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Biomedical subjects

C R Young

Publications and source records attributed to C R Young.

At least 37 records · Page 2Linked to original sources

Serum haptoglobin concentrations in Holstein dairy cattle with toxic puerperal metritis.

The serum concentration of haptoglobin was measured in 51 cows with toxic puerperal metritis which were being treated with one of three different antimicrobial regimens. The mean concentration of haptoglobin was 19.0 mg/dl on the day that the treatments began and declined steadily during the five day treatment period to a mean concentration of 7.35 mg/dl. There was no correlation between the serum haptoglobin concentrations and the rectal temperatures of the cows during the five days.

Animals↗

Management of the adverse effects of clozapine.

Clozapine has been found to be superior to traditional neuroleptics in the treatment of refractory schizophrenia and is increasingly being used to treat schizophrenia, affective disorders, some neurological disorders, and aggression. For many patients, clozapine offers new hope for the successful pharmacological management of a disabling mental disorder. However, up to 17 percent of patients must discontinue treatment with clozapine because of adverse effects, which also limit the rate at which the dose can be increased and the maximum dose that can be tolerated. This article reviews strategies for minimizing and managing the adverse effects of clozapine, including agranulocytosis, seizures, sedation, delirium, obsessive-compulsive symptoms, hypotension, tachycardia, weight gain, sialorrhea, elevated liver enzymes, constipation, nausea, enuresis, fever, and neuromuscular effects. Incidence and morbidity are presented first. Then, the known or hypothesized pathophysiology of the adverse effects are described. Finally, nonpharmacological and pharmacological interventions are reviewed. Under-standing the incidence, pathophysiology, and treatments of adverse effects is essential for a positive therapeutic outcome when prescribing clozapine.

Agranulocytosis↗

Characterization of the thermal stress response of Campylobacter jejuni.

Campylobacter jejuni, a microaerophilic, gram-negative bacterium, is a common cause of gastrointestinal disease in humans. Heat shock proteins are a group of highly conserved, coregulated proteins that play important roles in enabling organisms to cope with physiological stresses. The primary aim of this study was to characterize the heat shock response of C. jejuni. Twenty-four proteins were preferentially synthesized by C. jejuni immediately following heat shock. Upon immunoscreening of Escherichia coli transformants harboring a Campylobacter genomic DNA library, one recombinant plasmid that encoded a heat shock protein was isolated. The recombinant plasmid, designated pMEK20, contained an open reading frame of 1,119 bp that was capable of encoding a protein of 372 amino acids with a calculated molecular mass of 41,436 Da. The deduced amino acid sequence of the open reading frame shared similarity with that of DnaJ, which belongs to the Hsp-40 family of molecular chaperones, from a number of bacteria. An E. coli dnaJ mutant was successfully complemented with the pMEK20 recombinant plasmid, as judged by the ability of bacteriophage lambda to form plaques, indicating that the C. jejuni gene encoding the 41-kDa protein is a functional homolog of the dnaJ gene from E. coli. The ability of each of two C. jejuni dnaJ mutants to form colonies at 46 degreesC was severely retarded, indicating that DnaJ plays an important role in C. jejuni thermotolerance. Experiments revealed that a C. jejuni DnaJ mutant was unable to colonize newly hatched Leghorn chickens, suggesting that heat shock proteins play a role in vivo.

Amino Acid Sequence↗

Development of a simple enzyme immunoassay for blood haptoglobin concentration in cattle and its application in improving food safety.

OBJECTIVE: To verify the role of haptoglobin, a major acute-phase reactant protein in cattle, as a marker to identify health/disease status in cattle and further assess its potential in improving food safety. SAMPLE POPULATION: Serum samples from various cattle groups: clinically normal cattle comprising steers (n = 157) and culled dairy cows (n = 92) before death (antemortem [AM]); retained carcasses (n = 57) railed off the line during postmortem (PM) inspection; and apparently AM normal culled dairy cows (n = 57). PROCEDURE: Efficacy of the simplified monoclonal antibody-based enzyme immunoassay was established by comparing results of haptoglobin tests performed independently on aliquots of serum samples by 3 laboratories. RESULTS: Haptoglobin concentration was significantly (P< or = 0.0001) different between the PM retained carcass group (n = 57) and the AM steer (n = 157) and culled dairy cow (n = 92) groups. In addition, haptoglobin concentration in AM steers (n = 157) and culled dairy cows (n = 92) was significantly (P < or = 0.0012) different, possibly reflecting a higher percentage of underlying pathologic or inflammatory conditions in animals of the latter group. Evaluation in 3 laboratories of sera from a group of culled dairy cows (n = 57), each laboratory performing a different test procedure, indicated that correlation of haptoglobin concentrations was good between the reported test procedure and the unmodified test and the classical hemoglobin-binding assay that measures peroxidase activity. CONCLUSION: Haptoglobin determination is effective in identifying diseased and healthy cattle. It may be a potentially important tool for application at the farm and slaughterhouse as an aid in improving food safety.

Animals↗

Detection and quantification of poultry probiotic bacteria in mixed culture using monoclonal antibodies in an enzyme-linked immunosorbent assay.

