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Biomedical subjects

C M McManus

Publications and source records attributed to C M McManus.

14 recordsLinked to original sources
PubMed2006

Effects of condensed tannin from Acacia mearnsii on sheep infected naturally with gastrointestinal helminthes.

The effect of tannins on endoparasite control in hair sheep was investigated using 20 entire lambs of the Santa Inês breed. At the beginning of the experiment these animals were 6-months old and weighed 22.5kg+/-4.7. The treatments used were (10 animals each): GT (animals receiving 18g of Acácia negra containing 18% of condensed tannin/animal/week) and GC (animals not receiving tannin). The experiment lasted 84 days, with animals kept on an Andropogon gayanus pasture. Faeces were collected weekly, with weighing and blood collection carried out fortnightly. At slaughter, the adult worms were harvested for identification and counting. Although the GT animals weighed more than the GC lambs at slaughter, these differences were not significant (P>0.05). In general, the values for haemoglobin, hematocrit, total protein, urea, phosphorus and calcium in the serum were within normal levels and no significant differences between groups were observed. For faecal egg count (FEC), lower values were observed throughout the experiment in the group receiving tannin, but these differences were only significant in the eighth week. There was a lower output of eggs by regression for GT compared with GC (P<0.05). The species identified, in decreasing order of worm count, were: Trichostrongylus colubriformis, Haemonchus contortus, Oesophagostomum columbianum, Cooperia sp., Strongyloides papillosus, Trichuris globulosa and Moniezia expansa. The total worm count and number of each species of worm were lower for GT compared with GC for T. colubriformis and Cooperia sp. (P<0.05). Condensed tannin (CT) from A. negra had an antiparasitic effect, thereby representing an alternative for worm control in sheep.

Acacia↗
PubMed2006

Influence of protein supplementation on the resistance and resilience on young hair sheep naturally infected with gastrointestinal nematodes during rainy and dry seasons.

Thirty, 4-month-old entire Santa Ines lambs were grazed on an Andropogon gayanus pasture, during a 34-week period (rainy season weeks 0-20 and dry season weeks 21-34) and allocated in two treatment groups (n = 15) each with different protein supplementation: high protein (HP-19% CP) and low protein (LP-11% CP). These were subdivided into those receiving anthelmintic treatment (c) (n = 7) and without anthelmintic treatment (i) (n = 8). The objective was to evaluate the effects of supplementation with protein on resistance and resilience to natural helminth infection of hair breed lambs. Lamb weight, blood collection and faecal egg counts (FEC) were carried out monthly. The lambs were slaughtered after 34 weeks, when worm burdens, worm length and eosinophil cell counts were taken. The sheep on treatments HPc and HPi were heavier in live weight than those from LPi and LPc (P < 0.05) at the end of the rainy period. The HPc group finished heavier (P < 0.05) than the other groups in the dry season, which had no significant differences between them. The predominant species of nematode found was T. colubriformis followed by H. contortus, Trichuris globulosa and Moniezia expansa. Animals on HPi had lower FEC than LPi (P < 0.05). The number of worms was lower for both HP groups (P < 0.05) with worm length shorter in the HPc group (P < 0.05) compared with all other groups. The number of eosinophils was higher in animals in the LPi group, which also showed anaemia and lower plasma urea at the end of the dry season. Diet supplementation with high protein was able to improve resilience and resistance to natural infection by endoparasites during the rainy season. In the dry season there was a decrease in both of these traits, which were intimately linked to the quality of available forage under tropical conditions.

Animal Feed↗
PubMed2001

HIV envelope gp120 activates human arterial smooth muscle cells.

There have been increasing reports of acute coronary thrombotic events in patients with HIV. Although these clinical events have been attributed primarily to dyslipidemia associated with protease inhibitor therapy, autopsy studies in children with HIV suggest the presence of an underlying arteriopathy. This study demonstrates that the HIV envelope protein, gp120, activates human arterial smooth muscle cells to express tissue factor, the initiator of the coagulation cascade. The induction of tissue factor by gp120 is mediated by two biologically relevant coreceptors for HIV infection, CXCR4 and CCR5, and is also dependent on the presence of functional CD4. Induction of tissue factor by gp120 requires activation of mitogen-activating protein kinases, activation of protein kinase C, and generation of reactive oxygen species, signaling pathways that have protean effects on smooth muscle cell physiology. The activation of smooth muscle cells by gp120 may play an important role in the vascular, thrombotic, and inflammatory responses to HIV infection.

