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Biomedical subjects

C G Brown

Publications and source records attributed to C G Brown.

At least 109 records · Page 6Linked to original sources
PubMed1989

The effect of MHC compatibility between parasite-infected cell line and recipient in immunization against tropical theileriosis.

Lymphoblastoid cell lines, infected and transformed in vitro by a Moroccan stock of Theileria annulata, infected and immunized susceptible taurine cattle, at cell doses of 10(8), 10(6), 10(4) and 10(2), regardless of whether the recipients were BoLA matched or mismatched to the donor cell line. The MHC relationship between the cell line and recipient did affect the severity of the clinical response to cell line immunization which may reflect differences in the specific priming of the immune response. At the highest cell doses the BoLA-mismatched recipients reacted more severely than the BoLA-matched. This study shows that, unlike the closely related parasite T. parva, there is no histocompatibility barrier to immunization using T. annulata-infected cell lines which could be achieved with as few as 10(2) allogeneic infected cells. The role of MHC compatibility between cell line and recipient in the priming of a protective immune response is discussed.

Animals↗
PubMed1989

The development and specificity of cytotoxic cells in cattle immunized with autologous or allogeneic Theileria annulata-infected lymphoblastoid cell lines.

Two groups of animals were immunized with either 10(6) autologous or 10(6) allogeneic Theileria annulata-infected lymphoblastoid cells cultured in vitro. The development and specificity of cytotoxic cells generated in vivo were measured throughout immunization and challenge using a panel of target cells that were either Theileria-infected or uninfected blast cells of known bovine lymphocyte antigen (BoLA) specificities. After inoculation of the cell lines the two groups showed distinct differences in both their clinical responses and the target specificity of the cytotoxic cells detected. The allogeneic T. annulata cell line recipients showed a very mild clinical response, and on day 9 after inoculation a strong cytotoxic response was detected. The response appeared to be directed against the allogeneic major histocompatibility complex (MHC) antigens of the inoculated cell line in some form of graft rejection response. By day 23 the predominant cytotoxic response was directed against the recipient animals' own cells infected with the parasite. In contrast, the autologous T. annulata cell line recipients showed very severe clinical reactions, and low levels of cytotoxicity were detected. The cytotoxicity was directed against parasite-infected targets but did not appear to be MHC restricted until day 20. Both groups were immune to a heterologous sporozoite challenge that proved lethal to two susceptible control animals, and on day 10 after challenge a peak of cytotoxicity was detected which was directed against the autologous infected target cell. This would suggest that this cytotoxic response was MHC restricted and was also cross-reactive between the heterologous parasite stocks used.

Animals↗
PubMed1989

Studies on the effects of omeprazole on thyroid function in the rat.

The effects of omeprazole (an H+, K+ -ATPase inhibitor) on thyroid parameters in rats have been examined. SK&F Wistar rats were dosed orally with omeprazole (up to 500 mg kg-1) or vehicle. Treatment for 7 or 14 days resulted in generally decreased plasma T3 concentrations in males (with little change or slight increases in females) and increased serum TSH concentrations (22%-68% increases). No changes were detected in thyroid 125I uptake or organification. Liver 5'-deiodinase activity was decreased in male rats after 7 days treatment. Thyroxine clearance was not altered after a single dose of omeprazole. In-vitro studies showed omeprazole to be only a weak inhibitor of TSH-stimulated 125I organification in cultured porcine thyrocytes. It is concluded that omeprazole has weak effects on the pituitary-thyroid-liver axis, its main action being to inhibit the peripheral deiodination of thyroid hormones.

Animals↗
PubMed1989

Theileria parva: the immune status of calves born of dams immunised against East Coast fever.

Eight Friesian cross cows three months pregnant to a single Friesian bull were immunised against East Coast fever by infection with Theileria parva (Muguga) sporozoite stabilate and treatment with pyrrolidino-methyl tetracycline. They were challenged with the homologous stock four times before calving and a fifth time after calving, and resisted all five challenges which killed all of the five groups of five susceptible controls. Calves born to these hyperimmunised dams were fully susceptible on challenge with the same stabilate, as were susceptible cows from the same farm and their calves. In both instances the calves died three to seven days earlier than the cows which were approximately 10 times heavier. These results show that one- to two-month-old taurine calves from artificially immunised dams are not protected from experimental T parva sporozoite challenge and that there is no inherent calfhood resistance to East Coast fever.

Animals↗
PubMed1989

In vitro infection of bovine alloreactive cytotoxic T cell lines with sporozoites of Theileria annulata and T parva.

