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Variable Degrees (variable + degree)
Selected AbstractsRole of histone and transcription factor acetylation in diabetes pathogenesisDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2005Steven G. Gray Abstract Globally, diabetes (and, in particular, type 2 diabetes) represents a major challenge to world health. Currently in the United States, the costs of treating diabetes and its associated complications exceed $100 billion annually, and this figure is expected to soar in the near future. Despite decades of intense research efforts, the genetic basis of the events involved in the pathogenesis of diabetes is still poorly understood. Diabetes is a complex multigenic syndrome primarily due to beta-cell dysfunction associated with a variable degree of insulin resistance. Recent advances have led to exciting new developments with regard to our understanding of the mechanisms that regulate insulin transcription. These include data that implicate chromatin as a critical regulator of this event. The ,Histone Code' is a widely accepted hypothesis, whereby sequential modifications to the histones in chromatin lead to regulated transcription of genes. One of the modifications used in the histone code is acetylation. This is probably the best characterized modification of histones, which is carried out under the control of histone acetyltransferases (HATs) and histone deacetylases (HDACs). These enzymes also regulate the activity of a number of transcription factors through acetylation. Increasing evidence links possible dysregulation of these mechanisms in the pathogenesis of diabetes, with important therapeutic implications. Copyright © 2005 John Wiley & Sons, Ltd. [source] Soil solution concentration of Cd and Zn canbe predicted with a CaCl2 soil extractEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 1 2003F. Degryse Summary Risk assessment of heavy metals in soil requires an estimate of the concentrations in the soil solution. In spite of the numerous studies on the distribution of Cd and Zn in soil, few measurements of the distribution coefficient in situ, Kd, have been reported. We determined the Kd of soils contaminated with Cd and Zn by measuring metal concentrations in the soil and in the soil solution and attempted to predict them from other soil variables by regression. Soil pH explained most of the variation in logKd (R2 = 0.55 for Cd and 0.70 for Zn). Introducing organic carbon content or cation exchange capacity (CEC) as second explanatory variable improved the prediction (R2 = 0.67 for Cd and 0.72 for Zn), but these regression models, however, left more than a factor of 10 of uncertainty in the predicted Kd. This large degree of uncertainty may partly be due to the variable degree of metal fixation in contaminated soils. The labile metal content was measured by isotopic dilution (E value). The E value ranged from 18 to 92% of the total metal content for Cd and from 5 to 68% for Zn. The prediction of Kd improved when metals in solution were assumed to be in equilibrium with the labile metal pool instead of the total metal pool. It seems necessary therefore to discriminate between ,labile' and ,fixed' pools to predict Kd for Cd and Zn in field contaminated soils accurately. Dilute salt extracts (e.g. 0.01 m CaCl2) can mimic soil solution and are unlikely to extract metals from the fixed pool. Concentrations of Cd and Zn in the soil solution were predicted from the concentrations of Cd and Zn in a 0.01 m CaCl2 extract. These predictions were better correlated with the observations for field contaminated soils than the predictions based on the regression equations relating logKd to soil properties (pH, CEC and organic C). [source] Expression of melanoma-associated antigens in melanoma cell culturesEXPERIMENTAL DERMATOLOGY, Issue 7 2005Mirjana Urosevic Abstract:, The efficiency of melanoma immunotherapy appears to depend on both melanoma- and immune system-specific factors. Melanoma-specific factors include melanoma-associated antigen (MAA) expression as well as HLA class I molecule expression. We investigated the expression of five MAA , Melan-A/MART-1, tyrosinase, gp100, MAGE-1 and MAGE-3 , by means of FACS analysis in 50 melanoma cell cultures and compared them to the cultures of human foreskin-derived melanocytes and melanoma cell line UKRV-Mel2. Melan-A, tyrosinase and gp100 expression was frequently reduced in melanoma cell cultures, compared to that in foreskin melanocytes, whereas MAGE-1 and MAGE-3 expression showed variable degree of upregulation, compared to that in foreskin melanocytes. The expression of all tested MAA demonstrated high interindividual variability. We further show that cell cultures derived from the same tissue sample are oligoclonal in nature, by demonstrating the presence of up to three cell populations bearing distinct MAA profile. Analysing samples derived from the same patient but each at a different time point, we show that MAA expression profile changes over time either in positive (increase) or in negative (decrease) direction. Finally, we demonstrate that brain metastasis-derived cell cultures significantly overexpress Melan-A and MAGE-3, compared to primary tumours and other metastatic sites (P -value range: 0.05,0.001). Elucidation of the MAA expression patterns and the kinetics within the same patient as well as during the course of the disease may help improve current and develop new immunotherapeutic strategies. [source] LDL-receptor mutations in Europe,HUMAN MUTATION, Issue 6 2004George V.Z. Dedoussis Abstract Familial hypercholesterolemia (FH) is a clinical definition for a remarkable increase of cholesterol serum concentration, presence of xanthomas, and an autosomal dominant trait of either increased serum cholesterol or premature coronary artery disease (CAD). The identification