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Biomedical subjects

T J Connor

Publications and source records attributed to T J Connor.

At least 37 records · Page 2Linked to original sources

Development of an experimental model of bacterial chondronecrosis with osteomyelitis in broilers following exposure to Staphylococcus aureus by aerosol, and inoculation with chicken anaemia and infectious bursal disease viruses.

A series of experiments was designed in an attempt to reproduce bacterial chondronecrosis with osteomyelitis in broiler chickens using a natural route of infection. Birds in isolators were exposed to a suspension of Staphylococcus aureus by aerosol or exposed to S. aureus and subsequently inoculated with chicken anaemia virus (CAV) alone, or with CAV and infectious bursal disease virus (IBDV). Subsequently, S. aureus was recovered and bacterial chondronecrosis with osteomyelitis was diagnosed, by histology, in the proximal end of the femur and/or tibiotarsus of lame birds exposed to S. aureus with and without CAV and IBDV infections. Birds fed 60% of the recommended feed intake for the breed developed a lower incidence of S. aureus infection and/or bacterial chondronecrosis (P < 0.05) than birds fed 100% of the recommended intake. A significantly lower incidence of S. aureus was recovered (P < 0.05) in birds simultaneously exposed to S. aureus and inoculated with CAV and IBDV at day 21, than in birds exposed to S. aureus at day 10, and inoculated with CAV and IBDV at day 21. With the exception of birds exposed to S. aureus at 1 day old, a higher incidence of bacterial chondronecrosis was diagnosed in birds exposed to S. aureus and inoculated with CAV and IBDV than in birds exposed to S. aureus alone. It is hypothesised that inoculation with CAV and IBDV at day 21 enhanced the development of bacterial chondronecrosis in birds exposed to S. aureus at day 10 and fed 100% of the recommended feed intake or ad libitum.

Journal Article↗

Depression, stress and immunological activation: the role of cytokines in depressive disorders.

Traditionally, both stress and depression have been associated with impaired immune function and increased susceptibility to infectious and neoplastic disease. However over the last number of years a large body of evidence suggests that major depression is associated with signs of immunological activation. Moreover it has been suggested that cytokine hypersecretion may be involved in the aetiology of depressive disorders. The present article reviews the evidence from both clinical and experimental studies which implicates immunological activation and particularly hypersecretion of cytokines in the onset and maintenance of depressive illness. Both clinical and experimental studies indicate that stress and depression are associated with increased circulating concentrations of cytokines such as IL-1beta, IL-6 and gamma-IFN and positive acute phase proteins, and hyperactivity of the HPA-axis. In addition, it has been reported that immunological activation induces "stress-like" behavioural and neurochemical changes in laboratory animals. Although for many years it has been suggested that stress acts a predisposing factor to depressive illness, the precise mechanisms by which stress-induced depressive symptoms occur are not fully understood. Nevertheless, behavioural changes due to stress have often been explained in terms of changes in neurotransmitter function in the brain. In the present article increased cytokine secretion is implicated as a mechanism whereby stress can induce depression.

Animals↗

Forced swim test-induced endocrine and immune changes in the rat: effect of subacute desipramine treatment.