Bovine alloreactive cytotoxic lymphocyte (CTL) lines of known target specificity were infected in vitro with sporozoites of Theileria annulata and T parva and cultured in limiting dilution. The phenotypes of the CTL lines both pre- and post infection were assessed using a panel of monoclonal antibodies specific for defined bovine lymphocyte subpopulations. The effector function of the resultant infected cell lines was determined using a Cr51 release assay and compared to the uninfected control CTL line. The results indicated that T parva sporozoites consistently infected and transformed the CTL lines very efficiently even at the lowest cell doses. In contrast the T annulata sporozoites were largely unable to infect and transform the alloreactive CTL except at the very highest cell and sporozoite doses. A factor which appeared to influence susceptibility to T annulata infection was an increased level of class II expression on the CTL line. None of the cell lines showed cytotoxic effector function after infection with either T annulata or T parva sporozoites.

Animals↗
PubMed1989

Theileria annulata and T. parva infect and transform different bovine mononuclear cells.

Bovine peripheral blood mononuclear cells (PBMC) were labelled with monoclonal antibodies recognizing bovine MHC class II, sIgM, monocyte, T-helper and T-cytotoxic cell phenotypes. They were sorted into positive and negative populations with a fluorescence-activated cell sorter (FACS). The cell populations were infected in vitro with sporozoites of either Theileria annulata or T. parva, and the degree of infection and transformation determined. The results showed that despite the many similarities between these two parasites, they infected different cells of the immune system. T. annulata preferentially infected MHC class II-positive cells but did not infect T cells. Monocytes were infected very efficiently by T. annulata but were uninfectable with T. parva. B cells were infected much more efficiently by T. annulata than T. parva. Cell lines derived from infections with T. annulata were analysed phenotypically. Virtually all reactivity was lost for the anti-sIgM and the anti-monocyte monoclonal antibodies post-infection and no T-cell markers were detected.

Animals↗
PubMed1988

Differential effects of D- and L-isomers of triiodothyronine on pituitary TSH secretion and peripheral deiodinase activity in the rat.

The effects of D- and L-T3 were compared in male SK & F Wistar rats to define overall effects on the 'pituitary-thyroid-liver axis' at high doses. After in vivo administration of L-T3 (up to 1 mg/kg orally, or up to 0.1 mg/kg subcutaneously) serum TSH and T4 were decreased in a dose-related manner. Similarly, following in vivo exposure to L-T3, both basal and TRH-stimulated TSH output from isolated superfused pituitary glands was decreased, but only the latter was affected by direct in vitro exposure to L-T3.D-T3 had between 1% and 10% the activity of L-T3 in decreasing these parameters both in vivo and in vitro. In contrast, both enantiomers increased liver and kidney deiodinase activity to approximately the same extent, presumably as a compensatory response to clear hormone from the body. These observations indicate that, following treatment with L- or D-T3 by oral gavage for 14 days, the 'no effect' dose (i.e. the dose which did not significantly decrease serum TSH concentrations as compared with controls) for L-T3 was below 0.01 mg/kg whereas that for D-T3 was 0.1 mg/kg.

Animals↗
PubMed1988

A model for regional blood flow measurements during cardiopulmonary resuscitation in a swine model.

Recent reports examining regional blood flow during cardiopulmonary resuscitation (CPR) have been criticized for several reasons: (1) cardiac arrest times of 5 min or less are not reflective of the prehospital setting, (2) anesthetic agents may significantly influence autonomic control of regional blood flow, (3) canine cardiac anatomy and coronary blood supply are not reflective of humans and (4) precise validation data for blood flow measurements have not been reported. This study presents a methodology and model for measuring regional blood flow during CPR after a prolonged cardiac arrest. Fifteen swine weighing 15-25.4 kg were instrumented for regional blood flow measurements using tracer microspheres. Regional cerebral and myocardial blood flow were measured during normal sinus rhythm (NSR) and during CPR following a 10-min cardiopulmonary arrest. Regional blood flow (ml/min/100 g) to the cerebral cortices averaged less than 3% of baseline flow (NSR: right cortex = 41.2 +/- 13.8; left cortex = 41.2 +/- 12.2; CPR: right cortex = 1.3 +/- 1.2; left cortex = 1.3 +/- 1.3). Total myocardial blood flow averaged less than 5% of baseline flow (NSR = 211.5 +/- 104.9; CPR = 9.5 +/- 14.9). The flow data demonstrates minimal cardiac and cerebral perfusion with standard CPR following a 10-min arrest. The variability in the pilot data may be used in determining sample sizes for future studies.

