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Biomedical subjects

M T Collins

Publications and source records attributed to M T Collins.

At least 19 recordsLinked to original sources

Conditional dependence between tests affects the diagnosis and surveillance of animal diseases.

Dependence between the sensitivities or specificities of pairs of tests affects the sensitivity and specificity of tests when used in combination. Compared with values expected if tests are conditionally independent, a positive dependence in test sensitivity reduces the sensitivity of parallel test interpretation and a positive dependence in test specificity reduces the specificity of serial interpretation. We calculate conditional covariances as a measure of dependence between binary tests and show their relationship to kappa (a chance-corrected measure of test agreement). We use published data for toxoplasmosis and brucellosis in swine, and Johne's disease in cattle to illustrate calculation methods and to indicate the likely magnitude of the dependence between serologic tests used for diagnosis and surveillance of animal diseases.

Animals↗

Corrigendum to "A linear programming assessment of the profit from strategies to reduce the prevalence of Staphylococcus aureus mastitis" [Prev. Vet. Med. 33 (1998) 183-193].

We used a linear programming model to estimate the financial returns to a Staphylococcus aureus testing and control program over a 1-year period for a 100-cow herd, with a 8636kg rolling-herd average. Six tests, which vary in sensitivity from 0.80 to 0.98 and specificity of 0.99, were examined in simulated herds with 10, 20, and 30% prevalence of S. aureus infection. Sensitivity of these results to a range of assumptions regarding rolling-herd average, milk price, somatic cell-count premium, and cost and cure rate of dry treatment were examined to determine the profits from the program. The profits of a control program are most dependent upon prevalence and cell-count premium. In our simulation for a 100-cow herd, a testing and control program results in a profit ranging from US$1.50 to US$20 per cow per year, except under the lowest prevalence and most-adverse conditions (low yield or low SCC premium).

Agriculture↗

Effect of three factors in cheese production (pH, salt, and heat) on Mycobacterium avium subsp. paratuberculosis viability.

Low pH and salt are two factors contributing to the inactivation of bacterial pathogens during a 60-day curing period for cheese. The kinetics of inactivation for Mycobacterium avium subsp. paratuberculosis strains ATCC 19698 and Dominic were measured at 20 degrees C under different pH and NaCl conditions commonly used in processing cheese. The corresponding D values (decimal reduction times; the time required to kill 1 log(10) concentration of bacteria) were measured. Also measured were the D values for heat-treated and nonheated M. avium subsp. paratuberculosis in 50 mM acetate buffer (pH 5.0, 2% [wt/vol] NaCl) and a soft white Hispanic-style cheese (pH 6.0, 2% [wt/vol] NaCl). Samples were removed at various intervals until no viable cells were detected using the radiometric culture method (BACTEC) for enumeration of M. avium subsp. paratuberculosis. NaCl had little or no effect on the inactivation of M. avium subsp. paratuberculosis, and increasing NaCl concentrations were not associated with decreasing D values (faster killing) in the acetate buffer. Lower pHs, however, were significantly correlated with decreasing D values of M. avium subsp. paratuberculosis in the acetate buffer. The D values for heat-treated M. avium subsp. paratuberculosis ATCC 19698 in the cheese were higher than those predicted by studies done in acetate buffer. The heat-treated M. avium subsp. paratuberculosis strains had lower D values than the nonheated cells (faster killing) both in the acetate buffer (pH 5, 2% [wt/vol] NaCl) and in the soft white cheese. The D value for heat-treated M. avium subsp. paratuberculosis ATCC 19698 in the cheese (36.5 days) suggests that heat treatment of raw milk coupled with a 60-day curing period will inactivate about 10(3) cells of M. avium subsp. paratuberculosis per ml.

Cheese↗

Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone.

