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Biomedical subjects

P Barnard

Publications and source records attributed to P Barnard.

16 recordsLinked to original sources

Oxygen and carbon dioxide kinetic challenges for thermophilic mineral bioleaching processes.

Agitated bacterial tank bioleaching reactors are currently sparged with air to satisfy both oxygen and CO(2) requirements of microbial cells. Under high-sulphide loading conditions, as is the case with high-grade metal sulphide concentrates, the microbial and chemical demand for oxygen is significantly increased during the bioleaching process. Sparging with enriched oxygen gas may offer an alternative process option to increased agitation and sparged aeration, to overcome the mass transfer difficulties at elevated temperatures where thermophilic Archaea, rather than Bacteria, are used. In the case of air sparging, the DO (dissolved oxygen) concentration in tank reactors could not be increased to a point where it would become inhibitory due to the limited oxygen content of air (20.9% O(2)). The use of enriched oxygen in such reactors at large scale does, however, pose its own set of process risks. The first aim of this investigation was, therefore, to determine the effects of various DO concentrations, in both the limiting and inhibitory ranges, on the microbial activity of Sulfolobus sp. U40813, a typical thermophilic mineral-leaching archaeon. Secondly, the effect of CO(2) concentration on the rate of ferrous iron oxidation was investigated. Both the oxygen and CO(2) kinetics were examined in controlled batch cultures at 78 degrees C, using ferrous sulphate and potassium tetrathionate as energy sources. The optimal DO concentration for iron oxidation was found to be between 1.5 and 4.1 mg.l(-1). The use of elevated DO concentrations (above 4.1 mg.l(-1)) inhibited the ferrous oxidation rates. The optimal gas CO(2) concentration for ferrous iron oxidation was found to be in the range 7-17% (v/v). The iron oxidation rates were, however, severely limited at CO(2) concentrations less than 7%, indicating that the CO(2) supply was limiting in this range and inhibited the microbial growth rate.

Carbon Dioxide↗

Development of respirometry methods to assess the microbial activity of thermophilic bioleaching archaea.

Respirometry methods have been used for many years to assess the microbial activity of mainly heterotrophic bacteria. Using this technique, the consumption of oxygen and evolution of carbon dioxide for heterotrophic carbon catabolism can be used to assess microbial activity. In the case of autotrophic bioleaching bacteria, carbon dioxide is used as a carbon source resulting in the consumption of both oxygen and carbon dioxide. The use of such respirometry techniques at high temperatures (up to 80 degrees C) for the investigation of bioleaching Archaea, however, poses particular difficulties. At these elevated temperatures, the solubility of oxygen into the liquid phase is particularly poor. This work details specific methods by which high temperature constraints are overcome while monitoring the activity of thermophilic Archaea using a Micro-Oxymax respirometer (Columbus Instruments). The use of elevated headspace oxygen concentrations, in order to overcome low oxygen solubility, is demonstrated as well as the effect of such elevated oxygen concentrations on microbial oxygen consumption rates. The relative rates of oxygen and carbon dioxide consumption are also illustrated during the oxidation of a chalcopyrite concentrate. In addition, this paper details generic methods by which respirometry data can be used to quantify inhibitory effects of a compound such as Na(2)SO(4). The further use of such data in predicting minimum hydraulic reactor retention times for continuous culture bioleaching reactors, as a function of concentration of potentially inhibitory compounds, is also demonstrated.

Archaea↗

Empirical model for the autotrophic biodegradation of thiocyanate in an activated sludge reactor.

