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T McElwain

Publications and source records attributed to T McElwain.

16 recordsLinked to original sources

Cloning, characterization, and expression of a 200-kilodalton diagnostic antigen of Babesia bigemina.

Current serological tests for Babesia bigemina use semipurified merozoite antigens derived from infected erythrocytes. One of the major drawbacks of these tests is that antigen quality can vary from batch to batch. Since the quality of the antigen contributes to the sensitivity and specificity of serological tests, the use of standardized recombinant antigens should ensure consistency in assay quality. Previously, a 200-kDa merozoite antigen (p200) was identified as a candidate diagnostic antigen for use in a serological assay for the detection of B. bigemina antibodies in infected cattle. In this study, we have cloned, characterized, and expressed p200. A 3.5-kbp cDNA clone encoding p200 was isolated and shown to be almost full length, lacking approximately 300 bp at the 5' end. The predicted amino acid sequence shows that p200 consists of a long, highly charged central repeat region of an uninterrupted alpha helix, indicative of a fibrous protein. Immunoelectron microscopy localized p200 to the merozoite cytoplasm, suggesting that the antigen may be a structural protein involved in forming filament structures within the cytoskeleton. The 3.5-kbp cDNA was expressed in bacteria as a fusion protein with glutathione S-transferase (GST), but the yield was poor. To improve the yield, cDNA fragments encoding antigenic domains of p200 were expressed as fusions with GST. One of these fusion proteins, C1A-GST, is composed of a 7-kDa fragment of the p200 repeat region and contains epitopes that react strongly with sera from cattle experimentally infected with B. bigemina. Recombinant C1A-GST should permit the development of an improved enzyme-linked immunosorbent assay for the detection of antibodies against B. bigemina.

Amino Acid Sequence↗

Antibody against an Anaplasma marginale MSP5 epitope common to tick and erythrocyte stages identifies persistently infected cattle.

A protein epitope of major surface protein 5 (MSP5), defined by monoclonal antibody (MAb) ANAF16C1, is conserved among Anaplasma species (E. S. Visser, T. C. McGuire, G. H. Palmer, W. C. Davis, V. Shkap, E. Pipano, and D. P. Knowles, Jr., Infect. Immun. 60:5139-5144, 1992) and is expressed in the salivary glands of infected ticks. A competitive inhibition ELISA (cELISA) for the detection of bovine anti-MSP5 antibodies was developed by using purified recombinant MSP5 fusion protein and MAb ANAF16C1. The specificity of the recombinant-MSP5 cELISA within North America was established by using 261 serum samples from cattle in the regions of Hawaii and Northern Ontario where anaplasmosis is not endemic and from cattle proven by splenectomy or subinoculation of whole blood into susceptible splenectomized recipients to be uninfected. The maximum percent inhibition by these sera was 18%. Sera known to be positive were obtained from 35 cattle either experimentally inoculated with infected erythrocytes or exposed to infected Dermacentor andersoni ticks. Thirty-four of the 35 serum samples inhibited MAb ANAF16C1 binding by > or = 25%. During acute infection, the MSP5 cELISA detected antibodies prior to or concomitantly with the appearance of rickettsiae in erythrocytes. Antibodies were detectable in sera from persistently infected cattle inoculated as long as 6 years previously.

Anaplasma↗

Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma.

The efficacy and toxicity of a high-dose multiagent consolidation regimen, OMEC (vincristine, melphalan, etoposide and carboplatin), with autologous bone marrow rescue was studied in patients with poor-prognosis neuroblastoma, 20 patients were treated with OMEC, 18 after induction chemotherapy and 2 following relapse. All patients received, per m2, vincristine 4 mg, etoposide 1 g, carboplatin 1.0-1.75 g and melphalan 180 mg followed by bone marrow rescue. 4 patients (20%) died of treatment-related complications. Severe gastrointestinal toxicity occurred in all of these patients, and in 75% of patients overall. 1 of 5 patients with evaluable disease achieved complete remission. 13 patients (65%) have relapsed a median of 10 months (range 3-26) after receiving OMEC. Thus, OMEC was not more effective, yet more toxic, than high-dose melphalan given alone, and the use of similar multiagent regimens with overlapping toxicities in advanced neuroblastoma appears inadvisable.

Antineoplastic Combined Chemotherapy Protocols↗

A prospective comparison between magnetic resonance imaging, meta-iodobenzylguanidine scintigraphy and marrow histology/cytology in neuroblastoma.

A prospective comparison between magnetic resonance imaging (MRI), 123I meta-iodobenzylguanidine (mIBG) scintigraphy and posterior iliac crest marrow aspiration and trephine biopsy in 30 assessments (19 patients) showed concordance between the three techniques in 16 assessments (53.3%). In 10 (33.3%), MRI and mIBG revealed abnormalities not detected by marrow biopsy. MRI was the only technique to demonstrate marrow abnormality in four assessments (13.3%). In addition, MRI revealed more sites of abnormality in 16 parallel assessments. We conclude that MRI shows promise as a non-invasive means of detecting bone marrow infiltration by neuroblastoma, but that further evaluation of the specificity of MRI in this setting is indicated.

