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Biomedical subjects

A C Moore

Publications and source records attributed to A C Moore.

18 recordsLinked to original sources
PubMed2006

Safety of recombinant fowlpox strain FP9 and modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-immune volunteers.

The ability to generate potent antigen-specific T cell responses by vaccination has been a major hurdle in vaccinology. Vaccinia virus and avipox viruses have been shown to be capable of expressing antigens in mammalian cells and can induce a protective immune response against several mammalian pathogens. We report on two such vaccine constructs, modified vaccinia virus Ankara and FP9 (an attenuated fowlpox virus) both expressing the pre-erythrocytic malaria antigen thrombospondin-related adhesion protein and a string of CD8+ epitopes (ME-TRAP). In prime-boost combinations in a mouse model MVA and FP9 are highly immunogenic and induce substantial protective efficacy. A series of human clinical trials using the recombinant MVA and FP9 malaria vaccines encoding ME-TRAP, both independently and in prime-boost combinations with or without the DNA vaccine DNA ME-TRAP, has shown them to be both immunogenic for CD8+ T cells and capable of inducing protective efficacy. We report here a detailed analysis of the safety profiles of these viral vectors and show that anti-vector antibody responses induced by the vectors are generally low to moderate. We conclude that these vectors are safe and show acceptable side effect profiles for prophylactic vaccination.

Adolescent↗
PubMed2006

Assessment of tube current modulation in pelvic CT.

An anatomically shaped polymethylmethacrylate (PMMA) phantom was used to assess the effect of the Siemens CARE Dose mA modulation system on pelvic CT scans. The effect of the system on absorbed dose to air, image percentage noise and the signal to noise ratio of clinically relevant details was assessed. The signal to noise ratio was calculated using Polytetrafluoroethylene (PTFE) and distilled water inserts; PTFE was used to represent bony structure and distilled water was used to represent soft tissue abscess. Pelvis protocols identified from local hospitals and the UK CT Dose Survey (2002), were assessed and compared with those provided by Siemens Medical (UK). These protocols were tested on a Siemens Sensation 4 CT scanner, both with and without CARE Dose. Results were obtained which showed that dose savings were possible with no significant increase in image noise. Dose reductions were 8% in the lateral positions in the phantom and 42% in the centre, top and bottom. The calculated "CTDIvol" was 32% lower with CARE Dose than without CARE Dose. This is slightly greater than the 25% change in the effective mAs values that was found. This implies that the reduction in the effective mAs values is a reasonable predictor of the total reduction in absorbed dose to air, whilst slightly underestimating the actual change. The results also showed a non-significant trend towards decreased signal to noise ratios for clinically relevant CT numbers when CARE Dose was activated. This suggests that tube current modulation may detrimentally affect signal detection due to changes in image noise.

Equipment Design↗
PubMed2004

Meeting the needs of patients with COPD: patients' preference for the Diskus inhaler compared with the Handihaler.

This study assessed preference and ease of use of the Diskus and the Handihaler in symptomatic chronic obstructive pulmonary disease (COPD) patients. No patient had used either device before. Patients were given a questionnaire to assess the inhalers and to rank the most important feature of an inhaler. Patients in Germany (n = 125) and The Netherlands (n = 131) with a mean age of 60 participated. Fifty-eight percent of German patients and 69% of Dutch patients had no problems using the Diskus compared to only 11 and 32%, respectively, using the Handihaler (p < 0.001). Overall, 79% of patients would be happy to use the Diskus and 46% the Handihaler if their physician suggested it. However, 35% of Dutch patients and 72% of German patients stated they would not be happy to use the Handihaler. The Diskus was rated higher than the Handihaler for the top three features of an ideal inhaler. Overall the Diskus inhaler was preferred by 67% of patients.

Administration, Inhalation↗
PubMed1997

An improved method for the measurement of lidocaine and its metabolites in rat plasma.

An improved method is described for the quantitation of lidocaine and its dominant metabolites in rat plasma, 3-hydroxy-lidocaine glucuronide and 3-hydroxy-MEG-X glucuronide. Frozen plasma samples (100-200 microliters) were thawed and deproteinated by precipitation with acetonitrile, before the conversion of glucuronidates into their respective hydroxylated forms by acid hydrolysis. After extraction with solid-phase C18 cartridge chromatography, the metabolites and parent drug were analyzed by capillary gas chromatography-nitrogen phosphorus detection, without derivativization. A detection limit of 0.005 microgram/ml for lidocaine and nonglucuronidated metabolites and 0.01 microgram/ml for glucuronidated metabolites was achieved. The method offers significant improvements in sensitivity relative to existing techniques, which should be of specific benefit to studies in which sample volume is limited, such as those concerned with the pharmacokinetics of lidocaine metabolism in small-animal pain state models.

