Cutaneous lymphocyte antigen expression on human effector B cells depends on the site and on the nature of antigen encounter

In contrast to T cells, information on skin-homing B cells expressing the cutaneous lymphocyte antigen (CLA) is sparse. CLA expression on human B cells was investigated among circulating immunoglobulin-secreting cells (ISC) and among antigen-specific antibody-secreting cells (ASC) elicited by parenteral, oral or rectal primary immunization, or by parenteral or oral secondary immunization with Salmonella typhi Ty21a. CLA expression was examined by combining cell sorting with an enzyme-linked immunospot assay. Among all ISC, the proportion of CLA(+) cells was 13-21%. Parenteral immunization induced antigen-specific ASC of which 13% were CLA(+), while oral and rectal immunizations were followed by only 1% of CLA(+) ASC (p<0.001). Oral re-immunization was followed by an up-regulation of CLA (34-48%) regardless of the route of priming. Parenteral re-immunization elicited ASC of which 9-14% were CLA(+). In conclusion, the expression of CLA on human effector B cells depends on the site of antigen encounter: intestinal stimulation elicits cells with no CLA, while parenteral encounter elicits significant numbers of CLA(+) cells. Even though primary antigen encounter in the intestine failed to stimulate CLA expression, up-regulation of CLA was found upon intestinal antigen re-encounter. These findings may be of relevance in the pathogenesis of some cutaneous disorders.     

Linguistic and pragmatic aspects of narration in Finnish typically developing children and children with specific language impairment

This study investigates narratives of Finnish children with specific language impairment (SLI) from linguistic and pragmatic perspectives, in order to get a comprehensive overview of these children’s narrative abilities. Nineteen children with SLI (mean age 6;1 years) and 19 typically developing age-matched children participated in the study. Their picture-elicited narrations were analysed for linguistic productivity and complexity, grammatical and referential accuracy, event content, the use of mental state expressions and narrative comprehension. Children with SLI showed difficulties in every aspect of narration in comparison to their peers. Only one measure of productivity, the number of communication units, did not reach statistical significance. Not only was linguistic structure fragile but also pragmatic aspects of storytelling (referencing, event content, mental state expressions and inferencing) were demanding for children with SLI. Results suggest that pragmatic aspects of narration should be taken into account more often when assessing narrative abilities of children with SLI.     

Carbohydrate intake, serum lipids and apolipoprotein E phenotype show association in children

Aim:  To study the association between carbohydrate intake and serum lipids in children, and influence of apolipoprotein E phenotype (apoE) on the association.
Subjects/methods:  A total of 644 children from a prospective, randomized atherosclerosis prevention trial (STRIP) participated in this longitudinal study at age 5 (n = 644), 7 (n = 585) and 9 (n = 550) years. ApoE phenotype, fasting triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations and 4-day food records were analysed.
Results:  An increase in the total carbohydrate intake by 1 E% (percentage of total daily energy intake) associated with a decrease in HDL cholesterol by 0.006 mmol/L (p < 0.001) when adjusted for saturated, monounsaturated and polyunsaturated fatty acid, age, gender, body mass index and STRIP study group. The inverse association between total carbohydrate intake and HDL cholesterol was evident in children with apoE3 (p < 0.001) or apoE4 (p < 0.001), but not in those with apoE2 (p = 0.78). An increase in total carbohydrate intake by 1 E% increased triglycerides by 0.02 mmol/L (p < 0.001) independently of apoE phenotype, while 1 E% increase in sucrose intake increased triglycerides by 0.01 mmol/L (p < 0.001).
Conclusion:  Carbohydrate intake has a relatively small effect on serum lipids in children. Children with the apoE3 or E4 but not with E2 phenotype show reduction in HDL cholesterol with increasing carbohydrate intake indicating that genetic and environmental factors interact with children's lipoprotein metabolism.     

