A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements of Doctor of Philosophy. Johannesburg 1991 / Trimethoprim is a broad-spectrum antimicrobial agent frequently used either in combination with sulphamethoxazole (cotrimoxazole) or alone in the treatment of urinary and respiratory tract infections. Since the introduction of this drug in 1969 resistance to it has been monitored in several centres in Europe continuously but only intermittently in the United States of America and developing countries in Africa, Asia, Central and South America. In Europe the incidence of trimethoprim resistance has increased significantly in the last 20 years. In developing countries no trends have been established but the incidence of resistance appears to be greater in these countries than in Europe or the USA. / IT2018

A unique undescribed gram-negative rod is extensively characterized in this study. The cells of this unusual water isolate measure 1.2 x 6.5 microns. The most distinguishing characteristic of the bacterium is a polar tuft of 35-40 flagella that aggregate to function as a single organelle which is visible under phase contrast.

This study explored how psychodynamically oriented therapists understand and work with negative racial sentiments arising in traumatized clients. One of the aims of the study was to highlight and examine the technical, countertransferencial and ethical dilemmas faced when a patient brings ‘politically difficult’ material infused with negative racial sentiment to therapy. It was hoped that information gleaned would contribute to theoretical and technical understanding of this phenomenon and assist in working with such negative racial sentiments. In order to investigate the research questions eight therapists who identified themselves as ‘psychodynamically-oriented’ participated in semi-structured interviews on the topic of negative racial sentiment (NRS) in therapy. The study was located in the qualitative research tradition, and interview transcripts were subject to a critical thematic content analysis. The main themes were identified and presented under three sections, namely: how therapists understand, work with and respond to the phenomenon of NRS in traumatized clients. Understandings included the formation of NRS as inter alia reflecting the use of defenses such as splitting, projection, projective identification, the triumph of the bad object and a breakdown in the capacity to symbolize. Tensions in understanding the phenomenon of NRS post-trauma and related latent themes were also identified. Therapists’ approaches to working with NRS included the use of a range of implicit assessment criteria such as, whether, for example, the patient’s response was experienced as ego-dystonic or ego-syntonic. Technical strategies for intervention included adherence to a working model, interpretive interventions and cognitive strategies. The participating therapists’ countertransferential responses to negative racial sentiment were categorized, taking the form of: negative feeling towards or disidentification from the patient; negative feeling towards the perpetrator or identification with the patient and therapeutic impasse. Some guidelines proposed by the participating therapists for managing NRS, as it occurs in psychotherapy with traumatized clients, are presented.

Thesis advisor: Elizabeth Kensinger / Thesis advisor: Katherine Mickley / Current research suggests that viewing complex scenes composed of a background and a negative, centralized image results in an emotion-induced memory trade-off. This trade-off is often characterized by high rates of memory accuracy for negative central images at the expense of a neutral background. In the present study, I explored whether the same trade-off effect is present for positive emotional stimuli. Therefore, when viewing complex scenes composed of a background and a positive central image, do people tend to remember the positive image more than they do the background? I examined two related research questions: (1) will positive scene components elicit an emotional memory trade-off effect? and (2) how does the passage of time, with and without sleep, influence positive scene components in comparison to negative scene components? Participants were separated into a sleep group and a wake group. The experiment consisted of two parts: the first was a viewing of 90 compound scenes and the second included a memory recognition test. Although the trade-off effect was present for negative valence items as well as positive objects, no main group effect was found. In other words, the emotional memory trade-off effect was not enhanced with sleep. / Thesis (BA) — Boston College, 2010. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Psychology Honors Program. / Discipline: Psychology.

This paper analyzes the controllability of constant coefficient linear differential equations and presents two proofs of a major theorem on controllability. Properties of nearly-non-negative matrices are discussed and in particular a theorem on the behavior of the exponential matrix of nearly-non-negative matrices is proven. These results are then used to prove that the reachable set for systems with nearly-non-negative matrices is limited to the positive hyperoctant.

