Release of soluble transferrin receptor from the surface of human leukemic HL60 cells

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.     

Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis.

In human T cell lymphoma/leukemia virus (HTLV-1)-infected people with tropical spastic paraparesis (TSP), there are activated HTLV-1-specific cytotoxic T lymphocytes (CTL) in the circulation and lymphocytic infiltrates in spinal cord lesions that are rich in CD8+ T cells. These observations suggest a role for virus-specific CTL in the pathogenesis of TSP. We have examined the anti-HTLV-1 cytotoxic activity of freshly isolated CD8+ T cells from peripheral blood lymphocytes of eight subjects seropositive for HTLV-1. Four of five subjects with TSP had circulating activated anti-Tax CTL. However, two of three seropositive subjects without TSP also had activated anti-Tax CTL. These observations show that such activated CTL are not confined to patients with TSP and raise some uncertainty about their significance in the pathogenesis of the disease. In cultures of CD8+ T cells from two TSP subjects, we detected CTL with other HTLV-1 specificities, without exogenous antigenic stimulation. A CTL epitope in the middle region of Tax and one in the C terminus of Pol have been mapped at the peptide level and the HLA Class 1 molecules restricting their recognition have been defined.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.      

Development of the immune response in the foetal and newborn rhesus monkey: I. Response to bovine serum albumin

1. Foetal rhesus monkeys (at 10–16 weeks gestation) were treated in utero with bovine serum albumin (BSA) and subsequently, as neonates, were tested for immunity or tolerance.

2. Five out of six monkeys treated in utero with 100 mg BSA were tolerant to BSA at challenge.

3. Some foetuses responded to treatment with 1–8 mg BSA in adjuvant with formation of antibody.

4. One monkey treated with a total of 350 mg BSA during the first 3 weeks after birth was tolerant to BSA at challenge; two other neonatal monkeys treated with 100 mg BSA did not show tolerance.