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Regional organ procurement (ROP) crossmatch trays are used by members of the South-Eastern Organ Procurement Foundation (SEOPF) to facilitate sharing of cadaver kidneys for highly sensitized patients. ROP trays carry a single representative serum sample from over 900 patients with panel reactive antibody (PRA) levels of greater than or equal to 60%. Trays are centrally prepared periodically and distributed to member laboratories where they are used for preliminary crossmatching against locally obtained donors. Crossmatching results are used in conjunction with the SEOPF computer match program for sharing of kidneys. Proficiency testing studies by the 40-member laboratories show a greater than 90% concordance rate on results with these highly and broadly reactive sera. Data were available from 3 centers on 74 kidneys shared between SEOPF-member institutions on the basis of a remote, preliminary, negative ROP tray crossmatch. Of these, 44 (59%) crossmatched negative locally with the same and other sera, and were thus considered acceptable to be transplanted to the intended highly sensitized patients. Sixteen (22%) donors had a positive crossmatch locally, but with sera other than that present on the ROP tray used for screening. In 14 cases (19%) the same serum as on the ROP tray gave a positive crossmatch. The majority of ROP tray inconsistencies appeared to be due to use of more sensitive crossmatching techniques at the recipient center. Of the 27 patients transplanted at these 3 centers with kidneys received on the basis of ROP tray results, none experienced hyperacute or early irreversible rejection and actual graft survival at 6-48 months is 74%. These studies indicate that regional sharing of patient sera by the existing network of histocompatibility testing laboratories is an effective and reliable mechanism to identify crossmatch-negative donors for highly sensitized patients.

Marmosets are natural blood chimeras, this condition resulting from the high frequency of fraternal twinning and the consistent development of placental vasular anastomoses between the two embryos. Identification of chimerism by sex-chromosome analysis of cultured blood lymphocytes provided a means of determining the proportion of chimerism among T and B lymphocytes. Peripheral blood lymphocytes were enriched for T or B cells by filtration through a nylon column (yields greater than 95 per cent T-cells) or inactivation of T lymphocytes by treatment with a goat anti-marmoset thymocyte antiserum in the presence of complement (yeilds greater than 95 per cent B cells). Mitogenic stimulation of these separated, enriched cell populations yielded metaphase plates which could be scored for percentage male and female cells. Tests on five different blood chimeras showed the T- and B-lymphocyte chimerism to be the same. Stimulation of blood lymphocytes with cells from another species of marmoset in a mixed lymphocyte culture test revealed the chimeric T-cell response (i.e., host and co-twin cells) to be similar to that obtained with a mitogenic lectin. The demonstration of equivalent T- and B-cell chimerism in these animals suggests derivation of these cells from a common stem cell pool and the response of both T-cell populations to an antigenic stimulus in proportions similar to their percentage chimerism suggests complete immunologic tolerance exists in this species for co-twin histocompatibility antigens.

1. Patients subjected to TDD prior to transplantation had a 4-yr graft survival rate of 65% compared to a comparably HL-A-matched group in which the survival rate was 35%9 2. Patients classified as non-responders to tissue antigens have a much higher graft retention rate than responders. Responders subjected to TDD have a 1 yr graft survival rate of 62% compared to a comparably HL-A-matched group with a survival rate of 28%. 3. Individuals with a positive crossmatch or receiving second or third transplants and subjected to TDD do much better than such individuals not subjected to TDD.

In a preliminary study of twenty-three patients with gonadal dysgenesis (Turner's syndrome) and their families, correlation was sought between their serum defined HLA allele frequencies and their known tendencies toward abnormal immune responses and diabetes mellitus, since individuals with the latter disorders have been shown to have an increased frequency of certain HLA types. We were unable to demonstrate an association between these major serum-defined histocompatibility antigens, immune homeostasis disturbances and sex chromosome aneuploidy in this group. It is felt, however, that testing involving the patterns of HLA-D and "HLA-D related" antigen frequencies should be obtained to further evaluate the possibility of such an association.

Between March 1963 and December 1983, 324 renal transplants were performed in 273 veteran patients at the Veterans Administration Medical Center, Nashville, Tenn. Cadaver donors were used in 273 transplants, with an overall one-year patient survival of 72.5% and one-year functional graft survival of 50%. Twenty-four living-related transplants were performed, with an overall one-year patient survival of 89% and one-year functional graft survival of 75%. For analytical purposes the 20-year transplant experience was divided into five eras. One-year patient survival increased from 45% in era 1 to 84% in era 5, while functional graft survival increased from 45% to 70%. Death has occurred in 139 patients, with sepsis being responsible for the largest number of early deaths. Cardiovascular disease was responsible for most late deaths.