Activating missense mutations of the GNAS1 gene, encoding the alpha subunit of the stimulatory G protein (Gs), have been identified in patients with the McCune-Albright syndrome (MAS; characterized by polyostotic fibrous dysplasia, café au lait skin pigmentation, and endocrine disorders). Because fibrous dysplasia (FD) of bone also commonly occurs outside of the context of typical MAS, we asked whether the same mutations could be identified routinely in non-MAS FD lesions. We analyzed a series of 8 randomly obtained, consecutive cases of non-MAS FD and identified R201 mutations in the GNAS1 gene in all of them by sequencing cDNA generated by amplification of genomic DNA using a standard primer set and by using a novel, highly sensitive method that uses a protein nucleic acid (PNA) primer to block amplification of the normal allele. Histologic findings were not distinguishable from those observed in MAS-related FD and included subtle changes in cell shape and collagen texture putatively ascribed to excess endogenous cyclic adenosine monophosphate (cAMP). Osteomalacic changes (unmineralized osteoid) were prominent in lesional FD bone. In an in vivo transplantation assay, stromal cells isolated from FD failed to recapitulate a normal ossicle; instead, they generated a miniature replica of fibrous dysplasia. These data provide evidence that occurrence of GNAS1 mutations, previously noted in individual cases of FD, is a common and perhaps constant finding in non-MAS FD. These findings support the view that FD, MAS, and nonskeletal isolated endocrine lesions associated with GNAS1 mutations represent a spectrum of phenotypic expressions (likely reflecting different patterns of somatic mosaicism) of the same basic disorder. We conclude that mechanisms underlying the development of the FD lesions, and hopefully mechanism-targeted therapeutic approaches to be developed, must also be the same in MAS and non-MAS FD.

Adolescent↗

Hormonal modulation of phagocytosis and intracellular growth of Mycobacterium avium ss. paratuberculosis In bovine peripheral blood monocytes.

In this study, we evaluated the effects of several hormones (i.e. growth hormone, prolactin, vitamin D3, luteinizing hormone, oxytocin) on the phagocytosis and intracellular survival of Mycobacterium avium ss. paratuberculosis within bovine peripheral blood monocytes. Phagocytosis of M. avium ss. paratuberculosis declined in a dose-dependent manner when monocytes were exposed to increasing amounts of recombinant bovine growth hormone, with little phagocytosis occurring at a growth hormone concentration of 50 ng/ml. The other hormones tested had little effect on phagocytosis. Continuous exposure of bovine monocytes to bovine growth hormone (10 ng per ml) resulted in enhanced intracellular bacillary growth. This was detected within 3 days of monocyte infection, and resulted in a 1 Log10 greater number of M. avium ss. paratuberculosis in growth hormone treated, than control, monocytes at 12 days of infection. When monocytes were incubated with growth hormone for only the first 5 days of a 12 day incubation period, a further increase in bacillary multiplication was observed. A similar increase in bacillary multiplication was observed when M. avium ss. paratuberculosis monocytes were incubated with prolactin for the first 5 days of a 12 day incubation period. These data indicate that varying levels of growth hormone and prolactin can affect the intracellular multiplication of M. avium ss. paratuberculosis in bovine monocytes.

Animals↗

Factors influencing the isolation of Mycobacterium avium subsp. paratuberculosis from bovine fecal samples.

A modified procedure was used for culture of Mycobacterium paratuberculosis (Mptb) from bovine feces. Bovine fecal samples were decontaminated with NaOH, exposed to a mixture of oxalic acid and malachite green, incubated in a mixture of neomycin and amphotericin B. Decontaminated specimens were inoculated onto modified Löwenstein-Jensen medium. Specimens processed by high-speed centrifugation showed growth earlier than specimens prepared by low-speed centrifugation. However, the overall number of positive cultures at 16 weeks was not different for the 2 methods. When infected dairy herds were sampled 4 times at 6-month intervals and culture-positive cows were culled, the prevalence of infected cattle declined over time. After selective culling, the cattle left in the herds shed low numbers of Mptb, which explains why it took longer for cultures to become positive. No heifers younger than 11 months were culture positive, but heifers 13-14 months of age were more frequently culture positive than were heifers of any other age. The 16-week culture period is needed with this method to detect cattle shedding low numbers of Mptb. High-speed centrifugation of samples does not increase the efficiency of identification of animals shedding Mptb.

Age Factors↗

Intracellular fate of Mycobacterium avium subspecies paratuberculosis in monocytes from normal and infected, interferon-responsive cows as determined by a radiometric method.