Animal research suggests that exposure to inescapable stressors can lead to an endogenous opioid-mediated form of pain inhibition, known as stress-induced analgesia (SIA). Similar results have been found with humans, although the literature is much less extensive and at times contradictory where uncontrollable stressors have led to an increase, rather than a decrease in pain. More recently, there has been some suggestion that emotions play an important role in pain modulation, and that particular negative moods are associated with opioid-mediated hypoalgesia. This research aimed to clarify the psychological (cognitive and affective) factors underlying endogenous opioid-mediated pain inhibition in humans. The purpose of Study 1 was to examine the effects of stressor controllability and predictability on pain intensity (PI) and unpleasantness (UP) ratings during a cold pressor task (CPT) in 56 male and female subjects. The stressor involved a timed mental arithmetic task during which three moderately noxious electrical shocks were delivered. Although subjects were informed that shock delivery was contingent on math performance, the shock schedule was preset and identical across conditions. Perceived control over the shocks was manipulated between subjects by altering the difficulty of the math task. Shock predictability was manipulated by changing the colour of the computer screen to warn of an impending shock. Subjects were randomly allocated to four experimental conditions (controllable-predictable, controllable-unpredictable, uncontrollable-predictable, and uncontrollable-unpredictable shocks). Visual analogue ratings of ‘perceived self-efficacy’ (to avoid the shocks) and mood (anxiety, confusion, discouragement, anger, sluggishness, liveliness) were completed before, during and after the math task. Significantly greater discouragement and lower self-efficacy was reported in ‘uncontrollable’ conditions indicating that ‘controllability’ was manipulated effectively. Results indicated that a perceived lack of control over shocks during the math task led to significantly greater decreases in PI, but not UP, ratings during the last stages of a 4-minute fixed interval CPT after the math task. Shock predictability failed to influence subjective pain ratings alone; however, unpredictability interacted with lack of control to initially increase pain, followed by analgesia. Stress-induced increases in negative affect (anxiety, discouragement, anger) were associated with decreases in cold pressor PI, but with increased shock PI and UP during the math task. It was concluded that lack of control over an aversive event and negative affect led to SIA during a prolonged pain stimulus, whereas shock predictability had little influence on pain. In Study 2, 70 male and female subjects received either an opioid antagonist (naltrexone) or a placebo before the math task (using a double-blind, counterbalanced design), in order to determine the role of endogenous opioids in SIA. Subjects were randomly assigned to one of three experimental conditions to investigate whether the shocks themselves may have contributed to analgesia observed after the math task: (1) easy task-few shocks, (2) hard task-few shocks, (3) hard task-many shocks. Increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), anxiety, anger and discouragement indicated that negative affect and sympathetic arousal were induced during the math task. Endogenous opioids inhibited the rise in anger, but not discouragement or anxiety, during the math task. There was some evidence that perceived lack of control over shocks, and not the shocks themselves, led to opioid-mediated decreases in cold pressor UP after the math task. In correlational analyses, discouraged subjects under opioid blockade reported more cold pressor UP after the math task than their placebo counterparts. However, this effect was not strong enough to reach statistical significance in regression analyses. Anxiety, anger, discouragement and lack of control over shocks increased shock PI and UP during the math task. A growing body of research with normotensive subjects has linked increased cardiovascular activity with insensitivity to pain, but the role of endogenous opioids remains contentious. In addition to the investigations outlined above, Study 2 aimed to examine the contribution of endogenous opioids in the cardiovascular-pain relationship. However, there was no evidence of an interaction between pain and cardiovascular activity in this study. Study 3 was carried out to investigate opioid involvement in the effects of an uncontrollable stressor and stress-induced negative mood on cold pressor PI, UP and pain tolerance, and onset/thresholds of the nociceptive flexion reflex (RIII). Forty-three male and female subjects were administered either naltrexone or a placebo using a double-blind, counterbalanced design before completing a timed mental arithmetic stressor (identical to the ‘hard task-many shocks’ condition in Study 2). Increases in physiological (SBP, DBP) and affective