Previously it has been reported that forced swim test (FST) exposure activates the HPA-axis and produces alterations in both cellular and noncellular immunity in rats. Furthermore, there is evidence to suggest that pretreatment with antidepressants has a protective effect against FST-induced immune changes. The purpose of the present study was to examine the effect of subacute treatment with the tricyclic antidepressant desipramine (DMI, 5 and 10 mg/kg; I.P.) on immobility in the FST, and on FST-induced changes in endocrine and immune parameters in the rat. DMI treatment at a dose of 10 mg/kg produced a significant reduction in immobility time in the FST, while the 5 mg/kg dose was ineffective. FST exposure produced a significant increase in serum corticosterone and a decrease in adrenal ascorbic acid concentrations, neither of which were significantly attenuated by DMI pretreatment. There was a slight but nonsignificant suppression of PHA-induced lymphocyte proliferation 15 min post-FST exposure. However, DMI treatment produced a significant increase in lymphocyte proliferation at this time point. FST exposure caused a reduction in the percentage of lymphocytes and an increase in the percentage of neutrophils in the peripheral blood; DMI treatment failed to significantly alter these stress-induced changes. There was a profound reduction in relative spleen weight observed in DMI-treated animals 120 min post-FST exposure and this was accompanied by an increase in circulating RBC concentrations. In conclusion, although the FST-induced behavioral changes were normalized by DMI treatment the peripheral aberrations induced by FST exposure (with the exception of lymphocyte proliferation) were not. In addition, DMI pretreatment induced stress-like changes in corticosterone, adrenal ascorbic acid and leucocyte subpopulations in the control animals.

Adrenal Glands↗

Acute 3,4-methylenedioxymethamphetamine(MDMA) administration produces a rapid and sustained suppression of immune function in the rat.

(+)-3,4-Methylenedioxymethamphetamine (MDMA;'Ecstasy') is a ring substituted phenylisopropylamine that is structurally related to both amphetamines and hallucinogens. The unique behavioural activating properties of MDMA have led to its widespread abuse. MDMA induces many neurochemical, behavioural and endocrine alterations which closely resemble those elicited by exposure to acute stress, suggesting that MDMA could be regarded as a 'chemical stressor'. In addition to the neurochemical, behavioural and endocrine effects of stressor exposure, it has been reported that stress produces alterations in immune function. However, to date the effects of MDMA on immune function have been restricted to in vitro investigations. In this study we report, for the first time, that acute in vivo administration of MDMA (20 mg/kg, i.p.) produced a rapid (within 30 min) suppression of Con A-induced lymphocyte proliferation and a profound reduction in the total leucocyte count in rats that persisted for at least 6 h following injection. These alterations in immune function were accompanied by a significant increase in plasma corticosterone concentrations 30 min post MDMA administration which had returned to baseline values within 6 h of drug administration. In addition, there was a significant depletion in cortical 5-HT concentrations both 30 min and 6 h after MDMA administration. The results of this study provide evidence that in addition to the well established toxic effects of MDMA on the central serotonergic system, a single administration of this widely abused drug induces a rapid and sustained suppression of immune function.

Animals↗

An assessment of the effects of central interleukin-1beta, -2, -6, and tumor necrosis factor-alpha administration on some behavioural, neurochemical, endocrine and immune parameters in the rat.

Despite a vast amount of research into the actions of cytokines within the central nervous system, the pharmacological role and/or physiological function of the various cytokines within the central nervous system is still not fully understood. The present study evaluated the effects of intracerebroventricular administration of interleukin-1beta, -2, -6 (20 ng) and tumour necrosis factor-alpha (40 ng) on elevated plus maze behaviour, monoamine levels in the hypothalamus, hippocampus and amygdala, plasma corticosterone and catecholamine concentrations and Concanavalin A-induced splenic lymphocyte proliferation in the rat. Both interleukin-1beta and tumour necrosis factor-alpha induced "anxiogenic-like" effects on the elevated plus maze, whereas interleukin-2 and interleukin-6 did not. However only interleukin-1beta led to endocrine variations often associated with stress and anxiety. Cytokine specific alterations in monoamine levels were evident in the hypothalamus and hippocampus, while neurotransmitter concentrations in the amygdala were not significantly altered by cytokine treatment. In addition, interleukin-1beta reduced Concanavalin A-induced lymphocyte proliferation, whereas the other cytokine treatments failed to significantly alter this response. These results demonstrate that in some, but not all, respects interleukin-1beta administration produced "stress like" effects on behaviour, monoamine neurotransmitters, hypothalamic pituitary adrenal axis activity and immune function, while the other cytokines produced less consistent effects on these parameters. It is noteworthy that although interleukin-1beta and tumour necrosis factor-alpha provoked an anxiogenic response in the elevated plus maze test of anxiety, neither cytokine significantly altered amygdaloid noradrenergic or serotonergic activity, as many previous studies have implicated increased amygdaloid noradrenergic and/or serotonergic activity in the pathophysiology of anxiety.