of the low-density lipoprotein (LDL)-receptor (LDLR) as the underlying cause and its genetic characterization in FH patients revealed more insights in the trafficking of LDL, which primarily transports cholesterol to hepatic and peripheral cells. Mutations within LDLR result in hypercholesterolemia and, subsequently, cholesterol deposition in humans to a variable degree. This confirms the pathogenetic role of LDLR and also highlights the existence of additional factors in determining the phenotype. Autosomal dominant FH is caused by LDLR deficiency and defective apolipoprotein B-100 (APOB), respectively. Heterozygosity of the LDLR is relatively common (1:500). Clinical diagnosis is highly important and genetic diagnosis may be helpful, since treatment is usually effective for this otherwise fatal disease. Very recently, mutations in PCSK9 have been also shown to cause autosomal dominant hypercholesterolemia. For autosomal recessive hypercholesterolemia, mutations within the so-called ARH gene encoding a cellular adaptor protein required for LDL transport have been identified. These insights emphasize the crucial importance of LDL metabolism intra- and extracellularly in determining LDL-cholesterol serum concentration. Herein, we focus on the published European LDLR mutation data that reflect its heterogeneity and phenotypic penetrance. Hum Mutat 24:443,459, 2004. © 2004 Wiley-Liss, Inc. [source] Characterization of micro-organisms isolated from dairy industry after cleaning and fogging disinfection with alkyl amine and peracetic acidJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2005E. Bore Abstract Aims:, To characterize micro-organisms isolated from Norwegian dairy production plants after cleaning and fogging disinfection with alkyl amine/peracetic acid and to indicate reasons for survival. Methods and Results:, Microbial samples were collected from five dairy plants after cleaning and fogging disinfection. Isolates from two of these production plants, which used fogging with alkylamino acetate (plant A), and peracetic acid (plant B), were chosen for further characterization. The sequence of the 16S ribosomal DNA, fatty acid analysis and biochemical characteristics were used to identify isolates. Three isolates identified as Rhodococcus erythropolis, Methylobacterium rhodesianum and Rhodotorula mucilaginosa were isolated from plant A and one Sphingomonas sp. and two M. extorquens from plant B. Different patterns of resistance to seven disinfectants in a bactericidal suspension test and variable degree of attachment to stainless steel were found. The strains with higher disinfectant resistance showed lower degree of attachment than susceptible strains. Conclusions:, The study identifies and characterizes micro-organisms present after cleaning and fogging disinfection. Both surface attachment and resistance were shown as possible reasons for the presence of the isolates after cleaning and disinfection. Significance and Impact of the Study:, These results contribute to the awareness of disinfectant resistance as well as attachment as mechanisms of survival in dairy industry. It also strengthens the argument of frequent alternation of disinfectants in the food processing industry to avoid the establishment of resistant house strains. [source] Cytotoxic Bacillus spp. belonging to the B. cereus and B. subtilis groups in Norwegian surface watersJOURNAL OF APPLIED MICROBIOLOGY, Issue 5 2004Ø. Østensvik Abstract Aims:, To investigate the presence and numbers of Bacillus spp. spores in surface waters and examine isolates belonging to the B. cereus and B. subtilis groups for cytotoxicity, and to discuss the presence of cytotoxic Bacillus spp. in surface water as hazard identification in a risk assessment approach in the food industry. Methods and Results:, Samples from eight different rivers with variable degree of faecal pollution, and two drinking water sources, were heat shocked and examined for the presence of Bacillus spp. spores using membrane filtration followed by cultivation on bovine blood agar plates. Bacillus spp. was present in all samples. The numbers varied from 15 to 1400 CFU 100 ml,1. Pure cultures of 86 Bacillus spp. isolates representing all sampling sites were characterized using colony morphology, atmospheric requirements, spore and sporangium morphology, and API 50 CHB and API 20E. Bacillus spp. representing the B. cereus and B. subtilis groups were isolated from all samples. Twenty-one isolates belonging to the B. cereus and B. subtilis groups, representing eight samples, were screened for cytotoxicity. Nine strains of B. cereus and five strains belonging to the B. subtilis group were cytotoxic. Conclusions:, The presence of cytotoxic Bacillus spp. in surface water represents a possible source for food contamination. Filtration and chlorination of surface water, the most common drinking water treatment in Norway, do not remove Bacillus spores efficiently. This was confirmed by isolation of spores from tap water samples. Significance and Impact of the Study:, Contamination of food with water containing low numbers of Bacillus spores implies a risk for bacterial growth in foods. Consequently, high numbers of Bacillus spp. may occur after growth in some products. High numbers of cytotoxic Bacillus spp. in foods may represent a risk for food poisoning. [source] Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin testJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2009H.