The carcinoid endocardial plaque; an ultrastructural study

Ultrastructural studies disclosed that the plaque-like endocardial thickenings in three patients with the carcinoid syndrome were composed of smooth muscle cells embedded in a stroma that was rich in acid mucopolysaccharides, collagen, and microfibrils, but devoid of elastic fibers. The smooth muscle cells contained variable numbers of myofilaments and cisterns of rough surfaced endoplasmic reticulum, and their basement membranes were greatly thickened, reduplicated, and arranged in layers. The endocardial plaques appeared histologically and ultrastructurally similar regardless of their location in the heart. The smooth muscle cells in these plaques appear to have been derived from primitive mesenchymal cells, which normally are present in the subendocardial endothelial space. These observations are interpreted as indicating that the plaques develop as a result of healing of a superficial endocardial injury, which may be initiated by release of bradykinin from hepatic metastases of a carcinoid tumor.     

Liposome accumulation in ischaemic intestine following experimental mesenteric occlusion

Chromosome complements of murine thymic lymphomas induced by an alkylating agent N-methyl-N-nitrosourea (MNUA) were analyzed microscopically and karyotypically using the Q-banding technique. The chemical carcinogen was injected intraperitoneally into either neonatal or 7-week-old CFW/D mice. In addition, thymic lymphomas induced in 7-week-old AKR mice and thymic lymphomas developed spontaneously in this strain were also examined. All six lymphomas induced in neonatal CFW/D had hyperdiploid cell lines that accounted for 90% of the cells analyzed. Chromosome analysis of lymphomas induced in adult DFW/D mice showed that only out of nine lymphomas had predominantly hyperdiploid cell lines. The remaining five lymphomas had diploid modal chromosome number although they also carried a variant line characterized by 41 chromosomes. All eight lymphomas induced in adult AKR mice and six out of seven spontaneous AKR lymphomas showed predominantly diploid modal line. The remaining spontaneous lymphoma had a hyperdiploid stem line of 41 chromosomes. Microscopic and karyotypic analysis further identified trisomy 15 as the regular chromosome abnormality in the hyperdiploid cells in lymphomas of each group, whereas cells with diploid chromosome number had no detectable chromosome abnormality. Additional trisomies were also found, but their appearance was restricted to individual tumors. Thus, the incidence of trisomy 15 in lymphomas induced by MNUA in adult CFW/D and AKR mice, as well as in the spontaneous AKR lymphomas, is significantly lower than that in lymphomas induced in neonatal mice by the same carcinogen.     

Plates and edges

The backscattering from a rectangular plate at edge-on incidence is due essentially to the individual contributions from the front and trailing edges. The contribution of the front edge is analogous to that of a wire illuminated by a plane wave, but the rear edge excitation is almost wholly determined by current waves along the side edges of the plate.     

CYTOCENTERING: a novel technique enabling automated cell-by-cell patch clamping with the CYTOPATCH chip

Automats for patch clamping suspended cells in whole-cell configuration must (1) bring isolated cells in contact with patch contacts, (2) form gigaseals, and (3) establish stable intracellular access that allows for high quality recording of ionic currents. Single openings in planar substrates seem to be intriguing simple solutions for these problems, but due to the low rate of formation of whole-cell configurations we discarded this approach. Single openings are not suited for both attracting cells to the opening by suction and forming gigaseals with subsequent membrane rupture. To settle the three tasks with a mechanical microstructure we developed the socalled CYTOCENTERING technique to apply to suspended cells the same operation sequence as in conventional patch clamping. With this method we immobilized selected cells from a flowing suspension on the tip of a patch pipette by suction with a success rate of 97% and formed gigaseals with a success rate of 68%. Subsequent whole-cell recordings and intracellular staining with Lucifer yellow proved the stable access to the cytoplasm. Currently, a chip with an embedded suction opening in glass surrounding the microstructured contact pipette is under development. The processing of this CYTOPATCH chip is compatible to large-volume production. The CYTOPATCH automat will allow for fully automated, parallel, and asynchronous whole-cell recordings.     

