Brown adipose tissue function is accompanied by cerebral activation in lean but not in obese humans

Brown adipose tissue (BAT) is able to generate heat and dissipate energy in response to cold exposure in mammals. It has recently been acknowledged that adult humans also have functional BAT, whose metabolic activity is reduced in obesity. In healthy humans, the cerebral mechanisms that putatively control BAT function are unclear. By using positron emission tomography (PET), we showed that cold-induced BAT activation is associated with glucose metabolism in the cerebellum, thalamus, and cingulate, temporoparietal, lateral frontal, and occipital cortices in lean participants, whereas no such associations were found under warm control conditions. The cold-induced increase in cerebral glucose metabolism was more robust in lean than obese participants. Cerebral glucose metabolism was not associated with skeletal muscle or white adipose tissue glucose uptake under warm or cold conditions. In conclusion, BAT metabolism was accompanied by the activation of specific cerebral regions, and this shows an uncharacterized role that the brain plays in the regulation of BAT function. In obese participants, the cold-induced response in cerebral activity was attenuated that provides a clue for obesity-induced impairment in BAT metabolism.     

Association of findings in flow-volume spirometry with high-resolution computed tomography signs in asbestos-exposed male workers

Introduction: Disorders of pulmonary tissue and pleura are visualized by findings in high‐resolution computed tomography (HRCT), and the impairment caused by these findings is assessed by pulmonary function tests. Our aim was to determine how some commonly used spirometric variables are related to certain HRCT signs, in order to find out which HRCT signs are associated with restrictive and which with obstructive ventilatory impairment. Methods: Altogether 590 asbestos‐exposed workers, 95% of whom were smokers or ex‐smokers, were studied with HRCT; 19 pathological signs were scored. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, forced expiratory flow at 50% of FVC (MEF50) and total lung capacity (TLC) were measured, and their relationship with HRCT signs was examined with bivariate correlations and multiple regression analysis. Results: FVC and TLC were negatively correlated with fibrosis score, parenchymal bands, extent of pleural thickenings and positively with widened retrosternal space. FEV1/FVC ratio was negatively correlated with emphysema types and widened retrosternal space and positively with parenchymal bands and subpleural nodules. Thickened bronchial walls did not separate between restrictive and obstructive ventilatory function. Conclusions: HRCT signs showed distinctive patterns in restrictive and obstructive ventilatory impairment. These results can be used to help to analyse the lung function of patients simultaneously exposed to asbestos and smoking, when this relationship requires elucidation. In addition, the results may be helpful in explaining some radiological findings.     

The role of genetics and environment in lifting force and isometric trunk extensor endurance

BACKGROUND AND PURPOSE: Our understanding of what different back performance tests are measuring is limited. The purpose of this study was to investigate the relative contributions of genetics and unique and common environmental factors for 3 tests of back muscle performance in a classic twin analysis. SUBJECTS: The subjects were a population-based sample of 122 monozygotic and 131 dizygotic male twin pairs aged 35 to 69 years (mean=49.9, SD=7.7). METHODS: Variance component analysis was applied to estimate genetic and environmental influences on isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. The Cholesky decomposition genetic factor model was used to estimate genetic and environmental correlations of these variables. Path analysis was applied to study determinants of isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. RESULTS: Genetic effects accounted for 60%, 33%, and 5% of the total variance of isokinetic and psychophysical lifting forces and isometric trunk extensor endurance, respectively, and unique environmental factors accounted for 35%, 49%, and 61% of the variance. DISCUSSION AND CONCLUSION: Genetics had a dominant role in isokinetic lifting and unique environmental factors in isometric trunk extensor endurance. The relatively high role of genetics in lifting force suggests the potential to increase and sustain changes in back muscle force in the general population may be particularly challenging.     