-L. Qiao MD PhD Summary Background:, Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. Methods:, A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. Results:, The rate of positive reactions for the specific IgE antibodies was 59·40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39·10% (52) and 42·86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7·5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P < 0·01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Conclusion:, Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increaes with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity. [source] Oligodendrocyte injury in multiple sclerosis: a role for p53JOURNAL OF NEUROCHEMISTRY, Issue 3 2003Karolina Wosik Abstract Multiple sclerosis (MS) is a neurological disorder characterized by myelin destruction and a variable degree of oligodendrocyte death. We have previously shown that overexpression of the transcription factor p53 can induce oligodendrocyte apoptosis. We investigated the mechanism of p53-induced apoptosis using primary cultures of central nervous system-derived adult human oligodendrocytes. Adenovirus-mediated p53 overexpression resulted in up-regulation of the death receptors Fas, DR4 and DR5 with subsequent caspase-mediated apoptosis of the oligodendrocytes. The oligodendrocytes were protected from p53-induced cell death by blocking signaling through Fas and/or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. Although lower levels of p53 did not induce apoptosis, the increase in death receptor expression was sufficient to render the oligodendrocytes susceptible to apoptosis in the presence of exogenous Fas ligand and TRAIL. These ligands are present in the inflammatory milieu of active MS lesions. In situ analysis of active MS lesions revealed increased p53 expression in oligodendrocytes in lesions that featured oligodendrocyte apoptosis and cell loss. Our data provide evidence for a novel role for p53 in the pathogenesis of MS. [source] Intercostal nerve transfer in infants with obstetric brachial plexus palsyMICROSURGERY, Issue 7 2008Tarek A. El-Gammal M.D. The use of intercostal nerve (ICN) transfer to repair brachial plexus lesions associated with root avulsions is a well known procedure in adults. However, there is a paucity of reports on the use of ICN in infants with obstetrical brachial plexus palsy (OBPP). This study included 46 infants with obstetric brachial plexus palsy who underwent 62 neurotization procedures. Clinically, 2 cases had upper trunk injury, 19 had upper-middle trunk injury, 3 had lower trunk injury, and 22 had total palsy. The average age at surgery was 14 months. Twelve patients underwent surgery younger than 6 months of age, 11 patients at 6 to <9 months, 9 patients at 9,12 months, and 14 patients at >12 months. The average follow-up period was 49 months. ICN transfer resulted in 76% satisfactory (good and excellent) outcome, and was best for restoration of elbow flexion (93.5%). Functional results were best when the operation was done before the age of 9 months; however, the difference between age groups was statistically insignificant. Functional results were also independent of the extent of the original injury. Nine children had preoperative and postoperative CT chest scans. All the nine children developed basal pulmonary atelectasis postoperatively. Pulmonary atelectasis was mostly ipsilateral and was not correlated to the patient age (months), or the duration of anesthesia (in minutes). We conclude that, intercostals nerve transfer is an effective procedure for restoration of function in infants with OBPP and root avulsions. The procedure is associated with variable degree of ipsilateral pulmonary atelectasis. © 2008 Wiley-Liss, Inc. Microsurgery, 2008. [source] Day-to-day reproducibility of anorectal sensorimotor assessments in healthy subjectsNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2004A. E. Bharucha Abstract, The reproducibility of tests widely utilized to assess anorectal sensorimotor functions is not well established. Our aims were to assess the intra-individual day-to-day reproducibility of these parameters in healthy subjects. Anal sphincter pressures were assessed by perfusion manometry on two separate days in 19 healthy subjects. Rectal pressure,volume (p,v) curves and sensory thresholds were assessed in 12/19 subjects by inflating a highly compliant polyethylene balloon from 0 to 32 mmHg in 4 mmHg steps. Subjects also rated intensity of perception by visual analogue scale (VAS) during phasic distentions 8, 16 and 24 mmHg above operating pressure, in randomized sequence. Resting and squeeze anal pressures and rectal compliance were highly reproducible (rs , 0.7) in the same subject on separate days. Pressure thresholds for urgency appeared less reproducible than thresholds for initial perception and the desire to defecate. VAS scores were highly reproducible only during the 24-mmHg distention. Thus, anal pressures and rectal compliance are highly reproducible within healthy subjects on separate days, while sensory thresholds are reproducible to a variable degree, dependent on the intensity of stimulation and the perception being assessed. [source] ,This is like my comfort zone': Senses of place and belonging within Oru,mo/Beachhaven, New ZealandNEW ZEALAND GEOGRAPHER, Issue 3 2006Tim McCreanor Abstract:, This paper examines the culturally specific experiences of belonging within Oru,mo/Beachhaven, a suburb in North Shore City. In-depth interviews with 32 caregivers of young children expose the fact that the ethnic groups represented , M,ori, Samoan and P,keh,, vary in their uses and understandings of, as well as feelings for, residential neighbourhood. Examination of the themes of natural environment, social relations, continuity of residence, facilities, organisations and place transformation reveal that, while representatives of all groups had views on these matters, there was a variable degree of engagement with and priority afforded to these concerns. [source] Determination of the phosphorylation level and deamidation susceptibility of equine ,-caseinPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 12 2006Jean-Michel Girardet Dr. Abstract ,-Casein was isolated from