CD4 Antigens↗
PubMed2000

Expression and coreceptor function of APJ for primate immunodeficiency viruses.

APJ is a seven transmembrane domain G-protein-coupled receptor that functions as a coreceptor for some primate immunodeficiency virus strains. The in vivo significance of APJ coreceptor function remains to be elucidated, however, due to the lack of an antibody that can be used to assess APJ expression, and because of the absence of an antibody or ligand that can block APJ coreceptor activity. Therefore, we produced a specific monoclonal antibody (MAb 856) to APJ and found that it detected this receptor in FACS, immunofluorescence, and immunohistochemistry studies. MAb 856 also recognized APJ by Western blot, enabling us to determine that APJ is N-glycosylated. Using this antibody, we correlated APJ expression with coreceptor activity and found that APJ had coreceptor function even at low levels of expression. However, we found that APJ could not be detected by FACS analysis on cell lines commonly used to propagate primate lentiviruses, nor was it expressed on human PBMC cultured under a variety of conditions. We also found that some viral envelope proteins could mediate fusion with APJ-positive, CD4-negative cells, provided that CD4 was added in trans. These findings indicate that in some situations APJ use could render primary cell types susceptible to virus infection, although we have not found any evidence that this occurs. Finally, the peptide ligand for APJ, apelin-13, efficiently blocked APJ coreceptor activity.

Adipokines↗
PubMed2000

Human vascular smooth muscle cells possess functional CCR5.

CC chemokine receptors are important modulators of inflammation. Although CC chemokine receptors have been found predominantly on leukocytes, recent studies have suggested that vascular smooth muscle cells respond to CC chemokines. We now report that human smooth muscle cells express CCR5, a co-receptor for human immunodeficiency virus. CCR5 mRNA was detectable by RNA blot hybridization in human aortic and coronary artery smooth muscle cells. The cDNA generated by reverse transcription-polymerase chain reaction from aortic smooth muscle cells had 100% identity throughout the entire coding region with the CCR5 cloned from THP-1 cells. By immunohistochemistry, CCR5 and the CCR5 ligand, macrophage inflammatory protein-1beta (MIP-1beta), were detected in smooth muscle cells and macrophages of the atherosclerotic plaque. In smooth muscle cell culture, MIP-1beta induced a significant increase in intracellular calcium concentrations, which was blocked by an antibody to CCR5. In addition, MIP-1beta caused a calcium-dependent increase in tissue factor activity. Tissue factor is the initiator of coagulation and is thought to play a key role in arterial thrombosis. These data suggest that human arterial smooth muscle cells express functional CCR5 receptors and MIP-1beta is an agonist for these cells.

Aorta↗
PubMed2000

Differential induction of chemokines in human microglia by type I and II interferons.

Chemokines are secreted proteins that function as chemoattractants, mediating the recruitment of specific subsets of leukocytes to sites of tissue damage and immunological reactions. Chemokines may also function as antiviral agents, since viruses such as human immunodeficiency virus type 1 (HIV-1) use chemokine receptors as co-receptors for viral entry. This study examines whether virus-induced interferon, IFNbeta, or immune-related interferon, IFNgamma, affects the production of beta-chemokines by CNS microglia and peripheral monocytes. When IFNbeta was used as the stimulus, induction of MIP-1alpha, MIP-1beta, MCP-1, and RANTES mRNA and protein was observed within 12 h of stimulation in microglia. By contrast, when IFNgamma was used as the stimulus, only MCP-1 was induced. IFNbeta stimulation of blood monocytes resulted in upregulation of MIP-1alpha, MIP-1beta, and MCP-1. Thus, type I and II interferons differentially regulate beta-chemokines in human fetal microglia and peripheral blood monocytes. These observations may have relevance for the therapeutic activity of IFNbeta in multiple sclerosis and for the antiviral effects of IFNbeta for HIV-1 infection of monocytes and microglia.

Cells, Cultured↗
PubMed2000

Chemokine and chemokine-receptor expression in human glial elements: induction by the HIV protein, Tat, and chemokine autoregulation.