The ability of Mycobacterium avium subsp. paratuberculosis to survive in bovine monocytes was studied using radiometric (BACTEC) culture, standard plate counting and microscopic counting of acid-fast stained monocyte monolayers. Results of microscopic counts sharply contrasted with results of viable counts determined both by plate counting and radiometric counting. We observed an early phase (the first 6 d after in vitro infection) of intracellular bacillary growth, followed by a later phase of mycobacteriostasis or killing (up to 12 d after in vitro infection) in monocytes from non-infected cows. The data suggest that multiplication and death of M. avium subsp. paratuberculosis occur simultaneously in bovine monocytes infected in vitro. Using the BACTEC method, we compared the ability of bovine monocytes from normal cows and cows infected with M. avium subsp. paratuberculosis and showing evidence of a strong Thl-like cellular immune response to ingest and inhibit the intracellular growth of M. avium subsp. paratuberculosis. There was a trend toward greater phagocytosis and faster killing of Mycobacterium avium subsp. paratuberculosis by monocytes from the infected, immune responder cows. However, the observed numbers of viable M. avium subsp. paratuberculosis at each time after monocyte infection were not significantly different between normal and infected cows.

Animals↗

Epizootic of paratuberculosis in farmed elk.

After multiple cases of chronic diarrhea and weight loss in a farmed elk herd, 3 yearlings and 1 adult elk with similar clinical signs were euthanatized and necropsied. Gross and histologic evidence of paratuberculosis were found in the yearlings. Evidence of serum antibody to Mycobacterium paratuberculosis was detected in the 2 elk with the most disseminated infection. Acid-fast organisms were isolated from multiple organs in all 4 elk and identified as M paratuberculosis by DNA probe. Thirty-five percent of 1 calf crop (n = 31) died or were euthanatized because of paratuberculosis before they were 2 years old. The organism was believed to have been spread by standing water that was used by calves as a wallow and a source of drinking water. The water was believed to have been contaminated by an infected adult female elk introduced to the herd just before calving season.

Animals↗

A linear programming assessment of the profit from strategies to reduce the prevalence of Staphylococcus aureus mastitis.

We used a linear programming model to estimate the financial returns to a Staphylococcus aureus testing and control program over a 1-year period for a 100-cow herd, with a 8636-kg rolling-herd average. Six tests, which vary in sensitivity from 0.80 to 0.98 and specificity of 0.99, were examined in simulated herds with 10, 20 and 30% prevalence of S. aureus infection. Sensitivity of these results to a range of assumptions regarding rolling-herd average, milk price, somatic cell-count premium, and cost and cure rate of dry treatment were examined to determine the profits from the program. The profits of a control program are most dependent upon prevalence, cell-count premium, and cost of dry treatment. In our simulation for a 100-cow herd, a testing and control program appears to cost less than US$10 per cow per year, and pays for itself within 1 yr, except under the lowest prevalence and most-adverse conditions (low yield, high cost of dry treatment, or low SCC premium.

Animals↗

Thermal tolerance of Mycobacterium paratuberculosis.

D values (decimal reduction time; the time required to kill 1 log concentration of bacteria) were determined for both human and bovine strains (Dominic, Ben, BO45, and ATCC 19698) of Mycobacterium paratuberculosis in 50 mM lactate solution (pH 6.8) and in milk at four temperatures (62, 65, 68, and 71 degrees C). Viable M. paratuberculosis organisms were quantified by a radiometric culture method (BACTEC). Thermal death curves for the M. paratuberculosis strains tested were generally linear, with R2 of > or = 0.90, but a few curves (R2, 0.80 to 0.90) were better described by a quadratic equation. The human strains (Dominic and Ben) had similar D values in milk and in lactate solution. However, D values for the bovine strains (BO45 and ATCC 19698) were significantly different depending on the menstruum. D values for low-passage clinical strains (Dominic, Ben, and BO45) were lower than those of the high-passage laboratory strain (ATCC 19698). The D value based on pooled data for clinical strains of M. paratuberculosis in milk at 71 degrees C (D71 degrees C) was 11.67 s. Pooled D62 degrees C, D65 degrees C, and D68 degrees C of clinical M. paratuberculosis strains in milk were 228.8, 47.8, and 21.8 s, respectively. The Z value (the temperature required for the decimal reduction time to traverse 1 log cycle) of clinical strains in milk was 7.11 degrees C. The D values of clumped and single M. paratuberculosis cells were not significantly different. The D values of all M. paratuberculosis strains tested were considerably higher than those published for Listeria, Salmonella, and Coxiella spp. and estimated for Mycobacterium bovis, indicating that M. paratuberculosis is more thermally tolerant. This study supports the premise that M. paratuberculosis may survive high-temperature, short-time pasteurization when the initial organism concentration is greater than 10(1) cells/ml.

