Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.

A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms.

A novel approach to measuring cell-mediated lympholysis using quantitative flow and imaging cytometry.

In this study, we established a novel isotope-free approach for the detection of cell-mediated lympholysis (CML) in MHC defined peripheral blood mononuclear cells (PBMCs) using multiparameter flow and imaging cytometry. CML is an established in vitro assay to detect the presence of cytotoxic effector T-lymphocytes precursors (CTLp). Current methods employed in the identification of CTLp in the context of transplantation are based upon the quantification of chromium ((51)Cr) released from target cells. In order to adapt the assay to flow cytometry, primary porcine PBMC targets were labeled with eFluor670 and incubated with major histocompatibility complex (MHC) mismatched effector cytotoxic lymphocytes (CTLs). With this method, we were able to detect target-specific lysis that was comparable to that observed with the (51)Cr-based assay. In addition, the use of quantitative cell imaging demonstrates the presence of accessory cells involved in the cytotoxic pathway. This innovative technique improves upon the standard (51)Cr release assay by eliminating the need for radioisotopes and provides enhanced characterization of the interactions between effector and target cells. This technique has wide applicability to numerous experimental and clinical models involved with effector-cell interactions.

Assessment of body composition in heart transplant patients.

Orthotopic heart transplantation (OHT) recipients often experience increased body weight (BW) following surgery. Using hydrostatic weighing (HW), this study assessed the body density (BD) and body composition of 17 white and seven black male OHT patients. It examined the cross-validity of the Jackson and Pollock seven and three site skinfold (SF) regression equations for predicting BD in these patients. We hypothesized that both prednisone (P) dose and months post-operative (MPO) would be inversely related to BD. The average of the last five of ten HW trials was used in computing BD. BW and % body fat (BF) were 88.5 +/- 17.8 kg (mean +/- SD) and 33.5 +/- 9.4%, respectively. The correlation coefficient between hydrostatically determined BD and BD determined via two of the three intercept revised Jackson and Pollock SF equations was r = 0.89, SE = 0.009. A polynomial regression model for BD using P dose and MPO provided a correlation coefficient of r = 0.71, SE = 0.015. Partial correlation techniques incorporating SF, age, MPO, and P dose indicated that neither P dose or MPO provided any significant additive effect, above SF and age, when predicting BD. We conclude that in OHT patients receiving glucocorticoids, the intercept revised Jackson and Pollock SF regression equations are generally applicable and associated with a SE of +/- 4 BF percentage points. Up to 49 months after OHT, both P dose and MPO are inversely related to BD but provide no additive value above SF for predicting BD.

Public hearings and public preferences: the case of the White House Conference on Families.

To provide input into Arizona's participation in the White House Conference on Families, the Arizona Governor's Council on Children, Youth, and Families commissioned a random statewide survey to assess the relative priority given to 41 selected family-related needs and preferences for institutional responses to those needs. A similar survey was administered to participants at each of six regional public hearings held throughout the state prior to the 1980 White House Conference on Families. A comparison of the two surveys provides an opportunity to test the representativeness of public hearings participants with respect to the population from which they were drawn. Fundamental differences in the priorities of these two samples cast considerable doubt on the assumption that public hearings are an effective means of gauging public sentiment.

Physiology of IgD. I. Compensatory phenomena in B lymphocyte activation in mice treated with anti-IgD antibodies.

The role of delta-positive cells in the immune response was studied by comparing the effects of treatment with allotype-specific IgD hybridoma antibody on homozygous BALB/c or SJL/J and heterozygous (BALB x SJL)F1 mice. Homozygous mice, injected from birth with the relevant anti-delta antibody, made primary or secondary immune responses to intravenously injected trinitrophenyl (TNP)-Brucella abortus, TNP-Ficoll, and TNP-keyhole limpet hemocyanin, which did not differ significantly from those of control mice, despite the fact that IgD+ cells were depleted and Ig+ cells were markedly reduced in the spleens of treated mice. Responses in nodes draining a local injection of TNP-Brucella abortus were, however, significantly suppressed. Heterozygous mice, injected from birth with either anti-Ig-5a or anti-Ig-5b, showed a marked reduction in the number cells producing IgG antibody of linked allotype specificity in the secondary response to intravenously injected sheep erythrocytes. A corresponding decrease in the amount of serum IgG2a of that allotype specificity was also noted. However, in agreement with the results obtained in homozygotes, heterozygotes injected simultaneously with anti-IgD directed against each of the allotypes made normal, if not enhanced, plaque-forming cell responses of both allotype specificities. Similarly, serum IgG2a levels were normal in all but one mouse treated in this fashion. These results indicate that IgD+ cells are not essential for an immune response in vivo. Although the delta-positive cell is used preferentially under normal conditions, it appears that an alternative mechanism exists by which, in the absence of these cells, the animal is able to make a normal immune response.

Clinical and roentgenographic findings in splenic abscess.

A splenic abscess developed in a 16-year-old boy following a supposed viral illness and left lower thoracic trauma. Preoperative diagnosis was at first obscured, but a spleen scan suggested fractured spleen and a splenic arteriogram showed a "subcapsular hematoma" and an aneurysm of the left hepatic artery. A 1,800-gm spleen containing one large abscess and one small one was removed. Splenic abscess is rare and, before modern methods of spleen scan and arteriography, rarely diagnosed.