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Biomedical subjects

L Williams

Publications and source records attributed to L Williams.

At least 55 records · Page 3Linked to original sources
PubMed2000

Interleukin 10 modulation of tumour necrosis factor receptors requires tyrosine kinases but not the PI 3-kinase/p70 S6 kinase pathway.

We have previously shown that interleukin (IL-)10-induced proliferation of the murine mast cell line D36, was dependent upon the activation of PI 3-kinase and p70 S6 kinase. Conversely, we were able to show that this pathway was not involved in the signal transduction pathway mediating IL-10 inhibition of pro-inflammatory cytokine release from monocytes. We have extended these studies to investigate the induction of p75 tumour necrosis factor receptor (TNF-R) shedding, another anti-inflammatory property of IL-10. Using the inhibitors of PI 3-kinase (LY294002 and wortmannin) and an inhibitor of p70 S6 kinase activation (rapamycin), we were able to show that this anti-inflammatory effect of IL-10 was not mediated by the PI 3-kinase/p70 S6 kinase pathway, indicating that another signalling cascade(s) was involved. Further studies also investigated the role of tyrosine kinases in the response to IL-10. Two distinct tyrosine kinase inhibitors, herbimycin and genistein affected the expression of TNF-R in response to IL-10 but, surprisingly, with opposite effects. However, both compounds inhibited the activation of both PI 3-kinase and p70 S6 kinase, with a concomitant inhibition of IL-10-induced proliferation. We observed that whilst tyrosine kinase activity was involved in the regulation of TNF-R expression, IL-10-induced activation of JAK kinases was not sensitive to inhibition by the tyrosine kinase inhibitors. These data suggest that multiple unknown tyrosine kinases are mediating the IL-10-induced signal transduction pathways leading to the regulation of TNF-R expression and IL-10-induced proliferation.

Animals↗
PubMed2000

Misattribution of sensory input reflected in dysfunctional target:non-target ERPs in schizophrenia.

BACKGROUND: While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls. METHODS: EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately. RESULTS: There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls. CONCLUSIONS: These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the 'match:mismatch' of novel (target) and familiar (non-target) sensory input compared with stored information.

Adult↗
PubMed2000

Time-kill studies of tea tree oils on clinical isolates.

Tea tree oil has recently emerged as an effective topical antimicrobial agent active against a wide range of organisms. Tea tree oil may have a clinical application in both the hospital and community, especially for clearance of methicillin-resistant Staphylococcus aureus (MRSA) carriage or as a hand disinfectant to prevent cross-infection with Gram-positive and Gramnegative epidemic organisms. Our study, based on the time-kill approach, determined the kill rate of tea tree oil against several multidrug-resistant organisms, including MRSA, glycopeptide-resistant enterococci, aminoglycoside-resistant klebsiellae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, and also against sensitive microorganisms. The study was performed with two chemically different tea tree oils. One was a standard oil and the other was Clone 88 extracted from a specially bred tree, which has been selected and bred for increased activity and decreased skin irritation. Our results confirm that the cloned oil had increased antimicrobial activity when compared with the standard oil. Most results indicated that the susceptibility pattern and Gram reaction of the organism did not influence the kill rate. A rapid killing time (less than 60 min) was achieved with both tea tree oils with most isolates, but MRSA was killed more slowly than other organisms.

Anti-Infective Agents, Local↗
PubMed2000

Clausa, a tomato mutant with a wide range of phenotypic perturbations, displays a cell type-dependent expression of the homeobox gene LeT6/TKn2.