Murine monoclonal antibodies were used in an enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of selected probiotic bacteria present in a continuous-flow competitive exclusion culture known to be effective at reducing chicken cecal and crop colonization by Salmonella typhimurium. Veillonella, Enterococcus avium and S. typhimurium were grown anaerobically in batch culture of Viande Levure broth in pure culture and mixed culture. The mixed cultures produced significantly more acetate and propionate than any of the pure cultures with acetate and propionate being the predominant volatile fatty acids. The association in mixed culture resulted in a significant increase in cell numbers compared to the respective pure cultures. The ELISA was capable of detecting 10(4) cells per ml of the bacteria. The plots of cell numbers determined by the ELISA versus direct plating increased in accordance with increases in cell numbers with r2 values of 0.950, 0.922 and 0.940 for the pure culture incubations and 0.901, 0.924 and 0.905 in the mixed culture incubation for E. avium, S. typhimurium and Veillonella, respectively. The results indicate that the monoclonal antibodies can be used to quantitatively assay individual probiotic bacterial species grown in a mixed culture incubation.

Animals↗

Production and characterization of monoclonal antibodies to a Veillonella species from a continuous-flow culture system of chicken cecal bacteria.

Administering native intestinal flora to newly hatched chicks protects against cecal Salmonella colonization, and is known as competitive exclusion. Continuous-flow culture systems have been used to maintain defined competitive exclusion cultures. We have recently demonstrated that such a stable continuous-flow culture, CF3, contains 29 bacterial strains representing ten genera. Broiler chicks treated with CF3 are protected against Salmonella colonization of the ceca. Such protection is correlated with elevated concentrations of proprionic acid in the cecal contents of treated chicks. In this study we report on the preparation and characterization of monoclonal antibodies to one of the proprionic acid producing anaerobes contained in CF3, namely Veillonella CF3. Five different monoclonal antibodies were characterized with respect to: (1) isotype; (2)Veillonella specificity as judged by cross-reactivity profiles with other bacteria; (3) sensitivity as measured by the limit of detection of the number of colony forming units of Veillonella; and (4) antigen recognition of Veillonella by Western Blot analysis. These antibodies have been used to enumerate Veillonella in both the CF3 cultures and in the ceca of young chicks.

Journal Article↗

Myocardial infarction resulting from caffeine overdose in an anorectic woman.

A 20-year-old bulimic woman ingested 20 g of caffeine in a suicide attempt. After being evaluated and discharged from the emergency department, she was readmitted with ECG changes and ultimately found to have sustained a subendocardial infarction. This case highlights the wide-ranging health consequences of eating disorders and the toxicity of caffeine overdose.

Adult↗

The expanding indications for clozapine.

Clozapine is increasingly being used for clinical indications in addition to treatment-resistant schizophrenia; this article reviews the relevant literature. The first section reassesses the risks associated with clozapine treatment, particularly agranulocytosis. The next section discusses its use for schizophrenia in patients who are treatment resistant, not treatment resistant, and intolerant of traditional drug treatments. Subsequent sections address its use in mood disorders, neurologic conditions, comorbid substance abuse, aggressive behavior, and childhood schizophrenia. Each includes the initial rationale for the use of clozapine in the disorder, a critical evaluation of the relevant literature, and theories as to why clozapine's unique pharmacodynamic profile may be efficacious for the specific condition. This body of literature suggests clozapine may be an effective treatment for a wide range of disorders.

Animals↗

Serum haptoglobin concentrations in a population of feedlot cattle.

OBJECTIVE: To determine serum haptoglobin concentrations in a population of feedlot cattle and evaluate their usefulness in predicting subsequent clinical respiratory tract disease. DESIGN: Prospective longitudinal study. ANIMALS: 366 beef calves. PROCEDURE: Serum samples were obtained at feedlot entry and 40 and 65 days on feed (DOF). Calves were observed daily for clinical signs of respiratory tract disease. The lungs of 144 of the calves were evaluated at slaughter for the presence of gross lesions of pneumonia. RESULTS: 58% of the calves had detectable serum haptoglobin concentration in at least 1 sample. The proportion of calves with detectable haptoglobin were similar at each sample collection time. A higher proportion of the calves had values > 10 mg/dl at 40 DOF. The proportion of calves observed with clinical disease during the 10-day period after the 40 DOF sample increased (P < 0.10) as serum haptoglobin concentration increased. At 65 DOF, calves with serum haptoglobin value > 10 mg/dl had a higher (P < 0.05) rate of subsequent clinical respiratory tract disease than did calves with lower values. The proportion of calves with gross pulmonary lesions slaughter increased (P < 0.05) from 39% among calves without detectable serum haptoglobin concentration in any of the 3 samples to 63% among calves with at least 1 observed value > 10 mg/dl. CONCLUSIONS: We observed associations between serum haptoglobin concentration and subsequent clinical respiratory tract disease and pulmonary lesions at slaughter. However, serum haptoglobin concentration alone is not adequate for prediction of clinical disease. CLINICAL RELEVANCE: The usefulness for cross-sectional sampling of serum haptoglobin concentration as a diagnostic tool for clinical respiratory tract disease in feedlot cattle appears to be limited.

