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MM
Kinds of MM Terms modified by MM Selected AbstractsModeling dioxygen binding to the non-heme iron-containing enzymesINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 10 2006A. V. Nemukhin Abstract The structures and properties of the complexes formed upon binding the oxygen molecule to the iron sites in non-heme 2-oxoglutarate-dependent enzymes are characterized by QM(CASSCF)/MM and density functional theory (DFT) calculations. Molecular models for the calculations are constructed following the crystal structure of hypoxia-inducible factor asparaginyl hydroxylase (FIH-1). DFT calculations for the 37-atomic cluster have been carried out at the B3LYP(LANL2DZdp) level. The flexible effective fragment potential method is used as a combined quantum mechanical,molecular mechanical (QM/MM) technique to characterize the fragment of the enzymatic system, including 1,758 atoms in the MM part and 27 atoms in the QM part. In these calculations, the CASSCF(LANL2DZdp) approach is applied in the QM subsystem, and AMBER force field parameters are used in the MM subsystem. With both approaches, equilibrium geometry configurations have been located for different spin states of the system. In DFT calculations, the order of the states is as follows: septet, triplet (+7.7 kcal/mol), quintet (+10.7 kcal/mol). Geometry configurations correspond to the end-on structures with no evidences of electron transfer from Fe(II) to molecular oxygen. In contrast, QM(CASSCF)/MM calculations predict the quintet state as the lowest one, while the septet structure has slightly (<2 kcal/mol) higher energy, and the triplet state is considerably more energetic. In QM/MM calculations, in both quintet and septet states, the electronic configurations show considerable electron charge transfer from iron to oxygen, and the oxidation state of iron in the metal binding site can be characterized as Fe(III). © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006 [source] Comparison of BrdU and cyclin A as markers of the S-phase in oral precancerous lesionsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2000Richard J. Oliver Abstract: A study comparing bromodeoxyuridine (BrdU) and cyclin A as markers of cells in the S-phase in oral precancerous lesions was performed. These were also compared with the growth fraction (GF) as assessed by Ki-67. Biopsies of 15 lesions were obtained, presenting clinically as leukoplakia or erythroplakia of the lateral tongue or floor of mouth. Half of each biopsy was incubated in BrdU and routinely fixed and processed. Sequential sections from each block were cut and stained immunohistochemically with antibodies against the following proteins: BrdU, Ki-67 and cyclin A. Stained sections were quantified and the labelling indices (LI) expressed per 100 of the total nucleated cell population (%) and per millimetre basement length (/mm). The mean LI% for BrdU was 11.24% (SD 2.83), for cyclin A it was 12.76% (SD 3.88) and the GF% was 29.25% (SD 11.88). The mean LI/mm for BrdU was 40.93/mm (SD 11.88), for cyclin A it was 47.59/mm (SD 18.28) and the GF/mm was 110.72/mm (SD 49.30). The BrdU and cyclin A indices were significantly correlated with each other. In the more dysplastic cases, the cyclin A LI was quantitatively much larger than that for BrdU, suggesting that the protein was being overexpressed. It was concluded that as a tool to study the kinetic aspects of the cell cycle in dysplastic lesions cyclin A was limited by the fact that it is overexpressed. In minimally dysplastic lesions and normal epithelia, however, cyclin A may be a viable alternative to BrdU for the study of the S-phase. [source] Preparation and Characterization of a Tin Pentacyanonitrosylferrate-Modified Carbon Ceramic Electrode: Application to Electrocatalytic Oxidation and Amperometric Detection of L -CysteineELECTROANALYSIS, Issue 7 2009H. Razmi Abstract The sol-gel technique was used to construct tin pentacyanonitrosylferrate (SnPCNF) modified composite carbon ceramic electrode (CCE). This involves two steps: construction of CCE containing metallic Sn powder and then electrochemical creating of SnPCNF on the surface of CCE. The SnPCNF modified CCE (SnPCNFlCCE) was characterized by energy-dispersive X-ray (EDX), FTIR and cyclic voltammetry (CV) techniques. The SnPCNF film showed electrocatalytic activity toward the oxidation of L -cysteine. A linear calibration plot was obtained over the L -cysteine concentration range 1,51,,M using chronoamperometry. L -cysteine was determined amperometrically at the surface of this modified electrode. The detection limit (for a signal to noise of 3) and sensitivity were found to be 0.62,,M and 126,,A/mM, respectively. [source] Theoretical Study on Co3+ in Aqueous Solution in Terms of ABEEM/MM ModelCHINESE JOURNAL OF CHEMISTRY, Issue 6 2007Qing-Mei Guan Abstract A detailed theoretical investigation on Co3+ hydration in aqueous solution has been carried out by means of molecular dynamics (MD) simulations based on the atom-bond electronegativity