Class I knox genes play an important role in shoot meristem function and are thus involved in the ordered development of stems, leaves, and reproductive organs. To elucidate the mechanism underlying the expression pattern of these homeobox genes, we studied a spontaneous tomato (Lycopersicon esculentum) mutant that phenotypically resembles, though is more extreme than, transgenic plants misexpressing class I knox genes. This mutant was found to carry a recessive allele, denoted clausa:shootyleaf (clau:shl)-a newly identified allele of clausa. Mutant plants exhibited abnormal leaf and flower morphology, epiphyllus inflorescences, fusion of organs, calyx asymmetry, and navel-like fruits. Analysis by scanning electron microscopy revealed that such fruits carried ectopic ovules, various vegetative primordia, as well as "forests" of stalked glandular trichomes. In situ RNA hybridization showed a peculiar expression pattern of the class I knox gene LeT6/TKn2; expression was restricted to the vascular system and palisade layer of mature leaves and to the inner part of ovules integuments. We conclude that CLAUSA regulates various aspects of tomato plant development, at least partly, by rendering the LeT6/TKn2 gene silent in specific tissues during development. Considering the expression pattern of LeT6/TKn2 in the clausa mutant, we suggest that the control over a given homeobox gene is maintained by several different regulatory mechanisms, in a cell type-dependent manner.

Base Sequence↗
PubMed2000

Routine blood test ordering for patients in intensive care.

Current practice is for a number of blood tests to be routinely performed on intensive care unit (ICU) patients. A survey of routine blood testing amongst ICUs in Australia and New Zealand was conducted. Ninety-six ICUs completed the survey form. Blood electrolytes, liver function, arterial blood gases and full blood count were the most frequently ordered tests. Routine blood testing was not practised in 12.6% of ICUs. The presence or absence of written guidelines did not influence the frequency of the most commonly performed routine blood tests. Clinical and operational factors specific to each ICU appear to impact on such blood tests and guidelines for their use.

Australia↗
PubMed2000

Family adaptation to a child's transplant: pretransplant phase.

The purpose of this study was to explore the relationship between family stress, family coping, social support, perception of stress, and family adaptation from the mother's perspective during the pretransplant period in the context of the Double ABC-X Model of Family Adaptation. The process of seeking a transplant for a child is very stressful, and before interventions can be developed, clinicians need to understand how aspects of family life are affected. Twenty-nine mothers whose children were being evaluated for a liver transplant constituted the sample for this exploratory study. Higher family strains, fewer coping skills, and higher perception of stress were related to more unhealthy family adaptation during the pre-transplant phase. Data point to the need for close evaluation not only for the child's needs but for the family's needs as the family begins the process of seeking a transplant for the child.

Adaptation, Psychological↗
PubMed2000

Induction of antibodies against GM2 ganglioside by immunizing melanoma patients using GM2-keyhole limpet hemocyanin + QS21 vaccine: a dose-response study.

In a previous randomized Phase III trial (P. O. Livingston et al, J. Clin. Oncol., 12: 1036-1044, 1994), we demonstrated that immunization with GM2 and bacille Calmette-Guerin reduced the risk of relapse in stage III melanoma patients who were free of disease after surgical resection and who had no preexisting anti-GM2 antibodies. That vaccine formulation induced IgM anti-GM2 antibodies in 74% but induced IgG anti-GM2 antibodies in only 10% of the patients. To optimize the immune response against GM2, a reformulated vaccine was produced conjugating GM2 to keyhole limpet hemocyanin (KLH) and using the adjuvant QS21 (GM2-KLH/QS21). In pilot studies, 70 microg of vaccine induced IgG anti-GM2 antibodies in 76% of the patients. We wished to define the lowest vaccine dose that induced consistent, high-titer IgM and IgG antibodies against GM2. Fifty-two melanoma patients who were free of disease after resection but at high risk for relapse were immunized with GM2-KLH/QS21 vaccine at GM2 doses of 1, 3, 10, 30, or 70 ILg on weeks 1, 2, 3, 4, 12, 24, and 36. Serum collected at frequent and defined intervals was tested for anti-GM2 antibodies. Overall, 88% of the patients developed IgM anti-GM2 antibodies; 71% also developed IgG anti-GM2 antibodies. GM2-KLH doses of 3-70 microg seemed to be equivalent in terms of peak titers and induction of anti-GM2 antibodies. At the 30-microg dose level, 50% of the patients developed complement fixing anti-GM2 antibodies detectable at a serum dilution of 1:10. We conclude that the GM2-KLH/QS21 formulation is more immunogenic than our previous formulation and that 3 microg is the lowest dose that induces consistent, high-titer IgM and IgG antibodies against GM2.

Adult↗
PubMed2000

Laparoscopic surgical simulator and port placement study.