AIMS: The aim of this investigation was to develop an empirical model for the autotrophic biodegradation of thiocyanate using an activated sludge reactor. METHODS AND RESULTS: The methods used for this purpose included the use of a laboratory scale activated sludge reactor unit using thiocyante feed concentrations from 200 to 550 mg x l(-1). Reactor effluent concentrations of <1 mg x l(-1) thiocyanate were consistently achieved for the entire duration of the investigation at a hydraulic retention time of 8 h, solids (biomass) retention of 18 h and biomass (dry weight) concentrations ranging from 2 to 4 g x l(-1). A biomass specific degradation rate factor was used to relate thiocyanate degradation in the reactor to the prevailing biomass and thiocyanate feed concentrations. A maximum biomass specific degradation rate of 16 mg(-1) x g(-1) x h(-1) (mg thiocyanate consumed per gram biomass per hour) was achieved at a thiocyanate feed concentration of 550 mg x l(-1). The overall yield coefficient was found to be 0.086 (biomass dry weight produced per mass of thiocyanate consumed). CONCLUSION: Using the results generated by this investigation, an empirical model was developed, based on thiocyanate feed concentration and reactor biomass concentration, to calculate the required absolute hydraulic retention time at which a single-stage continuously stirred tank activated sludge reactor could be operated in order to achieve an effluent concentration of <1 mg x l(-1). The use of an empirical model rather than a mechanistic-based kinetic model was proposed due to the low prevailing thiocyanate concentrations in the reactor. SIGNIFICANCE AND IMPACT OF THE STUDY: These results represent the first empirical model, based on a comprehensive data set, that could be used for the design of thiocyanate-degrading activated sludge systems.

Bacteria↗

The human papillomavirus E7 protein is able to inhibit the antiviral and anti-growth functions of interferon-alpha.

It is now well recognized that cervical cancer is caused by infection with certain human papillomavirus (HPV) subtypes and while interferon-alpha (IFN-alpha) is used to treat HPV-infected lesions, HPV appears to have developed a means to avoid the effects of IFN-alpha. Clinically, resistance appears to be associated with the expression of the E7 oncoprotein. Here we investigated the effects of expression in cells of the E7 protein from high- and low-risk papillomavirus subtypes on a range of responses to IFN-alpha. 2fTGH, a cell line dependent on IFN-alpha for growth in selection medium, grew significantly less well in the presence of E7, and the antiproliferative effects of IFN-alpha upon epithelial cells was lost upon E7 expression. The antiviral effects of IFN-alpha were abrogated in E7-expressing cells. Loss of response to IFN-alpha was found to occur in both high- and low-risk papillomaviruses. Finally, deletion of amino acids 21-24 of HPV type 16 E7 protein partially reversed repression. We conclude that E7 inhibits the functional effects of IFN-alpha and that this property is shared by all HPV subtypes tested.

Antiviral Agents↗

The human papillomavirus E7 oncoprotein abrogates signaling mediated by interferon-alpha.

Greater than 95% of all cervical carcinomas have been found to be associated with "high-risk" human papillomavirus (mainly types 16 and 18) infections, with the viral E6 and E7 oncoproteins essential for neoplastic development and maintenance. Interferon-alpha (IFNalpha) is used in the treatment of HPV infections yet both in vivo and in vitro data suggest that the virus has developed mechanisms to avoid the effects of interferon. Here we show that the HPV16 E7 oncoprotein is able to inhibit the induction of IFNalpha-inducible genes but has no effect of IFNgamma-inducible genes. Expression of E7 correlates with the loss of formation of the interferon-stimulated gene factor 3 (ISGF3) transcription complex. Moreover, in the presence of E7, p48, the DNA-binding component of ISGF3, was unable to translocate to the nucleus upon IFNalpha stimulation. A direct protein-protein interaction was identified between E7 and p48 with the site of interaction within E7 defined as the region between amino acids 17-37, a domain that includes the binding site for the retinoblastoma protein, pRb. These results suggest that HPV, via E7, targets p48, resulting in the loss of IFNalpha-mediated signal transduction and may provide a means by which HPV can avoid the innate immune system.

Blotting, Western↗

Potential strategies utilised by papillomavirus to evade host immunity.

The co-evolution of papillomaviruses (PV) and their mammalian hosts has produced mechanisms by which PV might avoid specific and non-specific host immune responses. Low level expression of PV proteins in infected basal epithelial cells, together with an absence of inflammation and of virus-induced cell lysis, restricts the opportunity for effective PV protein presentation to immunocytes by dendritic cells. Additionally, PV early proteins, by a range of mechanisms, may restrict the efficacy of antigen presentation by these cells. Should an immune response be induced to PV antigens, resting keratinocytes (KC) appear resistant to interferon-gamma-enhanced mechanisms of cytotoxic T-lymphocyte (CTL)-mediated lysis, and expression of PV antigens by resting KC can tolerise PV-specific CTL. Thus, KC, in the absence of inflammation, may represent an immunologically privileged site for PV infection. Together, these mechanisms play a part in allowing persistence of PV-induced proliferative skin lesions for months to years, even in immunocompetent hosts.