Animals↗

Forced swim test-induced neurochemical endocrine, and immune changes in the rat.

The forced swim test (FST) is a behavioral paradigm that is widely used as a screening test for antidepressant activity in rodents. The objectives of the present study were to characterize the corticosterone and immune responses and in addition to examine neurotransmitter levels, in five brain regions at intervals (15, 30, 60, 90, and 120 min) following the second exposure to the FST. There was a significant but transient reduction in noradrenaline and 5-HT concentrations, in the hypothalamus 15 min post-FST exposure. 5-HT turnover in the frontal cortex and amygdala was significantly increased between 20-120 min post-FST exposure. The FST elicited a robust corticosterone response that peaked significantly at 30 min and had almost returned to baseline 120 min after exposure. There was a significant reduction in total white blood cell count 120 min after the FST, which was accompanied by a significantly reduced percentage of lymphocytes 90 and 120 min post-FST exposure. In addition, there was a significant but transient suppression of both PHA and Con A-induced lymphocyte proliferation 15 min following FST exposure. This study demonstrates that there are neurochemical changes that are coincident with the endocrine and immune changes associated with FST exposure in rats. Furthermore, this model could be used to examine the effects of manipulation of this stress response by antidepressant drugs. Such an investigation could add to our understanding of the interactions between antidepressants, stress and the neuroendocrine and immune systems.

Animals↗

Investigation of the attenuation exhibited by a molecularly cloned chicken anemia virus isolate by utilizing a chimeric virus approach.

Molecular cloning of the Cux-1 isolate of chicken anemia virus (CAV), which had been passaged 173 times in cell culture, resulted in the isolation of an attenuated strain, designated cloned isolate 10, which reverted to virulence following 10 passages in young chicks (D. Todd, T. J. Connor, V. M. Calvert, J. L. Creelan, B. M. Meehan, and M. S. McNulty, Avian Pathol. 24:171-187, 1995). The attenuated cloned isolate 10 differs from the molecularly cloned pathogenic Cux-1 isolate in that it possesses a 21-nucleotide insertion within the nontranscribed region of the CAV genome and 17 individual nucleotide substitutions dispersed throughout the genome. Comparative analyses with other published CAV sequences indicated that cloned isolate 10 was unique at nine nucleotide positions and at five amino acid positions. The molecular basis of the attenuation exhibited by cloned isolate 10 was investigated by evaluating the pathogenicities of two sets of complementary chimeric viruses. These sets were produced by transfection with chimeric double-stranded replicative-form (RF) DNA equivalents that contained DNA sequences derived from cloned isolate 10 and the pathogenic cloned Cux-1 isolate. The construction of the chimeric RFs exploited the occurrence of unique EcoRI, PstI, and BamHI restriction sites, which allowed their respective circular CAV RFs to be manipulated as three restriction fragments of 0.58, 0.93, and 0.71 kbp. Examination of the levels of anemia and gross pathology in the thymuses and bone marrows of 14 day-old specific-pathogen-free chicks following infection of 1-day-old chicks with the chimeric and cloned parental isolates indicated that nucleotide changes in each of the three genomic regions contributed towards attenuation. The significance of this result to the development and use of live attenuated CAV vaccines is discussed.

Animals↗

Standardization of enzyme-linked immunosorbent assays (ELISAs) for quantitative estimation of antibodies specific for infectious bovine rhinotracheitis virus, respiratory syncytial virus, parainfluenza-3 virus, and bovine viral diarrhea virus.