Animals↗

Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent.

Parathyroid carcinoma is one cause of primary hyperparathyroidism, a condition in which there is hypercalcemia and dysregulated hypersecretion of PTH. In normal, and in some neoplastic parathyroid cells, PTH secretion is mediated by the cell surface calcium-sensing receptor. We describe the first therapeutic use of a novel molecule, a calcimimetic, that has agonist action at the calcium-sensing receptor. A 78-yr-old man with parathyroid carcinoma was admitted with hypercalcemia, markedly elevated PTH, and a change in mental status. He was treated for 17 days with conventional therapy, which included saline hydration, furosemide, pamidronate, and calcitonin. This was ineffective, and on hospital day 18, calcimimetic at a dose of 50 mg, orally, every 6 h was added. On hospital day 25, the dose was increased to 100 mg, orally, every 6 h, and on hospital day 30, saline and furosemide were discontinued. He was discharged on hospital day 40. With several dose adjustments, he has been treated with monotherapy calcimimetic for over 600 days and has not required any other interventions for his parathyroid carcinoma. Mean daily precalcimimetic treatment values of serum ionized calcium and PTH were 1.83 mmol/L and 872 pg/mL, respectively. During hospitalization, at the lower dose of calcimimetic, calcium and PTH decreased to 1.67 mmol/L and 538 pg/mL; with the higher dose they further decreased to 1.51 mmol/L and 444 pg/mL. Since discharge, and despite increasing levels of PTH, serum calcium has remained high, but lower than the admission level and acutely responsive to changes in calcimimetic doses. This compound, a calcimimetic, the first of a new class of compounds with activity at the calcium-sensing receptor, has been used to treat a patient with parathyroid carcinoma. During 2 yr of treatment, no adverse clinical effects have been observed, and it appears to have been effective at controlling hypercalcemia.

Acute Disease↗

Study of T-lymphocyte subsets of healthy and Mycobacterium avium subsp. paratuberculosis-infected cattle.

The relative contributions of T-lymphocyte subsets to host defense in cattle infected with Mycobacterium avium subsp. paratuberculosis is reported. The subsets were purified with appropriate monoclonal antibodies and a magnetic bead column separation system, and their purity was verified by flow cytometry. Biological activity of each subset, expressed as lymphoproliferation and gamma interferon (IFN-gamma) production, was measured in response to phytohemagglutinin (PHA) and an M. avium antigen preparation (A-PPD). IFN-gamma was measured by antibody capture enzyme-linked immunosorbent assay. The results showed a correlation between proliferation and IFN-gamma production in response to A-PPD but not to PHA. In response to PHA, CD4+ lymphocytes were the most prolific producers of IFN-gamma. CD8+ lymphocytes produced IFN-gamma to a lesser extent, whereas gammadelta+ T lymphocytes produced little or no IFN-gamma. Differences observed between the amount of IFN-gamma produced by CD4+ versus CD8+ cells and CD4+ versus gammadelta+ cells were significant (P < 0.01), but those between peripheral blood mononuclear cells (PBMC) and CD4+ T cells were not. Similar responses to A-PPD were observed except that PBMC produced higher levels of IFN-gamma than did CD4+ T cells. These data for cattle are similar to observations made for other animal species, where CD4+ cells are the major type of T lymphocytes producing IFN-gamma. They further suggest that whatever the role gammadelta+ T cells may play in paratuberculosis, it is not likely to be mediated by IFN-gamma production.

Animals↗

Effects of gamma interferon and nitric oxide on the interaction of Mycobacterium avium subsp. paratuberculosis with bovine monocytes.

