Gamma-interferon modulates human monocyte/macrophage transferrin receptor expression

Although circulating human monocytes do not express transferrin (Tf) receptors, cultured adherent blood cells display high-affinity Tf binding sites. In the present studies, effects of various cytokines and biologically active proteins on human monocyte/macrophage Tf receptors were investigated. After culture, Tf receptor expression by adherent blood cells was time dependent and plateaued by 7 days. The addition of interleukin-1 (IL-1), alpha-interferon (alpha-IFN), granulocyte/macrophage-colony stimulating factor (GM-CSF), or human IgG to macrophages cultured for 4 days did not alter Tf receptor expression. Fe-saturated, human Tf caused a significant, dose-dependent decrease in receptor expression. At a dose of 100 U/mL, gamma- interferon (gamma-IFN) significantly increased Tf receptor expression by macrophages cultured for 4 (230% +/- 51% of control) or 7 days (150% +/- 22%). Scatchard analyses showed increased binding sites but no change in receptor affinity. Northern and slot blot analysis of cellular mRNA from macrophages cultured for 4 to 7 days and exposed to gamma-IFN showed a two- to fivefold increase in Tf receptor mRNA, but less than or equal to 30% increase in beta-actin mRNA. Ferritin content of gamma-IFN-treated macrophages was 47% to 63% of control cells. Net uptake of 59Fe from Tf by gamma-IFN-treated cells was 10% to 17% of control, but uptake of radiolabeled Tf was comparable. When macrophages were labeled with 59Fe and then exposed to gamma-IFN, cell-associated Fe was reduced by 43%, indicating that gamma-IFN caused macrophage Fe release. gamma-IFN specifically modulates Tf receptor display by inducing Fe release and reducing cellular Fe content. Regulation of Tf receptor expression in macrophages is controlled by cellular Fe content and is thus similar to regulatory mechanisms in dividing cells.     

Flexible implant arthroplasty of the proximal interphalangeal joint of the fingers

The use of an intramedullary stemmed flexible (silicone) hinge in reconstruction of the proximal interphalangeal joint has allowed us to obtain more predictable, durable, and reproducible results. The indications, surgical technique, and postoperative rehabilitation of this technique vary with each type of deformity presented and must be carefully followed. Adequate reconstruction of the extensor mechanism and the collateral ligament system, and appropriate postoperative rehabilitation are essential to obtain good balance of the digit, with functional mobility and stability of the reconstructed proximal interphalangeal joint.     

Racial differences in cancer incidence: the significance of age-specific patterns

Racial differences in cancer incidence between black and white populations are examined for leading cancer sites by age at diagnosis. The analysis was based on 116,858 incidents, invasive cancer cases occurring between 1973 and 1982 in black and white, male and female residents of the Detroit metropolitan area. Cases were drawn from the population-based Metropolitan Detroit Cancer Surveillance System. The results indicate that racial differences in age-specific incidence rates for many forms of cancer are more pronounced when cancer occurs in early adulthood and middle age (20 to 44 and 45 to 54 years) than in persons aged 65 and over. This is especially the case for male subjects. This may suggest that blacks and whites who survive to their senior years before developing cancer may be more alike in terms of behavior, exposures, or host susceptibility than blacks and whites for whom cancer occurs in early adulthood or middle age. The etiologic and public health implications of these race and age patterns must be considered in greater detail. Future case-control studies should include sufficient numbers of patients in both the youngest and oldest age groups to ensure that black and white differences can be adequately examined by age at diagnosis.     

Comparison of a discontinuous Percoll Gradient Method Versus A Swim-Up Method: Effects On Sperm Morphology and other Semen Parameters: Vergleich der diskontinuierlichen Percoll-Gradient-Methode mit einer Swim-up-Methode: Einfluß auf die Spermatozoenmorphologie und andere Spermaparameter

Increasing the proportion of motile and normal spermatozoa is an important objective for assisted reproductive procedures. The aim of this study was to compare the results of a Percoll and swim-up-method, especially on the sperm morphology. The Percoll technique gave a recovery rate of 81.3% of motile spermatozoa against a recovery rate of 28.98% for the swim-up technique. When the percentage of normal spermatozoa was also brought into calculation the recovery rate with the Percoll technique decreased to 62.03% and increased to 31.81% for the swim-up technique. This was due to a decrease in the resultant morphology of the Percoll technique to a median of 8.0% and an increase to 11.5% for the swim-up technique from a median of 10.5% of the original samples.     