Animals↗

A case of chronic mountain sickness diagnosed by routine pulmonary function tests.

In summary, this is a patient who presented with respiratory acidosis and cor pulmonale. The major diagnostic challenge was in differentiating primary cardiopulmonary disease from a central abnormality of ventilatory drive. The arterial blood gases showed a normal A-a gradient suggesting hypoventilation as the etiology of his hypoxemia. Pulmonary function testing showed air trapping, but a relatively normal FEV1/FVC and airways resistance. The literature suggests that most altitude natives have depressed hypoxemic and hypercapnic drives with a distinct subset demonstrating a profoundly depressed drive to ventilation. This latter group has been labeled as having chronic mountain sickness or Monge's disease. As one might expect, ventilatory control during sleep is also abnormal in these patients with CMS. Our patient indeed showed typical frequent severe desaturations with hypopnea. The diagnosis of CMS in our patient was made with routine arterial blood gases and standard pulmonary function tests. Additional tests of ventilatory responsiveness to oxygen and carbon dioxide could have been performed, but are not necessary to make the diagnosis.

Altitude Sickness↗

Pulmonary function after heart-lung transplantation using larger donor organs.

Restrictive pulmonary function after heart-lung transplantation (HLT) has been attributed to the use of smaller donor lungs and/or an inability to generate normal negative pleural pressures. Pleural pressure generation depends on both the size of the recipient thoracic cage and its neuromuscular integrity. To determine whether lung volumes after heart-lung transplantation are more dependent on donor lung size or on recipient chest wall characteristics, seven HLT recipients were evaluated before and after transplantation. Postoperative values initially (average, 2 months), 6, and 12 months after transplantation were compared with predicted lung volumes for the recipient and donor organs. TLC dropped from a mean of 5.2 +/- 0.5 L preoperatively to 3.7 +/- 0.3 L (p less than 0.05) 2 months after HLT, but it improved with time and ultimately was not different from preoperative values. The predicted TLC of the HLT donor organs were significantly larger than those of the recipient's predicted TLC, with a mean of 6.9 +/- 0.4 versus 5.3 +/- 0.3 L (p less than 0.05). DLCO, arterial PO2, and PCO2 did not change after surgery. Within limits, larger donor lungs appear to adapt to the constraints of the recipient chest and may be used with clinical success, without apparent adverse effects.

Adolescent↗

Time-dependent effect of hypoxia on carotid body chemosensory function.

The time-dependent effects of hypoxia on the discharge rate carotid chemoreceptors were measured in anesthetized cats. Hypoxic exposure of two different durations were used: a short-term exposure (2-3 h) was used to measure the response of the same carotid chemoreceptors; and a long-term exposure (28 days at inspired PO2 of 70 Torr) to study carotid chemoreceptor properties in one group of cats relative to those of a control group. In the chronically hypoxic and control groups, determinations were made of the 1) steady-state responses to four levels of arterial PO2 (PaO2) at constant levels of arterial PCO2; 2) steady-state responses to acute hypercapnia during hyperoxia; and 3) maximal discharge rates during anoxia. We found that the acute responses of carotid chemoreceptor afferents to a given level of hypoxia (PaO2 = 30-40 Torr) did not significantly change within 2-3 h. After long-term exposure the carotid chemoreceptor responses to hypoxia significantly increased, with no significant changes in the hypercapnic response and in the maximal discharge rate during anoxia. We conclude that isocapnic hypoxia may not elicit a sufficient cellular response within 2-3 h in the cat carotid body to sensitize the O2 responsive mechanism, but hypoxia of longer duration will sensitize such a mechanism, thereby augmenting the chemosensory activity.

Acid-Base Equilibrium↗

Reduction of hypertonicity by early casting in a comatose head-injured individual. A case report.

The patient in this report sustained a closed-head injury. Within six days of the injury, he demonstrated generalized hypertonicity accompanied by alternating strong decerebrate and decorticate posturing. By Day 10 after injury, normal passive ROM could no longer be maintained using neurophysiological therapeutic techniques. Therefore, we applied plaster casts to both ankles. Within 24 hours of cast application, the patient's general hypertonus had decreased, and by 72 hours after casting, the patient demonstrated seemingly purposeful movements of the left extremities. Although casts have been used previously to maintain ROM or decrease contractures and to improve balance of muscle function of the joint that was immobilized, we believe that the marked, generalized reduction in tone in body segments far removed from the ankles was an important clinical observation. We explored several possible mechanisms for these observations. Because the usual casting conditions for reflex inhibition were not obtained with this patient, other factors were suggested to be important: total even pressure and neutral warmth. Research is currently in progress at the Medical Center Hospital of Vermont to study further the effects of plaster casting and to understand the mechanisms underlying the effects.

