Melanin-concentrating hormone and neuropeptide EI projections from the lateral hypothalamic area and zona incerta to the medial septal nucleus and spinal cord: a study using multiple neuronal tracers.

PubMed

Bittencourt, J C; Elias, C F

1998-09-14

The projection pathways of neurons containing melanin-concentrating hormone (MCH) and neuropeptide EI (NEI), two peptides colocalized in the lateral hypothalamic area (LHA) of the rat, were mapped using the retrogradely transported fluorescent dyes, true blue (TB) and diamidino yellow (DY). TB and DY were injected into the medial septum/diagonal band complex (MS/DBC) and the thoracic level of the spinal cord (SpCd), respectively. Brains from rats receiving only one or both tracer injections were immunohistochemically stained for MCH in the spinal cord and NEI in the forebrain. In the MS/DBC, NEI-immunoreactive (-ir) fibers are concentrated in the MS and in the vertical and horizontal limbs of the DBC. In the SpCd, MCH-ir fibers are concentrated primarily in lamina X. Of the diencephalic NEI-ir neurons, 37.15% project to the MS/DBC and reside in the rostromedial zona incerta (ZIm), in the LHAt and LHAp, and in the perifornical region. Of the diencephalic MCH-ir neurons, 20.2% project to the SpCd and reside in the LHAt and LHAp. In addition, 2. 2% of the MCH-ir cells and 8.7% of the NEI-ir cells in the hypothalamus were labeled with both retrograde tracers and thus project to both the MS/DBC and SpCd. These dual projection neurons are located mainly in the LHAt and LHAp. Anterograde injections of the tracer Phaseolus vulgaris leucoagglutinin into the LHAt and ZIm corroborated our findings in the retrograde studies. Potential autonomic and behavioral roles of the NEI and MCH systems in the MS/DBC and the SpCd are discussed. Copyright 1998 Elsevier Science B. V.

The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mesarosova, Monika; Valovicova, Zuzana; Srancikova, Annamaria

2011-09-15

The environmental pollutant 7H-dibenzo[c,g]carbazole (DBC) and its derivative, 5,9-dimethylDBC (DiMeDBC), produced significant and dose-dependent levels of micronuclei followed by a substantial increase in the frequency of apoptotic cells in the V79MZh3A4 cell line stably expressing the human cytochrome P450 (hCYP) 3A4. In contrast, neither micronuclei nor apoptosis were found in cells exposed to the sarcomagenic carcinogen, N-methylDBC (N-MeDBC). A slight but significant level of gene mutations and DNA adducts detected in V79MZh3A4 cells treated with N-MeDBC, only at the highest concentration (30 {mu}M), revealed that this sarcomagenic carcinogen was also metabolized by hCYP3A4. Surprisingly, DBC increased the frequency of 6-thioguaninemore » resistant (6-TG{sup r}) mutations only at the highest concentration (30 {mu}M), while DiMeDBC failed to increase the frequency of these mutations. The resistance to 6-thioguanine is caused by the mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene. The molecular analysis of the coding region of Hprt gene showed a deletion of the entire exon 8 in DiMeDBC-induced 6-TG{sup r} mutants, while no changes in the nucleotide sequences were identified in 6-TG{sup r} mutants produced by DBC and N-MeDBC. Based on our results, we suggest that hCYP3A4 is involved in the metabolism of DBC and its tissue-specific derivatives. While hCYP3A4 probably plays an important role in biotransformation of the liver carcinogens, DBC and DiMeDBC, it might only have a marginal function in N-MeDBC metabolism. - Highlights: > DBC activation via CYP3A4 resulted in micronuclei, DNA adduct formation and mutations in V79MZh3A4 cells. > The CYP3A4-mediated DiMeDBC activation caused micronuclei followed by apoptosis in V79MZh3A4 cells. > The genotoxic effects produced by N-MeDBC in V79MZh3A4 cells were negligible. > The hCYP3A4 may play an important role in DBC and DiMeDBC metabolism. > The CYP3A4 might only have a marginal function in N-MeDBC metabolism.« less

Hydrothermal systems are a sink for dissolved black carbon in the deep ocean

NASA Astrophysics Data System (ADS)

Niggemann, J.; Hawkes, J. A.; Rossel, P. E.; Stubbins, A.; Dittmar, T.

