Risk factors for respiratory syncytial virus bronchiolitis hospital admission in New Zealand.

This study assessed risk factors for respiratory syncytial virus (RSV) hospitalization and disease severity in Wellington, New Zealand. During the southern hemisphere winter months of 2003--2005, 230 infants aged < 24 months hospitalized with bronchiolitis were recruited. RSV was indentified in 141 (61%) infants. Comparison with data from all live hospital births from the same region (2003--2005) revealed three independent risk factors for RSV hospitalization: birth between February and July [adjusted risk ratio (aRR) 1.62, 95% confidence interval (CI) 1.5-2.29], gestation <37 weeks (aRR 2.29, 95% CI 1.48-3.56) and Maori ethnicity (aRR 3.64, 95% CI 2.27-5.85), or Pacific ethnicity (aRR 3.60, 95% CI 2.14-6.06). The high risk for Maori and Pacific infants was only partially accounted for by other known risk factors. This work highlights the importance of RSV disease in indigenous and minority populations, and identifies the need for further research to develop public health measures that can reduce health disparities.

Role of eosinophils in the pathogenesis of Mycobacterium bovis BCG infection in gamma interferon receptor-deficient mice.

A profound eosinophil infiltration of granulomas is observed in the lungs of Mycobacterium bovis bacillus Calmette Guérin-infected gamma interferon receptor-deficient mice. Blockade of eosinophil proliferation and recruitment into the lung by treatment with anti-interleukin-5 monoclonal antibody marginally reduced mycobacterial growth within the lung but did not affect dissemination of the infection to other tissues.

Constitutive expression of interleukin 4 in vivo does not lead to the development of T helper 2 type CD8+ T cells secreting interleukin 4 or interleukin 5.

Interleukin 4 (IL-4) has been shown to commit CD8+ T cells to a T helper (Th) 2 functional phenotype in vitro. To study the effects of IL-4 on CD8+ T cell development in vivo we analysed the CD8+ T cell phenotype in mice constitutively expressing IL-4. Purified CD8+ T cells from uninfected or flu infected IL-4 transgenic (tg) animals produced no detectable IL-4 or IL-5 after in vitro stimulation on anti-CD3 coated plates. However, CD8+ T cells from IL-4 tg mice could be converted into IL-4 and IL-5 producers in vitro in the presence of exogenous added IL-4, showing that these cells were still responsive to IL-4. IL-4 tg mice also showed a delay in influenza virus clearance from the lung, which was probably due to the observed reduction of total CD8+ T cell numbers in the IL-4 tg animals since IL-4 tg CD8+ T cells showed normal levels of influenza-specific cytotoxicity in comparison to controls. Taken together these results suggest that CD8+ T cells are not necessarily switched to a Th2 phenotype by the presence of IL-4 and that some other factor(s) may be important in the switch process of CD8+ T cells in vivo, since the addition of IL-4 during CD8+ T cell activation in vitro leads to Th2 type CD8+ T cells secreting IL-4 and IL-5.

Infection of mice with Mycobacterium bovis-BCG induces both Th1 and Th2 immune responses in the absence of interferon-gamma signalling.

A murine pulmonary infection model using Mycobacterium bovis-BCG was used to study the development of Th1 and Th2 type responses in mice lacking a functional IFN-gamma receptor (IFN-gamma R-/-). Strikingly, the IFN-gamma R-/- mice maintained the Th1 response and developed a profound M. bovis-BCG, specific Th2 type immune response characterized by IL-5-producing CD4+ T cells, eosinophil infiltration of granulomas, and significantly elevated serum IgE levels. The increase in IL-5 production and eosinophil recruitment into the lung could be detected within the first 1-2 weeks of infection, indicating that the Th2 response was not due to greatly enhanced bacterial numbers observed later in infection. These results clearly indicate that IFN-gamma acts during M. bovis-BCG infection to suppress the development of Th2 immune responses. Furthermore, they demonstrate that IFN-gamma is not a necessary cofactor in the development of Th1 type cells secreting IFN-gamma. In conclusion, these data demonstrate that IFN-gamma plays a major role in suppressing a potentially disease-promoting Th2 immune response during mycobacterial infections.

