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Biomedical subjects

H D Alexander

Publications and source records attributed to H D Alexander.

At least 19 recordsLinked to original sources
PubMed2005

All-trans retinoic acid-induced downregulation of annexin II expression in myeloid leukaemia cell lines is not confined to acute promyelocytic leukaemia.

Most acute promyelocytic leukaemia (APL) patients suffer from disordered haemostasis. APL can be treated successfully in most instances by all-trans retinoic acid (ATRA) therapy, which induces endpoint maturation of the leukaemic promyelocytes with the characteristic t(15;17). Annexin II (AnII), a profibrinolytic protein, has been implicated in the bleeding manifestation seen in APL. Our group has shown previously that high levels of AnII are expressed on other acute myeloid leukaemia subtypes that are sometimes associated with disordered haemostasis, albeit less frequently than APL. This study examined the effects of ATRA on AnII expression and cell differentiation, on myeloid leukaemia cell lines to determine whether a regulatory influence on AnII may contribute to the return of haemostatic stability in APL following treatment. The results confirmed that AnII expression in the APL cell line (NB4) was significantly downregulated in response to ATRA (P < 0.01), with associated morphological and immunophenotypical evidence of myeloid differentiation. ATRA also downregulated AnII expression on other myeloid cell lines, albeit to a lesser extent than observed on NB4 cells. The results provide evidence that ATRA may resolve the hyperfibrinolysis in APL by downregulation of AnII expression.

Analysis of Variance↗
PubMed2004

ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement.

ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.

Adult↗
PubMed2004

Annexin A2 expression during cellular differentiation in myeloid cell lines.

Annexin A2 is a calcium-dependent, phospholipid-binding protein found on many cell types. It consists of a short hydrophobic tail (Ser(2)-Asn(32)), which dictates its function, and a core domain (Phe(33)-Asp(339)), which is involved in phospholipid binding. Annexin A2 has been implicated in a number of biochemical processes, including cell proliferation, foetal immune tolerance, ion-channel activation, cell-cell interactions and the bridging of membranes. Annexin A2 is reported to be a powerful activator of plasminogen and, therefore, is implicated in many normal and pathological processes such as haemostasis and metastasis. Myeloid cell lines are used, extensively, to study many aspects of cellular proliferation, differentiation and function. In the present study, we have used flow cytometry and real-time PCR to investigate the role of annexin A2 expression in the proliferation and differentiation of a number of myeloid cell lines. The results demonstrated that annexin A2 expression was affected when the cells were induced to differentiate by stimulation with all-trans-retinoic acid. Annexin A2 may, therefore, be an important player in cellular differentiation and its disorders.

Animals↗
PubMed2004

WHO reclassification of breast lymphomas.

Fourteen cases of breast lymphoma, identified from hospital records between 1990 and 2004, were reclassified according to the World Health Organisation criteria. Primary cases occurred more frequently and all cases were of B cell origin, predominantly involving the right breast. Most primary cases were diffuse large B cell lymphomas, whereas secondary cases were heterogeneous in type and most had a poor prognosis.

Aged↗
PubMed2003

Plasma levels of the immunomodulatory cytokine interleukin-10 during normal human pregnancy: a longitudinal study.

Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve foetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p<0.05, p<0.01 and p<0.0001, respectively), and in mothers post-delivery (p<0.01) when compared to non-pregnant control subjects. Furthermore, there was no significant effect of gestational time on IL-10 concentration. Results from the current study suggest that elevated IL-10 is a physiological consequence of normal healthy pregnancy. These findings help clarify previous conflicting results and establish a range for plasma levels of IL-10 in normal healthy pregnancy.

Adjuvants, Immunologic↗
PubMed2003

Immunoglobulin gene rearrangement investigations in the diagnosis of lymphoid malignancies from formaldehyde-fixed biopsies.

