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MF
Terms modified by MF Selected AbstractsPhotodynamic Therapy of Cutaneous Lymphoma Using 5-Aminolevulinic Acid Topical ApplicationDERMATOLOGIC SURGERY, Issue 8 2000Arie Orenstein MD Background. Photodynamic therapy (PDT) with topical application of 5-aminolevulinic acid (ALA) is a new and effective modality for treatment of superficial basal and squamous cell carcinomas. Objective. We present the kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of ALA PDT treatment on two patients with different stages (stage I and stage III) of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). Methods. ALA-Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence measurements of PP accumulation were carried out before, during, and 1 hour after photoirradiation (580,720 nm) using the VersaLight system. Results. Different patterns of PP fluorescence kinetics were observed in patients with early and advanced stages of the disease. During photoirradiation the intensity of fluorescence decreased depending on the lesion thickness. One hour after the photoirradiation procedure no PP fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP fluorescence reappeared; after an additional 10,15 minutes of irradiation PP fluorescence disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively). Conclusion. The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment. [source] Treatment planning in cutaneous T-Cell lymphomaDERMATOLOGIC THERAPY, Issue 4 2003Eric C. Vonderheid ABSTRACT:, Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires administration of skin-directed therapies such as topically applied nitrogen mustard or photochemotherapy to achieve a complete response in clinically early disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the concomitant administration of well-tolerated drugs with systemic effects such as interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor phase MF or erythrodermic CTCL). The author's approach is provided as a guide for dermatologists in private practice. [source] Treatment of patch-stage mycosis fungoides with topical corticosteroidsDERMATOLOGIC THERAPY, Issue 4 2003Herschel S. Zackheim ABSTRACT:, Experience at the University of California, San Francisco (UCSF), in the management of patch-stage mycosis fungoides (MF) with topical, predominantly high-potency, corticosteroids is reviewed. The technique of applications is discussed in detail. Approximately 200 patients have been treated. The results are very favorable. The response rate is over 90%. Side-effects are minor. Topical clobetasol is the first-line treatment for early stage MF at UCSF. [source] Transgenic , medaka as a new model for germ cell mutagenesisENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2008Richard N. Winn Abstract To address the need for improved approaches to study mutations transmitted to progeny from mutagen-exposed parents, we evaluated , transgenic medaka, a small fish that carries the cII mutation target gene, as a new model for germ cell mutagenesis. Mutations in the cII gene in progeny derived from ethyl-nitrosourea (ENU)-exposed males were readily detected. Frequencies of mutant offspring, proportions of mosaic or whole body mutant offspring, and mutational spectra differed according to germ cell stage exposed to ENU. Postmeiotic germ cells (spermatozoa/late spermatids) generated a higher frequency of mutant offspring (11%) compared to premeiotic germ cells (3.5%). Individuals with cII mutant frequencies (MF) elevated more than threefold above the spontaneous MF (3 × 10,5) in the range of 10,4 to 10,3 were mosaic mutant offspring, whereas those with MFs approaching 1 × 10,2 were whole body mutant offspring. Mosaic mutant offspring comprised the majority of mutant offspring derived from postmeiotic germ cells, and unexpectedly, from spermatogonial stem cells. Mutational spectra comprised of two different mutations, but at identical sites were unusual and characteristic of delayed mutations, in which fixation of a second mutation was delayed following fertilization. Delayed mutations and prevalence of mosaic mutant offspring add to growing evidence that implicates germ cells in mediating processes postfertilization that contribute to genomic instability in progeny. This model provides an efficient and sensitive approach to assess germ cell mutations, expands opportunities to increase understanding of fundamental mechanisms of mutagenesis, and provides a means for improved assessment of potential genetic health risks. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] 3,-azido-3,-deoxythymidine induces deletions in L5178Y mouse lymphoma cells,,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3-4 2007Jianyong Wang Abstract 3,-Azido-3,-deoxythymidine (AZT), a nucleoside analogue used for the treatment of acquired immunodeficiency syndrome (AIDS), induced a significant dose-related increase in the thymidine kinase (Tk) mutant frequency (MF) in L5178Y/Tk+/, 3.7.2C mouse lymphoma cells. Treatment with 1 mg/ml (3,742 ,M) AZT for 24 hr resulted in a MF of 407 × 10,6 compared to a control MF of 84 × 10,6. The MFs of the large and small colony mutants resulting from AZT exposure were 142 × 10,6 and 265 × 10,6, respectively. One hundred and fifty mutants from the 1 mg/ml (3,742 ,M) AZT-treated culture and sixty-nine mutants