Intestinal histoplasmosis mimicking Whipple's disease.
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Antifungal Agents↗
Biomedical subjects
K McCullough
Publications and source records attributed to K McCullough.
PMWS: an emerging disease identified in archived porcine tissues.
Postweaning multisystemic wasting syndrome (PMWS) is a disease caused by porcine circovirus type 2 (PCV-2). The disease was present as early as 1986 in Spain, 1989 in Japan and 1993 in Thailand. In view of this, we considered it possible that the disease may also have been present in Switzerland prior to its first description in 2001. A retrospective investigation was performed on paraffin-embedded lymphoid organs and ileum from 496 pigs aged 5-13 weeks collected between 1976 and mid-2001. The sections were investigated immunohistochemically using a monoclonal antibody specific for PCV-2 capsid antigen encoded by ORF2. Virus antigen was detected in tissue samples of 39 pigs from 28 farms. The earliest positive sample originated from 1986. After 1989, positive pigs were found almost every year among the 20-40 cases investigated annually. These results indicate that PCV-2 has been present in Switzerland for some time, and at least since 1986.
Animals↗
Utility of clinical swallowing examination measures for detecting aspiration post-stroke.
The purpose of this investigation was to determine the utility of clinical swallowing examination (CSE) measures for detecting aspiration as defined by videofluoroscopic swallowing examination (VFSE). This study, involving 165 participants, is a follow-up to a previously published investigation of 60 participants. Findings are compared with that investigation as well as with other research on CSEs. The results suggest that clinicians can make an accurate judgment of the occurrence of aspiration in most post-stroke patients. However, ruling out aspiration when it is absent appears more problematic. More work needs to be done if data collected from non-instrumented examinations are to be strongly predictive of the presence and absence of aspiration on VFSE. At present, there are no data to suggest that CSEs can be used to quantify aspiration or make adequate recommendations regarding patient care.
Adult↗
PMWS: experimental model and co-infections.
Porcine circovirus type 2 (PCV2) is now recognised as the causal agent of porcine multisystemic wasting syndrome (PMWS), an economically important wasting disease of young pigs [J. Vet. Diagn. Invest. 12 (2000) 3]. Gross lesions of PMWS include generalised lymphadenopathy, hepatitis, nephritis and pneumonia and typical histological lesions include lymphocytic depletion and multinucleated giant cell formation in lymph nodes, degeneration and necrosis of hepatocytes, and multifocal lymphohistocytic interstitial pneumonia. This communication will review the results of experimental infections of gnotobiotic (GN), colostrum-deprived (CD) and colostrum-fed (CF) pigs within our group, and elsewhere, with PCV2 and the conclusions that can be drawn from this work.
Animals↗
Porcine circovirus as a possible cause of postweaning wasting in pigs in Switzerland.
Postweaning wasting is a major worldwide problem in pig production, particularly with respect to the disease termed postweaning multisystemic wasting syndrome (PMWS). In addition to wasting, PMWS symptoms include respiratory distress, diarrhoea, pallor and occasional cases of jaundice. The causative agent is porcine circovirus type 2 (PCV-2). The objective of the present study was to determine the significance of PMWS and similar conditions in Switzerland. A total of 72 weaned piglets from 26 farms showing wasting were examined for the presence of PCV-2 by immunohistochemical and histological analysis and 57 piglets from 21 farms were examined serologically. Possible causes for wasting other than PCV-2 were investigated by macroscopic, histological and bacteriological methods. PCV-2 antigen was identified immunohistochemically in the lymphatic organs in 11 of these 72 piglets. However, only 4 animals showed histological changes typical of PMWS. PCV-2 antibodies were found in 70% of the piglets. Piglets with wasting syndrome not associated with PCV-2 infection suffered from conditions including porcine proliferative enteropathy, gastric ulcers, polyserositis and polyarthritis. The most frequent condition was chronic enteritis not associated to circovirus infection. The results from the serological analyses indicate a wide distribution of PCV-2 in the Swiss pig population. However, confirmed cases of PMWS were rare in the investigated piglets.
Animals↗
In vitro studies on the infection and replication of porcine circovirus type 2 in cells of the porcine immune system.
