Vaccine immune response and side effects with the use of acetaminophen with influenza vaccine.

The purpose of this study was to determine whether acetaminophen impairs the immune response to influenza vaccine. Influenza vaccine is an under-utilized preventive measure, partly because of the unfounded perception that fever and myalgias frequently follow vaccination. While acetaminophen may decrease these infrequent side effects, it may also alter the immune response to vaccination. We compare the effect of acetaminophen with placebo on the humoral immune response to the 1991-1992 commercially available influenza vaccine. We studied 60 healthy, elderly subjects from a geriatric clinic and 20 infirm, elderly subjects from a nursing home. The subjects were randomly assigned to receive placebo or acetaminophen (1,000 mg every 6 h) for 2 days. Acetaminophen did not depress or enhance the immune development of serum hemagglutination inhibition antibody to the three vaccine antigens. The systemic side effects of fever and myalgia were uncommon in both groups. The healthy elderly subjects mounted a significantly better immune response to the influenza virus A/Taiwan/1/86 (H1N1) vaccine strain than did the infirm elderly subjects (geometric mean titer, 115 versus 51; P = 0.003). The functional activity score obtained by using the chronic healthy evaluation component of the Acute Physiology and Chronic Health Evaluation system could be used to distinguish the healthy from the infirm elderly (scores of 1.27 versus 3.75, P < 0.001). Acetaminophen neither depressed nor enhanced the serum antibody response to the vaccine in the healthy and infirm elderly subjects studied.     

Long-term growth of human T cell lines and clones on anti-CD3 antibody-treated tissue culture plates

Long-term growth of antigen-specific human T cells requires, in addition to IL-2, periodic exposure to antigen and accessory cells. In certain cases, accessory cells are not available or their presence in culture is undesired. We have developed a method of growing and sustaining human T cell lines and clones in long-term tissue culture in the absence of specific antigen or accessory cells. The requirement for antigen and/or accessory cells could be replaced by a monoclonal antibody to the CD3 determinant of human T cells (OKT3) bound to the surface of plastic tissue culture wells. Autoreactive, alloreactive, and antigen-reactive T cell lines and clones were maintained in culture for 8-12 weeks without antigen or accessory cells. The antigen specificity of these T cells was maintained.     

Bacterial Clearance and Cytokine Profiles in a Murine Model of Postsurgical Nosocomial Pneumonia

The development of a nosocomial pneumonia is facilitated by alterations in host innate pulmonary antibacterial defenses following surgical trauma, which can result in decreased pulmonary bacterial clearance and increased morbidity and mortality. In a murine model of postoperative nosocomial infection, surgical stress (laparotomy) decreased Escherichia coli clearance from the lungs of animals that underwent surgery. Consistent with previous studies, (i) pulmonary levels of tumor necrosis factor alpha at 6 h and of interleukin-1β (IL-1β), IL-6, and gamma interferon (IFN-γ) at 24 h post-bacterial infection (PBI) were decreased in animals that underwent laparotomy 24 h prior to E. coli infection (LAP/E. coli) compared to animals that received E. coli only; (ii) KC and macrophage inhibitory protein 2 were elevated at 6 h PBI in LAP/E. coli animals compared to E. coli-only animals; however, at 24 h PBI, levels were higher in the E. coli-only group; (iii) at 24 h PBI, monocyte chemoattractant protein 1 was lower in the LAP/E. coli group compared to the E. coli-only group; (iv) IL-10 levels were unaffected at all time points evaluated; and (v) the total number of neutrophils present in the lungs of LAP/E. coli animals at 6 h PBI was decreased in comparison to that in E. coli-only animals, resulting in decreased bacterial clearance and increased mortality in LAP/E. coli animals by 24 h PBI. Similar changes in cytokine profiles, pulmonary bacterial clearance, and mortality were consistent with reported findings in patients following surgical trauma. This model, therefore, provides a clinically relevant system in which the molecular and cellular mechanisms that lead to the development of nosocomial pneumonia can be further explored.     

Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study

A systematic analysis of both tumors and the surrounding urothelium to help identify what lies behind the mechanism of multifocal tumor development has not yet been performed. In this study we investigated chromosome 1, 7, 9, and 17 aneusomy in 25 superficial papillary carcinomas and in 51 tissue samples taken from sites of macroscopically uninvolved urothelium surrounding the tumors, using the fluorescence in situ hybridization method. Our data demonstrated a close genetic relationship between all examined tumors and normal-appearing mucosa. Numeric aberrations of chromosomes 1, 7, 9, and 17 were found to exhibit similar patterns in all analyzed specimens, although with different frequencies.     

