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Biomedical subjects

J I Craig

Publications and source records attributed to J I Craig.

At least 19 recordsLinked to original sources
PubMed2001

Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells.

Langerhans cells are a subset of dendritic cells (DCs) found in the human epidermis with unique morphological and molecular properties that enable their function as "sentinels" of the immune system. DCs are pivotal in the initiation and regulation of primary MHC class I restricted T lymphocyte immune responses and are able to present both endogenous and exogenous antigen onto class I molecules. Here, we study the MHC class I presentation pathway following activation of immature, CD34-derived human Langerhans cells by lipopolysaccharide (LPS). LPS induces an increase in all components of the MHC class I pathway including the transporter for antigen presentation (TAP), tapasin and ERp57, and the immunoproteasome subunits LMP2 and LMP7. Moreover, in CD34-derived Langerhans cells, the rapid increase in expression of MHC class I molecules seen at the cell surface following LPS activation is because of mobilization of MHC class I molecules from HLA-DM positive endosomal compartments, a pathway not seen in monocyte-derived DCs. Mobilization of class I from this compartment is primaquine sensitive and brefeldin A insensitive. These data demonstrate the regulation of the class I pathway in concert with the maturation of the CD34-derived Langerhans cells and suggest potential sites for antigen loading of class I proteins.

Antigens, CD34↗
PubMed2001

Antibody responses to vaccinations given within the first two years after transplant are similar between autologous peripheral blood stem cell and bone marrow transplant recipients.

As a consequence of the significantly larger inoculum of lymphoid cells present in peripheral blood stem cell (PBSC) harvests compared to bone marrow (BM), it is possible that autoPBSCT recipients may have an earlier and*or enhanced response to vaccines. Until data to confirm this become available, the European Blood and Marrow Transplantation Association (EBMT) recommend that all transplant recipients be immunized in the same way regardless of stem cell source. We performed a prospective study comparing serological responses to influenza, pneumococcal polysaccharide and tetanus toxoid vaccines between autoPBSCT with autoBMT recipients. Antibody responses in sibling HLA-matched allogeneic BMT (alloBMT) survivors were also evaluated. All vaccines were administered within the first 2 years after stem cell transplantation. Fifty patients were enrolled. The time of vaccination after transplant was similar between autoPBSCT (mean 11 months for each vaccine) and autoBMT recipients (mean 12 months except 13 months for tetanus toxoid) (P = NS). Serological responses were poor and no significant difference in response to any of the vaccines used was seen between the three transplant cohorts. We provide no evidence that current EBMT guidelines be modified. Large prospective vaccine studies are needed to address the issue more fully.

Adolescent↗
PubMed1999

A novel 8-bp insertion in codon 281 of p53 in a patient with acute lymphoblastic leukaemia and 2 separate leukaemic clones. Mutations in brief no. 219. Online.

We report a novel p53 insertion in a case of aggressive acute lymphoblastic leukaemia in a 16 year old male, in which 2 separate leukaemic clones were previously identified by T-cell receptor sigma and immunoglobulin heavy chain gene rearrangement studies. Initial p53 mutation screening of blast cells from 29 patients with acute leukaemia by PCR-denaturing gradient gel electrophoresis showed that 2 had a silent codon 213 polymorphism and only the index case had a somatic mutation identified to be an 8 bp insertion in codon 281 (5'CCGGGGGG-3'). This insertion was associated with the second, more aggressive clone which underwent clonal evolution and became resistant to cytotoxic chemotherapy. With an allele-specific primer in PCR, we were able to demonstrate the presence of this clone as a minority at disease presentation, and in 2 of 3 collections of peripheral blood progenitor cells.

Adolescent↗
PubMed1999

Nurse practitioner support for transfusion in patients with haematological disorders in hospital and at home.

We prospectively studied the effects of dedicating a nurse to manage the provision of blood product support in a hospital haematology unit and at home to 45 patients with haematological disorders requiring regular transfusion. During the study 335 home blood tests, 65 home platelet transfusions and 155 hospital transfusions were managed by the nurse who organized the whole transfusion process, made home visits for blood tests and platelet transfusions and arranged hospital visits for red cell transfusions. Two hundred clinic visits and 65 day hospital attendances were avoided. The nurse-led service resulted in a significant reduction in the waiting time from admission to transfusion and in the total length of in-patient stay. The importance of and satisfaction with different aspects of the care of the transfusion process assessed by a ranking questionnaire showed improved satisfaction scores for all aspects of care. Preference for home blood sampling instead of hospital increased from 24% before to 100% after intervention. We have shown that a dedicated transfusion nurse provides a quality service between hospital and home that is greatly appreciated by patients requiring regular transfusions.