2016-02-01

Exposure to heat during fires on land or geothermal processes in Earth's crust induces modifications in the molecular structure of organic matter. The products of this thermogenesis are collectively termed black carbon. Dissolved black carbon (DBC) is a significant component of the oceanic dissolved organic carbon (DOC) pool. In the deep ocean, DBC accounts for 2% of DOC and has an apparent radiocarbon age of 18,000 years. Thus, DBC is much older than the bulk DOC pool, suggesting that DBC is highly refractory. Recently, it has been shown that recalcitrant deep-ocean DOC is efficiently removed during hydrothermal circulation. Here, we hypothesize that hydrothermal circulation is also a net sink for deep ocean DBC. We analyzed DBC in samples collected at different vent sites in the Atlantic, Pacific and Southern oceans. DBC was quantified in solid-phase extracts as benzenepolycarboxylic acids (BPCAs) following nitric acid digestion. Concentrations of DBC were much lower in hydrothermal fluids than in surrounding deep ocean seawater, confirming that hydrothermal circulation acts as a net sink for oceanic DBC. The relative contribution of DBC to bulk DOC did not change during hydrothermal circulation, indicating that DBC is removed at similar rates as bulk DOC. The ratio of the oxidation products benzenehexacarboxylic acid (B6CA) to benzenepentacarboxylic acid (B5CA) was significantly higher in hydrothermally altered samples compared to ratios typically found in the deep ocean, reflecting a higher degree of condensation of DBC molecules after hydrothermal circulation. Our study identified hydrothermal circulation as a quantitatively important sink for refractory DBC in the deep ocean. In contrast to photodegradation of DBC at the sea surface, which is more efficient for more condensed DBC, i.e. decreasing the B6CA/B5CA ratio, hydrothermal processing increases the B6CA/B5CA ratio, introducing a characteristic hydrothermal DBC signature.

Environmental Dynamics of Dissolved Black Carbon in the Amazon River

NASA Astrophysics Data System (ADS)

Roebuck, J. A., Jr.; Gonsior, M.; Enrich-Prast, A.; Jaffe, R.

2016-02-01

Dissolve black carbon (DBC) is an important component in the global carbon cycle and constitutes a significant portion of dissolved organic carbon (DOC) in aquatic systems. While global fluxes of DBC may be well understood, little is known about systematic processing of this carbon pool in fluvial systems. Similar to DOC, DBC composition may change as it moves throughout a river continuum before it is eventually deposited into the ocean. This is especially important for large river systems that are major sources of DOC to the ocean and may have significant impacts on ocean biogeochemistry and carbon cycling. To better understand variations in DBC dynamics throughout a large fluvial system, DBC was quantified using the benzene polycarboxylic acid method (BPCA) in three major tributaries of the Amazon River, each with varying biogeochemical characteristics. Principal component analysis of the BPCA abundances was used to assess the DBC compositional differences between sampling locations. In some rivers, light availability appeared to influence both DBC quantity and quality. Higher concentrations of DBC characterized by a larger, more aromatic DBC pool was found in the Rio Negro, a black water river with high levels of chromophoric dissolved organic matter and low light penetration. In the Rio Tapajós, a clear water river with higher light penetration, lower DBC concentrations characterized by higher abundances of the less polycondensed DBC pool provided evidence of photodecomposition under such conditions. The Rio Madeira, characterized as a white water river with high suspended sediment yields and high mineral/clay content, had the lowest DBC concentrations and the least polycondensed DBC content, suggesting a preferential adsorption of the more highly polycondensed DBC components onto clay particles.

Utilizing Colored Dissolved Organic Matter to Derive Dissolved Black Carbon Export by Arctic Rivers

NASA Astrophysics Data System (ADS)

Stubbins, Aron; Spencer, Robert; Mann, Paul; Holmes, R.; McClelland, James; Niggemann, Jutta; Dittmar, Thorsten

2015-10-01

Wildfires have produced black carbon (BC) since land plants emerged. Condensed aromatic compounds, a form of BC, have accumulated to become a major component of the soil carbon pool. Condensed aromatics leach from soils into rivers, where they are termed dissolved black carbon (DBC). The transport of DBC by rivers to the sea is a major term in the global carbon and BC cycles. To estimate Arctic river DBC export, 25 samples collected from the six largest Arctic rivers (Kolyma, Lena, Mackenzie, Ob’, Yenisey and Yukon) were analyzed for dissolved organic carbon (DOC), colored dissolved organic matter (CDOM), and DBC. A simple, linear regression between DOC and DBC indicated that DBC accounted for 8.9 ± 0.3% DOC exported by Arctic rivers. To improve upon this estimate, an optical proxy for DBC was developed based upon the linear correlation between DBC concentrations and CDOM light absorption coefficients at 254 nm (a254). Relatively easy to measure a254 values were determined for 410 Arctic river samples between 2004 and 2010. Each of these a254 values was converted to a DBC concentration based upon the linear correlation, providing an extended record of DBC concentration. The extended DBC record was coupled with daily discharge data from the six rivers to estimate riverine DBC loads using the LOADEST modeling program. The six rivers studied cover 53% of the pan-Arctic watershed and exported 1.5 ± 0.1 million tons of DBC per year. Scaling up to the full area of the pan-Arctic watershed, we estimate that Arctic rivers carry 2.8 ± 0.3 million tons of DBC from land to the Arctic Ocean each year. This equates to ~8% of Arctic river DOC export, slightly less than indicated by the simpler DBC vs DOC correlation-based estimate. Riverine discharge is predicted to increase in a warmer Arctic. DBC export was positively correlated with river runoff, suggesting that the export of soil BC to the Arctic Ocean is likely to increase as the Arctic warms.

The longitudinal relationship between behavior and emotional disturbance in young people with intellectual disability and maternal mental health

PubMed Central

Gray, Kylie M; Piccinin, Andrea M; Hofer, Scott M; Mackinnon, Andrew; Bontempo, Daniel E; Einfeld, Stewart L; Parmenter, Trevor; Tonge, Bruce J

2011-01-01

Although elevated rates of parent psychosocial distress have been associated with child behavior and emotional problems, little is known about the nature of this relationship over time. This study followed an epidemiological cohort of children and adolescents over 11 years with 4 waves of data collection. Within this cohort, complete data were available on 238 mothers and their children. Behavior and emotional problems were assessed using the DBC, maternal mental health with the GHQ. Multivariate growth curve modelling was used to evaluate the commonality of individual change patterns. High levels of mental health problems were reported, which were stable over time. Higher scores on the DBC were associated with higher rates of mental health problems. Increases in child social relating problems were associated with increases mental health symptoms, particularly depression and anxiety. PMID:21295442

The Proteomic Profile of Deleted in Breast Cancer 1 (DBC1) Interactions Points to a Multifaceted Regulation of Gene Expression*

PubMed Central

Giguère, Sophie S. B.; Guise, Amanda J.; Jean Beltran, Pierre M.; Joshi, Preeti M.; Greco, Todd M.; Quach, Olivia L.; Kong, Jeffery; Cristea, Ileana M.

2016-01-01

Deleted in breast cancer 1 (DBC1) has emerged as an important regulator of multiple cellular processes, ranging from gene expression to cell cycle progression. DBC1 has been linked to tumorigenesis both as an inhibitor of histone deacetylases, HDAC3 and sirtuin 1, and as a transcriptional cofactor for nuclear hormone receptors. However, despite mounting interest in DBC1, relatively little is known about the range of its interacting partners and the scope of its functions. Here, we carried out a functional proteomics-based investigation of DBC1 interactions in two relevant cell types, T cells and kidney cells. Microscopy, molecular biology, biochemistry, and mass spectrometry studies allowed us to assess DBC1 mRNA and protein levels, localization, phosphorylation status, and protein interaction networks. The comparison of DBC1 interactions in these cell types revealed conserved regulatory roles for DBC1 in gene expression, chromatin organization and modification, and cell cycle progression. Interestingly, we observe previously unrecognized DBC1 interactions with proteins encoded by cancer-associated genes. Among these interactions are five components of the SWI/SNF complex, the most frequently mutated chromatin remodeling complex in human cancers. Additionally, we identified a DBC1 interaction with TBL1XR1, a component of the NCoR complex, which we validated by reciprocal isolation. Strikingly, we discovered that DBC1 associates with proteins that regulate the circadian cycle, including DDX5, DHX9, and SFPQ. We validated this interaction by colocalization and reciprocal isolation. Functional assessment of this association demonstrated that DBC1 protein levels are important for regulating CLOCK and BMAL1 protein oscillations in synchronized T cells. Our results suggest that DBC1 is integral to the maintenance of the circadian molecular clock. Furthermore, the identified interactions provide a valuable resource for the exploration of pathways involved in DBC1-associated tumorigenesis. PMID:26657080

