Sudden,Severe Mitral Insufficiency

Five male patients with sudden, severe mitral insufficiency due solely to ruptured chordae tendineae or papillary muscle had an abrupt onset of symptoms of left and right heart failure and the sudden appearance of a harsh, widely propagated apical pansystolic murmur. None had a history of rheumatic fever. All were in sinus rhythm and had but mild left atrial and ventricular enlargement. Giant left atrial “v” waves were characteristic and exceeded pulmonary artery pressure in two instances.In contrast, when ruptured chordae tendineae were superimposed on chronic rheumatic mitral insufficiency, females predominated and there was a long history of disability. Atrial fibrillation, less elevation of left atrial pressure, and marked left atrial and ventricular enlargement were characteristic. These latter patients closely resembled patients with chronic rheumatic mitral insufficiency alone.It is concluded that the syndrome of sudden, severe mitral insufficiency develops if ruptured chordae tendineae occur on a previously normal or insignificantly diseased mitral valve. If ruptured chordae tendineae are superimposed on chronic rheumatic mitral insufficiency, the syndrome resembles that seen in the latter alone.     

Mucosubstance histochemistry of pleomorphic adenoma of parotid and submandibular salivary glands of man: light and electron microscopy

Summary Lumina and adluminal cells in human salivary gland pleomorphic adenomas were found to contain neutral, carboxylated, and occasionally sulphated glycoproteins. A variable component of luminal contents and secretory granules did not appear to contain glycoprotein and possibly consisted of protein. Glycosaminoglycans, which appeared to be hyaluronic acid and chondroitin sulphate, were demonstrated rarely in lumina, often between epithelial cells, and forming the matrix of myxoid tissue and, together with collagen, chondroid tissue. No differences were seen between tumours from parotid glands and those from submandibular glands. Glycoproteins demonstrated in the epithelium are similar to those of intercalary ducts of parotid and submandibular glands, and may represent a primitive form of salivary secretion. Glycosaminoglycans secreted intercellularly by epithelial cells cause their increasing separation to form myxoid or chondroid tissue. This stromalization extends to lumina to produce a loss of epithelium. Pleomorphic adenoma appears to be a manifest example of variable derepression of the genotype.     

A novel approach for studying angiogenesis: A human skin equivalent with a capillary-like network

Angiogenesis results from an ordered set of events that can be modulated in vivo by a variety of angiogenesis-enhancing or inhibiting agents. We review in vitro angiogenesis models and the agents that enhance or inhibit angiogenesis. We also discuss a new in vitro angiogenesis model created within a skin equivalent. Briefly, endothelial cells were combined with the cutaneous cells of a standard skin equivalent and cultured in a chitosan cross-linked collagen-glycosaminoglycan scaffold of this endothelialized skin. This model enables the formation of capillary-like structures in a coculture environment containing newly synthesized extracellular matrix by fibroblasts and keratinocytes. Several morphological characteristics associated with the microvasculature in vivo were observed in the endothelialized skin equivalent such as histotypic organization of tubular structures, basement membrane deposition, and intercellular junction formation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Morphology and differential physiological ageing in a group of Quebec workers

Nearly half the adult males of our population are obese. The biological consequences of this obesity were measured as they developed through physiological testing. Individuals with adipose tissue greater than 25% of body weight are compared with those of less than 10% adipose tissue. Physiological differences between the two groups are the same whatever the age of the indiviudals, being roughly a 6 years difference between actual and physiological age.     

Molecular identification and phylogenetic analysis of spider mites (Prostigmata: Tetranychidae) of Turkey

The family Tetranychidae includes many agriculturally important species known as spider mites. Their morphological identification is quite difficult due to the tiny size of their taxonomic characters and the requirement for high-level expertise. This may lead to pest misidentification and thus failure in pest management. DNA-based species identification seems to offer an alternative solution to overcome these issues. In the present study, two common molecular markers—Cytochrome oxidase subunit I (COI) and Internal transcribed spacer 2 (ITS2)—were used to identify 10 spider mite species from Turkey. Furthermore, genetic distances for several of them were assessed. Panonychus ulmi and Bryobia kissophila had the lowest (1.1%) and highest (4.5%) intra-specific genetic distances, respectively. In addition, integrative taxonomy allowed to identify Eotetranychus quercicola in Turkey as a new record. The sequences herein obtained will allow rapid species identification using molecular techniques and will contribute to resolve the phylogenetic history of spider mites.

