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Biomedical subjects

C G Brown

Publications and source records attributed to C G Brown.

At least 73 records · Page 4Linked to original sources
PubMed1993

Synthesis of tumour necrosis factor-alpha and interferons by mononuclear cells from Theileria annulata-infected cattle.

Bovine macrophage-derived tumour necrosis factor-alpha/cachectin (TNF-alpha) was synthesized when peripheral blood mononuclear cells (PBMC) and purified adherent PBMC from naive and Theileria annulata-infected cattle were incubated in vitro with concanavalin A (Con-A) or bovine recombinant interferon gamma (Bo rIFN-gamma). TNF-alpha production was also induced when adherent PBMC were cultured with T. annulata macroschizont-infected cells. In contrast, non-adherent PBMC from sublethally infected cattle produced interferon (IFN) when incubated with Hu rIL-2, Con-A, phytohaemagglutinin (PHA) or T. annulata macroschizont-infected cells growing as cell lines in vitro. Whilst PBMC from lethally infected cattle spontaneously produced IFN-gamma during advanced stages of infection, the sera of such animals contained type 1 IFN (alpha/beta). IFN was also produced by T. annulata macroschizont-infected cell lines maintained in vitro. This work suggests that cytokines serve as crucial links between proliferating Theileira-infected cells and the characteristic clinical symptoms of tropical theileriosis.

Animals↗
PubMed1992

A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group.

BACKGROUND: Experimental and uncontrolled clinical evidence suggests that intravenous epinephrine in doses higher than currently recommended may improve outcome after cardiac arrest. We conducted a prospective, multicenter study comparing standard-dose epinephrine with high-dose epinephrine in the management of cardiac arrest outside the hospital. METHODS: Adult patients were enrolled in the study if they remained in ventricular fibrillation, or if they had asystole or electromechanical dissociation, at the time the first drug was to be administered to treat the cardiac arrest. Patients were randomly assigned to receive either 0.02 mg of epinephrine per kilogram of body weight (standard-dose group, 632 patients) or 0.2 mg per kilogram (high-dose group, 648 patients), both given intravenously. RESULTS: In the standard-dose group 190 patients (30 percent) had a return of spontaneous circulation, as compared with 217 patients (33 percent) in the high-dose group; 136 patients (22 percent) in the standard-dose group and 145 patients (22 percent) in the high-dose group survived to be admitted to the hospital. Twenty-six patients (4 percent) in the standard-dose group and 31 (5 percent) in the high-dose group survived to discharge from the hospital. Ninety-two percent of the patients discharged in the standard-dose group and 94 percent in the high-dose group were conscious at the time of hospital discharge. None of the differences in outcome between the groups were statistically significant. CONCLUSIONS: In this study, we were unable to demonstrate any difference in the overall rate of return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, or neurologic outcome between patients treated with a standard dose of epinephrine and those treated with a high dose.

Aged↗
PubMed1992

Stage-specific responses following infection with Theileria annulata as evaluated using ELISA.

An enzyme-linked immunosorbent assay (ELISA) using sporozoite, schizont and piroplasm antigens was developed to study the immune response of animals that had been immunised with either Theileria annulata sporozoites or schizont-infected cells and then challenged with sporozoites. The aim was to identify the most suitable antigen for a routine screening test and to compare the sensitivity of the latter with that of the indirect fluorescent antibody test (IFAT). As determined by ELISA, cattle produced antibodies to all three antigens, regardless of the method of immunisation. The schizont antigen was the least sensitive, whereas the sporozoite antigen displayed high pre-inoculation values. In contrast, the piroplasm antigen exhibited low non-specific pre-infection levels and high post-immunisation and post-challenge values according to both ELISA and IFAT. Therefore, the latter was though to be the most appropriate antigen for use in ELISA.

Animals↗
PubMed1992

Model of muscle-tendon interaction during frog semitendinosis fixed-end contractions.

