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At least 325 records · Page 18Linked to original sources
PubMed1997

Low frequency of p57KIP2 mutation in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an autosomal dominant disorder of increased prenatal growth and predisposition to embryonal cancers such as Wilms tumor. BWS is thought to involve one or more imprinted genes, since some patients show paternal uniparental disomy, and others show balanced germ-line chromosomal rearrangements involving the maternal chromosome. We previously mapped BWS, by genetic linkage analysis, to 11p15.5, which we and others also found to contain several imprinted genes; these include the gene for insulin-like growth factor II (IGF2) and H19, which show abnormal imprint-specific expression and/or methylation in 20% of BWS patients, and p57KIP2, a cyclin-dependent kinase inhibitor, which we found showed biallelic expression in one of nine BWS patients studied. In addition, p57KIP2 was recently reported to show mutations in two of nine BWS patients. We have now analyzed the entire coding sequence and intron-exon boundaries of p57KIP2 in 40 unrelated BWS patients. Of these patients, only two (5%) showed mutations, both involving frameshifts in the second exon. In one case, the mutation was transmitted to the proband's mother, who was also affected, from the maternal grandfather, suggesting that p57KIP2 is not imprinted in at least some affected tissues at a critical stage of development and that haploinsufficiency due to mutation of either parental allele may cause at least some features of BWS. The low frequency of p57KIP2 mutations, as well as our recent discovery of disruption of the K(v)LQT1 gene in patients with chromosomal rearrangements, suggest that BWS can involve disruption of multiple independent 11p15.5 genes.

Beckwith-Wiedemann Syndrome↗
PubMed2005

Enhanced lubricity in mixed alkanethiol monolayers.

The frictional properties of two-component mixed alkanethiol monolayers were investigated with frictional force microscopy. With large chain length differences, the two types of molecules segregated into large islands and reveal similar frictional properties as those of single-component monolayers. With small chain length differences, the completely mixed monolayers display a decreased friction as compared with single-component monolayers. This observation indicates that development of gauche kinks in the top portion of the mixed monolayers can enhance lubrication rather than increase friction, perhaps due to suppression of other energy dissipation channels.

Journal Article↗
PubMed2001

Unleash innovation in foreign subsidiaries.

In multinational corporations, growth-triggering innovation often emerges in foreign subsidiaries from employees closest to customers and least attached to the procedures and politeness of the home office. But too often, heavy-handed responses from headquarters squelch local enthusiasm and drive out good ideas--and good people. The authors' research into more than 50 multinationals suggests that encouraging innovation in foreign subsidiaries requires a change in attitude. Companies should start to think of foreign subsidiaries as peninsulas rather than as islands--as extensions of the company's strategic domain rather than as isolated outposts. If they do, innovative ideas will flow more freely from the periphery to the corporate center. Basing their arguments on a rich array of examples, the authors say that encouraging such "innovation at the edges" also requires a new set of practices, with two aims: to improve the formal and informal channels of communication between headquarters and subsidiaries and to give foreign subsidiaries more authority to see their ideas through. The challenge for executives of multinationals is to find ways to liberalize, not tighten, internal systems and to delegate more authority to local subsidiaries. It isn't enough to ask subsidiary managers to be innovative; corporate managers need to give them incentives and support systems to facilitate their efforts. The authors suggest four approaches: give seed money to subsidiaries; use formal requests for proposals as a way of increasing the demand for seed money; encourage subsidiaries to be incubators for fledgling businesses; and build international networks. As part of the last approach, multinationals also need to create roles for idea brokers who can link entrepreneurs in foreign subsidiaries with other parts of the company.

Commerce↗
PubMed2005

ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome.

Loss of genomic imprinting is involved in a number of developmental abnormalities and cancers. ZAC is an imprinted gene expressed from the paternal allele of chromosome 6q24 within a region known to harbor a tumor suppressor gene for several types of neoplasia. p57(KIP2) (CDKN1C) is a maternally expressed gene located on chromosome 11p15.5 which encodes a cyclin-dependent kinase inhibitor that may also act as a tumor suppressor gene. Mutations in ZAC and p57KIP2 have been implicated in transient neonatal diabetes mellitus (TNDB) and Beckwith-Wiedemann syndrome, respectively. Patients with these diseases share many characteristics. Here we show that mouse Zac1 and p57Kip2 have a strikingly similar expression pattern. ZAC, a sequence-specific DNA-binding protein, binds within the CpG island of LIT1 (KCNQ1OT1), a paternally expressed, anti-sense RNA thought to negatively regulate p57(KIP2) in cis. ZAC induces LIT1 transcription in a methylation-dependent manner. Our data suggest that ZAC may regulate p57(KIP2) through LIT1, forming part of a novel signaling pathway regulating cell growth. Mutations in ZAC may, therefore, contribute to Beckwith-Wiedemann syndrome. Furthermore, we find changes in DNA methylation at the LIT1 putative imprinting control region in two patients with TNDB.