from independent untreated cultures were isolated and analyzed. LOH analysis using a heteromorphic microsatellite locus located in the Tk gene was performed to determine the presence or absence of the Tk+ allele. Eight other microsatellite markers spanning the entire mouse chromosome 11 also were examined for heterozygosity to determine the extent of LOH. In addition, Tk gene dosage analysis was conducted using Real-Time PCR in those mutants showing LOH at the Tk locus. The presence of only one Tk allele based on Real-Time PCR indicated that the mutant resulted from deletion while the presence of two alleles was consistent with a recombination event. More mutants from the AZT-treated culture showed Tk LOH than did independent mutants from the untreated cultures (91% vs. 64%) and the induced mutants also showed distinct chromosome 11 LOH patterns. The mutation spectrum of mutants from AZT-treated cells was also significantly different from that of spontaneous mutants. More deletions and fewer intragenic mutations were observed in the mutants from the AZT-treated culture than independent mutants from the untreated control. Our data indicate that AZT primarily induced LOH mutations in L5178Y mouse lymphoma cells and a large number of LOH mutations resulted from deletions. Environ. Mol. Mutagen., 2007. Published 2007 Wiley-Liss, Inc. [source] Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2005Tao Chen Abstract A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats. Environ. Mol. Mutagen., 2005. Published 2005 Wiley-Liss, Inc. [source] Evaluation of mutant frequencies of chemically induced tumors and normal tissues in ,/cII transgenic miceENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Jon C. Mirsalis Abstract Genomic instability has been implicated as an important component in tumor progression. Evaluation of mutant frequencies (MFs) in tumors of transgenic mice containing nontranscribed marker genes should be useful for quantitating mutation rates in tumors as the physiologically inactive transgene provides neither a positive nor a negative selective pressure on the tumor. We have conducted long-term carcinogenicity studies in ,/cII transgenic B6C3F1 mice using a variety of genotoxic and nongenotoxic test agents and have evaluated the mutant frequencies in both tumors and normal tissues from these animals. Mice were administered diethylnitrosamine (DEN) as three intraperitoneal injections of 15 mg/kg; phenobarbital (PB) or oxazepam (OXP) provided ad libitum at 0.1% or 0.25% in the diet, respectively; DEN initiation plus PB in the diet; or urethane (UTH) provided ad libitum at 0.2% in the drinking water. Normal tissues and tumors were isolated at various times over a 2-year period and half of each tissue/tumor was evaluated histopathologically and the other half was evaluated for MF in the cII transgene. Approximately 20 mutants from each of 166 individual tissues (tumor and nontumor) were sequenced to determine whether increases in MF represented unique mutations or were due to clonal expansion. UTH produced significant increases in MF in normal liver and lung. DEN either with or without PB promotion produced significant increases in MF in liver and correction of MF for clonality produced little change in the overall MF in these groups. PB produced a twofold increase in liver MF over controls after 27 weeks of treatment, but a similar increase was not observed with longer dosing times; at later time points, the MF in the PB groups was lower than that of the control group, suggesting that PB is not producing direct DNA damage in the liver. OXP failed to produce an increase in MF over controls, even after 78 weeks of treatment. Selected cases of genomic instability were observed in tumors from all treatments except OXP, with individual liver tumors showing very high MF values even after clonal correction. One rare and interesting finding was noted in a single mouse treated with UTH, where a mammary metastasis had an MF approximately 10-fold greater than the parent tumor, with 75% of the mutations independent, providing strong evidence of genomic instability. There was no clear correlation between tumor phenotype and MF except that pulmonary adenomas generally had higher MFs than normal lung in both genotoxic and nongenotoxic treatment groups. Likewise, there was no correlation between tumor size and MF after correction for clonality. The results presented here demonstrate that individual tumors can show significant genomic instability, with very significant increases in MF that are not attributed to clonal expansion of a single mutant cell. Environ. Mol. Mutagen., 2005. © 2004 Wiley-Liss, Inc. [source] Myocardial perfusion defects in Bartter and Gitelman syndromesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2008R. Scognamiglio ABSTRACT Background, Normotensive hypokalaemic tubulopathies (Bartter and Gitelman syndromes (BS/GS)) are genetic diseases that are considered benign. However, QT prolongation, left ventricular dysfunction and reduction of cardiac index upon exercise leading to arrhythmias and sudden cardiac death have been reported in these patients. Hence, we aimed to verifying whether an isometric exercise could represent a useful tool for the identification of patients at risk for future cardiac events. Patients and methods, Myocardial function (MF) and perfusion, evaluated as myocardial blood flow (MBF) of 10 BS/GS patients and 10 healthy controls, were investigated at rest and during isometric exercise. MF and MBF were evaluated using quantitative two-dimensional and myocardial contrast echocardiography. Results, BS/GS patients had normal baseline MF and MBF. During exercise in BS/GS patients, corrected QT (QTc) was prolonged to peak value of 494 ± 9·1 ms (P < 0·001). In controls, MF increased from resting to peak exercise (left ventricular ejection fraction: 65 ± 4% to 78 ± 5%, P < 0·003) while in seven BS/GS patients (Group 1) it declined (64 ± 5% to 43 ± 9%, P < 0·001). Myocardial perfusion increased upon exercise in controls as shown by changes of its markers: , (a measure of myocardial flow velocity; 0·89 ± 0·12 vs. 0·99 ± 0·12, P < 0·001) and myocardial blood volume (14·4 ± 2 vs. 20·2 ± 0·25, P < 0·001), while in Group 1 BS/GS it decreased (0·87 ± 0·15 vs. 0·67 ± 0·15, P < 0·001; and 14·5 ± 1·9 vs. 8·3 ± 0·22, P < 0·001, respectively). Conclusions, Our results document for the first time that exercise induce coronary microvascular and myocardial defects in BS/GS patients. Therefore, this may challenge the idea that BS/GS are benign diseases. In addition, the diagnostic approach to these syndromes should include an in-depth cardiac assessment in order to identify patients at higher risk. [source] Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shuntEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Elena Mishchenko Abstract Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension. [source] Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype,phenotype associationsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Domenica Caramazza Abstract Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype,phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL -negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplications (e.g. 1q12,1q32 in PV, 1q21,32,1q32,44 in post-PV MF or PMF), deletions (e.g. 1p13,36,pter in PV or PMF, 1q21 in PMF) and unbalanced translocations involving chromosome 6, such as der(6)t(1;6)(q21,25;p21.3,23), and other partner chromosomes involving 1q10/1p11 and 1q21,25 breakpoints. Although occasionally seen in chronic phase MPN, unbalanced 1;7 translocations, e.g. der(1;7)(q10;p10), are usually seen in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and post-MPN AML/MDS. These observations suggest that certain chromosome 1 regions, especially 1q21,1q32 and 1p11,13, might harbor oncogenes or tumor suppressor genes that are pathogenetically relevant to both chronic and advanced phases of MPN. [source] Conventional cytogenetics in myelofibrosis: literature review and discussionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Kebede Hussein Abstract The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include ,7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either ,favorable' or ,unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1 -positive or PDGFRB -rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q). [source] Facile Synthesis of Bastnaesite -Type LaF[CO3] and Its Thermal Decomposition to LaOF for Bulk and Eu3+ -Doped SamplesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 3 2009Oliver Janka Abstract Rare-earth metal(III) oxide fluorides with the composition MOF (M = La,Lu) seem to offer promising host lattices for luminescence applications by doping these materials with trivalent lanthanoid cations. Unfortunately, there was no simple and practicable way to synthesize the compounds in phase-pure quality with classical solid-state chemistry reactions. However, by using the rare-earth metal(III) fluoride oxocarbonates, MF[CO3], as solution-born precursor materials that crystallize with a bastnaesite -type structure, easy access is now possible by mild thermal decomposition. Synthetic details, investigations on the phase purity and the presence of the oxocarbonate anion [CO3]2, proved by IR measurements as well as from X-ray powder diffraction data are given in this paper for the example of bulk LaF[CO3] and Eu3+ -doped samples. The latter (LaF[CO3]:Eu3+) shows a bright orange-red luminescence that is stronger than that of the product of its thermal decomposition: trimorphic LaOF:Eu3+.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Calorimetric study of milk fat/rapeseed oil blends and their interesterification productsEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 4 2009Mario Aguedo Abstract Milk fat (MF) and rapeseed oil (RO) blends were analyzed by differential scanning calorimetry (DSC). It was shown that peak and onset temperatures can be used to determine the percentage of each fat in the blend and that the relative enthalpy of one peak assigned to low-melting triacylglycerols (TAG) can also be used to determine the percentage of RO in the blend. A linear relation was also established between MF content of the blend and its dropping point (DP), indicating that DP can be linearly related with the above DSC data. A blend of MF/RO 70,:,30 (wt/wt) was then chosen as a model system for enzymatic interesterification (EIE). The applicability of DSC analyses to EIE products was checked and a correct correlation could be established between DSC values and the interesterification degree and DP. Among the data from the DSC profiles, the peak associated with low-melting TAG was the best indicator of the reaction course. In the same way, a high-melting MF stearin fraction was interesterified with RO. In that case, onset temperatures and peak "a" were better reaction indicators than for the interesterified MF/RO blend. We therefore suggest that values from DSC endotherms could be used to monitor EIE of fat blends. [source] Enamel microhardness and bond strengths of self-etching primer adhesivesEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2010Olabisi A. Adebayo Adebayo OA, Burrow MF, Tyas MJ, Adams GG, Collins ML. Enamel microhardness and bond strengths of self-etching primer adhesives. Eur J Oral Sci 2010; 118: 191,196. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci The aim of this study was to determine the relationship between enamel surface microhardness and microshear bond strength (,SBS). Buccal and lingual mid-coronal enamel sections were prepared from 22 permanent human molars and divided into two groups, each comprising the buccal and lingual enamel from 11 teeth, to analyze two self-etching primer adhesives (Clearfil SE Bond and Tokuyama Bond Force). One-half of each enamel surface was tested using the Vickers hardness test with 10 indentations at 1 N and a 15-s dwell time. A hybrid resin composite was bonded to the other half of the enamel surface with the adhesive system assigned to the group. After 24 h of water storage of specimens at 37º°C, the ,SBS test was carried out on a universal testing machine at a crosshead speed of 1 mm min,1 until bond failure occurred. The mean ,SBS was regressed on the mean Vickers hardness number (VHN) using a weighted regression analysis in order to explore the relationship between enamel hardness and ,SBS. The weights used were the inverse of the variance of the ,SBS means. Neither separate correlation analyses for each adhesive nor combined regression analyses showed a significant correlation between the VHN and the ,SBS. These results suggest that the ,SBS of the self-etch adhesive systems are not influenced by enamel surface microhardness. [source] In vitro culture of skin-homing T lymphocytes from inflammatory skin diseasesEXPERIMENTAL DERMATOLOGY, Issue 5 2005Karen Bang Abstract:, We, in this study, describe how T lymphocytes in a skin biopsy can proliferate in vitro for up to 3 months by using T-cell growth factors , interleukin-2 (IL-2) and IL-4 yielding approximately 100,160 million T lymphocytes within 1 month. We established cell lines from three tuberculin skin tests, four positive patch tests, 15 of 16 biopsies from atopic dermatitis (AD), 15 of 19 biopsies from mycosis fungoides (MF), 12 of 24 biopsies from psoriasis vulgaris, which was significantly less than AD (P < 0.05), and with a reduced cumulative number of lymphocytes (P < 0.05). Omitting IL-2 and IL-4 led to immediate halt of proliferation. Blood mononuclear cells from patients and biopsies from healthy persons never gave cell lines. All cells were T lymphocytes expressing CD45RO+, HLA-DR+ and CD150. The CD7 expression was significantly increased in cell lines from AD (P < 0.05). T-cell receptor ,-chain studies by using reverse transcription-polymerase chain reaction showed that all T lymphocytes had access to the skin compartment. Single-stranded conformational analysis showed clonally expanded T cells numbering between 40 and 60 clones. After approximately 2 months of growth, the mean CD4+ : CD8+ ratio was for AD 1.20, MF 0.65 and psoriasis 0.85. Patients with AD treated with cyclosporin-A had almost no growth of CD8+ cells in vitro. Our findings indicate a changed homeostasis among skin-homing lymphocytes for in vitro culture. Our culture system of skin-homing T lymphocytes leads to a prominent cellular expansion allowing for a range of studies of in vivo activated skin T lymphocytes. [source] Multilineage progression of genetically unstable tumor subclones in cutaneous T-cell lymphomaEXPERIMENTAL DERMATOLOGY, Issue 8 2004Albert Rübben Abstract:, Molecular analysis of solid malignant tumors has suggested multilineage progression of genetically unstable subclones during early stages of tumorigenesis as a common mechanism of tumor cell evolution. We have investigated whether multilineage progression is a feature of cutaneous T-cell lymphoma (CTCL). To identify individual tumor cell subclones, we determined the pattern of mutations within microsatellite DNA obtained from multiple histomorphologically confined tumor cell nests of mycosis fungoides (MF) and lymphomatoid papulosis (LyP) lesions. Tumor cells were isolated by laser microdissection, and allelotypes were determined at microsatellite markers D6S260, D9S162, D9S171, D10S215, TP53.PCR15, and D18S65. Nine cases of MF and one patient with anaplastic large cell lymphoma (ALCL) originating from LyP were analyzed at 277 different microdissected areas obtained from 31 individual lesions. Three specimens of cutaneous lichen planus microdissected at 26 areas served as the control tissue. Microsatellite instability in microdissected tissue [MSI(md-tissue)] was detected in tumor tissues of all CTCL patients. One hundred and fifty-seven of 469 analyzed polymerase chain reaction (PCR) amplifications contained mutated microsatellite alleles (34%). In lichen planus, MSI(md-tissue) was seen in only four of 76 PCR products (5%) (P < 0.0001). The distribution of allelotypes in tumor cells from different disease