A structural model was developed to explain sarcomere shortening at the expense of tendon lengthening in the frog semitendinosis (ST) muscle-tendon system. The model was based on the data of Lieber et al. [Am. J. Physiol. 261, C86-C92 (1991)], who determined the relationship between the sarcomere length, tendon load (as a fraction of maximum isometric tension) and tendon, bone-tendon junction (BTJ), and aponeurosis strain. The model was generated assuming a finite time-course of cross-bridge attachment [Huxley, Prog. Biophys. 7,255-318 (1957)], an ideal sarcomere length-tension relationship [Gordon et al., J. Physiol. 184, 170-192 (1966)] and an ideal force-velocity relationship [Katz, J. Physiol. 96, 45-64 (1939); Edman, J. Physiol. 291, 143-159 (1979)]. Functionally, sarcomeres operated on three distinct regions of the length-tension curve: (1) regions where the muscle force decreased as sarcomeres shortened (the shallow and steep ascending limbs); (2) regions where the muscle force increased as sarcomeres shortened and there was little passive tension (descending limb, where sarcomere length greater than or equal to 3.0 microns); and (3) regions where the muscle force increased as sarcomeres shortened and there was a significant passive tension (descending limb where sarcomere length greater than 3.0 microns). Using such a physiological model, it was found that the effect of tendon compliance was to 'skew' the sarcomere length-tension curve to the right and to increase the operating range of the muscle-tendon unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tropical theileriosis in Bos taurus and Bos taurus cross Bos indicus calves: response to infection with graded doses of sporozoites of Theileria annulata.

This work extends basic knowledge of tropical theileriosis in taurine and crossbred cattle. Infection of Bos taurus and Bos taurus cross Bos indicus (Sahiwal) calves with graded doses of sporozoites of Theileria annulata (Hissar), an Indian stock of the parasite, showed the following to be dose dependent in both cattle types: the time to appearance and population size of macroschizonts, microschizonts and piroplasms, time and severity of pyrexia, anaemia manifested by erythrocyte counts and haematocrit. All infections were accompanied by a prompt and severe panleucopenia. This effect was dose related in both the taurine and the Sahiwal crossbred calves. Lymphocyte counts returned to preinfection levels in the blood of animals which recovered, but death from theileriosis was characteristically accompanied by a persistent and severe lymphocytopenia. Flow cytometry using monoclonal antibodies to bovine mononuclear cells was used to identify the lymphocyte subsets involved in lymphocytopenia. The outcome of infection was dose dependent in the crossbred calves but not in taurine calves. Although the results obtained did not differ qualitatively between the two cattle types, they provided some preliminary evidence for resistance to tropical theileriosis in Sahiwal crossbred calves.

Animals↗
PubMed1992

Common and stage-specific antigens of Theileria annulata.

Western blot analysis of Theileria annulata antigens was carried out using sera collected from cattle which had been immunised and challenged with either T. annulata sporozoites or schizont-infected cells. Three antigens between 71 and 73 kDa proved to be common to the three stages of parasite studied: sporozoites, schizonts and piroplasms. An antigen was found at 32 kDa which was specific to T. annulata piroplasms. Results were reproducible using sera from Morocco and the UK. At least one of the proteins at 71-73 kDa, but not that at 32 kDa were also recognised by sera from animals infected with Babesia species.

Animals↗
PubMed1992

Regional cerebral blood flow with manual internal cardiac massage versus direct mechanical ventricular assistance.