In this study, we examined the effects of recombinant bovine gamma interferon (rIFN-gamma) and nitric oxide (NO) on the interaction of M. avium subsp. paratuberculosis with bovine monocytes. Monocytes pretreated with rIFN-gamma exhibited slightly increased phagocytosis of M. avium subsp. paratuberculosis and modest inhibition of the intracellular growth of this microorganism. The number of viable intracellular bacilli decreased earlier in rIFN-gamma-pretreated monocytes than in control monocytes. After infection with M. avium subsp. paratuberculosis, NO was not constitutively released, but NO release from infected monocytes was induced by treatment with rIFN-gamma or with rIFN-gamma and lipopolysaccharide (LPS). Release of nitric oxide was inhibited by addition of N(G)-monomethyl-L-arginine; however, inhibition of nitric oxide did not alter the pattern of intracellular survival of M. avium subsp. paratuberculosis in rIFN-gamma-treated bovine monocytes. Although chemically generated nitric oxide killed M. avium subsp. paratuberculosis in a cell-free system in vitro, the amount of nitric oxide required was far greater than that released from infected monocytes stimulated with rIFN-gamma and LPS. Our data suggest that rIFN-gamma activates M. avium subsp. paratuberculosis-infected bovine monocytes to release nitric oxide but only modestly increases antimycobacterial activity of monocytes against this organism. This may be due, in part, to the fact that the amount of nitric oxide produced by rIFN-gamma-activated bovine monocytes is insufficient to kill intracellular M. avium subsp. paratuberculosis bacilli in vitro.

Animals↗

Mycobacterium paratuberculosis: a potential food-borne pathogen?

Mycobacterium paratuberculosis commonly infects dairy cattle, leading to Johne's disease, which is also known as paratuberculosis. The infection is chronic progressive, and incurable. As the infection progresses, excretion of M. paratuberculosis in feces and milk occurs, and the bacterium spreads through the blood to multiple internal organs. Consequently, raw products originating from cattle may harbor M. paratuberculosis. Thermal treatments, such as pasteurization, are commonly relied on to kill food-borne bacterial pathogens that can infect humans. The small number of studies conducted to determine the thermal resistance of M. paratuberculosis suggest that it is less susceptible to destruction by heat killing than are milkborne zoonotic bacterial pathogens such as Listeria spp. or Mycobacterium bovis. Published reports concerning the thermal resistance of M. paratuberculosis in milk are reviewed herein, and key issues concerning the efficacy of pasteurization for elimination of M. paratuberculosis from milk are summarized.

Animals↗

Radiometric culture of Mycobacterium avium paratuberculosis from the feces of tule elk.

To determine if Mycobacterium avium paratuberculosis has persisted in tule elk (Cervus elaphus nannodes) at Point Reyes National Seashore (California, USA), 100 fresh fecal samples were collected. Feces were cultured on a modified BACTEC 12B radiometric medium for detection of M. avium paratuberculosis. Four samples, coming from two separate groups of elk tested positive for M. avium paratuberculosis. Thus, a noninvasive technique was used to document the continued presence of M. avium paratuberculosis in elk at Point Reyes National Seashore. These findings document persistence of this organism for a period of at least 13 yr in a free ranging herd of elk, with a 6 yr absence of observed clinical signs.

Animals↗

Associations between subclinical paratuberculosis and milk production, milk components, and somatic cell counts in dairy herds.

OBJECTIVE: To determine associations between subclinical Mycobacterium paratuberculosis infection and milk production, milk components, and somatic cell counts of dairy cattle. DESIGN: Cross-sectional epidemiologic survey. ANIMALS: 23 dairy herds in Wisconsin containing 1,653 adult cows were studied. The herds had above average milk production and a history of bovine paratuberculosis in the herd within the previous 12 months. PROCEDURE: All adult cows in the herds were tested for paratuberculosis by use of an absorbed ELISA. Milk yield, fat, protein, and somatic cell count data were retrieved electronically from Dairy Herd Improvement Association records. RESULTS: 147 ELISA-positive and 1,506 ELISA-negative cows were identified. ELISA-positive cows had a mature-equivalent milk production of 376 kg (829 lb)/lactation less than that for ELISA-negative herdmates. Significant difference was not found in lactation average percent-ages of fat and protein, or somatic cell count linear score. When comparing ELISA-positive and -negative cow's current mature equivalent milk with all previous lactations, significant difference was found only from the immediate-preceding lactation. When this difference was examined by parity group, significant difference was confined to cows in the second lactation. CLINICAL IMPLICATIONS: Subclinical paratuberculosis infections, as determined by ELISA, are associated with a 4% reduction in milk yield and add to the already substantial costs of clinical M paratuberculosis infection in the dairy industry.

Analysis of Variance↗