Herpesviruses in brains in Alzheimer's and Parkinson's diseases

We evaluated the association of HSV-1, HHV-6, and VZV with Alzheimer's disease (AD) and Parkinson's disease (PD). Brain specimens for viral DNA polymerase chain reaction represented 34 patients with AD, 40 with PD, and 40 controls. One AD patient (2.9%) was positive for HSV-1 DNA, 88.2% for HHV-6 DNA, and 26.5% for VZV DNA; 17.5% of PD patients were HSV-1 DNA-positive and 75% HHV-6-positive, whereas 40% had VZV DNA. Twenty-five percent of the controls were positive for HSV-1 DNA, 87.5% for HHV-6, and 27.5% for VZV. HSV-1, VZV, or HHV-6 DNA in brains was no additional risk factor for AD.     

Computed tomography of asbestos-related pleural abnormalities

OBJECTIVES: To study the observer agreement in several asbestos-related pleural abnormalities and to define criteria to discriminate between pleural changes in workers with occupational disease, and those in controls. METHODS: Pleural abnormalities in spiral computed tomography of 602 construction workers with asbestosis or bilateral pleural plaques and 49 controls were reviewed by three radiologists using structured forms. RESULTS: Intra- and inter-observer agreement (weighted kappa) was 0.4 or better with regard to the calcification, extent and thickness of pleural disease. These factors all correlated positively with the duration of asbestos exposure. There were significant differences in these pleural changes between the workers (mean extent per side 83 cm(2)) and controls (mean extent per side 40 cm(2)). Of the controls, 84% showed pleural lesions with an estimated extent of 10 cm(2) or more, bilateral in 64%. The extent of 45 cm(2) in pleural disease was the best value for discriminating between the controls and diseased workers, with a sensitivity of 82% and a specificity of 66%. The degree of pleural calcification, however, was the best discriminator between these groups, but quantitative methods are necessary for its use in the diagnostics of individuals. CONCLUSIONS: The extent, calcification and thickness were well-repeatable indicators of benign pleural pathology and thus their use in future classification systems in computed tomography is recommended. In our material, the extent of 45 cm(2) and the degree of calcification were helpful in discriminating between pleural changes in workers with occupational disease, and those in controls who also presented marked pleural pathology.     

Blood biochemistry and the risk of cancer

A longitudinal study based on a serum sample bank was carried out in Finland to find out the association between biochemical substances and the subsequent risk of cancer. The objective was to evaluate the consistency between means of individually estimated levels of these compounds and levels based on pooling. Levels of alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and ceruloplasmin were estimated by primary site and sex and partly by age and morphology. The concentrations in pooled samples were consistently lower than the averages of the individual samples. On the basis of individual samples, all the five biochemical compounds had a rather consistent protective effect on the risk of cancers at most primary sites. This protective effect disappeared in the pool analyses, and more than half of exposure contrasts showed an opposite sign. For ceruloplasmin, the effect of pooling was smaller but not negligible. The results of this study emphasize the demand to standardize the collecting, handling, and analysing of samples in serum banks. They are, furthermore, consistent with the hypothesis that pooling of biochemical samples affects the levels of the substances and may affect the conclusions of epidemiological studies on causes of diseases.     

Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease

We investigated regional cerebral glucose metabolic rates (rCMRgluc) with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in 7 monozygotic twin pairs discordant for Alzheimer's disease (AD). Ten healthy volunteers with comparable mean age and educational level served as controls. In the hippocampus, the mean +/- SD rCMRgluc were 0.20 +/- 0.03 micromol/ml/min for the demented twins, 0.21 +/- 0.03 micromol/ml/min for their non-demented co-twins, and 0.23 +/- 0.02 micromol/ml/min for the controls. The mean hippocampal rCMRgluc was reduced in the demented twins (p = 0.006), compared with the controls. In the lateral temporal cortex, the mean +/- SD rCMRgluc were 0.27 +/- 0.05, 0.28 +/- 0.04, and 0.32 +/- 0.02 micromol/ml/min, respectively. These mean rates were reduced both in the demented (p = 0.02) and the non-demented (p = 0.01) twins, compared with the controls. In conclusion, in the demented twins, the reduction of rCMRgluc was detected in the hippocampus and lateral temporal cortex, i.e. the 2 brain areas which show early changes in pathological and imaging studies in AD. Their non-demented co-twins showed milder reductions, which may be an indication of genetic susceptibility for dementia, and an early sign of a dementing illness in them.     