Animals↗
PubMed2006

Clinical and nonclinical correlates of adherence to prescribing guidelines for hypertension in a large managed care organization.

To examine correlates of guideline adherence in a population with access to health care and prescription drug benefits, the authors conducted a cross-sectional analysis among 5789 patients undergoing hypertension treatment with a single medication in a large New England managed care organization. Logistic regression was used to determine correlates of adherence, defined as use of diuretics or beta blocker as antihypertensive monotherapy during the 1-year study period. Women were more likely than men to receive guideline-adherent therapy (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.45-1.85). Compared with patients covered by health maintenance organization plans, Medicare coverage was positively associated with guideline adherence (OR, 1.38; 95% CI, 1.13-1.69), but fee-for-service coverage was negatively associated (OR, 0.66; 95% CI, 0.48-0.91). Patient age was not a significant correlate of adherence to guidelines (OR, 1.01; 95% CI, 0.94-1.09). Understanding these observations may lead to strategies to improve guideline adherence and reduce health care disparities.

Adrenergic alpha-Antagonists↗
PubMed2004

CLCA2 tumour suppressor gene in 1p31 is epigenetically regulated in breast cancer.

The calcium-activated chloride channel gene family is clustered in the 1p31 region, which is frequently deleted in sporadic breast cancer. Recent studies have indicated the association of the second member of this gene family (CLCA2) with the development of breast cancer and metastasis. We have now shown the absence of expression of CLCA2 in several breast cancer tumours and cell lines, which confirms the results from other reports. When overexpressed in CLCA2-negative cell lines, their tumorigenicity and metastasis capability were significantly reduced, suggesting a tumour suppressor role for CLCA2 in breast cancer. The mechanisms behind the silencing of CLCA2 in breast cancer, however, have not been elucidated to date. Although we were able to identify CLCA2 mutations in breast cancers, somatic mutations are not the major cause of CLCA2 gene silencing. On the other hand, treatment of breast cancer CLCA2-negative cell lines with demethylating agents was able to restore CLCA2 expression, suggesting an epigenetic inactivation of this gene. Bisulphite-sequencing of the promoter-associated CpG island of the CLCA2 gene in breast tumours demonstrated that the absence of expression in these tumours was caused by hypermethylation of the promoter CpG island. In contrast, in breast cancer cell lines, tumours, and control cell lines that express CLCA2, a much lower level, and often absence, of methylation of the promoter were demonstrated. These findings demonstrate that CLCA2 is frequently inactivated in breast cancer by promoter region hypermethylation, which makes it an excellent candidate for the 1p31 breast cancer tumour suppressor gene.

Base Sequence↗
PubMed1993

Enhancement of fluorescein perfusion in experimental skin flaps following postischemic washout with iloprost, urokinase, verapamil, and University of Wisconsin solution.

The enhancement of blood flow in experimental skin flaps following postischemic perfusion washout was investigated in rats. Unilateral island skin flaps based on the superficial epigastric vessels were raised and subjected to 6 hr of primary ischemia. Group 1 was designated as a control and did not undergo postischemic perfusion washout. In the remaining rats, postischemic washout was performed with one of five agents: Group 2--lactated Ringer's solution; Group 3--University of Wisconsin solution, an organ preservation medium; Group 4--verapamil, a calcium channel blocker; Group 5--urokinase, a thrombolytic agent; Group 6--iloprost, a stable prostacyclin analog. Two hours following perfusion washout, fluorometric analysis revealed a statistically significant enhancement of blood flow in Groups 4, 5, and 6, compared to Groups 2 and 3 (p < 0.05). Furthermore, a significant increase in skin surface fluorescence was demonstrated in all the flaps that underwent perfusion washout, compared to the control flaps (p < 0.05). By analyzing skin surface fluorescence, the enhancement of nutritive blood flow in flaps, following postischemic perfusion washout, was evaluated. This is the first study in which the above pharmacologic agents were compared in a quantitative manner.

Adenosine↗
PubMed2002

Sediments and sediment-derived soils in Illinois: pedological and agronomic assessment.