Haflinger mare's milk by RP-HPLC, and displayed microheterogeneity by urea-electrophoresis and 2-DE probably due to a variable degree of phosphorylation. To investigate the degree of phosphorylation, the primary structure of equine ,-casein was determined by tryptic hydrolysis and MS of peptides released and by MS of the protein treated by alkaline phosphatase. The molecular mass found for the apo-form of Haflinger mare's ,-casein (25,514 ± 3,Da) was close to the theoretical mass of the reported sequence (GenBank,AAG43954) modified by insertion of a region (residues,27,34) encoded by an exon sometimes out-spliced (25,511.40,Da). Hence, the ,-casein isolated from Haflinger mare's milk corresponded to a variant of 226,amino acid residues. The latter was composed by highly multi-phosphorylated isoforms with three to seven phosphate groups, and pIs, determined by 2-DE, ranging from 4.74 to 5.30. Moreover, the equine ,-casein was able to deamidate spontaneously, at the level of Asn in the potential deamidation motif 135Asn-Gly136. Approximately 80% of the protein was deamidated after 96,h of incubation under physiological conditions. [source] Prognostic factors of tracheobronchial mucoepidermoid carcinoma,15 years experienceRESPIROLOGY, Issue 2 2008Chien-Hung CHIN Background and objectives: Mucoepidermoid carcinoma of the tracheobronchial tree is a rare tumour which displays a variable degree of clinical aggressiveness and malignancy. The relationship between the patient's prognosis and the tumour's histological features and clinical behaviour is uncertain. The aim of this study was to identify the clinicopathological features and analyse the outcomes of patients with this type of cancer. Methods: A retrospective analysis of the medical records of patients diagnosed with mucoepidermoid carcinoma of the lung between 1991 and 2006 was conducted. Results: The study comprised 15 patients. Higher histological grade tumours had a higher proportion of squamoid cells (P = 0.019); the tumours of patients with lymph node metastases also had a higher proportion of squamoid cells than did the tumours of patients without lymph node metastases (P = 0.015). Patients with early stage tumours (stage IA, IB, IIB) had better outcomes (10-year survival rate = 87.5%), than did patients with late-stage tumours (stage IIIB, IV) (1-year survival rate = 28.6%; 2-year survival rate = 0%, P = 0.001). Patients with lower-grade tumours (grade 1 and grade 2) had better outcomes (1-year survival rate = 80%; 5-year survival rate = 57.1%) than did patients with higher-grade tumours (grade 3) (1-year survival rate = 20%, P = 0.035). Tumour staging was a significant independent predictor of survival on Cox proportional hazards analysis. Conclusions: The proportion of squamoid cells on tumour histology may be an indicator of the level of tumour malignancy. Tumour, node, metastasis staging is a significant determinant of prognosis in patients with tracheobronchial mucoepidermoid carcinoma. [source] An unexpected co-crystal with a variable degree of order: 1:1 rac -1,2-cyclohexanediol/triphenylphosphine oxideACTA CRYSTALLOGRAPHICA SECTION B, Issue 6 2007Maxime A. Siegler A 1:1 co-crystal of rac - trans -1,2-C6H10(OH)2 and (C6H5)3PO has been found that is unusual because there are no strong interactions between the two kinds of molecules, which are segregated into layers. Furthermore, neither pure rac -1,2-cyclohexanediol (CHD) nor pure triphenylphosphine oxide (TPPO) has any obvious packing problem that would make the formation of inclusion complexes likely. The TPPO layers are very much like those found in two of the four known polymorphs of pure TPPO. The hydrogen-bonded ribbons of CHD are similar to those found in other vic -diol crystals. The co-crystals are triclinic (space group P), but the deviations from monoclinic symmetry (space group C2/c) are small. The magnitudes of those deviations depend on the solvent from which the crystal is grown; the deviations are largest for crystals grown from acetone, smallest for crystals grown from toluene, and intermediate for crystals grown from ethanol. The deviations arise from incomplete enantiomeric disorder of the R,R and S,S diols; this disorder is not required by symmetry in either space group, but occupancy factors are nearly 0.50 when the structure is refined as monoclinic. When the structure is refined as triclinic the deviations of the occupancy factors from 0.50 mirror the deviations from monoclinic symmetry because information about the partial R,R/S,S ordering is transmitted from one diol layer to the next through the very pseudosymmetric TPPO layer. Analyses suggest individual CHD layers are at least mostly ordered. The degree of order seems to be established at the time the crystal is grown and is unlikely to change with heating or cooling. Thermal data suggest the existence of the co-crystal is a consequence of kinetic rather than thermodynamic factors. [source] Leukocyte cDNA Analysis of NSD1 Derived from Confirmed Sotos Syndrome PatientsANNALS OF HUMAN GENETICS, Issue 6 2007M. Duno Summary Background: Haploinsufficiency of the NSD1 gene leads to Sotos syndrome (Sos), which is characterised by excessive growth, especially during childhood, distinct craniofacial features and variable degree of mental impairment. A wide spectrum of NSD1 mutations have been described in Sos patients, ranging from more than 100 different single nucleotide changes, to partial gene deletions, and to microdeletions of various sizes comprising the entire NSD1 locus. Objective: To investigate the NSD1 cDNA sequence in genetically confirmed Sos patients harbouring truncating and missense mutations. Method: Total RNA was isolated from a 250 ,l standard EDTA blood sample from nine genetically verified Sos patients, and subsequent reverse-transcribed into cDNA followed by PCR and direct sequencing