Animals↗
PubMed1996

Brush border membrane vesicles from rats and gerbils can be utilized to evaluate the intestinal uptake of all-trans and 9-cis beta-carotene.

Intestinal brush border membrane vesicles (BBMV) have previously been used to investigate the absorptive processes of a wide variety of nutrients. The first objective of this work was to develop a BBMV system to study carotenoid uptake using rat small intestine. The uptake of all-trans beta-carotene by rat BBMV was linear up to 5.9 micromol/L, suggesting passive uptake at the concentrations used in this study. Both all-trans beta-carotene and 9-cis beta-carotene were taken up at a similar rate by the rat BBMV. The vesicle system was then utilized to investigate the uptake of retinol and beta-carotene by BBMV isolated from Mongolian gerbils which had been subjected to three different vitamin A depletion and refeeding protocols. Three groups of gerbils (n = 10/group) were fed vitamin A-deficient diets for 8 wk. One group was killed at that point (marginally depleted), a second group was refed vitamin A for 5 d and a third group was further depleted of vitamin A for 5 d. Pooled BBMV from the marginally depleted group demonstrated greater uptake of all-trans beta-carotene than pooled BBMV from the other two groups of gerbils while those from the group refed vitamin A for 5 d had greater uptake than the group that was depleted for 5 additional days (P < 0.01). In contrast, the uptake of retinol by BBMV was not significantly different among the three groups of gerbils. The results of the gerbil study suggest that as they become increasingly vitamin A deficient, impairment of all-trans beta-carotene uptake by intestinal mucosal cells may be taking place. The BBMV system should prove valuable for the evaluation of the intestinal mucosal cell membrane uptake of carotenoids and retinoids under various nutritional conditions.

Animals↗
PubMed1995

Cerebrospinal fluid analyses in migraine patients and controls.

To investigate the role of central neurotransmitters in the pathogenesis of migraine, we measured cerebrospinal fluid (CSF) levels of certain amino acids (glycine, taurine, glutamine) and metabolites of biogenic amines (5-hydroxyindoleacetic acid and homovanillic acid) in 38 migraine patients and compared them with the levels from 10 headache-free controls. The levels of taurine, glycine and glutamine were significantly higher in the migraine patients (p < 0.0001 for taurine and glycine; p < 0.0009 for glutamine); there were no significant differences among the three migraine subgroups (infrequent migraine, frequent migraine and transformed migraine). In seven patients subsequently treated with divalproex sodium, CSF taurine levels decreased significantly from pretreatment baseline values. These data support the concept that migraine is at least in part a disorder of central neurotransmission.

Adult↗
PubMed1995

Seroprevalence of cysticercosis in an Orthodox Jewish community.

Neurocysticercosis cases were identified in 1991 in an Orthodox Jewish community. Transmission was linked to tapeworm-infected immigrant housekeepers from countries where Taenia solium is endemic. To evaluate the extent of and risks for locally acquired cysticercosis, a seroprevalence survey was conducted in 9% of the households in this community. Cysticercosis antibodies were detected in 23 (1.3%) of 1,789 persons from 612 families. All 23 seropositive persons were asymptomatic, and no intracerebral lesions were found for the 21 seropositive persons who underwent brain imaging. Seropositivity was associated with female sex (relative risk [RR] = 2.45, P = 0.049), hiring a domestic worker for child care duties (RR = 3.79, P = 0.05), and with employees from Central America (RR = 2.70, P = 0.0001). Exposure to T. solium in this community is unexpectedly high. Widespread employment of domestic workers from endemic regions and high employee turnover contributes to exposure risk.

Adolescent↗
PubMed1993

Surveillance for waterborne disease outbreaks--United States, 1991-1992.