Malingering and associated syndromes

Malingering is the false and fraudulent simulation or exaggeration of physical and/or psychological symptoms. It is not a mental disorder, but rather a behavior pattern that may coexist with objectively diagnosed disease. Whatever form it takes, malingering is defined as conscious, voluntary, goal-directed behavior; the presence of a clearly definable goal differentiates malingerers from those with other forms of factitious illness.     

Inhibition of synaptosomal membrane Na+-Ca2+ exchange transport by amiloride and amiloride analogues

Na+-Ca2+ exchange in rat brain synaptosomal plasmalemma vesicles is reversibly inhibited by amiloride (3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide++ +). This drug (pKa = 8.7) inhibits Na+-dependent Ca2+ uptake more effectively at basic pH values than at neutral pH values, indicating that the positively charged form of amiloride is the active moiety. Twenty amiloride analogues were examined for ability to inhibit Na+-Ca2+ exchange. These studies demonstrate that the 6-chloro group, the 5-amino substituent, and the carbonyl guanidinium moiety are essential for drug inhibition of Na+-Ca2+ exchange. N-Benzyl amiloride derivatives such as 3,5-diamino-6-chloro-N-(benzylamino-aminomethylene)pyrazinecarb oxamide (benzamil) and 3,5-diamino-6-chloro-N-(2-phenethylamino-aminomethylene)p yrazinecarboxamide are more potent inhibitors of Na+-dependent Ca2+ uptake than is amiloride. The amiloride analogue pattern of interaction with the Na+-Ca2+ exchange system is distinct from the inhibition patterns of the epithelial Na+ channel and the Na+-H+ exchange transport system.     

Chronic hypersensitivity pneumonitis produced in the rabbit by the adjuvant effect of inhaled muramyl dipeptide (MDP).

An established rabbit model of acute hypersensitivity pneumonitis was used to evaluate adjuvant properties of synthetic muramyl dipeptide (MDP), the minimal adjuvant-active structure of mycobacteria. The authors studied MDP as a substitute for mycobacteria in immunization and as adjuvant during repeated inhalation of antigen (ovalbumin). They found that MDP could substitute successfully for mycobacteria in sensitizing animals for acute alveolitis following subsequent inhalation of a combination of ovalbumin and MDP aerosol for 4 to 14 weeks resulted in the development of chronic granulomatous pneumonitis, characterized by alveolar wall thickening, granulomas, and infiltrations with lymphocytes and macrophages. In addition, MDP boosted systemic and local IgG and IgA antigen-specific antibodies. Inhaled MDP, itself neither antigenic nor mitogenic, acted therefore as adjuvant for continued immunologic inflammatory effector mechanisms in the rabbit lung, which are ordinarily suppressed when antigen alone is inhaled. Possible mechanisms include stimulation of effector T cells and macrophages or the failure of suppressive mechanisms, with or without participation of immune complexes. This is the first successful model of chronic granulomatous alveolitis produced by inhalation of soluble materials. Further exploration of adjuvant mechanisms in this system should help clarify the pathogenesis of immunologic lung diseases in man.     

Intrinsic labeling of chicken products with a stable isotope of selenium (76Se)

Chicken tissues were intrinsically labeled with a stable isotope of selenium (76Se) and were evaluated for use in a human feeding study. Laying hens were fed a low Se (0.06 ppm) basal diet for 39 days and then fed the basal diet supplemented with 0.3 ppm enriched 76Se (as selenite) for 35 days. Incorporation of 76Se into samples was determined by use of a double isotope dilution technique and a combined gas chromatography/mass spectrometry analysis. The 76Se content of the basal diet was increased by a factor of 9.7 with the addition of the enriched stable isotope. This maximal level of enrichment was approached in egg yolk (9.5-fold) and liver (9.0-fold). Enrichment was lower in egg white (7.2-fold) and breast meat (5.0-fold). Level of enrichment in a given tissue reflected both the turnover rate of the tissue and its natural selenium content. Selenium-depleted laying hens continuously fed 76Se at the 0.3 ppm level produced egg yolks and livers that were enriched sufficiently with the stable isotope for use in a human metabolic study.