Porcine circovirus type 2 (PCV2) nucleic acid and/or antigens are consistently observed in cells of monocytic morphology in lesions of pigs affected by post-weaning multisystemic wasting syndrome (PMWS). In this study, PCV2 antigen was detected in the cytoplasm of monocytes, pulmonary macrophages (PMs) and monocyte-derived macrophages exposed to the virus in vitro, by immunofluorescence analysis (IFA) and the phenotype of these cells confirmed by detection of monocytic cell surface markers using flow cytometry. Viral antigen was not observed in lymphocytic cells. Replication of the virus in PMs was investigated further by comparison to that observed in the continuous pig kidney cell line (PK15A) using quantitative virus titration, quantitative PCR and by the detection of double stranded DNA intermediates of viral replication by Southern blotting analyses. Although increases in viral DNA and levels of infectious virus progeny and the presence of replicative intermediates, indicative of viral replication, were observed in PK15A cells, no such changes were observed in PMs in spite of the fact that infectious virus, viral antigen and viral DNA persisted in the cells for at least the duration of the experiment. These results suggest that in vivo, monocytic cells may not represent the primary target for PCV2 replication.
Animals↗
Summary of workshop findings for porcine myelomonocytic markers.
About 65 monoclonal antibodies (mAb) including 17 internal controls were analyzed for their ability to recognize and bind to various cells of the myelomonocytic lineage. Flow cytometry (FCM) utilizing both single and double staining, and immunoprecipitation (IP) assays were used in the analysis. About 38 of the mAb were reactive with myelomonocytic cells, resulting in nine clusters of interest. Although the exact identity of many of the molecules on the cells bound by the mAb remains undetermined, information obtained about the mAb analyzed in this workshop should be helpful in further identifying various populations of myelomonocytic cells and their stages of differentiation. Out of 12 mAbs with potential CD11 specificity, seven were assigned to three different swine specific alpha chains of the CD11/CD18 integrin heterodimer, the assignment of the remaining four was tentative. One antibody had a binding specificity consistent with SWC3 and one with SWC8. CD14 expression on pig cells was characterized with a panel of CD14-positive antibodies, two of these antibodies were assigned to swine CD14. Two antibodies were assigned to CD163. Further work is required to determine the antigens recognized by many of the other mAb.
Animals↗
Workshop studies on monoclonal antibodies in the myeloid panel with CD11 specificity.
Several putative anti-human and swine CD11-specific monoclonal antibodies (mAbs) were included in the myeloid section of the Third International Swine CD Workshop. Failure of clustering analysis to group these mAbs together prompted additional analyses to define the specificities of these mAb. Combination of one and two-color flow cytometry (FCM) and immunoprecipitation (IP) allowed the definition of the mAb into three CD11 groups. Cellular distribution of the molecules recognized by anti-human CD11b and c mAbs on swine cells proved to be significantly different from that found in humans.
Animals↗
Predicting death from ruptured abdominal aortic aneurysms.
BACKGROUND: We have previously reported preoperative and immediate postoperative formulae to estimate mortality in patients with ruptured abdominal aortic aneurysms (rAAA). In this study, we prospectively compared these formulae in patients with rAAA with their actual outcomes. METHODS: Information was collected on 134 patients from two centers over a 3-year period. Preoperative mortality risk was estimated using coefficients for age, level of consciousness, and cardiac arrest. Mortality risk in the immediate postoperative state was based on the presence of coagulopathy, ischemic colitis, prolonged requirement for inotropes, time from arrival at hospital to surgery, patient age, perioperative myocardial infarction, renal failure, and pre-operative hemoglobin level. RESULTS: The average age was 73 years (range 30 to 92 y) and 20 of 134 (15%) patients were women. Sixty-three patients (47%) survived. For patients with a calculated preoperative mortality risk of >90%, the sensitivity, specificity, and positive and negative predictive values were 25%, 98%, 95%, and 54%, respectively. For a mortality risk >80%, these values were 37%, 94%, 87%, and 57%, respectively. For patients with an estimated immediate postoperative mortality risk > or = 90%, the sensitivity, specificity, and positive and negative predictive values were 17%, 87%, 60%, and 49%, respectively. For a predicted mortality > or = 80%, these values were 22%, 84%, 60%, and 50%, respectively. CONCLUSIONS: Our formula for predicting mortality for preoperative rAAA patients may be useful for patients with an estimated mortality risk >/=90%, based on the high positive predictive value. The formula for immediate postoperative rAAA patients was not useful in predicting death.
Aged↗
Body mass index and mortality in 'healthier' as compared with 'sicker' haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).
