Comparison of abilities of recombinant interleukin-1α and -β and noninflammatory IL-1β fragment 163–171 to upregulate C3b receptors (CR1) on human neutrophils and to enhance their phagocytic capacity

Both recombinant IL-1 and - caused an upregulation of C3b receptors (CR1) on human neutrophils and caused a receptor-mediated enhancement of phagocytosis of C3b·IgG-coated microspheres by these leukocytes. The and forms of the recombinant cytokine were of comparable potency regarding CR1 upregulation, although both generally had less than 25% of the potency of FMLP in this respect. Recombinant IL-1 was slightly more potent than the form of the cytokine regarding phagocytosis of opsonized microspheres and, again, both forms were less potent than FMLP in causing an enhancement of phagocytosis by neutrophils. The synthetic noninflammatory immunostimulatory nonapeptide corresponding to residues 163–171 of IL-1 was completely inert with respect to upregulation of CR1 on neutrophils and the enhancement of phagocytosis by these cells. Thus this domain in the intact IL-1 molecule apparently is not involved in CR1 upregulation and the ensuing enhancement in phagocytosis by neutrophils, although it is apparently important in the immunostimulatory activity regarding the proliferation of lymphocytes.     

Antibody responses to Toxoplasma gondii antigen in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient mice reproduce the immunological status of the lymphocyte donor

These studies describe the production of specific antibodies in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient (PBL-SCID) mice following vaccination with antigen from the protozoan parasite Toxoplasma gondii. To determine the effect of previous exposure of the lymphocyte donor to antigen, human-PBL-SCID animals were created by transferring peripheral blood lymphocytes from either a single T. gondii-seronegative or a single seropositive donor. These reconstituted animals were subsequently inoculated with T. gondii soluble tachyzoite antigen (STAg) entrapped within non-ionic surfactant vesicles as an immunological adjuvant. Animals were bled at pre-determined time points post-vaccination and the expression of human anti-STAg antibodies in the plasma determined by enzyme-linked immunosorbent assay. Human antibodies specific for STAg were readily inducible in both groups of reconstituted animals, although the pattern of isotype production differed markedly between groups. The response in animals reconstituted with lymphocytes from the T. gondii-seronegative donor consisted primarily of IgM and subsequently of IgG (predominantly IgG1). In animals reconstituted with lymphocytes from the seropositive donor, no parasite-specific IgM could be demonstrated. The detectable response to STAg consisted entirely of human antibodies of the IgG isotype (IgG1), indicative of a memory-type response. These results mimicked exactly the antibody responses that would be expected had the lymphocyte donors been directly challenged with either the antigen or the live infectious agent, demonstrating that the immune system within these animals is functional and reproducible with regard to both the primary and secondary responses of the human donors.     

Cytotoxic and immunoregulatory function of intestinal lymphocytes in Chlamydia trachomatis proctitis of nonhuman primates.

To study the role of natural killer cells and immunoregulatory T cells in the pathogenesis of proctitis due to Chlamydia trachomatis (L2 serovar), lymphocytes were obtained from the rectal mucosa and other sites of nonhuman primates and studied by using phenotypic and functional assays. In animals with lymphogranuloma venereum (LGV) proctitis, the percentage of lymphocytes with the natural killer cell phenotype (Leu-11+) was not significantly higher at any site in LGV infection, and natural killer cell function of lymphocytes isolated from the rectum was lower during LGV infection. This was not due to the suppressive effect of factors in serum, rectal lymphocytes, or LGV elementary bodies. In studies of regulatory T cells, the Leu-3+/Leu-2+ ratio was lower in the peripheral blood and the spleen during LGV infection, but the ratio did not decrease in lamina propria T cells. Both peripheral blood and rectal lymphocytes had higher helper T-cell function for polyclonal immunoglobulin G (IgG) synthesis in pokeweed mitogen-stimulated cultures 2 weeks following LGV infection. Increased suppressor T-cell function for pokeweed mitogen-stimulated IgG synthesis was found only in the peripheral blood of animals 2 weeks after infection, but not in isolated rectal lymphocytes. These results indicate that in LGV proctitis natural killer cells are not an important component of the inflammatory infiltrate at the site of infection, and helper T-cell function increases in peripheral blood and rectal lymphocytes.     

Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.     

Humoral indices of stress in rats

Rats, bearing chronic venous cannulas, were subjected to 30 sec of constant current grid shock at 1 of 6 intensities (0, 0.25, 0.5, 1, 2, 4 mA), after being allowed to acclimate to the test chamber overnight. Blood, sampled before and after shock, was assayed for epinephrine, norepinephrine and corticosterone. Peak levels of both catecholamines increased in a stepwise fashion (i.e., monotonically) with increasing magnitude of stress, as reflected by current intensity of foot shock. Plasma corticosterone did not increase monotonically but instead showed similar increases in the 5 groups of rats that actually received shock. These data support earlier work which indicate that plasma corticosterone is not a sensitive index of stress; this is probably the case because of the relatively narrow range of responsiveness of the adrenal cortex to ACTH. In contrast, both plasma catecholamines appear to satisfy some of the requisites for a sensitive visceral index of stress.     

Posttransplant CD30+ (Ki-1) anaplastic large cell lymphoma: a case report and review of the literature

Posttransplant CD30(+) (Ki-1) anaplastic large cell lymphoma (ALCL) is rare. A review of the literature revealed only 3 such cases. All 3 cases were developed after single-organ transplantation. We describe CD30(+) (Ki-1) ALCL in a dual-organ (liver and heart) transplantation recipient. The patient was a 68-year-old white female who underwent an orthotopic heart transplantation in 1999 and a liver transplantation in 2000. She presented with nausea and was found to have CD30(+) (Ki-1) ALCL by pathologic examination of the gastric antrum biopsy specimen. To our knowledge, this patient represents the first reported case of posttransplant CD30(+) ALCL following a dual-organ transplantation.     

Cardiac Exposure History as a Determinant of Symptoms and Emergency Department Utilization in Noncardiac Chest Pain Patients

Although comparative studies differentiate noncardiac chest pain (NCCP), panic disorder, and coronary artery disease (CAD), little research has examined the defining features of NCCP, such as cardiac complaints, medical utilization, and learning history. We administered self-report measures to 80 Emergency Department (ED) patients with a primary complaint of chest pain who were subsequently found to not have CAD. Forty-eight percent of the ED utilization variance was accounted for by NCCP duration, age, cardiac distress symptoms, and prior exposure to both siblings' and friends' cardiac distress symptoms. In turn, 67% of the variance in cardiac distress symptoms was explained by education, age, NCCP duration, number of illnesses, noncardiac panic symptoms, prior exposure (friends), and prior observation of others' cardiac distress. No effects emerged for gender, ethnicity, avoidance, or depression. Results suggest that beyond the effects of age and distress intensity, prior exposure to other people's cardiac distress may influence NCCP.     

Comprehensive Assessment of Pain in Juvenile Rheumatoid Arthritis: An Empirical Model

A comprehensive assessment model of variables hypothesized toinfluence pediatric pain perception was empirically investigatedin 23 families who had a child with juvenile rheumatoid arthritis.To determine the effects of family environment, child psychologicaladjustment, and disease parameters on child pain perception,a developmentally appropriate model was developed. Childrenbetween the ages of 5 and 15 were found to be reliable judgesof their pain intensity. Several family environmental and childpsychological factors were found to interact with specific diseaseparameters in determining pediatric pain perception and report.A multidimensional age-appropriate assessment model is suggestedfor use in the further examination of pediatric chronic andrecurrent pain.     

Bulimia in male patients

Bulimia is not exclusively a disorder of women. Twelve men with bulimia were evaluated and found to have demographic variables and eating behaviors similar to those of female bulimia patients. Eleven of the 12 men were binge eating more than once a day, and ten of the 12 also self-induced vomiting on a regular basis. Three patients had initiated bulimic behavior in association with athletic training. Eight patients followed through with treatment referrals and responded favorably to therapy.