Cell-Mediated Lympholysis after Sensitization in Unidirectional Mixed Lymphocyte Culture in Man

The cytotoxicity of human peripheral blood lymphocytes (PBL), after a 6-day allogeneic stimulation in unidirectional mixed lymphocyte culture (UMLC). was studied. PBLs stimulated with phytohemagglutinin (PHA) and labeled with ⁵¹Cr were used .as target cells. The effector cells were incubated with the target cells at I 100:1 ratio for 6 In. The amount of isotope released into the supernatant was used to calculate lysis. Cell-mediated lympholysis (CML) was specific, as shown by an innocent-bystander experiment and by the lack of lysis of target alls autologous with the effector cells. The specific lysis had the following features: linear increase between 2 and H hr of incubation, linear increase with the logarithm of the number of effector cells, and inhibition by EDTA and by cytochalasm B. Under the UMLC conditions used, potent effector cells were present already on day 4. A reduction in the number of stimulating cells to one third of the number of responding Cells in UMLC resulted in a decrease of thymidine incorporation and in an increase of CML. The significance of CML for transplantation biology is discussed.     

Chronic loss of subcutaneous adipose tissue in HIV-associated lipodystrophy may not be associated with accelerated apoptosis

HIV-associated lipodystrophy (HIV-LD) is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue (SAT). The present study examined the rate of apoptosis in SAT with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders. Individuals with HIV-LD were compared with HIV-infected subjects without LD and subjects without HIV disease. Although apoptosis was observed in subjects with HIV-LD, there was no difference in the incidence of individuals with apoptosis among those with HIV-LD (10 of 22 subjects), those with HIV but no LD (13 of 25 subjects), and those without HIV disease (13 of 27 subjects). These data suggest that HIV-related chronic loss of SAT may not always be associated with increased frequency of adipocyte apoptosis.     

Legionella feeleii Serotype 2 Pneumonia in a Man with Chronic Lymphocytic Leukemia: a Challenging Diagnosis

Legionella feeleii has rarely been reported as causing pneumonia in patients with hematologic malignancies. We present a case of Legionella feeleii serotype 2 pneumonia with empyema in a man with chronic lymphocytic leukemia and describe the methods of identifying this organism using both standard methods and newer diagnostic techniques.     

The Incidence and Significance of Pattern-Recognition Receptors in Chronic Viral Hepatitis Types B and C in Man

Chronic viral hepatitis B and C are among the most common and devastating liver diseases worldwide. Immune response plays a crucial role in the course of both diseases. In spite of the importance of the adaptive arm of the immune response, there is a growing role of innate immunity, the earliest confronted with viral attack. Pattern-recognition receptors (PRRs) and, in particular, Toll-like receptors (TLRs) are molecules which are able not only to recognize foreign invaders, but also quickly mount an antiviral defense. Activation of PRRs has been demonstrated in both hepatitis types, i.e. in situ in the liver and on while blood cells. Both viruses, HCV and HBV, are able to subvert the PRR-mediated antiviral response by means of various proteins and enzymes. HCV acts via the non-structural proteins NS2 and NS3/4A, while HBV HBeAg is inversely correlated with TLR activity. Viral counterattack is particularly directed toward dendritic cells, those creating the link with the adaptive immune response. Apart from TLRs, other PRRs such as RIG-1 and MDA-5 are also able to recognize viral infection and participate in the activation of type I interferon synthesis. TLRs manifest gene polymorphism, which was shown to affect several consequences associated with chronic viral hepatitis such as liver cirrhosis and the outcome of liver allotransplantation. There have been numerous attempts to take advantage of the existence and activity of PRRs for the patients’ benefit. Several authors examined the role of TLR synthetic agonists as inducers of TLR activation. In hepatitis C the most promising agonists appear to be TLR3, 7, and 9 for potential antiviral therapy. PRRs may also act as potent adjuvants in HBV vaccines. Their baseline mRNA levels may have predictive value in the course of antiviral therapy.     

Rothia aeria Neck Abscess in A Patient with Chronic Granulomatous Disease: Case Report and Brief Review of the Literature

Rothia aeria caused a necrotic lymphadenitis and neck abscess in a patient with CGD. This infection was aggressive, crossed tissue planes, required two surgeries, as well as prolonged antibiotics for complete resolution. Rothia aeria is a rare pathogen that can be added to the spectrum of agents causing disease in CGD, a finding that further reinforces the importance of microbiologic identification of infections in this patient population.     

