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Biomedical subjects

P Williamson

Publications and source records attributed to P Williamson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Continuous analysis of the mechanism of activated transbilayer lipid movement in platelets.

Dithionite reduction of fluorescent (NBD) phospholipids was used as the basis of a continuous assay of transbilayer lipid movement to the cell surface during platelet activation. This assay reveals that virtually all previously internalized phosphatidylserine passes through the external leaflet of the membrane within 90 s after activation with Ca2+ and ionophore or with thrombin and thapsigargin. We demonstrate that this lipid scrambling is reversible, bidirectional, and insensitive to the lipid headgroup. Prolonged activation gradually results in inactivation of the scramblase. The assay also reveals that activation of the scrambling activity is sensitive to the sulfhydryl reagent pyridyldithioethylamine, suggesting the involvement of a protein in the process of activated transbilayer lipid scrambling.

4-Chloro-7-nitrobenzofurazan↗
PubMed1995

Mapping of the mouse homologue of the Wilson disease gene to mouse chromosome 8.

ATP7B, the gene altered in Wilson disease (WD) patients, lies in a block of homology shared between human chromosome 13q14 and the central region of mouse chromosome 14. However, we have mapped the murine homologue of ATP7B (Atp7b) to mouse chromosome 8 by somatic cell hybrid analysis. Analysis of 80 interspecific backcross offspring was used to position Atp7b close to D8Mit3 and another ATPase locus, Atp4b, on mouse chromosome 8. ATP4B lies in 13q34 and is separated from ATP7B by several loci whose mouse homologues map to mouse chromosome 14. The assignment of Atp7b to mouse chromosome 8 identifies a previously unrecognized region of homology between this chromosome and human chromosome 13. This assignment suggests a possible location for the toxic milk mutation in the mouse, which has been proposed as a homologue of WD.

Animals↗
PubMed1995

Identification and chromosomal mapping of a third mouse runt-like locus.

The Drosophila runt gene, which controls early events in embryogenesis, has been shown to have homologues in human and mouse. The human gene on 21q22 is involved in the t(8;21) associated with acute myeloid leukemia. Two mouse runt-like loci encoding DNA-binding proteins have been identified. We report here the isolation and partial sequence of a molecular clone of a third mouse runt-like locus. By using a panel of somatic cell hybrids and interspecific backcross mice, we map the novel locus to the telomeric region of mouse chromosome 4.

Amino Acid Sequence↗
PubMed1995

Clinical photographs as teaching aids: how reliable are they?

A study to investigate the value and reliability of clinical photographs as teaching aids was undertaken. Twenty colour photographs were taken using the StarMed video-otoscopic system. The pictures, which were a mixture of normal and abnormal ears, were shown to 21 experienced otolaryngologists from the UK and Canada. These clinicians were asked to identify the abnormality if any. The median score for correctly identified pictures was 15 (range 12-18). This score was identical for both the UK and Canadian subgroups. Although the abnormalities were consistently well recognized with an average correct identification rate of 90 per cent (range 67-100 per cent), the 'normals' were recognized significantly less well at only 41 per cent (range 5-71 per cent) (chi-squared = 110.6; 1 df; p < 0.001). This result is probably due to failure of the camera to capture the huge variation and subtleties in the range of normal, and the clinicians' natural inclination to identify pathology, when in doubt. We would conclude that as long as this failing is recognized, clinical photographs, and specifically those from the video-otoscope, represent a useful and reliable teaching tool.

Audiovisual Aids↗
PubMed1995

Indexing the census: a by-product of the simulation of whole populations by means of SAS and SAR data.

"Amongst the new output formats adopted for the 1991 [U.K.] census were the Small Area and Local Base Statistics tables and the Samples of Anonymised Records. During an attempt to combine these data sources to estimate whole populations, a need was recognised for a computer algorithm to aggregate SAR data flexibly into LBS and SAS table look-alikes. This paper is a report on progress in the development of such an algorithm, including the concomitant development of a meta-database of census tables and variables required as an input to the algorithm. Out of this work a user-friendly, freely disseminable version of the census meta-database has been created, of interest to all census users."

Censuses↗
PubMed1995

Defining potential targets for immunotherapy in Burkholderia cepacia infection.