Innervation of the intestinal muscular coat

Summary Nerve bundles have an uneven distribution in the muscularis externa of the guinea-pig ileum. They are absent in the longitudinal muscle layer, and are mainly concentrated between the two muscle layers and between the bulk of the circular layer and its innermost portion. The latter is formed by muscle cells which are smaller and more electron dense than the ordinary smooth muscle cells. In cross sections of the circular layer there are 5425 intramuscular axons (of which 921 contain vesicles) per 10000 smooth muscle cells, and they are grouped in bundles, mainly formed by 10–40 axons. The gap between axons and smooth muscle cells is generally hundreds of nanometres; only a few junctions with a gap smaller than 20 nm occur. Interstitial cells have a cytoplasm occupied mainly by smooth reticulum and ribosomes, and processes containing filaments. These processes are closely associated with smooth muscle cells and nerve bundles. Interstitial cells have no basal lamina. Nexuses are found in the circular but not in the longitudinal muscle layer. Attachment plaques and invaginating processes are found in both muscle layers. More complex interdigitations appear between contacting muscle cells. There are 84 intramuscular blood vessels per 10 000 cross-sectioned smooth muscle cells (or 1700 per mm²).     

Origin and filiation of human plasmacytoid dendritic cells

Human plasmacytoid dendritic cells represent a rare population of leukocytes which produce high amounts of type I interferon in response to certain viruses. Although those cells were first described in 1958, there are still unsolved issues related to their origin and function. Recently, a leukemic counterpart of plasmacytoid dendritic cells was identified. Molecular approaches using either normal or leukemic plasmacytoid dendritic cells provide some new insights into the controversial lymphoid origin of those cells. The need for specific markers is still a critical aspect for the identification of plasmacytoid dendritic cells, whatever stage of differentiation, in normal as well as in pathological conditions. Hopefully, novel markers will allow delineation of the relationships between dendritic cells at different stages of differentiation/maturation along the myeloid and lymphoid lineages.     

Inhibition of microglial inflammatory responses by norepinephrine: effects on nitric oxide and interleukin-1β production

Background

Under pathological conditions, microglia produce proinflammatory mediators which contribute to neurologic damage, and whose levels can be modulated by endogenous factors including neurotransmitters such as norepinephrine (NE). We investigated the ability of NE to suppress microglial activation, in particular its effects on induction and activity of the inducible form of nitric oxide synthase (NOS2) and the possible role that IL-1β plays in that response.

Methods

Rat cortical microglia were stimulated with bacterial lipopolysaccharide (LPS) to induce NOS2 expression (assessed by nitrite and nitrate accumulation, NO production, and NOS2 mRNA levels) and IL-1β release (assessed by ELISA). Effects of NE were examined by co-incubating cells with different concentrations of NE, adrenergic receptor agonists and antagonists, cAMP analogs, and protein kinase (PK) A and adenylate cyclase (AC) inhibitors. Effects on the NFκB:IκB pathway were examined by using selective a NFκB inhibitor and measuring IκBα protein levels by western blots. A role for IL-1β in NOS2 induction was tested by examining effects of caspase-1 inhibitors and using caspase-1 deficient cells.

Results

LPS caused a time-dependent increase in NOS2 mRNA levels and NO production; which was blocked by a selective NFκB inhibitor. NE dose-dependently reduced NOS2 expression and NO generation, via activation of β2-adrenergic receptors (β2-ARs), and reduced loss of inhibitory IkBα protein. NE effects were replicated by dibutyryl-cyclic AMP. However, co-incubation with either PKA or AC inhibitors did not reverse suppressive effects of NE, but instead reduced nitrite production. A role for IL-1β was suggested since NE potently blocked microglial IL-1β production. However, incubation with a caspase-1 inhibitor, which reduced IL-1β levels, had no effect on NO production; incubation with IL-receptor antagonist had biphasic effects on nitrite production; and NE inhibited nitrite production in caspase-1 deficient microglia.

Conclusions

NE reduces microglial NOS2 expression and IL-1β production, however IL-1β does not play a critical role in NOS2 induction nor in mediating NE suppressive effects. Changes in magnitude or kinetics of cAMP may modulate NOS2 induction as well as suppression by NE. These results suggest that dysregulation of the central cathecolaminergic system may contribute to detrimental inflammatory responses and brain damage in neurological disease or trauma.