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Climate change and land-use activities are increasing fire activity across much of the Siberian boreal forest, yet the climate feedbacks from forest disturbances remain difficult to quantify due to limited information on forest biomass distribution, disturbance regimes and post-disturbance ecosystem recovery. Our primary objective here was to analyse post-fire accumulation of Cajander larch (Larix cajanderi Mayr.) aboveground biomass for a 100 000 km2 area of open forest in far northeastern Siberia. In addition to examining effects of fire size and topography on post-fire larch aboveground biomass, we assessed regional fire rotation and density, as well as performance of burned area maps generated from MODIS satellite imagery. Using Landsat imagery, we mapped 116 fire scar perimeters that dated c. 1966–2007. We then mapped larch aboveground biomass by linking field biomass measurements to tree shadows mapped synergistically from WorldView-1 and Landsat 5 satellite imagery. Larch aboveground biomass tended to be low during early succession (≤ 25 yr, 271 ± 26 g m−2, n = 66 [mean ± SE]) and decreased with increasing elevation and northwardly aspect. Larch aboveground biomass tended to be higher during mid-succession (33–38 yr, 746 ± 100 g m−2, n = 32), though was highly variable. The high variability was not associated with topography and potentially reflected differences in post-fire density of tree regrowth. Neither fire size nor latitude were significant predictors of post-fire larch aboveground biomass. Fire activity was considerably higher in the Kolyma Mountains (fire rotation = 110 yr, fire density = 1.0 ± 1.0 fires yr−1 × 104 km−2) than along the forest-tundra border (fire rotation = 792 yr, fire density = 0.3 ± 0.3 fires yr−1 × 104 km−2). The MODIS burned area maps underestimated the total area burned in this region from 2000–2007 by 40%. Tree shadows mapped jointly using high and medium resolution satellite imagery were strongly associated (r2 ≈ 0.9) with field measurements of forest structure, which permitted spatial extrapolation of aboveground biomass to a regional extent. Better understanding of forest biomass distribution, disturbances and post-disturbance recovery is needed to improve predictions of the net climatic feedbacks associated with landscape-scale forest disturbances in northern Eurasia.

Permafrost soils store between 1,330–1,580 Pg carbon (C), which is three times the amount of C in global vegetation, almost twice the amount of C in the atmosphere, and half of the global soil organic C pool. Despite the massive amount of C in permafrost, estimates of soil C storage in the high latitude permafrost region are highly uncertain, primarily due to under sampling at all spatial scales; circumpolar soil C estimates lack sufficient continental spatial diversity, regional intensity, and replication at the field-site level. Siberian forests are particularly under sampled, yet the larch forests that dominate this region may store more than twice as much soil C as all other boreal forest types in the continuous permafrost zone combined. Here we present above and belowground C stocks from twenty sites representing a gradient of stand age and structure in a larch watershed of the Kolyma River near Cherskiy, Sakha Republic, Russia. We found that the majority of C stored in the top 1 m of the watershed was stored belowground (91 %), with 20 % in the top 10 cm of soil and 42 % in the top 30 cm. Carbon was more variable in surface soils (10 cm; coefficient of variation (CV) = 0.35 between stands) than in the top 30 cm (CV = 0.14) or soil profile to 1 m (CV = 0.12). Combined active layer and deep frozen deposits (surface – 15 m) contained 205 kg C m-2 (yedoma, non-ice wedge) and 331 kg C m-2 (alas), which, even when accounting for landscape-level ice content, is an order of magnitude more C than that stored in the top meter of soil and two orders of magnitude more C than in aboveground biomass. Aboveground biomass was composed of primarily larch (53 %) but also included understory vegetation (30 %), woody debris (11 %) and snag (6 %) biomass. While aboveground biomass contained relatively little (9 %) of the C stocks in the watershed, aboveground processes were linked to thaw depth and belowground C storage. Thaw depth was significantly negatively related to stand age, and variability of soil C in the top 10 cm was related to soil moisture and moss and lichen cover. These results suggest that as the climate warms, changes in stand age and structure may be as important as direct climate effects on belowground environmental conditions and permafrost C vulnerability.

Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies. Clinical staging, recurring acquired cytogenetic aberrations, and serum biomarkers such as β-2 microglobulin, and free light chains are in widespread use but often fail to predict the disease progression or inform treatment decision making. Recent scientific advances have provided considerable insight into the biology of myeloma. For example, gene expression profiling is already making a contribution to enhanced understanding of the biology of the disease whilst Next Generation Sequencing has revealed great genomic complexity and heterogeneity. Pathways involved in the oncogenesis, proliferation of the tumour and its resistance to apoptosis are being unravelled. Furthermore, knowledge of the tumour cell surface and its interactions with bystander cells and the bone marrow stroma enhance this understanding and provide novel targets for cell and antibody-based therapies. This review will discuss the development in understanding of the biology of the tumour cell and its environment in the bone marrow, the implementation of new therapeutic options contributing to significantly improved outcomes, and the progression towards more personalised medicine in this disorder.

Background Rheumatoid arthritis (RA) is an autoimmune condition characterised by inflamed joints. Disease-modifying anti-rheumatic drugs (DMARD) are ineffective in 30–40% of patients. CD169 (Siglec-1) is expressed by monocytes and correlates with disease activity in RA. It drives pro-inflammatory processes including the suppression of Tregs through its cognate ligand, CD169L. This study aims to define the relationship between CD169, CD169L and disease activity, as a potential early biomarker of treatment response. Methods Peripheral blood mononuclear cells were isolated from healthy controls and RA patients who failed DMARD treatment. FACS was used to: (i) immunophenotype CD169+ monocytes and CD169L+ Tregs, and (ii) assess levels of FoxP3 within Tregs. Results RA patients had a significantly higher percentage of CD169+ monocytes (28.47 ± 7.17, (mean ± SEM), n=19) compared to healthy controls (8.03 ± 1.48, n=19, p= Conclusion These results provide preliminary evidence of a relationship between CD169 and CD169L, and further define how their balance is associated with disease activity. Low levels of FoxP3 in RA patients indicates reduced Treg activation, which may cause increased disease activity. We postulate that this balance of cells is key in the immune response and could be used as a surrogate measure of disease activity.

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.

SUMMARY The characteristic finding of autoantibodies in patients with vasculitis has raised the possibility that these antibodies play a role in the pathogenesis of the disease. The expression of adhesion molecules (AM) on leucocytes and endothelial cells is believed to be integral to the development of vasculitis. We therefore investigated the effect of sera, positive for anti-neutrophil cytoplasmic antibodies (ANCA) or anti-nuclear antibodies (ANA) from patients with vasculitis, on granulocyte expression of the adhesion molecule Mac-1 (CD11b). Autoantibody-positive sera from 15 out of 35 patients with vasculitis stimulated an up-regulation of Mac-1 on granulocytes. In most cases this effect was reproduced by the autoantibody-positive purified IgG fraction. Autoantibody-negative samples did not stimulate AM up-regulation. Of interest, preincubation of sera with purified antigens did not inhibit AM up-regulation by the autoantibody samples. Blocking the Fc receptors on granulocytes did result in a decrease of Mac-1 up-regulation, but this trend was not statistically significant. These results suggest that both ANCA and ANA have the capacity to up-regulate granulocyte AM expression, and that while Fc interaction with granulocyte Fc receptors is important, it is not the only mechanism whereby such autoantibodies activate cells.