In humans the XY ovary is degenerative, there being scant evidence of persistence of that organ beyond the perinatal period. Here we describe indications of functional ovarian tissue in a 17-year-old female with male karyotype, H-Y+ cellular phenotype, and some signs of the Turner syndrome. Her gonads were removed after the onset of secondary amenorrhea. Histological examination revealed a degenerative right ovary devoid of germ cells and follicles, and a left streak gonad. There was no trace of testicular development in either side.

Twenty-two patients with aplastic anemia were treated with antilymphocyte serum or antithymocyte globulin at Vanderbilt University and affiliated hospitals from 1980 to 1986. The median age was 42 (eight to 73 years); the male:female ratio was 8:14. Nineteen patients had severe aplastic anemia, and three had moderate disease. Twenty patients received antilymphocyte serum initially while two patients received antithymocyte globulin. Fifteen patients received fluoxymesterone 10 mg by mouth three times a day with antilymphocyte serum, and all received prednisone during the course of antilymphocyte serum or antithymocyte globulin. There were seven responses (31.8 percent) to the first course with four complete responses and three partial responses. Six of 15 patients who received fluoxymesterone showed a response, compared with zero of five treated without androgens (p less than 0.05). Eight patients with no initial response and a patient who experienced a relapse after a complete response were re-treated with either antithymocyte globulin (six) or antilymphocyte serum (three), with four of nine patients (44 percent) having a response (three complete responses, one partial response). Overall, 10 of 22 patients (45 percent) had a response (six complete responses, four partial responses). Median survival for those without a response is six months. Median survival for those with a response has not been reached, with follow-up ranging from 18 to 70 months. This study shows the benefit of a second cycle of antilymphocyte serum or antithymocyte globulin and a possible role for concomitant androgens in this treatment of aplastic anemia.

Animal studies have reported that the blastocyst produces immunosuppressive factors that are critical to successful implantation. The production of such factor(s) by the human blastocyst has not yet been described. To test that hypothesis, the spent media of 67 human embryos developed in vitro was evaluated using either the allogeneic one-way mixed lymphocyte response (MLR) or the concanavalin A (Con-A) stimulated lymphocyte response (SLR). Conditioned embryo media was obtained at in vitro fertilization (IVF) in aliquots of (A) the first 24 hours in vitro, (B) the second 24 hours in vitro, and (C) from 24 hours until development of the blastocyst stage. Control media consisted of Ham's F-10 medium (Gibco, Grand Island, NY) with identical maternal serum concentration to test media. Conditioned media (either A, B, or C) or control media was added to 200-microL wells containing lymphocytes in either the MLR or SLR. A significant suppressive effect of 25% to 60% was observed in seven of nine samples of blastocyst-conditioned media (P less than 0.05). No significant suppressive effect was found in the earlier embryo media (A or B) in either the MLR or the SLR. These data suggest that the human blastocyst produces a factor(s) that interferes with lymphocyte proliferation.

During a 2-year interval 206 patients underwent renal transplantation at a single center, 38 of whom underwent bilateral nephrectomy and other adjuvant operations as part of the transplant procedure. The indications for this type of procedure were reviewed, with special emphasis on the control of hypertension. The morbidity and mortality (16 per cent) in this group were compared in detail to those in patients not undergoing a concomitant adjuvant operation. The results with regard to renal function were similar to the group as a whole and the indications for appropriate patient selection are discussed.

