Biomedical subjects

A Fox

Publications and source records attributed to A Fox.

At least 55 records · Page 3Linked to original sources

PubMed2000

Innate immunity and graft rejection.

Although innate immunity evolved to combat pathogens, increasing awareness of a pivotal role in driving and shaping adaptive immunity has prompted this review on the role of innate immunity in graft rejection. We present evidence that grafts, especially xenografts, elicit innate responses, required for adaptive immunity. Particular attention is paid to studies by ourselves and others demonstrating the important role of innate immunity in T-cell trafficking. The mechanisms by which grafts elicit innate immunity are a fertile subject for further investigation and an important target for therapeutic intervention.

Adoptive Transfer↗

PubMed2000

Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat.

Inflammatory processes occurring within the central nervous system (CNS) can produce 'illness induced behaviours' which include fever, sleep and the development of allodynia and hyperalgesia. Here we demonstrate the effects of the pro-inflammatory mediators, bacterial endotoxin, and rat recombinant interleukin 1 beta (rrIL-1 beta) or tumour necrosis factor-alpha (rrTNF alpha) on the integration of somatosensory information at the single neuronal level, via recordings from wide-dynamic range neurones in the dorsal horn of the spinal cord in anaesthetized rats. Intrathecal administration of E. coli lipopolysaccharide (LPS, 10 and 100 microg, i.t.) enhanced the activity of dorsal horn neurones, including facilitation of neuronal post-discharge. Intrathecal administration of IL-1 beta (5-5000 pg) or TNF-alpha (5-5000 pg) enhanced dorsal horn neuronal responses, including the acute responses to C-fibre stimulation, wind-up and post-discharge, however, the effects of IL-1 beta were more robust than those of TNF alpha. Intrathecal administration of IL-1 beta (1-1000 pg) also leads to the development of mechanical allodynia and hyperalgesia. On the other hand intrathecal application of TNF alpha did not produce changes in sensitivity to mechanical stimuli. Changes in the activity of spinal wide-dynamic range neurones induced by local inflammation may provide a pathomechanism for the clinical pathology of central pain syndrome, which can accompany CNS disease or acute CNS injury.

Animals↗

PubMed2000

Imposed vibration influences perceived tactile smoothness.

According to the duplex theory of tactile texture perception, detection of cutaneous vibrations produced when the exploring finger moves across a surface contributes importantly to the perception of fine textures. If this is true, a vibrating surface should feel different from a stationary one. To test this prediction, experiments were conducted in which subjects examined two identical surfaces, one of which was surreptitiously made to vibrate, and judged which of the two was smoother. In experiment 1, the vibrating surface was less and less often judged smoother as the amplitude of (150 Hz) vibration increased. The effect was comparable in subjects who realized the surface was vibrating and those who did not. Experiment 2 showed that different frequencies (150-400 Hz) were equally effective in eliciting the effect when equated in sensation level (dB SL). The results suggest that vibrotaction contributes to texture perception, and that, at least within the Pacinian channel, it does so by means of an intensity code.

Adolescent↗

PubMed2000

Investigation of the concentration of bacteria and their cell envelope components in indoor air in two elementary schools.

Bacterial cell envelope components are widely distributed in airborne dust, where they act as inflammatory agents causing respiratory symptoms. Measurements of these agents and other environmental factors are assessed in two elementary schools in a southeastern city in the United States. Muramic acid (MA) was used as a marker for bacterial peptidoglycan (PG), and 3-hydroxy fatty acids (3-OH FAs) were used as markers for Gram-negative bacterial lipopolysaccharide (LPS). Culturable bacteria were collected using an Andersen sampler with three different culture media. In addition, temperature (T), relative humidity (RH), and CO2 were continuously monitored. Concentrations of airborne MA and 3-OH FAs were correlated with total suspended particulate (TSP) levels. Outdoor MA (mean = 0.78-1.15 ng/m3) and 3-OH FA levels (mean = 2.19-2.18 ng/m3) were similar at the two schools. Indoor concentrations of airborne MA and 3-OH FAs differed significantly between schools (MA: 1.44 vs. 2.84 ng/m3; 3-OH FAs: 2.96 vs. 4.57 ng/m3). Although indoor MA levels were low, they were significantly related to teachers' perception of the severity of indoor air quality (IAQ) problems in their classrooms. Concentrations of CO2 correlated significantly with all bacteria measurements. Because CO2 levels were related to the number of occupants and the ventilation rates, these findings are consistent with the hypothesis that the children and teachers are sources of bacterial contamination. Many culturable bacteria present in indoor air are opportunistic organisms that can be infectious for compromised individuals, while both culturable and nonculturable bacterial remnants act as environmental toxins for both healthy and compromised individuals. Measuring the "total bacteria load" would be most accurate in assessing the biotoxicity of indoor air. Chemical analysis of MA and 3-OH FAs, when coupled with the conventional culture method, provides complementary information for assessing biocontamination of indoor air.