stages was consistent with multilineage progression in five MF cases, as well as in the LyP/ALCL patient. Our results suggest that CTCL may evolve by multilineage progression and that tumor subclones in MF can be detected in early disease stages by mutation analysis of microsatellite DNA obtained from multiple microdissected areas. [source] Establishment of a mouse xenograft model for mycosis fungoidesEXPERIMENTAL DERMATOLOGY, Issue 7 2004Sonja Thaler Abstract:, Mycosis fungoides (MF) is the most frequent variant of cutaneous T-cell lymphomas (CTCLs). MF primarily involves the skin initially with patches and plaques. In later stages, cutaneous tumors develop and tumor cells may spread to lymph nodes and finally to visceral sites. Here, we describe an animal model for MF in immune-deficient nude mice, using the CTCL cell line MyLa. Subcutaneous transplantation of MyLa cells leads to the formation of cutaneous tumors in 80% of the mice (50/60 total). Spread of tumor cells to visceral sites was detected by immunohistochemistry and polymerase chain reaction (PCR)-based detection of specific T-cell receptor-, rearrangement. MyLa cells were found circulating in the blood, lymph nodes, and in blood vessels of heart, kidney, lung, and liver. In lung and liver tissue, tumor cells presented perivascular invasion, but no large secondary tumors developed. The nude mouse model described here will be a valuable test system for new therapeutic approaches for the treatment of MF and opens the unique opportunity to study the disease in vivo. [source] IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent increase in mycosis fungoides progressionEXPERIMENTAL DERMATOLOGY, Issue 4 2000K. Asadullah Abstract: Cytokines are of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth factors for the malignant T cells in these entities. To investigate the expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T-cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing skin biopsies from CTCL patients at different stages in comparison to psoriatic and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL entities. Remarkably, there was some evidence for a stage-dependent increase during MF progression. We found only slight overexpression in early stage MF, when only few tumor cells are detectable within the infiltrates, whereas marked overexpression was found in more advanced lesions, which are characterized by a higher density of malignant cells. These results suggested that CTCL cells themselves might produce the cytokines. To further elucidate this hypothesis, two CTCL cell lines were analyzed but gave conflicting results. Therefore, the cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear. Considering the significant overexpression of IL-15 and IL-16 and their biological capacities it is likely that these cytokines contribute to the tumor development. So, they might be involved in growth and skin homing of CTCL cells. [source] Modelflow estimates of cardiac output compared with Doppler ultrasound during acute changes in vascular resistance in womenEXPERIMENTAL PHYSIOLOGY, Issue 4 2010Kenneth S. Dyson We compared Modelflow (MF) estimates of cardiac stroke volume (SV) from the finger pressure-pulse waveform (Finometer®) with pulsed Doppler ultrasound (DU) of the ascending aorta during acute changes in total peripheral resistance (TPR) in the supine and head-up-tilt (HUT) postures. Twenty-four women were tested during intravenous infusion of 0.005 or 0.01 ,g kg,1 min,1 isoprenaline, 10 or 50 ng kg,1 min,1 noradrenaline and 0.3 mg sublingual nitroglycerine. Responses to static hand-grip exercise (SHG), graded lower body negative pressure (LBNP, from ,20 to ,45 mmHg) and 45 deg HUT were evaluated on separate days. Bland,Altman analysis indicated that SVMF yielded lower estimates than SVDU during infusion of 0.01 ,g kg,1 min,1 isoprenaline (SVMF 92.7 ± 15.5 versus SVDU 104.3 ± 22.9 ml, P= 0.03) and SHG (SVMF 78.8 ± 12.0 versus SVDU 106.1 ± 28.5 ml, P < 0.01), while larger estimates were recorded with SVMF during ,45 mmHg LBNP (SVMF 52.6 ± 10.7 versus SVDU 46.2 ± 14.5 ml, P= 0.04) and HUT (SVMF 59.3 ± 13.6 versus SVDU 45.2 ± 11.3 ml, P < 0.01). Linear regression analysis revealed a relationship (r2= 0.41, P < 0.01) between the change in TPR from baseline and the between-methods discrepancy in SV measurements. This relationship held up under all of the experimental protocols (regression for fixed effects, P= 0.46). These results revealed a discrepancy in MF estimates of SV, in comparison with those measured by DU, during acute changes in TPR. [source] Different roles of proteolipids and 70-kDa subunits of V-ATPase in growth and death of cultured human cellsGENES TO CELLS, Issue 6 2003Hong Zhan Background: The vacuolar-type proton-translocating adenosine triphosphatase (V-ATPase) plays important roles in cell growth and tumour progression. V-ATPase is composed of two distinct structures, a hydrophilic catalytic cytosolic sector (V1) and a hydrophobic transmembrane sector (V0). The V1 sector is composed of 5,8 different subunits with the structure A3B3C1D1E1F1G1H1. The V0 sector is composed of 5 different subunits with the structure 1161381191166. The over-expression of 16-kDa proteolipid subunit of V-ATPase in the perinuclear region of the human adventitial fibroblasts promotes phenotypic modulation that contributes to