BACKGROUND: Haemodialysis (HD) patients with lower body mass index (BMI) have a higher relative mortality risk (RR), irrespective of race. However, only Asian Americans treated with HD have been found to have an elevated RR with higher BMI. Asian Americans on HD are 'healthier' than other race groups (i.e. have better overall survival). We hypothesized that an increased mortality risk might be associated with high BMI in a variety of other 'healthier' subgroups of HD patients. METHODS: The prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) provided baseline demographic, comorbidity and BMI data on 9714 HD patients in the US and Europe (France, Germany, Italy, Spain, and the UK) from 1996-2000. Using multivariate survival analyses, we evaluated BMI-mortality relationships in HD subpopulations defined by continent, race (black and white), gender, tertiles of severity of illness (based on a score derived from comorbid conditions and serum albumin concentration), age (<45, 45-64, >or=65), smoking, and diabetic status. RESULTS: Relative mortality risk decreased with increasing BMI. This was statistically significant (P<0.007) except for the smallest subgroup of patients who were <45 years old and were also in the healthiest tertile of comorbidity. All else equal, BMI <20 was consistently associated with the highest relative mortality risk. Overall a lower relative mortality risk (RR) as compared with BMI 23-24.9, was found for overweight (BMI 25-29.9; RR 0.84, P=0.008), for mild obesity (BMI 30-34.9; RR 0.73, P=0.0003), and for moderate obesity (BMI 35-39.9; RR 0.76, P=0.02). CONCLUSION: In a wide variety of HD patient subgroups, differing with respect to their baseline health status, increasing body size correlates with a decreased mortality risk. This contrasts with the association between BMI and mortality in the general population, and deserves further study.
Adult↗
Interspecies major histocompatibility complex-restricted Th cell epitope on foot-and-mouth disease virus capsid protein VP4.
T-cell epitopes within viral polypeptide VP4 of the capsid protein of foot-and-mouth disease virus were analyzed using 15-mer peptides and peripheral blood mononuclear cells (PBMC) from vaccinated outbred pigs. An immunodominant region between VP4 residues 16 and 35 was identified, with peptide residues 20 to 34 (VP4-0) and 21 to 35 (VP4-5) particularly immunostimulatory for PBMC from all of the vaccinated pigs. CD25 upregulation on peptide-stimulated CD4(+) CD8(+) cells-dominated by Th memory cells in the pig-and inhibition using anti-major histocompatibility complex class II monoclonal antibodies indicated recognition by Th lymphocytes. VP4-0 immunogenicity was retained in a tandem peptide with the VP1 residue 137 to 156 sequential B-cell epitope. This B-cell site also retained immunogenicity, but evidence is presented that specific antibody induction in vitro required both this and the T-cell site. Heterotypic recognition of the residue 20 to 35 region was also noted. Consequently, the VP4 residue 20 to 35 region is a promiscuous, immunodominant and heterotypic T-cell antigenic site for pigs that is capable of providing help for a B-cell epitope when in tandem, thus extending the possible immunogenic repertoire of peptide vaccines.
Amino Acid Sequence↗
Delta opioid binding selectivity of 3-ether analogs of naltrindole.
Masking of the 3-phenol of naltrindole as a range of ethers caused a decrease in binding affinity at all three opiate receptors (mu, kappa, delta), however for the methyl ether, the reduction in affinity at both mu and kappa was greater than at delta, thereby increasing delta binding selectivity.
Naltrexone↗
Synthesis and biological activity of 3-substituted 3-desoxynaltrindole derivatives.
The 3-unsubstituted and substituted analogs of naltrindole (NTI) were synthesized using palladium-catalyzed transformations, and their binding affinity to opioid receptors was determined. Although the 3-desoxy analog showed comparable delta selectivity with that of NTI, all of the novel compounds possessed low affinity for delta receptors indicating the important role of the 3-oxygen atom of NTI for interaction with delta-opioid receptors.
Animals↗
Summary of the first round analyses of the Second International Swine CD Workshop.
The reactivity of 176 monoclonal antibodies (mAb) submitted to the Second International Swine CD Workshop, together with 19 internal standards, was analyzed by flow cytometry on 16 different cell types as a means of establishing the proper cell subset for later detailed clustering analyses. The exact CD subset reactivity of the 19 internal standard mAb had been characterized in the First International Swine CD Workshop. The flow cytometric analyses resulted in 40 data sets which were then subjected to statistical clustering using the Leukocyte Typing Database IV (LTDB4) software. As result of this work, 22 clusters were defined. After review of these results, panels of mAb from the defined first round clusters were assigned to cell subsets. The respective mAb in those first round clusters were then distributed to subset group researchers for further examination during the second round of the workshop.
