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At least 685 records · Page 38Linked to original sources
PubMed2002

RHO-GTPases and cancer.

The RAS oncogenes were identified almost 20 years ago. Since then, we have learnt that they are members of a large family of small GTPases that bind GTP and hydrolyse it to GDP. This is then exchanged for GTP and the cycle is repeated. The switching between these two states regulates a wide range of cellular processes. A branch of the RAS family--the RHO proteins--is also involved in cancer, but what is the role of these proteins and would they make good therapeutic targets?

Animals↗
PubMed1998

Stable reintroduction of wild-type P53 (MTmp53ts) causes the induction of apoptosis and neuroendocrine-like differentiation in human ductal pancreatic carcinoma cells.

Pancreatic ductal adenocarcinoma is one of the major causes of cancer mortality in the industrialized world, having among the poorest prognosis of any malignancy. Mutations or alterations in the p53 tumor suppressor gene/protein are observed in 50-70% of these cancers, yet little information is available regarding the phenotypic effects of restoration of wild-type (wt) p53 function in pancreatic ductal carcinoma cells. The consequences of stable reintroduction of wt p53 on apoptosis and differentiation was examined in a poorly differentiated pancreatic carcinoma cell line (Panc-1), possessing only mutant (mt) p53 (codon 273 mutation). Cells were transfected with a temperature-sensitive mouse p53val135 (tsp53) vector under additional control of a genetically-modified metallothionein promoter. This tsp53 has a 'mt' phenotype at 37.5 degrees C, and a 'wt' phenotype at 32.5 degrees C and the presence of 100 microM ZnCl2. Stable expression of wt p53 caused upregulation of the p21/WAF1 gene, and G1 growth arrest as shown by flow cytometry and BrdU labeling. Additionally, apoptosis was induced 8-12 post-induction in the majority of the cells (60-70%), as demonstrated by morphological changes, in situ TdT labeling and internucleosomal laddering. However, a subpopulation (30%) of the transfectants survived this apoptotic fate. Unlike the epithelial parental Panc-1 cells, these cells exhibited the appearance of a neuroendocrine-like phenotype with extensive branch-like processes, and marked cytoplasmic and cytoskeletal immunostaining for tau-2, synaptophysin, and chromogranin A. These studies suggest that stable and regulated expression of wt p53 can have multiple phenotypic consequences (apoptosis and altered differentiation to a neuroendocrine-like phenotype) in poorly-differentiated pancreatic carcinoma cells.

Apoptosis↗
PubMed2002

The molecular control of renal branching morphogenesis: current knowledge and emerging insights.

Mammalian kidney development requires the formation of a patterned, branched network of collecting ducts, a process termed renal branching morphogenesis. Disruption of renal branching morphogenesis during human kidney development results in renal dysplasia, the major cause of renal failure in young children. Genetic evidence, combined with in vitro data, have implicated transcription factors, secreted growth factors, and cell surface signaling peptides as critical regulators of renal branching morphogenesis. This review discusses the current knowledge regarding the regulation of renal branching morphogenesis in vivo provided by the analysis of genetic mutations in mice and humans which disrupt collecting duct system development. In addition, in vivo and in vitro evidence regarding the functions of several other gene families are considered, rendering new insight into emerging regulatory roles for these molecules in renal branching morphogenesis.

Animals↗
PubMed2003

Human intervertebral disc cell morphology and cytoskeletal composition: a preliminary study of regional variations in health and disease.

Classically, intervertebral disc cells have been described as fibrocytic in the anulus fibrosus and chondrocytic in the nucleus pulposus. Recent animal studies, however, have suggested that disc cell morphology may be more complex than previously considered. Here, by utilizing labelling of components of the cytoskeleton in combination with confocal microscopy, we have examined the detailed morphology of human intervertebral disc cells in pathological and non-pathological tissue. Filamentous-actin- and vimentin-positive cells that appeared either fibrocytic or chondrocytic were observed in all intervertebral discs. However, in localized areas of the disc, stellate cells that extended multiple, branching cytoplasmic processes into their surrounding matrix were also seen. This stellate appearance formed a marked feature of disc cells regionally in certain pathologies, i.e. in cells of the outer anulus fibrosus in scoliotic discs and in inner anulus/nucleus pulposus cells in one spondylolisthetic disc. We conclude that the phenotypic variation of human intervertebral disc cells should be extended to include cells with a stellate appearance, which may be more prevalent in tissue that has been subjected to abnormal load or tension.

Actins↗
PubMed2005

Species lifetime distribution for simple models of ecologies.

Interpretation of empirical results based on a taxa's lifetime distribution shows apparently conflicting results. Species' lifetime is reported to be exponentially distributed, whereas higher-order taxa, such as families or genera, follow a broader distribution, compatible with power-law decay. We show that both forms of evidence are consistent with a simple evolutionary model that does not require specific assumptions on species interaction. The model provides a zero-order description of the dynamics of ecological communities, and its species lifetime distribution can be computed exactly. Different behaviors are found as follows: an initial t(-3/2) power law, emerging from a random walk type of dynamics, which crosses over to a steeper t(-2) branching process-like regime and finally is cut off by an exponential decay that becomes weaker and weaker as the total population increases. Sampling effects also can be taken into account and shown to be relevant. If species in the fossil record were sampled according to the Fisher log-series distribution, lifetime should be distributed according to a t(-1) power law. Such variability of behaviors in a simple model, combined with the scarcity of data available, casts serious doubt on the possibility of validating theories of evolution on the basis of species lifetime data.

Animals↗
PubMed1976

Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.

A single cell clonal line which responds reversibly to nerve growth factor (NGF) has been established from a transplantable rat adrenal pheochromocytoma. This line, designated PC12, has a homogeneous and near-diploid chromosome number of 40. By 1 week's exposure to NGF, PC12 cells cease to multiply and begin to extend branching varicose processes similar to those produced by sympathetic neurons in primary cell culture. By several weeks of exposure to NGF, the PC12 processes reach 500-1000 mum in length. Removal of NGF is followed by degeneration of processes within 24 hr and by resumption of cell multiplication within 72 hr. PC12 cells grown with or without NGF contain dense core chromaffin-like granules up to 350 nm in diameter. The NGF-treated cells also contain small vesicles which accumulate in process varicosities and endings. PC12 cells synthesize and store the catecholamine neurotransmitters dopamine and norepinephrine. The levels (per mg of protein) of catecholamines and of the their synthetic enzymes in PC12 cells are comparable to or higher than those found in rat adrenals. NGF-treatment of PC12 cells results in no change in the levels of catecholamines or of their synthetic enzymes when expressed on a per cell basis, but does result in a 4- to 6-fold decrease in levels when expressed on a per mg of protein basis. PC12 cells do not synthesize epinephrine and cannot be induced to do so by treatment with dexamethasone. The PC12 cell line should be a useful model system for neurobiological and neurochemical studies.

Catecholamines↗
PubMed1994

Gastrointestinal autonomic nerve tumors: a clinicopathological, immunohistochemical and ultrastructural study of 10 cases.

Gastrointestinal Autonomic Nerve Tumors (GANTs) are an underrecognized group of gastrointestinal stromal tumors (GISTs) putatively arising from the neural plexuses of the bowel wall. Approximately 24 cases have been previously reported. Their histogenesis, malignant potential, morphology and phenotypic features are not well defined. We present details of 10 GANTs iterating features, predominantly ultrastructural, allowing distinction from other GISTs. Clinical details are: sex-7M, 3F; age range 31-79 yrs, mean 53; symptoms/signs--abdominal pain 3, GI bleeding 3, mass 2, anemia 2. Follow-up ranged from 1-102 mths, mean 29. Seven tumors involved the small intestine and 3 were gastric. Tumor size ranged from 30-160 mm, mean 79. They were solid and cystic, often transmural and usually involved mesentery and retroperitoneum. Spindled and epithelioid cells were "compartmentalized" by a branching microvasculature. Eosinophilic, PAS positive stromal globules were prominent. Paraffin immunostaining results were (number positive/total): vimentin (8/9), NSE (10/10), S100 protein (6/10), neurofilament protein (0/9), synaptophysin (3/9), desmin (2/9, focal), smooth-muscle actin (0/9). Ultrastructural diagnostic features were elaborate, branching cytoplasmic processes containing microtubules, intermediate filaments and varying numbers of neurosecretory granules. Characteristic features were elaborate smooth endoplasmic reticulum enmeshed with intermediate filaments, pleomorphic mitochondria with lamellar cristae, mitochondrial-RER complexes, confronting RER cisternae, and circumscribed collections of stromal "skeinoid" fibres. There were no features of smooth muscle, Schwannian or perineurial differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1960

The fine structure of some blood vessels of the earthworm, Eisenia foetida.