neointimal formation and medial thickening. A relationship between oncogenicity and the expression of the 16-kDa proteolipid has also been suggested in human pancreatic carcinoma tissue. Results: We found that the mRNA levels of the 16-kDa proteolipid but not of the 70-kDa subunit of V-ATPase in human myofibroblasts were more abundant in serum-containing medium (MF(+) cells) than serum-free medium (MF(,) cells). In HeLa cells, the levels of mRNA and protein of the 16-kDa, 21-kDa or 70-kDa were clearly suppressed when the corresponding anti-sense oligonucleotides were administered to the culture medium. The growth rate and viability (mostly due to necrosis) of HeLa cells were reduced markedly by the 16-kDa and 21-kDa anti-sense, but little by the 70-kDa anti-sense, and not at all by any sense oligonucleotides. The localization of 16-kDa/21-kDa proteolipid subunits was different from that of the 70-kDa subunit in HeLa cells. Conclusion: These results suggest that the 16-kDa and 21-kDa proteolipid subunits of the V0 sector play crucial roles in growth and death of cultured human cells. Our results may provide new insights into the mechanism and therapeutic implications for vessel wall hyperplasia and tumorigenesis. [source] Spatiotemporal mapping of cortical activity accompanying voluntary movements using an event-related beamforming approachHUMAN BRAIN MAPPING, Issue 3 2006Douglas Cheyne Abstract We describe a novel spatial filtering approach to the localization of cortical activity accompanying voluntary movements. The synthetic aperture magnetometry (SAM) minimum-variance beamformer algorithm was used to compute spatial filters three-dimensionally over the entire brain from single trial neuromagnetic recordings of subjects performing self-paced index finger movements. Images of instantaneous source power ("event-related SAM") computed at selected latencies revealed activation of multiple cortical motor areas prior to and following left and right index finger movements in individual subjects, even in the presence of low-frequency noise (e.g., eye movements). A slow premovement motor field (MF) reaching maximal amplitude ,50 ms prior to movement onset was localized to the hand area of contralateral precentral gyrus, followed by activity in the contralateral postcentral gyrus at 40 ms, corresponding to the first movement-evoked field (MEFI). A novel finding was a second activation of the precentral gyrus at a latency of ,150 ms, corresponding to the second movement-evoked field (MEFII). Group averaging of spatially normalized images indicated additional premovement activity in the ipsilateral precentral gyrus and the left inferior parietal cortex for both left and right finger movements. Weaker activations were also observed in bilateral premotor areas and the supplementary motor area. These results show that event-related beamforming provides a robust method for studying complex patterns of time-locked cortical activity accompanying voluntary movements, and offers a new approach for the localization of multiple cortical sources derived from neuromagnetic recordings in single subject and group data. Hum. Brain Mapping 2005. © 2005 Wiley-Liss, Inc. [source] Representing elevation uncertainty in runoff modelling and flowpath mappingHYDROLOGICAL PROCESSES, Issue 12 2001Theodore A. Endreny Abstract Vertical inaccuracies in terrain data propagate through dispersal area subroutines to create uncertainties in runoff flowpath predictions. This study documented how terrain error sensitivities in the D8, Multiple Flow (MF), DEMON, D-Infinity and two hybrid dispersal area algorithms, responded to changes in terrain slope and error magnitude. Runoff dispersal areas were generated from convergent and divergent sections of low, medium, and high gradient 64-ha parcels using a 30 m pixel scale control digital elevation model (DEM) and an ensemble of alternative realizations of the control DEM. The ensemble of alternative DEM realizations was generated randomly to represent root mean square error (RMSE) values ranging from 0·5 to 6 m and spatial correlations of 0 to 0·999 across 180 m lag distances. Dispersal area residuals, derived by differencing output from control and ensemble simulations, were used to quantify the spatial consistency of algorithm dispersal area predictions. A maximum average algorithm consistency of 85% was obtained in steep sloping convergent terrain, and two map analysis techniques are recommended in maintaining high spatial consistencies under less optimum terrain conditions. A stochastic procedure was developed to translate DEM error into dispersal area probability maps, and thereby better represent uncertainties in runoff modelling and management. Two uses for these runoff probability maps include watershed management indices that identify the optimal areas for intercepting polluted runoff as well as Monte-Carlo-ready probability distributions that report the cumulative pollution impact of each pixel's downslope dispersal area. Copyright © 2001 John Wiley & Sons, Ltd. [source] In vivo astaxanthin treatment partially prevents antioxidant alterations in dental pulp from alloxan-induced diabetic ratsINTERNATIONAL ENDODONTIC JOURNAL, Issue 11 2010M. F. Leite Leite MF, de Lima A, Massuyama MM, Otton R.In vivo astaxanthin treatment partially prevents antioxidant alterations in dental pulp from alloxan-induced