Chk2 and REGγ-dependent DBC1 regulation in DNA damage induced apoptosis

PubMed Central

Magni, Martina; Ruscica, Vincenzo; Buscemi, Giacomo; Kim, Ja-Eun; Nachimuthu, Benjamin Tamilselvan; Fontanella, Enrico; Delia, Domenico; Zannini, Laura

2014-01-01

Human DBC1 (Deleted in Breast Cancer 1; KIAA1967; CCAR2) is a protein implicated in the regulation of apoptosis, transcription and histone modifications. Upon DNA damage, DBC1 is phosphorylated by ATM/ATR on Thr454 and this modification increases its inhibitory interaction with SIRT1, leading to p53 acetylation and p53-dependent apoptosis. Here, we report that the inhibition of SIRT1 by DBC1 in the DNA damage response (DDR) also depends on Chk2, the transducer kinase that is activated by ATM upon DNA lesions and contributes to the spreading of DNA damage signal. Indeed we found that inactivation of Chk2 reduces DBC1-SIRT1 binding, thus preventing p53 acetylation and DBC1-induced apoptosis. These events are mediated by Chk2 phosphorylation of the 11S proteasome activator REGγ on Ser247, which increases REGγ-DBC1 interaction and SIRT1 inhibition. Overall our results clarify the mechanisms underlying the DBC1-dependent SIRT1 inhibition and link, for the first time, Chk2 and REGγ to the ATM-DBC1-SIRT1 axis. PMID:25361978

Dissolved black carbon in grassland streams: is there an effect of recent fire history?

PubMed

Ding, Yan; Yamashita, Youhei; Dodds, Walter K; Jaffé, Rudolf

2013-03-01

While the existence of black carbon as part of dissolved organic matter (DOM) has been confirmed, quantitative determinations of dissolved black carbon (DBC) in freshwater ecosystem and information on factors controlling its concentration are scarce. In this study, stream surface water samples from a series of watersheds subject to different burn frequencies in Konza Prairie (Kansas, USA) were collected in order to determine if recent fire history has a noticeable effect on DBC concentration. The DBC levels detected ranged from 0.04 to 0.11 mg L(-1), accounting for ca. 3.32±0.51% of dissolved organic carbon (DOC). No correlation was found between DBC concentration and neither fire frequency nor time since last burn. We suggest that limited DBC flux is related to high burning efficiency, possibly greater export during periods of high discharge and/or the continuous export of DBC over long time scales. A linear correlation between DOC and DBC concentrations was observed, suggesting the export mechanisms determining DOC and DBC concentrations are likely coupled. The potential influence of fire history was less than the influence of other factors controlling the DOC and DBC dynamics in this ecosystem. Assuming similar conditions and processes apply in grasslands elsewhere, extrapolation to a global scale would suggest a global grasslands flux of DBC on the order of 0.14 Mt carbon year(-1). Copyright © 2012 Elsevier Ltd. All rights reserved.

Deleted in breast cancer 1 (DBC1) protein regulates hepatic gluconeogenesis.

PubMed

Nin, Veronica; Chini, Claudia C S; Escande, Carlos; Capellini, Verena; Chini, Eduardo N

2014-02-28

Liver gluconeogenesis is essential to provide energy to glycolytic tissues during fasting periods. However, aberrant up-regulation of this metabolic pathway contributes to the progression of glucose intolerance in individuals with diabetes. Phosphoenolpyruvate carboxykinase (PEPCK) expression plays a critical role in the modulation of gluconeogenesis. Several pathways contribute to the regulation of PEPCK, including the nuclear receptor Rev-erbα and the histone deacetylase SIRT1. Deleted in breast cancer 1 (DBC1) is a nuclear protein that binds to and regulates both Rev-erbα and SIRT1 and, therefore, is a candidate to participate in the regulation of PEPCK. In this work, we provide evidence that DBC1 regulates glucose metabolism and the expression of PEPCK. We show that DBC1 levels decrease early in the fasting state. Also, DBC1 KO mice display higher gluconeogenesis in a normal and a high-fat diet. DBC1 absence leads to an increase in PEPCK mRNA and protein expression. Conversely, overexpression of DBC1 results in a decrease in PEPCK mRNA and protein levels. DBC1 regulates the levels of Rev-erbα, and manipulation of Rev-erbα activity or levels prevents the effect of DBC1 on PEPCK. In addition, Rev-erbα levels decrease in the first hours of fasting. Finally, knockdown of the deacetylase SIRT1 eliminates the effect of DBC1 knockdown on Rev-erbα levels and PEPCK expression, suggesting that the mechanism of PEPCK regulation is, at least in part, dependent on the activity of this enzyme. Our results point to DBC1 as a novel regulator of gluconeogenesis.