Air Microbiology↗

PubMed2000

Failure To detect muramic acid in normal rat tissues but detection in cerebrospinal fluids from patients with Pneumococcal meningitis.

Muramic acid serves as a marker for the presence of bacterial cell wall debris in mammalian tissues. There have been a number of controversial and sometimes conflicting results on assessing the levels of muramic acid in health and disease. The present report is the first to use the state-of-the art technique, gas chromatography-tandem mass spectrometry, to identify and quantify the levels of muramic acid in tissues. Muramic acid was not found in normal rat brain or spleen. However, when tissues were spiked with muramic acid, it was readily identified. The detection limit was <1 ng of muramic acid/100 mg (wet weight) of tissue. The levels of muramic acid reported in diseased human spleen and spleen of arthritic rats, previously injected with bacterial cell walls, were 100- to 1,000-fold higher. In the present study, muramic acid was also readily detected in the cerebrospinal fluid of patients with pneumococcal meningitis (6.8 to 3,900 ng of muramic acid/ml of cerebrospinal fluid). In summary, there can be an enormous difference in the levels of muramic acid found in different mammalian tissues and body fluids in health and disease. This report could have great impact in future studies assessing the role of bacterial cell wall remnants in the pathogenesis of certain human inflammatory diseases.

Animals↗

PubMed1999

hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation.

We have identified a novel human zinc finger protein, hFOG-2, which is related to but distinct from the murine transcription factor Friend-of-GATA-1 (mFOG-1). The hFOG-2 gene was initially detected in K562 cells using a polymerase chain reaction approach with degenerate primers corresponding to zinc finger regions of mFOG-1. A murine homologue of hFOG-2 was also identified in the mouse expressed sequence tag data banks, indicating that a family of FOG genes exists in mammals. hFOG-2 appears to be widely expressed, while mFOG-1 is expressed primarily in erythroid and megakaryocytic cells and plays a fundamental role in the development of these lineages. Sequencing of the full-length hFOG-2 cDNA indicates that the interaction domains for transcription factors GATA-1 and mCtBP2 are both conserved and we have shown that this new FOG protein also physically interacts with these factors. We have demonstrated that hFOG-2, like mFOG-1, can act in concert with GATA-1 to activate gene expression from the p45 NF-E2 promoter region, but that it can also act to repress GATA-mediated activation of additional reporter constructs. Finally, we have identified a repression domain in hFOG-2 and show that repression is dependent upon the integrity of the mCtBP2 interaction motif Pro-Ile-Asp-Leu-Ser.

Alcohol Oxidoreductases↗

PubMed1999

Electrospray quadrupole mass spectrometry analysis of model oligonucleotides and polymerase chain reaction products: determination of base substitutions, nucleotide additions/deletions, and chemical modifications.

ESI FTICR mass spectrometry is the only technique currently used for accurate molecular weight analysis of PCR products above 100 bp in size. This is important in demonstrating the potential for MS in making major contributions in the molecular biology and genomics areas. In the near future, it is more likely that less expensive, more user friendly MS techniques will be used for high-throughput analyses (including MALDI TOF and ESI quadrupole). There have been numerous reports on the use of MALDI TOF. The current report is to the first to evaluate the use of ESI-quadrupole analysis of PCR products. Synthetic oligonucleotides (30 and 89 mers) and polymerase chain reaction products of varying molecular weight (62, 88, 89, and 114 bp) were analyzed by ESI using a quadrupole MS. The mass accuracy for nucleic acids in the 30-62 bp range was shown to allow determination of nucleotide substitutions and additions/deletions. For higher molecular weight PCR products (88-114 bp), the mass accuracy of ESI-MS distinguishes single or multiple nucleotide insertions/deletions. In addition, ESI quadrupole MS allows determination of molecular weight of both strands of higher molecular weight ds PCR products and can distinguish nucleotide modifications (e.g., with biotin). In conclusion, it is demonstrated that ESI-MS occupies an intermediate position (as compared to MALDI TOF and ESI FTICR) with regard to mass accuracy and resolution in analysis of nucleic acids.

Base Sequence↗

PubMed1999

Modulation of acetylcholine release from parasympathetic nerves innervating guinea-pig and human trachea by endomorphin-1 and -2.

Endomorphin-1 and -2 (mu-opioid receptor agonists) produced a concentration-dependent and naloxone-sensitive inhibition of cholinergic contractile responses in guinea-pig trachea (at 10 microM, 46.1 +/- 8.0% and 33.8 +/- 8.6%, respectively). Endomorphin-1 and -2 also inhibited electrically-evoked acetylcholine release from cholinergic nerves innervating guinea-pig (at 0.1 microM, 41.8 +/- 10.9%; at 1 microM 60.1 +/- 6.3%, respectively) and human trachea (at 10 microM, 76.2 +/- 18.1%, and 77.7 +/- 14.3%, respectively). Naloxone prevented the inhibition by endomorphin-1 and -2 in both guinea-pig and human trachea, suggesting that these peptides can inhibit cholinergic, parasympathetic neurotransmission to the airways via the activation of classical opioid receptors.

Acetylcholine↗

PubMed1999

Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins.

The development of effective vaccines against serogroup B meningococci is of great public health importance. We assessed a novel genetically engineered vaccine containing six meningococcal class 1 (PorA) outer membrane proteins representing 80% of prevalent strains in the UK. 103 infants were given the meningococcal vaccine at ages 2, 3 and 4 months with routine infant immunisations, with a fourth dose at 12-18 months. The vaccine was well tolerated. Three doses evoked good immune responses to two of six meningococcal strains expressing PorA proteins contained in the vaccine. Following a fourth dose, larger bactericidal responses to all six strains were observed, suggesting that the initial course had primed memory lymphocytes and revaccination stimulated a booster response. This hexavalent PorA meningococcal vaccine was safe and evoked encouraging immune responses in infants. Vaccines of this type warrant further development and evaluation.

Antibodies, Bacterial↗

PubMed1999

Carbohydrate profiling of bacteria by gas chromatography-mass spectrometry and their trace detection in complex matrices by gas chromatography-tandem mass spectrometry.

Bacterial cellular polysaccharides are composed of a variety of sugar monomers. These sugars serve as chemical markers to identify specific species or genera or to determine their physiological status. Some of these markers can also be used for trace detection of bacteria or their constituents in complex clinical or environmental matrices. Analyses are performed, in our hands, employing hydrolysis followed by the alditol acetate derivatization procedure. Substantial improvements have been made to sample preparation including simplification and computer-controlled automation. For characterization of whole cell bacterial hydrolysates, sugars are analyzed by gas chromatography-mass spectrometry (GC-MS). Simple chromatograms are generated using selected ion monitoring (SIM). Using total ion GC-MS, sugars can be readily identified. In more complex clinical and environmental samples, markers for bacteria are present at sufficiently low concentrations that more advanced instrumentation, gas chromatography-tandem mass spectrometry (GC-MS-MS), is preferred for optimal analysis. Using multiple reaction monitoring, MS-MS is used (replacing more conventional SIM) to ignore extraneous chromatographic peaks. Triple quadrupole and ion trap GC-MS-MS instruments have both been used successfully. Absolute chemical identification of sugar markers at trace levels is achieved, using MS-MS, by the product spectrum.

Acetates↗

PubMed1999

Sheep perforin: identification and expression by gammadelta T cells from pregnant sheep uterine epithelium.

GammadeltaTCR-positive intraepithelial lymphocytes (IEL) in sheep uterus have been shown in previous studies to express CD8 and to contain prominent intracytoplasmic granules, indicating that they may be cytotoxic. Sheep perforin, which has not previously been described, was identified in the present study using RT-PCR based on primers from human and mouse perforin sequences. A 290 base pair (bp), partial sheep perforin sequence was obtained which showed 80.3% and 66.2% nucleotide identity with human and mouse perforin, respectively. GammadeltaTCR+ IEL from sheep pregnant uteri were found to express perforin mRNA providing further evidence that these cells are cytotoxic.

Animals↗

PubMed1999

Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory.