PROBLEM/CONDITION: Since 1971, CDC and the U.S. Environmental Protection Agency have maintained a collaborative surveillance program for collection and periodic reporting of data on the occurrence and causes of waterborne disease outbreaks. REPORTING PERIOD COVERED: January 1991 through December 1992. DESCRIPTION OF SYSTEM: The surveillance system includes data about outbreaks associated with water intended for drinking and also about those associated with recreational water. State and local public health departments are the agencies with primary responsibility for the detection and investigation of outbreaks. State and territorial health departments report these outbreaks to CDC on a standard form. RESULTS: For the 2-year period 1991-1992, 17 states and territories reported 34 outbreaks associated with water intended for drinking. The outbreaks caused an estimated 17,464 persons to become ill. A protozoal parasite (Giardia lamblia or Cryptosporidium) was identified as the etiologic agent for seven of the 11 outbreaks for which an agent was determined. Five (71%) of the outbreaks caused by protozoa were associated with a surface-influenced groundwater source. One outbreak of cryptosporidiosis was associated with filtered and chlorinated surface water. Shigella sonnei and hepatitis A virus were implicated in one outbreak each; both were linked to consumption of contaminated well water. Two outbreaks due to acute chemical poisoning were reported; one had an associated fatality. No etiology was established for 23 (68%) of the 34 outbreaks, including the largest one reported during this period, in which an estimated 9,847 persons using a filtered surface water supply developed gastroenteritis. Most (76%) of the 34 outbreaks were associated with a well water source. Twenty-one states reported 39 outbreaks associated with recreational water, in which an estimated 1,825 persons became ill. The most frequently reported illness was hot tub- or whirlpool-associated Pseudomonas dermatitis (12 outbreaks). Of 11 outbreaks of swimming-associated gastroenteritis, six were caused by Giardia or Cryptosporidium, including three outbreaks associated with chlorinated, filtered pool water. The first reported outbreak of Escherichia coli O157:H7 infection associated with recreational exposure occurred during this period. Primary amebic meningoencephalitis, caused by Naegleria fowleri infection, resulted in six deaths. INTERPRETATION: The number of waterborne disease outbreaks reported per year has not changed substantially in the past 5 years. However, etiologic agents only recently associated with waterborne disease, such as E. coli O157:H7 and Cryptosporidium, are being reported more frequently and from new settings. Water quality data for outbreaks during the period 1991-1992 indicate that available water disinfection technology is not always in place or used reliably.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Neurocysticercosis in an Orthodox Jewish community in New York City.

BACKGROUND AND METHODS: From June 1990 through July 1991, intracerebral infection with the larval stage of the pork tapeworm Taenia solium was diagnosed in four unrelated persons in an Orthodox Jewish community in New York City. None of the patients had eaten pork, and only one had traveled to a country in which T. solium infection was endemic. We investigated this outbreak, screened serum samples from family members and household contacts for antibodies to cysticercosis, and examined stool specimens from household employees for eggs of taenia species. RESULTS: The four patients had recurrent seizures and brain lesions that were radiologically consistent with the presence of cysticerci. The diagnosis was confirmed in two patients by a brain biopsy, and in two by immunoblot assays for cysticercus antibodies. Of 17 immediate family members screened serologically, 7 from two families had cysticercus antibodies. Magnetic resonance imaging of the brain showed cystic lesions in two of the seropositive family members, one of whom had had a seizure. Examinations of six domestic employees from all four households revealed an active infection with taenia species in one and a positive serologic test in another. Since these women had recently emigrated from Latin American countries where T. solium infection is endemic, they were the most likely sources of infection in the members of these households. CONCLUSIONS: A diagnosis of neurocysticercosis should be considered in patients with seizures and radiologic evidence of cystic brain lesions, even in those who do not eat pork and who have not traveled to a country in which T. solium infection is endemic. Recent emigrants from countries in which T. solium infection is endemic should be screened for tapeworm infection in their stools before they are employed as housekeepers or food handlers.

Adolescent↗
PubMed1988

Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis.

TCR beta chain gene expression of individual T cell clones that share the same MHC class II restriction and similar fine specificity for the encephalitogenic NH2 terminus of the autoantigen myelin basic protein (MBP) has been examined. TCR V beta expression was examined by FACS analysis with mAbs specific for the V beta 8 subfamily of TCR beta chain genes. 14 of 18 (78%) NH2-terminal MBP-specific clones examined express a member of the TCR V beta 8 subfamily. Southern analysis was used to identify which member(s) of the TCR V beta 8 subfamily is expressed by these clones. Each of four clones examined uses V beta 8.2, though two different V beta 8.2-J beta 2 combinations were identified. Our findings indicate that there is restricted TCR V beta usage in the autoimmune T cell response to the dominant encephalitogenic NH2-terminal epitope of the MBP. The use of an mAb to the antigen-specific TCR in the prevention of T cell-mediated autoimmune disease has been investigated. Our results demonstrate that in vivo administration of a TCR V beta 8-specific mAb prevents induction of autoimmune encephalomyelitis.

Animals↗
PubMed1987

T cell specificity for class II (I-A) and the encephalitogenic N-terminal epitope of the autoantigen myelin basic protein.

The role of class II restriction in T cell recognition of an epitope of the autoantigen myelin basic protein (MBP) has been investigated. Encephalitogenic PL/J(H-2u) and (PL/J X SJL/J(H-2s))F1 ((PLSJ)F1) clones, isolated after immunization with intact MBP, recognize the N-terminal 11 amino acid residues of MBP in association with I-Au class II molecules. The synthetic peptide MBP 1-11 has been tested in vivo for induction of EAE. Clinical and histological EAE occurs in PL/J and (PLSJ)F1 mice but not SJL/J. The class II restriction of T cells primed with MBP 1-11 has been examined in primary cultures in vitro. Similar to encephalitogenic T cell clones, isolated after continuous selection in vitro, the population of MBP 1-11-specific proliferative PL/J and (PLSJ)F1 T cells, recognize this epitope in association with I-Au class II molecules. Not all MBP-specific T cell clones which are restricted to I-Au class II molecules cause autoimmune encephalomyelitis. The specificity of these non-encephalitogenic clones has been examined in this report. These clones also recognize MBP 1-11. Thus recognition of an encephalitogenic T cell epitope is not sufficient for induction of EAE.

