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Biomedical subjects

A Hardy

Publications and source records attributed to A Hardy.

At least 19 recordsLinked to original sources
PubMed2005

5-Hydroxytryptamine action in the rat olfactory bulb: in vitro electrophysiological patch-clamp recordings of juxtaglomerular and mitral cells.

The olfactory bulb, first relay of olfactory pathways, is densely innervated by serotoninergic centrifugal fibers originating from the raphe nuclei. Although serotonin innervation was reported to be involved in olfactory learning in mammals, the action of this neurotransmitter on its putative cellular targets has been never described through unitary recordings. This lack of data initiated the present study where the effects of 5HT on juxtaglomerular and mitral cells are analyzed using whole-cell recordings on olfactory bulb slices. Serotonin depolarizes 34% of 525 JG cells. A multivariate statistical analysis of juxtaglomerular cells characteristics shows that the serotonin responsive cell group can be individualized regarding their tonic discharge-mode in response to a direct current injection, their lower expression of hyperpolarization-activated cation current and their low membrane capacities. The use of ion channel blockers and ramp voltage protocol indicate that serotoninergic depolarization of juxtaglomerular cells may be due to a nonselective cation current with a reversal potential of -44 mV. Pharmacological tests with serotonin receptor antagonists and agonists reveal that 5HT action on juxtaglomerular cells would be mainly mediated by 5HT2C receptors. In mitral cells, serotonin acts on 49.1% of the 242 tested cells, inducing two types of responses. A first subset of mitral cells (26.8%, n=65) were hyperpolarized by serotonin. This response would be indirect and mediated by action of GABA on GABAA receptors since it was antagonized by bicuculline. The involved GABAergic neurons are hypothesized to be juxtaglomerular and granular cells, on which serotonin would act mainly via 5HT2C and via 5HT2A receptors respectively. The second subset of mitral cells (22.3%, n=54) were directly depolarized by serotonin acting through 5HT2A receptors. Our data on serotonin action on juxtaglomerular cells and mitral cells reveal a part of functional mechanisms whereby serotonin can act on olfactory bulb network. This is expected to enrich the understanding of its determining role in olfactory learning.

4-Aminopyridine↗
PubMed2004

Salmonella: a continuing problem.

Salmonella was the archetypal food poisoning organism of the 20th century. It achieved a high public profile following the salmonella-in-eggs crisis of 1988-89, but by then had been the subject of public health concern and scientific interest for over a century. Early associated with animal foods, the advent of phage typing in the 1940s began to reveal the complexity of its environmental associations. This paper explores the story of salmonella as a continuing problem in epidemiology, microbiology and public health, in the food chain, and in the kitchen.

Cooking↗
PubMed2003

Identifications of two different mechanisms for sorghum midge resistance through QTL mapping.

Sorghum midge is the one of the most damaging insect pests of grain sorghum production worldwide. At least three different mechanisms are involved in midge resistance. The genetic bases of these mechanisms, however, are poorly understood. In this study, for the first time, quantitative trait loci associated with two of the mechanisms of midge resistance, antixenosis and antibiosis, were identified in an RI (recombinant inbred) population from the cross of sorghum lines ICSV745 x 90562. Two genetic regions located on separate linkage groups were found to be associated with antixenosis and explained 12% and 15%, respectively, of the total variation in egg numbers/spikelet laid in a cage experiment. One region was significantly associated with antibiosis and explained 34.5% of the variation of the difference of egg and pupal counts in the RI population. The identification of genes for different mechanisms of midge resistance will be particularly useful for exploring new sources of midge resistance and for gene pyramiding of different mechanisms for increased security in sorghum breeding through marker-assisted selection.

Animals↗
PubMed2001

Methods of outbreak investigation in the "era of bacteriology" 1880-1920.

The advent of bacteriological methods in the later 19th century has been seen, on the examples of America and Germany, to have been followed by a new laboratory-based, contact-tracing method of investigating outbreaks of epidemic disease. In Britain, however, this new approach never took firm root, and practising epidemiologists continued to follow an observational and deductive tradition in field investigations, rejecting any primary dependence on bacteriological methods. Alongside this persistent observational practice, there emerged a new statistical approach, based in Pearsonian biometrics, which allied itself with experimental laboratory techniques to develop a more systematic, theoretical trajectory for explaining disease outbreaks in the years after World War I.

Bacteriology↗
PubMed2001

Non-spatial acquisition and retention deficits following small excitotoxic lesions within the hippocampus in monkeys.

Marmoset monkeys with excitotoxic lesions confined to cornu ammonis subfields 1-3, subiculum and pre-subiculum, but sparing the entorhinal cortex, were impaired on retention and learning of conditional object-choice discriminations. For each of these discriminations, the monkeys were required to choose one of two objects depending on which of two patterned backgrounds was used on each trial. Two styles of order of trial presentation were used: 'random' presentation which maximised the degree of interference between trials, and 'runs' presentation which was intended to encourage the monkeys to learn each component of the discrimination separately. Before surgery monkeys found the discriminations more difficult to learn when the trials were presented in the 'runs' style than when presented in the 'random' style suggesting that the task is best learnt by applying a conditional rule. After surgery a significant 'group x style' interaction indicated that the 'runs' style was especially difficult for the lesioned monkeys. From these results we suggest that the hippocampus is involved in learning about and remembering non-spatial, conditional relations between objects.

Animals↗
PubMed2001

A degeneration-based hypothesis for interpreting fibrillar changes in the osteoarthritic cartilage matrix.