Commercial enzyme-linked immunosorbent assays (ELISAs) for detection of serum antibodies to bovine viral diarrhea virus (BVDV), parainfluenza-3 virus (PI3V), respiratory syncytial virus (RSV), and infectious bovine rhinotracheitis virus (IBRV) were standardized to give a quantitative result when testing was performed at a single optimum dilution. For each test, serum samples were titrated and their end point titers calculated by an algebraic method directly from a plot of each titration series and also from a regression line fitted to this plot. The corrected optical density (COD) of each sample when tested at dilutions of 1/25, 1/50, and 1/100 was expressed as a percentage of the COD of a positive reference serum included on each plate, this value was the sample/positive (S/P) ratio. For each test, the linear relationship between the S/P ratio obtained at a dilution of 1/25, 1/50, and 1/100 and the end point titer calculated by each method was determined. In each case, the best linear relationship existed when samples were tested at a dilution of 1/100 (r = 0.973 for BVDV, 0.962 for PI3V, 0.961 for RSV, 0.947 for IBRV). From the equation of these lines, an increase in the S/P ratio between acute and convalescent serum samples of 31%, 23%, 21%, and 35% would correspond to a 4-fold rise in ELISA titer to BVDV, PI3V, RSV, and IBRV, respectively. ELISA titers calculated from S/P ratios at 1/100 were significantly related to virus neutralization titers to BVDV, RSV, and IBRV and to hemagglutination inhibition titers to PI3V (P < < 0.001 in all cases). Samples with low S/P ratios had the greatest intraassay and interassay variation. Intraassay reproducibility ranged from 3.5% to 22.3% (coefficient of variation), with a median value of 9.5%. Interassay reproducibility was lower, ranging from 6.0% to 50.6%, with a median of 17.4%.

Animals↗

Diagnostic laparoscopy for suspected appendicitis.

One hundred consecutive patients who underwent diagnostic laparoscopy for suspected appendicitis were evaluated to assess the appropriate clinical setting for laparoscopic appendectomy. The usefulness of diagnostic laparoscopy in the setting of acute abdominal pain has been well documented. However, there is debate about the use of laparoscopy for definitive therapy. The purpose of this study is to evaluate the decision making process during diagnostic laparoscopy for suspected appendicitis. When pathology is identified other than in the appendix, the majority of patients can be treated without converting to an open procedure. In patients found to have no obvious pathology, incidental appendectomy can be performed laparoscopically. When appendicitis was identified, the majority of patients could be treated safely without converting to an open technique. However, there were certain clinical situations that necessitated conversion to an open operation. Involvement of the cecum or perforation at the base of the appendix puts the appendiceal stump at risk for leak and abscess formation. Evaluation of the cecum by palpation for a mass should also be performed in this situation. Another situation in which conversion to an open technique is warranted is an appendiceal abscess with adherent small bowel. The friability of bowel wall greatly increases the risk for bowel injury in this setting. Laparoscopy is a useful technique for the diagnosis and treatment of abdominal pain even if the appendix is normal on inspection. Conversion to an open operation should be employed when inflammation or perforation occurs at the base of the appendix and when bowel is found to be adherent to an appendiceal abscess.

Abdomen, Acute↗

Biological characterisation of Australian isolates of chicken anaemia agent.

Three Australian isolates of chicken anaemia agent (CAA) resisted treatment at 70 degrees C for 5 min and chloroform treatment. Although minor antigenic differences were detected using monoclonal antibodies to CAA, the Australian isolates were indistinguishable from the reference Cux-1 and Gifu-1 isolates in cross-immunofluorescence and cross-neutralisation tests employing polyclonal chicken antiserums. The Australian viruses were pathogenic for intramuscularly inoculated 1-day-old SPF chicks, but were less pathogenic for 7-day-old chicks. Thus the Australian isolates of CAA did not differ significantly in these properties from previously characterised CAA isolates from other continents.

Anemia↗