CTLA-4 blockade enhances the immune response induced by mycobacterial infection but does not lead to increased protection.

The murine immune response to a pulmonary mycobacterial infection is slow to develop, allowing bacterial numbers to increase in the lung for several weeks after infection. We sought to enhance the protective immune response induced during Mycobacterium bovis BCG infection by administering an antibody that blocks the interaction of CTLA-4 with its ligands, CD80 and CD86. We found that injection of anti-CTLA-4 monoclonal antibody (MAb) greatly enhanced and accelerated the immune response, as measured by increased cellularity of the draining mediastinal lymph nodes, and enhanced antigen-inducible proliferation and gamma interferon production by mediastinal lymphocytes in vitro. However, despite the apparently enhanced immune response in the mediastinal lymph node following treatment with anti-CTLA-4 MAb, there was no improvement in clearance of mycobacteria in the lungs, liver, or spleen. Examination of the primary site of infection, the lung, revealed that CTLA-4 blockade had no effect on the number or function of lymphocytes infiltrating the infected lung tissue. Taken together, these data suggest that in vivo CTLA-4 blockade enhances mycobacterial-infection-induced lymphocyte expansion and effector cell cytokine production in the draining lymph node but does not alter the number or function of lymphocytes at the primary site of infection and therefore does not lead to enhanced clearance of the infection.

Identification of potential CD8+ T-cell epitopes of the 19 kDa and AhpC proteins from Mycobacterium tuberculosis. No evidence for CD8+ T-cell priming against the identified peptides after DNA-vaccination of mice.

Mycobacterium tuberculosis is one of the major killers among infectious agents. It is of great importance to develop an efficient vaccine against M. tuberculosis since the only available vaccine, M. bovis-BCG, has a low efficacy. Furthermore, the emergence of multi-drug-resistant M. tuberculosis strains makes it difficult to cure the disease. CD8+ T cells have been implied to play an important role in protective immunity against M. tuberculosis. A good vaccination strategy for the induction of cytotoxic CD8+ T-cell responses is naked DNA-injection of eukaryotic expression vectors. The use of DNA-injection in an attempt to induce cytotoxic CD8+ T-cell responses against epitopes of the 19 kDa or AhpC proteins from M. tuberculosis in mice was studied. MHC class I binding assays, of peptides derived from these proteins, demonstrated the presence of potential CD8+ T-cell epitopes. However, CD8+ T-cell responses against the peptides after DNA-injection were not detected. Furthermore, no difference in the kinetics of bacterial clearance was observed in vaccinated versus unvaccinated animals, even though 19 kDa and AhpC specific antibodies were readily detected in the serum of vaccinated animals. Taken together these results suggest that the 19 kDa and AhpC genes are not good candidates for DNA vaccines against M. tuberculosis.

IL-4, IL-5 and IL-10 are not required for the control of M. bovis-BCG infection in mice.

Mycobacterial infections in mice are normally characterized by a profound Th1 cell-mediated immune response, in which T cells secrete large amounts of IFN-gamma. Recent evidence suggests that this response also includes a Th2 component. In order to investigate whether production of IL-4, IL-5, or IL-10 influenced the outcome of a Mycobacterium bovis-bacille Calmette-Guérin (BCG) infection, we intranasally infected IL-4, IL-5, and IL-10 gene-deficient and control mice and monitored the resulting immune response and bacterial clearance. IL-4, IL-5, and IL-10 deficient mice cleared the mycobacteria with the same kinetics as control mice. Furthermore, T cells of cytokine deficient and control mice produced similar levels of IFN-gamma following in vitro stimulation with purified protein derivative (PPD) from M. bovis. We conclude that the cytokines IL-4, IL-5 and IL-10 are not essential for and do not negatively influence the protective immune response against M. bovis-BCG in the lung of mice.

Working with anger in groups: a modern analytic approach.

The development of Modern Psychoanalytic psychotherapy with schizophrenic and borderline patients is briefly traced, and the major themes of the treatment approach that derived from that early work are discussed with attention to their application in group therapy. These themes include the concepts of the narcissistic defense, narcissistic transference, joining or reinforcing defenses, emotional communication, and a shift away from the classical psychoanalytic emphasis on interpretation and insight to a strategy of helping the patient put all his or her thoughts and feelings into language in a constructive manner. These principles are discussed in connection with three kinds of problems involving anger in therapy groups: members' anger destructively turned against their own egos, anger expressed toward the leader within a negative transference, and anger destructively expressed toward others in the group. Lastly, consideration is given to the group leader's anger and its expression within the group. Some contrasts are made between the Modern Analytic approach and the classical Freudian position as well as Kohut's self psychology.

Vibrotactile frequency recognition: forward and backward masking effects.

Forward and backward vibrotactile recognition masking was investigated in 4 subjects with 240-Hz and 160-Hz targets of 20 ms duration and four 200-Hz masks, using interstimulus intervals (ISIs) ranging from -500 to 500 ms. Two of the masks (short) were 20 ms and two (long) were 200 ms in duration. One of each set of masks was matched in subjective intensity to the targets, but the others were more intense. The range of ISIs over which masking was obtained was comparable to that found by Massaro (1970) with auditory stimuli. Both short masks produced more masking than either long mask except at short ISIs. Larger mask intensities increased masking only at very short ISIs, and longer mask durations increased backward but not forward masking.

Vibrotactile frequency discrimination at short durations.

This experiment investigated how frequency discrimination of a sinusoidal, mechanical vibration applied to the tip of the right index finger is affected by shortening the duration of the stimuli from 200 ms to 30 ms. Using a standard stimulus of 100 Hz at 30 dB above threshold, seven comparison frequencies (at intervals of 10 Hz) were judged as higher or lower in frequency according to the method of constant differences. Vibrotactile stimuli were matched for subjective intensity across both frequency and duration. Difference limens for vibrotactile frequency were found to decline slightly from 200 ms to 50 ms (attributable to practice) and to increase noticeably at 30 ms. This result is discussed in relation to the seemingly contradictory results for auditory pitch discrimination.

A new tactile illusion: temporal limits on the processing of spatiotemporal patterns.

A novel illusion was observed when 12 tactile point-stimulators arranged in a circle were sequentially activated so that each quadrant was first traced in a clockwise manner, then counterclockwise, and again in a clockwise manner, after which the next quadrant was similarly traced. Under certain temporal conditions this stimulus pattern was experienced as a point moving through an overall circular path but looping inwardly about once per quandrant. The effects of variations in rate of presentation of such stimuli were investigated by having subjects make drawings of their perceptual experiences. Three skin surfaces were used (palm, fingers, and forearm), and all produced similar results except for lower confidence and reliability of drawings made from forearm stimulation. Pattern presentation rate, however, had a consistent and powerful effect, with the looping illusion most frequently observed at rates around 25 pattern points per s and with different perceptual organizations dominating as rates departed widely from this optimum. The illusory perceptual organizations were interpreted as compromises between past and present stimulation necessitated by the relative slowness of tactile processing of spatiotemporal patterns.

Forward and backward tactile recognition masking.

Forward and backward tactile recognition masking were investigated with a 15 by 15 array of tactile point-stimulators with the use of targets consisting of line segments differing in location and orientation and a random-dot embedding mask. Ss were paid graduate student volunteers (three males and one female). Durations of targets and masks were varied, and interstimulus intervals ranged from zero to 300 msec. Increases in target duration over mask duration decreased forward, but not backward masking. Small increases in mask duration over target duration increased both forward and backward masking. Further large increases in mask duration increased backward masking, but had no effect on forward masking. The results were interpreted as indicating that forward masking is predominantly influenced by peripheral processes, while backward masking is the result of a combination of peripheral and central processes, in agreement with similar findings in audition and vision.