Biomedical subjects

R Nichols

Publications and source records attributed to R Nichols.

At least 37 records · Page 2Linked to original sources

PubMed1999

Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults.

BACKGROUND & AIMS: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults. METHODS: Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 microg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. RESULTS: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1. 58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fold (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13. 6/10(6) vs. 5.4 +/- 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. CONCLUSIONS: H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.

Administration, Oral↗

PubMed1999

Neural transmitters and a peptide modulate Drosophila heart rate.

Neural messengers affect Drosophila heart rate. Serotonin increases larval, pupal, and adult heart rate. Octopamine and dopamine are inactive in larva, decrease pupal rate, and increase adult heart rate. Acetylcholine and nicotine decrease larval and pupal heart rate, while acetylcholine decreases and nicotine increases adult heart rate. Muscarine decreases pupal heart rate, but is inactive in larva and adult. GABA is inactive in larva and adult, but decreases pupal heart rate. Glutamate is inactive in larva and pupa, but decreases adult heart rate. Proctolin decreases heart rate in all three stages. Caffeine acts only to decrease adult heart rate.

Acetylcholine↗

PubMed1999

Regulating the activity of a cardioacceleratory peptide.

We measured the effect of crustacean cardioactive peptide on Drosophila heart rate in the animal and in a tissue preparation. Crustacean cardioactive peptide increased in vivo basal heart rate 1%, 6%, and 19% and increased in vitro basal heart rate 52%, 25%, and 35% in larvae, pupae, and adults, respectively. In the tissue preparation, the acceleratory period was followed by decreased in vitro heart rates of 42%, 16%, and 13% in larvae, pupae, and adults, respectively. The effects observed in the animal and tissue and in larvae, pupae, and adults suggest that Drosophila crustacean cardioactive peptide cardiac signaling is modulated and developmentally regulated.

Animals↗

PubMed1999

Genetic variation affecting heart rate in Drosophila melanogaster.

Heart rate in pre-pupae of Drosophila melanogaster is shown to vary over a wide range from 2.5 to 3.7 beats per second. Quantitative genetic analysis of a sample of 11 highly inbred lines indicates that approaching one-quarter of the total variance in natural populations can be attributed to genetic differences between flies. A hypomorphic allele of the potassium channel gene ether-a-gogo, which is homologous to a human long-QT syndrome susceptibility gene (HERG), has a heart rate at the low end of the wild-type range, but this effect can be suppressed in certain wild-type genetic backgrounds. This study provides a baseline for investigation of pharmacological and other physiological influences on heart rate in the model organism, and implies that quantitative genetic dissection will provide insight into the molecular basis for variation in normal and arrhythmic heart function.

Animals↗

PubMed1999

Variation in fruit and vegetable consumption among adults in Britain. An analysis from the dietary and nutritional survey of British adults.

OBJECTIVES: Using a national representative sample to examine variation in fruit and vegetable consumption among adults in the UK, with particular reference to consumers with high and low reported intakes. DESIGN: National representative dietary survey using 7-d weighed diet records of men and women aged 16-64 y living in private households in the UK in 1986-1987. SETTING: The UK. SUBJECTS: 1087 men and 1110 women. The sample was selected by a multi-stage random probability design. The response was 70%. Subjects with low energy intake were subsequently excluded. MAIN OUTCOME MEASURES: Food group, nutrient intake, physiological measures socio-economic, demographic and behavioural characteristics. RESULTS: Consumption of fruit and vegetables was estimated. The sample was divided by sex into four quarter groups according to fruit and vegetable consumption. There were significant similarities between quarter groups in fruit and vegetable and other food intake, nutrient intake, physiological measures, and socioeconomic, demographic and behavioural variable. The lowest consumers of fruit and vegetables had a mean intake of 738 g/week (men) and 630 g/week (women), equivalent to 1.3 and 1.1 portion/d, respectively. Conversely, the mean intake of both men women with the highest consumption was 3137 g/week (5.6 portions day). There were more than twice as many adults in the age group 16-24 located in Q1 than in Q4. The Manual social class and those in receipt of benefits were negatively associated with fruit and vegetable consumption. Smokers were significantly associated with low fruit and vegetable intake. Being married was associated with increased fruit and vegetable intake and being single or divorced/separated was associated with low fruit and vegetable intake. Eating home grown produce was associated with high intake. Consumers who lived in London or the South-East were associated with higher fruit and vegetable intake. CONCLUSIONS: The analysis draws attention to the wide variation in reported fruit and vegetable consumption among British adults. High consumers merit further investigation to elucidate practical strategies for increasing fruit and vegetable consumption. Strategies to increase consumption should be targeted at groups most likely to include low consumers of fruits and vegetables. SPONSORSHIP: London School of Hygiene and Tropical Medicine.

Adolescent↗

PubMed1999

Antisera to multiple antigenic peptides detect neuropeptide processing.

Peptides act as critical messengers of essential physiological function. Frequently, several peptides are encoded in the same precursor and, often, there is structure relatedness among the gene products. The complexity of protein precursors and presence of homologous peptides raises issues about regulation of gene expression and function of structurally-related peptides. We have determined the cellular location of DPKQDFMRFamide and SDNFMRFamide encoded in the Drosophila FMRFamide gene. We raised antisera that distinguish between the two peptides and conducted double label immunostaining utilizing antisera raised in the same host species. We found that DPKQDFMRFamide and SDNFMRFamide are present in distinct distribution patterns. We also established that the peptides are present in cells stained by FMRFamide antisera. Thus, our data are consistent with the conclusion that Drosophila contains cell-specific proteolytic processing enzymes capable of posttranslationally cleaving a polypeptide protein precursor to yield unique expression patterns of neuropeptides that may have diverse activities.

Animals↗

PubMed1999

Evaluation of the impact of Chernobyl on the prevalence of congenital anomalies in 16 regions of Europe. EUROCAT Working Group.

BACKGROUND: Surveillance data from population-based congenital anomaly registers in 16 regions of Europe (mainly Western Europe) were analysed to assess the impact of the Chernobyl accident on the prevalence of selected congenital anomalies. METHODS: Three cohorts of pregnancies were defined: those exposed during the first month following Chernobyl (External Exposure Cohort), the first year (Total Exposure Cohort) and the two subsequent years (Control Cohort). Expected numbers of congenital anomalies in these cohorts were calculated from 1980-1985 baseline rates. Registries were grouped into three exposure categories according to first-year exposure estimates. RESULTS: There was no overall or dose-related increase in prevalence in the two exposed cohorts for Down's Syndrome, neural tube defects, other central nervous system defects or eye defects. There was a statistically significant overall 22% (95% CI: 13-31%) excess of Down's Syndrome in the Control Cohort, with no dose-response relationship. CONCLUSIONS: Chernobyl had no detectable impact on the prevalence of congenital anomalies in Western Europe, suggesting that in retrospect the widespread fear in the population about the possible effects of exposure on the unborn fetus was not justified. An increasing prevalence of Down's Syndrome in the 1980s, probably unrelated to Chernobyl, merits further investigation.

Abnormalities, Radiation-Induced↗

PubMed1999

Structure, function, and expression of Drosophila melanogaster FMRFamide-related peptides.

In 1977, Price and Greenberg identified the tetrapeptide FMRFamide as a cardioexcitatory molecule from mollusc. Subsequent to this discovery, FMRFamide-related peptides (FaRPs) have been identified in both invertebrates and vertebrates. Peptides in the FaRP family contain a common RFamide C-terminus and act as modulators and messengers of neural and gastrointestinal functions. Like other organisms, Drosophila melanogaster contains several genes that encode for numerous FaRPs. Elucidating the processing and activities of multiple FaRPs encoded in a single precursor is critical to establishing their roles in physiology. In this manuscript, we describe the distribution of FMRFamide immunoreactive materials in the Drosophila central nervous system and gut, and correlate it with the expression of specific FaRPs and their activities. The unique distributions and biological activities of Drosophila FaRPs suggest that the precursors are highly processed and the structurally related peptides are not functionally redundant. The complete distribution of FaRPs in the central nervous system and gut as detected by FMRFamide antisera is not accounted for by the sum of the individual expression patterns of the known Drosophila peptides. Thus, these data suggest that one or more Drosophila FaRPs or structurally related peptides remain to be discovered.

Amino Acid Sequence↗

PubMed1999

Differential processing of neuropeptides influences Drosophila heart rate.

Peptides that play critical physiological roles are often encoded in precursors that contain several structurally-related gene products. Differential processing of a precursor by cell-specific processing enzymes can yield multiple messengers with diverse distributions and activities. We have reported the isolation of SDNFMRFamide, DPKQDFMRFamide, and TPAEDFMRFamide from adult Drosophila melanogaster. The peptides are encoded in the FMRFamide gene and have a common C-terminal FMRFamide but different N-terminal extensions. In order to investigate the processing of the FMRFamide polypeptide protein precursor, we generated antisera to distinguish among the structurally-related neuropeptides. Utilizing a triple-label immunofluorescent protocol, we mapped the distribution of the peptides. Each peptide has a unique, non-overlapping cellular expression pattern in neural tissue suggesting that the precursor is differentially processed. In order to identify a biological activity of the peptides, we established an in vivo heart rate assay. SDNFMRFamide decreases heart rate but DPKQDFMRFamide and TPAEDFMRFamide do not, indicating that the N-terminal residues are critical for this activity. SDNFMRFamide immunoreactivity is present in the aorta, implying that SDNFMRFamide acts locally to affect heart rate; DPKQDFMRFamide and TPAEDFMRFamide antisera do not stain cardiac tissue. Our data support the conclusion that Drosophila contains cell-specific proteolytic enzymes to differentially process a polypeptide protein precursor resulting in unique expression patterns of structurally-related, yet functionally distinct neuropeptides.

Analysis of Variance↗

PubMed1998

Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses.

We examined the roles of cell- and antibody-mediated immunity in urease vaccine-induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [beta2-microglobulin (-/-)] but not MHC class II knockout mice [I-Ab (-/-)]. In B cell knockout mice [microMT (-/-)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4(+) cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II-restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.

Adjuvants, Immunologic↗

PubMed1998

Lung function following thermal injury in children--an 8-year follow up.

INTRODUCTION: despite the frequency of pulmonary complications and the reports of abnormal lung function as a sequela of severe thermal injury, most of the lung function studies following thermal injury have been directed at the immediate post-burn period. This investigation is designed to evaluate late residual respiratory impairment in patients with severe thermal injury. METHODS: spirometry and lung volumes were completed on 17 children with severe thermal injury 8 years post-injury. None of the patients had pre-existing lung disease prior to injury. RESULTS: the patient demographic data was as follows: nine male, eight female patients; mean TBSB=67+/-29%; mean third degree=62+/-32%; 13 patients had inhalation injury diagnosed by bronchoscopy. Spirometry and lung volumes at examination as a percentage of predicted values were: [see table in text]. Spirometry and lung volumes show: two patients had an obstructive disease process; nine patients had an obstructive and restrictive disease process; five patients had a purely restrictive process; and one patient had a diffusion defect. CONCLUSION: the data indicate that children who survive severe thermal injury may not regain normal lung function.

Adolescent↗

PubMed1998

Isolation and immunocytochemical characterization of three tachykinin-related peptides from the mosquito, Culex salinarius.

Three myotropic peptides belonging to the Arg-amide insect tachykinin family were isolated from whole-body extracts of the mosquito, Culex salinarius. The peptides, APSGFMGMR-NH2, APYGFTGMR-NH2 and APSGFFGMR-NH2 (designated culetachykinin I, II, and III) were isolated and purified on the basis of their ability to stimulate muscle contractions of isolated Leucophaea maderae hindgut. Biologically inactive methionine sulfoxides of two of the three peptides were isolated using an ELISA system based upon antiserum raised against APYGFTGMR-NH2 and identified with mass spectrometry. Immunocytochemistry localized these peptides in cells in the brain, antennae, subesophageal, thoracic and abdominal ganglion, proventriculus and midgut. Nerve tracts containing these peptides were found in the median nerve of the brain, central body, nervi corpus cardiaci, cervical nerve, antennal lobe and on the surface of the midgut.

Amino Acid Sequence↗

PubMed1998

Dietary magnesium intake and blood pressure: a qualitative overview of the observational studies.