Somatic mutation analysis of <Emphasis Type="Italic">MYH11</Emphasis>in breast and prostate cancer

Background  

MYH11 (also known as SMMHC) encodes the smooth-muscle myosin heavy chain, which has a key role in smooth muscle contraction. Inversion at the MYH11 locus is one of the most frequent chromosomal aberrations found in acute myeloid leukemia. We have previously shown that MYH11 mutations occur in human colorectal cancer, and may also be associated with Peutz-Jeghers syndrome. The mutations found in human intestinal neoplasia result in unregulated proteins with constitutive motor activity, similar to the mutant myh11 underlying the zebrafish meltdown phenotype characterized by disrupted intestinal architecture. Recently, MYH1 and MYH9 have been identified as candidate breast cancer genes in a systematic analysis of the breast cancer genome.     

Evaluation of cocktail approach to standardise Caco-2 permeability experiments.

The purpose of this study was to investigate the suitability and reliability of n-in-one approach using FDA suggested compounds for standardising Caco-2 permeability experiments. Special attention was paid to the evaluation of rank order correlation and mechanistic insights of compound permeability. Transport studies with antipyrine, metoprolol, ketoprofen, verapamil, hydrochlorothiazide, ranitidine, mannitol and fluorescein were performed in 12- and 24-well formats, as single compounds and in cocktails under iso-pH 7.4 and pH-gradient (pH 5.5 vs. 7.4) conditions. Compounds were quantified using n-in-one LC/MS/MS analysis. The cocktail-dosing proved to be a feasible method to determine the permeability of the Caco-2 cell line and to introduce external standards for permeability tests. Even though sink conditions were lost in cocktail experiments for highly permeable compounds, the rank order of compound permeability and the classification to low and high permeability compounds remained unchanged between single and cocktail studies and permeability values of 12- and 24-well formats were directly comparable. Under pH-gradient conditions the margin between high and low permeability compounds was narrower due to the lower permeability (higher fraction of ionisation) of basic molecules. Of the compounds studied, antipyrine, metoprolol, hydrochlorothiazide and mannitol are suitable for evaluation and standardisation purposes of passive permeability, while fluorescein would function as paracellular marker under iso-pH 7.4. As efflux activity may vary between cell batches, verapamil is a useful marker for P-glycoprotein.     

Intracellular Reservoir of Streptococcus pyogenes In Vivo: A Possible Explanation for Recurrent Pharyngotonsillitis

Numerous theories have been presented that attempt to explain the frequent recurrences of pharyngotonsillitis caused by Streptococcus pyogenes; these recurrences occur after seemingly adequate antibiotic treatment. We previously have demonstrated that S pyogenes can survive for up to 7 days intracellularly in immortalized human respiratory epithelial cells grown in an antibiotic supplemented medium. Viable S pyogenes were externalized and established an extracellular infection, whenever the extracellular antibiotic was removed. We have investigated the presence of intracellular S pyogenes in two in vivo studies using respiratory epithelial cells collected from patients with tonsillitis and the tonsils of asymptomatic carriers. Electron microscopy and immunohistochemistry demonstrated intracellular S pyogenes in pharyngeal epithelial cells in 13 of 14 patients with tonsillitis (93%). Furthermore, intracellular S pyogenes were found in macrophage-like cells in eight (73%) and in epithelial cells in four (36%) tonsils from 11 asymptomatic S pyogenes carriers. These in vivo data strongly support the hypothesis that intracellular S pyogenes can constitute a reservoir of bacteria with the potential to cause reinfections