Determination of the biologic potential of lymphoid proliferations in biopsies can be difficult by standard histological or even immunohistochemical examination. Polymerase chain reaction (PCR) has been used with increasing frequency to detect clonal rearrangements of the immunoglobulin heavy chain (IgH) in formaldehyde fixed, paraffin wax embedded tissues. Sensitivity ranges between 50 and 80%, and therefore at least 20% of neoplasms remain undetected by these approaches. Few investigators have attempted to detect immunoglobulin light chain (IgL) gene rearrangements by PCR using paraffin wax embedded samples. We studied 29 cases of B-cell neoplasms, along with 21 cases with equivocal histology and 4 reactive biopsies, using degenerate oligoprimers to amplify Ig(kappa) and Ig(lambda) light chain genes, along with IgH (Fr 1, 2 and 3) gene rearrangement analysis. The combination of these methods detected clonality in 93% of cases (27/29) with histological diagnosis of B-NHL. Fr2 and Fr3 primers detected clonality in 79% (23/29) of cases. IgL chain rearrangements detected 4 cases (14%), negative for IgH rearrangements, improving sensitivity from 79 to 93%. Clonality was detected in 52% (11/21) of histologically equivocal lymphoid proliferations, including one case detected by IgL rearrangements which was negative for IgH rearrangements. Archival material from 4 cases with reactive histology produced polyclonal results. These results confirm that PCR based immunoglobulin gene rearrangement is a sensitive and specific method for demonstrating B-cell clonality in paraffin-wax embedded sections. The addition of IgL analysis to the IgH assay allows the detection of greater than 90% of B-cell lymphoproliferative disorders from routine histological specimens with poor preservation of genomic DNA.

Biopsy↗
PubMed2003

Spontaneous splenic rupture in atypical (Philadelphia chromosome negative) chronic myeloid leukaemia following blastic crisis.

Philadelphia chromosome negative and bcr/abl negative chronic myeloid leukaemia (CML) is an uncommon atypical CML. We describe a patient with this disorder who experienced an acute blastic transformation that resulted in rapid splenic enlargement and subsequent atraumatic splenic rupture. Clinically, spontaneous splenic rupture may be a difficult diagnosis to make and this case highlights the importance of considering atraumatic splenic rupture as a cause for unexplained abdominal pain in a patient with a haematological malignancy.

Aged↗
PubMed2002

Immunohistochemical expression of CD10 and t(14;18) chromosomal translocation may be indicators of follicle centre cell origin in nodal diffuse large B-cell lymphoma.

AIMS: Although diffuse large B-cell lymphoma is categorized as a distinct entity in the REAL classification of lymphomas, it represents a heterogeneous group of neoplasms. A subgroup is probably of follicle centre cell origin and may evolve from a pre-existing follicular lymphoma. The t(14;18) chromosomal translocation can be demonstrated in the majority of follicular lymphomas and the aim of this study was to investigate the prevalence of t(14;18) translocation in a series of de novo nodal diffuse large B-cell lymphomas. We correlated this with the immunohistochemical expression of CD10, bcl2 and bcl6, markers which are usually expressed by the neoplastic cells in follicular lymphomas. We also correlated these parameters with the presence or absence of p53 protein expression by the neoplastic cells. METHODS AND RESULTS: Nodal diffuse large B-cell lymphomas (n=34) were stained immunohistochemically with monoclonal antibodies to CD10, bcl2, bcl6 and p53 (D07). Polymerase chain reaction (PCR) for the t(14;18) translocation was also performed. Fourteen, 24 and 29 (41%, 71%, 85%) cases exhibited positivity for CD10, bcl2 and bcl6, respectively. In 12 cases there was positivity with D07 (35%). By PCR, the t(14;18) translocation was identified in five cases (15%), four of which were positive for CD10 and bcl2 and all of which were positive for bcl6. One of five cases positive for the chromosomal translocation exhibited positivity with D07. CONCLUSIONS: In this study the t(14;18) translocation was identified in 15% of diffuse large B-cell lymphomas, all but one of which exhibited positivity for CD10, bcl2 and bcl6. These may represent cases of follicle centre cell origin which may or may not have evolved from a pre-existing follicular lymphoma. It is possible that positivity for CD10 especially may identify cases which are of follicle centre cell origin and that the absence of t(14;18) translocation in some of these cases may reflect the fact that the translocation cannot normally be demonstrated in all follicular lymphomas. Whether the presence or absence of the translocation and the immunophenotype are prognostically important should be investigated further.

Biomarkers, Tumor↗
PubMed2002

Red cell aplasia due to erythrovirus parvovirus B19 infection in a Jehovah's witness with post-transplant EBV-induced aggressive lymphoma: management considerations.

