The impact of obesity on skin disease and epidermal permeability barrier status.

BACKGROUND: Obese subjects frequently show skin diseases. However, less attention has been paid to the impact of obesity on skin disorders until now. OBJECTIVE: The purposes of this study are: to highlight the incidence of some dermatoses in obese subjects and to study the water barrier function of the obese skin using transepidermal water loss (TEWL). METHODS: Sixty obese subjects and 20 normal weight volunteers were recruited. Obese group was further divided into three body mass index (BMI) classes: class I (BMI 30-34.9 kg/m(2)), class II (BMI 35-39.9 kg/m(2)) and class III (BMI 40 g/m(2)). All subjects attended dermatological examination for skin diseases. To assess barrier function, TEWL measurements were performed on the volar surface of the forearm using a tewameter. RESULTS: The results of this study showed that: (i) obese subjects show a higher incidence of some dermatoses compared with normal-weight controls; in addition the dermatoses are more, frequent as BMI increases; (ii) the rate of TEWL is lower in obese subjects, than in the normal-weight subjects, particularly in patients with intra-abdominal obesity. CONCLUSION: Specific dermatoses as skin tags, striae distensae and plantar hyperkeratosis, could be considered as a cutaneous stigma of severe obesity. The low permeability of the skin to evaporative water loss is observed in obese subjects compared with normal weight control. Although the physiological mechanisms are still unknown, this finding has not been previously described and we believe that this may constitute a new field in the research on obesity.

Inducers of erythroid differentiation in K562 human leukemia cells.

A variety of agents, including many known to induce erythroid differentiation in Friend murine erythroleukemia cells, were tested for their ability to induce erythroid differentiation in K562 humane erythroleukemia cells. Cells were grown in suspension culture and scored for erythroid differentiation by benzidine staining. Of 39 agents tested, 19 induced erythroid differentiation in K562 cells and 20 did not. A striking effect of the type of serum employed in the medium was observed. The majority of the agents inducing erythroid differentiation in medium containing fetal calf serum showed little activity in medium containing newborn calf serum.

Induction of the fms proto-oncogene product in HL-60 cells by vitamin D: a flow cytometric analysis.

Agents which induce monocytic characteristics in HL-60 human acute promyelocytic leukemia cells induce mRNA for the fms proto-oncogene, which encodes the receptor for M-CSF. Previous studies of fms expression in HL-60 cells have characterized chiefly induction by phorbol esters of fms mRNA. Our studies of fms expression in HI-60 cells have characterized induction by vitamin D3 of the fms protein. We have used flow cytometry to correlate fms antigen with a monocyte-specific differentiation antigen recognized by antibody MO2 (CD14), with DNA content, and with the nuclear antigen Ki-67, a marker of cell cycling. HL-60 cells were cultured with or without 1 microM vitamin D for 7 days. fms antigen was found on 42 +/- 5.8% of the cells cultured without vitamin D, but on 63 +/- 4.3% of the cells cultured with vitamin D. MO2 binding was detected on only 2 +/- 0.5% of the cells without vitamin D, but on 59 +/- 9% with vitamin D. Cells cultured with vitamin D that were fms-positive were also predominantly (83%) MO2-positive. Analysis of DNA content, measured by propidium iodide staining, showed that 57 +/- 1.5% of cells cultured without vitamin D, but 93 +/- 0.5% of cells cultured with vitamin D, were in the G0/G1 cell cycle phase. Analysis of nuclear antigen Ki-67 revealed that, of the vitamin D-treated cells that were fms-positive, a significant proportion (37%) were still cycling. We conclude that (1) fms is demonstrable on some uninduced HL-60 cells, (2) when HL-60 cells are induced to develop monocytic characteristics by vitamin D, fms induction is part of the program for monocytic differentiation that includes MO2 expression, yet (3) some induced cells expressing fms are still cycling.

Multipotent human hematopoietic cell line K562: lineage-specific constitutive and inducible antigens.

K562 cells have been reported to display a variety of non-erythroid properties. Using 28 lineage-specific monoclonal antibodies, we analysed which antigens are present spontaneously and which are inducible by a variety of agents. The data suggest that (1) antigens of a given lineage are preferentially responsive to certain inducers, e.g. megakaryocytic antigens to phorbol ester, and (2) a given inducer may influence antigens of different lineages in opposite directions, e.g. phorbol dibutyrate, not only induces megakaryocytic antigens, but also decreases granulocyte and erythroid antigens. We conclude that the K562 cell, despite its malignant origin, retains some capacity for expression of alternative programs of differentiation, a characteristic of the normal multipotent hematopoietic stem cell.

Single K562 human leukemia cells express and are inducible for both erythroid and megakaryocytic antigens.

In a previous study we explored the inducibility of erythroid, granulocytic, monocytic and megakaryocytic antigens in the human multipotent leukemia cell line K562. In this study we examine the relationship between induction into the two lineages for which inducibility is most marked: erythroid and megakaryocytic types. Specifically, does any cell manifest markers of both lineages? We show that 1) cultured without inducer, a minority of single cells expresses both erythroid and megakaryocytic antigens, i.e., glycophorin A and Plt-1 antigen, 2) thymidine-hypoxanthine and phorbol dibutyrate each induce each antigen, 3) the percentage of individual cells carrying both antigens increases under each of these inducing conditions, 4) the induction of each is not only relative in terms of percentage of total cells that are positive, but also absolute in terms of mean antigen per cell and (taking into account cell multiplication) total antigen per ml of culture, and 5) the inducibility of individual cells bearing both erythroid and megakaryocytic markers is confirmed by using a different inducer (butyric acid) and antibodies for different inducer (butyric acid) and antibodies for different erythroid and megakaryocytic antigens (VIE-G4 and AP-3, respectively).

Hemin preferentially stimulates synthesis of alpha-globin in K562 human erythroleukemia cells.

K562 human erythroleukemia cells are an established cell line derived from an adult with chronic myelogenous leukemia. Hemin stimulates their synthesis of embryonic and fetal hemoglobins. We have found that their globin synthetic pattern depends on the concentration of added hemin. Clone RA6 was cultured with 0--100 microM hemin and the globin synthetic pattern determined by 3H-leucine incorporation and analysis of 3H-globins by polyacrylamide gel electrophoresis in Triton X acid urea followed by fluorography and densitometry. The higher the hemin concentration, the greater the synthetic rate of each type of globin. However, the relative increase was greatest for alpha-globin. We propose that the differential dependence of alpha synthesis on added hemin is a reflection of translational inefficiency of alpha messenger RNA and that this property is exposed when the translational capacity of the cell is limited by hemin deficiency. We suggest that the differential dependence of alpha-chain synthesis on added hemin in clone RA6 is evidence of an intrinsic deficiency in heme synthesis.