Social security disability: guidelines for medical practitioners.

The purpose of this paper is to introduce medical practitioners to the concepts and function of the Social Security Administration's process of awarding disability benefits. Better understanding of this massive and important program will enable physicians to focus on and present appropriate information. This will facilitate processing of applications to the benefit of physicians, patients, and society.

Intravenous cyclophosphamide and methylprednisolone for the treatment of bronchiolitis obliterans and interstitial fibrosis associated with crysotherapy.

A patient with rheumatoid arthritis receiving intramuscular gold developed severe pulmonary insufficiency. Histopathology revealed both bronchiolitis obliterans and interstitial fibrosis possibly related to gold therapy. The patient was successfully treated with IV cyclophosphamide and prednisone. During the course of therapy, hypogammaglobulinemia without detectable IgM developed.

Cellular cooperation in the expression of murine delayed-type hypersensitivity (DTH): dual roles of accessory cells.

A recently described murine local passive transfer (LPT) system was modified to investigate accessory cell function in the expression of in vivo delayed-type hypersensitivity (DTH). An enriched antigen-presenting accessory cell population was prepared by overnight culturing and antigen pulsing. These cells, when cotransferred locally with enriched populations of immune DTH effector T lymphocytes, induced antigen-specific DTH responses. A consistently positive relationship between DTH expression and quantity of pulsed cells transferred was demonstrated. The further addition of fresh accessory cells to the transfer mixture provided 'augmentation' of DTH responses. In contrast to antigen presentation, 'augmentation' appeared restricted to an optimal range of augmenting cell: T cell ratios. That antigen presentation and augmentation were separate accessory cell functions was further supported by differential selection during overnight culture and differential sensitivity to paraformaldehyde (pCHO) exposure. The demonstration of multiple accessory cell functions indicates considerable promise for this system in the investigation of in vivo immune expression.

Cellular cooperation in the expression of murine delayed-type hypersensitivity (DTH). 1. A normal accessory cell population enhances DTH produced by immune peritoneal exudate T lymphocytes.

A murine system for local passive transfer of delayed-type hypersensitivity (DTH) has recently been described. It was determined that untreated and T-lymphocyte-enriched (nylon-wool-nonadherent) fractions of peritoneal exudate (PE) cells from immunized donors could be transferred with soluble antigen to normal recipient footpads to efficiently produce a local DTH response. Untreated spleen or lymph node (LN) cell populations were strikingly less capable in this regard. It is now reported that addition of normal untreated PE cell populations to immune T-enriched PE cells markedly enhanced the DTH response transferred by the latter. Specific swelling was dose dependent with respect to each cell type. Removal of T lymphocytes from the normal PE cell population did not affect its enhancement of DTH. By cotransfer of 1 X 10(7) normal PE cells, significant specific swelling was obtained using 1-3 X 10(5) T-enriched immune PE cells. This represented a three- to seven-fold reduction in the requirement for the latter cell type. This scheme of DTH enhancement was employed to evaluate the mechanisms for decreased capability of immune LN and spleen for DTH transfer when compared to PE. No evidence was found that either adherent or nonadherent suppressor cells are operative at the time of DTH expression. Cotransfer of a DTH-enhancing population failed to equalize DTH expression by LN and spleen with that of PE. It is concluded that DTH effector-T-cell activity is enriched in immune peritoneal exudate and that non-T-cell population(s) from that source actively enhance DTH expression.

Defective elicitation of delayed-type hypersensitivity in W/Wv and SI/SId mast cell-deficient mice.

Previous studies have indicated that cutaneous mast cells are involved in the elicitation of delayed-type hypersensitivity (DTH) in mice. Mast cells are thought to be required in DTH to release serotonin to open gaps between endothelial cells, allowing entrance of effector cells into the tissue. Two different strains of mice with independent genetic defects that lead to a substantial mast cell deficiency (W/Wv and SI/SId), and their normal littermate +/+ controls, were studied for their ability to express DTH. Both strains were shown to be deficient in serotonin-containing mast cells at skin sites of preferential elicitation of DTH in normal mice, such as the ear or footpad. Defective DTH was found in both mast cell-deficient strains by using two different systems: 1) sheep erythrocyte-induced footpad DTH, and 2) picryl chloride-induced contact sensitivity ear swelling responses. Adoptive transfer experiments demonstrated that abnormal DTH in mast cell-deficient mice was due to a defect in the elicitation of DTH, rather than a defect in the induction of effector T cells. In these experiments, the ability to elicit DTH could be transferred to normal +/+ mice with sensitized cells from mast cell-deficient mice, but sensitized cells from +/+ mice could not transfer DTH responsiveness to mast cell-deficient mice. In addition, no defects in numbers of epidermal Langerhans cells or in antigen-presenting cell function were found in W/Wv or SI/SId mice. We therefore concluded that abnormal elicitation of DTH in W/Wv and SI/SId mice was probably due to their mast cell deficiency. The inability of mast cell-deficient mice to express DTH was overcome when sensitized T cells and specific antigen were placed in the extravascular tissues by local passive transfer. These results suggest that mast cell release of vasoactive mediators, such as serotonin, is required in DTH to allow effector T cells to leave the intravascular space, enter the tissues, and become activated by antigen to release chemoattractant lymphokines that recruit a nonspecific infiltrate of inflammatory cells.

Local passive transfer of delayed-type hypersensitivity in the mouse.

A means for local passive transfer of DTH in the mouse has been discovered and partially characterized. Briefly, peritoneal exudates (PE) are induced with incomplete Freund's adjuvant 5 to 7 days after immunization with antigen (usually picGPA) emulsified with complete Freund's adjuvant. Five days later, PE cells are harvested and transferred with soluble antigen into a hind footpad of a naive mouse. Antigen-specific swelling is defined as the change in diameter of footpads over the 24 hr after injection of PE cells plus immunizing antigen minus change in diameter of footpads injected with PE cells plus control antigen. Antigen-specific footpad swelling of 20 to 80% was found in contrast to meager swelling when lymph node or spleen cells were used. The magnitude was dependent on dose of both cells and antigen over a broad range (1 to 12 X 10(6) cells, 1 to 100 micrograms of antigen per recipient). Specific swelling was reduced to nil after treatment of PE cells with anti-theta serum, indicating T cell dependence. Carrier specificity of the response was similar to DTH in the guinea pig. Time course and histology are compatible with a DTH response as well. The superiority of PE cells in local transfer of DTH and the modest requirements of this murine local transfer system provide potent tools for identification of the cell(s) that mediate DTH and their interactions. This system, in addition, should provide a sensitive indicator of immunomodulating activity in cellfree supernatants.