Fluid shear stress and the vascular endothelium: for better and for worse

As blood flows, the vascular wall is constantly subjected to physical forces, which regulate important physiological blood vessel responses, as well as being implicated in the development of arterial wall pathologies. Changes in blood flow, thus generating altered hemodynamic forces are responsible for acute vessel tone regulation, the development of blood vessel structure during embryogenesis and early growth, as well as chronic remodeling and generation of adult blood vessels. The complex interaction of biomechanical forces, and more specifically shear stress, derived by the flow of blood and the vascular endothelium raise many yet to be answered questions:How are mechanical forces transduced by endothelial cells into a biological response, and is there a "shear stress receptor"?Are "mechanical receptors" and the final signaling pathways they evoke similar to other stimulus-response transduction systems?How do vascular endothelial cells differ in their response to physiological or pathological shear stresses?Can shear stress receptors or shear stress responsive genes serve as novel targets for the design of diagnostic and therapeutic modalities for cardiovascular pathologies?The current review attempts to bring together recent findings on the in vivo and in vitro responses of the vascular endothelium to shear stress and to address some of the questions raised above.     

Recognition of leukemia in skeletal remains: Report and comparison of two cases

Recognition of disease in the archeologic record is facilitated by characterization of the skeletal impact of documented (in life) disease. The present study describes the osteological manifestations of leukemia as identified in the skeletons of two individuals diagnosed during life: a 3-year-old black girl with acute lymphocytic leukemia and a 60-year-old white male with acute myelogenous leukemia in the Hamann-Todd collection. Contrasting with the lack of specificity of radiologic findings, macroscopic skeletal changes appear sufficiently specific to allow distinguishing leukemia from other forms of cancer. While leukemia appears confidently diagnosable, distinguishing among the varieties (e.g., myelogenous and lymphocytic) does not appear possible at this time. Skeletal findings in leukemia are presented in tabular form to facilitate their application to future diagnosis of the disease in the archaelogical record. Am J Phys Anthropol 102:481–496, 1997. © 1997 Wiley-Liss, Inc.     

Programming cell growth into different cluster shapes using diffusible signals

Advances in genetic engineering technologies have allowed the construction of artificial genetic circuits, which have been used to generate spatial patterns of differential gene expression. However, the question of how cells can be programmed, and how complex the rules need to be, to achieve a desired tissue morphology has received less attention. Here, we address these questions by developing a mathematical model to study how cells can collectively grow into clusters with different structural morphologies by secreting diffusible signals that can influence cellular growth rates. We formulate how growth regulators can be used to control the formation of cellular protrusions and how the range of achievable structures scales with the number of distinct signals. We show that a single growth inhibitor is insufficient for the formation of multiple protrusions but may be achieved with multiple growth inhibitors, and that other types of signals can regulate the shape of protrusion tips. These examples illustrate how our approach could potentially be used to guide the design of regulatory circuits for achieving a desired target structure.     

Clues potentially distinguishing lytic lesions of multiple myeloma from those of metastatic carcinoma

This study was conducted to determine whether individual bony lesions are specific for recognizing multiple myeloma and thereby distinguish it from metastatic cancer and leukemia. The lytic skeletal lesions of multiple myeloma are characterized by sharply defined, spheroid lesions. They have smooth borders and effaced/erased trabeculae. Unique spheroid myeloma lesions appear to be responsible for the “punched out” appearance of affected bone. The total absence of remodeling in myeloma forms a contrast to irregular preservation of trabeculae and buttressing, isolated “fronts of” cortical bone “resorption” coalescing to confluence, and the “golf-ball surface” phenomenon observed in metastatic cancer. The uniform effacement of both cortical and trabecular bone in multiple myeloma also contrasts with some cortical preservation in metastatic cancer. Leukemic lesions are more numerous than those of myeloma, but they lack the latter's “space-occupied” appearance. The relatively small holes and “fronts of resorption” of leukemia are quite different from the “space-occupied” lesions of multiple myeloma. Uniform size is a characteristic traditionally attributed to the bone lesions of multiple myeloma. The occurrence of isolated examples of uniform size lesions in metastatic cancer and of variable size lesions in some individuals with multiple myeloma precludes unequivocal use of size in differential diagnosis. Fortunately, the newly recognized macroscopic characteristics appear to separate multiple myeloma from metastatic cancer, and also distinguish myeloma from leukemia. Am J Phys Anthropol 105:241–250, 1998. © 1998 Wiley-Liss, Inc.     

The effect of growth medium salinity of Photobacterium damselae subsp. piscicida on the immune response of hybrid bass (Morone saxatilis x M. chrysops)

Photobacterium damselae subsp. piscicida (P. damselae) was grown on various media and the effect of media salinity on certain immune responses of hybrid bass was studied. In Israel, pasteurellosis outbreaks have not been reported at water salinities below 1.38 per thousand. During vaccination experiments the salinity of the medium on which P. damselae is grown, was shown to affect stimulation of the immune system. No correlation was found between antibody response and protection. Bacterial envelopes separated by electrophoresis and subjected to western blot analysis revealed an antibody response against some protein bands. Band sequencing was performed to identify the protein stimulating the immune response. Sequence identity of 80% was seen in 10-amino-acid overlap of the 36-kDa band with a specific gene of alkalophilic Bacillus firmus. A preparation of P. damselae grown in a 2.5% NaCl medium at 25 degrees C is the most effective vaccine against pasteurellosis, providing hybrid bass with quite good protection.     

The childhood component of the ICP model is appropriate for growth analysis of short Israeli children

OBJECTIVE: To determine whether the childhood component of the infancy-childhood-puberty (ICP) model is appropriate for growth analysis of short Israeli children. SUBJECTS AND METHODS: From 204 short, prepubertal children, 2-16 years of age, 1,516 height measurements were analyzed. For each child's measurements, a best-fitted line based on C equation of ICP has been drawn and the distribution of measurement points around that line was calculated. RESULTS: Ninety percent of the measurements were at a distance of no more than +/- 2 cm from the best-fitted ICP line. CONCLUSION: The C component of ICP model can be used as a growth analysis tool for shorter than average, prepubertal, Israeli children, older than 2 years of age.     

Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion

The mitochondrial DNA (mtDNA) depletion syndrome is a quantitative defect of mtDNA resulting from dysfunction of one of several nuclear-encoded factors responsible for maintenance of mitochondrial deoxyribonucleoside triphosphate (dNTP) pools or replication of mtDNA. Markedly decreased succinyl-CoA synthetase activity due to a deleterious mutation in SUCLA2, the gene encoding the beta subunit of the ADP-forming succinyl-CoA synthetase ligase, was found in muscle mitochondria of patients with encephalomyopathy and mtDNA depletion. Succinyl-CoA synthetase is invariably in a complex with mitochondrial nucleotide diphosphate kinase; hence, we propose that a defect in the last step of mitochondrial dNTP salvage is a novel cause of the mtDNA depletion syndrome.     

Ribosomal DNA evidence and disjunctions of western American Portulacaceae

Phylogenetic analysis of ribosomal DNA internal transcribed spacer sequences from 35 members of western American Portulacaceae plus seven Portulacaceae outgroups generally supports morphologically based interpretations of multiple intercontinental disjunctions. The data neither support nor refute monophyly of the western American group but strongly support a group comprising the western American taxa plus Phemeranthus, the only strictly American genus of the morphology-based eastern American/African group of Portulacaceae, along with the Australian genus Parakeelya. Support is strong for the monophyly of Calandrinia, Montiopsis, Lewisia, Claytonia, and Montia, along with a sister relationship of the last two. The data neither strongly support nor refute the morphologically based diagnosis of Cistanthe, but they strongly support a clade including the North American Cistanthe section Calyptridium and the South American Cistanthe sections Amarantoideae and Philippiamra. The internal transcribed spacer data fail to resolve the phylogenetic relationships among most of the western American lineages, suggesting either rapid radiation or, alternatively, erratic evolution of the internal transcribed spacer. The internal transcribed spacer and morphological evidence together suggest that in this group there have been 8-13 dispersal and colonization events across >2000 km (1 for every 15-26 extant species in this group). The internal transcribed spacer data document complex molecular evolutionary patterns, including strong substitution biases, among-site rate heterogeneity, positional bias for deamination-type substitutions, nonstationarity, and variable rates of insertion/deletion. Our phylogenetic conclusions, however, do not appear to be sensitive to these patterns.     

Photoinactivation of Acinetobacter baumannii and Escherichia coli B by a Cationic Hydrophilic Porphyrin at Various Light Wavelengths

Photodynamic treatment by the cationic TMPyP photosensitizer was undertaken on the multiple antibiotic-resistant bacteria Acinetobacter baumannii and Escherichia coli. Total eradication of the bacterial cultures was determined immediately after initiation of illumination when these bacteria were treated with 5, 10, 15, 20-tetra (4-N methylpyridyl)porphine (TMPyP) at a concentration of 29.4 μmol/L and illuminated by blue, green, or red light. Total eradication of both bacteria was obtained also after treatment of bacterial cultures with 3.7 μmol/L TMPyP and illumination with blue light (400–450 nm). On the other hand, an 8- or 16- to 20-fold higher light intensity, respectively, was required for total eradication upon illumination with green (480–550 nm) or red light (600–700 nm). A 407-nm blue light only 7 and 9 joules/cm², respectively, was needed for total eradication of both bacteria even at a concentration of 3.7 μmol/L TMPyP. X-ray-linked microanalysis demonstrated loss of potassium and a flood of sodium and chloride into the cells, indicating serious damage to the cytoplasmic membrane. Transmission electron microscopy (TEM) revealed structural changes and damage to the membrane of treated E. coli. In A. baumannii-treated cells, mesosomes and black dots that resemble aggregation of polyphosphate polymers could be seen. DNA breakage appeared only after a long period of illumination, when the bacterial cell was no longer viable. It can be concluded that cytoplasmic membrane damage and not DNA breakage is the major cause for bacterial death upon photosensitization. Received: 13 October 2000 / Accepted: 17 November 2000     

Learning to Control Actions: Transfer Effects following a Procedural Cognitive Control Computerized Training

Few studies have addressed action control training. In the current study, participants were trained over 19 days in an adaptive training task that demanded constant switching, maintenance and updating of novel action rules. Participants completed an executive functions battery before and after training that estimated processing speed, working memory updating, set-shifting, response inhibition and fluid intelligence. Participants in the training group showed greater improvement than a no-contact control group in processing speed, indicated by reduced reaction times in speeded classification tasks. No other systematic group differences were found across the different pre-post measurements. Ex-Gaussian fitting of the reaction-time distribution revealed that the reaction time reduction observed among trained participants was restricted to the right tail of the distribution, previously shown to be related to working memory. Furthermore, training effects were only found in classification tasks that required participants to maintain novel stimulus-response rules in mind, supporting the notion that the training improved working memory abilities. Training benefits were maintained in a 10-month follow-up, indicating relatively long-lasting effects. The authors conclude that training improved action-related working memory abilities.