Animals↗
PubMed1988

Statistical reasoning in clinical trials: hypothesis testing.

Hypothesis testing is based on certain statistical and mathematical principles that allow investigators to evaluate data by making decisions based on the probability or implausibility of observing the results obtained. However, classic hypothesis testing has its limitations, and probabilities mathematically calculated are inextricably linked to sample size. Furthermore, the meaning of the p value frequently is misconstrued as indicating that the findings are also of clinical significance. Finally, hypothesis testing allows for four possible outcomes, two of which are errors that can lead to erroneous adoption of certain hypotheses: 1. The null hypothesis is rejected when, in fact, it is false. 2. The null hypothesis is rejected when, in fact, it is true (type I or alpha error). 3. The null hypothesis is conceded when, in fact, it is true. 4. The null hypothesis is conceded when, in fact, it is false (type II or beta error). The implications of these errors, their relation to sample size, the interpretation of negative trials, and strategies related to the planning of clinical trials will be explored in a future article in this journal.

Clinical Trials as Topic↗
PubMed1988

Myocardial oxygen delivery/consumption during cardiopulmonary resuscitation: a comparison of epinephrine and phenylephrine.

Our study compared the effect of high-dose epinephrine with the pure alpha-agonist phenylephrine on regional myocardial blood flow (MBF), myocardial oxygen delivery (MDO2), myocardial oxygen consumption (MVO2), and defibrillation rates during CPR. Fifteen swine weighing more than 15 kg were instrumented for measurement of regional MBF using radiolabeled tracer microspheres. Measurements of regional MBF, MDO2, and MVO2 were made during normal sinus rhythm. Ventricular fibrillation was induced and persisted for ten minutes. CPR was begun using a pneumatic compression device. Regional MBF, MDO2, and MVO2 were measured during CPR. Following three minutes of CPR, animals (N = 15) were allocated to one of three groups (n = 5): Group 1, epinephrine 0.2 mg/kg; Group 2, phenylephrine 0.1 mg/kg; or Group 3, phenylephrine 1.0 mg/kg. Measurements of regional MBF, MDO2, and MVO2 were repeated after drug administration. Extraction ratios, defined as MVO2/MDO2, were calculated during normal sinus rhythm, CPR, and after drug administration. Defibrillation was attempted 3 1/2 minutes after drug administration. There was no significant difference in MBF, MDO2, MVO2, and extraction ratio during normal sinus rhythm and CPR for any of the groups. Total MBF following drug administration was 67.2 +/- 49.4 mL/min/100 g for the group receiving epinephrine 0.2 mg/kg; 7.0 +/- 7.1 mL/min/100 g for the group receiving phenylephrine 0.1 mg/kg; and 36.7 +/- 21.1 mL/min/100 g for the group receiving phenylephrine 1.0 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of standard doses of epinephrine on myocardial oxygen delivery and utilization during cardiopulmonary resuscitation.

This preliminary study was conducted to evaluate the effects of 0.02 mg/kg of epinephrine (E) on myocardial blood flow (MBF), myocardial oxygen consumption (MVO2), and delivery (MDO2) when administered during CPR after 10-min cardiopulmonary arrest. Five miniature swine were instrumented for MBF measurements using tracer microspheres. Ventricular fibrillation was induced. After 10 min, CPR was begun with a pneumatic compressor. Measurements of MBF, arterial, and coronary sinus blood gases were made. After 3 min of CPR, each animal received 0.02 mg/kg of E. The measurements were repeated and defibrillation was attempted. During CPR, MDO2 and MVO2 were 0.2 +/- 0.3 and 0.2 +/- 0.3 ml/min/100 g tissue, respectively. The myocardial oxygen extraction ratio (ER) was 94.2 +/- 3.0%. After 0.02 mg/kg of E, MDO2 was 1.1 +/- 1.4, MVO2 was 1.0 +/- 1.3, and ER was 93.9 +/- 0.7% (p greater than .05). There were no successful defibrillations. These data indicate that MDO2 improves slightly during CPR after 0.02 mg/kg of E, but it does not meet the oxygen demands of the fibrillating heart.

Animals↗
PubMed1988

Bovine mononuclear cell lines transformed by Theileria parva or Theileria annulata express different subpopulation markers.

Bovine mononuclear cell lines infected with the protozoan parasites Theileria annulata and T. parva have been studied with a panel of monoclonal antibodies reacting with bovine lymphocyte subpopulation markers. All infected lines are MHC class II positive, though the amount of class II antigen expressed varied between lines, and within individual lines there was variation in the proportion of positive cells from 100% with many, to less than 10%. All lines were negative for a macrophage/monocyte marker and for surface IgM. The T. parva lines tested were all positive for BoT4 or BoT8 or both, whereas T. annulata lines were uniformly negative for both of these markers. These results suggest that the two parasites preferentially infect different lymphocyte subpopulations.

