Expression of natural killer cell activating receptors in patients with chronic lymphocytic leukaemia

Recent advances in chronic lymphocytic leukaemia (CLL) treatment, more particularly through upfront use of anti-CD20 monoclonal antibodies, have prolonged patient progression-free survival. Nonetheless, apart from allogeneic stem cell transplantation, no curative treatment is available. One possible explanation for the lack of cure in CLL could be a defective immune anti-tumour response. As the result of abnormal HLA class I molecule expression, CLL cells escape from specific T-lymphocyte immunity but should be the target for the innate natural killer (NK) cell-mediated immune response. Defective NK cytotoxicity as the result of decreased expression of the natural cytotoxicity receptors (NCRs) NKp30/NCR3, NKp44/NCR2 and NKp46/NCR1 has been described in haematological malignancies such as acute myeloid leukaemia. This prompted us to focus our attention on NCR expression on NK cells from patients with CLL. Although we failed to detect any difference between CLL patients and healthy age-matched controls, a precise analysis of clinical data showed a correlation between decreased NCR expression and poor prognosis factors such as low haemoglobin level, high (>30×10(9) per litre) lymphocyte count or elevated C-reactive protein. Together, these observations support the rationale for restoration of normal NK cell functions in patients with CLL, putatively through the use of immune therapy protocols that already have demonstrated some benefit in acute myeloid leukaemia such as interleukin-2 plus histamine dihydrochloride.     

Challenging the sleep homeostat: sleep in depression is not premature aging

ObjectivesThe close relationship between major depression and sleep disturbances led to the hypothesis of a deficiency in homeostatic sleep pressure in depression (S-deficiency hypothesis). Many observed changes of sleep characteristics in depression are also present in healthy aging, leading to the premise that sleep in depression resembles premature aging. In this study, we aimed at quantifying the homeostatic sleep–wake regulation in young women with major depression and healthy young and older controls under high sleep pressure conditions.MethodsAfter an 8-h baseline night nine depressed women, eight healthy young, and eight healthy older women underwent a 40-h sustained wakefulness protocol followed by a recovery night under constant routine conditions. Polysomnographic recordings were carried out continuously. Sleep parameters as well as the time course of EEG slow-wave activity (SWA) (EEG spectra range: 0.75–4.5 Hz), as a marker of homeostatic sleep pressure, were analyzed during the recovery night.ResultsYoung depressed women exhibited higher absolute mean SWA levels and a stronger response to sleep deprivation, particularly in frontal brain regions. In contrast, healthy older women exhibited not only attenuated SWA values compared to the other two groups, but also an absence of the frontal SWA predominance.ConclusionsHomeostatic sleep regulation and sleep architecture in young depressed women are not equal to premature aging. Moreover, our findings demonstrate that young moderately depressed women exhibit no deficiency in the sleep homeostatic process S as predicted by the S-deficiency hypothesis, but, rather, live on an elevated level of homeostatic sleep pressure.     

Bone marrow transplantation in Fanconi anemia using matched sibling donors

Eighteen patients with Fanconi anemia (FA) with evidence of bone marrow (BM) aplasia underwent allogenic BM transplants (BMT) from matched sibling donors (MSD). Median age at BMT was 7.6 years. Conditioning consisted of low-dose cyclophosphamide (CY; 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI; 400 cGy). Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A and prednisone. In addition antithymocyte globulin (ATG) was administered in the pretransplant period to promote engraftment and in the posttransplant period for additional GVHD prophylaxis. Engraftment occurred rapidly (median, 12 days for an absolute neutrophil count > or = 0.5 x 10(9)/L; median, 22 days for platelet count > or = 50 x 10(9)/L). Seventeen patients have sustained engraftment and are transfusion-independent, with Lansky scores of 100% at median follow-up of 27 months. One patient developed graft failure 4 months after initial engraftment and required a second BM infusion. None of the patients developed acute GVHD; 3 patients (16%) developed chronic GVHD. BMT is a feasible option for FA patients having an MSD and should be performed at a young age and early in the course of the disease, before the development of complications. We believe the addition of ATG to the transplant regimen of low-dose CY, TAI, and cyclosporin was responsible for improvement in the survival of FA patients undergoing BMT. The regimen was well tolerated and was associated with a low incidence of complications including GVHD.     

Bronchopulmonary dysplasia: radiographic appearance in middle childhood

Chest radiographs were compared for three groups of children 8-9 years old: 23 survivors of bronchopulmonary dysplasia (BPD), 33 survivors of hyaline membrane disease without BPD, and 35 survivors of premature birth without neonatal respiratory problems. Only four children in the second group and three in the third had abnormal lungs. Linear shadows, apparently representing strands of fibrosis or deep pleural fissuring, were seen more frequently (15 of 23) in the BPD group than in the others (P less than .0001). Seventeen children in the BPD group had definite pulmonary abnormalities, none of them severe. The anteroposterior dimension of the chest in survivors of BPD tended to be decreased (P less than .001 vs that of reported control subjects).     

Effects and mechanisms of PCB ecotoxicity in food chains: Algae  fish  seal  polar bear 1

Wildlife populations are adversely affected in polluted environments. Nevertheless, a cause‐and‐effect relationship between excessive exposure to chlorinated hydrocarbons and induction of pathologic disorders in animals, is difficult to demonstrate without verification from experiments following the rationale of Koch's postulates. Deleterious effects of chlorinated chemicals such as DDT on songbird reproduction, as demonstrated by the clutch size of eggs in a nest, however, is an example, where exposure and causation are apparent. With amelioration of DDT pollution, clutch size increases, and the cause‐and‐effect relationship is established. Similar examples of exposure to DDT and PCBs inducing reproductive disorders and endocrine disruption among marine mammals have been documented in industrialized nations of northern Europe and in the upper latitudes of the Northern Hemisphere. Population declines in ringed, grey and harbor seals are apparently due to a rapid decrease in their rates of reproduction¹. These latter observations are best interpreted in light of experiments conducted by Reijnders². Reijnders exposed harbor seals to relatively high dietary levels of PCBs and induced PCB‐blood‐lipids among seals to an average of 25 mg/kg compared to 10 mg/kg among controls. The treated seals had a significantly reduced reproductive rate. A relationship between increased PCB‐blood‐levels in vivo and the decrease in reproductive rates in this experiment is highly instructive for interpreting the decline of fertility in seal populations in polluted Baltic Sea waters. These linked observations are dependent upon demonstration of pathologic mechanisms associated with occlusion and stenosis of the uterine lumen among affected females in seal populations.

PCB congeners apparently disrupt endocrine‐system‐functions leading to, or associated with, increases in endometriosis, fetal abortion, glomerulonephropathies and osteoporosis. This observation is further highlighted by Reijnders experiment, which closely replicated the range of PCB concentrations found in seal populations living in a variety of PCB polluted waters.

Various PCB congeners differentially accumulate in brain, liver and adipose tissues in young and old seals. Further research of PCB toxic effects on organ systems of these animals and other species is thus indicated.

This report, then, examines the process of PCB bioaccumulation within the marine food chain from fish to seals, whales, other marine mammals and to polar bears. Environmental toxic pollutants affect animals within the food chain in different ways but ultimately they affect humans as well.