We have developed a virtual laparoscopic surgical simulator and gathered data during student trial runs. The students performed simulated surgical dissections from 3 pairs of port positions with angles between the cutting and grasping instruments set to 60, 90, and 120 degrees. Preliminary data indicates improved performance at the 90 degree angle. Study updates can be found at http:¿www.hitl.washington.edu/research/lss

Cholecystectomy, Laparoscopic↗
PubMed2000

Relationship of skeletal muscle mass, muscle strength and bone mineral density in adults with cystic fibrosis.

Few studies have investigated peripheral muscle strength and quality in patients with cystic fibrosis (CF). The present study tested the isometric and isokinetic strength of the quadriceps and hamstrings using an isokinetic dynamometer and a strength-testing chair in 25 CF adults and 25 controls. Total body and leg muscle mass were determined by dual-energy X-ray absorptiometry, and bone mineral density (BMD) was also measured. Both muscle strength and muscle mass (total body and leg) were decreased in the CF group. In both groups there was a highly significant relationship between quadriceps strength and leg muscle mass (CF, r=0.7, P=0.0002; controls, r=0.6, P=0.0013). When strength was normalized for muscle size, there was no significant difference between the two groups. Total body and leg BMD were significantly reduced in CF subjects compared with controls. However, when corrected for height, the differences disappeared. There was a significant relationship found between leg muscle mass and leg BMD. We conclude that CF adults are significantly weaker than controls. This is due to lower muscle mass, and not to a reduced force-generating capacity of the muscle, implying that there is no decrease in the quality of CF muscle. BMD is also reduced in CF subjects, and this appears to be related to shorter stature in this group.

Absorptiometry, Photon↗
PubMed2000

Vaccination with a bivalent G(M2) and G(D2) ganglioside conjugate vaccine: a trial comparing doses of G(D2)-keyhole limpet hemocyanin.

Immunization with GMK vaccine (G(M2) ganglioside conjugated to keyhole limpet hemocyanin mixed with QS-21 adjuvant) induces anti-G(M2) antibodies in close to 100% of patients. We found previously that anti-G(D2) antibodies could be induced in some patients using G(D2)-keyhole limpet hemocyanin + QS-21 (GDK). In this trial, we wished: (a) to determine whether immunization with both GMK and GDK vaccines could induce antibodies against both G(M2) and G(D2); and (b) to determine the optimal dose of GDK. Thirty-one patients with melanoma or sarcoma who had no evidence of disease after complete surgical resection were immunized with both GMK (30 microg of G(M2)) and GDK on weeks 1, 2, 3, 4, 12, 24, and 36. Patients were assigned to one of five GDK dose levels (3, 10, 30, 70, or 130 microg of G(D2)). Anti-G(M2) IgM or IgG were induced in 97% of patients. The dose of GDK did not affect the anti-G(M2) response, although at the highest GDK dose level, 3 of 7 patients did not make anti-G(M2) IgG. GDK was less immunogenic; overall 45% of patients developed either IgM or IgG against G(D2). At GDK doses of 30 or 70 microg, 8 of 11 patients (73%) made either IgM or IgG anti-G(D2) antibodies. We conclude that both GMK and GDK vaccines can induce antibodies against G(M2) and G(D2) in a majority of patients and are safe. The optimal dose of GDK appears to be either 30 or 70 microg when administered with GMK vaccine.

Cancer Vaccines↗
PubMed2000

A comprehensive interactive competency program. Part I: Development and framework.

The department of medicine/oncology nursing of an academic medical center developed and implemented a comprehensive interactive competency program. The program proved to be valuable to nurses and the organization. Part I of this two-part series describes the process of program development and the resulting framework.

Academic Medical Centers↗
PubMed2000

Data acquisition, data storage, and data presentation in a modern genetics laboratory.

