The c-kit ligand potentiates the allogeneic mixed lymphocyte reaction.

The allogeneic mixed lymphocyte reaction (MLR) is a complex in vitro assay of T-cell recognition and responsiveness in which interleukin-2 (IL-2) plays a central role. We have previously demonstrated that c-kit ligand (KL) can enhance IL-2-induced proliferation in a subset of human natural killer cells expressing the c-kit tyrosine kinase receptor. In the present study, we asked whether KL could enhance IL-2-mediated T-cell proliferation in the allogeneic MLR. We demonstrate that the vast majority of activated human T-cell clones express the c-kit mRNA transcript. Binding studies performed on activated T cells with radioiodinated KL were consistent with the expression of a single class of c-kit receptors. The addition of exogenous KL to the MLR led to an increase in tritiated thymidine (3[H]-TdR) incorporation in the absence of other exogenous cytokines, and did so in a dose-dependent fashion. A reproducible increase in 3[H]-TdR incorporation was noted at concentrations of KL, which approximate those normally found in vivo. Antibody blocking of KL binding to c-kit, T-cell depletion and sorting experiments suggest that the action of KL is mediated at least in part by a direct effect on both CD4+ and CD8+ T-cells. KL's enhancement of the MLR also requires the binding of IL-2 to its high-affinity IL-2 receptor. Given the abundance of KL normally found in human serum, these data suggest that this cytokine may have a role during T-cell activation in vivo.

Stem cell factor production by human marrow stromal fibroblasts.

To characterize the production of stem cell factor (SCF, the ligand for the c-kit receptor protein) and its regulation by inflammatory cytokines and glucocorticoids, primary marrow stromal fibroblasts were isolated from normal individuals and two patients with Diamond-Blackfan anemia. Unstimulated normal marrow stromal fibroblasts constitutively expressed a low level of SCF mRNA (9 +/- 2 copies/cell [mean +/- SEM]), continually secreted soluble SCF into the supernatant of 1- to 5-day-old cultures (0.16 +/- 0.02 to 0.73 +/- 0.04 ng/mL per 10(6) cells, respectively), and expressed membrane-bound SCF. Stimulation with interleukin-1 beta (IL-1 beta) only modestly increased SCF mRNA levels, soluble SCF production at 24 hours, and membrane-bound SCF. In comparison, hydrocortisone or tumor necrosis factor alpha (TNF-alpha) exposure increased SCF mRNA levels 3.5- to four-fold above controls, but with different kinetics. The peak TNF-alpha effect was at 6 hours, with return to near control levels at 24 hours, whereas hydrocortisone induced maximal mRNA increases at 12 to 18 hours, and the levels remained high at 24 hours. Similarly, a sustained increase in soluble SCF production was detected during 1 to 5 days of hydrocortisone exposure (0.27 +/- 0.03 to 1.10 +/- 0.08 ng/mL per 10(6) cells), while TNF-alpha stimulation modestly increased the production of soluble SCF in 24-hour cultures only. Unstimulated normal marrow fibroblasts expressed predominantly the long species of alternatively spliced SCF mRNA, and the relative amounts of long and short mRNAs did not change after stimulation with IL-1 beta, hydrocortisone, or TNF-alpha. SCF production by marrow stromal fibroblasts from a symptomatic patient with Diamond-Blackfan anemia was equivalent to simultaneously studied normal marrow fibroblasts. In contrast, marrow fibroblasts from a Diamond-Blackfan anemia patient in untreated hematologic remission constitutively expressed high levels of SCF mRNA (21 +/- 4 copies/cell) and soluble protein (0.40 ng/mL per 10(6) cells at 24 hours). Together, these observations suggest that SCF is constitutively produced by fibroblasts in the human marrow microenvironment and that hydrocortisone induces a modest but sustained increase in SCF gene expression and protein production, compared to only a transient increase induced by TNF-alpha. In addition, these findings support the hypothesis that endogenous or corticosteroid-induced increases in the production of SCF could play a physiologic role in the clinical improvement of congenital anemia.

Systemic lupus erythematosus in Jamaica

45 cases of Systemic Lupus Erythematosus were presented and discussed. Attention was drawn to three main points. Firstly, difficulties in diagnosis; secondly, the apparent increase in incidence of the disease; and lastly, the high incidence of biologically false positive tests for Syphilis in this condition. It was also noted that the possibility exists that treatment for positive serological tests may be determined in this disorder (AU)

The use of griseofulvin in the treatment of the dermatomycoses

A brief review of the history leading from research begun in 1939 to Gentles' successful cure of guinea pigs infected with fungi in 1958 and the first clinical use of griseofulvin by Williams, Blank and Riehl (1958), is given. The use and misuse of griseofulvin is discussed. Dosage, duration and control of treatment are described and the rare and never dangerous side effects are mentioned. An account of 84 personal cases of dermatomycosis treated with griseofulvin is presented. This includes a report on a case of chromomycosis which was cured by combined treatment with vitamin D2 and griseofulvin (AU)

Squamous cell carcinoma arising in discoid lupus erythematosus

A case of "carcinoma erythematosum" is reported. One would expect this complication of lupus erythematosus to be more common in Jamaica. The literature is reviewed (Summary)

Chromomycosis: report of four more cases in Jamaica

Four more cases of chromomycosis in Jamaica are described. One case exhibited the classical picture of verrucous nodules, plaques and cauliflower growths. Two other cases showed a pseudo-epitheliomatous picture. The fourth case showed the not uncommon 'mossy foot' appearance. The pleomorphism of the clinical picture is emphasized and treatment by surgery with skin grafting is recommended. The opinion is expressed that the disease is not as uncommon in Jamaica as was once thought (AU)

Observations on lymphogranuloma venereum

Lymphogranuloma venereum is a venereal disease caused by a virus belonging to the lymphogranuloma-psittacosis group. This disease is by no means limited to tropical countries. Acute infections with lymphogranuloma venereum show a conspicuous predilection for the male sex, whereas the later stages, elephantiasis genito-anorectalis and esthiomene, are much more frequent in the female. The value and limitations of Frei's intradermal test are discussed. The significance of transmission of the virus to animals and the results of virus research and their bearing on Frei's test and C.F.T. are surveyed. The three clinical stages of lymphogranuloma venereum are described and reference is made to the general manifestations of the disease as seen in eyes, joints and skin. A short evaluation of diagnostic procedures is presented and the principles of modern treatment of the disease are outlined. Some personal observations derived from the author's experience during war service in the Far East are mentioned (AU)