Climate change and land-use activities are increasing fire activity across much of the Siberian boreal forest, yet the climate feedbacks from forest disturbances remain difficult to quantify due to limited information on forest biomass distribution, disturbance regimes, and post-disturbance ecosystem recovery. Our primary objective here was to analyze post-fire accumulation of Cajander larch (Larix cajanderi Mayr.) aboveground biomass for a 100 000 km2 area of open forest in far northeastern Siberia. In addition to examining effects of fire size and topography on post-fire larch aboveground biomass, we assessed regional fire rotation and density, as well as performance of burned area maps generated from MODIS satellite imagery. Using Landsat imagery, we mapped 116 fire scar perimeters that dated ca. 1969–2007. We then mapped larch aboveground biomass by linking field biomass measurements to tree shadows mapped synergistically from WorldView-1 and Landsat 5 satellite imagery. Larch aboveground biomass tended to be low during early succession (≥ 25 yr, 271 ± 26 g m−2, n=66 [mean ± SE]) and decreased with increasing elevation and northwardly aspect. Larch aboveground biomass tended to be higher during mid-succession (33–38 yr, 746 ± 100 g m−2, n=32), though was highly variable. The high variability was not associated with topography and potentially reflected differences in post-fire density of tree regrowth. Neither fire size nor latitude were significant predictors of post-fire larch aboveground biomass. Fire activity was considerably higher in the Kolyma Mountains (fire rotation = 110 yr, fire density = 1.0 ± 1.0 fires yr−1 × 104 km−2 than along the forest-tundra border (fire rotation = 792 yr, fire density = 0.3 ± 0.3 fires yr−1 × 104 km−2. The MODIS burned area maps underestimated the total area burned in this region from 2000–2007 by 40%. Tree shadows mapped jointly using high and medium resolution satellite imagery were strongly associated (r2≈0.9) with field measurements of forest structure, which permitted spatial extrapolation of aboveground biomass to a regional extent. Better understanding of forest biomass distribution, disturbances, and post-disturbance recovery is needed to improve predictions of the net climatic feedbacks associated with landscape-scale forest disturbances in northern Eurasia.

Complete functional deficiency of the phagocytic cell enzyme, myeloperoxidase, is described in a patient with rheumatoid arthritis. Measurement of oxygenation and free radical activity by blood monocytes and polymorphonuclear leucocytes shows gross reduction in myeloperoxidase-dependent chemiluminescence. Implications of these data for theories linking reactive oxygen species to inflammatory tissue damage in rheumatoid arthritis are discussed.

AIMS: To determine if leucocyte volume distribution analysis (LVDA), obtained using a Coulter Counter Model S Plus IV, can be used to aid differentiation of chronic lymphoproliferative disorder (CLPD) subtypes. METHODS: Mean lymphocyte volume and lymphocyte distribution width were measured on each patient (n = 90) using a hard copy of an amplified LVDA histogram. The mean lymphocyte volume was taken as the mean of the values on either side of the peak at half maximum height. The lymphocyte distribution width was taken as the range of cell values between the two values used to calibrate the mean lymphocyte volume. A template showing typical histograms from commonly occurring CLPD was also produced on an acetate sheet. This was used to examine the histogram from each new patient to evaluate its usefulness as an alternative to the calculation of mean lymphocyte volume and lymphocyte distribution width. RESULTS: Mean lymphocyte volume and lymphocyte distribution width were significantly higher in B cell lymphocytic leukaemia of mixed cell type (B CLL/PL), B cell non-Hodgkin's lymphoma with peripheral blood spill, hairy cell leukaemia and T cell prolymphocytic leukaemia than in B cell chronic lymphocytic leukaemia (B CLL). The mean lymphocyte volume, but not the lymphocyte distribution width, was also significantly higher in T cell chronic lymphocytic leukaemia than in B CLL. The template gave an immediate preliminary indication of possible subtype(s) of disorder and could be used as an alternative to measurement of mean lymphocyte volume and lymphocyte distribution width. CONCLUSIONS: Electronic haematology analysers producing an LVDA provide a useful, cost effective cell sizing analysis which can aid the differentiation of subtypes of CLPD.

Summary We recently demonstrated a higher incidence of monocyte esterase deficiency in patients with lymphoproliferative neoplasia and gastrointestinal carcinoma than in the normal population. Using lactoferrin to stimulate monocyte cytotoxicity we have now compared the abilities of esterase positive and esterase deficient monocytes to lyse K562 cells. The esterase deficient monocytes were from normal subjects whose monocytes have consistently failed to show cytoche-mical esterase staining over 30–72 months and which lack specific monocyte isoenzymes. The esterase positive monocytes were from age and sex matched control subjects. Esterase positive monocytes responded to lactoferrin stimulation by a five-fold increase in cytotoxicity whereas deficient monocytes failed to produce any response. These results indicate a possible defect in cytotoxicity of esterase deficient monocytes and together with the epidemiological findings suggest a link between monocyte esterase deficiency and neoplasia.