Animals↗
PubMed1982

Biochemical characterization of the tetrodotoxin binding protein from Electrophorus electricus.

Biochemical properties of a detergent-solubilized tetrodotoxin binding component from Electrophorus electricus have been examined and compared with those found for the membrane-bound protein. The toxin binding component was solubilized with high efficiency by a variety of nonionic detergents and with lower efficiency by sodium cholate and deoxycholate. Detergent-solubilized preparations bound tetrodotoxin and saxitoxin tightly and specifically, and this binding was observed to be rapidly and irreversibly blocked by carboxylate-modifying reagents. Inactivation by carbodiimide and glycine ester or by a trimethyloxonium salt could be prevented by tetrodotoxin occupancy of the binding site. Tetrodotoxin binding activity in both solubilized preparations and in membranes was found to be highly resistant to proteases. In contrast, the activity was extremely sensitive to the action of phospholipase A2. The biochemical properties of the tetrodotoxin binding component solubilized in mixed lipid-detergent micelles are similar to those found in native membranes, with respect to the characteristics of equilibrium toxin binding and to the sensitivity of toxin binding activity to chemical modification and degradative enzymes. There were some differences with respect to the kinetics of tetrodotoxin binding. In addition, the tetrodotoxin binding component from eel is shown to behave as a glycoprotein, being selectively absorbed to resins coupled to concanavalin A, wheat germ agglutinin, Lens culinaris lectin, and ricin with the appropriate glycoside.

Animals↗
PubMed1980

Binding of regulatory nucleotides to aspartate transcarbamylase: nuclear magnetic resonance studies of selectively enriched carbon-13 regulatory subunit.

Specifically enriched [gamma-13C]phenylalanine, -tyrosine, and -histidine have been biosynthetically incorporated into aspartate transcarbamylase from Escherichia coli. These nonperturbing NMR probes have been used to characterize the interaction of the regulatory sites on the enzyme with nucleotide effectors. The C gamma carbons of the three tyrosines and four histidines per regulatory chain give narrow, well-resolved resonances, and the signals from the five phenylalanines per chain are partially resolved in the presence of bound inhibitor. Spectral changes in regulatory subunit were monitored as a function of concentration of the inhibitor, CTP, and the activator, ATP. Three histidine residues responded to ATP and CTP in an identical manner while two phenylalanine residues were sensitive to CTP but not ATP binding. The tyrosine resonances were not perturbed by effectors. The chemical shift response of the single observable histidine resonance to bound nucleotides in the reconstituted enzyme was identical with that observed for isolated regulatory subunit. This histidine spectrum was undisturbed by the T to R conformational transition of the enzyme. The results suggest that the regulatory subunit experiences minimal rearrangement of tertiary structure on binding effectors and that at least one phenylalanine and one histidine residue are present in the region of the CTP binding site.

Adenosine Triphosphate↗
PubMedDate not supplied

T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis.

Chronic relapsing paralysis and demyelination within the central nervous system (CNS), features associated with the human disease multiple sclerosis (MS), develop in mice after injection of murine T-cell clones specific for the autoantigen myelin basic protein (MBP). We examined the fine specificity of three independently derived encephalitogenic T-cell clones using synthetic polypeptides derived from portions of the N-terminal sequence of MBP. These clones appear functionally identical; they all respond to an epitope in the N-terminal nine amino acid residues in association with the same class II (I-A) molecules of the major histocompatibility complex (MHC). Both the N-terminal acetyl moiety and the first residue (Ala) are necessary for recognition. Only N-terminal MBP peptides recognized by these clones were found to cause encephalomyelitis (EAE) in vivo. These results show that the N-terminal MBP-specific T lymphocytes that mediate autoimmune encephalomyelitis are a small population with a limited repertoire; they all recognise the same combination of MHC and target.

Animals↗
PubMedDate not supplied

Crisis intervention: a care plan for families of hospitalized children.

Hospitalization of a child following a traumatic injury often precipitates a crisis for the patient's entire family. Although pediatric intensive care unit (PICU) nurses are in key positions to assist these families, time constraints, in addition to inadequate staff education regarding family assessment and counseling, often lead to the family being overlooked. Nurses need a quick and accurate method for assessing and intervening with families in crisis.

Aftercare↗