equalization method fused into molecular mechanics (ABEEM/MM). The effective Co3+ ion-water potential has been constructed by fitting to ab initio structures and binding energies for ionic clusters. And then the ion-water interaction potential was applied in combination with the ABEEM-7P water model to molecular dynamics simulations of single Co3+(aq.) solution, managing to reproduce many experimental structural and dynamical properties of the solution. Here, not only the common properties (radial distribution function, angular distribution function and solvation energy) obtained for Co3+ in ABEEM-7P water solution were in good agreement with those from the experimental methods and other molecular dynamics simulations but also very interesting properties of charge distributions, geometries of water molecules, hydrogen bond, diffusion coefficients, vibrational spectra are investigated by ABEEM/MM model. [source] A new task scheduling method for distributed programs that require memory managementCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 9 2006Hiroshi Koide Abstract In parallel and distributed applications, it is very likely that object-oriented languages, such as Java and Ruby, and large-scale semistructured data written in XML will be employed. However, because of their inherent dynamic memory management, parallel and distributed applications must sometimes suspend the execution of all tasks running on the processors. This adversely affects their execution on the parallel and distributed platform. In this paper, we propose a new task scheduling method called CP/MM (Critical Path/Memory Management) which can efficiently schedule tasks for applications requiring memory management. The underlying concept is to consider the cost due to memory management when the task scheduling system allocates ready (executable) coarse-grain tasks, or macro-tasks, to processors. We have developed three task scheduling modules, including CP/MM, for a task scheduling system which is implemented on a Java RMI (Remote Method Invocation) communication infrastructure. Our experimental results show that CP/MM can successfully prevent high-priority macro-tasks from being affected by the garbage collection arising from memory management, so that CP/MM can efficiently schedule distributed programs whose critical paths are relatively long. Copyright © 2005 John Wiley & Sons, Ltd. [source] A PM3/d specific reaction parameterization for iron atom in the hydrogen abstraction catalyzed by soybean lipoxygenase-1JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2007Ismael Tejero Abstract This paper reports a specific reaction parameter (SRP) PM3/d model for iron that can reproduce the DFT/MM results of the hydrogen abstraction reaction from the C11 position of linoleic acid by the Soybean lipoxygenase-1 enzyme. A suite of nonlinear optimization methods is outlined for semiempirical parameter development based on integrated evolutionary (genetic) and direction set minimization algorithms. The PM3/d-SRP Fe parameters are derived along three consecutive steps. The final parameterization step includes the effect of the whole enzyme in order to get a better quantum mechanical/molecular mechanical description. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [source] The interplay between experiment and theory in charge-density analysisACTA CRYSTALLOGRAPHICA SECTION A, Issue 5 2004Philip Coppens The comparison of theory and experiment remains a cornerstone of scientific inquiry. Various levels of such comparison applicable to charge-density analysis are discussed, including static and dynamic electron densities, topological properties, d -orbital occupancies and electrostatic moments. The advantages and drawbacks of the pseudoatom multipole are discussed, as are the experimentally constrained wavefunctions introduced by Jayatilaka and co-workers, which combine energy minimization with the requirement to provide a reasonable fit to the X-ray structure factors. The transferability of atomic densities can be exploited through construction of a pseudoatom databank, which may be based on analysis of ab initio molecular electron densities, and can be used to evaluate a host of physical properties. Partitioning of theoretical energies with the Morokuma,Ziegler energy decomposition scheme allows direct comparison with electrostatic interaction energies obtained from electron densities represented by the pseudoatom formalism. Compared with the Buckingham expression for the interaction between non-overlapping densities, the agreement with theory is much improved when a newly developed hybrid EP/MM (exact potential/multipole model) method is employed. [source] In Vivo Study of Wound Bursting Strength and Compliance of Topical Skin AdhesivesACADEMIC EMERGENCY MEDICINE, Issue 12 2008Adam J. Singer MD Abstract Objectives:, Over the past decade, the use of topical skin adhesives (TSA) for wound closure has increased. Among TSA characteristics, strength and flexibility are most important. Prior studies have compared the wound