Animals↗
PubMed1988

Macrophage-mediated cytostasis and lymphocyte cytotoxicity in cattle immunized with Theileria annulata sporozoites or macroschizont-infected cell lines.

Immunization with either sporozoites or macroschizont-infected cell lines protected calves against challenge with lethal doses of sporozoites of Theileria annulata. Stocks from India, Turkey and Morocco all conferred protective immunity to each other, irrespective of the immunizing regime. Although heterogeneous clinical responses were induced by the two immunizing regimes, both stimulated similar patterns of macrophage cytostasis as expressed as an inhibition of proliferation of macroschizont-infected cell lines. Macrophage cytostasis was detected consistently after immunization and after challenge, arising at the same time as macroschizonts were detectable. Its expression was sustained and inhibited the proliferation of both autologous and allogeneic (BoLA-mismatched) cell lines. In contrast, these two immunizing regimes differed in their ability to stimulate the production of cytotoxic cells. Calves immunized with autologous cell lines or sporozoites developed very transient populations of cytotoxic cells expressing only a low level of specific lysis for autologous infected cells; agglutinating antibodies for immunizing or autologous cell lines were not detected in these calves. Calves immunized with allogeneic cell lines produced cytotoxic cells which were specific only for the immunizing cell lines; these calves also produced antibodies which agglutinated the immunizing cell lines.

Animals↗
PubMed1987

The perchlorate discharge test for examining thyroid function in rats.

A perchlorate discharge test was developed for rats to detect changes in the thyroidal iodide accumulation and organification mechanisms. Rats were pretreated with compounds that alter thyroid function by different mechanisms: SK&F 93479 (an H2-antagonist that enhances pituitary thyroid stimulating hormone drive by increasing thyroid hormone clearance) and propylthiouracil (an inhibitor of iodide organification). Six hours following administration of 125I, either potassium perchlorate (10 mg/kg x 2.5 min) or saline was given i.p. Perchlorate significantly reduced the thyroid: blood 125I ratio in propylthiouracil-treated rats but had no effect in those pretreated with SK&F 93479, indicating an iodide organification block in the former. At the same time thyroidal radioiodide accumulation in SK&F 93479-treated rats (no perchlorate) was enhanced, whereas that in propylthiouracil-treated animals (no perchlorate) was depressed.

Animals↗
PubMed1987

Effects of toxic doses of a novel histamine (H2) antagonist on the rat thyroid gland.

The oral administration of high doses of a histamine H2 antagonist SK&F 93479 (up to 1000 mg/kg/day) to male rats for up to 21 days resulted in alterations in thyroid morphology indicative of increased activity of the thyroid gland. Measurement of thyroidal 125I incorporation substantiated these findings. Treatment with SK&F 93479 resulted in a dose-dependent increase in thyroidal iodide incorporation. This was apparent after a single dose of the compound and was reversible after dosing for 7 days. The increased incorporation of 125I into the thyroid gland was apparently dependent on thyroid-stimulating hormone (TSH) since both hypophysectomy and pretreatment with thyroxine (T4) markedly reduced thyroidal 125I uptake. Hypothalamic thyrotropin-releasing hormone (TRH) and pituitary TSH concentrations were not altered by SK&F 93479 treatment, and in TRH challenge experiments circulating TSH concentrations showed no change from control levels. These data suggest that hypothalamic-pituitary sensitivity was unaltered by treatment with SK&F 93479. Pharmacological ablation of thyroidal mast-cell function did not alter the thyroid response to 125I accumulation after SK&F 93479 dosing, indicating that the action of the compound is probably not dependent on changes in thyroid mast-cell histamine. Circulating T4 and TSH levels were altered in SK&F 93479-treated rats. Generally, T4 levels were reduced 6 hr after dosing and TSH levels were elevated 24 hr after dosing. Triiodothyronine (T3) levels were unaffected by SK&F 93479 treatment. The effect of SK&F 93479 treatment on T4 clearance was measured by examining the elimination of radioactivity from the circulation of rats previously injected with 125I-labelled T4. One oral dose of 1000 mg SK&F 93479/kg markedly increased T4 clearance. These results suggest that SK&F 93479 affects thyroid activity indirectly by a primary effect on T4 clearance. Reductions in circulating T4 lead to increased TSH levels and subsequent stimulation of thyroid activity.

Animals↗