Chronic subcutaneous leptin infusion diminishes the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in female rhesus monkeys

The fat derived protein leptin has its anorexic action through a number of neuropeptides including an upregulation of corticotropin releasing hormone (CRH) expression in the hypothalamus. However, the influence of leptin on these neuropeptides may be different during stress. The present study used ovariectomized female rhesus monkeys (n=8) to further define the effect of leptin on HPA responsivity. To accomplish this, we assessed the effects of constant leptin infusion on cortisol and ACTH secretion in both a predictable and unpredictable situation as well as in response to dexamethasone suppression-CRH stimulation test. We hypothesized that leptin would attenuate the increase in cortisol and ACTH to a novel, unpredictable situation and would enhance glucocorticoid negative feedback and diminish the response to CRH. Animals were assessed under control placebo conditions and during a 28 day infusion with recombinant human leptin (6 microg/kg/day, SC). Within each treatment condition, HPA responsivity was assessed during no estradiol replacement and acute estradiol replacement that produced serum concentrations of approximately 40 pg/ml. However, the results indicated that neither estradiol alone or in combination with leptin had any consistent effect on the outcome measures. Compared to the control condition, leptin had no effect on the cortisol diurnal rhythm; however, evening but not morning plasma ACTH concentrations were significantly lower during leptin infusion. In contrast, the response in plasma cortisol and ACTH to an unpredictable situation was significantly attenuated by chronic leptin infusion. Furthermore, leptin enhanced glucocorticoid negative feedback and blunted CRH-induced increase in both cortisol and ACTH. Taken together, these data suggest that in the female monkey, leptin has little effect on basal cortisol. However, when the HPA axis is activated, leptin attenuates the neuroendocrine response by enhancing glucocorticoid negative feedback. These data underscore the potential importance of leptin in maintaining homeostasis through its diverse interaction with the HPA axis.     

Ascites Produced in Rats Without Tubercle Bacilli or Tumor Cells

Intraperitoneal injection of rats with two doses of pertussis vaccine produces a small amount of ascitic fluid. Much larger amounts of fluid are produced when two spaced injections of the vaccine are preceded by a small amount of liquid petrolatum. A similar result is obtained by a single injection of pertussis vaccine emulsified in liquid petrolatum and Arlacel A. Ascites produced without tubercle bacilli or tumor cells may increase the use of rats for antibody production.     

Growth of Typhoid and Paratyphoid Bacilli in Intravenously Infected Mice

The in vivo growth of Salmonella paratyphi A, S. paratyphi B, S. paratyphi C, and S. typhi, as well as of an S. typhi-typhimurium hybrid, was studied in three different strains of mice. S. paratyphi A and B and S. typhi demonstrated very little growth potential in any of the intravenously infected mice, even after as many as 20 serial mouse passages. It was noted, however, that small numbers of viable S. paratyphi B and S. typhi persisted in the spleens of infected mice for up to 28 days. Salmonella paratyphi C and the S. typhi-typhimurium hybrid gave rise to progressive systemic infections beginning from very small intravenous inocula. The median lethal doses for the C57B1 strain of mouse were about five organisms. The relevance of these findings with regard to the development of an animal model for studying human typhoid fever vaccines is discussed.     

Plaque-Forming Cells in Man

The influence of acetylsalicylic acid (ASA) and steroid (ST) on the number of plaque-forming cells (PFC) developed in pokeweed mitogen-activated cultures of peripheral blood lymphocytes (PBL) was investigated. Cultures of 10(6) PBL were established from blood samples of 16 healthy volunteers before and after intake of 2 g of ASA, and parallel cultures were supplemented with ST in vitro. The immunoglobulin secretion was monitored with a protein A assay. Our results show that pharmacological doses of ASA in vivo decrease the number of PFC by 41%, whereas the distribution of the subpopulations was unaltered. In cultures of PBL obtained before the intake of ASA and supplemented with 10, 50 or 100 micrograms/ml of dexamethasone the number of PFC was decreased by 50%, 41% and 44%, respectively. In cultures of PBL obtained after the intake of ASA and supplemented with 10, 50 or 100 micrograms of ST, the number of PFC was further decreased by 22%, 32% and 38%. The effects of ASA in vivo and ST in vitro were additive. The ratio of IgM, IgG and IgA PFC was unaffected by ASA and ST. It is suggested that the modulation of the PFC response induced by ASA and ST is mediated by the prostaglandin system.