The safety, immunogenicity, and immunologic priming of 2 dosages (2 microgram or 10 microgram) of a meningococcal C oligosaccharide-CRM197 conjugate vaccine was evaluated in 114 infants vaccinated at ages 2, 3, and 4 months. Antibody persistence and response to boosting with 10 microgram of meningococcal C polysaccharide were assessed. The meningococcal conjugate vaccine produced fewer local reactions than concurrent routine immunizations. Total serogroup C-specific immunoglobulin geometric mean concentration (GMC) increased from 0.3 microgram/mL before vaccination to 13.1 microgram/mL at age 5 months. Serum bactericidal antibody (SBA) geometric mean titers (GMTs) rose from <1:4 to 1:1057 at 5 months and fell by 14 months to 1:19. Following boosting, anti-C-specific immunoglobulin GMC rose to 15.9 microgram/mL and SBA GMT to 1:495. Antibody responses in the 10-microgram dose cohort were significantly higher at 5 months (P<.01) than in the 2-microgram dose cohort but were lower after polysaccharide boosting (P=.02). This meningococcal conjugate vaccine was well tolerated and immunogenic and induced immunologic memory in infants.

Bacterial Capsules↗

PubMed1999

A rationalised virological electron microscope specimen testing policy. PHLS North West Viral Gastroenteritis and Electron Microscopy Subcommittee.

The aim of this project was to produce guidance for a rationalised virological electron microscopy specimen testing policy for PHLS North West, to facilitate centralisation of a groupwide diagnostic electron microscopy service on a single site. Careful specimen selection to limit numbers and the groupwide use of commercially available enzyme immunoassays has allowed PHLS North West to reduce the number of specimens prepared for electron microscopy. The rationalised virological electron microscopy specimen testing policy has enabled a diagnostic electron microscopy service to be provided from a single site with a manageable workload. Implementation of this specimen testing policy by PHLS North West has been successful and may be applicable to other laboratories (or groups of laboratories) to maximise the use of expensive electron microscopy facilities.

Aged↗

PubMed1998

Evidence that macrophages are required for T-cell infiltration and rejection of fetal pig pancreas xenografts in nonobese diabetic mice.

BACKGROUND: Host macrophages are abundant within fetal pig pancreas xenografts undergoing rejection, but their role is unknown. Therefore, we examined the effect of host macrophage depletion on xenograft rejection. METHODS: Nonobese diabetic (NOD) mice were given clodronate-loaded liposomes intravenously to deplete macrophages. Controls received phosphate-buffered saline (PBS) or PBS-liposomes. General immune status was assessed after 2, 3, and 7 days by (1) fluorescence-activated cell sorter analysis of peripheral blood, spleen, and lymph node cells, (2) immunohistochemistry on spleens, and (3) mixed lymphocyte reaction. Organ-cultured fetal pig pancreas was transplanted under the kidney capsule of NOD mice 3 days after clodronate or PBS injection. Grafts were assessed histologically at 4, 5, 6, and 8 days after transplantation. RESULTS: Splenic macrophages and peripheral blood monocytes were depleted 2 days after clodronate treatment but had recovered within 11 days. T cell, B cell, and dendritic cell numbers were normal in spleen, peripheral blood, and lymph nodes of clodronate-treated mice, and T cells and antigen-presenting cells from these mice functioned normally in mixed lymphocyte reaction. Clodronate treatment markedly reduced graft infiltration by macrophages, T cells, and eosinophils at 4, 5, and 6 days after transplantation, and was associated with maintenance of endocrine cell viability and insulin expression. However, all grafts were rejected 8 days after transplantation, concordant with reappearance of splenic macrophages. CONCLUSIONS: Short-term, specific depletion of macrophages markedly delayed cellular infiltration and rejection of xenografts. The results provide the first evidence that macrophages promote T-cell infiltration and rejection of fetal pig pancreas xenografts in NOD mice.

Animals↗

PubMed1998

Heterogeneity in Bacillus cereus PCR products detected by ESI-FTICR mass spectrometry.

PCR amplification of a segment of the 16/23S rDNA interspace region (ISR) from Bacillus cereus 6464 produced a mixture of products. An 89-bp product was predicted on the basis of the reported sequence. The ESI-FTICR analysis revealed three double-stranded products, differing in size by a single nucleotide corresponding to two homoduplexes of 89 and 88 base pairs and a heteroduplex of 89 and 88 nucleotide strands. These were produced from a single preparation of genomic DNA and a single primer pair. ESI-FTICR analysis of the single strands identified a deletion of a T in the coding strand and a corresponding loss of an A in the noncoding strand of this product. The ESI-FTICR analysis indicated the presence of an unreported sequence variation between rRNA operons in this organism. This report illustrates that PCR products amplified from templates differing by a single nucleotide can be resolved and identified using ESI-FTICR at the 89-bp level. Furthermore, the ESI-FTICR mass measurements provided the identity of the deletion, which is indicative of interoperon variability.