Dredging sediments from water bodies in Illinois is done to preserve reservoir capacity, maintain navigation and recreation channels, and restore habitats, but the fate of the sediments is an issue. In anticipation of a major sediment dredging operation in Lake Peoria in the Illinois River, a retrospective study of sediment placement operations was performed. Sediments previously dredged from reservoirs and placed in retaining ponds were sampled along with adjacent upland soils which served as references. Sediments from the Illinois River above Peoria were sampled from islands, river bottom, and adjacent floodplain. Dredged sediment retention ponds initially support wetland vegetation. After dewatering, the physical properties of sediments tend to become similar to upland soils and the retention basins are then able to support conventional agriculture. Sediment organic matter content was similar to local reference surface soils, and soil pH of the sediments was neutral or above. Sediment textures are dominated by silts and clays, with the Lake Peoria samples being most clayey. Calcium was the dominant cation in all the samples, and micronutrients measured were in adequate supply for plant growth. However, because the Illinois River watershed includes industrial inputs, river sediments contained elevated levels of some metals, but they were generally below levels of regulatory concern. Results indicated that properly handled dredge sediments could make high quality agricultural soils. In addition, sediment placement on poor soils could improve their productivity.

Agriculture↗
PubMed2000

Nonlinear-resonance analysis of halo formation excited by beam-core oscillation

The emittance growth and halo formation for a mismatched beam of a one-dimensional Gaussian distribution in a uniform focusing channel were examined by means of a macroparticle simulation. The results were analyzed by isolated nonlinear resonance theory. The second-harmonic resonance driven by beam-core oscillation was both numerically and analytically shown to assume a key role in forming a halo. An analytic estimation of the halo location was explored, and the halo location was proved to correspond to the outer edge of the resonance islands. Nonlinear fields in an actual particle distribution have been shown to significantly affect both the halo's location and size.

Journal Article↗
PubMed2006

Malignant hyperthermia and central core disease causative mutations in Swedish patients.

BACKGROUND: Malignant hyperthermia (MH) susceptibility is a pharmacogenetic disorder of intracellular calcium homeostasis. In susceptible individuals, halogenated anaesthetics and/or suxamethonium may trigger an MH reaction. The diagnosis of MH susceptibility is made by an in vitro contracture test of biopsied muscle strips. METHODS: In 27 MH susceptible (MHS) probands and four MH negative (MHN) probands, exons 17, 39, 40, 45 and 46 of the RYR1 gene were screened for MH causative mutations. In addition, in three patients with established central core disease (CCD), exons 17, 39, 40, 45 and 46 and exons 95, 100, 101 and 102 were screened for MH and CCD causative mutations. All screenings were performed by direct sequencing of the entire exons. RESULTS: MH causative mutations were found in five of the 27 MHS probands (19%). CCD causative mutations were found in two of three CCD patients in the C-terminal exons. None of the CCD patients showed a mutation in N-terminal exon 17 or in the central exons. CONCLUSIONS: In a Swedish population, screening of N-terminal exon 17 and the central exons for MH causative mutations in the RYR1 gene covers 19% of families. Thus, other mutations must also be responsible for MH susceptibility in Sweden. Although the number of CCD patients in this study was small, screening of the C-terminal exons for CCD causative mutations seems to be a promising tool in the process of making a diagnosis.

Adolescent↗
PubMed2006

[Molecular diagnosis of adult dominant polycystic kidney disease in the Canary Islands].

Adult dominant polycystic kidney disease is an hereditary condition responsible for 6% of end-stage renal failure in Spain. Two genes were located in chromosomes 16 and 4 as related to this age-dependent disease in the 90s (PKD1 and PKD2). The diagnosis can be easily achieved by sonographic study, but molecular analysis by means of linkage analysis has the advantage of an early diagnosis in asymptomatic genetic carriers, with a view to the preventive follow-up of these subjects and genetic counselling. In this paper we present the results of molecular analysis of 30 families with Adult Dominant Polycystic Kidney Disease (from the province of Las Palmas Spain), carried out linkage analysis with two series of microsatellite markers located within or in the vicinity ofPKD1 (D16S521, KG8, AC2.5, CW2, SM7) and PKD2 (D4S1538, D4S1534, D4S423,D4S414) genes. The objectives of the study were: first, to verify the informativeness, and therefore, the usefulness of these markers for family studies in our population; and second,to assess the sensitivity and specificity of the genetic analysis in our population. Most of the markers showed a high heterozygosity, comparable to data in other studies. Considering the alleles of the different markers together in a chromosome as an haplotype increased the informativeness of the markers, and allowed the unequivocal identification of genetic data in 97.7% of patients and 88.7% of healthy subjects. The sensitivity and specificity of the genetic analysis were 90.7% (CI 95%: 85.7-95.7) and 86.8% (CI 95%: 80.6-93.0), respectively.