The distribution of circulating CD4 lymphocyte subpopulations determined by reactivity with monoclonal antibodies anti-2H4 (CD45RA), anti-UCHL1 (CD45RO), anti-4B4 (CD29) and anti-Leu8, and analysed by dual colour immunofluorescence flow cytometry is described in a series of patients with B-CLL and in age-matched control subjects. The percentages and absolute numbers of CD4 cells reactive with anti-CD45RA, anti-CD45RO and anti-CD29 reagents were similar in the patient and control groups. In contrast, CD4+ Leu8+ cells (percentages and absolute numbers) were significantly reduced in B-CLL patients resulting in an inversion of the normal CD4+ Leu8+ :CD4+Leu8- ratio. The patients' clinical or therapeutic status did not appear to influence the levels of the respective CD4 subpopulations; nor was evidence of hypogammaglobulinaemia associated with specific numerical alterations in any of the CD4 subpopulations studied. It is proposed that, in B-CLL, the alterations in the CD4Leu8 subpopulations are associated with the disease process, whereas the distributions of CD4+CD45RA+, CD4+ CD45RO+ and CD4+ CD29+ cells reflect the normal physiological levels of these subpopulations in elderly subjects.

Deletions of chromosome 14 recurrently observed in B-cell malignancies are particularly frequent in chronic lymphocytic leukemia (CLL), multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia.1 To characterize these aberrations, we initially mapped the deletions in 23 leukemia/lymphoma cases using a tiling path chromosome 14-array CGH (aCGH) platform (resolution of approximately 42 kb) comprising 838 bacterial artificial chromosome/P1 artificial chromosome (BAC/PAC) clones from the Chori 32K set (www.ensembl.org). Del(14)(q) have been successfully mapped in all 23 cases (Figure 1a) and subdivided into two main categories: (1) involving or (2) not involving 14q32.33. This latter category grouped eight cases with interstitial deletions ranging in size from 17 to 70 Mb and distributed along chromosome 14 (q13 ter) and one case with three dispersed deletions of 1.5, 7.5 and 2.5 Mb. The first category of del(14)(q) comprised 14 cases showing the common distal breakpoint mapped in the 105.26–105.41 Mb region harboring the IGH genes cluster. The size of the deleted region varied in six cases; their proximal breakpoints were bordered by RP11-164H3/95.19 Mb, CTD-2053J06/83.56 Mb, RP11-340F04/74.66 Mb, RP11-350H11/67.94 Mb, RP11-769O09/66 Mb and RP11-520H13/65 Mb. Particularly intriguing was the finding of exactly the same del(14)(q24.1q32.33) covering the region of approximately 36 Mb in eight cases (Figure 1b). The proximal border of this deletion was consistently flanked by RP11-35D12 (68.24 Mb)( 2) and RP11-720I19 (68.45 Mb)( 1), and the distal breakpoint was bordered by RP11-448N05 (105.26 Mb)( 1) and RP11-284A08 (105.43 Mb)( 2). Given that these terminal BACs are assigned to IGCH and IGVH, respectively, aCGH results were additionally validated by fluorescence in situ hybridization (FISH) with the LSI-IGH break-apart probe. As expected, all eight analyzed cases (as well as the remaining six cases with nonrecurrent IGH-involving deletions) showed a one-fusion one-green signal pattern due to loss of the 3'IGH flanking sequences (red signal). The proximal breakpoint of the del(14)(q24.1q32.33) validated with RP11-35D12 and RP11-720I19 showed lost or diminished signal from the latter clone (Figure 1b) and thereby pointed to a breakpoint in the region covered by the overlapping extremities of these BAC clones. The only gene located in this region was ZFP36L1. For FISH detection of the del(14)(q24.1q32.33) in other B-cell non-Hodgkin's lymphoma (B-NHL), a dual-color break-apart assay for the 14q24.1 breakpoint (RP11-35D12-SO/RP11-720I19-SG) and LSI-IGH were applied. The screening of 58 B-NHL cases with cytogenetic and/or FISH evidence of del(14)(q) led to identification of 13 additional cases with del(14)(q24.1q32.33), including one with the deletion masked by t(14;22)(q32;q11)/IGH-IGL (case 7). Additional FISH screening of 60 random CLL cases, seven MM cell lines, including four (RPMI-8226, L-363, OPM-1 and LP-1) with a previously described del(14),2 and 20 various B-NHL cases with structural aberrations of 14q21–q24, failed to identify ZFP36L1 and/or IGH rearrangements, indicating that these deletions are rare molecular events.