Human immunodeficiency virus (HIV) encephalitis is a prominent pathology seen in children infected with HIV. Immunohistochemical analyses of pediatric brain tissue showed distinct differences in expression of C-C chemokines and their receptors between children with HIV encephalitis and those with non-CNS-related pathologies. Evidence suggests that soluble factors such as HIV Tat released from HIV-infected cells may have pathogenic effects. Our results show Tat effects on chemokines and their receptors in microglia and astrocytes as well as chemokine autoregulation in these cells. These results provide evidence for the complex interplay of Tat, chemokines, and chemokine receptors in the inflammatory processes of HIV encephalitis and illustrate an important new role for chemokines as autocrine regulators.

Adolescent↗
PubMed2000

Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons.

Functional chemokine receptors and chemokines are expressed by glial cells within the CNS, though relatively little is known about the patterns of neuronal chemokine receptor expression and function. We developed monoclonal antibodies to the CCR1, CCR2, CCR3, CCR6, CXCR2, CXCR3 and CXCR4 chemokine receptors to study their expression in human fetal neurons cultured from brain tissue as well as the clonally derived NT2.N human neuronal cell line (NTera 2/cl.D1). Specific monoclonal antibody labeling demonstrated expression of CCR2, CXCR2, CXCR3 and CXCR4 on neurons from both sources. Co-labeling studies revealed strong expression of CXCR3 and CXCR4 on both dendritic and axonal processes, with a weaker expression of CXCR2 and CCR2. Reverse transcriptase-polymerase chain reaction analysis of pure NT2.N neurons confirmed RNA expression for CCR2, CXCR2, CXCR3 and CXCR4. No changes in the neuronal labeling pattern of chemokine receptor expression were noted when NT2.N neurons were grown on a supporting layer of astrocytes, again consistent with similar patterns seen in primary human fetal brain cultures. Analysis of single-cell calcium transients revealed a robust response to stromal derived factor-1alpha (CXCR4) and melanocyte growth-stimulating activity (CXCR2), and variable response to monocyte chemoattractant protein-1 (CCR2) or interferon-gamma inducible protein-10 (CXCR3). Finally, we detected the release of monocyte chemoattractant protein-1 from pure cultures of NT2.N neurons, but not undifferentiated NT2 cells. These data indicate that individual neurons may not only co-express multiple functional chemokine receptors, but also that neurons themselves produce chemokines which may influence cellular function within the central nervous system.

Astrocytes↗
PubMed2000

Mechanisms of leukocyte trafficking into the CNS.

HIV-1 encephalitis occurs in up to one-third of HIV-1-infected individuals. The mechanisms through which this pathology develops are thought to involve viral passage across the blood-brain barrier (BBB), as well as entry of HIV-infected and/or uninfected inflammatory cells into the central nervous system (CNS). Viral proteins and cytokines may also contribute to the pathogenesis of encephalitis. We show that the chemokines SDF-1 and MCP-1 induce transmigration of uninfected human lymphocytes and monocytes across our model of the BBB, a co-culture of human fetal astrocytes and endothelial cells. We also demonstrate that the HIV-1 protein Tat induces adhesion molecule expression and chemokine production by human fetal astrocytes and microglia, which could further contribute to leukocyte entry into the CNS. Finally, our data indicate that inflammatory cytokines modulate the expression of CXCR4, a co-receptor for HIV-1, on human fetal astrocytes, suggesting that these cytokines may potentially modulate the infectability of astrocytes by HIV-1. These findings support the hypothesis that there may be several different mechanisms that contribute to the development and progression of HIV-1 encephalitis.

Adult↗
PubMed1999

Transthoracic needle aspiration biopsy: variables that affect risk of pneumothorax.