Bacillus cereus↗

PubMed1998

Preemptive treatment for the prevention of cytomegalovirus disease: in lung and heart transplant recipients.

BACKGROUND: Rapid quantifiable diagnostic techniques for the diagnosis of cytomegalovirus (CMV) infection may predict patients at risk of CMV pneumonitis and allow preemptive antiviral treatment. METHODS: Using CMV antigenemia as a prospective surveillance technique for CMV infection, we compared the outcome of preemptive treatment (PT) with ganciclovir, 10 mg/kg/day for 21 days directed by "high levels" of CMV antigenemia (PT group, n= 19), with the outcome in a group of historical controls (n=18) treated with ganciclovir when CMV illness occurred. Greater than 50 antigen-positive cells per 2 x 10(5) polymorphonuclear leukocytes was considered to be high-level antigenemia. RESULTS: Nine of the 18 controls developed high-level CMV antigenemia at a median of 33 days (range: 13-65 days) and 5 of the 9 developed CMV disease. Ten of the 19 PT group had high levels of CMV antigenemia detected at a median of 47 days (range: 20-63 days) and were given ganciclovir; none developed CMV disease. There was a significantly lower incidence of CMV disease in the PT group in comparison to controls (0 of 19 vs. 5 of 18: P=0.019). CONCLUSION: We have reduced the incidence of CMV disease using preemptive treatment, and because of a 100% negative predictive value, we omitted unnecessary antiviral prophylaxis for many at-risk patients.

Antibodies, Viral↗

PubMed1998

Acquisition and carriage of meningococci in marine commando recruits.

Meningococcal acquisition is a prerequisite for invasive disease. Three hundred and eleven male marine commando recruits were studied throughout 29 weeks of basic training to identify factors influencing meningococcal carriage and acquisition including troop number, season, smoking, respiratory infection, antibiotic usage and nasopharyngeal bacterial interference flora. A high carriage rate on entry to training (118/311, 37.9%) and subsequent sustained high rates of meningococcal acquisition were found. Of the potential factors examined, only active and passive smoking were found to be associated significantly with meningococcal carriage on entry. The association between active smoking and meningococcal carriage was dose-dependent, with odds ratios (OR) of 2.2 (95% CIs 1.0-4.8) and 7.2 (95% CIs 2.3-22.9) for light and heavy smokers respectively. Passive smoking predisposed independently to carriage (OR 1.8, 95% CIs 1.1-3.0). Active and passive smoking combined to give an attributable risk for meningococcal carriage of 33%. In contrast, despite a high and sustained rate of meningococcal acquisition in the study population, none of the risk factors investigated, including active smoking, was associated significantly with meningococcal acquisition. No cases of meningococcal disease occurred during the 16-month study period. Therefore smoking may increase the duration of meningococcal carriage rather than the rate of acquisition, consistent with the increased risk of meningococcal disease from passive as opposed to active smoking. Public health measures that reduce the prevalence of smoking should reduce the risk of meningococcal disease.

Adult↗

PubMed1998

Morbidity of homebound versus inpatient elderly psychiatric patients.

This study compares the demographic and clinical characteristics of homebound (HB) elders referred for psychiatric services (N = 251) with those of inpatients (IP) admitted to a geriatric psychiatry unit (N = 594). Demographically, HB patients were older (78.8 vs 74.7 years), were more likely to be women (83% vs 68%), were widowed (54% vs. 44%), and had fewer years of education (10.3 vs. 11.1), but were similar in race, income, and proportion living alone. Clinically, HB patients had less functional disability, less severe depression, less cognitive impairment, and fewer medical problems. However, they were similar in the distribution of most psychiatric diagnoses except dementia (higher in the IP group) and dementia with depression (higher in the HB group). Outcome data for the HB group over 15 (range, 1 to 38) months revealed medical hospitalization in 20.7%, psychiatric hospitalization in 16.3%, nursing home placement in 9.2% and mortality in 8.4%. These preliminary data show that the HB group had psychiatric problems that were comparable to those of the IP group but were not as severely impaired.

Age Distribution↗