of specific NSD1 cDNA sequences. Results: All nine mutations, including missense, nonsense and whole exon deletions, previously identified in genomic DNA, could confidently be detected in cDNA. Several NSD1 transcript splice variants were detected. Conclusion: Despite the fact that Sos is caused by haploinsufficiency, NSD1 transcripts containing nonsense and frame shift mutations can be detected in leukocyte-derived cDNA. The possibility therefore exists that certain NSD1 mutations are expressed and contribute to the phenotypic variability of Sos. NSD1 cDNA analysis is likely to enhance mutation detection in Sos patients. [source] Antioxidant Activity of Newly Synthesized 2,7-DiazaphenothiazinesARCHIV DER PHARMAZIE, Issue 5 2010Beata Morak-M, odawska Abstract A series of 19 derivatives of 2,7-diazaphenothiazine was synthesized and evaluated for their antioxidant activity bearing in mind the structural similarity with "classical" phenothiazines several of which are considered powerful antioxidants. Among the new derivatives that inhibited in vitro Fe2+/ascorbate-induced lipid peroxidation of rat liver microsomal membranes, several exhibited significant antioxidant activity with IC50 values in the range of 64,125 ,M. Although N -substitution led to a variable degree of antioxidant activity, the latter appears to correlate with the lipophilicity (expressed as clogP values) of the substituted derivatives. Reduced lipophilicity may also explain the relatively lower protection offered by these derivatives against lipid peroxidation when compared to their "classical" phenothiazine counterparts. Thus, modification of the phenothiazine structure by a substitution of two benzene rings with pyridine rings to form this new type of azaphenothiazines does not enhance antioxidant activity, although it retains it. [source] Synthesis and Biological Evaluation of Some Novel Polysubstituted Pyrimidine Derivatives as Potential Antimicrobial and Anticancer AgentsARCHIV DER PHARMAZIE, Issue 5 2009Sherif A. F. Rostom Abstract Synthesis and evaluation of the antimicrobial and cytotoxic activity of two series of polysubstituted pyrimidines comprising the thioether functionality and other pharmacophores, reported to contribute to various chemotherapeutic activities are described. All newly synthesized compounds were subjected to in-vitro antibacterial and antifungal screening. Out of the compounds tested, 18 derivatives displayed an obvious inhibitory effect on the growth of the tested Gram-positive and Gram-negative bacterial strains, with special effectiveness against the Gram-positive strains. Compounds 1, 2, 6, 7, 9, 10, 11, 21, and 24 revealed remarkable broad antibacterial spectrum profiles. Among those, compounds 1, 2, 6, 7, 9, and 24 exhibited an appreciable antifungal activity against C. albicans. Compound 2 proved to be the most active antimicrobial member identified here as it showed twice the activity of ampicillin against B. subtilis and the same activity of ampicillin against M. Luteus and P. aeruginosa together with a moderate antifungal activity. Further, eleven analogs were evaluated for their in-vitro cytotoxic potential utilizing the standard MTT assay against a panel of three human cell lines: breast adenocarcinoma MCF7, hepatocellular carcinoma HePG2, and colon carcinoma HT29. The obtained data revealed that six of the tested compounds 1, 3, 7, 12, 13, and 15 showed a variable degree of cytotoxic activity against the tested cell lines at both the LC50 and LC90 levels. Compound 7 proved to be the most active cytotoxic member in this study with special effectiveness against the colon carcinoma HT29 and breast cancer MCF7 human cell lines for LC50 and LC90. Thus, compounds 1 and 7 could be considered as possible dual antimicrobial-anticancer agents. [source] The management of low-flow priapism with the immediate insertion of a penile prosthesisBJU INTERNATIONAL, Issue 9 2002R.W. Rees Objective ,To evaluate the outcome of patients undergoing the immediate insertion of a penile prosthesis as a treatment for acute low-flow priapism. Patients and methods ,Eight patients presenting with low-flow priapism with a mean duration of 91 h (range 32,192) were prospectively evaluated. All had failed conservative management with the instillation of ,-adrenergic agents, and four had already undergone shunt procedures elsewhere. Immediate management consisted of the insertion of a malleable prosthesis in six patients and an inflatable prosthesis in two. One of the malleable prostheses was subsequently changed to an inflatable device. Results ,There were no early complications, with all patients being satisfied with the end result, and seven having sexual intercourse. One patient developed a penile deformity after surgery, cause by fibrosis around one inflatable cylinder. All patients have maintained their penile length. Conclusions ,Prolonged low-flow priapism results in a variable degree of cavernosal fibrosis and a subsequent loss of penile length. The delayed insertion of a penile prosthesis can be difficult, with high complication rates. The immediate insertion of a penile prosthesis in patients with prolonged low-flow priapism is simple and maintains penile length. This should always be offered to the patient at initial presentation, as the complication rate is low and the subsequent outcome excellent. [source] Treatment of pruritus by capsaicin in a patient with pityriasis rubra pilaris receiving RE-PUVA therapyCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2000Clinical dermatology, Concise report Pityriasis rubra pilaris (PRP) is characterized by redness of the skin, scaling and a variable degree of pruritus. We present a patient with extremely itchy PRP successfully treated with oral retinoids and photochemotherapy with 8-methoxypsoralene (RE-PUVA) and topical capsaicin. The PRP-related pruritus