Prefrontal TMS produces smaller EEG responses than motor-cortex TMS: implications for rTMS treatment in depression

Rationale The stimulus intensity of prefrontal repetitive transcranial magnetic stimulation (rTMS) during depression treatment is usually determined by adjusting it with respect to the motor threshold (MT). There is some evidence that reactivity of the prefrontal cortex to transcranial magnetic stimulation (TMS) is lower than that of the motor cortex at MT stimulation. However, it is unknown whether this is true when other stimulus intensities are used. We investigated whether the magnitude and shape of the overall TMS-evoked electroencephalographic (EEG) responses differ between prefrontal and motor cortices. Methods Magnetic pulses to the left motor and prefrontal cortices (the middle frontal gyrus identified from magnetic resonance images) were delivered at four intensities (60, 80, 100, and 120% of MT of the right abductor digiti minimi muscle) for six subjects. Simultaneously, EEG was recorded with 60 scalp electrodes. Results Global mean-field amplitudes (GMFAs) reflecting overall cortical activity were significantly smaller after prefrontal- than after motor-cortex TMS. A significant positive correlation (r _s=0.84, p<0.01) was found between GMFAs of motor- and prefrontal-cortex TMS across the experiments. However, when correlation between the responses of motor and prefrontal cortices was examined, significant positive correlations were found at 80 and 100% intensities only. Conclusions This study provides further evidence that the prefrontal and motor cortices have different reactivity to TMS, but the MT may be used for determining the stimulus intensity of prefrontal rTMS treatment in depression, at least at motor threshold intensities or near to it.     

Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVE: We tested the hypothesis that topiramate is more effective than placebo in reducing symptoms in patients with treatment-resistant schizophrenia when combined with ongoing antipsychotic medication. METHOD: Twenty-six hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia participated in a randomized, double-blind, placebo-controlled trial in which 300 mg/day of topiramate was gradually added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week crossover treatment periods. Data were collected from April 2003 to November 2003. RESULTS: In intention-to-treat analysis, topiramate was more effective than placebo in reducing Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms. CONCLUSION: Glutamate antagonist topiramate may be an effective adjuvant treatment in reducing general psychopathologic symptoms in patients with schizophrenia resistant to treatment with second-generation antipsychotics.     

Permeant lipophilicity and vehicle composition influence accumulation of dyes in hair follicles of human skin

In skin and hair research drug targeting to the hair follicle is of great interest. Therefore the influence of permeant lipophilicity and vehicle composition on local accumulation has been examined using confocal laser scanning microscopy (CLSM). Formulations saturated with either Oregon Green^® 488, Bodipy^® FL C₅ or Bodipy^® 564/570 C₅ were prepared. The dyes were applied in citric acid buffer, 8% (w/v) surfactants in citric acid buffer or 8% (w/v) surfactants/20% (w/v) propylene glycol in citric acid buffer. Flow-through diffusion experiments were performed with fresh human scalp skin, after which the skin was imaged using CLSM. Diffusion studies showed for Oregon Green^® 488 (low lipophilicity) a higher flux when applied in citric acid buffer compared to surfactants. In contrast the fluxes of the more lipophilic dyes (Bodipy^® FL C₅ and Bodipy^® 564/570 C₅) are highest when applied in surfactants/propylene glycol. CLSM studies revealed that follicular accumulation increased with (i) a lipophilic dye and (ii) application of lipophilic dyes in surfactants–propylene glycol. Therefore we conclude that targeting to the hair follicle can be increased by the use of lipophilic drugs in combination with surfactant solutions and propylene glycol.     

Systematic Review and Meta-analysis of Circulatory Disease from Exposure to Low-Level Ionizing Radiation and Estimates of Potential Population Mortality Risks

Background: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels.Objectives: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures.Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms “radiation” AND “heart” AND “disease,” OR “radiation” AND “stroke,” OR “radiation” AND “circulatory” AND “disease.” Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.Results: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.Conclusions: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).     

Carnitine deficiency and L-carnitine supplementation in lysinuric protein intolerance

The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with lysinuric protein intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral L-carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.     

All known human rhinovirus species are present in sputum specimens of military recruits during respiratory infection

Human rhinoviruses (HRV) are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004-2005). The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8%) specimens were HRV-positive and 36 (9.3%) HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%), belonged to HRV-A, while HRV-B strains constituted five (17.2%) of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens.