bluuebunny/crossref_metadata_2025 huggingface dataset:
Sociodemographic Predictors of Pattern and Volume of Alcohol Consumption Across Hispanics, Blacks, and Whites: 10‐Year Trend (1992–2002)
Authors: Caetano Raul , Baruah Jonali , Ramisetty‐Mikler Suhasini , Ebama Malembe S.
Published: July 2010

Background:  There have been limited trend studies examining variations on the patterns of alcohol consumption among Whites, Blacks, and Hispanics in the United States. The current paper reports national trends in drinking patterns, volume of drinking (number of drinks per month), binge drinking, and drinking to intoxication among Blacks, Whites, and Hispanics over a period of 10 years and identifies sociodemographic predictors of these behaviors across the 3 ethnic groups.

Methods:  Data are from the 1991 to 1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES; n = 42,862) and the 2001 to 2002 National Epidemiologic Study on Alcohol and Related Conditions (NESARC; n = 43,093). Both surveys used multistage cluster sample procedures to select respondents 18 years of age and older from the U.S. household population.

Results:  Trends varied across different dimensions of drinking and ethnic groups. There were no statistically significant differences in the mean number of drinks consumed per month among men and women in any of the 3 ethnic groups between 1992 and 2002, but there was a significant rise in the proportion of current drinkers in both genders and in all 3 ethnic groups. Multivariate analysis indicated that, compared to Whites in 1992, Blacks and Hispanics did not increase their volume of drinking, but Whites did. Drinking 5 or more drinks in day at all did not increase between 1992 and 2002, but drinking 5 or more drinks at least once a month was more likely for all groups in 2002 compared to Whites in 1992. Drinking to intoxication at all was more likely among Whites in 2002 than 1992, but drinking to intoxication at least once a month was more likely among Whites and Blacks in 2002 than 1992.

Conclusion:  The only common trend between 1992 and 2002 across both genders and 3 ethnic groups was a rise in the proportion of drinkers. There was also a rise in drinking 5 or more drinks in a day (Whites, Blacks, and Hispanics) and drinking to intoxication (Whites and Blacks), but this was limited to those reporting such drinking at least once a month. The reasons for these changes are many and may involve complex sociodemographic changes in the population. It is important for the field to closely monitor these cross‐ethnic trends in alcohol consumption.
The Impact of Maternal Age on the Effects of Prenatal Alcohol Exposure on Attention
Authors: Chiodo Lisa M. , Da Costa David E. , Hannigan John H. , Covington Chandice Y. , Sokol Robert J. , Janisse James , Greenwald Mark , Ager Joel , Delaney‐Black Virginia
Published: July 2010

Background:  Prenatal exposure to alcohol has a variety of morphologic and neurobehavioral consequences, yet more than 10% of women continue to drink during pregnancy, placing their offspring at risk for fetal alcohol spectrum disorders (FASD). Identification of at‐risk pregnancies has been difficult, in part, because the presence and severity of FASD are influenced by factors beyond the pattern of alcohol consumption. Establishing maternal characteristics, such as maternal age, that increase the risk of FASD is critical for targeted pregnancy intervention.

Methods:  We examined the moderating effect of maternal age on measures of attention in 462 children from a longitudinal cohort born to women with known alcohol consumption levels (absolute ounces of alcohol per day at conception) who were recruited during pregnancy. Analyses examined the impact of binge drinking, as average ounces of absolute alcohol per drinking day. Smoking and use of cocaine, marijuana, and opiates were also assessed. At 7 years of age, the children completed the Continuous Performance Test, and their teachers completed the Achenbach Teacher Report Form.

Results:  After controlling for covariates, stepwise multiple regression analyses revealed a negative relation between levels of prenatal binge drinking and several measures of attention. The interaction between alcohol consumption and maternal age was also significant, indicating that the impact of maternal binge drinking during pregnancy on attention was greater among children born to older drinking mothers.