STUDY HYPOTHESIS: Previous studies have not discerned the best method for generating regional cerebral blood flow during internal cardiac massage. We hypothesized that regional cerebral blood flow generated by a mechanical method--direct mechanical ventricular assistance (DMVA)--would be superior to manual internal cardiac massage (MAN). STUDY POPULATION: Twelve adult Yucatan minipigs weighing more than 44 kg each were studied. METHODS: Swine were instrumented for regional cerebral blood flow measurements using tracer microspheres. After 15 minutes of ventricular fibrillation, swine were randomized to receive either MAN or DMVA. Regional cerebral blood flow was measured during normal sinus rhythm and at one minute (VF-1) and six minutes (VF-2) after initiation of circulatory support. Regional cerebral blood flow values were compared using a Wilcoxon rank sum test. RESULTS: During VF-1, there was a tendency for DMVA to produce greater regional cerebral blood flow than MAN, although these differences were not statistically significant (DMVA vs MAN as mL/min/100 g): cerebral cortex, 28 versus 11; cerebellum, 49 versus 22; midbrain, 43 versus 16; pons, 55 versus 18; medulla, 55 versus 19; and spinal cord, 33 versus 10. During VF-2, DMVA produced greater regional cerebral blood flows than were produced by MAN: cerebral cortex, 39 versus 12 (P less than .06); cerebellum, 58 versus 20 (P less than 0.5); midbrain, 50 versus 18 (P less than .05); pons, 52 versus 22 (P less than .06); medulla, 53 versus 20 (P less than .05); and spinal cord, 31 versus 12 (P less than .05). CONCLUSION: DMVA produces greater regional cerebral blood flow than is produced during MAN after 15 minutes of ventricular fibrillation. DMVA is effective at maintaining regional cerebral blood flow after a prolonged cardiac arrest.

Animals↗
PubMed1992

Theileria annulata-infected cells produce abundant proteases whose activity is reduced by long-term cell culture.

Lysates of Theileria annulata-infected bovine lymphoblastoid cells and their uninfected counterparts were tested for protease activity using gelatin substrate SDS-PAGE. The infected cells produced a number of extra activities at pH 8.0 in the presence of Ca2+. Calcium was found to enhance the activities but was not an absolute requirement. Studies using inhibitors, including E64, 3,4-dichloroisocoumarin, pepstatin and 1, 10-phenanthroline suggested that the activities were metalloproteases. We analysed two vaccine lines; the Ode line from India and the Ankara Pendik line from Turkey. In the Ode line the later passage had very much reduced levels of the enzyme activities. In the case of the Ankara Pendik line both stages analysed had very low protease activities, but a reduction from the early to late passage was also observed. The reduction in the level of protease activity was also observed as a gradual process during on-going culture of lines derived from the Hissar and Ode stocks. In the Ode line we demonstrated a parallel decrease in the production of microschizonts upon temperature shift in vitro.

Animals↗
PubMed1992

Cytokines inhibit the development of trophozoite-infected cells of Theileria annulata and Theileria parva but enhance the proliferation of macroschizont-infected cell lines.

The following bovine (Bo) and human (Hu) cytokines--Bo rTNF-a, Bo rIFN-g, Hu IFN-a, Hu rIL-1, Hu rIL-2--significantly inhibited the in vitro development of trophozoite-infected cells of three stocks of Theileria annulata and of Theileria parva (Muguga). However, none of these cytokines inhibited the proliferation of established T. annulata or T. parva macroschizont-infected cell lines. Indeed, Bo rTNF-a and Hu rIL-2 consistently enhanced the proliferation of macroschizont-infected cell lines of both species and the blastogenesis of uninfected lymphocytes in trophozoite-infected cultures. These results suggest that cytokines could help in resistance to challenge infections by preventing the further development of trophozoite-infected cells but provide no evidence that any of the above cytokines directly help to resolve primary infections by inhibiting the growth of macroschizont-infected cells. These findings also suggest that both TNF-a and IL-2 could play a role in the pathogenesis of Theileria infections by promoting the proliferation of macroschizont-infected cells and the associated lymphoid hyperplasia.

Animals↗
PubMed1992

Sarcomere length-joint angle relationships of seven frog hindlimb muscles.

