Fenfluramine challenge, self-injurious behavior, and aggression in rhesus monkeys

Self-injurious behavior (SIB) and aggression have been linked to reduced serotonergic (5-HT) functioning in both humans and nonhuman primates. The present study examined serum prolactin and cortisol responses to the 5-HT releasing agent D,L-fenfluramine (FEN) in 24 individually housed rhesus monkeys (Macaca mulatta), 15 of which carried a veterinary record of self-wounding (SW). Subjects received two doses of FEN, 4 and 2 mg/kg, separated by an interval of at least 2 months. For control purposes, monkeys were given an intramuscular saline injection 1 week prior to each FEN challenge. The relationship between the hormonal responses to FEN, wounding history, the rates of self-directed biting and aggression were determined for each animal based on 100 five-minute observations conducted over a period of 12 months surrounding the challenge procedures. Prolactin and cortisol responses to FEN were unrelated either to wounding history or to rates of self-directed biting. However, there were significant inverse correlations between levels of aggression and the prolactin response to both doses of FEN. The present findings provide no evidence for reduced 5-HT system function in rhesus monkeys with SIB under the present challenge conditions. However, the results are consistent with a previously reported inverse relationship between serotonergic activity and aggression. Moreover, a dose-dependent response to FEN was observed only for prolactin, suggesting that this variable is more appropriate than cortisol as an endpoint for FEN challenge in monkeys.     

The role of T cell — Macrophage interactions in tuberculosis

Acquired resistance against tuberculosis paradigmatically depends on specific T lymphocytes and mononuclear phagocytes. The etiological agent,Mycobacterium tuberculosis is capable of replicating in mononuclear phagocytes which act both as habitat and as effectors of protection. Upon interaction with antigen-specific T lymphocytes infected mononuclear phagocytes acquire tuberculosis activities. Here, data from experimental tuberculosis studies in mice are summarized which show that: interleukins produced by cloned T cells and recombinant interferon-γ are capable of activating tuberculostatic capacities in macrophages; both CD4 and CD8 T cells, after adequate stimulation, produce interferon-γ; CD8 T cells lyse macrophages in an antigen-specific way; not only CD8 but also CD4 T cells possess an antigen-specific cytolytic potential; lysis of infected macrophages results in mycobacterial growth inhibition. Evidence is also presented that tuberculostatic activities of activated macrophages depend on phagosome-lysosome fusion and are independent of reactive oxygen metabolites and that some strains ofM. tuberculosis are resistant against interferon-γ activated macrophages. These findings suggest that both helper and cytolytic T cells participate in the immune response to tuberculosis and that similar T cell mechanisms contribute to resistance as well as pathogenesis. Protection against tuberculosis, therefore, depends on subtle coordination of the immune response.     

Disseminated infection with Nattrassia mangiferae in an immunosuppressed patient

Disseminated infection with the coelomycetous fungus Nattrassia mangiferae is a very rare disease affecting only the immunocompromised host. We report the first case of a disseminated infection with spondylodiscitis and granular skin lesions due to N. mangiferae in a renal transplant patient.     

Noninvasive measurement of cell volume changes by negative staining

To maintain the intracellular concentration of ions and small molecules on osmotic challenges, nature has developed highly sophisticated transport systems for regulating water and ion content. An ideal measurement technique for volume changes of cells during osmotic challenges has to fulfil two requirements: it has to be osmotically inert, and it should allow online monitoring of cell volume changes. Here, a simple fluorescence microscopy-based approach is presented. Using fluorescein as a negative stain, it is possible to monitor cell volume changes without affecting the functionality of cell membranes and cell osmolarity. Measurement of Madine-Darby canine kidney (MDCK) cells after hypo- and hyperosmotic challenges reveals the main advantages of this approach: besides providing precise and reproducible quantitative data on reversible cell volume changes, the viability of the cells can be assessed directly by the appearance of stain in the cytoplasm. This becomes evident especially after hypo-osmotic challenge of glutaraldehyde-treated cells, which become leaky after fixation, followed by a massive volume change. This new approach represents a very sensitive measurement technique for cell volume changes resulting from water or ion flux, and thus seems to be an ideal tool for studying cell volume regulatory processes.     