diabetic rats. International Endodontic Journal, 43, 959,967, 2010. Abstract Aim, To evaluate the effect of astaxanthin on antioxidant parameters of dental pulp from diabetic rats. The hypothesis tested was that supplementation of diabetic rats with astaxanthin might eliminate, or at least attenuate, the defect in their antioxidative status. Methodology, Wistar rats (n = 32) were divided into four groups: untreated control, treated control, untreated diabetic and treated diabetic rats. A prophylactic dose of astaxanthin (20 mg kg,1 body weight) was administered daily by gavage for 30 days. On day 23, diabetes was induced by injection of alloxan (60 mg kg,1 body weight). After 7 days of diabetes induction, the rats were killed, and pulp tissue from incisor teeth removed. Superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and reductase activities were determined. Data were compared by anova and the Newman,Keuls test (P < 0.05). Results, Diabetes caused a reduction in SOD, GPx and reductase activity in dental pulp tissue. Astaxanthin had no effect on SOD and catalase activities; however, it stimulated GPx in control and diabetic rats. Conclusions, Diabetes altered the antioxidant system in dental pulp tissue; astaxanthin partially improved the diabetic complications. [source] Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stromaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Takafumi Sangai Abstract Cancer-stromal interaction is well known to play important roles during cancer progression. Recently we have demonstrated that bone marrow-derived vascular endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10 kinds of human cancer cell line were implanted into the subctaneous tissue of the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG-1,/, ,-gal Tg or RAG-1,/, GFP Tg). The recruitment frequency of BMD-VE (%BMD-VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV), microvessel density (MVD) and stromal proportion (%St)] were measured. The correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0 to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD-VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the effect of tumor growth sites on the recruitment of the cells of interest, a human pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites: subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St = 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially up- or down-regulated in the cell line that induced an abundant stromal reaction. However they did not encoded the molecules that were directly involved in stromal cell recruitment (chemokines), differentiation (cytokines) or proliferation (growth factors). These results indicate that the recruitment of BMD-VE and -MF is required for stromal formation during cancer progression and that the cancer microenvironment is important in stromal reaction and the recruitment of BMD-VE and -MF. © 2005 Wiley-Liss, Inc. [source] Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and sezary syndrome)INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Arnaud Cirée Abstract Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4+ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3+ CD4+ CD45RO+, a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth. © 2004 Wiley-Liss, Inc. [source] Early-stage mycosis fungoides, parapsoriasis en plaque, and pregnancyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2007Iris Amitay-Layish MD Background, Non-Hodgkin's lymphoma (NHL) coincident with pregnancy is rare, and the literature regarding mycosis fungoides (MF), the most common primary cutaneous NHL, and pregnancy is strikingly sparse. The effect of pregnancy on MF, or on parapsoriasis en plaque (PPP), and the effect of these diseases on pregnancy, are still unknown. Objective, To study the effect of pregnancy on MF and PPP and the impact of these diseases on pregnancy. Methods, The files of the MF and PPP patients seen during the past 12 years in our department were reviewed to search for patients who had been pregnant during the course of their disease. Results, Nine women who met the study criteria were identified, seven with early-stage MF and two with PPP. A total of 12 pregnancies was recorded: nine in patients with MF and three in patients with PPP. In none of the patients was there any indication that pregnancy changed the course of MF or PPP. Of the 12 pregnancies, 11 were normal; one was naturally aborted. Two of the patients were treated with topical steroids during pregnancy. One patient was treated with narrow-band ultraviolet-B combined with topical steroids. The rest preferred to avoid any therapy. Conclusions, Pregnancy appeared to have no impact on the course of early MF or PPP, and no adverse effect was noted on pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF or PPP. [source] Milia in regressing plaques of mycosis fungoides: provoked by topical nitrogen mustard or not?INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2004Aylin Kalayciyan MD Objective, To report three cases of mycosis fungoides with milia formation in the regressing lesions. Patients and setting, Dermatology clinic of a university hospital (referral center). Three patients with mycosis fungoides with body surface involvement of 10% in one case (stage IIb) and exceeding 30% in two cases (stages IIb and III). All patients were treated with photochemotherapy and topical nitrogen mustard ointment in a concentration of 0.01%. After approximately 3 months multiple milia erupted on regressing plaques. Results, The presence of milia was evident and was confirmed by histopathology. Regression of mycosis fungoides was noted in these plaques both clinically and in comparison with the pretreatment histologic appearance. Two of the patients showed a histological picture of follicular mucinosis. Conclusions, We do not know the significance of milia in mycosis fungoides (MF). However, we suggest that follicular rupture or a degenerative process might result in milia formation. [source] Long-term control of mycosis fungoides of the hands with topical bexaroteneINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2003Ted Lain BA Background Limited Stage IA mycosis fungoides (MF) is often treated with topical steroids, which can cause atrophy, or with nitrogen mustard, which imposes several limitations on the patient's lifestyle. Topical bexarotene is a novel synthetic rexinoid with few side-effects that has shown efficacy for treatment of mycosis fungoides skin lesions in recent Phase II,III clinical trials. The Phase I,II trial involving 67 stage IA,IIA MF patients demonstrated complete response (CR) in 21% and partial response (PR) in 42% of the patients. The median time to response was approximately 20 weeks. In the phase III trial of refractory stage IA, IB and IIA MF, the patients demonstrated a 44% response rate (8% CR). Patients with no prior therapy for mycosis fungoides responded at a higher rate (75%) than those with prior topical therapies. Methods Case report of a patient with MF limited to the hands treated with topical bexarotene 0.1% gel in a open label phase II clinical trial. Results Partial response occurred after 2 weeks of topical bexarotene therapy and the lesions were well controlled for 5 years using bexarotene monotherapy, with only occasional mild local irritation. Conclusions Topical bexarotene is effective as long-term treatment monotherapy for limited MF lesions. To our knowledge this is the longest use of the drug by any individual. [source] Mycosis fungoides associated with malignant melanoma and dysplastic nevus syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2003J. A. Pielop MD Background The increased risk of second malignancies, including nonmelanoma skin cancers, in cutaneous T-cell lymphoma (CTCL) patients has been well documented. However, relatively few studies of malignant melanoma in CTCL patients have been reported. Methods A database of 250 CTCL patients registered over a 3-year period was searched to identify patients with diagnoses of both mycosis fungoides (MF) and malignant melanoma. Results We identified six cases of MF associated with malignant melanoma and one associated with dysplastic nevus syndrome, which is a marker of increased risk of melanoma. In four patients, melanoma was diagnosed along with or before MF. In the remaining two patients, MF was diagnosed prior to melanoma, although dysplastic nevi were noted at the time MF was diagnosed. These two patients received treatment for their MF (one with topical nitrogen mustard and another with radiation therapy and nitrogen mustard) prior to the histologic confirmation of melanoma. Six patients had early stages of MF (IA or IB), while one patient presented with simultaneous erythrodermic mycosis fungoides involving the lymph nodes as well as melanoma metastatic to the lymph nodes from an unknown primary. Conclusion There is an elevated prevalence of malignant melanoma in MF patients compared to the general US population (P < 0.00001) with a relative risk of 15.3 for observing malignant melanoma in MF patients (95% confidence interval 7.0,33.8). Possible pathologic links between the two diagnoses include effects of mycosis fungoides therapies, immunosuppression secondary to mycosis fungoides, and genetic alterations in the p16 tumor suppressor protein. [source] Effect of manufacturing treatments on the rheological character of Mozzarella cheese made from microfiltration retentate depleted of whey proteins,INTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 6 2001Randall L. Brandsma Low-moisture, part-skim (LMPS) Mozzarella cheeses were made from highly concentrated skim milk microfiltration (MF) retentate and butteroil. Differing combinations of rennet concentration, coagulation temperature and post-coagulation curd cutting time were used, with comparisons made of the rheological and functional characteristics of cheeses during ageing. Lubricated squeezing flow, stress relaxation, melt and stretch measurements demonstrated that commercial LMPS Mozzarella had substantial textural and functional change between 7 and 30 days of age, while the rheological and functional behaviour of LMPS MF Mozzarella (MFM) exhibited substantial change between 30 and 60 days of age. Rennet concentration was the only experimental factor to significantly affect MFM rheological and functional development. The delayed development of MFM was partially attributed to inhibition of normal cheese proteolysis via whey protein (WP) incorporation, lack of starter culture protease, and homogenization of MF cheesemilk. Use of starter culture in MFM led to improved rheological and functional behaviour. [source] | |||||||||||||||||||||||||||||||||||||||||||