The sarcomere length-joint angle relationship was measured in 7 different muscle-joint complexes (n = 43 muscles) of the frog hindlimb (Rana pipiens). Muscles studied included the cruralis, iliacus internus, gastrocnemius, gluteus magnus, gracilis major, semimembranosus and the semitendinosus. Muscle-joint complexes were mounted in a jig and submerged in chilled Ringer's solution. Joints were rotated throughout their range of motion, while sarcomere length was measured by laser diffraction. Muscles were then formalin fixed and architectural properties determined by microdissection of individual muscle fibers. Sarcomere length change per degree of joint rotation (dLs/d theta) ranged from a low of 3.7 nm/degree for the cruralis muscle acting at the knee to a high of 12.5 nm/degree for the semitendinosus muscle acting at the hip. Values for dLs/d theta were significantly different between all muscles (p < 0.001), and dLs/d theta values for muscles acting at the hip were significantly greater than those for muscles acting at the knee (p < 0.005). dLs/d theta was negatively correlated with fiber length, suggesting a balance between fiber length and moment arm in most muscle-joint systems. However, many exceptions to this generalization were noted. These data suggest that different muscle-joint systems are 'designed' for differential contribution of muscle force production to the joint torque profile. The low variability of these data also suggests that sarcomere number is tightly regulated in these muscle-joint systems but not simply as a result of the total in vivo muscle excursion.

Animals↗
PubMed1991

Frequency analysis of the human and swine electrocardiogram during ventricular fibrillation.

Recent studies in swine have suggested that estimating the duration of ventricular fibrillation (VF) could have important implications regarding the selection of the best therapeutic intervention during cardiopulmonary resuscitation (CPR). Successful defibrillation resulting in a pulsatile rhythm is more likely with VF of short duration, whereas VF of longer duration may require interventions designed to augment myocardial blood flow prior to defibrillation. Duration of VF has been estimated in a swine model by modelling the median frequency (FM) of the VF ECG signal. The purpose of this study was to characterize the time course of the FM ECG signal in humans during VF and compare the characteristics of the human VF ECG signal to that previously described in swine. Seven two-channel human VF ECG recordings were analyzed via fast Fourier transformation. The FM was extracted from each four-second segment of the recordings and plotted versus time. The FM in humans followed a repeatable time course during VF. The human data revealed an FM which had two peaks with subsequent gradual decline. The data in swine revealed an FM during VF which decreased initially then increased to a peak followed by a gradual decline. Our preliminary results demonstrate that a characteristic median frequency exists in humans which could be used to estimate the duration of VF.

Animals↗
PubMed1991

Median frequency--a new parameter for predicting defibrillation success rate.

STUDY HYPOTHESIS: Current American Heart Association guidelines recommend immediate defibrillation of ventricular fibrillation. When this is unsuccessful, there are no guidelines to help determine the optimum time at which to defibrillate after the administration of an alpha-adrenergic agonist. Previous studies have shown that the median frequency of the ventricular fibrillation ECG signal correlates with myocardial perfusion during CPR. We hypothesized that median frequency could predict the success of defibrillation and thus accurately determine the most appropriate time at which to defibrillate during ventricular fibrillation. STUDY POPULATION: Twenty-two mixed-breed swine weighing more than 15 kg were studied. METHODS: Ventricular fibrillation was induced electrically, and the ventricular fibrillation ECG signal was analyzed using fast Fourier analysis. After ten minutes of ventricular fibrillation, mechanical CPR was begun. After three minutes of CPR, the animals received one of three alpha-adrenergic agonists and CPR was continued. Defibrillation was attempted three and one-half minutes after drug administration. The average median frequency 20 seconds before defibrillation was calculated. Sensitivity and specificity of median frequency with respect to defibrillation success were determined. RESULTS: A median frequency of 9.14 Hz had a sensitivity of 100% and a specificity of 92.31% in predicting the results of defibrillation in this model. CONCLUSION: The median frequency may serve as a valuable parameter to guide defibrillation therapy during ventricular fibrillation.

Animals↗
PubMed1991

Estimation of myocardial ischemic injury during ventricular fibrillation with total circulatory arrest using high-energy phosphates and lactate as metabolic markers.