The fine structure of the main dorsal and ventral circulatory trunks and of the subneural vessels and capillaries of the ventral nerve cord of the earthworm, Eisenia foetida, has been studied with the electron microscope. All of these vessels are lined internally by a continuous extracellular basement membrane varying in thickness (0.03 to 1 micro) with the vessel involved. The dorsal, ventral, and subneural vessels display inside this membrane scattered flattened macrophagic or leucocytic cells called amebocytes. These lie against the inner lining of the basement membrane, covering only a small fraction of its surface. They have long, attenuated branching cell processes. All of these vessels are lined with a continuous layer of unfenestrated endothelial cells displaying myofilaments and hence qualifying for the designation of "myoendothelial cells." The degree of muscular specialization varies over a spectrum, however, ranging from a delicate endowment of thin myofilaments in the capillary myoendothelial cells to highly specialized myoendothelial cells in the main pulsating dorsal blood trunk, which serves as the worm's "heart" or propulsive "aorta." The myoendothelial cells most specialized for contraction display well organized sarcoplasmic reticulum and myofibrils with thick and thin myofilaments resembling those of the earthworm body wall musculature. In the ventral circulatory trunk, circular and longitudinal myofilaments are found in each myoendothelial cell. In the dorsal trunk, the lining myoendothelial cells contain longitudinal myofilaments. Outside these cells are circular muscle cells. The lateral parts of the dorsal vessels have an additional outer longitudinal muscle layer. The blood plasma inside all of the vessels shows scattered particles representing the circulating earthworm blood pigment, erythrocruorin.

Animals↗
PubMed2006

Single-base mismatch recognition using partially double-stranded probes having various lengths.

We have focused on the nucleation-synchronized DNA strand exchange reaction (ns-SER) as a format of a single-base mismatch detection. We employed a partially double-stranded (PDS) DNA probe having a single-stranded (ss) portion. We could rapidly resolve a single-base mismatch by the ns-SER rates of the PDS probe with target DNAs. Here, we reported the influence of probe length and operating conditions, such as temperature and buffer conditions, on a single-base mismatch recognition using the PDS probes. We could reliably recognize a single-base mismatch even with a 61mer long probe. However, the ns-SER rates were decreased with increasing probe length. We considered that a rate-limiting step of the ns-SER might be sifted from nucleation to branch migration processes. By an addition of cationic comb-type copolymers (PLL-g-Dex) in the buffer, the reaction rate was considerably increased 1-2 orders without disordering the resolution power.

Base Pair Mismatch↗
PubMed2001

Using DNA to construct and power a nanoactuator.

A DNA-based molecular machine is described which has two movable arms that are pushed apart when a strand of DNA, the fuel strand, hybridizes with a single-stranded region of the molecular machine. Through the process of branch migration, a second strand of DNA complementary to the fuel strand is able to remove the fuel strand from the molecular machine, restoring it to its original configuration. Compared with the molecular tweezers we had previously devised, this machine, which we call a nanoactuator, has a reduced tendency to form dimers.

DNA↗
PubMed2002

Deterministic single-photon source for distributed quantum networking.

A sequence of single photons is emitted on demand from a single three-level atom strongly coupled to a high-finesse optical cavity. The photons are generated by an adiabatically driven stimulated Raman transition between two atomic ground states, with the vacuum field of the cavity stimulating one branch of the transition, and laser pulses deterministically driving the other branch. This process is unitary and therefore intrinsically reversible, which is essential for quantum communication and networking, and the photons should be appropriate for all-optical quantum information processing.

Journal Article↗
PubMed2003

Phase modulated thermal conductance of Josephson weak links.

We present a theory for quasiparticle heat transport through superconducting weak links. The thermal conductance depends on the phase difference (phi) of the superconducting leads. Branch-conversion processes, low-energy Andreev bound states near the contact, and the suppression of the local density of states near the gap edge are related to phase-sensitive transport processes. Theoretical results for the influence of junction transparency, temperature, and disorder, on the conductance, are reported. For high-transmission weak links, D-->1, the formation of an Andreev bound state leads to suppression of the density of states for the continuum excitations, and thus, to a reduction in the conductance for phi approximately pi. For low-transmission (D<<1) barriers resonant scattering leads to an increase in the thermal conductance as T drops below T(c) (for phase differences near phi=pi).

Journal Article↗
PubMed2004

Universal dynamic fragmentation in D dimensions.

A generic model is introduced for brittle fragmentation in D dimensions, and this model is shown to lead to a fragment-size distribution with two distinct components. In the small fragment-size limit a scale-invariant size distribution results from a crack branching-merging process. At larger sizes the distribution becomes exponential as a result of a Poisson process, which introduces a large-scale cutoff. Numerical simulations are used to demonstrate the validity of the distribution for D=2. Data from laboratory-scale experiments and large-scale quarry blastings of granitic gneiss confirm its validity for D=3. In the experiments the nonzero grain size of rock causes deviation from the ideal model distribution in the small-size limit. The size of the cutoff seems to diverge at the minimum energy sufficient for fragmentation to occur, but the scaling exponent is not universal.

Journal Article↗
PubMed2002

From information management to protein annotation: preparing protein structures for drug discovery.

In contrast to academic pursuits of structural genomics, Structural GenomiX (SGX) solves protein structures at high throughput for the main purpose of enhancing drug-discovery projects, either internally or in partnership with pharmaceutical/biotechnology companies. This involves a radical redesign of the pipeline of methods that turn a gene sequence into a three-dimensional protein structure. The various processes all report electronically to a Laboratory Information Management System (LIMS) to make sure all the parameters of the experiment are recorded in an accessible and 'mineable' form, helping guarantee reproducibility of results. Quality control at several key points keeps the process from branching out on a wrong hypothesis. Protein annotation, in a broad sense, takes care of the interpretation of a protein crystal structure or the crystal structure of one or several protein-ligand complexes. This interpretation both gathers all necessary biological information (protein function, mechanism, specific features within a protein family etc.) and hands over this information in a form accessible to medicinal chemistry teams designing specific small-molecule agonists or antagonists.

Crystallization↗
PubMed2005

A stochastic model to analyze clonal data on multi-type cell populations.

This article presents a stochastic model designed to analyze experimental data on the development of cell clones composed of two (or more) distinct types of cells. The proposed model is an extension of the traditional multi-type Bellman-Harris branching stochastic process allowing for nonidentical time-to-transformation distributions defined for different cell types. A simulated pseudo likelihood method has been developed for the parametric statistical inference from experimental data on cell clones under the proposed model. The method uses simulation-based approximations of the means and the variance-covariance matrices of cell counts. The proposed estimator for the vector of unknown parameters is strongly consistent and asymptotically normal under mild regularity conditions, while its variance-covariance matrix is estimated by the parametric bootstrap. A Monte Carlo Wald test is proposed for the test of hypotheses. Finite sample properties of the estimator have been studied by computer simulations. The model and associated methods of parametric inference have been applied to the analysis of proliferation and differentiation of cultured O-2A progenitor cells that play a key role in the development of the central nervous system. It follows from this analysis that the time to division of the progenitor cell and the time to its differentiation (into an oligodendrocyte) are not identically distributed. This biological finding suggests that a molecular event determining the type of cell transformation is more likely to occur at the start rather than at the end of the mitotic cycle.

Biometry↗
PubMedDate not supplied

Interstitial Cajal-like cells (ICLC) in human atrial myocardium.

We present here visual evidence for the existence of a new type of interstitial cells in human atrial myocardium: interstitial Cajal-like cells (ICLC). These cells fulfil the so-called 'platinum standard' (a set of 10 ultrastructural criteria for the positive diagnosis of ICLC). Conventional transmission electron microscopy (TEM), followed by reconstructions from serial photomicrographs, revealed typical ICLC with 2 or 3 long, moniliform processes (several tens of micrometers long and 0.1-0.5 microm thick), emerging from the (small) cell body. Cell processes dichotomously branch and have mitochondria (at the level of dilations), caveolae and Ca(2+) release units. Cell prolongations establish close spatial relationships between each other, as well as with capillaries, myocardial cells, and other connective tissue cells. Our preliminary data suggest that ICLC exist in rat ventricular myocardium, too.

Animals↗
PubMed1984

High melanosome engulfing activity of cutaneous fibroblasts in macular amyloidosis: an electron microscopic study.

Six patients with macular amyloidosis were investigated by electron microscopy and various morphological changes in fibroblasts were identified. Many cells, which seemed to be macrophages by light microscopy, proved to be fibroblasts. The digesting action of fibroblasts was well developed and many melanosomes were taken into the cells making the cells resemble melanophages. The fibroblasts extended long, thin and branched cytoplasmic processes to surround the amyloid mass, and the cells selectively extended these into the narrow spaces between collagen and amyloid. The fibroblast showed highly developed endocytotic activity and probable ingestion of amyloid by pinocytosis or phagocytosis. The developed rough endoplasmic reticulum contained much protein and was active in secretion.

Amyloidosis↗
PubMed1974

Stochastic properties of spontaneous transmitter release at the crayfish neuromuscular junction.

1. Miniature excitatory junctional potentials (min.e.j.p.s) were recorded with an intracellular electrode from the adductor muscle of the dactyl of the first or second walking leg of the crayfish, Orconectes virilis.2. The intervals between the min.e.j.p.s were compared to the exponential prediction by five goodness of fit tests. The results indicate that the intervals are not exponentially distributed.3. The autocorrelogram of intervals shows that the intervals are unlikely to be independent.4. A stochastic analysis that includes the power spectrum of intervals, the variance-time curve, and the ln-survivor curve suggest that there is a clustering of min.e.j.p.s. The results are similar to those on the frog neuromuscular junction.5. An autocorrelogram of the min.e.j.p. amplitudes suggests that sizes are not independently distributed.6. These results, which are similar to those previously reported from the frog neuromuscular junction, support the use of the branching Poisson process as a theoretical model for the stochastic properties of spontaneous quantal release of transmitter.

Journal Article↗