3-Iodobenzylguanidine↗

Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia: double-blind, placebo-controlled trial.

In a randomised, double-blind trial 20 patients with leukaemia received human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and 20 received placebo, for 14 days after allogeneic, matched sibling, bone-marrow transplantation. The neutrophil count recovered to 0.5 x 10(9)/l 3 days earlier in the GM-CSF group than in the placebo group (not significant), and the median neutrophil count at 14 days was significantly higher in the GM-CSF group (1.90 vs 0.46 x 10(9)/l). The lymphocyte count was significantly higher in the GM-CSF than in the placebo group between days 10 and 15 after transplantation, but this difference was not associated with a higher incidence of graft-versus-host disease. There was no evidence that GM-CSF was associated with a greater incidence of leukaemic relapse. The GM-CSF group had lower haemoglobin concentrations and platelet counts and higher plasma urea, creatinine, and bilirubin than the placebo group. The duration of hospital stay was the same for both patient groups. Further studies are now indicated to assess the overall effect of GM-CSF on outcome after allogeneic bone-marrow transplantation.

Adolescent↗

BACUP--the first two years: evaluation of a national cancer information service.

The cancer information service of the British Association of Cancer United Patients (BACUP) was launched in October 1985 as a national service to patients and their relatives, the public, and health professionals. Information is provided by telephone and letter by seven nurses trained in oncology. In the first two years over 30,000 inquiries were received: 23,527 (80%) were from women; 9445 (32%) were from cancer patients 11,574 (39%) from relatives of patients, and 2869 (10%) from health professionals. Inquiries came from all over the United Kingdom and from all sections of society but users were predominantly middle class, aged between 30 and 49, and living in south east England. Information about specific cancer sites, treatment, and how to cope was most commonly sought. Nearly a third of all inquiries were related to breast cancer. Though the service is used more by particular groups focusing on particular diseases, clearly there is a need for a cancer information service in the UK.

Adolescent↗

Myelitis associated with protozoal infection in newborn calves.

Four newborn calves from different herds were examined because of recumbency and inability to rise. Abnormal physical findings were confined to the nervous and/or musculoskeletal systems. Because of poor prognosis, all calves were euthanatized and necropsied. The histopathologic findings were multifocal lymphocytic myelitis, meningitis, and encephalitis associated with protozoal cysts.

Animals↗

Tumour necrosis factor in man: clinical and biological observations.

Eighteen patients with advanced cancer have been treated intravenously with human recombinant tumour necrosis factor (rhTNF). The drug produced febrile reactions at all doses although these were preventable by steroids and indomethacin. Doses at or above 9 x 10(5) units (400 micrograms)m-2 were associated with hypotension, abnormal liver enzymes, leucopenia and mild renal impairment in a substantial proportion of patients. RhTNF was cleared from plasma with a half life of approximately 20 minutes but non-linear pharmacokinetics lymphoma, improvements in their tumours were recorded. RhTNF was noted to produce rapid increases in serum C-reactive protein concentrations. Endogenous TNF levels were not found to be elevated in 72 cancer patients. TNF deserves further therapeutic evaluation and these observations support its biological importance as an endogenous pyrogen, mediator of acute phase protein responses, and a mediator of endotoxic shock.

Adolescent↗

A viral etiology for Hodgkin's disease?

There have been numerous suggestive but inconclusive reports of a possible infectious etiology for Hodgkin's disease. The discovery of the causative agent of the adult T cell leukemia-lymphoma syndrome suggests that a similar agent to the human T cell leukemia-lymphoma virus may have a causal role in Hodgkin's disease.

Adolescent↗

Immunotherapy for acute myelogenous leukemia.

One hundred and seven untreated patients with acute myelogenous leukemia (AML) were admitted to St. Bartholomew's Hospital between the 10th October 1970 and the 31st January 1973. Before receiving drugs to induce remission they were allocated alternatively into 2 groups to decide their remission treatment, a group to receive chemotherapy alone and a group to receive the same chemotherapy with immunotherapy. The patients were then given induction chemotherapy and 45 of them attained complete remission. All patients in remission then received chemotherapy consisting of 5 days treatment every 28 days. Patients receiving immunotherapy were also given multiple weekly intradermal injections of irradiated stored AML cells and Glaxo BCG using a Heaf gun. There were 19 patients in the group which received only chemotherapy during remission; 7 of these patients remain alive (median survival after attaining remission--303 days) and only 5 are still in their first remission (median remission length 188 days). Twenty three patients were allocated to receive immunotherapy during remission in addition to chemotherapy and 16 remain alive (median 545 days) and 8 are in their first remission (median 312 days). The difference in survival of the 2 groups is significant with a sigma value of 0.003.

Age Factors↗