Psychopathology in Young People With Intellectual Disability

PubMed Central

Einfeld, Stewart L.; Piccinin, Andrea M.; Mackinnon, Andrew; Hofer, Scott M.; Taffe, John; Gray, Kylie M.; Bontempo, Daniel E.; Hoffman, Lesa R.; Parmenter, Trevor; Tonge, Bruce J.

2008-01-01

Context Comorbid severe mental health problems complicating intellectual disability are a common and costly public health problem. Although these problems are known to begin in early childhood, little is known of how they evolve over time or whether they continue into adulthood. Objective To study the course of psychopathology in a representative population of children and adolescents with intellectual disability. Design, Setting, and Participants The participants of the Australian Child to Adult Development Study, an epidemiological cohort of 578 children and adolescents recruited in 1991 from health, education, and family agencies that provided services to children with intellectual disability aged 5 to 19.5 years in 6 rural and urban census regions in Australia, were followed up for 14 years with 4 time waves of data collection. Data were obtained from 507 participants, with 84% of wave 1 (1991-1992) participants being followed up at wave 4 (2002-2003). Main Outcome Measures The Developmental Behaviour Checklist (DBC), a validated measure of psychopathology in young people with intellectual disability, completed by parents or other caregivers. Changes over time in the Total Behaviour Problem Score and 5 subscale scores of the DBC scores were modeled using growth curve analysis. Results High initial levels of behavioral and emotional disturbance decreased only slowly over time, remaining high into young adulthood, declining by 1.05 per year on the DBC Total Behaviour Problem Score. Overall severity of psychopathology was similar across mild to severe ranges of intellectual disability (with mean Total Behaviour Problem Scores of approximately 44). Psychopathology decreased more in boys than girls over time (boys starting with scores 2.61 points higher at baseline and ending with scores 2.57 points lower at wave 4), and more so in participants with mild intellectual disability compared with those with severe or profound intellectual disability who diverged from having scores 0.53 points lower at study commencement increasing to a difference of 6.98 points below severely affected children by wave 4. This trend was observed in each of the subscales, except the social-relating disturbance subscale, which increased over time. Prevalence of participants meeting criteria for major psychopathology or definite psychiatric disorder decreased from 41% at wave 1 to 31% at wave 4. Few of the participants (10%) with psychopathology received mental health interventions during the study period. Conclusion These results provide evidence that the problem of psychopathology comorbid with intellectual disability is both substantial and persistent and suggest the need for effective mental health interventions. PMID:17062861

Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism

PubMed Central

Hubbard, Basil P; Loh, Christine; Gomes, Ana P; Li, Jun; Lu, Quinn; Doyle, Taylor LG; Disch, Jeremy S; Armour, Sean M; Ellis, James L; Vlasuk, George P; Sinclair, David A

2013-01-01

SIRT1 is an NAD+-dependent deacetylase that counteracts multiple disease states associated with aging and may underlie some of the health benefits of calorie restriction. Understanding how SIRT1 is regulated in vivo could therefore lead to new strategies to treat age-related diseases. SIRT1 forms a stable complex with DBC1, an endogenous inhibitor. Little is known regarding the biochemical nature of SIRT1-DBC1 complex formation, how it is regulated and whether or not it is possible to block this interaction pharmacologically. In this study, we show that critical residues within the catalytic core of SIRT1 mediate binding to DBC1 via its N-terminal region, and that several carboxamide SIRT1 inhibitors, including EX-527, can completely block this interaction. We identify two acetylation sites on DBC1 that regulate its ability to bind SIRT1 and suppress its activity. Furthermore, we show that DBC1 itself is a substrate for SIRT1. Surprisingly, the effect of EX-527 on SIRT1-DBC1 binding is independent of DBC1 acetylation. Together, these data show that protein acetylation serves as an endogenous regulatory mechanism for SIRT1-DBC1 binding and illuminate a new path to developing small-molecule modulators of SIRT1. PMID:23892437

Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism.

PubMed

Hubbard, Basil P; Loh, Christine; Gomes, Ana P; Li, Jun; Lu, Quinn; Doyle, Taylor Lg; Disch, Jeremy S; Armour, Sean M; Ellis, James L; Vlasuk, George P; Sinclair, David A

2013-07-15

SIRT1 is an NAD (+) -dependent deacetylase that counteracts multiple disease states associated with aging and may underlie some of the health benefits of calorie restriction. Understanding how SIRT1 is regulated in vivo could therefore lead to new strategies to treat age-related diseases. SIRT1 forms a stable complex with DBC1, an endogenous inhibitor. Little is known regarding the biochemical nature of SIRT1-DBC1 complex formation, how it is regulated and whether or not it is possible to block this interaction pharmacologically. In this study, we show that critical residues within the catalytic core of SIRT1 mediate binding to DBC1 via its N-terminal region, and that several carboxamide SIRT1 inhibitors, including EX-527, can completely block this interaction. We identify two acetylation sites on DBC1 that regulate its ability to bind SIRT1 and suppress its activity. Furthermore, we show that DBC1 itself is a substrate for SIRT1. Surprisingly, the effect of EX-527 on SIRT1-DBC1 binding is independent of DBC1 acetylation. Together, these data show that protein acetylation serves as an endogenous regulatory mechanism for SIRT1-DBC1 binding and illuminate a new path to developing small-molecule modulators of SIRT1.

Dissolved black carbon in the global cryosphere: concentrations and chemical signatures

NASA Astrophysics Data System (ADS)

Khan, A. L.; Wagner, S.; Jaffe, R.; Xian, P.; Williams, M. W.; Armstrong, R. L.; McKnight, D. M.

2017-12-01

Black carbon (BC) is derived from the incomplete combustion of biomass and fossil fuels and can enhance glacial recession when deposited on snow and ice surfaces. Here we explore the influence of environmental conditions and the proximity to anthropogenic sources on the concentration and composition of dissolved black carbon (DBC), as measured by benzenepolycaroxylic acid (BPCA) markers, across snow, lakes, and streams from the global cryosphere. Data are presented from Antarctica, the Arctic, and high alpine regions of the Himalayas, Rockies, Andes, and Alps. DBC concentrations spanned from 0.62 μg/L to 170 μg/L. The median and (2.5, 97.5) quantiles in the pristine samples were 1.8 μg/L (0.62, 12), and non-pristine samples were 21 μg/L (1.6, 170). DBC is susceptible to photodegradation when exposed to solar radiation. This process leads to a less condensed BPCA signature. In general, DBC across the dataset was comprised of less-polycondensed DBC. However, DBC from the Greenland Ice Sheet (GRIS) had a highly-condensed BPCA molecular signature. This could be due to recent deposition of BC from Canadian wildfires. Variation in DBC appears to be driven by a combination of photochemical processing and the source combustion conditions under which the DBC was formed. Overall, DBC was found to persist across the global cryosphere in both pristine and non-pristine snow and surface waters. The high concentration of DBC measured in supra-glacial melt on the GRIS suggests DBC can be mobilized across ice surfaces. This is significant because these processes may jointly exacerbate surface albedo reduction in the cryosphere.

Delayed breast cellulitis: An evolving complication of breast conservation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Indelicato, Daniel J.; Grobmyer, Stephen R.; Newlin, Heather

2006-12-01

Purpose: Delayed breast cellulitis (DBC) is characterized by the late onset of breast erythema, edema, tenderness, and warmth. This retrospective study analyzes the risk factors and clinical course of DBC. Methods and Materials: From 1985 through 2004, 580 sequential women with 601 stage T0-2N0-1 breast cancers underwent breast conserving therapy. Cases of DBC were identified according to accepted clinical criteria: diffuse breast erythema, edema, tenderness, and warmth occurring >3 months after definitive surgery and >3 weeks after radiotherapy. Potential risk factors analyzed included patient comorbidity, operative technique, acute complications, and details of adjunctive therapy. Response to treatment and long-term outcomemore » were analyzed to characterize the natural course of this syndrome. Results: Of the 601 cases, 16%, 52%, and 32% were Stage 0, I, and II, respectively. The overall incidence of DBC was 8% (50/601). Obesity, ecchymoses, T stage, the presence and aspiration of a breast hematoma/seroma, removal of >5 axillary lymph nodes, and arm lymphedema were significantly associated with DBC. The median time to onset of DBC from the date of definitive surgery was 226 days. Ninety-two percent of DBC patients were empirically treated with antibiotics. Fourteen percent required more invasive intervention. Twenty-two percent had recurrent episodes of DBC. Ultimately, 2 patients (4%) underwent mastectomy for intractable breast pain related to DBC. Conclusion: Although multifactorial, we believe DBC is primarily related to a bacterial infection in the setting of impaired lymphatic drainage and may appear months after completion of radiotherapy. Invasive testing before a trial of antibiotics is generally not recommended.« less

Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshihara, Takashi; Collado, Denise; Hamaguchi, Masaaki

2007-07-13

The expression of tumor suppressor gene DBC2 causes certain breast cancer cells to stop growing [M. Hamaguchi, J.L. Meth, C. Von Klitzing, W. Wei, D. Esposito, L. Rodgers, T. Walsh, P. Welcsh, M.C. King, M.H. Wigler, DBC2, a candidate for a tumor suppressor gene involved in breast cancer, Proc. Natl. Acad. Sci. USA 99 (2002) 13647-13652]. Recently, DBC2 was found to participate in diverse cellular functions such as protein transport, cytoskeleton regulation, apoptosis, and cell cycle control [V. Siripurapu, J.L. Meth, N. Kobayashi, M. Hamaguchi, DBC2 significantly influences cell cycle, apoptosis, cytoskeleton, and membrane trafficking pathways. J. Mol. Biol. 346more » (2005) 83-89]. Its tumor suppression mechanism, however, remains unclear. In this paper, we demonstrate that DBC2 suppresses breast cancer proliferation through down-regulation of Cyclin D1 (CCND1). Additionally, the constitutional overexpression of CCND1 prevented the negative impact of DBC2 expression on their growth. Under a CCND1 promoter, the expression of CCNE1 exhibited the same protective effect. Our results indicate that the down-regulation of CCND1 is an essential step for DBC2's growth suppression of cancer cells. We believe that this discovery contributes to a better understanding of DBC2's tumor suppressor function.« less

Dissolved black carbon in the global cryosphere: Concentrations and chemical signatures

NASA Astrophysics Data System (ADS)

Khan, Alia L.; Wagner, Sasha; Jaffe, Rudolf; Xian, Peng; Williams, Mark; Armstrong, Richard; McKnight, Diane

2017-06-01

Black carbon (BC) is derived from the incomplete combustion of biomass and fossil fuels and can enhance glacial recession when deposited on snow and ice surfaces. Here we explore the influence of environmental conditions and the proximity to anthropogenic sources on the concentration and composition of dissolved black carbon (DBC), as measured by benzenepolycaroxylic acid (BPCA) markers, across snow, lakes, and streams from the global cryosphere. Data are presented from Antarctica, the Arctic, and high alpine regions of the Himalayas, Rockies, Andes, and Alps. DBC concentrations spanned from 0.62 μg/L to 170 μg/L. The median and (2.5, 97.5) quantiles in the pristine samples were 1.8 μg/L (0.62, 12), and nonpristine samples were 21 μg/L (1.6, 170). DBC is susceptible to photodegradation when exposed to solar radiation. This process leads to a less condensed BPCA signature. In general, DBC across the data set was composed of less polycondensed DBC. However, DBC from the Greenland Ice Sheet (GRIS) had a highly condensed BPCA molecular signature. This could be due to recent deposition of BC from Canadian wildfires. Variation in DBC appears to be driven by a combination of photochemical processing and the source combustion conditions under which the DBC was formed. Overall, DBC was found to persist across the global cryosphere in both pristine and nonpristine snow and surface waters. The high concentration of DBC measured in supraglacial melt on the GRIS suggests that DBC can be mobilized across ice surfaces. This is significant because these processes may jointly exacerbate surface albedo reduction in the cryosphere.