Animals↗
Porcine myelomonocytic markers: summary of the Second International Swine CD Workshop.
Forty five mAbs submitted to the Second International Swine CD workshop were analyzed by six different laboratories for their possible reactivity with porcine myelomonocytic cells using flow cytometry and immunohistochemistry. As a result of these analyses, a new swine workshop cluster, SWC9, composed of two mAbs that recognize an antigen selectively expressed on mature macrophages, was defined. In addition, several mAbs were identified, allowing the differentiation of granulocytes from monocytes/macrophages, or monocytes from macrophages. Further work is required to identify the antigen recognized by these mAbs. Nevertheless, they should already prove useful for the identification of different stages in the macrophage maturation/differentiation, and will certainly aid analyses on the complexity of the mononuclear phagocyte system in the pig. Finally, the cross-reactivity of three anti-human CD14 mAbs with porcine myelomonocytic cells was established in this workshop.
Animals↗
Workshop studies with monoclonal antibodies identifying a novel porcine differentiation antigen, SWC9.
Two monoclonal antibodies (mAb) within cluster M4 of the myeloid section of the Second International Swine CD Workshop, C4 (No. 144) and PM18-7 (No. 192), showed reactivity with thymocytes and among cells of myelomonocytic origin with mature macrophages but not with monocytes and granulocytes. Both mAb recognize a protein showing two bands of 205 kDa and 130 kDa under both reducing and non-reducing conditions. Although epitope mapping with these mAb could not be performed, this cluster received the SWC9 designation.
Animals↗
The efficacy of intra-articular morphine for postoperative knee arthroscopy analgesia.
This article describes two prospective, randomized, double-blind clinical trials designed to investigate this. Trial 1 compared a conventional local anaesthetic agent (100 mg bupivacaine) injected intra-articularly (i.a.) with a control (normal saline) and 1 mg of i.a. morphine. No significant difference was noted in the first 4 hours between the groups with respect to visual analogue pain (VAS) scores. However, at 6 and 24 hours, the group of patients who received 1 mg i.a. morphine recorded lower pain scores and required less supplementary analgesia. Trial 2 assessed the dose response relationship for i.a. morphine comparing 5 mg intravenous (i.v.) morphine (control) with 1 mg and 5 mg i.a. morphine. At early time points (1, 2, and 4 hours) similar VAS pain scores were recorded for both 5 mg i.v. morphine and 5 mg i.a. morphine, both significantly lower than the group receiving 1 mg i.a. morphine. At 6 and 24 hours, 5 mg of i.a. morphine produced significantly lower pain scores, less analgesic requirement, and less sleep disturbance on the first postoperative night than the other groups. It can be concluded from these two studies that 5 mg i.a. was the most effective analgesic following knee arthroscopy.
Adult↗
Peptide binding to MHC class I is determined by individual pockets in the binding groove.
H-2Kb and HLA-A2 are MHC4 class I molecules with a similar overall structure. Important differences between these two class I molecules reside in the structure of the individual pockets in the antigenic-peptide-binding groove. H-2Kb, which has a deep C pocket, binds specifically peptides with a tyrosine or a phenylalanine at position 5. In contrast, HLA-A2 has a shallow C pocket, which cannot accommodate large side chains at position 5. Site-directed mutagenesis was used to generate a chimera between the murine H-2Kb and the human HLA-A2 [H-2Kb/HLA-A2(C')]. The structure of this chimera is similar to H-2Kb except for the region around the deep C pocket, where residues at positions 9, 97 and 99 were substituted with those bulkier residues from HLA-A2. Peptide binding between this chimera and H-2Kb-binding peptides [VSV (52-59), OVA (257-264), and MCMV pp89 (168-176)], revealed that the deep C pocket of H-2Kb was crucial for high-affinity binding. While a peptide, VSV (52-59), was found to bind with severalfold lower 'affinity' to H-2Kb/HLA-A2(C') than to the wild-type H-2Kb, a VSV analogue with the tyrosine in position 5 (Tyr5) substituted with an alanine was found to bind with a similar 'affinity' to both MHC class I molecules. Computer-aided modelling of the H-2Kb/HLA-A2(C') complex indicates that the VSV (52-59) peptide probably binds to the chimeric MHC molecule with the peptide side chain of anchor residue Tyr5 pointing away from the groove. These results confirm a role of the individual pockets in determining peptide-binding affinity and specificity and suggest that this may be accomplished by changes in side-chain orientation.
Animals↗