bursting strengths (WBSs) of the cyanoacrylates immediately after wound closure. In this study the authors compared the WBS and flexibility of multiple TSAs immediately and up to 2 days after closure. Methods:, This was a controlled animal experiment. Two-centimeter incisions were created on both sides of 210 Sprague-Dawley rats and randomly closed with one of five commercially available TSAs (Dermabond [D], Indermil [I], Histoacryl [H], Liquiband [L], or GluStitch [G]). WBS and TSA flexibility were measured using the BTC-2000 device immediately after closure and at 1 and 2 days after closure. WBS and TSA flexibility were compared across groups with analysis of variance (ANOVA). Results:, Wound bursting strengths were higher (p < 0.05) at 0, 1, and 2 days for D (274, 388, 232 mm Hg) than for all other TSAs (I 182, 225, and 107; H 189, 214, and 69; L 146, 118, and 75; or G 161, 150, and 73). TSA flexibility was also greater (p < 0.05) at 0, 1, and 2 days for D (36, 27, and 29 mm Hg/mm) than for all other TSAs (I 18, 14, and 12; H 18, 13, and 15; L 19, 14, and 12; G 26, 23, and 18). Conclusions:, The octyl-cyanoacrylate,based adhesive is significantly stronger and more flexible than all the butyl-cyanoacrylate,based adhesives at 0, 1 and 2 days after closure. [source] G1 cyclins in oral epithelial dysplasiaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 2 2001R. J. Oliver Abstract: The G1 cyclins, D1, D3 and E, were investigated in 38 lesions of oral epithelial dysplasia from the floor of the mouth or the lateral border of the tongue. Their immunohistochemical expression was observed and compared with that of Ki-67 and with the degree of dysplasia assessed by the semi-objective technique of Smith & Pindborg. Antibody labelled cells were quantified and expressed as a percentage (LI%) of the total nucleated cell population and per mm basement membrane length (LI/mm). The labelling indices of all of the antibodies were high and quantitatively similar. There were no significant correlations with the degree of dysplasia assessed by the atypia scores. There was a correlation between labelling indices for the various antibodies expressed as LI/mm but little correlation between the indices expressed as LI%. The distribution of the D cyclins was similar to that of Ki-67 with relatively few of the basal cells demonstrating immunoreactivity. The reasons for this are discussed in the paper. Some cross-reactivity was observed with the cyclin antibodies. We conclude that the antibodies against the cyclins used in the present study are not a useful adjunct in the study of the cell kinetics of oral epithelial dysplasia. [source] Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction,CLINICAL TRANSPLANTATION, Issue 1 2005Kadriye Reis Abstract:, Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. [source] Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders,CYTOMETRY, Issue 4 2010Bruno Paiva Abstract In recent years, multiparameter flow cytometry (MFC) immunophenotyping has become mandatory in the clinical management of hematological malignancies, both for diagnostic and monitoring purposes. Multiple myeloma (MM) and other clonal plasma cell-related (PC) disorders should be no exception to this paradigm, but incorporation of immunophenotypic studies in the management of patients with PC disorders is still far from being routinely established in many diagnostic flow cytometry laboratories. For clonal PC disorders, MFC is of clear and established clinical relevance in: (1) the differential diagnosis between MM and other PC-related disorders; (2) the identification of high-risk MGUS and smoldering MM; (3) minimal residual disease investigation after therapy; additionally it may also be useful for (4) the definition of prognosis-associated antigenic profiles; and (5) the identification of new therapeutic targets. In this article, we review the clinical value of MFC in the study of PC disorders, with specific emphasis in those areas where consensus exists on the need to incorporate MFC into routine evaluation of MM and other clonal PC-related disorders. © 2010 Clinical Cytometry Society [source] Twenty-five-year course and outcome in anxiety and depression in the Upper Bavarian Longitudinal Community StudyACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010M. M. Fichter Fichter MM, Quadflieg N, Fischer UC, Kohlboeck G. Twenty-five-year course and outcome in anxiety and depression in the Upper Bavarian Longitudinal Community Study. Objective:, Assessment of 25-year course of pure and mixed anxiety and depression in a community sample. Method:, Participants were grouped into pure anxiety, pure depression, mixed anxiety and depression, and no anxiety or depressive syndrome at baseline. Assessments consisted of a: i) baseline survey, ii) 5-year follow-up, iii) 25-year follow-up. Self-rating scales as well as expert-rating interviews yielded data on social and psychopathological risk factors and outcome measures. Results:, Baseline prevalence for mixed anxiety and depressive syndrome was 8.7%. Subjects