The refusal of Jehovah's Witnesses to accept blood and blood products often poses a clinical dilemma to present day medicine. We present a case of a Jehovah's Witness who had undergone renal transplantation, only to develop an Epstein-Barr virus associated aggressive lymphoma post-transplant. His condition was further complicated by erythrovirus (parvovirus) B 19 infection resulting in red cell aplasia and severe anemia. The management of this difficult clinical situation is discussed together with a review of recommendations for chemotherapy treatment in Jehovah's Witnesses.

Adult↗
PubMed2002

Myelodysplasia terminating in acute myeloid leukemia in a hairy cell leukemia patient treated with 2-deoxycoformycin.

Purine analogs are effective in the treatment of several chronic lymphoproliferative disorders (CLPD) including hairy cell leukemia (HCL). To date, little evidence exists that these drugs are oncogenic. We report a case of HCL in a 66-year-old male treated with 2-deoxycoformycin. Just over 1 year following completion of his treatment, falling platelet and white cell counts were associated with the development of dysplastic features in his bone marrow and a rising blast cell count, culminating in the development of acute myeloid leukemia (AML). To the best of our knowledge only two previous cases of AML have been linked to treatment of HCL with purine analogs, both with 2-chlorodeoxyadenosine. We emphasize the need for long term follow up of patients treated with purine analogs and suggest that even those who are apparently cured be monitored periodically.

Acute Disease↗
PubMed2002

Soluble P-selectin levels during normal pregnancy: a longitudinal study.

OBJECTIVE: To investigate soluble P-selectin (sP-selectin) levels and platelet parameters in normal pregnant women compared with non-pregnant control subjects. DESIGN: A longitudinal case-control study. SETTING: Obstetric outpatient clinic in the Jubilee Maternity Hospital, Belfast. POPULATION: One hundred and twenty normal pregnant women and 41 non-pregnant age-matched control subjects. METHODS: The plasma concentration of sP-selectin in pregnant women sampled at 12, 20 and 35 weeks of gestation, and, in a subgroup at three days postpartum, and non-pregnant controls sampled in parallel, was determined using a commercial quantitative sandwich immunoassay kit. Platelet parameters on each blood sample were also recorded using a SYSMEX SE 9500 analyser. MAIN OUTCOME MEASURES: Plasma sP-selectin as a measure of platelet activation in normal pregnancy. RESULTS: Soluble P-selectin was significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation, (P < 0.01, and P < 0.001, respectively). Correlation analyses showed positive correlation between sP-selectin and platelet count in pregnant women at 20 and 35 weeks of gestation (r = 0.247, P < 0.05 and r = 0.360, P < 0.001, respectively). Soluble P-selectin concentration per platelet was also significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation (P < 0.001). CONCLUSIONS: Our results show that sP-selectin concentration is significantly higher in the second and third trimester of pregnancy when compared with non-pregnant control subjects sampled in parallel. This finding clarifies previous conflicting results on platelet activation in normal pregnancy, and is in agreement with those earlier studies which reported, using other methods, increased platelet activation in normal pregnancy.

Adolescent↗
PubMed2002

Tissue factor expression on monocyte subpopulations during normal pregnancy.

Pregnancy is often referred to as a hypercoagulable state due to changes in the haemostatic system. Tissue factor (TF) is the initiator of blood clotting in vivo. The effect of pregnancy on monocyte TF expression was determined in a longitudinal case control study (89 pregnant, 39 non-pregnant). Using whole blood flow cytometry and CD14 as a monocyte marker, TF expression was measured on all CD14 positive, CD14Bright and CD14Dim cells. TF expression was significantly lower in pregnant women than in non-pregnant control subjects, on all CD14 positive cells at 20 and 35 weeks, on CD14Bright cells at 12 and 35 weeks and on CD14Dim cells at 20 weeks. Additionally, we report that a higher percentage of CD14Dim than CD14Bright cells express TF. These results suggest that, in order to maintain homeostasis in haemostasis in an otherwise hypercoagulable state, monocyte TF expression is reduced during normal pregnancy.

Adult↗
PubMed2001

Mantle cell lymphoma presenting as a breast mass.