Published reports of 30 separate sets of analyses from 29 observational studies relating dietary intake of magnesium to blood pressure (BP) were identified through a comprehensive search using MEDLINE and BIDS-EMBASE. Three studies were prospective, 24 cross-sectional (25 reports), of which four also contained a longitudinal component, and two were obtained from baseline data in a trial. Various dietary methodologies were used: 24-h dietary recall (n = 12), food-frequency questionnaire (8), food record (7), and duplicate diet (2). Twelve reports compared magnesium intake or BP level between subgroups. Seven showed a negative association between magnesium intake and BP level, and five reported no association. From 18 of the 30 sets of analyses either a regression estimate or a Pearson correlation coefficient was reported. Many reports also allowed identification of subgroups by sex, age and race. Ninety population samples and subgroups could thus be identified from the 30 reports. All 11 Pearson-r correlation coefficients reported for systolic BP (SBP) (three significant, P < 0.05) and 10 (out of 12) Pearson-r correlation coefficients reported for diastolic BP (DBP) (four significant) were negative. Seven reports (13 subgroups for SBP, 11 subgroups for DBP) gave partial regression coefficients after adjustment; 10 (seven significant) and eight (six significant) were negative for SBP and DBP, respectively. For 13 subgroups in five papers, Pearson-r correlation coefficients were reported after adjustment for confounding factors. Eight (out of 13) showed a negative relationship for SBP and DBP. This review points to a negative association between dietary magnesium intake and BP. A systematic quantitative overview is needed to reconcile the inconsistencies of the results of individual studies and to quantify the size of such relationship.

Adolescent↗

PubMed1998

Rectal and intranasal immunizations with recombinant urease induce distinct local and serum immune responses in mice and protect against Helicobacter pylori infection.

To determine the optimal inductive sites for immunization against Helicobacter pylori infection, the protective efficacy of recombinant urease (rUre) was assessed for mice given the vaccine by either the oral (p.o.), intranasal (i.n.), or rectal route. When mice were immunized with rUre (25 microg p.o. or rectally or 10 microg i.n.) plus heat-labile toxin from Escherichia coli as the mucosal adjuvant, all routes afforded protection against challenge with H. pylori, as indicated by a significant reduction in gastric urease activity (P < 0.0005) compared to that of sham-immunized controls. Quantitative H. pylori culture of stomach tissue demonstrated a >97% reduction in bacterial burden in mice immunized by all routes (P < 0.05). Induction of antiurease immunoglobulin A (IgA) levels in gastric luminal secretions after p.o. immunization was greater than after i.n. administration (means, 6.0 and 1.02 ng/ml, respectively) and was dependent upon challenge with H. pylori. However, immunization by the rectal route resulted in the generation of the highest levels of gastric antiurease IgA (mean, 40. 89 ng/ml), which was detectable prior to challenge with H. pylori. Immunohistochemical staining of stomach tissue for cells secreting urease-specific antibody and CD4(+) T cells showed levels of recruitment to be dependent upon challenge with H. pylori and equivalent for all routes. These results identify both the rectum and nasal passages as suitable inductive sites for urease immunization.

Administration, Intranasal↗

PubMed1997

Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs.