PURPOSE: To analyze the influence of multiple variables on the rate of pneumothorax and chest tube placement associated with transthoracic needle aspiration biopsy of the lung. MATERIALS AND METHODS: In 346 patients, 331 computed tomographically (CT) guided and 24 fluoroscopically guided lung biopsies were performed. Variables analyzed were lesion size, depth, and location; number of pleural passes; needle size; presence of emphysema; and training level of the person who performed the biopsy. RESULTS: Pneumothorax occurred at 144 (40.4%) of 356 biopsies, including 139 (42.0%) CT-guided and five (21%) fluoroscopically guided biopsies. Chest tube placement was needed in 25 (17.4%) of 144 cases of pneumothorax (7% of all biopsies). An increased rate of pneumothorax was correlated with smaller lesion size (P = .001) and presence of emphysema (P = .01). Patients with emphysema were three times as likely to require chest tube placement. The pneumothorax rate was 15% (16 of 105) if no aerated lung was traversed and approximately 50% if aerated lung was penetrated. Lesion location, needle size, number of pleural passes, and level of training were not correlated with pneumothorax rate. CONCLUSION: Smaller lesion size and emphysema are strongly correlated with occurrence of pneumothorax. Pneumothorax was more than three times less frequent if no aerated lung was traversed. After pneumothorax, chest tube placements were related to the presence of emphysema.

Adolescent↗
PubMed1998

Cytokine induction of MIP-1 alpha and MIP-1 beta in human fetal microglia.

Leukocyte infiltration into the central nervous system (CNS) is a key event in the inflammatory processes of neuroimmunologic diseases. Microglia, resident macrophages of the CNS, may contribute to this process by elaborating chemoattractants that are capable of recruiting leukocytes across the blood-brain barrier. Such factors have been detected in the CNS of animal models of multiple sclerosis and in the brains of human and nonhuman primates with AIDS encephalitis. As the expression of these chemoattractants may play an important role in the initiation and progression of neuroimmunologic diseases, we analyzed expression of the chemokines MIP-1 alpha, MIP-1 beta, MCP-1, and RANTES in human fetal microglial cultures. Unstimulated microglia expressed minimal levels of MIP-1 alpha, MIP-1 beta, and MCP-1, while RANTES was undetectable. In response to LPS, TNF-alpha, or IL-1 beta, both MIP-1 alpha and MIP-1 beta were induced at the mRNA and protein levels in a dose- and time-dependent manner. IFN-gamma did not significantly induce chemokine expression. MCP-1 was detectable in LPS- and cytokine-treated microglia. TGF-beta, a cytokine with down-modulatory effects on other cell types, had little effect on chemokine expression in microglia when used concomitantly before or during treatment with LPS. These results illustrate the ability of certain inflammatory stimuli to induce expression of MIP-1 alpha, MIP-1 beta, and MCP-1 by human fetal microglia. The expression of these chemoattractants may function to recruit inflammatory cells into the CNS during the course of neuroimmunologic diseases and may modulate the ability of HIV to infect the CNS.

Brain↗
PubMed1997

Heartburn correlated to 24-hour pH monitoring and radiographic examination of the esophagus.

OBJECTIVES: Study relationship of gastroesophageal reflux disease to findings on radiographic examination of the esophagus. METHODS: We correlated heartburn (HB) in 360 patients (174 women; 186 men; mean age, 53 yr) to results of pH monitoring (pHM) and radiographic examination of the esophagus. Radiographic findings were categorized as normal (n = 129), hiatal hernia (HH) only (n = 173), reflux esophagitis (n = 50), or peptic stricture (n = 8) (ES; 58). Abnormal pHM was defined as total percentage of esophageal acid exposure time (pH < 4) of 6% or greater. RESULTS: pHM was abnormal in 41 (31%) of 132 patients with HB versus 54 (24%) of 228 without the symptom (p > 0.05). Radiographic correlation showed abnormal pHM in only 21 (16%) of 129 patients with a normal esophagus, 52 (30%) of 173 with HH, and 22 (38%) of 58 with ES, which was significantly lower for those with a normal esophagus. In 132 patients with HB, those with normal esophagus had lower abnormal pHM (2 of 38; 5%) compared with patients with HH (24 of 64; 38%) or with ES (15 of 30; 50%) (p < 0.05). In the 228 patients without HB, abnormal pHM was found in 19 (21%) of 91 with a normal esophagus, 28 (26%) of 109 with HH, and 7 (25%) of 28 with ES (p > 0.05). CONCLUSIONS: (1) pHM findings did not correlate with presence or absence of HB; (2) pHM is usually normal in patients with normal esophagus on RE; (3) pHM is also usually normal in patients with HB and normal esophagus on RE; and (4) pHM is often normal in patients with radiographic findings of reflux esophagitis or peptic stricture.

Esophageal Stenosis↗