Burkholderia cepacia has become a serious source of infection in patients with cystic fibrosis. Antibiotic therapy is difficult as the bacteria are intrinsically resistant to most antibiotics. The present study compared the antibody response by immunoblot of 50 negative control sera, 22 patients with cystic fibrosis and no evidence of B. cepacia, 9 clinically well patients with cystic fibrosis colonised by B. cepacia and 5 patients with cystic fibrosis and deteriorating or fatal B. cepacia infection. Nineteen antigenic bands varying in apparent molecular weights from 19 to 170 kDa were identified. Two bands at 19 and 21 kDa were only present when the organism was grown in an iron-deficient medium. The band at 30 kDa was identified as a porin and the possession of IgG antibody carried a statistically significant (P = 0.00003) better prognosis. This antigen was thus a potential target for immunotherapy.

Antibodies, Bacterial↗
PubMed1995

Management of suspected neuroleptic malignant syndrome.

OBJECTIVE: Neuroleptic Malignant Syndrome (NMS) is a rare but potentially lethal form of drug-induced hyperthermia. The objective of this paper is to provide data regarding early and suspected cases as well as offer guidelines for managing this condition. Knowledge of suspected cases will lead to early recognition and prompt management of this condition in the future. METHOD: To address the gap in knowledge, we present 2 case reports of patients with early NMS-like symptoms. The case reports are followed by a brief review of the literature on differential diagnoses, risk factors, early signs and treatment data. CONCLUSIONS: The most rational approach to treating NMS entails a hierarchy of interventions determined by the severity and progression of symptoms.

Adult↗
PubMed1994

Bedside filtration of blood products in the prevention of HLA alloimmunization--a prospective randomized study. Alloimmunisation Study Group.

To test the efficacy of poststorage bedside leucodepletion of blood products in the prevention of primary HLA alloimmunization and its clinical sequelae, 172 patients with hematologic malignancy requiring intensive red blood cell and platelet support were randomized to receive either standard or filtered red blood cells and platelets. Quality control of bedside filtration was explored by sequential sampling downstream of the filter, but this did not predict the total number of leucocytes transfused. After exclusions, 123 evaluable patients were assessed every two weeks until the end of therapy. HLA antibodies developed in 21 of 56 (37.5%) nonfilter (NF) and 15 of 67 (22%) filter (F) patients (risk ratio estimate, 0.60 [95% confidence interval, 0.34 to 1.05]; P = .07). Patients with acute myeloid leukemia (AML; n = 53) had higher alloimmunization rates in both arms of the study, with a greater effect of filtration (62.5% NF and 31.0% F; P = .025). Bedside filtration did not affect the overall incidence of febrile transfusion reactions (FTRs; 37% NF and 34% F; P = .71) or of platelet refractoriness assessed in 50 patients (30% NF and 26% F), despite an association between broad HLA reactivity and both FTRs and refractoriness. However, FTRs were also seen in 28 patients without HLA antibodies. Five alloimmunized refractory patients (2 F and 3 NF) required HLA-selected platelets. This report, the first prospective study of bedside filtration, has failed to show clear clinical benefit. Methodological limitations may account in part for this failure, notably the difficulties in accurately assessing the number of leucocytes transfused.

Adolescent↗
PubMed1994

Intraoperative use of Toradol facilitates outpatient hemorrhoidectomy.

UNLABELLED: Pain after hemorrhoidectomy is widely feared by many patients who are mostly still treated with oral/intramuscular narcotics to control their pain postoperatively. PURPOSE: In an effort to decrease posthemorrhoidectomy pain by applying newer methods of analgesia, a prospective trial was conducted to investigate the postoperative analgesic effect of Toradol (ketorolac tromethamine; Syntex Labs, Palo Alto, CA) injected into the sphincter muscle at the time of hemorrhoidectomy and taken orally during a five-day postoperative period in a group of 24 patients (Toradol group). Results were compared with two other groups of matching patients: one group (narcotics, n = 18) treated with standard postoperative narcotic intramuscular/oral analgesics after overnight hospital stay, and a group (SQMP, n = 21) previously treated by one of us with outpatient, subcutaneous infusion of morphine sulfate (Roxane Laboratories, Columbus, OH) via a home infusion pump. METHOD: The length of hospitalization, severity of postoperative pain and complications, costs, and side effects were analyzed by patient questionnaire at the time of the first postoperative visit and hospital and clinic records were reviewed. Differences between groups were analyzed using Student's t-test with P < 0.05 being significant. RESULTS: Subjective pain response and hospitalization cost were significantly less in the SQMP group; however, this was at the expense of increased postoperative complications (urinary retention) and side effects (day until first bowel movement, nausea) although without a decrease in satisfaction rating. The Toradol group had pain control equivalent to that of the narcotics group, a higher satisfaction rating, and suffered no increase in complications relative to either group. Significantly, there was no urinary retention in the Toradol group. CONCLUSION: Postoperative pain after hemorrhoidectomy can be safely controlled as an outpatient using newer methods of pain control. These include both constant-infusion pain pump or supplemental use of the nonsteroidal analgesic ketorolac, both of which allow early release of the patient the day of surgery by diminishing postoperative pain. An important advantage of local injection of ketorolac is the elimination of urinary retention in our study group, probably by blunting the pain reflex response facilitated by prostaglandins, thus allowing safe same-day discharge.