Conclusion:  These findings are consistent with previous findings that children born to older alcohol‐using women have more deleterious effects of prenatal alcohol exposure on other neurobehavioral outcomes.
Decomposition Analysis of Waste Generation From Stocks in a Dynamic System
Authors: Oguchi Masahiro , Tasaki Tomohiro , Moriguchi Yuichi
Published: July 2010

We conducted a decomposition analysis of material flows in a dynamic system, focusing on factors in the generation of waste consumer durables. A methodology for the analysis of consumer durables was developed and applied to three common consumer durables: cathode ray tube TVs, refrigerators, and passenger cars. The methodology decomposed changes in the numbers of waste products into three factors: changes in lifespan distribution, past trends in replacement sales, and past trends in sales for additional purchases. The decomposed equation clearly showed that the number of waste products would not necessarily be reduced by lifespan extension alone. This is because the number of waste products generated is affected not only by current lifespan distribution but also by past trends in sales for replacement and in additional purchases. The results show that changes in past replacement sales influence the current generation of waste, even if current replacement sales are declining. To reduce the generation of waste products on a short‐term basis, lifespan must be extended until the waste‐reducing effect of lifespan extension exceeds the waste‐increasing effect of the other two factors. From a long‐term perspective, controlling current replacement and additional purchases can be used to prevent future waste product generation.
Obama, Reagan and Zero Nukes
Authors: SHULTZ GEORGE
Published: July 2010

Is President Barack Obama's proposal for zero nuclear weapons realistic? Will it make the world more secure, or more prone to wars since they are no longer unthinkable?

To evaluate this bold strategic initiative, we have invited comments from two former US secretaries of state, a former director of the CIA and the former head of the International Atomic Energy Agency who led the hunt for Saddam's non‐existent weapons of mass destruction on the eve of the Iraq war.
The BRICs Come of Global Age
Authors: LULA DA SILVA LUIZ INÁCIO
Published: July 2010

The world is rapidly evolving on many fronts. Brazil, Turkey and other emerging powers are taking their own initiatives and building their own global links outside the old frameworks of the G‐8, the United Nations Security Council and NATO. The “third way” politics of Tony Blair that embraced globalization from the left of center in Britain has given way to the Tory party once again. Just as recovery from the financial crash seemed on the horizon, Europe's sovereign debt crisis has erupted. The historically unprecedented pace and scale of urbanization in China is transforming the politics of the Communist Party.

President Lula of Brazil, former US treasury secretary Henry Paulson, Singapore's foreign minister George Yeo and others take stock of these manifold developments.
Turkey's Emergence as a “Center Power” Is a Game Changer
Authors: OZEL SOLI
Published: July 2010

The world is rapidly evolving on many fronts. Brazil, Turkey and other emerging powers are taking their own initiatives and building their own global links outside the old frameworks of the G‐8, the United Nations Security Council and NATO. The “third way” politics of Tony Blair that embraced globalization from the left of center in Britain has given way to the Tory party once again. Just as recovery from the financial crash seemed on the horizon, Europe's sovereign debt crisis has erupted. The historically unprecedented pace and scale of urbanization in China is transforming the politics of the Communist Party.

President Lula of Brazil, former US treasury secretary Henry Paulson, Singapore's foreign minister George Yeo and others take stock of these manifold developments.
Protectionism Against China Is No Answer to America's Woes
Authors: FUKUYAMA FRANCIS , PAULSON HENRY
Published: July 2010

The world is rapidly evolving on many fronts. Brazil, Turkey and other emerging powers are taking their own initiatives and building their own global links outside the old frameworks of the G‐8, the United Nations Security Council and NATO. The “third way” politics of Tony Blair that embraced globalization from the left of center in Britain has given way to the Tory party once again. Just as recovery from the financial crash seemed on the horizon, Europe's sovereign debt crisis has erupted. The historically unprecedented pace and scale of urbanization in China is transforming the politics of the Communist Party.

President Lula of Brazil, former US treasury secretary Henry Paulson, Singapore's foreign minister George Yeo and others take stock of these manifold developments.
Greece Is Tip of Sovereign Debt Iceberg
Authors: ROUBINI NOURIEL
Published: July 2010

The world is rapidly evolving on many fronts. Brazil, Turkey and other emerging powers are taking their own initiatives and building their own global links outside the old frameworks of the G‐8, the United Nations Security Council and NATO. The “third way” politics of Tony Blair that embraced globalization from the left of center in Britain has given way to the Tory party once again. Just as recovery from the financial crash seemed on the horizon, Europe's sovereign debt crisis has erupted. The historically unprecedented pace and scale of urbanization in China is transforming the politics of the Communist Party.

President Lula of Brazil, former US treasury secretary Henry Paulson, Singapore's foreign minister George Yeo and others take stock of these manifold developments.
China's Megacity Mandarinate
Authors: YEO GEORGE
Published: July 2010

The world is rapidly evolving on many fronts. Brazil, Turkey and other emerging powers are taking their own initiatives and building their own global links outside the old frameworks of the G‐8, the United Nations Security Council and NATO. The “third way” politics of Tony Blair that embraced globalization from the left of center in Britain has given way to the Tory party once again. Just as recovery from the financial crash seemed on the horizon, Europe's sovereign debt crisis has erupted. The historically unprecedented pace and scale of urbanization in China is transforming the politics of the Communist Party.

