Cytoplasmic proteins involved in thyroid hormone response also bind Neisseria gonorrhoeae Opa outer membrane proteins.
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Biomedical subjects
Publications and source records attributed to J M Williams.
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Three major methods have been described for the isolation of fetal cells from maternal blood: fluorescence-activated cell sorting (FACS), immunomagnetic beads, and magnetic-activated cell sorting (MACS). To date, no study has directly compared fetal cell recovery using each of these methods. Here we describe our system using a "model' male fetal cell mixed into female peripheral blood mononuclear cells. Fetal cell yields and purities were assayed by a quantitative polymerase chain reaction (qPCR) using chromosomes Y- and 7-specific sequences. Fetal cell recovery was investigated by selection of CD71+ cells or depletion of CD45+ cells. Our data demonstrated variation in fetal cell recovery for all methods tested, although CD71+ selection by FACS gave the best and most consistent results.
Colonic tissue obtained at surgery from control individuals and patients with ulcerative colitis was used to isolate mucins and to prepare mucin glycopolypeptides by pronase digestion. These were compared with mucins labelled with [35S] sulfate and [3H]-glucosamine after organ culture tissue samples from the same patients. A significant loss of mucin sulfation was detected in the colitis patients by both metabolic labelling and chemical analysis of the glycopolypeptides. A change in the size distribution of purified mucin oligosaccharides fractionated on BioGel P6 after release by beta-elimination was seen in both radiolabelled and non-labelled colitis mucins compared with controls. Amino acid analysis of the glycopolypeptides showed a close similarity to the expected ratio of serine:threonine:proline for MUC2 and did not vary between control and colitis groups. Analysis of the mucins confirmed > 90% purity in the labelling experiments, characteristic behaviour on density gradient centrifugation and agarose gel electrophoresis in control and ulcerative colitis groups and differences in sulfation and turnover at various sites in the normal colon.
Although the application of cognitive techniques to both the measurement and modification of delusional beliefs has recently been developed in more theoretical detail (e.g. Chadwick & Lowe, 1994, Behaviour Research and Therapy, 32, 355-367) there has not been an effort to examine the variability of delusional phenomenology across time. In the present study we report on the treatment of 6 individuals who fulfilled DSM-III-R (American Psychiatric Association, 1987) criteria for Delusional Disorder and who received cognitive therapy targeted specifically on the single symptom of their delusional belief(s). Single-case time-series methodology was used to examine the associations between different aspects of delusional phenomenology through baseline and intervention study phases. Belief maintenance factors were found to be significantly associated with conviction in all 3 individuals who responded to the intervention. Negative behaviours, affect associated with the belief, preparedness to talk to others about the belief and insight were associated with conviction in some individuals but not others. Preoccupation and acting on the belief were aspects of delusional phenomenology that were found to systematically vary independent of belief conviction. The results support a multidimensional view of delusional phenomenology and the process of change during cognitive intervention.
A series of 2,5-diarylisothiazolones is reported that inhibit the IL-1 beta-induced breakdown of bovine nasal septum cartilage in an organ culture assay. The synthesis and preliminary SAR of these compounds are described. These compounds represent a novel, nonpeptide lead series approach to the mediation of the chronic cartilage breakdown associated with arthritic disease. These compounds are relatively resistant to reductive metabolism by liver microsomal preparations and appear to inhibit cartilage breakdown by interfering with the proteolytic activation of matrix metalloproteinases.
PURPOSE: We studied a case of Fuchs' superficial marginal keratitis in which cystic corneal hydrops developed in one eye, and spontaneous corneal perforation occurred in the fellow eye. METHODS: The patient underwent bilateral annular corneoscleral lamellar patch grafts for tectonic support. RESULTS: The patient had an uncomplicated postoperative course and visual acuity of 20/25 bilaterally. CONCLUSION: Stromal loss in Fuchs' superficial marginal keratitis may be severe enough to result in cystic corneal hydrops. Patients with this disorder should be counseled regarding the possibility of corneal perforation.
