Tumor necrosis factor-alpha and interferon-gamma, but not HTLV-I tax, are likely factors in the epidermotropism of cutaneous T-cell lymphoma via induction of interferon-inducible protein-10.

We have previously shown that Interferon-Inducible Protein-10 (IP-10), a cytokine chemotactic for CD4-positive lymphocytes, is overexpressed by lesional epidermal keratinocytes and probably accounts for the epidermotropism of cutaneous T-cell lymphoma (CTCL). The tax gene of human T-lymphotropic virus-I (HTLV-I) immortalizes CD4-positive lymphocytes, induces IFN-gamma, and has been detected in patients with classical CTCL who are seronegative for HTLV-I. TNF-alpha is synergistic with IFN-gamma for the induction of IP-10. We therefore decided to define the presence of tax, IFN-gamma, TNF-alpha, and IP-10 in lesions of 19 adults with classical CTCL who were seronegative for HTLV-I. Lesional mRNAs for actin, TNF-alpha, IFN-gamma, and tax were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) amplification. In addition IP-10, TNF-alpha, and IFN-gamma were detected and localized with immunocytochemistry of frozen sections. In agreement with previous observations IP-10 was overexpressed in lesional keratinocytes of all 19 patients. By RT-PCR, mRNA for IFN-gamma was detected in lesions of 8, and for TNF-alpha in lesions of 13 patients. By immunocytochemistry, TNF-alpha was expressed by lesional keratinocytes in 10 of 13 tested patients, whereas IFN-gamma was focally expressed by lesional lymphocytes and faintly by lesional keratinocytes in 9 of 13 tested patients. tax mRNA was not detected in lesions of any patient, but was easily detectable in cutaneous lesions or peripheral blood of control patients who were seropositive for HTLV-I. We conclude that TNF-alpha and IFN-gamma may cause epidermotropism by inducing IP-10. However, the tax gene of HTLV-I does not appear to be involved in the pathogenesis of classical CTCL.

Effect of melatonin alone or in combination with human chorionic gonadotropin or ovine luteinizing hormone on the in vitro secretion of estrogens or progesterone by granulosa cells of rats.

This work was undertaken to learn what effect, if any, melatonin might have on estrogen and progesterone production in vitro. Granulosa cells (10(6)/tube) were harvested from immature Sprague-Dawley rats, previously primed with diethylstilbestrol. Such cells were incubated for 90 min in medium only or in medium to which hCG (10 or 100 IU) or melatonin (3, 30, or 300 pg) had been added separately and in combination. Melatonin alone had no significant effect on the amount of estrogen produced, but in combination with hCG, a significant increase in estrogen followed (P less than 0.05). Estrogen was measured by RIA. More mature granulosa cells from rats primed with both diethylstilbestrol and porcine FSH were similarly collected and incubated in medium alone or in medium containing ovine LH (oLH; 0.3 or 3 ng) and/or melatonin (23 or 23 X 10(2) pg). The progesterone produced was measured by a competitive protein-binding method. A significant increase (P less than 0.05) in progesterone followed the addition of either melatonin or oLH alone, but a substantially greater increase was seen when oLH and melatonin were combined. These results show that, at least over a short period (90 min), melatonin is progonadal, in that it augments gonadotropic stimulation of granulosa cells and leads to increased synthesis of estrogen or progesterone. Melatonin may also independently stimulate granulosa cell production of progesterone.

Behavior therapy: a promising drug abuse treatment and research approach of choice.

Behavior therapy appears a promising drug abuse treatment and research approach of choice, reporting effective pilot studies utilizing such techniques as token economy, aversive conditioning, relaxation training, contract writing, covert conditioning, and combinative approaches. Behavior therapy appears to merit considerable investment of funds, time, and facilities to design and to execute carefully controlled research studies with systematic follow-up. Behavioral research and treatment is also consistent with presently available diagnostic techniques--the highly structured interview and the Synanon Game--and seems eminently applicable in specific work sites, to problems of staff selection and training, and to patient screening problems.