The daily transport of human plasma apolipoproteins A-I and A-II, triglyceride, and total cholesterol from the thoracic duct lymph into plasma was measured in two subjects before and three subjects after renal transplantation. Lymph triglyceride transport was approximately 83% of the daily ingested fat loads, whereas lymph cholesterol transport was consistently greater than the amount of daily ingested cholesterol. Lymph apolipoprotein transport significantly (P < 0.05) exceeded the predicted apolipoprotein synthesis rate by an average of 659+/-578 mg/d for apolipoprotein A-I and 109+/-59 mg/d for apolipoprotein A-II among the five subjects. It is estimated that 22-77% (apolipoprotein A-I) and 28-82% (apolipoprotein A-II) of daily total body apolipoprotein synthesis takes place in the intestine. Lymph high density lipoprotein particles are mostly high density lipoprotein(2b) and high density lipoprotein(2a) and have a greater overall relative triglyceride content and a smaller relative cholesteryl ester content when compared with homologous plasma high density lipoproteins. The major quantity of both lymph apolipoprotein A-I (81+/-8%) and apolipoprotein A-II (90+/-11%) was found within high density lipoproteins with almost all of the remainder found in chylomicrons and very low density lipoproteins. The combined results are consistent with a major contribution of the intestine to total body synthesis of apolipoprotein A-I and apolipoprotein A-II. An important role of lymph in returning filtered apolipoprotein to plasma in association with high density lipoproteins is proposed. Accompanying the return of filtered apolipoprotein to the plasma is a probable transformation, both in size and composition, of at least some of the lymph high density lipoprotein(2b) and high density lipoprotein(2a) particles into high density lipoprotein(3).

The thymus-derived (T) lymphocyte and bone marrow-derived (B) lymphocyte populations of the marmoset were characterized using specific cell surface markers Approximately 85% of the thymocyates formed rosettes with neuraminidase-treated sheep erythrocytes (En). The percentage (approximately 69%) of peripheral blood lymphocytes (PBL) forming rosettes with En was the same as that which stained with fluorescently labelled goat anti-marmoset thymocyte serum (ATS). These two assays identified the same cell population since treatment of cells with ATS and complement resulted in a concomitant decrease in En rosette formation. Marmoset PBL also formed rosettes with human erythrocytes sensitized with antibody and complement (HEAC); since the percentage (approximately 20%) HEAC rosette was the same as that of cells stained with fluorescently labelled goat anti-marmoset IgG, these cells were considered to be B cells. A small percentage of cells (approximately 1-5%) possessed both types of receptors. The mean percentages of T and B cells present in PBL of single-born, presumably non-chimeric animals, were the same as that of iso-sexual and heterosexual chimeras.

Twenty patients with autoimmune endocrinopathies experienced 45 episodes of pleural and/or pericardial serositis. Seventeen of these patients were women and 15 had clinical or serologic evidence of 2 or more endocrinopathies. Idiopathic primary hypoadrenalism (10 cases), Graves' disease (8 cases), Hashimoto's disease (4 cases), atrophic thyroiditis with hypothyroidism (3 cases), idiopathic primary hypogonadism (3 cases), transient thyroiditides (2 cases), and type I diabetes mellitus (1 case) were diagnosed at a mean age of 24 years. Serositis recurred after asymptomatic intervals of months to years even in patients treated for endocrine dysfunction. Fourteen of 16 Caucasians had circulating immune complexes, including all 9 patients with a C4AQ0 (C4A null) phenotype and including all 12 patients with HLA antigens B8 and DR3, antigens associated with systemic lupus and with autoimmune endocrinopathies. Serositides associated with autoimmune endocrinopathies can occur with chest pain, fever, and exudative effusions in young Caucasian women with the HLA B8 DR3 C4AQ0 phenotype. These serositides may have a common pathophysiologic mechanism.

This study is a multifactorial analysis of 389 transplants performed from June 1977 to December 1981. Analysis of the effects of transfusions antilymphocyte serum (ALS), histocompatibility testing, gender, and patient risk factors (presence of concomitant disease, greater than 50 years of age, etc.) was done. Two-hundred fifty-three patients received cadaver kidneys and 136 patients obtained kidneys from a relative. Two-hundred eighty-three (73%) patients received blood transfusions prior to transplantation. Our data showed that recipients receiving transfusions prior to transplantation had a significantly higher graft survival than those who were not transfused in both cadaveric and related graft recipients. Two-hundred twenty-one (56%) patients received ALS following the transplant. This group had a 15% higher graft survival than a comparable group. Analysis of histocompatibility testing data shows approximately 5% higher functional graft survival between each match grade. Surprisingly, female patients receiving kidneys from living related donors had a 16% higher graft survival than male patients. In cadaver recipients female patients had a 10% higher patient survival as compared to male patients. The risk factor status of recipients affected not only graft survival but patient survival, which probably is due to the consequences of immunotherapy. The authors' conclusion is that the above mentioned factors may be additive in nature. Further, multivariable analysis is necessary in order to correctly transplant data.