PURPOSE: We studied a case of chronic, recurrent, bilateral, corneal ulcerations associated with smokeable methamphetamine abuse, commonly known as "ice," in an otherwise healthy 31-year-old woman. METHODS: Every few months the patient had recurrent corneal ulcerations. Each time, she was hospitalized and treated successfully with topical antibiotics. RESULTS: Even though she had undergone numerous formal attempts at drug rehabilitation, she continued to have relapses, and ulceration recurred only during periods of smokeable methamphetamine abuse. CONCLUSION: Illicit use of smokeable methamphetamine may result in corneal ulceration.
STUDY OBJECTIVE: To describe the development of an emergency department-based injury surveillance system, to describe the problems encountered, and to briefly describe the data output and potential applications. METHODS: Within our university-based hospital system and Level I trauma center register, injury data currently exist on all ED patients. Over a 1-year period, these data sets were linked with our ED log using the hospital identification number and date of service as the key merge variables. Elements in our data set included demographic information, ED-related variables, and codes for nature of injury and circumstances of injury. Data files for 1 month were inspected manually to validate the success of the merger. Problems encountered in developing the system were summarized. RESULTS: A manual review of 1 month of data files from our hospital system, trauma register, and ED log revealed that the records of more than 97% (2,802) of 2,878 injury patients seen in our ED had additional data attached after the merger. No errors of commission were found, but errors of omission occurred. The barriers that were encountered during the development of this injury surveillance system are described. CONCLUSION: Hospital data can be linked to the ED log to create an injury surveillance system that captures valuable information on patients admitted and discharged from the ED.
A cognitive science analysis of the interaction between psychological stress and the neurobiology of affective illness highlights a number of mechanisms relevant to the study of recurrence in major depressive disorder. It builds on observations previously offered by Post (1992) regarding the importance of kindling and sensitization effects in determining activation of neural structures, and proposes a model of knowledge structure activation that follows similar parameters. Vulnerability to depressive relapse/recurrence is determined by the increased risk of particular negative patterns of information processing being activated in depressed states. As is found in studies of kindling and behavioural sensitization, the likelihood of cognitive patterns being activated is dependent on the frequency of past usage, and increased reliance on these patterns of processing makes it easier for their future activation to be achieved on the basis of increasingly minimal cues. This model suggests that the processes related to relapse/recurrence and episode onset may not be isomorphic and, as such, treatments that emphasize relapse prevention strategies should take this distinction into account.
This paper reports the results of a study designed to explore the validity of a shiftwork model of affective disorders. Fifty-five student nurses doing nightwork for the first time were recruited to a study designed both to replicate an earlier study of the effects of nightwork on cognitive, emotional and neurovegetative measures and to assess the effects of nightwork on personality measures and the role of personality factors and nightwork induced disturbances in predicting accommodation to nightwork. As in the earlier study, concentration, interest, energy, sleep and appetite were significantly disturbed by nightwork and there was an increased perception of recent criticism from other. The findings from both studies were, therefore, aggregated to explore further possible relations between outcomes and the pre-nightwork level of affective symptoms and sensitivity to interpersonal criticism. These predicted poor response. In contrast, measures of cognitive style and symptom interpretation did not predict outcome. The findings are not inconsistent with proposals that disturbance of circadian rhythms consequent on psychosocial disruptions may play a part in the genesis of or maintenance of depression. They also support a proposal that nightwork induced changes may be a suitable human model for investigation of aspects of the affective disorders.
A 31-yr-old woman demonstrated intact neuropsychological functioning after being submerged for at least 30 minutes in icy cold water. Following submersion, the patient received CPR for approximately 1 hr. Eight hours after submersion, the patient's temperature was 31 degrees C (87 degrees F). She remained nonresponsive for 2 days after the accident. Extensive neuropsychological testing was completed 3 mo after the accident with no objective or subjective deficits evidenced. This case of hypothermically mediated neuroprotection from anoxia in an adult supports the need for further research on the putative neurophysiological mechanisms invoked and the potential for application of clinically induced hypothermia in the acute management of other types of cerebral insults.
Attentional bias is a central feature of many cognitive theories of psychopathology. One of the most frequent methods of investigating such bias has been an emotional analog of the Stroop task. In this task, participants name the colors in which words are printed, and the words vary in their relevance to each theme of psychopathology. The authors review research showing that patients are often slower to name the color of a word associated with concerns relevant to their clinical condition. They address the causes and mechanisms underlying the phenomenon, focusing on J.D. Cohen, K. Dunbar, and J.L. McClelland's (1990) parallel distributed processing model.