Atlantic Islands↗
PubMed1999

Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice.

We previously demonstrated the essential role of the flt-1 gene in regulating the development of the cardiovascular system. While the inactivation of the flt-1 gene leads to a very severe disorganization of the vascular system, the primary defect at the cellular level was unknown. Here we report a surprising finding that it is an increase in the number of endothelial progenitors that leads to the vascular disorganization in flt-1(-/-) mice. At the early primitive streak stage (prior to the formation of blood islands), hemangioblasts are formed much more abundantly in flt-1(-/-) embryos. This increase is primarily due to an alteration in cell fate determination among mesenchymal cells, rather than to increased proliferation, migration or reduced apoptosis of flt-1(-/-) hemangioblasts. We further show that the increased population density of hemangioblasts is responsible for the observed vascular disorganization, based on the following observations: (1) both flt-1(-/-) and flt-1(+/+) endothelial cells formed normal vascular channels in chimaeric embryos; (2) wild-type endothelial cells formed abnormal vascular channels when their population density was significantly increased; and (3) in the absence of wild-type endothelial cells, flt-1(-/-) endothelial cells alone could form normal vascular channels when sufficiently diluted in a developing embryo. These results define the primary defect in flt-1(-/-) embryos at the cellular level and demonstrate the importance of population density of progenitor cells in pattern formation.

Animals↗
PubMed2006

Both alpha-haemolysin determinants contribute to full virulence of uropathogenic Escherichia coli strain 536.

Uropathogenic Escherichia coli strain 536 possesses two intact copies of the alpha-haemolysin determinant localised on distinct pathogenicity islands. The coding regions of the two hlyCABD operons are conserved; however, upstream sequences are entirely dissimilar. Consequently, expression of the encoded toxin molecules in vitro is highly different. On the other hand, the contribution of the individual determinants to the strain's virulence is the same. Isogenic mutants lacking individual hly determinants have a similar increase in LD50 value in a mouse model of urinary tract infection. Mouse lung toxicity as well as in vitro assays reveals a significant decrease in acute cytotoxicity of both mutants in comparison to the parent wild-type strain; however, the two hly mutants do not significantly differ from each other in these respects. Single channel recordings show no difference in electrophysiological characteristics of the pores formed by the individual HlyA molecules on synthetic planar lipid membranes. Nor do the paralogues have any target cell preference in an in vitro cytotoxicity assay. Our data suggest that the two hly paralogues encode identical toxin functions; however, due to different regulation of expression, they participate at distinct stages of the infectious process. Interestingly, the unrelated uropathogenic E. coli strain J96 shares the same two hly alleles, suggesting that acquisition of the two paralogues accorded a selective evolutionary advantage.

5' Flanking Region↗
PubMed2001

Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population.

The gene MCOLN1 is mutated in Mucolipidosis type IV (MLIV), a neurodegenerative, recessive, lysosomal storage disorder. The disease is found in relatively high frequency among Ashkenazi Jews due to two founder mutations that comprise 95% of the MLIV alleles in this population [Bargal et al., 2000]. In this report we complete the mutation analysis of Jewish and non-Jewish MLIV patients whose DNA were available to us. Four novel mutations were identified in the MCOLN1 gene of severely affected patients: two missense, T232P and F465L; a nonsense, R322X; and an 11-bp insertion in exon 12. The nonsense mutation (R322X) was identified in two unrelated patients with different haplotypes in the MCOLN1 chromosomal region, indicating a mutation hotspot in this CpG site. An in-frame deletion (F408del) was identified in a patient with unusual mild psychomotor retardation. The frequency of MLIV in the general Jewish Ashkenazi population was estimated in a sample of 2,000 anonymous, unrelated individuals assayed for the two founder mutations. This analysis indicated a heterozygotes frequency of about 1/100. A preferred nucleotide numbering system for MCOLN1 mutations is presented and the issue of a screening program for the detection of high-risk families in the Jewish Ashkenazi population is discussed.

Codon, Nonsense↗
PubMed2002

Identification and characterization of an N-acylhomoserine lactone-dependent quorum-sensing system in Pseudomonas putida strain IsoF.