Accidents, Home↗

Dopaminergic efferent inhibition of carotid body chemoreceptors in chronically hypoxic cats.

The observations that the dopamine concentration of the carotid body and efferent inhibition of carotid chemoreceptors are increased during chronic hypoxia led to the hypothesis that the inhibition was due to the effect of an increased dopamine release by the activity of carotid sinus nerve (CSN) efferents. The hypothesis was tested by measuring the effect of dopamine receptor blockade on efferent inhibition of carotid chemosensory responses to graded levels of arterial O2 partial pressure in chronically hypoxic and normoxic cats. Chronically hypoxic cats were prepared by exposing the cats to 10% O2 at sea level for 30-34 days. Carotid chemosensory activity was first measured from a slip of an otherwise intact CSN. The measurements were then repeated after sectioning the remaining nerve trunk. The effect of sectioning the CSN provided the measure of efferent inhibition. In each group of cats the effects of sectioning the CSN with and without dopamine receptor blockade by haloperidol were also studied. CSN section augmented the chemosensory responses in the chronically hypoxic cats. Haloperidol, a dopamine antagonist, augmented the responses further, indicating that a part of the endogenous dopamine effect was independent of the CSN efferents. After haloperidol treatment CSN section did not influence the chemosensory responses. This study confirmed that the efferent inhibition significantly increased in the chronically hypoxic cats and demonstrated that haloperidol blocked the efferent inhibition, suggesting that the mechanism of the augmented inhibition is dopaminergic.

Animals↗

Efferent inhibition of carotid body chemoreception in chronically hypoxic cats.

The effects of chronic hypoxia on carotid chemoreceptor afferent activity before and after sectioning the carotid sinus nerves (CSN) were studied in cats exposed to 10% O2 for 21-49 days in a chamber at sea level. For comparison, chronically normoxic cats at sea level were also studied. The cats were anesthetized, paucifiber preparation for the measurement of carotid chemosensory activity from a small slip of CSN was made, and their steady-state responses to 4-5 levels of arterial pressure of O2 (PaO2) at a constant PaCO2 and to 3-4 levels of PaCO2 in hyperoxia were measured before and after sectioning the CSN. The chemosensory response to hypoxia in the cats with intact CSN after chronic exposure to hypoxia was not reduced relative to the cats that breathed room air at sea level. Sectioning the CSN significantly augmented the chemosensory responses to hypoxia in all the chronically hypoxic but not significantly in the normoxic cats. The responses to moderate hypercapnia during hyperoxia were not significantly changed by cutting the CSN in either group. We conclude that there is a significant CSN efferent inhibition of chemosensory activity due to chronic hypoxia in the cat. This implies that without the efferent inhibition the hypoxic chemosensitivity is increased by chronic hypoxia.

Animals↗

Asking multiple questions about several items: the design of matrix structures on application forms.

It is common practice on application forms to locate questions in column headings. Two experiments are reported both showing that this yields poorer performance than having the same questions as row headings. Siting questions in row headings also makes it easier to include short notes alongside the questions, rather than having them located elsewhere on the form. When several questions share a column or row heading the form filler must use letter codes to indicate which question is being answered. The present data show that the use of letter codes can lead to unnecessary errors and wastes time. It is preferable to arrange the information in a matrix so that answers can be given as ticks.

Journal Article↗

'Just fill in this form' - a review for designers.

This paper reviews the behavioural research, particularly on language and comprehension, which can be related to the design of forms. Such research gives rise to a number of simple rules which can be implemented by forms' designers. These rules concern the structure, content and organisation of sentences and questions. The paper illustrates how these rules can be applied to forms currently in use. Research findings which point to exceptions to the general rules are discussed in an appendix. The paper recognises that we do not yet have enough information to design perfect forms, but that there is enough for many forms to be improved and potential pitfalls avoided.

Journal Article↗