measures (anxiety, anger and discouragement) indicated that the math task induced a marked state of stress. Negative affect increased shock PI and UP during the task, whereas self-efficacious subjects taking the placebo experienced less shock pain. However, uncontrollable stress led to an opioid-antagonised increase in cold pressor UP. Stressor controllability had a similar, but marginal, effect on cold pressor PI, but not pain tolerance. Tolerance of cold pressor pain was not associated with subjective PI and UP ratings, but was positively associated with endurance to non-painful, but unpleasant tasks (Valsalva Manoeuvre, Letter-Symbol Matching Task), indicating that pain tolerance was measuring the ability to tolerate discomfort, in addition to pain. Results of hierarchical multiple regressions demonstrated that increases in discouragement were positively related to increases in cold pressor UP after the math task, for naltrexone recipients only. These findings suggest that discouragement inhibits the UP of a prolonged pain stimulus via opioid mechanisms. RIII latencies and thresholds were not affected by the math task or by opioid blockade; however, these null effects may be due to methodological limitations. Unlike Study 2, higher blood pressure was associated with shock and cold pressor pain inhibition in normotensive subjects, and this relationship appeared to be mediated by opioids. The strong association between chronic pain and depression has led to speculation that the endogenous opioid system and pain modulatory mechanisms may be impaired in depression. At the time that this research was carried out, no studies had examined whether this was the case. In Study 4, the effect of a cognitive stressor (math task used in Study 3) on foot cold pressor PI, UP and pain tolerance and the nociceptive, or R2 component, of the blink reflex was investigated in 61 participants with or without major depression (as met by DSM-IV diagnostic criteria and confirmed by psychometric testing). Naltrexone or placebo was administered to subjects an hour before the math task using a double-blind, counterbalanced design. Increases in physiological (SBP, DBP) and affective measures (anxiety, anger and discouragement) confirmed that the math task induced the targeted emotional state. An opioid-mediated reduction in anxiety occurred mid-way through the math task. Opioid-mediated decreases in foot cold pressor PI and UP were observed in depressed and non-depressed subjects after the math task. R2 onset to 10 mA was facilitated after the task regardless of opioid blockade, suggesting that endogenous opioids are not involved in the modulation of the BR. Increased anxiety and discouragement led to opioid-mediated inhibition of shock PI and UP during the task and, to a lesser extent, foot cold pressor PI and UP after the math task. Anger increased shock pain without being influenced by opioid blockade. Pain tolerance was not influenced by depression, opioid blockade or mood. These findings failed to support the idea that SIA is impaired in major depression, suggesting instead that uncontrollable aversive events and negative mood (anxiety, discouragement) lead to opioid activation and insensitivity to acute pain. Multiple regression analyses revealed that the inverse relationship between resting blood pressure and foot cold pressor PI and UP was opioid-mediated in controls only, suggesting that opioid dysregulation in depression might influence regulatory functions other than SIA. In Study 4, opioid involvement in hetero-segmental pain inhibitory phenomena termed diffuse noxious inhibitory controls (DNIC) was examined separately, before psychological stress. Specifically, the effect of a heterotopic noxious conditioning stimulus (CS i.e., hand CPT) on R2 onset latency was compared before and after drug absorption (before the math task). An inhibitory effect of the first CS was detected at each electrical stimulus intensity consistent with a DNIC effect. However, this effect was not detected during the second CS, suggesting that some other process masked the DNIC effect. In summary, the findings indicate that uncontrollable aversive events and negative emotion (primarily discouragement) activates endogenous opioids and inhibits pain in human subjects, whether depressed or not. Notably, opioids inhibited the affective component of pain perception, or pain UP, more consistently than PI, suggesting that the antinociceptive function of opioids may be secondary to an important emotional-modulatory role. Endogenous opioids also appeared to mediate the cardiovascular-pain relationship in normotensive non-depressed subjects, suggesting an important stress-regulatory role for these peptides. Opioid-mediated masking of this relationship in major depression suggests that functioning of the endogenous opioid system may be impaired in baroreceptor-mediated analgesia. This finding provides preliminary support for the notion that opioid antinociceptive system dysfunction may contribute to cardiovascular disease in depression.