which clearly preceded photochemotherapy and for which no other cause was apparent was relieved with capsaicin. This single case report provides evidence that topical capsaicin may be a useful therapeutic option in treating PRP-associated pruritus where antihistamines have been unsuccessful. [source] Expression of constructs of the neuronal isoform of myosin-Va interferes with the distribution of melanosomes and other vesicles in melanoma cellsCYTOSKELETON, Issue 2 2002João Carlos da Silva Bizario Abstract Myosin-Va has been implicated in melanosome translocation, but the exact molecular mechanisms underlying this function are not known. In the dilute, S91 melanoma cells, melanosomes move to the cell periphery but do not accumulate in the tips of dendrites as occurs in wild-type B16 melanocytes; rather, they return and accumulate primarily at the pericentrosomal region in a microtubule-dependent manner. Expression of the full-length neuronal isoform of myosin-Va in S91 cells causes melanosomes to disperse, occupying a cellular area approximately twice that observed in non-transfected cells, suggesting a partial rescue of the dilute phenotype. Overexpression of the full tail domain in S91 cells is not sufficient to induce melanosome dispersion, rather it causes melanosomal clumping. Overexpression of the head and head-neck domains of myosin-Va in B16 cells does not alter the melanosome distribution. However, overexpression of the full tail domain in these cells induces melanosome aggregation and the appearance of tail-associated, aggregated particles or vesicular structures that exhibit variable degrees of staining for melanosomal and Golgi ,-COP markers, as well as colocalization with the endogenous myosin-Va. Altogether, the present data suggest that myosin-Va plays a role in regulating the direction of microtubule-dependent melanosome translocation, in addition to promoting the capture of melanosomes at the cell periphery as suggested by previous studies. These studies also reinforce the notion that myosin-V has a broader function in melanocytes by acting on vesicular targeting or intracellular protein trafficking. Cell Motil. Cytoskeleton 51:57,75, 2002. © 2002 Wiley-Liss, Inc. [source] Assessing the relationship between forest types and canopy tree beta diversity in AmazoniaECOGRAPHY, Issue 4 2010Thaise Emilio Planning of conservation priorities has often taken mapped forest types as surrogates for biological complementarity. In the Brazilian Amazon, these exercises have given equal weight to each forest type as if they were all equally distinct. Here, we examine floristic similarity between forest types to assess the reliability of vegetation maps as a surrogate for canopy tree-community composition. We analyzed floristic differences at the genus level between twelve Amazonian forest types using 1184 one-hectare inventories of large trees with three complementary approaches. First, we compared a map of floristic composition, from a uni-dimensional NMDS ordination of the inventories, with a map of coarser-level forest types commonly recognized as distinct by classification systems across Amazonia. Using Mantel and means-difference tests, we next examined the distance-decay of floristic similarity for all paired samples and for the pairs drawn from within and between twelve more finely divided forest types. Finally, we examined the degree of floristic separation of each pair of the twelve forest types using non-parametric analysis of variance. Maps of floristic composition and coarse-level forest types were highly congruent. At the finer level of classification, similarity was only slightly higher when pairs were drawn from the same versus from different forest types. This was true for all geographic distances. Nonetheless, eighty percent of the 66 paired combinations of forest types were significantly different in the unreduced genus-space and nearly half showed little or no overlap in a two-dimensional ordination. Three types were most distinct from all others: white sand, seasonally dry, and bamboo-dominated forests. Here, we show that forest types exhibit variable degrees of separation. For this reason, treating all fine-level forest types as equally distinct results in poor representation of canopy tree beta diversity. We recommend explicitly considering the degree of floristic separation between all forest types , as presented here for Amazonian flora , as a way to improve the use of this biodiversity surrogate. [source] Development of renal bone diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2006A. Ferreira Abstract Renal osteodystrophy (ROD) develops as the early stages of chronic renal failure (CRF) and covers a spectrum of bone changes observed in the uraemic patient, which extend from high remodelling bone disease (frequently known as osteitis fibrosa) to low turnover, or adynamic disease. Between these two extremes there are also cases of bone mineralization compromised in variable degrees, as is the case of ,mixed bone disease' and osteomalacia. The dynamic process of bone remodelling is compromised in CRF, and a positive or negative bone balance can be observed in uraemic patients. In addition to the classic modulators of bone remodelling, like parathyroid hormone, calcitriol and calcitonin, other factors were recently identified as significant modulators of osteoblast and osteoclast activation in uraemic patients. In fact, different cytokines and growth factors, acting at an autocrine or paracrine level, seem to play a relevant role in the bone and mineral changes observed in uraemia. Recently, observations have been made of the development of more sensitive and specific techniques to assay different biochemical markers of bone turnover and mineral metabolism. Analogously, new contributions of conventional bone histology, bone immunocytochemistry and molecular