with combined anxiety and depressive syndrome were more predisposed towards later adverse mental health outcomes and reduced functionality. The transition from anxiety syndrome (pure and mixed) to depressive syndrome over the 25-year study is more likely than the reverse. Logistic regression analysis emphasized the impact of early anxiety syndromes on later depression. Conclusion:, Results underscore the long-term risks of suffering from a combined anxiety and depressive syndrome. [source] Electroconvulsive therapy is equally effective in unipolar and bipolar depressionACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010S. Bailine Bailine S, Fink M, Knapp R, Petrides G, Husain MM, Rasmussen K, Sampson S, Mueller M, McClintock SM, Tobias KG, Kellner CH. Electroconvulsive therapy is equally effective in unipolar and bipolar depression. Objective:, To determine the relative efficacy of electroconvulsive therapy (ECT) in the treatment of bipolar (BP) and unipolar (UP) depressive illness and clarify its role in BP depression. Method:, Patients referred for ECT with both UP and BP depressions. [classified by Structured Clinical Interview for DSM (SCID-I) criteria for history of mania] were included in a multi-site collaborative, double-masked, randomized controlled trial of three electrode placements , right unilateral, bifrontal or bitemporal , in a permutated block randomization scheme. Results:, Of 220 patients, 170 patients (77.3%) were classified as UP and 50 (22.7%) as BP depression in the intent-to-treat sample. The remission and response rates and numbers of ECT for both groups were equivalent. Conclusion:, Both UP and BP depressions remit with ECT. Polarity is not a factor in the response rate. In this sample ECT did not precipitate mania in depressed patients. Treatment algorithms for UP and BP depression warrant re-evaluation. [source] Indicators of pretreatment suicidal ideation in adults with major depressive disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010D. W. Morris Morris DW, Trivedi MH, Husain MM, Fava M, Budhwar N, Wisniewski SR, Miyahara S, Gollan JK, Davis LL, Daly EJ, Rush AJ. Indicators of pretreatment suicidal ideation in adults with major depressive disorder. Objective:, In order to evaluate the presence of treatment emergent suicidal ideation (SI), it becomes necessary to identify those patients with SI at the onset of treatment. The purpose of this report is to identify sociodemographic and clinical features that are associated with SI in major depressive disorder (MDD) patients prior to treatment with a selective serotonin reuptake inhibitor. Method:, This multisite study enrolled 265 out-patients with non-psychotic MDD. Sociodemographic and clinical features of participants with and without SI were compared post hoc. Results:, Social phobia, bulimia nervosa, number of past depressive episodes, and race were independently associated with SI by one or more SI measure. Conclusion:, Concurrent social phobia and bulimia nervosa may be potential risk factors for SI in patients with non-psychotic MDD. Additionally, patients with more than one past depressive episode may also be at increased risk of SI. [source] Definition and spatial annotation of the dynamic secretome during early kidney developmentDEVELOPMENTAL DYNAMICS, Issue 6 2006Gemma Martinez Abstract The term "secretome" has been defined as a set of secreted proteins (Grimmond et al. [2003] Genome Res 13:1350,1359). The term "secreted protein" encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants. Developmental Dynamics 235:1709,1719, 2006. © 2006 Wiley-Liss, Inc. [source] Functional gait comparison between children with myelomeningocele: shunt versus no shuntDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2007Simone Battibugli MD The aim of this study was to compare functional gait differences between patients with myelomeningocele (MM) who have a ventriculoperitoneal shunt (VPS) with those who do not. Our analyses were adjusted for confounding by age, lesion level, orthotic use, and assistive device use. The Functional Mobility Scale (FMS) was used to compare the shunted group (n=98; 60 males, 38 females; mean age 10y 2mo [SD 3y 11mo]; 73 sacral/19 low lumber/six high lumbar lesion level) with the non-shunted group (n=63; 32 males, 31 females; mean age 9y 11mo [SD 3y 11mo]; 45 sacral/12 low lumber/six high lumbar lesion level). Participants with a shunt had lower FMS 500 and FMS 50 scores compared with participants without a shunt; hence the participants without a shunt were more independent in their ambulation at medium and longer distances. For a subset of participants who underwent a three-dimensional gait analysis, we also collected temporal,spatial gait parameters (velocity, cadence, and stride length). Our results show that participants with MM and no shunt who underwent gait analysis(11 males, 10 females; mean age 9y 6mo [SD 4y]; 15 sacral/6 low lumber/0 high lumbar lesion level) tend to walk at a significantly greater velocity and stride length as compared with those with a shunt (33 males, 18 females; mean age 10y [SD 4y]; 38 sacral/13 low lumber/zero high lumbar lesion level). These data allow the treatment team to present more specific information regarding functional ambulatory expectations to patients with MM and their families. [source] Effusion cytomorphology and immunocytochemistry of malignant melanoma: Five cases of melanotic melanoma and one case of amelanotic melanomaDIAGNOSTIC CYTOPATHOLOGY, Issue 7 2009I.A.C., Katsuhide Ikeda C.T. Abstract Effusion cytological analyses of amelanotic malignant melanoma (AMM) are very rare and no concise description of AMM related cytomorphologic features using effusion have been reported. Here, we report the cytomorphological, immunohistochemical, and immunocytochemical findings in the effusion cytology of six cases of malignant melanoma (MM), one case of AMM, and five cases of melanotic malignant melanoma. Papanicolaou-stained smears exhibited conspicuous nucleoli, multinucleation, and cytoplasmic vacuolization in all of the MM cases. In addition, the AMM case displayed numerous mitotic figures and intranuclear cytoplasmic inclusions. With regard to the immunohistochemistry findings, all six cases of melanoma were positive for Melan-A/MART-1, HBME-1, and S-100. In the immunohistochemistry analyses, five of six cases of melanoma were positive for WT-1, as was the AMM specimen. Furthermore, because the effusion analysis of malignant mesothelioma proved positive for WT-1, it should be noted that WT-1 effusion analysis is not an appropriate means to distinguish between MM and malignant mesothelioma. We suggest that it is important to recognize cytomorphologic characteristics, such as melanin pigment, conspicuous nucleoli, multinucleation, and cytoplasmic vacuolization, and to choose appropriate antibodies for the correct diagnosis of MM in effusion. Diagn. Cytopathol., 2009. © 2009 Wiley-Liss, Inc. [source] Kallikrein 4 is expressed in malignant mesothelioma,Further evidence for the histogenetic link between mesothelial and epithelial cellsDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2007Ben Davidson M.D., Ph.D. Abstract The objective of this study was to analyze Kallikrein 4 protein (hK4) expression in effusions and solid tumors of patients diagnosed with malignant mesothelioma (MM) and compare hK4 expression in MM with that in breast and ovarian adenocarcinomas. Sections from 65 MM (21 effusions, 44 solid tumors) and 63 breast carcinomas (28 effusions, 35 solid tumors) were stained for hK4 using immunohistochemistry. Results were compared with our previously published data for 284 ovarian carcinomas (181 effusions, 103 solid tumors). Expression of hK4 was detected in 26/65 (40%) MM and 52/63 (83%) breast carcinomas. Ovarian carcinoma showed staining values that were comparable to those in breast carcinoma (expression of hK4 in 144/181; 80% effusions and 85/103; 83% solid tumors). As opposed to our previous findings in ovarian carcinoma, hK4 expression was higher in solid tumors when compared with to effusions in both MM (P = 0.013) and breast carcinoma (P = 0.002). Comparative analysis of the three tumor types showed significantly higher expression in ovarian and breast adenocarcinomas when compared with MM (P < 0.001). In conclusion, hK4 is frequently expressed in MM, with higher levels detected in solid tumors, although its expression is more limited than in gynecological adenocarcinomas. The presence of hK4 in MM, a non-hormonally regulated tumor, provides further support to the histogenetic link between mesothelial and epithelial cells. Diagn. Cytopathol. 2007;35:80,84. © 2007 Wiley-Liss, Inc. [source] The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvementDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2006Ph.D., Reda S. Saad M.D. Abstract Differentiating malignant mesothelioma (MM) from pulmonary carcinoma in pleural fluid cytology can be challenging. Recent studies have suggested that D2-40, a novel lymphatic marker, may be a useful marker for mesothelial differentiation in surgical specimens. However, there are no available data regarding its utility in effusion cytology specimens. We investigated the utility of D2-40 in pleural fluid cytology in differentiating MM from pulmonary carcinomas. Twenty cases of pleural effusion smears of surgically confirmed MM with their corresponding cell blocks were retrieved from the database of the hospital computer system. We also included 10 cases of metastatic pulmonary adenocarcinoma (PA) and 10 cases metastatic pulmonary squamous cell carcinoma (PSCC) involving the pleural fluid. Cell blocks were formalin-fixed, paraffin embedded, and immunostained for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40. Cases were scored as negative (<5% positivity) or positive (>5% moderate/strong positivity). The positive rates for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40 were as follows: MM (0/20), (0/20), (17/20), (18/20), (19/20), (17/20), for PA (8/10), (0/10), (3/10), (0/10), (0/10), (0/10), and for PSCC (1/10), (10/10), (6/10), (10/10), (0/15), (0/10). The staining pattern for D2-40 was characterized by thick membranous staining. Diffuse cytoplasmic staining by D2-40 was seen in 2 cases of pulmonary carcinoma, counted as negative. Our study showed that in differentiating MM from PA, CK5/6, WT-1, and D2-40 have high specificity and sensitivity for MM. Although calretinin is a sensitive IHC marker for MM, it is not specific since it stained 30% of PA. Conversely, to differentiate between MM and PSCC, p63 and WT-1 are the best available markers. We recommend a panel of CK5/6, p63, D2-40, and WT-1 to differentiate MM from pulmonary carcinomas in effusion cytology specimens. Diagn. Cytopathol. 