     

First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage

BACKGROUND: Conflicting findings with regard to the teratogenic risks of first trimester use of paroxetine have prompted the FDA, Health Canada, and the manufacturer of the drug to issue warnings against its use during pregnancy. Given that untreated depression during pregnancy can lead to deleterious effect on the mother and her unborn fetus, data on the relationship between the dose and the range of malformations is warranted. This study attempts to quantify the association between first trimester exposure to paroxetine and congenital cardiac malformations, adjusting for possible confounders, and to quantify the dose-response relationship between paroxetine use and cardiac defects. METHODS: The Medication and Pregnancy registry was used. This population-based registry was built by linking three administrative databases (RAMQ, Med-Echo, and ISQ), and includes all pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of entry in the registry is the date of the first day of the last menstrual period. To be eligible for this study, women had to: 1) be 15-45 years of age at entry; 2) be covered by the RAMQ drug plan >or=12 months before and during pregnancy; 3) be using only one type of antidepressant during the first trimester; and 4) have a live birth. Two nested case-control studies were carried out comparing the prevalence of paroxetine use in the first trimester of pregnancy to the prevalence of other antidepressant exposures during the same time period. Cases were defined as: 1) any major malformations; or 2) any cardiac malformations diagnosed in the first year of life; controls were defined as no major or minor malformations. Multivariate logistic regression techniques were used to analyze data. RESULTS: Among the 1,403 women meeting inclusion criteria, 101 infants with major congenital malformations were identified; 24 had cardiac malformations. Adjusting for possible confounders, the use of paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-2.84) during the first trimester of pregnancy did not increase the risk of congenital cardiac malformations compared with the use of non-SSRI antidepressants. When considering the dose, however, a dose-response relationship was observed, thus women exposed to >25 mg/day of paroxetine during the first trimester of pregnancy were at increased risk of having an infant with major congenital malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42). CONCLUSIONS: Gestational exposure to paroxetine is associated with major congenital malformations and major cardiac malformations for only first trimester exposure above 25 mg/day.     

ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism

The mitotic kinesin KSP (kinesin spindle protein, or Eg5) has an essential role in centrosome separation and formation of the bipolar mitotic spindle. Its exclusive involvement in the mitotic spindle of proliferating cells presents an opportunity for developing new anticancer agents with reduced side effects relative to antimitotics that target tubulin. Ispinesib is an allosteric small-molecule KSP inhibitor in phase 2 clinical trials. Mutations that attenuate ispinesib binding to KSP have been identified, which highlights the need for inhibitors that target different binding sites. We describe a new class of selective KSP inhibitors that are active against ispinesib-resistant forms of KSP. These ATP-competitive KSP inhibitors do not bind in the nucleotide binding pocket. Cumulative data from generation of resistant cells, site-directed mutagenesis and photo-affinity labeling suggest that they compete with ATP binding via a novel allosteric mechanism.     

Spontaneous fibroblast‐derived pericyte recruitment in a human tissue‐engineered angiogenesis model in vitro

Cooperation between endothelial cells and pericytes is essential to the stabilization and maturation of blood microvessels. We developed a unique in vitro tissue‐engineered model to study angiogenesis. The human endothelialized reconstructed connective tissue model promotes the formation of a three‐dimensional branching network of capillary‐like tubes (CLT) with closed lumens. The purpose of this work was to investigate whether pericytes were spontaneously recruited around CLT in the model. We demonstrated that smooth muscle α‐actin (SMA)‐positive cells were found closely associated with PECAM‐1‐positive capillaries in the model. Twelve percent (±2.6) of SMA‐positive cells were detected along with 15% (±1.64) von Willebrand factor‐positive endothelial cells in the culture system after 31 days of in vitro maturation. Conversely, no SMA‐positive cells were detected in reconstructed connective tissues made solely of fibroblasts. Knowing that PDGF is a major factor in the recruitment of pericytes, we showed that blockade of the PDGFB receptor using the inhibitor AG1296 induced an overall 5, 2.6, and 2.4‐fold decrease in the SMA‐positive cells, von Willebrand factor‐positive cells, and number of capillaries, respectively. Using combinations of human GFP‐positive fibroblasts and endothelial cells, we demonstrated that pericytes were recruited from the fibroblast population in the model. In conclusion, our tissue‐engineered culture system promotes the spontaneous formation of a network of capillaries and the recruitment of pericytes derived from fibroblasts. Since pericytes are essential components of the blood microvasculature, this culture system is a powerful model to study angiogenesis and endothelial cell/pericyte interactions in vitro. J. Cell. Physiol. 227: 2130–2137, 2012. © 2011 Wiley Periodicals, Inc.     

Human keratinocytes respond to direct current stimulation by increasing intracellular calcium: preferential response of poorly differentiated cells

A direct current (DC) endogenous electric field (EF) is induced in the wound following skin injury. It is potentially implicated in the wound healing process by attracting cells and altering their phenotypes as indicated by the response to an EF of keratinocytes cultured as individual cells. To better define the signalization induced by a direct current electric field (DCEF) in human keratinocytes, we took advantage of an in vitro model more representative of the in vivo situation since it promotes cell-cell interactions and stratification. Human keratinocytes were grown into colonies. Their exposure to a DCEF of physiological intensity induced an increase of intracellular calcium. This variation of intracellular calcium resulted from an extracellular calcium influx and was mediated, at least in part, by the L-type voltage-gated calcium channel. The increase in intracellular calcium in response to a DCEF was however not observed in all the cells composing the colonies. The intracellular calcium increase was only detected in keratinocytes that didn't express involucrin, a marker of differentiated cells. These results indicate that DCEF is able to induce a specific calcium response in poorly differentiated keratinocytes. This study brings a new perspective for the understanding of the signaling mechanism of endogenous EF in reepithelialization, a critical process during skin wound healing.