President Lula of Brazil, former US treasury secretary Henry Paulson, Singapore's foreign minister George Yeo and others take stock of these manifold developments.
Effect of Nutrient Concentration and Salinity on Immotile–Motile Transformation of Chromera velia
Authors: GUO JIN TAO , WEATHERBY KATE , CARTER DEE , ŠLAPETA JAN
Published: July 2010

ABSTRACT. Chromera velia (Chromerida: Alveolata) is a photosynthetic, unicellular organism closely related to parasitic apicomplexa. Diurnal rhythmicity of an immotile–motile transformation has been observed but its role in the life cycle remains largely unknown. Using a multiwell system, we show that salinity and f‐medium concentration significantly affect the percentage of motile C. velia cells. An inverse relationship between salinity and motility in C. velia occurred, and flagellation was also suppressed at high nutrient levels. These results suggest a low salinity environment with relatively low nutrient levels enables flagellate transformation during the diurnal cycle of C. velia.
Melatonin inhibits postischemic matrix metalloproteinase‐9 (MMP‐9) activation via dual modulation of plasminogen/plasmin system and endogenous MMP inhibitor in mice subjected to transient focal cerebral ischemia
Authors: Tai Shih‐Huang , Chen Hung‐Yi , Lee E‐Jian , Chen Tsung‐Ying , Lin Hsiao‐Wen , Hung Yu‐Chang , Huang Sheng‐Yang , Chen Ying‐Hsin , Lee Wei‐Ting , Wu Tian‐Shung
Published: July 2010

Abstract:  We have shown that melatonin attenuated matrix metalloproteinase‐9 (MMP‐9) activation and decreased the risk of hemorrhagic transformation following cerebral ischemia‐reperfusion. Herein, we investigate the possible involvement of the plasminogen/plasmin system and endogenous MMPs inhibitor underlying the melatonin‐mediated MMP‐9 inhibition. Mice were subjected to 1‐hr ischemia and 48‐hr reperfusion of the right middle cerebral artery. Melatonin (5 mg/kg) or vehicle was intravenously injected upon reperfusion. Brain infarction and hemorrhagic transformation were measured. Extracellular matrix damage was determined by Western immunoblot analysis for laminin protein. The activity and expression of MMP‐2 and MMP‐9 were determined by gelatin zymography, in situ zymography, and Western immunoblot analysis. In addition, the activities of tissue and urokinase plasminogen activators (tPA and uPA) were evaluated by plasminogen‐dependent casein zymography. Endogenous plasminogen activator inhibitor (PAI) and tissue inhibitors of MMP (TIMP‐1) were investigated using enzyme‐linked immunosorbent assay (ELISA) and Western immunoblot analysis, respectively. Cerebral ischemia‐reperfusion induced increased MMP‐9 activity and expression at 12–48 hr after reperfusion onset. Relative to controls, melatonin‐treated animals had significantly decreased MMP‐9 activity and expression (P < 0.05), in addition to reduced brain infarction and hemorrhagic transformation as well as improved laminin protein preservation. This melatonin‐mediated MMP‐9 inhibition was accompanied by reduced uPA activity (P < 0.05), as well as increased TIMP‐1 expression and PAI activity (P < 0.05, respectively). These results demonstrate the melatonin’s pluripotent mechanisms for attenuating postischemic MMP‐9 activation and neurovascular damage, and further support it as an add‐on to thrombolytic therapy for ischemic stroke patients.
Traditional Chinese medicine and oral diseases: today and tomorrow
Authors: Zheng LW , Hua H , Cheung LK
Published: July 2010

Oral Diseases (2010) 17, 7–12

With a history of over 2000 years, traditional Chinese medicine (TCM) evolves into a unique system of diagnosing and treating illnesses. It is a challenge to convey the fundamentals of this traditional medicine to our Western colleagues because of the differences in language, philosophy and concept of diagnosis and treatment. This review attempts to tackle these barriers by introducing several widely used Chinese medicines for treating oral diseases. China Journals Full‐text Database and Pubmed were used as the searching engines. Although many studies have demonstrated that the Chinese medicines are effective in treating oral diseases including recurrent aphthous stomatitis, oral lichen planus, leukoplakia, and Sjögren’s syndrome, most of them lacked standard criteria of post‐treatment assessment and laboratory evidence. Randomized controlled clinical trials with specific assessment criteria are required to close the gap between TCM and evidenced‐based medicine.
Deficient Knowledge Nursing Diagnosis: Identifying the Learning Needs of Patients With Cardiac Disease
Authors: Galdeano Luzia Elaine , Rossi Lídia Aparecida , Spadoti Dantas Rosana Aparecida
Published: July 2010

OBJECTIVES.  To identify the learning needs of patients with cardiac disease and the aspects of the disease and anesthetic and surgical procedures about which Brazilian patients have the greatest gaps in knowledge.

METHODS.  Eighty preoperative patients answered a General Evaluation Questionnaire, a Questionnaire to Evaluate Patient Knowledge, and the Mini‐Mental State Exam.

FINDINGS.  Fifty‐nine patients had learning needs. More than 50% of the patients were mistaken or unable to answer questions about the disease, and the goals of and type of surgery to be performed and anesthesia to be used.

CONCLUSIONS.  Most patients had poor performance on the questionnaire that assessed their knowledge about coronary artery disease and its treatment.

PRACTICE IMPLICATIONS.  This study can contribute to health professionals' assessment of patients' knowledge.

OBJETIVOS.  Identificar as necessidades de aprendizagem de pacientes com doença cardíaca e os aspectos da doença arterial coronariana e da revascularização do miocárdio do nos quais os pacientes brasileiros apresentam conhecimento deficiente.

MÉTODO.  Oitenta pacientes responderam o Questionário para avaliação geral, o Questionário para avaliar o conhecimento e o Mini‐Exame do Estado Mental.

RESULTADOS.  Cinqüenta e nove pacientes apresentaram necessidade de aprendizagem. Mais de 50% dos pacientes erraram ou não souberam responder as questões referentes ao nome da doença, aos sinais e sintomas de complicação da doença, aos objetivos e tipo de cirurgia e anestesia.

CONCLUSÃO.  Muitos pacientes não apresentaram bom desempenho no questionário para medir conhecimento em relação à Doença Arterial Coronária e seu tratamento.

IMPLICAÇÕES PRÁTICAS.  Este estudo poderá contribuir para a avaliação do conhecimento dos pacientes por profissionais da saúde.
Invited Paper: Teaching Nursing Diagnosis to Increase Utilization After Graduation
Authors: Carpenito‐Moyet Lynda Juall
Published: July 2010

BACKGROUND.  The majority of nursing programs identify the nursing process and diagnosis as critical elements in their curricula, yet it is often absent in classroom and clinical discussions. The failure of faculty to integrate the nursing process and diagnoses into learning experiences creates students spending endless hours creating a care plan document that requires little critical thinking, a document that does not improve the student's likelihood of utilizing nursing diagnosis after graduation.

PURPOSE.  This paper would outline the educational barriers for integration of these concepts into practice.

DISCUSSION.  Classroom and clinical strategies that guide the student to focused learning on nursing diagnoses and utilize standardized predicted care plans can produce desired curriculum outcomes, and ultimately, practice utilization will be presented.
Case Study: Child With Global Developmental Delay
Authors: Okumakpeyi Pearline , Lunney Margaret
Published: July 2010

PURPOSE.  This case study focused on the care of a child with global developmental delay.

DATA SOURCES.  Data were obtained through the author's clinical practice in long‐term care pediatric rehabilitation and literature sources.

DATA SYNTHESIS.  NANDA‐International Classifications, the Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC) were used to identify the appropriate nursing diagnosis, nursing interventions, and patient outcomes.

CONCLUSIONS.  This case study provides the pertinent nursing diagnoses, interventions, and outcomes for a child with global developmental delay. The interdisciplinary team approach and family involvement is addressed.

IMPLICATIONS FOR NURSING.  Use of NANDA, NIC, and NOC outcomes constructs for enhancing the care of a child with global developmental delay.
Let's Not Forget the Biodiversity of the Cities
Authors: Lugo Ariel E.
Published: July 2010

Cities contain over half of the world's population and are the source of many anthropogenic effects on the world's biota. Close examination of San Juan, Puerto Rico, a tropical city, reveals a significant green infrastructure. The city contains natural and human‐constructed forests, urban aquatic systems with native and introduced species, and a thriving and diverse biota adapted to urban conditions. It behooves tropical ecologists to pay attention to the biodiversity of urban environments to learn lessons about ecological persistence and adaptation to novel anthropogenic environments.
Remembering kauri on the ‘Kauri Coast’
Authors: Boswijk Gretel
Published: July 2010

