Opa proteins of pathogenic neisseriae initiate Src kinase-dependent or lipid raft-mediated uptake via distinct human carcinoembryonic antigen-related cell adhesion molecule isoforms

Several pathogenic bacteria exploit human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) for adhesion to and invasion into their host cells. CEACAM isoforms have characteristic expression patterns on epithelial, endothelial, or hematopoietic cells, providing bacteria with distinct sets of receptors on particular tissues. For example, while CEACAM1 and CEACAM6 have a wide tissue distribution, CEACAM3, CEACAM4, and CEACAM8 are uniquely expressed on primary human granulocytes, whereas CEA and CEACAM7 are limited to epithelia. By reconstitution of a CEACAM-deficient cell line with individual CEACAMs, we have analyzed the requirements for CEACAM-mediated internalization of Neisseria gonorrhoeae. Our results point to two mechanistically different uptake pathways triggered by either epithelial CEACAMs (CEACAM1, CEA, and CEACAM6) or the granulocyte-specific CEACAM3. In particular, CEACAM3-mediated uptake critically depends on Src family protein tyrosine kinase (PTK) activity, and CEACAM3 associates with the SH2 domains of several Src PTKs. In contrast, epithelial CEACAMs require the integrity of cholesterol-rich membrane microdomains and are affected by cholesterol depletion, whereas CEACAM3-mediated uptake by transfected cells or the opsonin-independent phagocytosis by human granulocytes is not altered in the presence of cholesterol chelators. These results allow the subdivision of all human CEACAMs known to be utilized as pathogen receptors into functional groups and point to important consequences for bacterial engagement of distinct CEACAM isoforms.     

The effects of a temporarily manipulated dental occlusion on the position of the spine: a comparison during standing and walking

Background context

The relationship between dental occlusion and body posture or even the spine position is often analyzed and confirmed. However, this relationship has not been systematically investigated for standing and walking.

Purpose

To examine whether a symmetric or asymmetric dental occlusion block, using 4 mm thick silicon panels, can significantly change the spine position (cervical, thoracic, or lumbar region) during standing and walking.

Study design

The following study is a cross-sectional study.

Patient sample

This study was carried out with 23 healthy subjects (18 women, 5 men) without discomfort in the temporomandibular system or body movement apparatus.

Outcome measures

Position changes (millimeter) of the spine (cervical, thoracic, lumbar) in frontal, sagittal, and transverse planes of motion.

Methods

The upper spine position was quantified with an ultrasonic distance measurement system (sonoSens Monitor). Every subject placed the 4 mm thick silicon panel systematically between the left/right premolars or the front teeth. Differences between the habitual and manipulated occlusion positions were determined by the Friedman test, followed by pairwise comparisons with applied Bonferroni-Holm correction.

Results

During standing and walking there were significant (p≤.05) differences between the occlusion block conditions and the habitual dental position in all body planes except in the right lumbar region during walking. In addition, differences within the manipulated occlusion position could be detected. Significant differences were also shown between the standing and walking trials in the frontal, sagittal, and transverse planes, particularly with respect to the lumbar region (p≤.001).

Conclusions

Symmetrical and asymmetrical occlusion blocks in the premolar region can be associated with changes in all three spine regions during standing and walking. The results showed highly similar reaction patterns in all spine positions, regardless of the location of the silicon panel. Between standing and walking, the main differences were in the lumbar spine. The results suggest a relationship between the chewing and the movement system. However, it must be stated that this study has no direct clinical impact. The study design cannot determine the causality of the observed associations; also the clinical significance of the small postural changes remains unknown.     

Magnetic tests for magnetosome chains in Martian meteorite ALH84001

Transmission electron microscopy studies have been used to argue that magnetite crystals in carbonate from Martian meteorite ALH84001 have a composition and morphology indistinguishable from that of magnetotactic bacteria. It has even been claimed from scanning electron microscopy imaging that some ALH84001 magnetite crystals are aligned in chains. Alignment of magnetosomes in chains is perhaps the most distinctive of the six crystallographic properties thought to be collectively unique to magnetofossils. Here we use three rock magnetic techniques, low-temperature cycling, the Moskowitz test, and ferromagnetic resonance, to sense the bulk composition and crystallography of millions of ALH84001 magnetite crystals. The magnetic data demonstrate that although the magnetite is unusually pure and fine-grained in a manner similar to terrestrial magnetofossils, most or all of the crystals are not arranged in chains.     

Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin treated man.

Two groups A and B each comprising 12 healthy young male subjects were used in a double blind, placebo controlled trial to assess the effects of 1.0 g sucralfate qid on prostaglandin (PG) generation and mucosal integrity in the intact and aspirin-treated stomach. Mucosal formation and luminal release of PGE2, 6-keto-PGE1 alpha and thromboxane B2, gastric microbleeding and DNA loss (integrity indicators) and basal and pentagastrin induced acid secretion were measured after placebo and sucralfate treatment in subjects without (group A) and with administration of 2.5 g aspirin (group B). Sucralfate significantly reduced spontaneous gastric microbleeding and DNA loss in group A and prevented blood loss but not DNA loss caused by aspirin in group B. The protective effects of sucralfate on spontaneous gastric microbleeding were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with a reduction in release of thromboxane B2. In aspirin treated subjects both mucosal generation and luminal release of prostaglandins and thromboxane B2 were greatly suppressed although sucralfate treatment did not influence these prostaglandins in spite of the reduction in mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and aspirin treated gastric microbleeding in man and that this protection may be partly because of the increased mucosal biosynthesis of prostaglandins.     

Diagnostic accuracy of multidetector computed tomography coronary angiography in patients with angiographically proven coronary artery disease

OBJECTIVES: The aim of the present study was to evaluate the diagnostic accuracy in detecting high-grade coronary stenoses in patients with known coronary artery disease (CAD) using multidetector computed tomography (MDCT). BACKGROUND: The MDCT systems with electrocardiographic (ECG)-gating permit visualization of the coronary arteries. However, severe calcifications and higher heart rates are known to degrade image quality and limit correct diagnosis. METHODS: Sixty-six patients with proven CAD as assessed by conventional coronary angiography (CCA) were studied by MDCT (mean time 24 months postangiography). Total calcium score and all coronary arteries, including distal segments and side branches, were assessed with respect to evaluability, presence of high-grade coronary artery stenoses (>70%), and correct diagnosis. Results were compared to CCA. RESULTS: A total of 105 lesions were detected by CCA. The MDCT correctly detected 39 lesions (sensitivity 37%, specificity 99%). The correct clinical diagnosis could be obtained in 24 patients (36%). Artifacts due to elevated heart rates or severe coronary artery calcification were the main cause of degraded image quality inhibiting correct diagnosis. In 21/66 patients (32%) all four major coronary vessel segments could be visualized. A threshold for maximum heart rate and a maximum calcification level were established (65 beats/min and an Agatston Score Equivalent of 335, respectively). A second analysis was made using these thresholds. Of all patients studied, 10/11 (91%) were correctly diagnosed when adhering to these thresholds. CONCLUSIONS: When using MDCT as a noninvasive diagnostic modality to assess advanced CAD, it appears to be mandatory to preselect patients in order to achieve reliable results.     

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.