Serum neopterin for early assessment of severity of severe acute respiratory syndrome

Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement.     

Long-term treatment with anti-alpha 4 integrin antibodies aggravates colitis in G alpha i2-deficient mice

Targeted deletion of the heterotrimeric G protein, Galphai2, in mice induces lethal colitis closely resembling ulcerative colitis. In chronic colitis, migration of circulating leukocytes into the intestinal mucosa is partially dependent on alpha4 integrins. In previous studies, short-term administration of anti-alpha4 integrin antibodies has been shown to attenuate intestinal inflammation, and here we elucidate the effect of long-term administration of anti-alpha4 integrin antibodies on colitis in Galphai2(-/- )mice. Long-term blockade of alpha4 integrin significantly increased the severity of colitis in Galphai2(-/-) mice. The inflammation was confined to the colon, associated with increased cancer in situ, destruction of crypt architecture, and increased production of IL-1beta, TNF-alpha and IFN-gamma. Blockade of alpha4 integrin reduced the recruitment of activated T cells to the small intestine. In strong contrast, there were significantly higher numbers of activated T cells in the colonic lamina propria and epithelium, most probably due to in situ proliferation. Furthermore, treatment with alpha4 integrin antibodies induced decreased levels of total IgA and IgG in sera, whereas total IgM levels were unchanged. These new findings may have implications in the understanding of the progression of chronic intestinal inflammation.     

Target motion measurement without implanted markers and its validation by comparison with manually obtained data

For an effective radiotherapy the exact tumor location must be determined. The localization has to take into account patient's setup position as well as internal organ motion. Among the different localization methods, the use of a computer tomography (CT) scanner in the therapy room has been proposed recently. Achieving a CT with the patient on the therapy couch, a patient's treatment position is captured. We present a method to locate tumor considering internal organ motion and displacements due to respiration. We tested the method with prostate and lung patients. The method found the most probable tumor position as well as, for high-mobility tumors located in the lung, its trajectory during the respiratory cycle. The results of this novel method were validated by comparison with manually determined target position.     

The music of speech: music training facilitates pitch processing in both music and language

The main aim of the present experiment was to determine whether extensive musical training facilitates pitch contour processing not only in music but also in language. We used a parametric manipulation of final notes' or words' fundamental frequency (F0), and we recorded behavioral and electrophysiological data to examine the precise time course of pitch processing. We compared professional musicians and nonmusicians. Results revealed that within both domains, musicians detected weak F0 manipulations better than nonmusicians. Moreover, F0 manipulations within both music and language elicited similar variations in brain electrical potentials, with overall shorter onset latency for musicians than for nonmusicians. Finally, the scalp distribution of an early negativity in the linguistic task varied with musical expertise, being largest over temporal sites bilaterally for musicians and largest centrally and over left temporal sites for nonmusicians. These results are taken as evidence that extensive musical training influences the perception of pitch contour in spoken language.     

Calmodulin permanently associates with rat olfactory CNG channels under native conditions

An important mechanism by which vertebrate olfactory sensory neurons rapidly adapt to odorants is feedback modulation of the Ca(2+)-permeable cyclic nucleotide-gated (CNG) transduction channels. Extensive heterologous studies of homomeric CNGA2 channels have led to a molecular model of channel modulation based on the binding of calcium-calmodulin to a site on the cytoplasmic amino terminus of CNGA2. Native rat olfactory CNG channels, however, are heteromeric complexes of three homologous but distinct subunits. Notably, in heteromeric channels, we found no role for CNGA2 in feedback modulation. Instead, an IQ-type calmodulin-binding site on CNGB1b and a similar but previously unidentified site on CNGA4 are necessary and sufficient. These sites seem to confer binding of Ca(2+)-free calmodulin (apocalmodulin), which is then poised to trigger inhibition of native channels in the presence of Ca(2+).     

Drug development strategies for asthma: in search of a new paradigm

The spiraling costs of asthma treatment seem set to continue rising, given the equivocal performance of the latest generation of specific anti-inflammatory drugs in trials in adult asthmatics. We argue that the continuation of this trend is inevitable unless there is a substantial realignment of entrenched drug development policy in the pharmaceutical industry and a parallel shift in licensing policy by regulatory authorities to encourage the development of drugs capable of halting the progression from acute to chronic asthma when the disease first manifests in childhood. The theoretical framework for such an approach, including proof-of-principle data from studies in children with early-stage disease and a range of candidate drugs, already exists. What is needed is informed debate on the risks versus potential benefits of this approach.     

COMT Gene Polymorphism Is Associated with Declarative Memory in Adulthood and Old Age

Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.