Adult↗
PubMed1998

Flow cytometry using annexin V can detect early apoptosis in peripheral blood stem cell harvests from patients with leukaemia and lymphoma.

Quantifying progenitor cells in peripheral blood stem cell (PBSC) harvests by flow cytometric enumeration of CD34+ cells does not account for cell viability. Cell membrane asymmetry in early apoptosis exposes phosphatidylserine on the cell surface. This can be detected by staining with annexin V FITC. Apoptosis in 30 autologous PBSC harvests mobilised by cyclophosphamide + G-CSF or standard chemotherapy + G-CSF was analysed immediately after collection by dual-colour flow cytometry with CD34 PE and annexin V FITC. Harvests contained a median of 3.4 x 10(6)/kg (range 0.3-91.8) CD34+ cells. Of these 87.6% (range 30-96.5) were annexin V-. In 10% of harvests more than 50% of CD34+ cells were apoptotic. Differences in PBSC mobilisation or collection could not explain the variation in annexin V binding. Cyclophosphamide + G-CSF significantly increased the yield of CD34+ cells but did not increase apoptosis. Comparison of consecutive harvests showed no difference in the numbers of CD34+ cells collected but found a significant decrease in apoptotic CD34+ cells through multiple collections. Analysis of annexin V binding in PBSC harvests is a simple flow cytometry technique which gives additional information on the status of CD34+ progenitor cells.

Annexin A5↗
PubMed1998

Fas antigen (CD95) expression in peripheral blood progenitor cells from patients with leukaemia and lymphoma.

Fas antigen (CD95) is a cell surface receptor belonging to the tumour necrosis factor/nerve growth factor superfamily and is able to induce apoptosis when triggered by its' natural ligand or an anti-Fas antibody. Fas expression is low on CD34+ bone marrow (BM) progenitor cells, but is increased by various cytokines in vitro. We investigated Fas expression on CD34+ cells from 39 peripheral blood progenitor cell (PBPC) harvests and from 5 normal BM harvests by dual colour flow cytometry to determine if Fas expression was altered during mobilisation. By including calibrated microbeads during flow cytometry, we quantified the number of Fas antigen molecules per cell. A low percentage of PBPC (22%) and normal BM (23%) CD34+ cells expressed Fas antigen. Fas expression varied on CD34+ cells from different diseases and the highest expression was found in ALL (52%). There was a significant three fold increase in the number of Fas molecules/cell expressed on CD34+ cells (PBPC 6,230 molecules/cell, BM 2,236; p = 0.0003). This level of expression was considerably less than that for CD3/CD19 lymphocytes (33,095 molecules/cell) and CD14 monocytes (47,467 molecules/cell) in the PBPC harvest. In conclusion, mobilisation including the use of growth of factors, has minimal effect on CD34 progenitor cell Fas expression.

Antigens, CD↗
PubMed1994

Causes and clinical consequences of Rhesus (D) haemolytic disease of the newborn: a study of a Scottish population, 1985-1990.

OBJECTIVE: To identify the reasons behind failures to prevent the development of Rhesus (D) haemolytic disease of the newborn. DESIGN: Retrospective analysis of the case records of all pregnancies that resulted in the birth of an infant with a positive direct antiglobulin test on the cord red cells born to Rh(D) negative women between 1 April 1985 and 31 March 1990. SETTING: Obstetric units in the South East Scotland region and the South East Scotland Regional Blood Transfusion Service Antenatal Laboratory. MAIN OUTCOME MEASURES: The causes and clinical consequences of maternal immunisation to the Rhesus (D) antigen. RESULTS: Between 1985 and 1990, 80 pregnancies resulted in the birth of an infant sensitised with anti-D on the cord red cells. There were no deaths due to haemolytic disease, but considerable resources were deployed in obstetric and neonatal care for these pregnancies. Sufficient data were available to categorise the cause of maternal immunisation in 70 pregnancies. Seven cases were due to immunisation by pregnancy before 1970. Sixty-three cases could be attributed to failure of the Rhesus programme: 10 cases (16%) were due to failure to implement the programme adequately, the other 53 cases (84%) were due to failure of the current guidelines to provide adequate protection. Late immunisation in an uncomplicated pregnancy was the single commonest identifiable cause. CONCLUSIONS: It is likely that substantial further reductions in Rhesus (D) immunisation and haemolytic disease of the newborn will require changes in the Rhesus prevention programme. In particular the role of antenatal prophylaxis requires detailed consideration.