biology, which enabled the understanding of some etiopathogenic mechanisms of ROD, were observed. [source] De novo mutations in monilethrixEXPERIMENTAL DERMATOLOGY, Issue 6 2003Liran Horev Abstract: Mutations in the hair keratins hHb1 and hHb6 have been recently reported to cause monilethrix, an autosomal dominant hair shaft disorder, characterized by variable degrees of hair fragility and follicular hyperkeratosis. We found 10 families with monilethrix in which the parents were not clinically affected, and sequenced the hair keratin hHb1, hHb3 and hHb6 genes in seven patients. In five patients no mutations were found, while in two patients we identified de novo germline missense mutations at the helix termination motif: E402K (hHb6) and E413K (hHb1). [source] Dynamics of in vitro acquisition of resistance by Candida parapsilosis to different azolesFEMS YEAST RESEARCH, Issue 4 2009Ana Teresa Pinto e Silva Abstract Candida parapsilosis is a common isolate from clinical fungal infectious episodes. Resistance of C. parapsilosis to azoles has been increasingly reported. To analyse the development of resistance in C. parapsilosis, four azole-susceptible clinical strains and one American Type Culture Collection type strain were cultured in the presence of fluconazole, voriconazole and posaconazole at different concentrations. The isolates developed variable degrees of azole resistance according to the antifungal used. Fluconazole was the fastest inducer while posaconazole was the slowest. Fluconazole and voriconazole induced resistance to themselves and each other, but not to posaconazole. Posaconazole induced resistance to all azoles. Developed resistance was stable; it could be confirmed after 30 days of subculture in drug-free medium. Azole-resistant isolates revealed a homogeneous population structure; the role of azole transporter efflux pumps was minor after evaluation by microdilution and cytometric assays with efflux pump blockers (verapamil, ibuprofen and carbonyl cyanide 3-chloro-phenylhydrazone). We conclude that the rapid development of azole resistance occurs by a mechanism that might involve mutation of genes responsible for ergosterol biosynthesis pathway, stressed by exposure to antifungals. [source] Growth and albitization of K-feldspar in crystalline rocks in the shallow crust: a tracer for fluid circulation during exhumation?GEOFLUIDS (ELECTRONIC), Issue 2 2003M. B. Holness Abstract A general feature of medium- to coarse-grained, sheet-silicate bearing, quartzo-feldspathic rocks of either metamorphic or igneous affinity is the retrograde development of lenses of pure K-feldspar at the grain boundaries between sheet silicate (0 0 1) faces and original feldspar grains. The growth of these lenses acts to displace and deform the sheet silicate grain by a force of crystallization, although the substrate feldspar and adjacent quartz are not deformed. Subsequent to the growth of the lenses they are replaced to variable degrees by pure albite, which grows into the lens from the substrate feldspar behind an irregular replacement front. The composition and texture of both K-feldspar and replacive albite suggest a strong affinity with authigenic feldspars, although it is considered likely that the K-feldspar of the lenses is derived from low-temperature biotite-breakdown reactions. A model is proposed whereby the lenses grow into open pores at dilatant sites in response to infiltration of aqueous fluids as the crystalline rocks are exhumed under brittle conditions. Continued circulation of infiltrating fluids in a temperature gradient results in the replacement of K-feldspar by albite via an alkali exchange process. The lenses point to a significant grain-scale permeability in crystalline rock at shallow levels in the crust. [source] A geometric morphometric study of regional differences in the ontogeny of the modern human facial skeleton,JOURNAL OF ANATOMY, Issue 3 2002Una Strand Viðarsdóttir Abstract This study examines interpopulation variations in the facial skeleton of 10 modern human populations and places these in an ontogenetic perspective. It aims to establish the extent to which the distinctive features of adult representatives of these populations are present in the early post natal period and to what extent population differences in ontogenetic scaling and allometric trajectories contribute to distinct facial forms. The analyses utilize configurations of facial landmarks and are carried out using geometric morphometric methods. The results of this study show that modern human populations can be distinguished based on facial shape alone, irrespective of age or sex, indicating the early presence of differences. Additionally, some populations have statistically distinct facial ontogenetic trajectories that lead to the development of further differences later in ontogeny. We conclude that population-specific facial morphologies develop principally through distinctions in facial shape probably already present at birth and further accentuated and modified to variable degrees during growth. These findings raise interesting questions regarding the plasticity of facial growth patterns in modern humans. Further, they have important implications in relation to the study of growth in the face of fossil hominins and in relation to the possibility of developing effective discriminant functions for the identification of population affinities of immature facial skeletal material. Such tools would be of value in archaeological, forensic and anthropological applications. The findings of this study underline the need to examine more deeply, and in more detail, the ontogenetic basis of other causes of craniometric variation, such as sexual dimorphism and hominin species differentiation. [source] Focal Atrial Fibrillation: Experimental Evidence for a Pathophysiologic Role of the Autonomic