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1.  Does Radar Technology Support the Diagnosis of Pneumothorax? PneumoScan—A Diagnostic Point-of-Care Tool 
Background. A nonrecognized pneumothorax (PTX) may become a life-threatening tension PTX. A reliable point-of-care diagnostic tool could help in reduce this risk. For this purpose, we investigated the feasibility of the use of the PneumoScan, an innovative device based on micropower impulse radar (MIR). Patients and Methods. addition to a standard diagnostic protocol including clinical examination, chest X-ray (CXR), and computed tomography (CT), 24 consecutive patients with chest trauma underwent PneumoScan testing in the shock trauma room to exclude a PTX. Results. The application of the PneumoScan was simple, quick, and reliable without functional disorder. Clinical examination and CXR each revealed one and PneumoScan three out of altogether four PTXs (sensitivity 75%, specificity 100%, positive predictive value 100%, and negative predictive value 95%). The undetected PTX did not require intervention. Conclusion. The PneumoScan as a point-of-care device offers additional diagnostic value in patient management following chest trauma. Further studies with more patients have to be performed to evaluate the diagnostic accuracy of the device.
PMCID: PMC3800628  PMID: 24187624
2.  Lava Cave Microbial Communities Within Mats and Secondary Mineral Deposits: Implications for Life Detection on Other Planets 
Astrobiology  2011;11(7):601-618.
Lava caves contain a wealth of yellow, white, pink, tan, and gold-colored microbial mats; but in addition to these clearly biological mats, there are many secondary mineral deposits that are nonbiological in appearance. Secondary mineral deposits examined include an amorphous copper-silicate deposit (Hawai‘i) that is blue-green in color and contains reticulated and fuzzy filament morphologies. In the Azores, lava tubes contain iron-oxide formations, a soft ooze-like coating, and pink hexagons on basaltic glass, while gold-colored deposits are found in lava caves in New Mexico and Hawai‘i. A combination of scanning electron microscopy (SEM) and molecular techniques was used to analyze these communities. Molecular analyses of the microbial mats and secondary mineral deposits revealed a community that contains 14 phyla of bacteria across three locations: the Azores, New Mexico, and Hawai‘i. Similarities exist between bacterial phyla found in microbial mats and secondary minerals, but marked differences also occur, such as the lack of Actinobacteria in two-thirds of the secondary mineral deposits. The discovery that such deposits contain abundant life can help guide our detection of life on extraterrestrial bodies. Key Words: Biosignatures—Astrobiology—Bacteria—Caves—Life detection—Microbial mats. Astrobiology 11, 601–618.
PMCID: PMC3176350  PMID: 21879833
3.  Pathways by which reconstituted HDL mobilizes free cholesterol from whole body and from macrophages 
Reconstituted HDL (rHDL), is of interest as a potential novel therapy for atherosclerosis due to its ability to promote free cholesterol (FC) mobilization after intravenous administration. We performed studies to identify the underlying molecular mechanisms by which rHDL promote FC mobilization from whole body in vivo and macrophages in vitro.
Methods and results
Wild type (WT), SR-BI-KO, ABCA1-KO and ABCG1-KO mice received either rHDL or PBS intravenously. Blood was drawn before and at several time points after injection for apoA-I, phosphatidylcholine and FC measurement. In WT mice, serum FC peaked at 20 min and rapidly returned towards baseline levels by 24 h. Unexpectedly, ABCA1-KO and ABCG1-KO mice did not differ from WT mice regard to the kinetics of FC mobilization. In contrast, in SR-BI-KO mice the increase in FC level at 20 min was only 10% of that in control mice (p<0.01). Bone marrow-derived macrophages from WT, SR-BI-KO, ABCA1-KO and ABCG1-KO mice were incubated in vitro with rHDL and cholesterol efflux determined. Efflux from SR-BI KO and ABCA1 KO macrophages was not different from WT macrophages. In contrast, efflux from ABCG1-KO macrophages was ∼ 50% lower as compared with WT macrophages (p<0.001).
The bulk mobilization of FC observed in circulation after rHDL administration is primarily mediated by SR-BI. However, cholesterol mobilization from macrophages to rHDL is primarily mediated by ABCG1.