The collagen fibrillar architectures in the general matrix of cartilage slices removed from both normal and osteoarthritic femoral heads were examined by both differential interference light microscopy and scanning electron microscopy. Whereas the normal general matrix contained a finely differentiated pseudo-random weave of fibrils developed from an interconnected array of radial elements, the osteoarthritic general matrix was characterised by the presence of structurally distinct regions consisting of strongly aligned radial bundles of fibrils and associated intense tangles or 'knotted' features. Simple structural models were developed to explore possible transformation structures based on two different types of interconnectivity in the three-dimensional fibrillar network. These models support the hypothesis that the distinctive ultrastructural features of the osteoarthritic general matrix can develop as a consequence of largely passive degradative changes occurring in the fibrillar weave originally present in the normal matrix. This could, in principle, occur independently of any new structure that might develop as a consequence of any upregulation of collagen associated with the osteoarthritic process.

Adult↗
PubMed1999

Food, hygiene, and the laboratory. A short history of food poisoning in Britain, circa 1850-1950.

Public health concern with food safety and food poisoning emerged in Britain in the 1880s following the first indication that acute gastric illness was caused by a specific organism. Although incidents were for many years only sparsely reported, the central medical department and its scientists were anxious to extend their knowledge of the incidence, specific causal organisms, and epidemiology of the illness. This paper argues for a widespread incidence of food poisoning in Britain in the nineteenth century and traces the social economic, and hygienic contexts within which it occurred. As deadlier infections retreated, food poisoning became an increasing concern of local and national health authorities, who sought both to raise public awareness of the condition as illness, and to regulate and improve food handling practices. Notification of cases was begun in 1939, and this, together with social changes during and after the Second World War, produced an escalating spiral of reported incidents which still continues. This trend, it is argued, is essentially an artefact, whose significance is reduced if considered in its broader historical context.

Food Contamination↗
PubMed1998

Heterogeneity of eel thyrotropin beta mRNAs is due to a minisatellite in the 3' untranslated region of the gene.

The aim of this study was to determine the causes of the high heterogeneity, in the number and the length, of the thyrotropin (TSH) beta mRNA in the European eel. Northern blot analysis showed that removal of the poly(A) tail did not affect this heterogeneity. PCR amplification on reverse-transcribed pituitary RNAs (RT) showed the main source of heterogeneity to be a highly variable region in the 3' untranslated region (UTR). PCR amplification of the 3' UTR from RTs and genomic DNAs demonstrated that the high variability reflected polymorphism within the eel TSH beta gene. Isolation and sequencing of 3' UTR amplification fragments showed that the variable region comprised more or less exact repetitions of a 26-42-bp fragment. The number of repetitions varied from one allele to another. This variable region could be characterized as a minisatellite. In conclusion, instability of a minisatellite in the 3' UTR of the TSH beta gene generated the multiple and widely differing TSH beta mRNAs.

Amino Acid Sequence↗
PubMed1998

The prediction of preeclampsia: reassessment of clinical value of increased plasma levels of fibronectin.

OBJECTIVE: To determine whether assessment of plasma fibronectin in primigravidae could predict the pregnant women expected to become preeclamptic. METHODS: We performed a prospective blinded analysis of 156 apparently normotensive primigravidae in an outpatient clinic. Blood samples were taken at 6 week intervals from the 18th week and immediately after delivery or at the onset of preeclampsia. Plasma fibronectin was evaluated by ELISA. Evolution with gestational age was studied using regression curves. RESULTS: We had 148 normal primigravidae (592 determinations). In three women, increased fibronectin anticipated preeclampsia by 3-4 weeks. Five women showed high levels only at the onset of preeclampsia. Sensitivity, specificity, positive and negative predictive values of increased fibronectin levels were 37.5% (95% CI=3.3-71.7), 96.6% (95% CI=93.7-99.6), 37.5% (95% CI=3.3-71.7) and 96.6% (95% CI=93.7-99.6), respectively. CONCLUSIONS: This study shows that plasma fibronectin levels could represent a specific marker for preeclampsia. Its sensitivity has to be improved but its high negative predictive value strongly argues against the development of preeclampsia within the next 4 weeks after the blood sampling.

Adult↗
PubMed1995

Gene expression, polarising activity and skeletal patterning in reaggregated hind limb mesenchyme.

The developing chick limb has two major signalling centres; the apical ectodermal ridge maintains expression of several important genes and outgrowth of the limb, and the polarising region specifies the pattern of skeletal elements along the anteroposterior axis. We have used reaggregated leg grafts (mesenchyme dissociated into single cells, placed in an ectodermal jacket and grafted to a host) to study patterning in a system where the developmental axes are severely disrupted. Reaggregates from different regions of leg mesenchyme developed correspondingly different digits, giving a system in which skeletal phenotype could be compared with the expression of genes thought to be important in patterning. We found that posterior third and whole leg reaggregates gave rise to different digits, yet expressed the same combination of HoxD, Bmp-2 and shh genes throughout their development. Anterior thirds initially only express the 3' end of the HoxD cluster but activate the more 5' members of the cluster sequentially over a period of 48 hours, a period during which Bmp-2 is activated but no shh or Fgf-4 expression could be detected. Our results suggest that there are two independent mechanisms for activating the HoxD complex, one polarising region-dependent and one independent, and that shh expression may not be necessary to maintain outgrowth and patterning once a ridge has been established.

Animals↗