Zugl.: Dortmund, Univ., Diss., 2006

No description available.

Burkholderia cepacia complex (Bcc) bacteria reside in soil, plant rhizospheres, and water, but the prevalence of Bcc in outdoor environments is not clear. In this study, we sampled a variety of soil and rhizosphere environments with which people may have contact: playgrounds, athletic fields, parks, hiking trails, residential yards and gardens. A total of 9l soil samples was obtained from three large U.S. cities (Philadelphia, PA, Cleveland, OH, and Portland, OR). In the first phase of the study, putative Bcc isolates were recovered on Burkholderia cepacia selective agar (BCSA) and trypan blue tetracycline medium (TBT). Isolates were sent to the Burkholderia cepacia Referral Laboratory and Repository, where they were identified using biochemical tests, growth at 32��C, and polymerase chain reaction (PCR) assays targeting both rRNA and recA gene sequences. Bcc isolates were genotyped by using RAPD, PFGE and rep-PCR. A total of 1013 bacterial isolates were examined, and 68 were identified as B. cepacia complex. The majority of these were B. pyrrocinia or genomovar VII (B. ambifaria); however, a few genomovar III isolates were also recovered. Fourteen (15%) of 91 soil samples yielded Bcc isolates. In the second phase of the study, DNA was extracted from 87 of the 91 soil samples and examined with PCR assays targeting Bcc 16S rRNA gene sequences. By using assays developed by LiPuma et al. (1999), 82% of the soil samples were positive for at least one Bcc genomovar, whereas 94% of samples were positive for at least one Bce genomovar using the Bauernfeind et al. (1999) assay system. Selected amplicons generated from four soil samples were cloned, and plasmids from multiple transformants (total=120) were screened by RFLP analysis. Among the clones evaluated from three of four soil samples, 90% or more had the "Burkholderia" RFLP pattern. In the remaining soil sample, only 9.5% of the evaluated clones displayed this profile. Sequence analysis of the 463bp 16S rRNA inserts from eight clones with the "Burkholderia" RFLP pattern indicated that all were from members of the Bcc. However, the four soil samples from which these clones were generated did not yield isolates identified as Bcc. This study indicates that the use of selective media may not be the best way to estimate the environmental prevalence of Bcc in soils. The natural populations of Bcc in soils with which people commonly have contact may be much higher than previously estimated. / Graduation date: 2002

Pannexins represent a recently discovered second family of gap junction proteins in vertebrates. However, instead of forming intercellular gap junction channels like connexins, pannexins operate as unpaired pannexons, allowing the flux of molecules from the cytoplasm to the extracellular space and vice versa. Pannexins appear to play a vital role in the local control loop of blood perfusion and oxygen delivery. The properties of Panx1 channels indicate that this protein is the most probable candidate for an ATP release channel and is involved in the propagation of intercellular calcium waves. It is also proposed to mediate the large pore formation of the P2X7 receptor death complex. Prolonged activation of this receptor can lead to cell death. There must be some mechanisms to stop this ATP-induced ATP release and opening of the lethal pore. Here we describe a negative feedback loop controlling pannexin 1 channel activity. ATP, permeant to pannexin 1 channels, was found to inhibit its permeation pathway when applied extracellularly. ATP analogues, including BzATP, suramine, and BBG were even more effective inhibitors of pannexin 1 currents than ATP. These compounds also attenuated the uptake of dyes by erythrocytes, which express pannexin 1. The rank order of the compounds in attenuation of pannexin 1 currents was similar to their binding affinities to the P2X7 receptor, except that receptor agonists and antagonists both were inhibitory to the channel. The ATP inhibitory effect is largely decreased when R75 on the first extracellular loop of Pannexin1 is mutated to alanine, strongly indicating that the ATP regulates this channel through binding. To further investigate the structural property of the ATP binding, we did alanine scanning mutagenesis of the extracellular loops and found that mutations on W74, S237, S240, I247 and L266 on the extracellular loops severely impair the BzATP inhibitory effect indicating that they might be direct binding partners for the ligands. Mutations on R75, S82, S93, L94, D241, S249, P259 and I267 have largely decreased BzATP sensitivity. Mutations on other residues didn't change the BzATP sensitivity compared to the wild type except for some nonfunctional mutants. All these data demonstrate that some amino acid residues on the extracellular loop of Pannexin 1 mediate ATP sensitivity. However, how these residues form the ATP-binding pocket remains to be elucidated.