OBJECTIVE: To determine an estimate of the period prevalence of medically attended injury in West Virginia via a statewide random telephone survey. METHODS: A statewide random telephone survey, the West Virginia Social Indicator Survey (WVSIS), was modified to incorporate questions regarding the incidence and mechanisms of injury. The WVSIS is periodically conducted on a representative cross-section of West Virginians to gather information about their social and economic conditions as well as to monitor change in the quality of their lives over time. RESULTS: Of the 1,498 households interviewed, 412 (28%) reported having sustained injuries for which medical care had been obtained. This translates to a conservative estimate of 231,000 medically attended injuries within West Virginia in 1993. The average age of those injured was 35 years. Falls were the most frequently reported causes of injury, with motor vehicle crashes being the second most reported cause. Most injury victims (70%) were treated in an ED. Most respondents (67%) were able to suggest ways in which the injuries might have been avoided. Only 37% of the respondents with children < 13 years of age reported ever having received injury prevention information from a physician. The most commonly reported physician advice concerned childhood poisoning (34%). CONCLUSIONS: Injury questions added to ongoing state health surveillance surveys provide valuable insight into population-based injury rates and potential preventive measures.
OBJECTIVES: To measure the incidence and age and sex distribution of self reported experience of injuries in the preceding 12 month period among a representative national sample of Scottish schoolchildren and to validate the findings against other data sources. DESIGN: Self completed questionnaire administered in schools, April-June 1994. SUBJECTS: 4710 pupils aged 11, 13, and 15 years drawn from a representative sample of 270 classes with returns from 224 classes (83.2% completion rate). OUTCOME MEASURES: Number, type, site, and severity of injuries reported. RESULTS: 41.9% of pupils reported a medically attended injury, with injury incidence significantly higher in boys than in girls. Using the abbreviated injury scale (maximum abbreviated injury score) one third of injuries were either moderate or severe. CONCLUSION: The incidence and distribution of self reported injury is consistent with estimates based on other data sources thus confirming the utility of this method of injury surveillance in this age group.
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We have used polarized light (POL) to monitor changes in the organization of the articular cartilage collagen network and matrix proteoglycans (PGs) after intra-articular injection of chymopapain (CP). POL viewing of sirius red stained sections revealed a loss of normal birefringence suggesting an apparent collapse of the collagen network following intra-articular CP. After 21 days, knees injected with 2.0 mg CP showed no return of normal birefringence, however, normal birefringence was noted in knees injected with only 0.2 mg CP. POL viewing of toluidine blue stained sections revealed a severe loss of matrix PGs followed by PG restoration in animals injected with 0.2 mg CP. The most important inference from the data is that articular cartilage can recover from enzyme-induced alterations in the spatial collapse of its fibrillar network. This is an important finding since it has often been inferred that damage to the collagen network leads invariably to progressive articular cartilage destruction.
The clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) is believed to result from the ability of these compounds to inhibit the inducible isoform of the enzyme cyclooxygenase, COX2. The gastrointestinal and renal side effects of these drugs, in contrast, are thought to relate to their ability to inhibit the constitutive isozyme, COX1. There is structural and pharmacological evidence that suggests that NSAIDs may also inhibit two unrelated enzymes, myeloperoxidase (MP) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), potentially with untoward consequences for the patient. Our laboratories have been investigating a new structural class of potential COX inhibitors, the tri-cyclic aromatics. In this study we have examined the inhibitory potency of selected compounds for the enzymes human COX1, human COX2, human MP, and rat liver 3 alpha-HSD. The compounds selected span a range of COX isoform selectivities, from specific for COX2 to selective for COX1 only, and include three representative tri-cyclic aromatics. We found that compounds within the tri-cyclic aromatic class do not act as potent inhibitors of either myeloperoxidase or 3 alpha-HSD. These results demonstrate the unique inhibitor selectivity that can be achieved with the tri-cyclic aromatics. Examples of COX1 selective, and COX2 selective inhibitors within this structural class are presented.