2006; 34:801,806. © 2006 Wiley-Liss, Inc. [source] Exfoliative sputum cytology of cancers metastatic to the lung,DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005Tehmina Z. Ali M.D. Abstract Although largely replaced by fine-needle aspiration (FNA) and bronchoscopy, cytological examination of sputum for exfoliated malignant cells still is considered a valuable initial diagnostic test in patients presenting with a lung mass. Thirty-five cases of secondary/metastatic tumors involving the lung and diagnosed on sputum were retrospectively reviewed from our cytopathology files for a period of 22 yr (1980,2001). Clinical history and the relevant histopathological material were examined and correlated with the cytological findings. In all cases, a history of malignancy was known. Cytological diagnoses included colonic adenocarcinoma (7 cases); non-Hodgkin's lymphoma (NHL; 5 cases); malignant melanoma (MM; 5 cases); breast carcinoma (5 cases); Hodgkin's lymphoma (HL; 3 cases); pancreatic adenocarcinoma (2 cases); prostatic adenocarcinoma (2 cases); and 1 case each of urothelial carcinoma, endometrial carcinoma, renal cell carcinoma, hepatic small-cell carcinoma, squamous-cell carcinoma (cervix), and leiomyosarcoma (LMS). Cellular preservation was optimal in all cases. The smear background was relatively clean in 25 (71%) cases and predominantly inflamed and/or necrotic in 10 (29%) cases. In non-lymphoid tumors (27 cases), isolated single malignant cells were seen in 7 (26%) cases (all cases of MM and prostatic adenocarcinoma), whereas 20 (74%) cases displayed fragments with intact tumor architecture. Overall, only 10/35 (29%) cases showed noticeable tumor-cell necrosis. In one case (LMS), cell block sections were used for immunoperoxidase (IPOX) studies with positive staining for desmin and actin. Exfoliation of cancer cells in sputum from secondary tumors in the lung is a rare phenomenon in current-day practice, with metastatic colonic adenocarcinoma seen most commonly. Intact tumor architecture was observed in exfoliated cells in 75% of the cases. Diagn. Cytopathol. 2005;33:147,151. © 2005 Wiley-Liss, Inc. [source] Relationship between Relative Aerobic Power and Echocardiographic Characteristics in Male AthletesECHOCARDIOGRAPHY, Issue 9 2007Zsuzsanna Kneffel M.Ed. The relationship between relative aerobic power (rel.VO2max) as a generally accepted indicator of endurance capacity and certain characteristics of the athlete's heart, such as body-size related (relative) left ventricular (LV) diastolic wall thickness (WTd), internal diameter (LVIDd), muscle mass (MM), WTd/IDd, heart rate (HR), fractional shortening (FS) and E/A ratio, were investigated in 346 young males (18,35 years, 291 athletes of various events and 55 nonathletic control subjects). Rel.VO2max was measured by spiroergometry; cardiac characteristics were determined by two-dimensionally guided M-mode and Doppler-echocardiography. When the groups were pooled, correlation of rel.VO2max with the cardiac parameters was significant: LVMM·BSA,1.5= 0.413, LVWTd·BSA,0.5= 0.327, LVIDd·BSA,0.5= 0.292, HR =,0.434, E/A = 0.272 (P < 0.001), but no significant relationship was seen with FS and WTd/IDd. In the endurance trained group, rel. VO2max correlated significantly with LVMM·BSA,1.5, LVWT·BSA,0.5, HR, and E/A, in the ballgame players with LVMM·BSA,1.5, LVWT·BSA,0.5, and E/A, in the power-and-sprint event athletes with HR and E/A. In the control group, no significant relationship was observed. Results indicate that in athletes having higher endurance capacity maximal oxygen consumption depends largely on cardiac condition, while in athletes with a lower endurance capacity it can be limited by peripheral conditions. [source] Achiral and chiral separations using MEKC, polyelectrolyte multilayer coatings, and mixed mode separation techniques with molecular micellesELECTROPHORESIS, Issue 6 2010Candace A. Luces Abstract Mixed mode (MM) separation using a combination of MEKC and polyelectrolyte multilayer (PEM) coatings is herein reported for the separation of achiral and chiral analytes. Many analytes are difficult to separate by MEKC and PEM coatings alone. Therefore, the implementation of a MM separation provides several advantages for overcoming the limitations of these well-established methods. In this study, it was observed that achiral separations using MEKC and PEM coatings individually resulted in partial resolution of eight very similar aryl ketones when the molecular micelle (sodium poly(N -undecanoyl- L -glycinate)) concentration was varied from 0.25 to 1.00%,w/v and the bilayer number varied from 2 to 4. However, when MM separation was introduced, baseline resolution was achieved for all eight analytes. In the case of chiral separations, temazepam, aminoglutethimide, benzoin, benzoin methyl ether, and coumachlor were separated using the three separation techniques. For chiral separations, the chiral molecular micelle, sodium poly(N -undecanoyl- L -leucylvalinate), was employed at concentrations of 0.25,1.50%,w/v for both MEKC and PEM coatings. Overall, the results revealed partial separation with MEKC and PEM coatings individually. However, MM separation enabled baseline separation of each chiral mixture. The separation of achiral and chiral compounds from different compound classes demonstrates the versatility of this MM approach. [source] Delayed complete remission in a patient with multiple myelomaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2008R. Ria Abstract We report a strikingly positive, late response to bortezomib in conjunction with pegylated liposomal doxorubicin in a 79-year old woman with multiple myeloma (MM). The patient obtained a partial remission after eight courses of therapy and a complete remission about 10 months after the end of therapy. This delayed complete remission may be similar to the spontaneous regression reported for other malignancies such as melanoma or lymphoma. We postulate that the immune response and a persistent anti-angiogenic effect of bortezomib could well explain the delayed complete remission in our patient. [source] Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controlsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2002B. Mackness Abstract Background The oxidation of low-density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High-density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL. Design Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications. Results Both PON1 activity and concentration were significantly lower by 16·7% and 19·2% (both P < 0·05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes. Conclusions Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established. [source] Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Fortunato Morabito Abstract The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as thalidomide, lenalidomide and bortezomib in the last decade, has resulted in a new scenario expected to impact favorably on the outcome of patients with MM. The introduction of new drugs in the treatment of patients eligible for autologous stem cell transplantation (ASCT) has allowed for a significant increase of complete response rate with a positive impact on progression-free survival. In patients not eligible for ASCT, randomized trials have shown that both thalidomide and bortezomib when combined with melphalan and prednisone (MP) are superior to MP and are now considered the standard of care. Ongoing trials are assessing whether MP plus lenalidomide or the combination of lenalidomide plus dexamethasone should be considered an attractive treatment option, while additional studies are needed to determine the role of routine maintenance or consolidation therapy with these new drugs. This new therapeutic armamentarium in light of adequate prophylaxis and supportive care allows clinicians to greatly improve the survival perspectives for both young and elderly patients. In this review, we report updated data for the front-line therapy of MM, examining the role of new drugs either when administered as induction therapy before ASCT in younger patients or when combined with alkylating agents for the treatment of older patients. The most relevant articles on therapy of MM published from November 1982 to January 2010 (selected through PubMed), and recent meeting abstracts were used as sources for this review. [source] BSc2118 is a novel proteasome inhibitor with activity against multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2010Jan Sterz Abstract Objectives:, The ubiquitin,proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC). Methods:, Human MM cell lines OPM-2, RPMI-8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118. Cytotoxicity levels were evaluated using the MTT-test. BSc2118-induced apoptosis was analyzed by annexin-V assay. Further methods used included proteasomal activity determination, cell cycle analysis, western blot, and transcription factor assays. Results:, In OPM-2, RPMI-8226, U266 cell lines and primary MM cells, BSc2118 caused dose-dependent growth inhibitory effects. After 48 h, dose-dependent apoptosis occurred both in cell lines and primary myeloma cells irrespective of t(4;14). A significant G2-M cell cycle arrest occurred after 24 h. Furthermore, we observed a marked inhibition of intracellular proteasome activity, an increase in intracellular p21 levels, and an inhibition of NF-,B activation. The toxicity against PBMNC remained