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T C Pearson

Publications and source records attributed to T C Pearson.

At least 91 records · Page 5Linked to original sources
PubMed1996

The diagnostic criteria of polycythaemia rubra vera.

There is no single diagnostic marker for polycythaemia vera (PV). The Polycythemia Vera Study Group established diagnostic criteria more than twenty years ago. Since some new laboratory and clinical investigations have developed, these criteria can now be updated. It is proposed that the overall pattern of major and minor criteria should remain. A raised red cell mass (greater than 25% above the patient's mean normal predicted value based on surface area) and absence of a cause of secondary polycythaemia are essential criteria. Then either palpable splenomegaly or the presence of a marker of clonal haemopoiesis would support the diagnosis of PV. In the absence of both of these latter major criteria, at least two minor criteria must be present to secure the diagnosis. These are: platelet count > 400 x 10(9)/l; neutrophil count > 10 x 10(9)/l; splenomegaly demonstrated by a scanning technique; characteristic BFU-E growth or reduced serum erythropoietin value.

Alkaline Phosphatase↗
PubMed1996

Evolving strategies in immunosuppressive therapy: the Emory experience.

We have reviewed our experience with various immunosuppression regimens over the past 11 years in 2,065 renal transplant recipients. Patients received triple-drug maintenance therapy with CsA, imuran and prednisone following either no induction therapy or treatment with polyclonal (PCA) or monoclonal (MCA) antibody. The most recent immunosuppressive regimen has included CsA, MMF, and prednisone without induction therapy. We observed that those patients receiving PCA had a better graft survival 5 years after transplantation than recipients with MCA induction or those receiving standard triple drug therapy without induction. Patients receiving MMF experienced superior one-year graft survival compared with those receiving induction with PCA, MCA or standard triple drug therapy. A similar one-year graft survival rate for both Black and White recipients was observed in the MMF group and raises the possibility of achieving improved long-term graft survival in Black recipients with a MMF-based immunosuppression strategy. Our experience indicates that excellent short-term graft survival can be achieved with an immunosuppressive protocol of MMF, CsA and prednisone without induction. Graft survival in MMF-treated recipients was equal to or superior to that which we previously achieved with induction therapy.

Antilymphocyte Serum↗
PubMed1995

Fas-mediated cytotoxicity. An immunoeffector or immunoregulatory pathway in T cell-mediated immune responses?

Fas/Fas ligand interactions serve as a signaling pathway for apoptosis (1-3), an important regulatory mechanism in the development and function of the immune system (4-9). Recent evidence that Fas-dependent apoptosis is also an important mode of T cell cytotoxicity (10-13) suggested that Fas might play a critical role in the effector phase of T-dependent immune responses, such as allograft rejection. We observed that Fas transcripts are constitutively expressed in syngeneic and allogeneic murine cardiac transplants, while Fas ligand (FasL) is up-regulated only in rejecting allografts. Surprisingly, the absence of an intact Fas/FasL pathway did not alter the tempo of allograft rejection, even CD4-dependent rejection. These results indicate that Fas/FasL interactions are not essential mediators of T cell-induced allograft damage. Rather, as suggested in other studies, the Fas pathway may be principally involved in the regulation of clonal expansion and subsequent contraction of T cell populations during immune responses.

Animals↗
PubMed1995

Donor-recipient microchimerism is not required for tolerance induction following recipient pretreatment with donor-specific transfusion and anti-CD4 antibody. Evidence of a clear role for short-term antigen persistence.

There is considerable current interest in the possibility that long-term graft acceptance in clinical solid-organ transplantation might be dependent upon the development of a microchimeric state between the donor and recipient. This possibility has been prompted by the observation that in some transplant patients cells of donor origin can be detected in peripheral sites such as the skin, and it has been proposed that these cells play an essential role in maintaining graft survival. The hypothesis that peripheral microchimerism is an absolute requirement for the long-term survival of solid-organ allografts was tested in a well-characterized model of transplantation tolerance in which adult recipient mice are pretreated 28 days before transplant with a single donor-specific transfusion under the cover of a depleting anti-CD4 antibody. Mice pretreated with this protocol accept donor-specific cardiac allografts (MST > 100 days) but reject those of a third party (MST 16.5 days). The protocol leads to operational tolerance in the long term in that donor-specific skin grafts show prolonged survival while those from a third party strain are rejected acutely. Since peripheral blood contains haematopoietic stem cells we speculated that the success of the anti-CD4/DST protocol might be dependent on the development of microchimerism. To address this possibility the DST was irradiated before administration under anti-CD4 antibody cover in order to prevent donor stem cells in the transfusion from establishing a microchimeric state in the recipient animals. Mice in this group rejected their grafts acutely (MST 12 days), suggesting indeed that stem cells might be very important in the success of this model. However, when the protocol was modified by giving three additional doses of irradiated whole blood to increase the possibility that recipient T cells would be engaged during antibody-induced immunocompromise, graft prolongation was restored (MST > 100 days). These results demonstrate that persistence of donor antigen at the time of anti-CD4 antibody treatment is critical for the induction of unresponsiveness in this model and show that microchimerism is not an absolute requirement for long-term graft survival.

Animals↗
PubMed1995

Interpretation of measured red cell mass and plasma volume in adults: Expert Panel on Radionuclides of the International Council for Standardization in Haematology.

Four European centres provided height and weight data on 202 males and 204 females undergoing red cell mass (RCM) and plasma volume (PV) measurements. For these populations, the RCM and PV predictions by the various published methods were compared. It was shown clearly that predictions based solely on body weight were inappropriate, particularly because approximately half of the male and female populations could be regarded as overweight or obese. Although there was reasonable agreement in the prediction values given by the formulae based on both height and weight, it was not possible to establish which formulae could be recommended. For that reason, the published literature containing normal RCM and PV measurements were re-examined. RCM data for 283 males and 171 females and PV data for 100 males and 67 females were included. Measurements were standardized for variables such as trapped plasma in the PCV, exclusion of buffy coat in the PCV and calculation of PV at zero time. As a result of this analysis, prediction formulae based on surface area for RCM and PV with 98/99% reference ranges have been established.

Adult↗
PubMed1995

Pregnancy in sickle cell disease in the UK: results of a multicentre survey of the effect of prophylactic blood transfusion on maternal and fetal outcome.

OBJECTIVE: To determine the outcome of pregnancies complicated by sickle cell disease in the UK during 1991-1993 and the effect of prophylactic blood transfusion programmes on maternal and fetal outcome. DESIGN: A multicentre study. SUBJECTS: Eighty-one pregnancies complicated by sickle cell disease and 100 pregnancies from women of black African descent without haemoglobinopathies to act as a comparative group. Pregnancies complicated by sickle cell disease were divided by the type of haemoglobinopathy and also by transfusion regimen. MAIN OUTCOME MEASURES: Antenatal and postnatal complications of sickle cell disease, proteinuric hypertension, preterm delivery, emergency delivery by caesarean section, fetal distress, birthweight, perinatal and maternal mortality. RESULTS: There were two maternal deaths in the 81 pregnancies and the perinatal mortality rate was 60/1000. Antenatal sickling complications occurred in 46.2% of pregnancies and postnatal sickling complications occurred in 7.7% of pregnancies. Pregnancies complicated by sickle cell disease were significantly more likely to be associated with anaemia, preterm delivery, proteinuric hypertension, birthweight below the 10th centile and caesarean section as an emergency procedure than the comparative group. Severe sickling complications occurred more commonly in the third trimester and there was some evidence that a prophylactic transfusion programme reduced the risk of this. Prophylactic transfusion did not improve obstetric outcome when compared with those pregnancies that were untransfused. CONCLUSIONS: Sickle cell disease remains a severe complicating factor to pregnancy and perinatal mortality and maternal mortality rates in the UK have increased since last reported. A policy of exchange transfusing all women with homozygous sickle cell disease (HbSS) from 28 weeks gestation is recommended to reduce the risk of maternal complications in the third trimester and puerperium. There remains a role for earlier prophylactic blood transfusion programmes in women with poor obstetric and haematological histories.