PMCID: PMC2842952  PMID: 20018934
reconstituted HDL; cholesterol efflux; apolipoprotein A-I; SR-BI; ABCA1; ABCG1
4.  Reiterative pattern of sonic hedgehog expression in the catshark dentition reveals a phylogenetic template for jawed vertebrates 
For a dentition representing the most basal extant gnathostomes, that of the shark can provide us with key insights into the evolution of vertebrate dentitions. To detail the pattern of odontogenesis, we have profiled the expression of sonic hedgehog, a key regulator of tooth induction. We find in the catshark (Scyliorhinus canicula) that intense shh expression first occurs in a bilaterally symmetrical pattern restricted to broad regions in each half of the dentition in the embryo jaw. As in the mouse, there follows a changing temporal pattern of shh spatial restriction corresponding to epithelial bands of left and right dental fields, but also a subfield for symphyseal teeth. Then, intense shh expression is restricted to loci coincident with a temporal series of teeth in iterative jaw positions. The developmental expression of shh reveals previously undetected timing within epithelial stages of tooth formation. Each locus at alternate, even then odd, jaw positions establishes precise sequential timing for successive replacement within each tooth family. Shh appears first in the central cusp, iteratively along the jaw, then reiteratively within each tooth for secondary cusps. This progressive, sequential restriction of shh is shared by toothed gnathostomes and conserved through 500 million years of evolution.
PMCID: PMC2660956  PMID: 19141424
catshark; sonic hedgehog; dentition development; tooth patterning; evolution dentition
5.  Spatial and temporal pattern for the dentition in the Australian lungfish revealed with sonic hedgehog expression profile 
We report a temporal order of tooth addition in the Australian lungfish where timing of tooth induction is sequential in the same pattern as osteichthyans along the lower jaw. The order of tooth initiation in Neoceratodus starts from the midline tooth, together with left and right ones at jaw position 2, followed by 3 and then 1. This is the pattern order for dentary teeth of several teleosts and what we propose represents a stereotypic initiation pattern shared with all osteichthyans, including the living sister group to all tetrapods, the Australian lungfish. This is contrary to previous opinions that the lungfish dentition is otherwise derived and uniquely different. Sonic hedgehog (shh) expression is intensely focused on tooth positions at different times corresponding with their initiation order. This deployment of shh is required for lungfish tooth induction, as cyclopamine treatment results in complete loss of these teeth when applied before they develop. The temporal sequence of tooth initiation is possibly regulated by shh and is know to be required for dentition pattern in other osteichthyans, including cichlid fish and snakes. This reflects a shared developmental process with jawed vertebrates at the level of the tooth module but differs with the lack of replacement teeth.
PMCID: PMC2660947  PMID: 19004755
tooth development; lungfish dentition; sonic hedgehog; osteichthyan stereotype; cyclopamine inhibition; pitx2 expression
6.  Conserved deployment of genes during odontogenesis across osteichthyans. 
Odontogenesis has only been closely scrutinized at the molecular level in the mouse, an animal with an extremely restricted dentition of only two types and one set. However, within osteichthyans many species display complex and extensive dentitions, which questions the extent to which information from the mouse is applicable to all osteichthyans. We present novel comparative molecular and morphological data in the rainbow trout (Oncorhynchus mykiss) that show that three genes, essential for murine odontogenesis, follow identical spatial-temporal expression. Thus, at all tooth bud sites, epithelial genes Pitx-2 and Shh initiate the odontogenic cascade, resulting in dental mesenchymal Bmp-4 expression, importantly, including the previously unknown formation of replacement teeth. Significantly, this spatial-temporal sequence is the same for marginal and lingual dentitions, but we find notable differences regarding the deployment of Pitx-2 in the developing pharyngeal dentition. This difference may be highly significant in relation to the theory that dentitions may have evolved from pharyngeal tooth sets in jawless fishes. We have provided the first data on operational genes in tooth development to show that the same signalling genes choreograph this evolutionary stable event in fishes since the osteichthyan divergence 420 Myr ago, with the identical spatial-temporal expression as in mammals.
PMCID: PMC1691870  PMID: 15556883
8.  Idiopathic granulomatous vasculitis: response to immunosuppressive therapy. 
Journal of Clinical Pathology  1995;48(6):579-582.
A case of idiopathic granulomatous vasculitis (disseminated visceral giant cell arteritis) is described in an old woman, the seventh case of this rare disorder reported to date. The main organ affected was the liver and, to our knowledge, this is the first patient to be diagnosed while still alive and the only case to have received medical treatment. It is also the first time that muscular involvement has been documented in this condition. Cyclophosphamide treatment resulted in disappearance of symptoms and increase in weight. The patient died of an unrelated condition.
PMCID: PMC502695  PMID: 7665707
10.  Cyclodextrins as catalysts for the removal of cholesterol from macrophage foam cells. 
Journal of Clinical Investigation  1997;99(4):773-780.
Low concentrations of cyclodextrins (< 1.0 mM) added to serum act catalytically, accelerating the exchange of cholesterol between cells and lipoproteins. J774 macrophages incubated with serum and 2-hydroxypropyl-beta-cyclodextrin (< or = 1 mM) released fivefold more labeled cholesterol than with serum alone. Increased efflux was not accompanied by a change in cell cholesterol mass; thus, cyclodextrin functioned as a cholesterol shuttle, enhancing cholesterol bidirectional flux without changing the equilibrium cholesterol distribution between cells and medium. The addition of phospholipid vesicles to serum and cyclodextrin shifted the equilibrium distribution to favor the medium, producing rapid and extensive depletion of cell cholesterol mass. The combination of serum, phospholipid vesicles, and cyclodextrin also stimulated the rapid clearance of both free and esterified cholesterol from mouse peritoneal macrophages loaded with free and esterified cholesterol. This study: (a) demonstrates that a compound can function as a catalyst to enhance the movement of cholesterol between cells and serum, (b) illustrates the difference between cholesterol exchange and net transport in a cell/serum system, (c) demonstrates how net movement of cholesterol is linked to concentration gradients established by phospholipids, (d) provides a basis for the development of the shuttle/sink model for the first steps in reverse cholesterol transport, (e) validates the model using artificial shuttles (cyclodextrins) and sinks (large unilamellar vesicles), and (f) suggests that cyclodextrin-like cholesterol shuttles might be of pharmacological significance in treating unstable atherosclerotic plaques.
PMCID: PMC507862  PMID: 9045882
11.  Cholesterol efflux potential of sera from mice expressing human cholesteryl ester transfer protein and/or human apolipoprotein AI. 
Journal of Clinical Investigation  1995;96(6):2613-2622.
The ability of whole serum to promote cell cholesterol efflux and the relationships between apoprotein and lipoprotein components of human serum efflux have been investigated previously (de la Llera Moya, M., V. Atger, J.L. Paul, N. Fournier, N. Moatti, P. Giral, K.E. Friday, and G.H. Rothblat. 1994. Arterioscler. Thromb. 14:1056-1065). We have now used this experimental system to study the selective effects of two human lipoprotein-related proteins, apoprotein AI (apo AI) and cholesteryl ester transfer protein (CETP) on cell cholesterol efflux, when these proteins are expressed in transgenic mice. The percent efflux values for cholesterol released in 4 h from Fu5AH donor cells to 5% sera from the different groups of mice were in the order: background = human apo AI transgenic (HuAITg) > human CETP transgenic (HuCETPTg) > human apo AI and CETP transgenic (HuAICETPTg) >> apo AI knockout mice. In each group of mice a strong, positive correlation (r2 ranging from 0.64 to 0.76) was found between efflux and HDL cholesterol concentrations. The slopes of these regression lines differed between groups of mice, indicating that the cholesterol acceptor efficiencies of the sera differed among groups. These differences in relative efficiencies can explain why cholesterol efflux was not proportional to the different HDL levels in the various groups of mice. We can conclude that: (a) HDL particles from HuAITg mice are less efficient as cholesterol acceptors than HDL from the background mice; (b) despite a lower average efflux due to lower HDL cholesterol concentrations, HDL particles are more efficient in the HuCETPTg mice than in the background mice; and (c) the coexpression of both human apo AI and CETP improves the efficiency of HDL particles in the HuAICETPTg mice when compared with the HuAITg mice. We also demonstrated that the esterification of the free cholesterol released from the cells by lecithin cholesterol acyltransferase in the serum was reduced in the HuAITg and AI knockout mice, whereas it was not different from background values in the two groups of mice expressing human CETP.
PMCID: PMC185966  PMID: 8675626
15.  Calcium intake in the first five days of life in the low birthweight infant. Effects of calcium supplements. 
Archives of Disease in Childhood  1978;53(10):784-787.
Sixteen low birthweight infants were allocated to two groups. Both groups 1 and 2 received a formula with Ca/PO4 ratio of 1.21. Group 2 infants received a supplement of 800 mg/kg per day of Ca and Mg lactate, and the daily Ca, Mg, and PO4 levels were measured. Calcium intakes (mg/kg per day) were, comparing groups 2 and 1: 82 v. 33 on the 1st day; 133 v 45 on 2nd; 170 v. 56 on 3rd; 224 v 72 on 4th; 263 v. 88 on 5th. Magnesium intake (mg/kg per day) was 4.9 v. 3.8 on the 1st day; 8.3 v. 5.3 on 2nd; 9.8 v. 6.5 on 3rd; 15.5 v. 8.3 on 4th; 16.0 v. 10.0 on 5th. Phosphate intake was similar in both groups. Mineral content of vomits and regurgitations showed more Ca than P, with a ratio of 1:68. Comparing the two groups, in the supplemented infants, serum Ca rose from the 3rd day by an amount which was related to Ca intake: serum Mg was lower from the 4th day and was negatively correlated with Ca intake.
PMCID: PMC1545405  PMID: 727791

Results 1-15 (15)