Recent reports have shown that several strains of Pseudomonas putida produce N-acylhomoserine lactones (AHLs). These signal molecules enable bacteria to coordinately express certain phenotypic traits in a density-dependent manner in a process referred to as quorum sensing. In this study we have cloned a genomic region of the plant growth-promoting P. putida strain IsoF that, when present in trans, provoked induction of a bioluminescent AHL reporter plasmid. Sequence analysis identified a gene cluster consisting of four genes: ppuI and ppuR, whose predicted amino acid sequences are highly similar to proteins of the LuxI-LuxR family, an open reading frame (ORF) located in the intergenic region between ppuI and ppuR with significant homology to rsaL from Pseudomonas aeruginosa, and a gene, designated ppuA, present upstream of ppuR, the deduced amino acid sequence of which shows similarity to long-chain fatty acid coenzyme A ligases from various organisms. Using a transcriptional ppuA::luxAB fusion we demonstrate that expression of ppuA is AHL dependent. Furthermore, transcription of the AHL synthase ppuI is shown to be subject to quorum-sensing regulation, creating a positive feedback loop. Sequencing of the DNA regions flanking the ppu gene cluster indicated that the four genes form an island in the suhB-PA3819 intergenic region of the currently sequenced P. putida strain KT2440. Moreover, we provide evidence that the ppu genes are not present in other AHL-producing P. putida strains, indicating that this gene cluster is so far unique for strain IsoF. While the wild-type strain formed very homogenous biofilms, both a ppuI and a ppuA mutant formed structured biofilms with characteristic microcolonies and water-filled channels. These results suggest that the quorum-sensing system influences biofilm structural development.

Amino Acid Sequence↗
PubMed2006

History, ocean channels, and distance determine phylogeographic patterns in three widespread Philippine fruit bats (Pteropodidae).

The comparative phylogeography of widespread, codistributed species provides unique insights into regional biodiversity and diversification patterns. I used partial DNA sequences of the mitochondrial genes ND2 and cyt b to investigate phylogeographic structure in three widespread Philippine fruit bats. Ptenochirus jagori is endemic to the oceanic region of the Philippines and is most abundant in lowland primary forest. Macroglossus minimus and Cynopterus brachyotis are most common in disturbed and open habitats and are not endemic. In all three, genetic differentiation is present at multiple spatial scales and is associated to some degree with Pleistocene landbridge island groups. In P. jagori and C. brachyotis, genetic distance is correlated with geographic distance; in C. brachyotis and M. minimus, it is correlated with the sea-crossing distance between islands. P. jagori has the least overall genetic structure of these three species, whereas C. brachyotis and M. minimus have more geographic association among haplotypes, suggesting that phylogeographic patterns are linked to ecology and habitat preference. However, contrary to expectation, the two widespread, disturbed habitat species have more structure than the endemic species. Mismatch distributions suggest rapid changes in effective population size in C. brachyotis and P. jagori, whereas M. minimus appears to be demographically more stable. Geologic and geographic history are important in structuring variation, and phylogeographic patterns are the result of dynamic long-term processes rather than simply reflecting current conditions.

Animals↗
PubMed2001

Mechanical Myocardial Injury and Angiogenesis: An Association with Therapeutic Potential for Advanced Ischemic Coronary Artery Disease.

The healing response of tissue after mechanical injury is a highly evolved complex response that serves as a natural defense mechanism. Tissue wounds typically heal in a temporal sequence of stages. A vital phase of wound healing is the generation of loose reparative tissue that is neovascularized and rich in angiogenic substrates--that of granulation tissue formation. A therapeutic strategy that has emerged for the treatment of patients with advanced atherosclerotic ischemic coronary disease is to therapeutically manipulate the wound healing process and induce injury in the myocardium to stimulate islands of neovascularization. This paper reviews the response of tissue, particularly the myocardium, to various forms of injury. Also discussed is the emerging hypothesis of a threshold of injury (balancing adequate injury to induce neovascularizatioin versus excessive injury resulting in adjacent myocardial damage with contractile dysfunction without additional angiogenic benefit). Initial animal and human studies from our laboratory and that of collaborators, with a new method of injury-induced angiogenesis referred to as mechanical myocardial channeling, are reviewed.

Journal Article↗
PubMed2002

[Foliage production of the mangrove from San Andrés Island, Colombian Caribbean coast].

Litter fall from a San Andres Island mangrove (12 degrees 32' N, 81 degrees 41' W, Colombian Caribbean coast), was collected monthly (1994-1995) with mesh baskets, keeping results separate for the three species (Rhizophora mangle, Avicennia germinans and Laguncularia racemosa), and taking a sample and a replica per case. Nine sampling sites were selected in two groups of woodlands: one in the inner side behind a sand-bar and the coast road (Mount Pleasant, Salt Creek, Sound Bay and Smith Channel) and a peripheral site, exposed to the waves (Bahía Hooker-Bahía Honda and El Cove). Productivity was greater for all species in the inner group, and higher in the rainy seasons. Rhizophora mangle was the only species contributing reproductive components throughout the year.

Analysis of Variance↗