Anemia, Sickle Cell↗
PubMed1995

Identification of latent myeloproliferative disease in patients with Budd-Chiari syndrome using X-chromosome inactivation patterns and in vitro erythroid colony formation.

Some patients with an early or latent myeloproliferative disorder (MPD) present with Budd-Chiari syndrome (BCS, hepatic vein thrombosis). Cell culture analysis of erythroid progenitors (BFU-E) can be used to discriminate primary from secondary MPD and examination of X-chromosome inactivation (in females) can be used to demonstrate clonality in neoplastic tissues. The present study used these techniques to examine whether a group of 7 female patients who presented with BCS had evidence to support a diagnosis of MPD. Unilateral X-inactivation and therefore clonality can be studied in females heterozygous for X-linked restriction fragment length polymorphisms (RFLP) by differences in methylation between active and inactive chromosomes. Probes for two polymorphic loci, phosphoglycerate kinase (PGK, at Xq13.3 [BstX1 RFLP]) and M27 beta (an anonymous locus DXS255 at Xp11.22 [Pst1 RFLP]) were used to study methylation patterns. All 7 patients were heterozygous using M27 beta and 2/7 were also heterozygous using the PGK probe. Polyclonal patterns of X-inactivation in granulocytes were demonstrated in 3/7, a skewed/monoclonal pattern in 1/7 and aberrant patterns in 3/7 using M27 beta. Two patients who had aberrant patterns of X inactivation with M27 beta demonstrated a skewed/monoclonal pattern with PGK. The results of BFU-E growth patterns and clonality were entirely concordant in 5/6 patients. Thus X-chromosome inactivation patterns, in conjunction with erythroid colony studies, can be used to assist in the diagnosis of an underlying MPD in BCS.

Biomarkers↗
PubMed1995

Activated phenotype in neutrophils and monocytes from patients with primary proliferative polycythaemia.

AIM: To investigate whether monocytes and neutrophils from patients with primary proliferative polycythaemia (PPP) exhibit increased expression of markers of cell activation and, if so, whether they are associated with the phagocytic activity of these cells and concentrations of circulating cytokines. METHODS: Expression of CD11b, CD14, CD18, and CD64 on monocytes and neutrophils was assessed by flow cytometry. Phagocytosis was analysed using immunoglobulin opsonised Escherichia coli. Serum concentrations of granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) were determined by bioassays, and interferon-gamma (IFN-gamma) by enzyme linked immunosorbent assay (ELISA). RESULTS: Patients with PPP (n = 18), when compared with normal subjects (n = 10), had increased percentages of CD64+ monocytes (52% v 36%) and neutrophils (42% v 11%) and of CD14+ neutrophils (36% v 18%). Monocytes from patients with PPP exhibited increased expression of CD64 (47 v 26) and of CD11b (65 v 36). These abnormalities were not found in patients with secondary (n = 8) or apparent (n = 13) polycythaemia. The percentage of neutrophils undergoing phagocytosis was higher in patients with PPP (mean 64%; n = 6) than in normal subjects (mean 42%; n = 5). G-CSF, GM-CSF and IFN-gamma concentrations in patients' serum samples were comparable with normal; M-CSF was not detected in any of the samples. There was no correlation between cytokine concentrations and the expression of CD11b, CD14, CD18, and CD64 on patients' phagocytes. CONCLUSIONS: Increased expression of CD11b and CD64 by monocytes, increased percentages of CD14+ and CD64+ neutrophils and the high phagocytic activity of neutrophils suggests that these cells are activated in vivo in patients with PPP. The phenotypic changes of PPP phagocytes were not associated with increased concentrations of circulating cytokines and probably reflect intrinsic abnormalities within the neoplastic PPP clone.

Antigens, CD↗
PubMed1995

Prolongation of murine cardiac allograft survival by microspheres containing TNF alpha and IL1-beta neutralizing antibodies.

Efficient delivery of therapeutic agents to a critical microenvironment may increase the efficacy of drugs used to modulate the allograft rejection response. This study demonstrates the ability of the combination of microspheres containing neutralizing anti-TNF alpha and anti-IL1-beta antibodies to significantly prolong murine cardiac allograft survival. These results suggest that the microsphere technique is an efficacious method to target antibody delivery to prolong allograft survival.

Animals↗
PubMed1995

Optimal haematocrit and haemoglobin S levels in pregnant women with sickle cell disease.

Sickle cell blood has abnormal rheological characteristics and its viscosity is determined by the level of haemoglobin S and the PCV. Rheological studies have shown that alteration of these parameters will improve oxygen delivery to the tissues. However, there is no agreed policy for optimum levels for haemoglobin S and PCV in the management of pregnancies complicated by sickle cell disease. In this study rheological measurements have been performed on pregnant women with sickle cell disease and compared with women without haemoglobinopathy. Potential oxygen delivery was not found to approach normal levels until very low levels of HbS were achieved. The optimal PCV for women with sickle cell disease was found to be 0.26 compared with 0.33 for normal women.

Anemia, Sickle Cell↗
PubMed1995

Low serum erythropoietin--a strong diagnostic criterion of primary polycythaemia even at normal haemoglobin levels.

Estimations of serum erythropoietin level by enzyme immunoassay (EIA) kit were made in 42 patients with primary polycythaemia, and in a comparison group consisting of 41 patients with secondary polycythaemia and 47 patients with idiopathic erythrocytosis. The majority of patients with primary polycythaemia were undergoing treatment by venesection and therefore had Hb levels in the normal range at the time of erythropoietin estimation. In primary polycythaemia, 64% of the first samples taken from each patient were below the reference range for serum erythropoietin in normal individuals. When two samples were taken from each patient 72% had low values in one or both samples. In the comparison group, analysis of those patients who had two samples taken showed only one individual with secondary polycythaemia and none with idiopathic erythrocytosis who had a serum erythropoietin level below the reference range. The finding of low serum erythropoietin in patients with primary polycythaemia, even when Hb levels are normal due to venesection, is of high diagnostic specificity (few false positive results) and useful diagnostic sensitivity (28% false negative results). It is proposed that future diagnostic criteria of primary polycythaemia should include the finding of a serum erythropoietin level below the lower limit of normal in at least one of two serum samples taken on different occasions.

Adult↗
PubMed1994

Transplantation tolerance induced by CTLA4-Ig.

The rejection of the transplanted allograft is dependent on T cell activation, which requires T cell receptor engagement by antigen and costimulatory signals delivered by T cell surface molecules such as CD28. CTLA4-Ig is a fusion protein that has previously been shown to block the CD28-mediated costimulatory signal and inhibit immune responses in vitro and in vivo. In this report we show that treatment of the C3H/He recipient of a BALB/c vascularized cardiac allograft with a 12-day course of CTLA4-Ig produced indefinite graft survival (> 100 days) in the majority of recipients. In addition, these recipients demonstrated donor-specific transplantation tolerance when tested with donor-specific (BALB/c) and third-party (C57BL/10) skin grafts. These results demonstrate that CTLA4-Ig can induce transplantation tolerance in the adult murine cardiac allograft model.

Abatacept↗
PubMed1994

Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells.

Dendritic cells (DC) play a critical role in the initiation of T cell-mediated immune responses, and express costimulatory molecules that are required for optimal activation of unprimed T cells. Studies on the regulation of the costimulatory molecules on DC have produced evidence from several systems that GM-CSF can up-regulate expression of CTLA4 counter receptor (CTLA4-CR) (but not intercellular adhesion molecule 1 (ICAM-1) and heat stable Ag (HsAg)) on DC. This is demonstrated on splenic DC, Langerhans cells, kidney DC in culture, and in a skin-explant culture system, in which the increased expression of CTLA4-CR on Langerhans cells (LC) occurs concomitantly with their migration out of skin. Interestingly, despite the ability of both GM-CSF and IFN-gamma to increase CTLA4-CR and maintain similar levels of ICAM-1, HsAg, and MHC molecule expression, the functional consequences of these cytokines on splenic DC are distinctly different. GM-CSF enhances the ability of DC to stimulate both T cell proliferation and cytokine release, whereas IFN-gamma causes no increase in immunostimulatory function. Further analysis of the CTLA4-CR on these cell populations by using the GL-1 and IG10 mAbs has shown that GM-CSF-cultured DC express high levels of both B7-1 and B7-2, whereas IFN-gamma-cultured DC express increased levels of only B7-2. These results suggest that optimal stimulation of unprimed T cells to proliferate and release cytokines may require participation of both of these CTLA4 counter receptors, and confirm the importance of GM-CSF for the maturation of DC into potent stimulators of T cell activation.

