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Biomedical subjects

J McInerney

Publications and source records attributed to J McInerney.

8 recordsLinked to original sources

Targeted remodeling of human beta-globin promoter chromatin structure produces increased expression and decreased silencing.

The chromatin structure of the human beta-globin gene locus assumes a transcriptionally-active conformation in erythroid cells. One feature of this chromatin reorganization is the formation of DNase 1 hypersensitive sites in the regions of active globin gene promoters. This reorganization requires the globin locus control region and is associated with normal expression of the beta-like globin genes. To determine whether it is possible to artificially enhance the opening of the chromatin structure of a minimal beta-globin promoter, we placed a 101bp, erythroid-specific DNase 1 hypersensitive site-forming element (HSFE) immediately upstream of the beta-globin promoter and gene. This element includes binding sites for NF-E2, AP-1, GATA-1 and Sp-1. Constructs were stably transfected into murine erythroleukemia cells and promoter chromatin structure and gene expression were analyzed. The HSFE induced an area of enhanced DNase 1 hypersensitivity extending from the transcriptional start site to -300bp of the artificial promoter and significantly increased the proportion of beta-globin promoters in an open chromatin configuration. This remodeling of promoter chromatin structure resulted in 3-fold increases in beta-globin gene transcription and induction, and inhibited long-term beta-globin gene silencing. These results indicate that a relatively small cis-acting element is able to enhance remodeling of promoter chromatin structure resulting in increased beta-globin gene expression.

Chromatin

Economic analysis of alternative AD control programmes.

The threat imposed by its virulence brings a presumption that Aujeszky's disease (AD) must be controlled because potential losses are high. Viewed as an economic problem, the decision on whether and how to control AD hinges on comparing the costs of doing so with the benefits (in terms of reduced production losses) to be gained. Four strategies are considered: (a) doing nothing, (b) suppressing and maintaining the disease at low prevalence levels by vaccination, (c) suppressing to low levels and then eradicating by culling remaining positive animals and (d) eradicating in one step by means of a test-and-slaughter policy. The net economic merits of each strategy are examined using data derived from specific vaccination studies established in Germany and the Netherlands. A computer model is developed to estimate disease costs under different technical, epidemiological and economic assumptions, allowing the economically optimal strategies to be explored. In general no single strategy can be recommended as the 'best' for dealing with AD, since it depends on a host of factors relating to pig density, prevalence levels, production system, trade relations, etc. As usual, economic realities complicate the quest for operational simplicity in disease control. However, for the regions of high pig density studied the most economic AD control strategy is to lower herd prevalence by intensive vaccination before completing eradication by test-and-removal of remaining positive animals.

Animals

Scombroid poisoning.

Scombroid poisoning is described in the literature as a toxic poisoning caused by ingestion of certain dark meat fish undergoing bacterial decomposition. Poisoning results from the ingestion of a heat-stable toxin. We describe the case of a man who presented to the emergency department several hours after eating tuna steak with evidence of scombroid poisoning that was associated with loss of vision and atrial tachycardia with block. All signs and symptoms resolved after treatment for scombroid poisoning.

Acute Disease

Prevalence of Mycobacterium bovis infection in feral pigs in the Northern Territory.

The prevalence of Mycobacterium bovis infection in populations of feral pigs from five areas in the Northern Territory was examined. In total 790 pigs were necropsied and positive cultures of M bovis were obtained from two pigs (0.25%) and a mycobacterial granuloma was found in one pig. The observed prevalence of M bovis infection in feral pigs is significantly less (chi 2 = 139.8, df = 1, P < 0.001) than the results of a comparable survey conducted during the early 1970s before the implementation of the Brucellosis and Tuberculosis Eradication Campaign. The prevalence of all types of macroscopic lesions resembling tuberculosis was significantly (chi 2 = 338.7, df = 1, P < 0.001) less than the earlier survey. The results are further support for the hypothesis that in the Northern Territory feral pigs are an end-host for M bovis infection, and that the previous high prevalence of M bovis recorded in feral pigs in the 1970s was caused by the close association between these animals and large populations of M bovis-infected buffalo and cattle.

Aging

An associative process maintains reflex facilitation of the unconditioned nictitating membrane response during the early stages of training.

The presentation of a neutral or conditioned stimulus (CS) at an appropriate interval prior to the presentation of a corneal airpuff, or a paraorbital shock (unconditioned stimulus, US) can facilitate the amplitude of the unconditioned nictitating membrane (NM) response in rabbit. In two experiments, it was demonstrated that an associative process mediates the maintenance of that facilitation during repeated CS-US pairings. Although CS-alone presentations produced a substantial decrease in the amount of reflex facilitation in animals not pretrained with the CS, pretraining that consisted of paired CS-US presentations prevented that decrease when CS-alone presentations were subsequently given. Conditioned facilitation of the unconditioned response occurred very rapidly (within 5-12 trials in these experiments) and long before the appearance of overt conditioned responses to the CS. In addition, it was demonstrated that conditioned facilitation can be relatively specific to the tonal frequency of the CS. These results indicate the first sign of conditioning of the NM response is exhibited in the amplitude of the unconditioned response.

Animals