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.     

Use of a scanning laser three-dimensional digitizer to evaluate dimensional accuracy of dental impression materials.

A steel die was machined to represent a dental arch with teeth prepared for complete crowns. Impressions and casts were made from the die, and critical dimensions were measured by two methods--one using micrometers and the other a scanning laser three-dimensional (3-D) digitizer. The digitizer recorded measurements were more precise than the micrometer's and virtually eliminated operator error because the acquisition of data was automatic. The digitizer could also be useful for high-precision analyses of the dimensional accuracy of dental impression materials, but the cost and complexity of the instrument makes it less desirable for low-precision work.     

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.      

Prolonged Replication of a Type 1 Vaccine-Derived Poliovirus in an Immunodeficient Patient

VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by ~10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 sequences at synonymous third-codon positions occurred at an overall rate of ~3.4% per year over the 189-day period. Assuming this rate to be constant throughout the period of infection, the infection was calculated to have started ~9.3 years earlier. This estimate is about the time (6.9 years earlier) the patient received his last oral poliovirus vaccine dose, approximately 2 years before the diagnosis of immunodeficiency. These findings may have important implications for the strategy to eliminate poliovirus immunization after global polio eradication.     

Safety and tolerability of combined treatment with moclobemide and SSRIs: a preliminary study of 19 patients

Nineteen major depressed patients, resistant to previous pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess the adverse events and tolerability. There were 77 emergent events, insomnia, headache, nausea and dizziness being the most common. Many events were rated as severe. The high rate of adverse events suggests that there may be clinically significant interactions between moclobemide and SSRIs. However, the uncontrolled data on effectiveness is encouraging and the combination deserves further attention as a strategy for treating intractable major depression.     

Specific staining of the axon membrane at nodes of Ranvier with ferric ion and ferrocyanide

Ferric ion and ferrocyanide were used as stains for light and electron microscopy of peripheral nerves. In rat sciatic nerves, it was found that ferric ion preferentially binds to the cytoplasmic surface of the axon membrane at nodes of Ranvier but not at internodal regions. In myelinated axons in the electric organ of the gymnotid fish, Sternarchus albifrons, the small excitable nodes are similarly stained, but the larger inexcitable nodes are not stained by ferric ion. Staining of the inner surface of the nodal membrane appears to be related to a structural specialization of this membrane, rather than accessibility to stain. Our data thus show a chemical differentiation of the inner surface of the axon membrane between nodes and internodes in normal peripheral nerve fibers and between the inner surface of the axon membrane at active nodes, inactive nodes, and the internodes in the Sternarchus electrocyte axons.