Naltrexone alteration of the nicotine-induced EEG and mood activation response in tobacco-deprived cigarette smokers.

The neural mechanisms contributing to the arousal-eliciting actions of smoking and nicotine involve multiple neurotransmitter systems. The current study examined the role of opioid neurotransmission in modulating the neuroelectric- and mood-activating response to acute nicotine administration in overnight tobacco-deprived smokers. In a randomized, double-blind, placebo-controlled design involving 18 (10 male, 8 female) overnight tobacco-abstinent smokers, spectrally analyzed electroencephalographic (EEG) activity and subjective reports of mood, euphoria, and smoking withdrawal were assessed in response to nicotine gum (4 mg) after pretreatment with placebo or with 50 mg of the opioid antagonist naltrexone. In addition to reducing withdrawal symptoms and increasing euphoria ratings, as well as subjective alertness in male participants, nicotine induced an EEG arousal response consisting of diffuse slow wave (delta, theta) amplitude reductions, frontal fast alpha wave amplitude increments, and elevations in beta wave amplitude, which were greater in female than in male smokers. Naltrexone attenuated the alerting and euphoric actions of nicotine but did not affect nicotine's ameliorating effects on withdrawal symptoms. Nicotine-induced frontal reductions in delta and global reductions in theta were prevented by naltrexone pretreatment, as were increases in anterior recordings of relative fast alpha. These findings suggest that the opioid system is involved in nicotine-induced subjective and neuroelectric arousal and implicate opioid-cholinergic interactions in the elicitation of these arousal responses to nicotine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Place of TRIZ in a Holistic Design Methodology

Design is key to a project’s profitability and therefore increased PROFIT by DESIGN is the goal of improvements to the design process. Business requirements can be summarised as Better, Faster, Cheaper and considerable investment has been made in technology and methods for the design process to enable this. There is evidence to suggest that these investments have resulted in products themselves getting better but not necessarily produced faster or cheaper. A model of the design process has been developed which makes explicit its key elements. The six key elements or dimensions of the design process are: Analyse; Understand; Decide; Create; Capture; and Know. Investments in design technology may not be reaching their full potential due to a mismatch between the relative importance of the attributes of a good designer and the areas where investments have been made, leading to a potential loss of balance in the design process. This is compounded by failure to take a holistic view of changes to the process including mitigation of any downside. In particular the Create dimension, which is seen as the most important attribute of a good designer, has had the least investment and also is the most vulnerable because it is optional. In recognition of this fact, Rolls‐Royce is using the TRIZ methodology to provide designers with an improved capability. However it also is recognised that providing capability alone is not enough. The right motivation and opportunity are also needed, and this requires the appropriate organisational and cultural features to be in place. What is needed is a people centred process that is business driven and product focused.     

Further evidence for the increased power of LOD scores compared with nonparametric methods

Platelet-derived growth factor (PDGF), a mitogen and chemoattractant for mesenchymal cells, occurs as cell-associated or released isoforms. To investigate their in vivo role, human keratinocytes, which normally synthesize both types of PDGF, were genetically modified to overexpress either wild-type PDGF-B (cell-associated) or the truncation mutant PDGF-B211 (released). Cells expressing the mutant isoform released 20 times more PDGF (145 ng/hour/10(7) cells) than cells expressing the wild-type isoform (6 ng/ hour/10(7) cells). When grafted as epithelial sheets onto athymic mice, modified cells formed a stratified epithelium and induced a connective tissue response that differed depending on the PDGF isoform expressed. Expression of PDGF-B211 induced a thick connective tissue with increased numbers of fibroblasts, mononuclear cells, and blood vessels evenly distributed throughout the connective tissue layer, whereas expression of PDGF-B induced a zone of fibroblasts and mononuclear cells localized to the interface of the epidermis and connective tissue, which often disrupted the continuity of the basement membrane. Immunostaining revealed that wild-type PDGF protein was deposited in the basement membrane region. These data suggest that the different binding properties of PDGF isoforms control the spatial organization of cellular events in regenerating mesenchymal tissue in vivo.