Interactions of ACTH and TGFβ on monocyte proliferation: Implications for trauma and burn patients

The purpose of this study was to try to elucidate a possible biobehavioral mechanism associated with decreased immune function in trauma patients by determining whether there is an interaction between the effects of ACTH, a stress hormone, and TGFβ, a cytokine, on peripheral blood lymphocyte proliferation. Peripheral mononuclear lymphocytes (PMLs) from healthy donors were preincubated with varying concentrations of ACTH for 24 hr, stimulated with Conconavalin A and increasing concentrations of TGFβ, and incubated for 72 hr. Proliferation was assayed by tritiated thymidine incorporation. A parallel aliquot of PMLs were incubated in the presence of ACTH to determine the direct effect of ACTH on mononuclear cell TGFβ production. While harvested supernatant from cells incubated in the presence of ACTH did not contain any detectable TGFβ, ACTH as well as TGFβ were found to significantly decrease cellular proliferation independent of one another. An even greater decrease in cellular proliferation was found when both ACTH and TGFβ were used, compared to either ACTH or TGFβ alone. These results suggest a biobehavioral interaction between ACTH and TGFβ at the cellular level and that interactions to relieve stress may assist in improving function and recovery from trauma. © 1996 John Wiley & Sons, Inc.     

Acylation of ghrelin is increased in heart failure and decreases post heart transplantation

Objectives. Ghrelin is an anabolic hormone that is elevated in heart failure (HF), with resistance to its anabolic effects. This resolves after heart transplantation (HTx). Ghrelin exists in acylated and des-acyl forms, with the acylated form being primarily responsible for endocrine actions. We tested the hypothesis that ghrelin derangements in HF are due to inadequate acylation and that this resolves post transplantation. Design. Plasma levels of des-acyl and acylated ghrelin and acylated/total ratios were assessed in HF (n = 20), post-HTx (n = 35), and healthy controls (n = 4), and correlated with each other and with clinical parameters. Results. Median (interquartile range) of des-acyl ghrelin level, was 167 (121–195) pg/ml in HF versus 149 (130–223) pg/ml in post-HTx, p = NS. Acylated ghrelin level was 76 (51–99) pg/ml versus 13 (0–30) pg/ml, p < 0.001. Acylated/total ratios were 0.33 (0.20–0.47) versus 0.08 (0–0.13), p < 0.001. The correlation between acylated and total ghrelin levels was greater in HF than that in HTx. Acyl ghrelin correlated inversely with body mass index in HF, but not in HTx. Conclusion. Acylated ghrelin and the acylated/total ratio were dramatically higher in HF compared with those in HTx. Acylation rather than secretion of ghrelin is upregulated in HF and the resistance to ghrelin's anabolic and appetite-stimulating effects is not at the level of acylation, but downstream at the ghrelin-receptor level.     

The liver in infectious mononucleosis

Summary 1. Twenty-two patients with infectious mononucleosis were studied by liver biopsy and paper electrophoresis of the serum proteins. The findings were compared with a similar group of 30 patients with infectious hepatitis.2. The essential histologic features of infectious mononucleosis were the presence in the hepatic sinusoids and portal tracts of chronic inflammatory cells resembling small lymphocytes, with essentially no parenchymal cell damage. Admixed with this lymphocytic infiltrate, but in relatively minimal numbers, were a few plasma cells and polymorphonuclear leukocytes. In addition, in infectious mononucleosis there were, with rare exceptions, no lipochrome-containing Kupffer cells. Thus, in the majority of cases, the histologic picture was distinct from that seen in infectious hepatitis. Only in comparing a few of the more severe infectious mononucleosis cases with subsiding infectious hepatitis cases was there any tendency for the two pictures to merge, and the distinction on histologic grounds between the two entities could be made in the great majority of cases.3. The most commonly seen abnormalities in the paper electrophoretic patterns of sera obtained from patients with infectious mononucleosis were decreased albumin, increased gamma globulin, not infrequent but variable changes in alpha₂ globulin, and the presence of abnormal proteins migrating with mobilities intermediate to alpha₂ and beta, and beta and gamma globulins. The abnormalities observed in infectious hepatitis were similar to those of infectious mononucleosis, except that in hepatitis alpha₂ globulin was decreased more consistently, gamma globulin increased less frequently, and beta globulin, which was normal in practically all the cases of infectious mononucleosis, was increased in a considerable number of cases.4. Treatment of patients with infectious mononucleosis need not include prolonged bed rest and restriction of activity in an effort to avoid the development of chronic liver disease.     

Common sense in the treatment of pilonidal disease

Summary The management of pilonidal cyst disease in a large military hospital is described. Of special interest to the military practice is the “buddy” system, in which patients help one another to keep their wounds clean and dry. The specific objectives of our technic are: 1) obtaining excellent hemostasis by the use of zinc peroxide paste; 2) avoiding recurrences by an open-wound method of treatment; 3) preservation of a pad of subcutaneous tissue over the postsacral fascia, thus reducing long-term morbidity by insuring a mobile scar; 4) decreasing the duration of hospitalization, achieved by frequently drying the wounds with warm air. Read at the meeting of the American Proctologic Society, Hollywood, Florida, April 12 to 16, 1970. The opinions or assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the Navy Department.     

Measurement of human growth hormone by immunoassays: Current status,unsolved problems and clinical consequences

Measuring the concentration of growth hormone (GH) in blood samples taken during dynamic tests represents the basis for diagnosis of growth hormone related disorders, namely growth hormone deficiency and growth hormone excess. Today, a wide spectrum of immunoassays are in use, enabling rapid and sensitive determination of growth hormone concentrations in routine diagnostics. From a clinical point of view several difficulties exist with the use and interpretation of GH assay results in the assessment of GH related disorders: Many physiological factors such as fat mass, age and gender influence the outcome of dynamic tests, overall leading to significant inter-individual differences in GH responses. However, in addition to the physiological variability, considerable variability exists in GH assay results obtained by different immunoassays. Unfortunately, all the new technical advances in the field of GH measurement techniques have not reduced this methodological variability. To a large extent, the actual values reported for the GH concentration in a sample depend on the method used by the respective laboratory. Obviously, such discrepancies limit the applicability of consensus guidelines on diagnosis and treatment in clinical practice.This review summarizes current practices for GH measurement with respect to the methods used, their limitations and the clinical consequences of the existing heterogeneity in GH immunoassay results.     

DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire

The majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4(+) T cell help. Candidate MHC class I-binding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitope derived from Friend murine leukemia virus gag protein (FMuLV(gag)) and vaccinated tolerant FMuLV(gag)-transgenic (gag-Tg) mice. Vaccination with the construct induced epitope-specific IFN-gamma-producing CD8(+) T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8(+) T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLV(gag) antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8(+) T cell responses from a residual tolerized repertoire.