Breast lymphoma accounts for less than 1% of all non-Hodgkin's lymphomas (NHLs) and approximately 0.1% of all breast neoplasms. Most breast lymphomas are classified as diffuse large B cell or mucosa associated lymphoid tissue (MALT) lymphomas. The case of a 53 year old woman presenting with a breast mass and found to have mantle cell lymphoma is described. Core biopsy of the breast lesion showed a B cell NHL, probably of large cell type and of high grade. Morphological and immunophenotypic analysis of peripheral blood and bone marrow samples suggested a mantle cell lymphoma (MCL). This was confirmed by the detection of a t(11;14) in the bone marrow aspirate and breast tissue by polymerase chain reaction analysis. There have been no previous reports of an MCL presenting as a breast lump. Because a diagnosis of MCL has prognostic and therapeutic implications, this case highlights the need for an awareness of MCL presenting in this way, and the requirement for specialised investigations in its detection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Total serum IL-12 and IL-12p40, but not IL-12p70, are increased in the serum of older subjects; relationship to CD3(+)and NK subsets.

Interleukin 12 (IL-12), a central cytokine acting on T and natural killer (NK) cells, directs proliferation of activated T lymphocytes towards a Th1 phenotype. The heterodimeric molecule IL-12p70, equates with IL-12 biological activity, while IL-12p40 may antagonize IL-12 and inhibit cytotoxic T lymphocyte (CTL) generation in vitro. This study characterizes age-related changes in serum total IL-12, IL-12p70 and IL-12p40 relating them with CD3(+), NK and related subsets from subjects, aged 30-96 years. Total IL-12, IL-12p40 and the IL-12p40/IL-12p70 ratio, but not IL-12p70, increased significantly with age (P<0.0001). Increases in total IL-12 and IL-12p40 were negatively associated with CD3(+)(P=0.003, P=0.002), CD3(+)CD4(+)(P=0.004, P=0.003), CD3(+)CD8(+)(P=0.04;P=0. 04) and CD4(+)45RA(+)(P=0.0003;P=0.0007) subsets, respectively. Conversely, increases in IL-12p40 showed a non-significant trend for association with increases in NK(P=0.07) and a related CD8(+low)CD57(+)(P=0.07) subset. These findings may have important implications for understanding the functional activity of IL-12 and its p40 and p70 subunits in vivo and with respect to T-or NK-cell activation in aging.

Adolescent↗
PubMed2000

Quantitative deficiency of monocyte-specific esterase (MSE) mRNA in monocyte esterase deficiency (MED).

Cytochemical staining of monocyte-specific esterase (MSE) is widely used for identification of the monocytic lineage in leukaemias. Deficiency of this enzymatic activity occurs as a familial trait and the deficiency has been shown to occur with greater frequency in patients with lymphoproliferative or gastrointestinal malignant neoplastic diseases than in normal blood donors. Reverse transcriptase polymerase chain reaction (RT-PCR), sequencing and quantification by Northern blot analysis was conducted on the MSE mRNA of 12 subjects with monocyte esterase deficiency (MED) and seven MSE-positive subjects to examine whether mutations were present or whether the defect was quantitative. Mutations were not found in the mRNA sequences. However, MED subjects had significantly less MSE mRNA than MSE-positive subjects (P = 0.001). These findings show that deficiency of monocyte esterase activity in MED is not as a result of the presence of inactive isoenzymes and may be owing to an abnormality in the regulation of mRNA production.

Anemia, Hemolytic, Autoimmune↗
PubMed2000

Red cell indices as predictors of iron depletion in blood donors.

The objective of this study was to investigate whether red cell indices mean cell volume (MCV) and mean cell haemoglobin (MCH) were lower in frequent blood donors and hence, indirectly, able to predict impending iron depletion. Serum ferritin and/or soluble transferrin receptor levels can be used to evaluate iron status but are not practical for routinely screening blood donors prior to donation. Hb, MCV and MCH were measured on venous blood from 886 blood donors using a Sysmex E-5000. Full details were obtained for all donors of each earlier donation over the previous 3 years. MCV and MCH levels were lowest in donors with the highest frequency of previous blood donation. There was a significant negative correlation between MCV and number of donations in males and females and between MCH and number of donations in females, over the 3 year period 1995-97. Similar trends were observed when only the previous year's donations (1997) were considered with all categories showing significant negative correlations and additionally, Hb levels in females showed negative correlation with number of donations in 1997. In conclusion, increased frequency of blood donations is associated with lower MCV and MCH. These red cell indices, or more sophisticated parameters such as percentage hypochromic cells, should be used to monitor early onset of iron depletion in frequent blood donors.

Blood Donors↗