L-selectin ligands in rat high endothelium: multivalent sialyl Lewis x glycans are high-affinity inhibitors of lymphocyte adhesion

Lymphocyte homing is initiated by their tethering to and rolling on the high endothelium and is followed by extravasation into the lymph nodes. We show here that glycosylated cell adhesion molecule-1 (GlyCAM-1), CD34, and sialyl Lewis x (sLex) are present on rat lymph node high endothelium analyzed by using monoclonal antibodies. α(1,3)fucosyltransferase VII (Fuc-TVII), the last enzyme involved in the synthesis of the sLex sequence is also expressed on the rat lymph node high endothelium. We have synthesized a family of sLex-decorated oligosaccharide structures and used them to inhibit lymphocyte binding to high endothelium in the Stamper-Woodruff assay. Monovalent sLex, branched di- and tetravalent sLex, as well as a linear tetravalent sLex significantly reduce lymphocyte binding to endothelium. The branched and linear forms of tetravalent sLex were clearly superior inhibitors of the L-selectin-dependent lymphocyte adhesion, with IC50 values in low nanomolar range. In contrast, the fucose-free analogs having the same charge and approximately the same size as the corresponding sLex glycans had no effect on lymphocyte binding and served as negative controls. Taken together, these data show the crucial importance of sLex in the endothelial ligands for L-selectin. Furthermore, we suggest that L-selectin acts as an oligomer on the lymphocyte surface as it binds multivalent sLex glycans.     

'Fat mass and obesity associated' gene (<Emphasis Type="Italic">FTO</Emphasis>): No significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents

Background  

We have previously identified strong association of six single nucleotide polymorphisms (SNPs) in FTO (fat mass and obesity associated gene) to early onset extreme obesity within the first genome wide association study (GWA) for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609) is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism.     

Relationship of angiotensin-converting enzyme gene polymorphism to carotid wall thickness in middle-aged men

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50-59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18 +/- 0.30, 1.22 +/- 0.24, and 1.08 +/- 0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis.     

Inter-laboratory validation of PCR-based detection of Mycobacterium tuberculosis in formalin-fixed, paraffin-embedded tissues

The present study is based on the initiative for quality assurance in pathology of the German Society of Pathology and the Professional Association of German Pathologists. Four panel laboratories with experience and expertise in polymerase chain reaction (PCR) detection of Mycobacterium tuberculosis were selected to establish the prerequisites for continuous external laboratory trials, in particular, by providing pre-tested specimens and evaluation criteria for participating institutes. In the first step, the four panel laboratories performed an internal trial to test their own reliability and reproducibility. Paraffin sections and DNA preparations from 34 tissues (25 clinical specimens and 9 controls) totalling to 66 samples were evaluated by each panel institute according to their own protocols. The methodologies differed and are described in detail. Despite these differences, a high degree of inter-laboratory reliability was achieved. In this report, we summarise our results including the correlation with the histology and provide recommendations for applying PCR-based methodology for the detection of mycobacterial DNA in surgical specimens. Supplementary data are available online at (rubric Forschung). Pre-tested specimens are now available for the external trial and can be ordered from the steering institute via Oligene (). All molecular pathology laboratories are invited to participate in this quality assurance initiative.     

Three hands: fragmentation of human bodily awareness

We describe patient E.P. who occasionally perceives a ‘ghost' hand which copies the previous positions of the left hand with a 0.5–1 min time lag, but follows the movement patterns of the right hand. The symptoms started after an operation of a ruptured aneurysm, followed by an infarction of the right frontal lobe; E.P. also has a previously lesioned corpus callosum. Neuromagnetic recordings revealed that activity of the left secondary somatosensory cortex was strongly suppressed during the ghost arm percept, thereby providing an objective correlate for E.P.'s sensations. We conclude that simultaneous mental contents about body scheme may be based on neural information extracted at considerably different times, resulting in fragmentation of bodily awareness.     

On lossy transform compression of ECG signals with reference to deformation of their parameter values

Electrocardiogram (ECG) signals are the most prominent biomedical signal type used in clinical medicine. Their compression is important and widely researched in the medical informatics community. In the previous literature compression efficacy has been investigated only in the context of how much known or developed methods reduced the storage required by compressed forms of original ECG signals. Sometimes statistical signal evaluations based on, for example, root mean square error were studied. In previous research we developed a refined method for signal compression and tested it jointly with several known techniques for other biomedical signals. Our method of so-called successive approximation quantization used with wavelets was one of the most successful in those tests. In this paper, we studied to what extent these lossy compression methods altered values of medical parameters (medical information) computed from signals. Since the methods are lossy, some information is lost due to the compression when a high enough compression ratio is reached. We found that ECG signals sampled at 400 Hz could be compressed to one fourth of their original storage space, but the values of their medical parameters changed less than 5% due to compression, which indicates reliable results.     

Antigenic sites of coxsackie A9 virus inducing neutralizing monoclonal antibodies protective in mice

A panel of murine IgG monoclonal antibodies (MAbs) was produced against coxsackievirus A9 (CAV9). Fifty-nine MAbs reactive in ELISA with purified CAV9 were identified. Eighteen of them could efficiently inhibit infection by CAV9 but not coxsackieviruses B. Neutralization-resistant CAV9 variants to four different MAbs were isolated and tested for resistance to neutralization by other MAbs of the panel. Three groups of reactivity including 10, 7, and 1 MAbs were thus identified. Sequencing of neutralization-escape virus mutants showed that neutralization by one MAb group was affected by change of VP3 amino acids 62 or 69. For the second group of reactivity, mutations included amino acids 154 or 165 of VP2. The only MAb of the third group selected for a change at residue 70 of VP2. Protection studies in a newborn mouse model of myositis suggested that either epitopes in VP2 or in VP3 mediate protection from CAV9 infection in vivo.     

Cardiorespiratory and thermal effects of wearing gas protective clothing

Summary Six healthy men aged 25 to 37 walked on a treadmill at work levels of 21 and 41% of their for 25 to 30 min wearing gas protective clothing (GPC) consisting of an impermeable suit with a self-contained breathing apparatus (total weight 25 kg) or shorts (control tests, CT) in a temperate environment (t _a 24.3°C ± 1.0°C, rh 30–50%). When the GPC was worn at 21 and 41% , the most prominent increases, compared with the CT, were noted in the heart rate ( ± SE, 120 ± 5 vs 76 ± 3 beats min^–1 and 171 ± 5 vs 103 ± 3 beats min^–1), mean skin temperature (36.1 ± 0.2 vs 31.3° C ± 0.1°C and 36.9 ± 0.3 vs 30.9°C ± 0.4°C) and sweat rate (473 ± 51 vs 70 ± 23 g m^–2 h^–1 and 766 ± 81 vs 135 ± 18 g m^–2 h^–1) indicating a high cardiovascular and thermoregulatory strain, which was not decreased by ventilating the suit with an air flow of 281 min^–1 at 41% . The ventilation, oxygen consumption and production of carbon dioxide increased in relation to the extra weight of the GPC, partly dependent on the dynamic work level. It was concluded that the increase in the physiological load caused by the GPC was so high that the work-rest regimens, workers' level of physical fitness, cardiovascular health and heat tolerance should be considered whenever gas protective clothing is used.     

Impact of COVID-19 pandemic lockdown on myocardial infarction care

European Journal of Epidemiology - The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors...