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Terms modified by MC Selected AbstractsO-13 ENDOMETRIAL CARCINOMA DETECTED WITH SUREPATH LIQUID BASED CERVICAL CYTOLOGY: COMPARISON WITH CONVENTIONAL CERVICAL CYTOLOGYCYTOPATHOLOGY, Issue 2006C. J. Patel Introduction:, Conventional Pap Smear (CPS) has had little impact on the detection of endometrial carcinoma (MC). Although Liquid Based Cytology (LBC) is replacing CPS in the UK, experience with identification of endometrial cancers with this is limited. A few studies of ThinPrep LBC show promise with reported increased detection rate, but to date, there has been no reported study of detection with SurePath LBC. Aim:, The purpose of this 2-year retrospective study was to compare the accuracy of the SurePath LBC with that of conventional smear in detecting endometrial cancers. Methods:, Our study group consisted of all SurePath cases of endometrial atypia/carcinoma diagnosed between 1st Jan 2004 and 31st Dec 2005, following 100% conversion of our laboratory to the SurePath system in 2001. Conventional smears reported over a 6-year period (1993,1998), comprised the control group. Histological follow up was obtained. Results:, Endometrial lesions were reported in 95 (0.07%) of 130352 SurePath LBC smears. These included 70 (0.053%) reports of endometrial atypia, 05 (0.003%) suspicious and 20 (0.015%) diagnostic of endometrial carcinoma. A total of 58 (0.014%) cases of 409495 CPS were diagnosed as endometrial carcinoma. Adequate histological follow up was available in 47 (49.5%) SurePath LBC and 52 (89.6%) conventional cases. In these, the positive predictive value (PPV) for endometrial carcinoma of SurePath LBC was 73.3% compared to 55.4% of CPS. The PPV for endometrial carcinoma of the atypical and suspicious LBC categories was 14.3% and 40% respectively. No categorisation as atypical or suspicious in the conventional study was available for comparison. The sensitivity of the SurePath LBC, calculated from retrograde analysis of histologically diagnosed endometrial cancers during the same period was 40%. Conclusion:, The SurePath LBC is at least an as accurate and sensitive method for detecting endometrial cancer as CPS. [source] The 10-year course of psychosocial functioning among patients with borderline personality disorder and axis II comparison subjectsACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2010M. C. Zanarini Zanarini MC, Frankenburg FR, Bradford Reich D, Fitzmaurice G. The 10-year course of psychosocial functioning among patients with borderline personality disorder and axis II comparison subjects. Objective:, The purpose of this study was to determine the 10-year course of the psychosocial functioning of patients with borderline personality disorder (BPD). Method:, The social and vocational functioning of 290 inpatients meeting both the Revised Diagnostic Interview for Borderlines (DIB-R) and DSM-III-R criteria for BPD and 72 axis II comparison subjects were carefully assessed during their index admission. Psychosocial functioning was reassessed using similar methods at five contiguous 2-year time periods. Results:, Borderline patients without good psychosocial functioning at baseline reported difficulty attaining it for the first time. Those who had such functioning at baseline reported difficulty retaining and then regaining it. In addition, over 90% of their poor psychosocial functioning was due to poor vocational but not social performance. Conclusion:, Good psychosocial functioning that involves both social and vocational competence is difficult for borderline patients to achieve and maintain over time. In addition, their vocational functioning is substantially more compromised than their social functioning. [source] Neuronal differentiation and long-term survival of newly generated cells in the olfactory midbrain of the adult spiny lobster, Panulirus argusDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Manfred Schmidt Abstract The fate of continuously generated cells in the soma clusters of the olfactory midbrain of adult spiny lobsters, Panulirus argus, was investigated by in vivo pulse-chase experiments with the proliferation marker 5-bromo-2,-deoxyuridine (BrdU) combined with immunostainings for neuropeptides of mature neurons. A BrdU injection after a survival time (ST) of 14 h labeled about 100 nuclei in the lateral soma clusters (LC), comprised of projection neurons, and about 30 nuclei in the medial soma clusters (MC), comprised of local interneurons. The BrdU-positive nuclei were confined to small regions at the inside of these clusters, which also contain nuclei in different phases of mitosis and thus represent proliferative zones. After STs of 2 weeks or 3 months, the number of BrdU-positive nuclei was doubled, indicating a mitosis of all originally labeled cells. Dependent on ST, the BrdU-positive nuclei were translocated from the proliferative zones towards the outside of the clusters, where somata of mature neurons reside. Immunostainings with antibodies to the neuropeptides FMRFamide and substance P, both of which label a large portion of somata in the MC and a pair of giant neurons projecting into the LC, revealed that in both clusters the proliferative zones are surrounded by, but are themselves devoid of, labeling. In the MC, some BrdU-positive somata were double-labeled by the FMRFamide antibody after an ST of 3 months, and by the substance P antibody after STs of 6 and 11/14 months, but not after 3 months. In the LC, BrdU-positive somata after an ST of 3 months partially and after 6 and 11/14 months widely overlapped with the arborizations of the giant neurons, indicating the establishment of synaptic input. The experiments show that cells generated in proliferative zones in the LC and MC of adult spiny lobsters after a final mitosis differentiate into neurons within months, survive for at least 1 year, and are integrated into the circuitry of the olfactory midbrain. A new hypothesis about the mechanism of adult neurogenesis in the central olfactory pathway of decapod crustaceans is developed, linking it to neurogenesis during embryonic and larval development. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 181,203, 2001 [source] The effect of diabetes on heart rate and other determinants of myocardial oxygen demand in acute coronary syndromesDIABETIC MEDICINE, Issue 9 2004K. Foo Abstract Aims To compare major determinants of myocardial oxygen demand (heart rate, blood pressure and rate pressure product) in patients with and without diabetes admitted with acute coronary syndromes. Methods A cross-sectional study of the relation between diabetes and haemodynamic indices of myocardial oxygen demand in 2542 patients with acute coronary syndromes, of whom 1041 (41.0%) had acute myocardial infarction and 1501 (59.0%) unstable angina. Results Of the 2542 patients, 701 (27.6%) had diabetes. Major haemodynamic determinants of myocardial oxygen demand were higher in patients with than without diabetes: heart rate 80.0 ± 20.4 vs. 75.2 ± 19.2 beats/minute (P < 0.0001); systolic blood pressure 147.3 ± 30.3 vs. 143.2 ± 28.5 mmHg (P = 0.002); rate-pressure product 11533 ± 4198 vs. 10541 ± 3689 beats/minute × mmHg (P < 0.0001). Multiple regression analysis confirmed diabetes as a significant determinant of presenting heart rate [multiplicative coefficient (MC) 1.05; 95% confidence interval (CI) 1.03,1.07; P < 0.0001], rate pressure product (MC 1.09; CI 1.05,1.12; P < 0.0001) and systolic blood pressure, which was estimated to be 3.9 mmHg higher than in patients without diabetes (P = 0.003). These effects of diabetes were independent of a range of baseline variables including acute left ventricular failure and mode of presentation (unstable angina or myocardial infarction). Conclusions In acute coronary syndromes, heart rarte and other determinants of myocardial oxygen demand are higher in patients with than without diabetes, providing a potential contributory mechanism of exaggerated regional ischaemia in this high-risk group. [source] Factors predictive of nephropathy in DCCT Type 1 diabetic patients with good or poor metabolic controlDIABETIC MEDICINE, Issue 7 2003L. Zhang Abstract Aims The study aim was to assess the time-related risk of developing diabetic nephropathy [albumin excretion rate (AER) , 40 mg/24 h] from baseline covariates in Type 1 diabetic patients with either good or poor metabolic control (MC). Methods Based on material from the Diabetes Control and Complications Trial study (n = 1441), patients were considered as under good or poor MC if their HbA1c mean level up to last visit fell in the lowest (, 6.9%) or highest (, 9.5%) quintile of the overall HbA1c distribution, respectively. Prevalence cases of nephropathy were excluded from the study. Survival analysis and Cox regression were applied to the data. Results Among patients with good MC (n = 277), 15% had developed nephropathy at the end of the study. Conversely, among patients with poor MC (n = 268), the proportion without the complication was 52%. When adjusting for MC, time to diabetic nephropathy was related to age (P < 0.0001), AER (P < 0.001), duration of diabetes (P < 0.005), body mass index (BMI) (P < 0.005), all at baseline, and to gender (P < 0.01). Patients with upper normal range AER levels, longer duration of diabetes and lower BMI were at higher risk, regardless of MC. The adverse effect of younger age on diabetic nephropathy was more marked in good than in poor MC. Although women tended to develop the complication more often under good MC, they appeared to be better protected under poor MC. Conclusions This study confirms occurrence of diabetic nephropathy under good MC and non-occurrence of the complication despite poor MC. It also demonstrates that some baseline covariates can affect, in a differential manner, time to diabetic nephropathy depending on MC. Diabet. Med. 20, 580,585 (2003) [source] Immunocytochemical typing of primary tumors on fine-needle aspiration cytologies of lymph nodesDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2008Alexandre Sherlley Casimiro Onofre M.Sc. Abstract The aim of this study was to analyze the role of immunocytochemistry as an ancillary method on routine FNACs of enlarged lymph nodes, using different markers. In a validating cohort study all patients had confirmatory histological and/or clinical follow-up. 10 FNACs were analyzed for the differentiation of Non-Hodgkin Lymphoma (NHL) from metastatic carcinoma (MC), 30 cases to identify the sites of metastatic unknown primary tumors and 16 cases were checked to confirm clinical suspicion of a specific MC. Accuracy to differentiate NHL from MC was 100%, 92.3% to identify a primary tumor site of MC, and 100% to confirm a clinical suspicion of a specific MC. In 7 cases, the site of the primary tumor remained clinically unknown. Application of immunocytochemical markers on the same slide used for microscopic diagnosis is a useful tool in the routine assessment of FNACs of lymph nodes. Diagn. Cytopathol. 2008;36:207,215. © 2008 Wiley-Liss, Inc. [source] Simultaneous medullary carcinoma of the thyroid gland and Hodgkin's lymphoma in bilateral lymph nodes of the neck: A potential pitfall in fine-needle aspiration cytologyDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2004Jesús Acosta-Ortega M.D. Abstract The clinicopathological features and the cytological findings of Hodgkin's lymphoma (HL) and medullary carcinoma (MC) of the thyroid gland are described appearing simultaneously in different organs of the cervical region of the same patient. Although the cytological features of both entities are well known, the rare clinical presentation and the epithelium-like Hodgkin and Reed-Sternberg (HRS) cells of the syncytial variant of HL led to an erroneous cytological diagnosis of metastatic carcinoma of the upper aerodigestive tract. Diagn. Cytopathol. 2004;31:255,258. © 2004 Wiley-Liss, Inc. [source] Ontogenetic diet shift in the June sucker Chasmistes liorus (Cypriniformes, Catostomidae) in the early juvenile stageECOLOGY OF FRESHWATER FISH, Issue 3 2010J. D. Kreitzer Kreitzer JD, Belk MC, Gonzalez DB, Tuckfield RC, Shiozawa DK, Rasmussen JE. Ontogenetic diet shift in the June sucker Chasmistes liorus (Cypriniformes, Catostomidae) in the early juvenile stage. Ecology of Freshwater Fish 2010: 19: 433,438. © 2010 John Wiley & Sons A/S Abstract,,, Ontogenetic diet shifts are common in fishes and often occur during early life stages. The larval and early juvenile period is critical in the life cycle of the endangered June sucker, Chasmistes liorus (Teleostei: Catostomidae). High larval and juvenile mortality leads to low recruitment to the breeding population and hence a declining natural population. To understand diet composition and dynamics in June sucker at early life stages, diet was quantified and compared to available food items in the natural environment during the early juvenile stage. Rotifers (Brachionus sp.) were the primary diet item at week 10, but by week 12 a small cyclopoid copepod (Microcyclops rubellus) became predominant. Availability of diet items varied little across the experimental period. The increase in size of young suckers may explain this rapid dietary shift, but there are some inconsistencies with the size selection argument. This diet shift represents an important nutritional change that should be considered in development of diets for young June sucker and in assessing suitability of nursery habitats. [source] Enhanced electrophoretic resolution of monosulfate glycosaminoglycan disaccharide isomers on poly(methyl methacrylate) chipsELECTROPHORESIS, Issue 3 2007Yong Zhang Abstract To improve the separation of monosulfate glycosaminoglycan disaccharide isomers by microchip electrophoresis, we found that addition of 1,4-dioxane,(DO) dramatically improved analyte resolution, probably due to solvation effects. Methylcellulose,(MC) was tested for the ability to suppress EOF and analyte adsorption to the chip. To improve analyte resolution, buffer pH, ,-CD, and DO were systematically investigated. Fast separation was achieved by increasing the electric field strength, and field-amplified sample stacking occurred with increasing buffer concentrations. Therefore, based on our findings, we describe an efficient method for the separation of monosulfate and trisulfate unsaturated disaccharides (,Di-UA2S, ,Di-4S, ,Di-6S, and ,Di-triS) derivatized with 2-aminoacridone hydrochloride. A mixture of monosulfate disaccharide isomers (,Di-UA2S, ,Di-4S, and ,Di-6S) was baseline-separated within 75,s on a poly(methyl methacrylate) chip using a mixed buffer (DO/running buffer 57:43,v:v), 0.5% MC, pH,6.81, with an Esep of 558,V/cm. The theoretical plate was in the range of 5×105 to 1×106,m,1. [source] In vivo exposure to microcystins induces DNA damage in the haemocytes of the zebra mussel, Dreissena polymorpha, as measured with the comet assayENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2007Guillaume Juhel Abstract The Comet assay was used to investigate the potential of the biotoxin microcystin (MC) to induce DNA damage in the freshwater zebra mussel, Dreissena polymorpha. Mussels maintained in the laboratory were fed daily, over a 21-day period, with one of four strains of the cyanobacterium, Microcystis aeruginosa. Three of the strains produced different profiles of MC toxin, while the fourth strain did not produce MCs. The mussels were sampled at 0, 7, 14, and 21 days by withdrawing haemocytes from their adductor muscle. In addition, a positive control was performed by exposing a subsample of the mussels to water containing cadmium chloride (CdCl2). Cell viability, measured with the Fluorescein Diacetate/Ethidium Bromide test, indicated that the MC concentrations, to which the mussels were exposed, were not cytotoxic to the haemocytes. The Comet assay performed on the haemocytes indicated that exposure to CdCl2 produced a dose-responsive increase in DNA damage, demonstrating that mussel haemocytes were sensitive to DNA-damaging agents. DNA damage, measured as percentage tail DNA (%tDNA), was observed in mussels exposed to the three toxic Microcystis strains, but not in mussels exposed to the nontoxic strain. Toxin analysis of the cyanobacterial cultures confirmed that the three MC-producing strains exhibit different toxin profiles, with the two MC variants detected being MC-LF and MC-LR. Furthermore, the DNA damage that was observed appeared to be strain-specific, with high doses of MC-LF being associated with a higher level of genotoxicity than low concentrations of MC-LR. High levels of MC-LF also seemed to induce relatively more persistent DNA damage than small quantities of MC-LR. This study is the first to demonstrate that in vivo exposure to MC-producing strains of cyanobacteria induces DNA damage in the haemocytes of zebra mussels and confirms the sublethal toxicity of these toxins. Environ. Mol. Mutagen., 2007. © 2006 Wiley-Liss, Inc. [source] Microcystin extracts induce ultrastructural damage and biochemical disturbance in male rabbit testisENVIRONMENTAL TOXICOLOGY, Issue 1 2010Ying Liu Abstract In the present research, the changes of ultrastructures and biochemical index in rabbit testis were examined after i.p. injection with 12.5 ,g/kg microcystin (MC) extracts. Ultrastructural observation showed widened intercellular junction, distention of mitochondria, endoplasmic reticulum, and Golgi apparatus. All these changes appeared at 1, 3, and 12 h, but recovered finally. In biochemical analyses, the levels of lipid peroxidation (MDA) and H2O2 increased significantly at 1 h, indicating MC-caused oxidative stress. Finally, H2O2 decreased to the normal levels, while MDA remained at high levels. The antioxidative enzymes (CAT, SOD, GPx, GST) and antioxidants (GSH) also increased rapidly at 1 h, demonstrating a quick response of the defense systems to the oxidative stress. Finally, the activity of CAT, SOD, and GPX recovered to the normal level, while the activity of GST and the concentration of GSH remained at a high level. This suggests that the importance of MCs detoxification by GST via GSH, and the testis of rabbit contained abundant GSH. The final recovery of ultrastructure and some biochemical indexes indicates that the defense systems finally succeeded in protecting the testis against oxidative damage. In conclusion, these results indicate that the MCs are toxic to the male rabbit reproductive system and the mechanism underlying this toxicity might to be the oxidative stress caused by MCs. Although the negative effects of MCs can be overcome by the antioxidant system of testis in this study, the potential reproductive risks of MCs should not be neglected because of their wide occurrence. © 2009 Wiley Periodicals, Inc. Environ Toxicol 2010. [source] Sampling and analysis of microcystins: Implications for the development of standardized methodsENVIRONMENTAL TOXICOLOGY, Issue 2 2007Angeline R. Tillmanns Abstract Microcystins (MC), a group of cyanotoxins, have been found in lakes and rivers worldwide. One goal of MC research is to develop models which predict MC concentrations, but these efforts have been hampered by a lack of standardized methods necessary for comparing data across studies. Here, we investigate the effect of chemical analysis (HPLC-PDA and ELISA), sample collection (whole water, plankton tow and surface scum), and choice of normalizing parameter (volume, dry weight, and chlorophyll a) on reported MC concentrations. Samples were collected over three years from a temperate mesotrophic, shallow lake with episodic blooms of cyanobacteria. We found that microcystins were up to four times higher in lake samples when analyzed by ELISA relative to HPLC-PDA and that MC concentration measured by HPLC explained less than half of the variation in MC concentrations measured by ELISA. Also, samples collected by plankton tow gave consistently higher concentrations than whole water samples. An additional HPLC analysis of two chlorophyte cultures revealed the presence of compounds with a similar UV absorbance spectrum to MC-LR, suggesting that identifying MC based solely on UV absorbance is not valid. Our results document the discrepancy in MC concentrations that can arise by using different methods throughout all stages of sampling, analysis, and reporting of MC concentrations. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 132,143, 2007. [source] Seasonal dynamics of the hepatotoxic microcystins in various organs of four freshwater bivalves from the large eutrophic lake Taihu of subtropical China and the risk to human consumptionENVIRONMENTAL TOXICOLOGY, Issue 6 2005Jun Chen Abstract So far, little is known on the distribution of hepatotoxic microcystin (MC) in various organs of bivalves, and there is no study on MC accumulation in bivalves from Chinese waters. Distribution pattern and seasonal dynamics of MC-LR, -YR and -RR in various organs (hepatopancreas, intestine, visceral mass, gill, foot, and rest) of four edible freshwater mussels (Anodonta woodiana, Hyriopsis cumingii, Cristaria plicata, and Lamprotula leai) were studied monthly during Oct. 2003,Sep. 2004 in Lake Taihu with toxic cyanobacterial blooms in the summer. Qualitative and quantitative determinations of MCs in the organs were done by LC,MS and HPLC. The major toxins were present in the hepatopancreas (45.5,55.4%), followed by visceral mass with substantial amount of gonad (27.6,35.5%), whereas gill and foot were the least (1.8,5.1%). The maximum MC contents in the hepatopancreas, intestine, visceral mass, gill, foot, and rest were 38.48, 20.65, 1.70, 0.64, 0.58, and 0.61 ,g/g DW, respectively. There were rather good positive correlation in MC contents between intestines and hepatopancreas of the four bivalves (r = 0.75,0.97, p < 0.05). There appeared to be positive correlations between the maximum MC content in the hepatopancreas and the ,13C (r = 0.919) or ,15N (r = 0.878) of the foot, indicating that the different MC content in the hepatopancreas might be due to different food ingestion. A glutathione (GSH) conjugate of MC-LR was also detected in the foot sample of C. plicata. Among the foot samples analyzed, 54% were above the provisional WHO tolerable daily intake (TDI) level, and the mean daily intakes from the four bivalves were 8,23.5 times the TDI value when the bivalves are eaten as a whole, suggesting the high risk of consuming bivalves in Lake Taihu. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 572,584, 2005. [source] Physiological and biochemical analyses of microcystin-RR toxicity to the cyanobacterium Synechococcus elongatusENVIRONMENTAL TOXICOLOGY, Issue 6 2004Zhi-quan Hu Abstract Freshwater Microcystis may form dense blooms in eutrophic lakes. It is known to produce a family of related cyclic hepatopeptides (microcystins, MC) that constitute a threat to aquatic ecosystems. Most toxicological studies of microcystins have focused on aquatic animals and plants, with few examining the possible effects of microcystins on phytoplankton. In this study we chose the unicellular Synechococcus elongatus (one of the most studied and geographically most widely distributed cyanobacteria in the picoplankton) as the test material and investigated the biological parameters: growth, pigment (chlorophyll-a, phycocyanin), photosynthetic activity, nitrate reductase activity, and protein and carbohydrate content. The results revealed that microcystin-RR concentrations above 100 ,g · L,1 significantly inhibited the growth of Synechococcus elongatus. In addition, a change in color of the toxin-treated algae (chlorosis) was observed in the experiments. Furthermore, MC-RR markedly inhibited the synthesis of the pigments chlorophyll-a and phycocyanin. A drastic reduction in photochemical efficiency of PSII (Fv/Fm) was found after a 96-h incubation. Changes in protein and carbohydrate concentrations and in nitrate reductase activity also were observed during the exposure period. This study aimed to evaluate the mechanisms of microcystin toxicity on a cyanobacterium, according to the physiological and biochemical responses of Synechococcus elongatus to different doses of microcystin-RR. The ecological role of microcystins as an allelopathic substance also is discussed in the article. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 571,577, 2004. [source] Occurrence of toxic cyanobacterial blooms in San Roque Reservoir (Córdoba, Argentina): A field and chemometric studyENVIRONMENTAL TOXICOLOGY, Issue 3 2003María Valeria Amé Abstract We evaluated the presence of cyanobacterial blooms in San Roque Reservoir (Córdoba, Argentina). Cyanobacterial blooms and water samples were collected over 4 years (1998,2002). We confirmed the presence of microcystin-LR and microcystin-RR in 97% of these blooms. The total amount of microcystin (MC) ranged between 5.8 and 2400.0 ,g g,1 of freeze-dried bloom material. These values suggest that guidelines for safe water consumption and recreational use should be established for this reservoir. Twenty-eight physical and chemical parameters were measured in water samples and evaluated by discriminant analysis (DA). A first DA was used to evaluate the factors promoting cyanobacteria occurrence, identifying nine parameters following three patterns associated with cyanobacterial growth. Inorganic phosphorous was found to promote the presence of blooms, whereas the highest proliferation of cyanobacteria was observed in the presence of smaller amounts of carbonate, bicarbonate, sulfate, and fecal coliform bacteria. The results observed during our fieldwork, analyzed using DA, agreed with the results of other laboratory studies, thus confirming the usefulness of DA to help with the evaluation of a complicated environmental data matrix. A second DA, using only water samples collected during the presence of cyanobacteria blooms, identified another nine parameters. The analysis of these parameters allowed us to identify certain environmental factors that could lead to the dominance of toxic strains, thus increasing the amount of MC. The results showed that, in our case, an increase in the water temperature was associated with higher amounts of MC per dry weight unit, whereas an increase in the concentrations of ammonia,nitrogen and iron were associated with lower amounts of MC, thus disfavoring the dominance of toxic strains. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 192,201, 2003. [source] A critical reappraisal of treatment response criteria in systemic mastocytosis and a proposal for revisionsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2010A. Pardanani Abstract Mast cell disease (MCD) is a hematopoietic stem cell neoplasm that is associated with infiltration of one or more organs with cytologically abnormal mast cells (MC). MCD is frequently but not always associated with a KIT mutation and, in some cases, is associated with clonal expansion of non-MC lineage cells. In adults, there is almost always MC infiltration of the bone marrow, which is a cardinal feature of systemic mastocytosis (SM). While, as members of the wider community of physician scientists, we recognize the contribution of the current consensus treatment response criteria for SM, as individuals with more than average clinical experience in SM, we would like to point out their limitations and engage in a constructive discussion that will hopefully lead to a consideration for revisions. We present here an alternative proposal for treatment response assessments we believe is more objective, reproducible, and importantly, SM-subtype specific, given the recent progress in our understanding of the natural history of this disease. We believe this proposal is timely given the prospects for new clinical trials in SM, and the related regulatory aspects of new drug approval that are currently not adequately addressed. The intent of this exercise is not to undermine the complexity of the disease or previous work by other investigators, but to come up with ideas for response criteria that are more practical and consider meaningful patient outcome. [source] A systematic approach to molecular quantitative determination of mixed chimaerism following allogeneic bone marrow transplantation: an analysis of its applicability in a group of patients with severe aplastic anaemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2004Rocío Hassan Abstract:, Mixed chimaerism (MC) following allogeneic bone marrow transplantation (allo-BMT) is defined as the persistent cohabitation of haematopoietic cells from recipients and donors. Its kinetics, clinical implications and more efficient laboratory approaches for MC detection are the object of ongoing research in view of the possibility of developing useful markers. Here we describe a sequential analysis of chimaerism using variable number of tandem repeat (VNTR) polymerase chain reaction (PCR) followed by quantitative, fluorescent labelled, short tandem repeat (STR) PCR. A set of four, highly discriminative VNTR and four STR markers was used to assess chimaerism. Sensitivity and regression analysis indicated that this approach was reliable for routine application in a single BMT centre. We studied 12 patients with severe aplastic anaemia (SAA) who had received allo-BMT, and had been conditioned with cyclosphosphamide (Cy) with or without anti-thymocyte globulin (ATG). We found a 50% prevalence of MC in the whole group, with levels between 4% and 37% of recipient cells. A sustained stable MC pattern after BMT was characteristic of the Cy-only conditioned patients but was also recorded in one patient treated with the Cy + ATG regime who showed a sustained MC pattern over a period of 24 months post-BMT. In none of our patients, MC was associated with an increased risk of graft rejection in a median follow-up of 39.5 months. [source] Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2005Kathrin Hochegger Abstract Recently, divergent reports on the role of mast cells (MC) in different glomerular diseases have brought our attention to their role in an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). Genetically MC-deficient KitW/KitW - v mice, MC-reconstituted KitW/KitW - v mice and Kit+/+ control mice were subjected to anti-GBM GN. Kit+/+ mice developed moderate proteinuria and glomerular damage following the induction of anti-GBM nephritis. In contrast, proteinuria and glomerular damage were dramatically increased in MC-deficient KitW/KitW - v mice. MC-reconstituted KitW/KitW - v mice showed proteinuria and glomerular damage comparable to Kit+/+ mice. A significant increase in infiltrating T cells and macrophages was detected in MC-deficient KitW/KitW - v mice as compared to Kit+/+ control mice and MC-reconstituted KitW/KitW - v mice. Accordingly, we observed an increase of TGF-,1 mRNA in kidneys from KitW/KitW - v mice. Interestingly, we did not detect MC in the kidney using either Giemsa staining or RT-real-time PCR, but MC were found in the regional lymph nodes. Finally, mortality of KitW/KitW - v mice was significantly increased after the induction of anti-GBM GN due to uremia. Our report provides the first direct evidence that MC are protective in anti-GBM GN, possibly by modulating the influx of effector T cells and macrophages to inflammatory sites in the kidney. [source] Effect of Decrease of Hydride-Induced Embrittlement in Nanocrystalline Titanium,ADVANCED ENGINEERING MATERIALS, Issue 8 2010M.A. Murzinova Abstract The room-temperature impact toughness, strength and ductility of nanocrystalline (NC) and microcrystalline (MC) titanium with hydrogen content ranging from 0.1 to 16,at.-% (0.002 to 0.450,wt.-%) are studied. NC titanium has higher strength and lower sensitivity to hydride-induced brittle fracture than the MC material. In contrast to MC titanium, the elongation and impact toughness in the NC material does not decrease dramatically with increasing hydrogen content. Moreover, the fracture toughness in hydrogenated NC condition is found to be higher than that in MC titanium. This unusual result may be associated with the precipitation of equiaxial nanoscale hydrides in the interior of ,-grains in the NC material, while platelet hydrides are formed in MC titanium. One can expect that the risk of hydride-induced embrittlement is lower in NC than in MC titanium, making the NC material attractive for potential application under conditions that may cause hydrogen saturation above the permissible level for MC titanium. [source] Load-Adaptive MUI/ISI-Resilient Generalized Multi-Carrier CDMA with Linear and DF ReceiversEUROPEAN TRANSACTIONS ON TELECOMMUNICATIONS, Issue 6 2000Georgios B. Giannakis A plethora of single-carrier and multi-carrier (MC) CDMA systems have been proposed recently to mitigate intersymbol interference (ISI) and eliminate multiuser interference (MUI). We present a unifying all-digital Generalized Multicanier CDMA framework which enables us to describe existing CDMA schemes and to highlight thorny problems associated with them. To improve the bit error rate (BER) performance of existing schemes, we design block FIR transmitters and decision feedback (DF) receivers based on an inner-code/outer-code principle, which guarantees MUI/ISI-elimination regardless of the frequency-selective physical channel. The flexibility of our framework allows further BER enhancements by taking into account the load in the system (number of active users), while blind channel estimation results in bandwidth savings. Simulations illustrate the superiority of our framework over competing MC CDMA alternatives especially in the presence of uplink multipath channels. [source] Mast cell lines HMC-1 and LAD2 in comparison with mature human skin mast cells , drastically reduced levels of tryptase and chymase in mast cell linesEXPERIMENTAL DERMATOLOGY, Issue 9 2010Sven Guhl Please cite this paper as: Mast cell lines HMC-1 and LAD2 in comparison with mature human skin mast cells , drastically reduced levels of tryptase and chymase in mast cell lines. Experimental Dermatology 2010; 19: 845,847. Abstract:, To circumvent the costly isolation procedure associated with tissue mast cells (MC), two human MC lines, i.e. HMC-1 and LAD2, are frequently employed, but their relation to mature MC is unknown. Here, we quantitatively assessed their expression of MC markers in direct comparison to skin MC (sMC). sMC expressed all lineage markers at highest and HMC-1 cells at lowest levels. LAD2 cells expressed comparable high-affinity IgE receptor , (Fc,RI,) and Fc,RI, but less Fc,RI, than sMC and displayed slightly reduced, but robust Fc,RI-mediated histamine release. Only minor differences were found for total histamine content and c-Kit expression. Huge, and to this level unexpected, differences were found for MC tryptase and chymase, with sMC >>> LAD2 > HMC-1. Taken together, HMC-1 cells represent very immature malignantly transformed MC, whereas LAD2 cells can be considered intermediately differentiated. Because of the minute levels of MC proteases, MC lines can serve as surrogates of tissue MC to a limited degree only. [source] The role of the cutaneous cholinergic system in guttate psoriasisEXPERIMENTAL DERMATOLOGY, Issue 7 2008W. Dyck In previous studies, high levels of acetylcholine (ACh) have been reported in psoriasis lesions. In addition, patients with guttate psoriasis respond to oral treatment with atropine. We wanted to know how the cutaneous cholinergic system could be involved in this process. Since mast cells (MC) are characteristic components of the inflammatory infiltrate of guttate psoriasis, we compared ACh receptor (AChR) composition and ACh production in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a MC line (HMC-1) using PCR. We could confirm the presence of numerous MC in guttate psoriasis lesion. Both in vivo and in vitro, MC lacked expression of cholinacetyltransferase (ChAT), vesicular acetylcholintransorter (VAChT) and cholintransporter-1 (ChT-1) but contained high levels of acetylcholinesterase (AChE). In mast cells of both involved and uninvolved skin we found both nicotinic (,3, ,5, ,7, ,9, ,10, ,2 and ,4 subunits) and muscarinic (M1, M3, M4, M5) AChR. In HMC-1 cells all AChR subunits found in skin where present on mRNA level, except ,7 and ,2. In lesional epidermis both ACh production and AChR expression was shifted from the basal to the suprabasal layers especially the nicotinic ,3, ,5, ,9, ,2 and ,4 and the muscarinic M3 and M5 AChR subunits. Our results exclude a role of the cholinergic system in the initiation of keratinocyte proliferation in the basal epidermal layer but point towards a role of epidermal AChR in suprabasal processes, most likely terminal differentiation and barrier formation as has been shown in other systems. Most importantly, mast cells are targets of paracrine and endocrine effects mediated by ACh and choline thus modulating inflammatory processes like guttate psoriasis and explaining the clinical efficacity of anticholinergic drugs like atropine. [source] Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and , -melanocyte-stimulating hormone in the skinEXPERIMENTAL DERMATOLOGY, Issue 10 2006Simone König Abstract:, The neuroendocrine precursor protein proopiomelanocortin (POMC) and its derived neuropeptides are involved in a number of important regulatory processes in the central nervous system as well as in peripheral tissues. Despite its important role in controlling the local activation of melanocortin (MC) receptors, the extracellular proteolytic processing of POMC peptides has received little attention. The mechanisms relevant for controlling the bioavailability of adrenocorticotropin and melanocyte-stimulating hormones for the corresponding MC receptors in the skin by specific peptidases such as neprilysin (neutral endopeptidase; NEP) or angiotensin-converting enzyme (ACE) have been addressed in a number of recent investigations. This review summarizes the current body of knowledge concerning the qualitative and quantitative POMC peptide processing with respect to the action and specificity of NEP and ACE and discusses relevant recent analytical methodologies. [source] R120G ,B-crystallin promotes the unfolding of reduced ,-lactalbumin and is inherently unstableFEBS JOURNAL, Issue 3 2005Teresa M. Treweek ,-Crystallin is the principal lens protein which, in addition to its structural role, also acts as a molecular chaperone, to prevent aggregation and precipitation of other lens proteins. One of its two subunits, ,B-crystallin, is also expressed in many nonlenticular tissues, and a natural missense mutation, R120G, has been associated with cataract and desmin-related myopathy, a disorder of skeletal muscles [Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, Faure A, Chateau D, Chapon F, Tome F, Dupret JM, Paulin D & Fardeau M (1998) Nat Genet20, 92,95]. In the present study, real-time 1H-NMR spectroscopy showed that the ability of R120G ,B-crystallin to stabilize the partially folded, molten globule state of ,-lactalbumin was significantly reduced in comparison with wild-type ,B-crystallin. The mutant showed enhanced interaction with, and promoted unfolding of, reduced ,-lactalbumin, but showed limited chaperone activity for other target proteins. Using NMR spectroscopy, gel electrophoresis, and MS, we observed that, unlike the wild-type protein, R120G ,B-crystallin is intrinsically unstable in solution, with unfolding of the protein over time leading to aggregation and progressive truncation from the C-terminus. Light scattering, MS, and size-exclusion chromatography data indicated that R120G ,B-crystallin exists as a larger oligomer than wild-type ,B-crystallin, and its size increases with time. It is likely that removal of the positive charge from R120 of ,B-crystallin causes partial unfolding, increased exposure of hydrophobic regions, and enhances its susceptibility to proteolysis, thus reducing its solubility and promoting its aggregation and complexation with other proteins. These characteristics may explain the involvement of R120G ,B-crystallin with human disease states. [source] Light-Triggered Self-Assembly of a Spiropyran-Functionalized Dendron into Nano-/Micrometer-Sized Particles and Photoresponsive Organogel with Switchable FluorescenceADVANCED FUNCTIONAL MATERIALS, Issue 1 2010Qun Chen Abstract The synthesis, self-assembly, and spectroscopic investigations of spiropyran (SP)-functionalized dendron 1 are reported. Under UV light irradiation, assembly of 1 into nano-/microparticles occurs due to the transformation of the closed form of SP into the open merocyanine (MC) form. The formation of these nano-/microparticles is confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) experiments in addition to the confocal laser scanning microscopy (CLSM) measurements. These nano-/microparticles exhibit relatively strong red emission. It is interesting to note that the direct cooling of the toluene/benzene solution of 1 to 0,°C leads to gel formation. Multivalent ,,, interactions due to the dendron in 1 may be the driving-force for the gelation. The UV light irradiation cannot destroy the gel phase, and in fact, the gel,gel transition is successfully realized. The purple-blue gel exhibits relatively strong red fluorescence; moreover, the fluorescence can be reversibly switched by alternating UV and visible light irradiation. The results clearly indicate that the MC form after aggregation becomes more stable and fluorescent. [source] The effects of dietary Microcystis aeruginosa and microcystin on the copepods of the upper San Francisco EstuaryFRESHWATER BIOLOGY, Issue 7 2010KEMAL A. GER Summary 1. Increasing blooms of Microcystis aeruginosa have unknown impacts on the copepods Eurytemora affinis and Pseudodiaptomus forbesi, which are the dominant zooplankters and key prey species for endangered larval fish in the upper San Francisco Estuary. 2. Laboratory feeding experiments were designed to measure the effect of Microcystis on copepod survival and to distinguish the effects of toxicity and nutrition. In a series of survival tests, copepods were fed a mixed diet of algae plus one of two strains of Microcystis, either producing (MC+) or lacking microcystin (MC,). 3. Microcystis significantly reduced survival even when it was a small proportion of the diet, indicating that toxicity was the major cause of mortality. Contrary to expectation, however, the MC+ strain did not result in higher mortality, suggesting that non-MC metabolites of Microcystis can be toxic to copepods. 4. Across treatments, survival of P. forbesi was greater than that of E. affinis, although the two copepods responded differently to both the ratio and the strain of Microcystis in their food. Survival of P. forbesi was greater on the MC+ strain and was inversely proportional to the ratio of dietary Microcystis (MC+ or MC,). In contrast, survival of E. affinis declined similarly across treatments and was not related to the proportion or strain of dietary Microcystis. Results indicate that the copepod P. forbesi can coexist with Microcystis while the other copepod E. affinis cannot. 5. Regardless of species, dietary Microcystis caused significant mortality to copepods, and it may cause adverse impacts to the potentially food-limited zooplankton community of the San Francisco Estuary. These impacts may not be related to the cellular MC concentration because Microcystis contains other metabolites that negatively affect copepods. [source] Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chainsGENETIC EPIDEMIOLOGY, Issue 4 2008Yunjung Kim Abstract A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD increases, the effects of high-order LD tends to get weaker due to the lack of observed multilocus haplotypes. The overall estimates of first, second, third, and fourth order LD across the ENCODE regions are 64, 23, 9, and 3%. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] Herbage growth rates on heterogeneous swards as influenced by sward-height classesGRASS & FORAGE SCIENCE, Issue 1 2009ahin Demirba Abstract The contribution of four classes of sward height to daily herbage growth rates of a heterogeneous sward in eight periods throughout a grazing season was investigated in two continuous cattle-grazing systems differing in intensity (moderate stocking rate: MC; lenient stocking rate: LC). At the beginning and end of periods of 12 to 28 d, the compressed sward height (CSH) was measured in exclusion cages at eighteen fixed points per cage to derive daily growth rates for the four classes of sward height. Stratified calibrations were made to relate sward height to herbage mass for each treatment in each period. Quadratic regressions described the relationship between herbage growth rate and initial CSH for each treatment in each period. For scaling up to the scale of the plot, CSH was measured monthly at 100 points per plot. Daily herbage growth rates declined from more than 100 kg dry matter (DM) ha,1 d,1 on both treatments at the beginning of the grazing season to 20 kg DM ha,1 d,1 or less, especially on treatment LC. This was due to the larger area covered by tall herbage on treatment LC than on treatment MC. On treatment MC, daily herbage growth rate was predominantly derived from short sward areas of up to 12 cm in height while sward areas taller than 12 cm contributed most to daily growth rates on treatment LC in early summer. The method used is considered suitable for estimating daily herbage growth rates of different classes of sward height in extensively managed pastures and can easily be adapted to deal with more heterogeneous swards than used in this study. [source] Hyaluronan and its receptors in mucoepidermoid carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2006Richard O. Wein MD Abstract Background. Hyaluronan (HA) is a prominent extracellular matrix component undergoing continuous production and degradation. Increased HA levels have been described in a variety of tumors. The objective of this study was to examine the staining patterns of HA and two of its associated receptors (CD44 and HARE) in relation to the metastatic potential of mucoepidermoid carcinoma (MC). Immunohistochemical staining of preserved surgical specimens was used. Methods. Tissues from 12 patients with a histologic diagnosis of salivary MC (10 parotid, one submandibular gland, one minor salivary gland) were studied. Half (six of 12) of the patients had regional metastases. Tumor, normal salivary tissue, and regional lymph nodes were stained for HA, CD44, and HARE expression. Specimens were graded for staining intensity and a percent of the specimen stained. Results. Normal salivary tissue did not demonstrate epithelial cell surface HA expression, whereas HA was expressed on tumor cells and in regional lymph nodes containing metastases. These differences were both significant using Student's t test (p < .00002, and p < .0022, respectively). Tumors with positive nodes tended to have greater cell surface HA. Decreased expression or downregulation of HARE was also noted in involved lymph nodes. No differences in CD44 expression were seen between primary specimens and lymph nodes. The observed staining patterns for CD44 and HARE were not reflective of the metastatic potential of the primary MC. Conclusions. Increased HA expression was seen on mucoepidermoid carcinoma cells compared with adjacent normal salivary gland epithelium. This observation may assist in explaining the development of regional metastasis in these tumors. We did not identify specific HA, CD44, or HARE staining patterns in primary lesions that were predictive of regional metastases. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Does the Impact of Managed Care on Substance Abuse Treatment Services Vary by Provider Profit Status?HEALTH SERVICES RESEARCH, Issue 6p1 2005Todd A. Olmstead Objective. To extend our previous research by determining whether, and how, the impact of managed care (MC) on substance abuse treatment (SAT) services differs by facility ownership. Data Sources. The 2000 National Survey of Substance Abuse Treatment Services, which is designed to collect data on service offerings and other characteristics of SAT facilities in the U.S. These data are merged with data from the 2002 Area Resource File, a county-specific database containing information on population and MC activity. We use data on 10,513 facilities, virtually a census of all SAT facilities. Study Design. For each facility ownership type (for-profit [FP], not-for-profit [NFP], public), we estimate the impact of MC on the number and types of SAT services offered. We use instrumental variables techniques that account for possible endogeneity between facilities' involvement in MC and service offerings. Principal Findings. We find that the impact of MC on SAT service offerings differs in magnitude and direction by facility ownership. On average, MC causes FPs to offer approximately four additional services, causes publics to offer approximately four fewer services, and has no impact on the number of services offered by NFPs. The differential impact of MC on FPs and publics appears to be concentrated in therapy/counseling, medical testing, and transitional services. Conclusion. Our findings raise policy concerns that MC may reduce the quality of care provided by public SAT facilities by limiting the range of services offered. On the other hand, we find that FP clinics increase their range of services. One explanation is that MC results in standardization of service offerings across facilities of different ownership type. Further research is needed to better understand both the specific mechanisms of MC on SAT and the net impact on society. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||