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.

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.

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.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.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.

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.

P-selectin is an adhesion molecule found in the alpha granules of platelets. Activation occurs in response to a range of inflammatory and thrombotic agents resulting in rapid up-regulation. Flow cytometry methods have recently been described for the analysis of platelet P-selectin expression in whole blood. While introducing these methods into our laboratory it was noted that expression could be stimulated, in vitro, in a number of ways. This study shows that red cell lysis, the anticoagulant K3 EDTA and the time elapse between blood collection and antibody labelling had statistically significant effects on P-selectin expression. Post-labelling fixation, with CellFIX, caused no significant effect. We conclude that blood for P-selectin analysis should be collected in sodium citrate and that red cell lysis and centrifugation should be avoided. When comparing samples, the time between collection and labelling should be standardized. The relatively high CV for the assay indicates that all samples should be labelled and analysed in duplicate with the mean level reported.

Small differences in levels of certain haemostatic components may be clinically significant. It is important therefore to eliminate potential sources of confounding variability. This study investigated the effect of removing tourniquet pressure prior to sample collection on plasma fibrinogen levels, platelet P-selectin and monocyte tissue factor expression. Blood was collected from the right arm under maintained tourniquet pressure and from the left arm following the release of pressure once the vein was sufficiently inflated for insertion of a needle. Whole blood was labelled within one hour of venepuncture to allow analysis of platelet P-selectin and monocyte tissue factor by flow cytometry. Plasma fibrinogen levels were analysed in samples stored at -70 degrees C, for all individuals at the end of the study using a method based on the Clauss technique. Intra-individual variability for each of the components was assessed by collecting samples under tourniquet pressure from four individuals on the same day on three consecutive weeks. Intra-individual variations were greater than assay CVs for all three components. There were no significant differences between the two tourniquet methods of collection for fibrinogen, P-selectin or tissue factor. In conclusion, there is no reason not to use a tourniquet during collection of blood for analysis of plasma fibrinogen, platelet P-selectin or monocyte tissue factor.

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.

Aging has been shown to be accompanied by various changes in the lymphocyte subset distribution in the elderly. We have investigated more fully, and in a large number of subjects, age-related changes within several subpopulations bearing natural killer (NK) cell-associated surface antigens and changes in several cytokines involved in NK cell expansion. A total of 229 healthy subjects from all decades of life from 20 to 98 years of age was included in this cross-sectional study. A significant increase with age was found in both the absolute counts and the proportions of CD3-CD(16+56)+, CD3+CD(16+56)+, CD57+CD8+, CD57+CD8(low)+, and CD57+CD8- cells, whereas the CD57+CD8(high)+ subset, which may represent the cytolytic T cell population more precisely, showed less change with age. Some evidence is also provided to suggest that these expanded NK cell populations are in an activated state. Soluble IL-2 receptor levels were also found to increase significantly with age and correlated with certain NK cell subsets. Although the functions of some of these subsets remain to be elucidated, their expansion in the elderly may represent a remodeling of the immune system with increasing age, with an increase in non-MHC-restricted cells perhaps compensating for the previously reported decline in T and B cells in the elderly. Alternatively, increased numbers of these cells may be a direct result of cytokine dysregulation or increased antigenic or neoplastic cell challenge.