OBJECTIVE: To determine whether measurement of baseline serum concentrations of total thyroxine (T4), and triiodothyronine (T3), free T4, and thyrotropin (thyroid-stimulating hormone; TSH) would aid in the diagnosis of hypothyroidism in dogs. DESIGN: Prospective case series. ANIMALS: 54 dogs with hypothyroidism, 54 euthyroid dogs with nonthyroidal disease initially suspected to have hypothyroidism, and 150 clinically normal dogs. PROCEDURE: In the 54 dogs with hypothyroidism, diagnosis was established on the basis of clinical signs, results of routine laboratory and TSH stimulation tests, exclusion of concurrent nonthyroidal disease, and a good clinical response to treatment with L-thyroxine. Blood samples were collected from all dogs and were tested for thyroid hormone and TSH concentrations. Reference ranges for hormone concentrations were established on the basis of results for the 150 clinically normal dogs. RESULTS: Of the 54 hypothyroid dogs, 48 (89%) had low total T4 concentrations, 3 had low-normal concentrations, and 3 had high concentrations because of T4 autoantibodies. In contrast, only 10 (18%) euthyroid dogs had low total T4 concentrations. Only 3 of 31 (10%) hypothyroid dogs had low T3 concentrations; 23 had concentrations within the reference range, and 5 had high concentrations because of T3 autoantibodies. Only 3 of 38 euthyroid dogs had low T3 concentrations. Of the hypothyroid dogs, 53 (98%) had low free T4 concentrations and 1 had a low-normal concentration. Only 4 (7%) euthyroid dogs had low free T4 concentrations. Of the hypothyroid dogs, 41 (76%) had high TSH concentrations, and 13 had TSH concentrations within the reference range. Of the euthyroid dogs, only 4 (8%) had high TSH concentrations. Of all single hormone measurements evaluated, measurement of free T4 concentration had the highest sensitivity (0.98), specificity (0.93), and accuracy (0.95) as a test for hypothyroidism; measurement of total T4 concentration had a lower sensitivity (0.89), specificity (0.82), and accuracy (0.85). Compared with measurement of total or free T4 concentration, measurement of TSH concentration had a lower sensitivity (0.76) and accuracy (0.84) but specificity (0.93) equal to that for measurement of free T4 concentration. When T4 (total or free) and TSH concentrations were evaluated together, specificity was higher than when T4 or TSH concentration was evaluated alone. Only 1 euthyroid dog had low T4 (total and free) and high TSH concentrations. CLINICAL IMPLICATIONS: Results indicate that measurement of serum free T4 and TSH concentrations is useful for diagnosis of hypothyroidism in dogs. About a quarter of the dogs with confirmed hypothyroidism, however, will have serum TSH concentrations within reference limits.

Animals↗

PubMed1997

Promoting action research in healthcare settings.

To coincide with the first annual Action Research conference taking place in London this week, this article promotes the idea of using action research for health care exploration and change. It also introduces the work of the Healthcare Subgroup of the Collaborative Action Research Network, the group's aims and how practitioners can make contact and be involved with the development. The article also describes the outcomes of a research study that underpin the philosophy, process and potential benefits of the network as a means to promote practice development and change in client care.

Clinical Nursing Research↗

PubMed1997

Dromyosuppressin and drosulfakinin, two structurally related Drosophila neuropeptides, are uniquely expressed in the adult central nervous system.

Drosophila myosuppressin (TDVDHVFLRFamide; DMS) and sulfakinin (FDDYGHMRFamide; DSK) have similar C-terminal structures. To determine the neuronal expression patterns of these structurally related peptides, we have generated DMS- and DSK-specific antisera to multiple antigenic peptides and performed double-label immunochemistry with antisera raised on different animals of the same species host animal. Our data indicate that DMS and DSK staining patterns in the adult central nervous system are unique and nonoverlapping.

Amino Acid Sequence↗

PubMed1997

Mechanistic studies of R67 dihydrofolate reductase. Effects of pH and an H62C mutation.

R67 dihydrofolate reductase (DHFR) is encoded by an R-plasmid, and expression of this enzyme in bacteria confers resistance to the antibacterial drug, trimethoprim. This DHFR variant is not homologous in either sequence or structure with chromosomal DHFRs. The crystal structure of tetrameric R67 DHFR indicates a single active site pore that traverses the length of the molecule (Narayana, N., Matthews, D. A., Howell, E. E., and Xuong, N.-H. (1995) Nat. Struct. Biol. 2, 1018-1025). A pH profile of enzyme activity in R67 DHFR displays an acidic pKa that is protein concentration-dependent. This pKa describes dissociation of active tetramer into two relatively inactive dimers upon protonation of His-62 and the symmetry-related His-162, His-262, and His-362 residues at the dimer-dimer interfaces. Construction of an H62C mutation results in stabilization of the active tetramer via disulfide bond formation at the dimer-dimer interfaces. The oxidized, tetrameric form of H62C R67 DHFR is quite active at pH 7, and a pH profile displays increasing activity at low pH. These results indicate protonated dihydrofolate (pKa = 2.59) is the productive substrate and that R67 DHFR does not possess a proton donor.

Circular Dichroism↗