Cross-reactive trinitrophenylated peptides as antigens for class II major histocompatibility complex-restricted T cells and inducers of contact sensitivity in mice. Limited T cell receptor repertoire

The induction of contact sensitivity in mice by hapten reagents such as trinitrochlorobenzene (TNCB) involves the activation of class II major histocompatibility complex (MHC)-restricted, hapten-specific, CD4⁺ T cells. Reports from different laboratories have indicated that the relevant antigenic epitopes in such reactions might include hapten-conjugated, MHC class II-associated peptides. This study for the first time directly demonstrates that hapten-peptides account for the majority of determinants recognized by trinitrophenyl (TNP)-specific CD4⁺ T lymphocytes. The sequences of those TNP carrier peptides do not have to be related to mouse proteins. Thus, we show that TNP-modified peptides derived from mouse IgG, pigeon cytochrome c or staphylococcal nuclease known to bind to I-A^b or from λ represser with specificity to I-A^d as well as TNP-proteins such as bovine serum albumin, ovalbumin or keyhole limpet hemocyanin all create class II-restricted hapten determinants for a number of TNP-specific T cell clones and hybridomas. All of these cells were induced with cells modified by trinitrobenzene sulfonic acid (TNBS). In addition, we present arguments indicating that individual TNP-specific helper T cells may cross-react with different TNP-peptides bound to identical class II molecules. Chemical treatment of antigen-presenting cells with TNCB or TNBS may thus result in a limited number of particularly repetitive immunodominant hapten epitopes. Immunodominant epitopes were also indicated by an overrepresentation of the TCR elements Vβ2 and Vα10 in I-A^b/TNP-specific T cells. Most importantly, however, we demonstrate that TNP attached to lysine 97 in the staphylococcal nuclease peptide 93–105 (i.e. a clearly “non-self” sequence) is able to prime mice for subsequent elicitation of contact sensitivity by TNCB in the absence of foreign protein. We take this to indicate that those TNP-peptide determinants defined by us as immuno-dominant are responsible for the induction of contact sensitivity to haptens.     

Hyperglycemic and Hyperosmolar Responses to Graded Hemorrhage

Changes of the arterial plasma osmolality and of the glucose concentration were followed during a 30 min period of graded hemorrhagic hypotension (80, 50, and 30 mmHg) in the cat. Bleeding evoked a significant plasma hyperosmolality at all three hypotension levels and the responses were quantitatively related to the degree of hypotension. An approximate steady state increase in the arterial plasma osmolality was reached about 20 min after the start of the bleeding and it then averaged 8, 20, and 25 mOsm/kg H₂O at 80, 50, and 30 mmHg, respectively. Bleeding also evoked an increase in the plasma glucose concentration, which almost entirely accounted for the observed hyperosmolality, especially at 80 and 50 mmHg. In late stages of hypotension at 30 mmHg, elevated plasma lactate and potassium concentrations contributed to the overall hyperosmolality. — Previous hemorrhagic hypotension experiments at 50 mmHg (Järhult 1975 b) have shown that hyperosmolality serves as an important regulator of the plasma and extracellular fluid volumes during bleeding. The present results indicate that such an osmolar compensatory mechanism is operating over wide ranges of hemorrhagic hypotension.     

Osteogenesis imperfecta lethal in infancy: Case report and scanning electron microscopic studies of the deciduous teeth

Radiologic evaluation of the skeleton and scanning electron microscopic studies of the teeth were performed on an infant boy with a lethal osteogenesis imperfecta (OI) syndrome who died at 10 mo of pneumonia. The skeletal findings included ribs that were focally expanded by fracture calluses, flat vertebral bodies, and wide limb bones. On fractured tooth surfaces, the enamel and dentin were normal as was the dentin calcification front. Although microscopic abnormalities have been noted in teeth from previously reported infants with lethal OI, a few studies also report infants with normal teeth. These differences in dental findings may indicate heterogeneity in OI lethal in infancy. Results of our study indicate that, until the primary biochemical defects in the OI syndromes are elucidated, examination of teeth from other infants with lethal OI and detailed evaluation of other clinical and skeletal features will aid in delineating heterogeneity and variation in expression in lethal OI.