STUDY OBJECTIVE: To define the time course of myocardial ischemic injury using high-energy phosphate (HEP) depletion and the cessation of lactate production as metabolic markers. SETTING: Data were collected in a laboratory animal model. TYPE OF PARTICIPANTS: Ten immature mixed breed swine weighing 23.2 +/- 3.5 kg. DESIGN: After thoracotomy, transmural myocardial biopsies were taken in vivo during normal sinus rhythm and at designated times during ventricular fibrillation with total circulatory arrest (VF-TCA). MEASUREMENTS AND MAIN RESULTS: Frozen tissue samples were analyzed for adenine nucleotides, by high-performance liquid chromatography, and lactate by enzymatic assay. At five minutes of VF-TCA, myocardial adenosine triphosphate averaged 50% of control. At 15 minutes of VF-TCA, 89% of animals had myocardial adenosine triphosphate levels above 20% of control and adenylate charge ratio above 0.60. With more than 30 minutes of VF-TCA, all animals had adenosine triphosphate levels below 10% of control and adenylate charge ratio below 0.30. In addition, myocardial lactate levels plateaued after 30 minutes of VF-TCA, indicating the cessation of lactate production. CONCLUSION: These results suggest that the myocardium can tolerate VF-TCA for as long as 15 minutes without irreversible injury; however, post-ischemic myocardial dysfunction may occur after as little as five minutes of VF-TCA. With more than 30 minutes of VF-TCA, myocardial injury is likely to be irreversible.

Adenosine Diphosphate↗
PubMed1991

Production of interferons by bovine and ovine cell lines infected with Theileria annulata or Theileria parva.

Three bovine cell lines and four ovine cell lines infected with Theileria parva or Theileria annulata were examined for the production of interferon (IFN). Biologically active IFN was detected in the tissue culture supernatants of four of the cell lines. Only one, a bovine cell line infected with T. parva, produced IFN-gamma as measured by specific neutralization with a monoclonal antibody to bovine IFN-gamma. This observation was confirmed by analysing RNA from the cell lines on Northern blots using an IFN-gamma cDNA probe. The other three cell lines which produced IFN were infected with T. annulata. The IFN produced by those lines was not IFN-gamma.

Animals↗
PubMed1991

Frog semitendinosis tendon load-strain and stress-strain properties during passive loading.

The mechanical properties of the frog semitendinosis (ST) tendon, bone-tendon junction, and aponeurosis were measured during passive loading to a tension equal to maximum isometric tension (Po). Stiffness and strain in these regions continuously increased as load increased. Tendon stiffness was approximately four times the aponeurosis stiffness. Tendon Young's modulus at Po was only 188 MPa, which is approximately 10 times less than the modulus reported for most mammalian tendons. Similarly, tendon stress at Po was only approximately 3 MPa, which is also less than that predicted for many tendons. Tendon strain at Po was approximately 2% after passive loading. We conclude that different regions of the frog ST tendon have different mechanical properties and that the frog ST tendon operates physiologically in the "toe" region of the stress-strain curve with a variable stiffness that increases with load. Taken together, these results have significant implications in understanding muscle-tendon design and neuromotor control strategies.

Animals↗
PubMed1991

Assessing the scientific strength of Chile.

We use analysis of co-citation and relative citation rates to assess the scientific strength of Chile as compared with other developing countries and to evaluate the potential for increased international collaboration between Chile and the United States in science and engineering. Co-citation is the citation of two scientific papers by a third paper. By examining frequency and patterns of co-citation, the intellectual structure and evolution of scientific disciplines and research specialties can be traced. Chile is especially "strong", as defined by the co-citation model we employ, in biomedicine and clinical medicine, and in astronomy. A relative citation rate is the ratio of the number of citations a paper receives to the average number of citations for all papers published in the same journal over time. Analysis of relative citation rates of papers published by authors with Chilean addresses show that Chilean physics, including earth and space sciences, is of unusually high quality, considerably higher than any other developing country and comparable to several industrialized countries. We conclude that Chile's scientific capacity is advanced enough to absorb and benefit significantly from strategic additions to the country's resources and capabilities for research. These would include increases in: exchanges of researchers in specific fields with U.S. and other Latin American academic, industrial, and government scientists and engineers; training at outstanding U.S. and Latin American institutions; laboratory equipment, computer time, communications links, and library materials; and funding from U.S. and international organizations. It is also apparent that Chile is strong enough in certain fields to cooperate with the U.S. in mutually beneficial international efforts.

Authorship↗