Cell markers in hairy cell leukemia studied in cells from 51 patients

To determine the maturation arrest of the neoplastic cells of hairy- cell leukemia (HCL) and the spectrum of the surface markers on these cells, a series of 51 patients with this disease was studied. The cells of all but two of the patients showed monoclonal surface Ig with respect to light chains. In about one-third of the cases, only gamma heavy chain determinants were present on the cells; the majority carried multiple heavy chain determinants as documented by the application of different fluorochromes. Two patients each showed two different clones of cells, both of the same light chain type. In one of these two patients, two paraproteins were present in the serum. Intracytoplasmic Ig was found in only 4 of 39 cases, in all instances being IgM. All cases studied concerned cells with FclgG receptors; however, the density of this receptor varied. FcIgM receptors also showed a spectrum of density, with some cases showing very few FcIgM- positive cells. Receptors C3 were not observed on the hairy cells. Serum immunoglobulin levels were normal or increased. Paraproteins were found in the sera of 4 of 38 patients. These data suggest that HCL is a neoplasm of B lymphocytes. The neoplastic cells are probably arrested at a more mature stage than the cells of chronic lymphocytic leukemia. The multiple isotypes on the cells indicate a block at the "switch" phase from the small micro-carrying lymphocyte to the larger Ig- producing lymphocyte or plasma cell.     

Glucose-stimulated insulin secretion: the hierarchy of its multiple cellular and subcellular mechanisms

Glucose-stimulated insulin secretion is ensured by multiple molecular, cellular and tissue events. In this issue of Diabetologia, Low et al (DOI: 10.1007/s00125-013-3019-5) have taken an important new step towards understanding the hierarchical organisation of these events, by monitoring in vitro the individual exocytosis of multiple beta cells within intact mouse islets. The authors show that glucose stimulation markedly increases the number of exocytotic events per cell and, to a lesser extent, the number of beta cells contributing to this event. In this commentary we discuss these novel observations and propose that metabolic and electrical coupling of islet beta cells is responsible for a more homogeneous glucose-induced secretory response of cells in an intact islet as compared with isolated beta cells.     

Multiple heavy chain isotypes on the membrane of the small B lymphocytes in human blood.

Small lymphocytes from adult human blood were examined for the presence of membrane-associated alpha, gamma, delta and mu Ig isotypes by means of a direct immunofluorescence technique. Since less than 10% of the small lymphocytes in blood are B cells as defined by positive reactivity with an anti-Fab conjugate, our experiments were performed on a T cell-depleted fraction in which about 80% of the small lymphocytes were B cells. With the two-wavelength immunofluorescence method, all of the double-isotype combinations were found. The percentage of cells bearing more than two isotypes was deduced. The delta mu and the alpha delta mu combinations were the most common, as previously found on tonsillar lymphocytes. In contrast with the tonsils, no lymphocytes bearing only delta were observed and the proportions of alpha gamma- and alpha gamma mu-bearing lymphocytes were very small. The presence of lymphocytes bearing four isotypes could practically be excluded.     

Kinetics of phagocyte response to group B streptococcal infections in newborn rats.

To test the hypothesis that inadequate in vivo mobilization of leukocytes may contribute to the unique susceptibility of neonates to infection, we studied the kinetics of phagocyte response to neonatal and adult rats to intraperitoneal infection with group B streptococcus, type Ia. The 50% lethal dose was considerably greater for adults than for neonates (1.1 x 10(7) colony-forming units per g versus 2.7 x 10(2) colony-forming units per g). After challenge with group B streptococcus, type Ia, the number of neonatal peritoneal leukocytes increased more slowly than did those of adult rats. For example, at 4 h, the adult neutrophil count was 41 times greater than that of the neonate, but at 24 h, neonatal peritoneal neutrophils had not yet reached the adult 4-h level. Peritoneal macrophages also increased more rapidly in adults than in neonates. After intraperitoneal infection, both adults and neonates developed bacteremia, but adults cleared the bacteria with greater efficiency. Adult blood neutrophils increased 247% by 12 h and then decreased; neonatal neutrophils steadily decreased to a 57% reduction by 24 h. These data suggest that the neonatal neutrophil response to group B streptococcus, type Ia, infection is inadequate and may contribute to the high mortality associated with this infection.     

Identification of mononuclear cells in human blood. II. Evaluation of morphological and immunological aspects of native and formaldehyde-fixed cell populations.

The presence of surface-associated immunoglobulins and Fc receptors on mononuclear cells from normal human blood was investigated by the direct immunofluorescence technique combined with phase-contrast microscopy. Formaldehyde-fixed cells were compared to unfixed cells and to cells preincubated at 37 degrees C. In the unfixed samples a separate population which showed Fc receptors in an immunofluorescence technique using a labelled antigen--antibody complex was detected. This cell population showed an atypical, i.e. not clearly membrane-associated, pattern of fluorescence with anti-Fab conjugates. This interaction most probably is due to autologous IgG molecules taken up by these cells from the donor serum. Using phase-contrast microscopy, these cells were morphologically distinct from lymphocytes and mature monocytes. They will be referred to as 'undefined mononuclear cells' (UMC). After formaldehyde fixation or preincubation at 37 degrees C the interaction of the UMC with anti-Fab conjugates could no longer be demonstrated. Mature monocytes show the same atypical fluorescence pattern with anti-Fab conjugates, but in contrast to the UMC the interaction persists after formaldehyde fixation or preincubation at 37 degrees C. No evidence was found for passive uptake of labelled IgG from conjugates by any mononuclear cell F(ab')2 fragments of IgG from antisera gave results similar to those obtained with intact IgG fractions. The morphology of the different cell subpopulations is described and their relative numbers in normal blood are given. Formaldehyde fixation proved to be a simple and useful procedure, especially for the determination of the number of B lymphocytes, because the Fc receptor of the undefined mononuclear cell does not give rise to confusion.     

Economic incentives and nutritional behavior of children in the school setting: a systematic review

The aim of the present review was to examine the existing literature on the effectiveness of economic incentives for producing sound nutritional behavior in schools. Studies published in the English-language literature that included baseline and/or outcome data regarding food and beverage intake of schoolchildren were eligible for inclusion. A systematic search of the literature was conducted to identify relevant primary studies and relevant systematic reviews of primary studies. Altogether, 3,472 research publications were identified in the systematic search, of which 50 papers were retrieved. Of these, 30 publications representing 28 studies fulfilled the criteria for inclusion. The studies addressing price incentives suggest that such incentives are effective for altering consumption in the school setting. Other types of economic incentives have been included in combined intervention schemes, but the inclusion of other intervention elements makes it difficult to draw conclusions about the effectiveness of the economic incentive instruments per se in these studies.