Modern genetic analysis can be divided into three main areas of investigation. The first is data acquisition, in the form of genomic sequence and the cataloguing of polymorphism data of the single nucleotide polymorphism variety (so called SNPs). Once identified, such genetic information can be adapted into high throughput tests to examine genetic information in large populations, making the analysis of sufficiently large numbers both cost and time effective so that relatively low-penetrant genetic effects can be accurately detected. The third step is correlating variation with phenotype (e.g. disease susceptibility or resistance) for a variety of disorders is paramount in our motivation and indeed is a common goal of modern human genetic analysis. While the technology to acquire vast amounts of genetic data is now well established and continues to expand, the ability to deal with such data, from the process of acquisition, storage, and analysis depends fundamentally on a solid informatics infrastructure as an essential component. Indeed, most of the major gains in productivity in this field are to be realized on the informatics front, and involve automating data acquisition, defining and sorting data in databases for quality control and analysis and facilitating access to data for the large variety of data analyses. Informatics-related issues including those relating to data acquisition, database structure, and analysis tools are summarized here in an effort to define some of the issues relevant to establishing informatics infrastructure in a small genetics laboratory focused on resequencing human immune response genes. From inherited diseases to drug efficacy to the specific genetic changes occurring during tumor development, this new field of medical genetics promises a profound impact on the state of human health. Ultimately, any and all advances in this field will continue to depend on major investments in informatics.

Computational Biology↗
PubMed1999

Patient risk factors for adverse drug events in hospitalized patients. ADE Prevention Study Group.

BACKGROUND: Adverse drug events (ADEs) are common in hospitalized patients, but few empirical data are available regarding the strength of patient risk factors for ADEs. METHODS: We performed a nested case-control study within a cohort that included 4108 admissions to a stratified random sample of 11 medical and surgical units in 2 tertiary care hospitals during a 6-month period. Analyses were conducted on 2 levels: (1) using a limited set of variables available for all patients using computerized data available from 1 hospital and (2) using a larger set of variables for the case patients and matched controls from both hospitals. Case patients were patients with an ADE, and the matched control for each case patient was the patient on the same unit as the case patient with the most similar prevent length of stay. Main outcome measures were presence of an ADE, preventable ADE, or severe ADE. RESULTS: In the cohort analysis, electrolyte concentrates (odds ratio [OR], 1.7), diuretics (OR, 1.7), and medical admission (OR, 1.6) were independent correlates of ADEs. Independent correlates of preventable ADEs in the cohort analysis were low platelet count (OR, 4.5), antidepressants (OR, 3.3), antihypertensive agents (OR, 2.9), medical admission (OR, 2.2), and electrolyte concentrates (OR, 2.1). In the case-control analysis, exposure to psychoactive drugs (OR, 2.1) was an independent correlate of an ADE, and use of cardiovascular drugs (OR, 2.4) was independently correlated with severe ADEs. For preventable ADEs, no independent predictors were retained after multivariate analysis. CONCLUSIONS: Adverse drug events occurred more frequently in sicker patients who stayed in the hospital longer. However, after controlling for level of care and preevent length of stay, few risk factors emerged. These results suggest that, rather than targeting ADE-prone individuals, prevention strategies should focus on improving medication systems.

Adult↗
PubMed1999

A differential neural response to threatening and non-threatening negative facial expressions in paranoid and non-paranoid schizophrenics.

Several studies have demonstrated impaired facial expression recognition in schizophrenia. Few have examined the neural basis for this; none have compared the neural correlates of facial expression perception in different schizophrenic patient subgroups. We compared neural responses to facial expressions in 10 right-handed schizophrenic patients (five paranoid and five non-paranoid) and five normal volunteers using functional Magnetic Resonance Imaging (fMRI). In three 5-min experiments, subjects viewed alternating 30-s blocks of black-and-white facial expressions of either fear, anger or disgust contrasted with expressions of mild happiness. After scanning, subjects categorised each expression. All patients were less accurate in identifying expressions, and showed less activation to these stimuli than normals. Non-paranoids performed poorly in the identification task and failed to activate neural regions that are normally linked with perception of these stimuli. They categorised disgust as either anger or fear more frequently than paranoids, and demonstrated in response to disgust expressions activation in the amygdala, a region associated with perception of fearful faces. Paranoids were more accurate in recognising expressions, and demonstrated greater activation than non-paranoids to most stimuli. We provide the first evidence for a distinction between two schizophrenic patient subgroups on the basis of recognition of and neural response to different negative facial expressions.

Adult↗