horseradish peroxidase coupled to gold particles] were made into the locus coeruleus and sections were processed for corticotropin-releasing factor-like immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Restriction of serum antibody reactivity to the V3 neutralizing domain of HIV gp120 with progression to AIDS.

OBJECTIVE: To identify epitopes on HIV-1 gp120 that correlate with disease resistance and/or prognostic indication. DESIGN: The identification of epitopes on HIV-1 gp120 was determined by testing the reactivity by immunoblotting of anti-HIV-positive human sera against partially cleaved Chinese hamster ovary (CHO) cell-derived recombinant gp120. Cleavage of recombinant gp120 occurs in the V3 loop region resulting in 70 and 50K cleavage bands if the protein is subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. Antibodies reactive with the 120 Mr band alone on immunoblotting indicate that binding is restricted to this cleavage site. Reactivity to either of the cleavage products is independent of gp120 cleavage and indicates that binding occurs in sites other than the V3 cleavage region. METHODS: A panel of anti-HIV-positive human sera was tested for virus neutralizing activity and reactivity by immunoblotting against CHO cell-derived gp120. RESULTS: All sera reacted with the uncleaved from of gp120 but reacted either weakly or did not react with its cleavage products. There was a statistically significant correlation between serum reactivity to cleavage products and clinical stage of disease [Centers for Disease Control (CDC) criteria]. Sera of asymptomatic individuals (CDC stage II/III) were more likely to recognize either one or both of the cleavage products compared with sera from patients presenting with symptoms of disease (CDC stage IV). Furthermore, sera reacting with either one or both of the cleavage products were more likely to have higher neutralizing antibody titres than those that were unreactive. CONCLUSIONS: There is a restriction of serum antibody reactivity (when tested by immunoblotting) to the V3 loop with progression to disease. Raised neutralizing antibody titres may be dependent on regions outside the V3 cleavage site.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Influence of breast versus formula milk on physiological gastroesophageal reflux in healthy, newborn infants.

The effect of milk type on physiological, gastroesophageal reflux (GER) was studied in 37 breast-fed and 37 formula-fed, healthy, term neonates aged 2-8 days. The neonates were randomly selected from the public maternity ward and studied for 4 h after their morning milk feed. GER was recorded by a pH microelectrode placed 6 cm above the gastroesophageal junction and analyzed in the third and fourth postprandial hours. Sleep state was accurately defined from the electroencephalogram, electrooculogram, electromyogram, breathing, and behavioral observations. Movement was recorded from a piezo-electric transducer. In active sleep, the breast-fed neonates demonstrated GER episodes of significantly shorter duration than the formula-fed neonates. The means and 95% confidence intervals (CI) were 3.0 (1.6,5.2) compared with 8.3 (5.0,13.3) min/h of active sleep respectively (p less than 0.05). This could not be explained by greater milk volume or increased movement before or during reflux in formula-fed neonates. However, the lower median pH values for GER in breast-fed neonates, 2.0 versus 2.5, were significantly different (p less than 0.05). This difference may reflect more rapid gastric emptying. The lower esophageal pH is more likely to stimulate peristalsis and thus limit the duration of reflux (shorter episodes), in the breast-fed neonates.

Animals↗
PubMed1992

Antibacterial properties of Ro 40-6890, a broad-spectrum cephalosporin, and its novel orally absorbable ester, Ro 41-3399.

Ro 41-3399 is a novel orally active ester of Ro 40-6890, an aminothiazolyl cephalosporin with potent in vitro activities against commonly encountered aerobic gram-positive bacteria (streptococci and methicillin-susceptible staphylococci) and gram-negative bacteria (members of the family Enterobacteriaceae, haemophili, meningococci, and gonococci). In terms of the MICs determined by the methods recommended by the National Committee for Clinical Laboratory Standards, for 50 and 90% of gram-positive organisms, the water-soluble free carboxylic acid Ro 40-6890 proved to be at least as active as or two- to fourfold more active than cefpodoxime, cefuroxime, cefaclor, amoxicillin, amoxicillin-clavulanic acid, and ceftriaxone; against aerobic gram-negative organisms, Ro 40-6890 was usually two- to fourfold more active than cefpodoxime, the next most potent of the oral drugs under comparison, but remained usually two- to fourfold weaker than ceftriaxone. Ro 40-6890 showed a high affinity for the essential penicillin-binding proteins of susceptible bacteria and was resistant to hydrolysis by a broad array of beta-lactamases. Ro 41-3399 bopentil was well absorbed in mice when administered by oral gavage and proved effective in several experimental bacterial infections. Further studies with Ro 41-3399 and Ro 40-6890 are in progress.

Animals↗
PubMed1991

Vaccine-induced CD4+ T cells against the simian immunodeficiency virus gag protein. Epitope specificity and relevance to protective immunity.

We have examined the induction and epitope specificity of T cells for the simian immunodeficiency virus (SIV) gag p27 protein in macaques immunized with either a recombinant SIV gag protein or an inactivated SIV vaccine. CD4+ MHC class II-restricted T cell lines and clones derived from five immunized macaques recognized a total of seven peptides in three immunodominant regions of p27. Two T cell clones generated from one of the lines, recognized a single 20 amino acid peptide that overlapped with a region previously shown to include a CTL epitope from SIV-infected macaques. Although this epitope is in a conserved region of the gag protein of SIV, its recognition by a CD4+ T cell clone was abrogated by sequence variation in the equivalent HIV protein. The specificity of the T cell lines for synthetic peptides demonstrated considerable overlap between T cells generated by immunization with the recombinant gag protein and inactivated SIV. However, in contrast to the protective efficacy of the whole virus vaccine in the syntex adjuvant formulation, immunization with the p27 protein with alum failed to generate a protective immune response. Furthermore, despite the consistent gag-specific T cell responses induced by the recombinant protein, there was no evidence of an enhanced antibody response to envelope (env) after live SIV challenge.

Amino Acid Sequence↗
PubMed1991

Anxiolytic activity of steroid anesthetic alphaxalone.

The synthetic steroid anesthetic alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione) was studied in two behavioral paradigms known to be sensitive to anxiolytic drugs. In an elevated plus maze, alphaxalone produced an anxiolytic profile, significantly increasing the percentage of entries made into the open arms as well as the percentage of time spent on the open arms. In the conflict test, alphaxalone (6 and 8 mg/kg) produced a significant dose-dependent increase in punished responding and a decrease (8 mg/kg) in unpunished responding. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide (2-8 mg/kg). The increase in punished responding was not altered by the benzodiazepine antagonist Ro 15-1788 and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophospate (10 and 15 micrograms/kg). The gamma-aminobutyric acid agonists picrotoxin (1 mg/kg) and bicuculline (1 mg/kg) also failed to suppress the rate-increasing effects of alphaxalone in the conflict test. Chronic administration of alphaxalone for 1 week produced no tolerance to the anxiolytic behavioral effects. In addition, no changes in pain threshold were noted with alphaxalone (8 mg/kg) in the tail-flick analgesia test. These results suggest that the pharmacologic substrates for the anxiolytic actions of alphaxalone may be independent of either the benzodiazepine or picrotoxinin binding sites of the gamma-aminobutyric acid/benzodiazepine receptor complex.

Anesthetics↗