Animals↗

Haptoglobin response to clinical respiratory tract disease in feedlot cattle.

OBJECTIVE: To quantify haptoglobin response to respiratory tract disease in feedlot cattle, and to investigate its ability to predict disease outcome and response to antibiotic treatment. DESIGN: Randomized clinical trial. ANIMALS: 60 feedlot calves with clinical respiratory tract disease. PROCEDURE: Calves were randomly assigned to receive a standard antibiotic treatment regimen (TRT), or to observation pens without antibiotic treatment. Serum haptoglobin concentration was measured at initial and final examinations. Calves were examined for presence of gross pulmonary lesions at slaughter. RESULTS: Mean +/- SD serum haptoglobin concentration at initial examination was 67 +/- 108 mg/dl, with range of 0 to 508 mg/dl. Haptoglobin concentration at initial examination was similar for the TRT group and the group that did not receive antibiotic treatment, but at final examination, TRT-group calves had lower (P < 0.01) mean values. Calves receiving antibiotic treatment had haptoglobin concentration at or near zero at final examination. Calves not receiving antibiotic treatment had only slightly lower mean haptoglobin concentration at final examination, compared with initial examination. Within treatment groups, haptoglobin concentration was similar for cases with different outcomes. Calves with gross pulmonary lesions at slaughter had numerically higher, although statistically similar, haptoglobin concentrations at initial examination, compared with calves without lesions. CONCLUSIONS: Feedlot cattle with clinical respiratory tract disease have a large and variable haptoglobin response. Antibiotic treatment resulted in lower serum haptoglobin values, although low values were not required for full clinical recovery. CLINICAL RELEVANCE: Serum haptoglobin concentration may be an indicator of response to antibiotic therapy, although it appears to be unrelated to case severity or need for treatment.

Animals↗

Modulation of immunity to Borrelia burgdorferi by ultraviolet irradiation: differential effect on Th1 and Th2 immune responses.

Ultraviolet B (UVB) radiation suppresses the delayed-type hypersensitivity (DTH) response to alloantigen by a mechanism involving interleukin (IL)-10. It has been hypothesized, based on this result, that UV irradiation shifts the immune response from a Th1 to a Th2 response. We tested this hypothesis using Borrelia burgdorferi (Bb) as an antigen under conditions where both DTH and antibody responses could be assessed. Mice were irradiated with a single dose of UV and then immunized with Bb in complete Freund's adjuvant (CFA). DTH was assessed by footpad challenge. At various time points thereafter, mice were bled, and the serum antibodies to Bb were quantitated. Only IgG1, IgG2a, and IgG2b were produced in response to Bb. The IgG2a and IgG2b antibody responses, as well as the DTH response to Bb, showed UV dose-dependent reductions after UV irradiation. The primary IgG1 response to Bb was very low and was unaffected by UV irradiation; however, the IgG1 secondary response was elevated in UV-irradiated mice. Injection of anti-IL-10 antibody into UV-irradiated mice within 24 h after UV exposure restored the DTH response, as well as the IgG2a and IgG2b antibody responses. In addition, injecting recombinant murine IL-10 mimicked some of the effects of UV radiation. Our results support the hypothesis that in vivo, UV irradiation down-regulates Th1 immune responses, while leaving Th2 responses intact, and suggest that IL-10 is an important mediator of this effect.

Animals↗

Experimental feline Lyme borreliosis as a model for testing Borrelia burgdorferi vaccines.

The feline model investigated establishes that domestic cats may act as an animal model for evaluating the pathogenesis of Lyme borreliosis. Specifically this feline model demonstrates: First, that animals seroconvert following either needle injection of, or arthropod delivery of, Borrelia burgdorferi. Clinical findings obtained are consistent with those observed in human Lyme disease; histopathological observations are also consistent with those observed in human Lyme disease. Therefore, cats may also be used as a representative animal model for measuring immune protection against Lyme borreliosis. Specifically we are exploring the protective capacity of Borrelia burgdorferi antigenic compounds in cats, namely OspA, OspB, OspC, heat shock proteins, flagellar antigens and various protective immunological combinations.

Animals↗

Validation of immunoassays for bovine haptoglobin.

Haptoglobin (Hp) is an acute phase protein. The plasma concentration of Hp increases rapidly following tissue damage associated with infection and inflammation. Thus Hp levels could be used as a screening test for organic disease, an objective index of disease activity and response to therapy, or as a sign of microbial infection. Recently, an enzyme-linked immunosorbent assay for bovine Hp was described. We have now developed three different immunoassay formats for bovine Hp and report on their validation and relative value to the diagnosis of bovine disease. Hp levels measured using these three immunoassays were compared and contrasted with results obtained for Hp estimation as measured by the increase in the protection of peroxidase activity against acid inactivation following binding with bovine haemoglobin. The quantitative Hp immunoassays evaluated in the present study are simple, rapid, inexpensive, reproducible, and well suited for both field and laboratory use.

Animals↗