Erythroblastosis, Fetal↗
PubMed1994

Molecular detection of tumor contamination in peripheral blood stem cell harvests.

A total of 96 peripheral blood stem cell harvests (PBSCH) were collected following standard chemotherapy from 27 patients with leukemia, lymphoma, and myeloma. Tumor molecular markers were analyzed in diagnostic samples by Southern blot [immunoglobulin heavy chain (IgHJ), T cell receptor (TcR) delta chain, TcR beta chain] and polymerase chain reaction (PCR) amplification [IgH, TcR delta, t(14;18) translocation] and found in 11 of 22 and 13 of 27 patients, respectively. At a sensitivity of 2 to 5%, Southern blot analysis failed to detect tumor in PBSCH. Using PCR with sensitivities of 10(-4) (IgH, TcR delta) to 10(-6) [t(14;18)] tumor was present in 34 PBSCH collected from five patients with acute lymphoblastic leukemia and two with lymphoma. In these patients, PBSCH collected after successive courses of chemotherapy remained consistently positive. However, no tumor was detected in 28 PBSCH from five patients with lymphoma and one with myeloma. Of eight patients who had bone marrow examined (six concurrently) within 3 weeks of PBSCH, one had tumor in the PBSCH but not in the bone marrow, and three had tumor in the bone marrow but not in the PBSCH, indicating a possible advantage in using PBSC for autologous transplantation in these patients. Although PBSC are an alternative source of stem cells to bone marrow and are considered to have a lower incidence of tumor contamination, the majority of PBSC in this study were positive by PCR analysis. PCR analysis was unable to determine if a positive result represents clonogenic cells capable of initiating relapse following transplant.

Acute Disease↗
PubMed1993

Peripheral blood stem cell mobilization using high-dose cyclophosphamide and G-CSF in pretreated patients with lymphoma.

Peripheral blood stem cell (PBSC) mobilization for autologous transplantation is more difficult in treated patients and those with bone marrow involvement. In 17 pretreated lymphoma patients, cyclophosphamide (4 g/m2) and G-CSF mobilized a median circulating peak of 1959 CFU-GM/ml on day 12.5. PBSC harvesting commenced when WBC was 1 x 10(9)/l at day 10.5 collected a median of 21.2 x 10(4)/CFU-GM/kg. 13/17 (76%) patients exceeded the 10 x 10(4) CFU-GM/kg threshold for engraftment. The CFU-GM yield was significantly higher in patients whose WBC recovered from 1-5 x 10(9)/l in less than 3 days and correlated with the maximum WBC pre and post the cyclophosphamide induced nadir. This regime safely mobilized adequate PBSC in the majority of pretreated lymphoma patients.

Adult↗
PubMed1993

Regressing atypical histiocytosis: report of two cases with progression to high grade T-cell non-Hodgkin's lymphoma.

Two cases of regressing atypical histiocytosis (RAH) are presented. Both patients followed a typical regressing/relapsing course for several years before progression to high-grade neoplasia. In both cases these high-grade tumors were diagnosed as T-cell non-Hodgkin's lymphoma on histopathologic and immunophenotypic grounds, and demonstrated T-cell receptor beta chain (TCR beta) gene rearrangement on Southern blotting. The original cases of RAH were considered to be indolent neoplasms of histiocytic lineage. A single case of a patient with RAH demonstrating TCR beta and gamma gene rearrangements has been described. Our cases lend further weight to the proposition that RAH is a neoplasm of T-cell lineage, and ultimately of aggressive potential. This description accords with current thinking that many of the conditions previously classified as malignant histiocytosis would be better classified as T-cell non-Hodgkin's lymphoma.

Adolescent↗
PubMed1993

Clonal selection in acute lymphoblastic leukaemia demonstrated by polymerase chain reaction analysis of immunoglobulin heavy chain and T-cell receptor delta chain rearrangements.