Nervous SystemJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2001PATRICK SCHAUERTE M.D. Focal AF and Autonomic Nerves.Introduction: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high-frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports. Methods and Results: In 21 mongrel dogs, local high-frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing highfrequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high-frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13 ± 8 V and AT/AF at 15 ± 9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19 ± 6 V and AT/AF at 26 ± 6 V (P < 0.01; n = 12). High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical stimulation was blunted or prevented after beta-receptor blockade and abolished by atropine. In vitro, high-frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89 ± 35 msec to 60 ± 22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolarizations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine. Conclusion: High-frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high-frequency electrical stimulation were caused by autonomic nerve stimulation. [source] A physiological interpretation of pattern changes in a flatfishJOURNAL OF FISH BIOLOGY, Issue 3 2008D. Burton The pattern-related capacity for the dispersion of previously aggregated melanosomes in low concentrations (3 × 10,6 to 10,8 M) of noradrenaline in vitro was observed in melanophores from winter flounder Pseudopleuronectes americanus. With 10,8 M noradrenaline, dispersion was completed more rapidly than in controls using the incubation vehicle alone. Melanophores from white-spot, dark-band and general background components of the integumentary pattern displayed different ,transition ranges' between melanosome aggregation and dispersion in higher and lower concentrations of noradrenaline. Within each ,transition range' individual noradrenaline concentration decrements could result in highly variable degrees of melanosome dispersion. The relative breadth of the noradrenaline ,transition range' concentrations could be represented as dark bands > general background > white spots. The threshold noradrenaline concentration for dispersion was highest for the dark bands. It is concluded that these differences represent variations in the transition from melanophore ,-adrenoceptor-mediated pigment aggregation to ,-adrenoceptor-mediated dispersion between localized areas of the skin. Such variations in ,transition range' will have an important role in the expression of flatfish patterns and in their changes in colour and texture. [source] EFFECTS OF COOKING AND DRYING PROCESSES ON PHYSICAL, CHEMICAL AND SENSORY PROPERTIES OF LEGUME BASED BULGURJOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 5 2009NERMIN BILGIÇLI ABSTRACT The changes in physical, chemical and sensory properties of common bean (CB) and chickpea (CP) bulgur prepared with different cooking (atmospheric, pressure and microwave) and drying (oven at 60, 70 and 80C; microwave at 350 and 700 W) processes were investigated. Neither the cooking methods nor the drying methods significantly affected the ash and protein contents of CB and CP bulgur. Pressure cooking gave lower phytate phosphorus and higher bulgur yield and volume increase values when compared to the other cooking methods. Average bulgur yields were found as 82% for CB and 84% for CP. Cooking processes decreased the phytic acid content of the bulgurs between 25.2 and 39.5% according to raw legume. Ca, K, Mg, P, Zn, Cu and Fe contents of the bulgurs decreased in variable degrees (8.69,28.5%) when compared to raw materials. Pressure cooked and oven (80C) dried bulgur samples in the case of bulgur pilaf were appreciated by the panelists in terms of overall acceptability. PRACTICAL APPLICATIONS Bulgur is a valuable cereal product with its high nutritional value and long shelf life. In this research, bulgur process was applied successfully on common bean and chickpea, and new legume-based bulgur products improved. The bulgur yield (BY) of the legumes was above 80%. Pressure cooking increased the nutritional, sensory and technological quality of the legume bulgurs. [source] Smoothing that does not blur: Effects of the anisotropic approach for evaluating diffusion tensor imaging data in the clinicJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2010Marta Moraschi MS Abstract Purpose: To compare the effects of anisotropic and Gaussian smoothing on the outcomes of diffusion tensor imaging (DTI) voxel-based (VB) analyses in the clinic, in terms of signal-to-noise ratio (SNR) enhancement and directional information and boundary structures preservation. Materials and Methods: DTI data of 30 Alzheimer's disease (AD) patients and 30 matched control subjects were obtained at 3T. Fractional anisotropy (FA) maps with variable degrees and quality (Gaussian and anisotropic) of smoothing were created and compared with an unsmoothed dataset. The two smoothing approaches were evaluated in terms of SNR improvements, capability to separate differential effects between patients and controls by a standard VB analysis, and level of artifacts introduced by the preprocessing. Results: Gaussian smoothing regionally biased the FA values and introduced a high variability of results in clinical analysis, greatly dependent on the kernel size. On the contrary, anisotropic smoothing proved itself capable of enhancing the SNR of images and maintaining boundary structures, with only moderate dependence of results on smoothing parameters. Conclusion: Our study suggests that anisotropic smoothing is more suitable in DTI studies; however, regardless of technique, a moderate level of smoothing seems to be preferable considering the artifacts introduced by this manipulation. J. Magn. Reson. Imaging 2010;31:690,697. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||