low, suggesting a broad therapeutic range of this agent. Conclusion:, Taken together, BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development. [source] Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairmentEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010Meletios A. Dimopoulos Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source] ThaDD plus high dose therapy and autologous stem cell transplantation does not appear superior to ThaDD plus maintenance in elderly patients with de novo multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2010Massimo Offidani Abstract Objectives:,With the aim to address the issue whether high-dose therapy (HDT) is required after new drugs combinations to improve outcome of elderly newly diagnosed multiple myeloma (MM) patients, we compared the toxicity and the outcome of ThaDD plus maintenance to those of ThaDD plus HDT-autologous stem cell transplantation (ASCT). Methods: Sixty-two patients not eligible for HDT receiving six courses of ThaDD regimen plus maintenance with thalidomide were compared to 26 patients eligible for HDT treated with four courses of ThaDD followed by melphalan 100,200 mg/m2 and ASCT. The two groups were matched for the main characteristics except for age favouring the HDT group. Results and conclusions:,Complete remission (CR) obtained with ThaDD plus maintenance was 24% whereas it was 57% after ThaDD plus HDT-ASCT (P = 0.0232). However, after a median follow-up of 36 months, median time to progression (TTP) and progression free survival (PFS) of the group of patients undergone HDT were not significantly different to those of patients receiving ThaDD plus maintenance (32 vs. 31 months: P = 0.962; 32 vs. 29 months: P = 0.726, respectively). Five-year overall survival (OS) was 49% in the first group and 46% in the latter one (P = 0.404). As expected, a significantly higher incidence of grade 3,4 neutropenia, thrombocytopenia, infections, mucositis and alopecia were observed in the ThaDD plus HDT group. Our results suggest that in elderly MM patients ThaDD plus HDT, albeit significantly increases CR rate, seems to be equivalent to ThaDD plus maintenance in terms of TTP, PFS and OS. These results challenge the requirement for HDT consolidation in this subset of patients. [source] Multiple myeloma: chemotherapy or transplantation in the era of new drugsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2010Antonio Palumbo Abstract Objective:,To review the current results of studies incorporating novel agents in multiple myeloma (MM) and discuss the role of autologous stem-cell transplantation (ASCT) in the era of new active drugs for the treatment of this disease. The outlook for patients with symptomatic MM is changing with the introduction of bortezomib, thalidomide, and lenalidomide into the repertoire of available chemotherapeutic agents. Compared with standard chemotherapy, a survival benefit has been reported for the first time in 30 yrs. Methods: Articles published in English between 1969 and 2008 were identified by searching PubMed for ,myeloma', ,diagnosis', ,thalidomide', ,bortezomib', ,lenalidomide', ,dexamethasone', ,prednisone', ,doxorubicin', ,cyclophosphamide', ,melphalan', ,combination chemotherapy', and ,autologous transplantation'. Results: In randomized studies, bortezomib, thalidomide, and lenalidomide have each been combined with dexamethasone, alkylating agents, or doxorubicin, and such combinations resulted in significant improvement in progression-free survival. Conclusions: The incorporation of new drugs as induction therapy along with ASCT appears to produce very good partial response rates, slightly superior to those achieved by conventional chemotherapy with new drugs. How to best optimize induction, consolidation, and maintenance therapy and how to best select and prepare patients for ASCT are still to be determined. Randomized trials are needed to directly compare the current best chemotherapeutic approach with best ASCT strategies and to guide clinical practice for patients with MM. [source] Over-expression of CCL3,,MIP-1, in a blastoid mantle cell lymphoma with hypercalcemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2010Norimichi Hattori Abstract We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin-6 (IL-6), tumor necrosis factor-, (TNF-,), macrophage inflammatory protein-1, (MIP-1,), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT-PCR) analysis, we found predominant expression of mRNA for MIP-1, in addition to those for receptor-activator of nuclear-factor kappa B ligand (RANKL), TNF-,, and IL-6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP-1, significantly stimulated 3H-thymidine uptake by isolated MCL cells in vitro. Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP-1,. In the present case, MIP-1,, an osteoclast-activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1, is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP-1, is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B-cell lymphoma. [source] | |||||||||||||||||||||||||||||||||||||||||||