Immunoglobulin heavy chain (IgH) and T-cell receptor (TcR) genes can be monitored as markers of clonality by polymerase chain reaction (PCR) analysis in acute lymphoblastic leukaemia (ALL). We report the short clinical course of a 16-year-old patient with ALL and a t(4;11) who relapsed early following treatment and subsequently received reinduction chemotherapy followed by peripheral blood stem cell transplantation with interleukin 2 therapy. Despite this, the patient relapsed and died 8 months after presentation. The leukaemic cells were analysed by PCR and showed rearrangements of TcR V delta 2-D delta 3 and IgH CDRIII genes. Direct sequence analysis of the TcR delta and IgH PCR products revealed two leukaemic clones at diagnosis with one present at minimal levels. After initial therapy the major clone was no longer detected even in subsequent relapse samples but the originally minimal clone persisted and increased despite further treatment, indicating drug resistance.

Adolescent↗
PubMed1992

Peripheral blood stem cell transplantation.

Haematopoietic stem cells are usually sessile within the bone marrow microenvironment. However, small numbers do circulate in the peripheral blood of normal individuals, and following chemotherapy and/or intravenous growth factors, a substantial transient rise in circulating stem cells occurs. Leukocytes harvested by cytapheresis at this time can be used for autologous reconstitution of the haematopoietic and lymphoid systems following high dosage chemo/radiotherapy for the treatment of malignant disease. Peripheral blood stem cell transplants give rise to similar disease response rates as autologous bone marrow transplants, but have the advantage of more rapid haematopoietic reconstitution, and in addition can be offered to patients in whom marrow harvest is not feasible due to bone marrow damage or infiltration. This article reviews the theoretical and historical background to haematopoietic stem cell research, current clinical practice in peripheral blood stem cell mobilisation and harvesting, addresses the potential advantages and disadvantages compared to bone marrow transplantation, and assesses current experience of comparative efficacy.

Animals↗
PubMed1992

Use of serum from patients with polycythaemia or haemochromatosis for laboratory external quality assurance exercises.

Some External Quality Assessment Schemes (EQAS) require large volumes of human serum. During a one year period, 595 units of blood were obtained from 87 patients with haemochromatosis and polycythaemia, who underwent therapeutic venesection at the Edinburgh and South East Scotland Blood Transfusion Service. Serum from 59% of these donations was used in the EQAS for peptide hormones and related substances. The cost of the serum collection was 109 pounds/litre, but was only 33 pounds/litre of serum if the cost of the actual venesection was excluded. Results from tests on the sera were satisfactory in a variety of immunoassays for several different hormones. EQA schemes with requirements for large volumes of serum should consider therapeutic venesection as a cost effective means of obtaining serum.

Adult↗
PubMed1991

Circulating progenitor cells in myelofibrosis: the effect of recombinant alpha 2b interferon in vivo and in vitro.

We have studied circulating progenitor cells in patients with myelofibrosis, the effects of recombinant alpha 2b interferon (IFN) treatment on these cells in vivo and in vitro and the patients' clinical response to IFN treatment. A 75-fold increase in circulating granulocyte macrophage colony forming units (CFU-GM) and a 25-fold increase in multilineage colonies (CFU-GEMM) were seen in the patients compared with controls. Patients who had undergone splenectomy had circulating progenitors within the normal range. IFN treatment of two patients resulted in clinical improvement and reduction in spleen size, but was complicated by a fall in platelet count and persistent malaise. Whilst on treatment the circulating progenitor cells increased up to 5-fold. In contrast, the addition of IFN in vitro to the CFU-GM and CFU-GEMM culture plates resulted in a dose-dependent inhibition of colony growth which was unaffected by the removal of T-cells and monocytes. Thus we confirm that circulating progenitors are raised in patients with myelofibrosis, IFN may be of benefit clinically, reducing spleen size but may increase levels of these cells in vivo. This is in contrast to the inhibitory effect of IFN in vitro on CFU-GM and CFU-GEMM growth.

Colony-Forming Units Assay↗
PubMed1990

The use of central venous catheters in paediatric oncology--a cautionary tale.

The use of indwelling central venous catheters has become widespread since their introduction by Broviac et al in 1973 and Hickman et al in 1974. They are of particular value in paediatric oncology where young children require intensive chemotherapy over a long period of time and where peripheral venous access may become a problem.

Adolescent↗