Ambulatory Surgical Procedures↗
PubMed1994

Intracellular Ca(2+)-containing vesicles in sickle cell disorders.

The frequency of red blood cells harboring Ca(2+)-containing vesicles was determined in patients with various sickle cell disorders; vesicles were identified by microscopy after the cells were stained with the fluorescent probe chlortetracycline. Specimens from 49 patients were studied. The highest frequencies of vesicle-containing cells were observed in samples from adults with homozygous sickle cell (SS) disease and in patients with S beta zero and SS(-alpha/alpha alpha) thalassemias. The frequency of cells with vesicles was less elevated in patients with SS(-alpha/-alpha) thalassemia and in patients with SS disease (Saudi Arabia high hemoglobin F), whereas a normal low frequency of positive cells was seen in patients with sickle cell-hereditary persistence of fetal hemoglobin and in patients with sickle trait. Deoxygenation induced an increase in the number of vesicle-containing cells that was proportional to the frequency of such cells in the oxygenated population. The frequency of Ca(2+)-containing vesicles in sickle red cells is associated with the clinical, hematologic, or clinical and hematologic severity of the sickle cell disorder.

Adult↗
PubMed1994

The membrane proximal segment of the IL-2 receptor beta-chain acidic region is essential for IL2-dependent protein tyrosine kinase activation.

The signal transduction mechanism of the interleukin-2 receptor (IL-2R) remains largely undefined. The cytosolic domain of the IL-2R beta subunit is known to be essential for coupling to intracellular signaling pathways such as protein tyrosine kinase (PTK) and for control of IL-2 dependent cellular proliferation. A panel of cell lines that express IL-2R beta chains that contain sequential truncation mutations within the cytosolic domain were constructed. These cell lines were used to map the interaction of IL-2R with PTK activation, and the linkage of PTK function to activation of the enzyme phosphatidylinositol-3-kinase (Pl3K). The data show that the amino terminal segment of the acidic region (residues 314-350) within IL-2R beta is a critical site for PTK activation, and that activation of Pl3K is linked to IL-2 dependent tyrosine phosphorylation.

Animals↗
PubMed1993

The serine-rich cytoplasmic domain of the interleukin-2 receptor beta chain is essential for interleukin-2-dependent tyrosine protein kinase and phosphatidylinositol-3-kinase activation.

The biological activity of interleukin-2 receptors (IL-2R) is dependent on the functional coupling of IL-2R beta molecules to intracellular enzymes such as protein tyrosine kinase. The serine-rich, S-domain within the cytosolic portion of IL-2R beta plays an essential role in transduction of the IL-2 proliferative signal. Cells bearing either wild type IL-2R beta (Baf alpha/beta) or deletions within the S-domain (Baf alpha/beta SD1) were used to evaluate the importance of the S-domain in linking ligand binding to protein tyrosine kinase induction. Multiparameter, side by side comparisons showed that only those cells that expressed wild type IL-2R beta responded to IL-2 by increased cellular proliferation, accumulation of the c-myc proto-oncogene, and activation of protein tyrosine kinase. Activation of protein tyrosine kinase was, in turn, linked to increased tyrosine phosphorylation and activation of phosphatidylinositol-3-kinase. These findings indicate that the S-domain of the IL-2R beta chain is an essential component in the signal transduction cascade that links IL-2 binding to tyrosine kinase and phosphatidylinositol-3-kinase activation.

1-Phosphatidylinositol 4-Kinase↗
PubMed1993

Mapping on human and mouse chromosomes of the gene for the beta-galactoside-binding protein, an autocrine-negative growth factor.

The structural gene for beta-galactoside-binding protein (Lgals-1), a cell growth regulatory molecule and cystostatic factor, is assigned to the E-region of mouse chromosome 15 and to the region q12-q13.1 of human chromosome 22. The evolutionary conservation of these two regions has been previously suggested from comparative mapping of several loci. These include the murine SIS oncogene (Pdgfb) and its human homolog, the platelet-derived growth factor-beta polypeptide, PDGFB. The findings presented here extend the genetic homology of the two regions.

Animals↗