Abatacept↗
PubMed1994

The in vitro effects of stem cell factor, interleukin 3 and granulocyte-macrophage colony stimulating factor on haemopoietic progenitor cells from premature infants.

Circulating haemopoietic progenitor cells from premature infants were assessed for their ability to respond to interleukin 3, granulocyte-macrophage colony stimulating factor and stem cell factor (SCF) in vitro. All three cytokines increased the number of colonies derived from burst forming units erythroid (BFU-E), colony forming units granulocyte-macrophage (CFU-GM) and multi-lineage progenitors (CFU-Mix) grown in the presence of erythropoietin (Epo). The size and haemoglobin content of BFU-E derived colonies also increased in the presence of the cytokines. Of those tested, SCF was found to be the most potent additive to Epo for the enhanced growth of BFU-E and CFU-Mix. In short-term liquid cultures without Epo, SCF alone induced globin synthesizing cells. Progenitors from premature infants were at least as responsive to all three cytokines as those from healthy adults. The use of SCF in combination with Epo in the prevention or treatment of anaemia in premature infants warrants further investigation.

Cells, Cultured↗
PubMed1994

Primary thrombocythaemia: a composite approach to diagnosis.

Traditional diagnostic criteria for primary thrombocythaemia (PT) remain essentially negative, aiming to exclude other myeloproliferative disorders and causes of reactive thrombocytosis (RT). It would be useful to have positive markers. We have examined several parameters to see how well they discriminate between PT and RT. Three groups of patients were studied: new, untreated PT (17), treated PT (12) and RT (17). Data consisted of: ESR, plasma fibrinogen, factor VIIIC, von Willebrand factor antigen (vWF:Ag), PDW, platelet nucleotide ratio (ATP:ADP) serum erythropoietin (Epo), ristocetin cofactor (vWF:RiCoF), multimeric structure of vWF, interleukin-6, evidence of clinical ischaemia and erythroid colony formation. Erythroid colonies were assayed in a serum-free system with the addition of Epo, IL3 or alpha-IFN to produce a discriminant function (DF) successfully used in the diagnosis of primary polycythaemia in an earlier study. Acute phase reactants (ESR, fibrinogen, VIIIC, vWF:Ag) and IL6 were the best discriminants, while PDW and serum Epo were less so. ATP:ADP and clinical ischaemia were nondiscriminatory in this study. Reduction in vWF:RiCof and in high molecular weight multimers were clearly associated with PT. Endogenous erythroid colonies were nondiscriminatory, but half the PT group and only one patient in the RT group obtained a DF suggestive of myeloproliferative disorder. Judicious use of a battery of tests may provide support for diagnosis of PT in difficult cases.

Adolescent↗
PubMed1994

Blood transfusion in pregnancies complicated by maternal sickle cell disease. Effects on blood rheology and uteroplacental Doppler velocimetry.

Doppler ultrasound gives a measure of downstream resistance to blood flow. In this study it has been used to assess the change in placental vascular resistance following blood transfusion in pregnancies complicated by sickle cell disease. Eight women with homozygous sickle cell disease were followed prospectively to assess the effect of transfusion on haemoglobin S percentage, blood and plasma viscosity and uteroplacental Doppler velocimetry. Measurements were made immediately pre and post-transfusion and after several weeks when the desired improvement in haemoglobin S had been achieved. Despite significant changes in haemoglobin S levels and consequent rheological change there was found to be no change in measurements of resistance in the uteroplacental circulation as assessed by Doppler ultrasound.

Anemia, Sickle Cell↗