This paper explores how the recent history of kauri is remembered and commemorated on the Kauri Coast, western Northland, focusing on three specific heritage sites: The Kauri Museum at Matakohe, Trounson Kauri Park, and Waipoua Forest Sanctuary. Each site was established to preserve elements of the past before they were lost or irrevocably altered. The museum commemorates the pioneers and the kauri timber and gum industries, while Trounson Kauri Park and Waipoua Forest were intended to represent primeval forest and stand as monuments to people who advocated their protection.
Performing a new regional geography
Authors: Winder Gordon , Lewis Nick
Published: July 2010

In this introduction to the Special Issue ‘Practising a New Regional Geography in Northland’, we call for a new regional geography. We use the experience of a field course to reflect upon the opportunities and challenges associated with doing ‘regional geography’ in the regions, a subdiscipline that has in recent decades been pushed into the backwaters of the discipline. We reinterpret the maxim ‘geography is what geographers do’ in a new way that emphasises pedagogy and research practice. The case of Northland and helping our students to learn experientially about community and environment under the rubric of sustainability allows us to argue the case for a reinterpretation of regional geography in these terms. We position the contributions in this Special Issue in terms of our call.
Effects of exercise training on adipogenesis of stromal‐vascular fraction cells in rat epididymal white adipose tissue
Authors: Sakurai T. , Endo S. , Hatano D. , Ogasawara J. , Kizaki T. , Oh‐ishi S. , Izawa T. , Ishida H. , Ohno H.
Published: July 2010

Aim:  Previous studies have shown that exercise training reduced white adipose tissue (WAT) mass compared to that in sedentary controls, and that the smaller mass contained fewer adipocytes. However, the effect of exercise training on adipogenesis is not completely clear. Therefore, we re‐examined the effect of exercise training on adipocyte numbers in WAT and, if such an effect was found tested the adipogenic responses of stromal‐vascular fraction (SVF) cells containing adipose tissue‐derived stem cells (ADSC) in epididymal WAT from exercise‐trained (TR) rats.

Methods:  Wistar male rats were divided into two groups: control (C) and TR. The TR rats were subjected to exercise on a treadmill for 9 weeks. SVF cells containing ADSC were separated from epididymal WAT by centrifugation. Expression of adipocyte differentiation‐related genes and adipogenesis of SVF cells were examined.

Results:  In SVF cells of TR rats, the expression of peroxisome proliferator‐activated receptor γ (PPARγ) and that of PPARγ target lipogenic genes was dramatically downregulated, whereas that of preadipocyte factor‐1 gene was significantly upregulated. Lipid accumulation in SVF cells of TR rats after the induction of adipocyte differentiation was significantly suppressed in comparison with that of C rats. Moreover, increased expression of hypoxia‐inducible factor‐1α (HIF‐1α) protein was observed in SVF cells of TR rats. Pre‐treatment of YC‐1, a potent HIF‐1α inhibitor, in SVF cells of TR rats restored adipogenesis.

Conclusion:  These results suggest that exercise training suppresses the ability of SVF cells to differentiate into adipocytes, and that underlying mechanisms involve the upregulation of HIF‐1α expression.
First record of Blastopsylla occidentalis Taylor, 1985 (Hemiptera: Psyllidae), a Eucalyptus psyllid in Cameroon, Central Africa
Authors: TAMESSE Joseph Lebel , LAURENTINE Soufo , WENCESLAS Yana , JOLY Dzokou Victor
Published: July 2010

In order to investigate the biodiversity of psyllids in Cameroon, we collected a psyllid on Eucalyptus spp. (Myrtaceae) for the first time. Morphometric and morphological studies of this psyllid enable us to identify it as Blastopsylla occidentalis Taylor (Hemiptera: Psylloidea). Blastopsylla occidentalis lives on four Eucalyptus species (Eucalyptus globulus, E. saligna, E. deglupta, E. camaldulensis) in the Western and Central regions of the country. A description and illustration of the different developmental stages of B. occidentalis will allow the identification of this pest of Eucalyptus.
Taxonomic study of Korean Eriborus Förster (Hymenoptera: Ichneumonidae: Campopleginae) new to Korea
Authors: CHOI Jin‐Kyung , LEE Jong‐Wook
Published: July 2010

We report one species, Eriborus vulgaris (Morley, 1913), new to Korea. A revised key to the species of Korean Eriborus Förster, redescriptions and photographs of diagnostic characters are provided.
Apoptosis: A Two‐edged Sword in Aging
Authors: WARNER HUBER R.
Published: July 2010

Here we summarize briefly what is known about both the positive and negative impacts of apoptosis during aging in mammalian systems and also update an earlier review. It is important to understand both of these impacts to devise useful interventions. Such interventions include both physiological and molecular approaches, including transgenic interventions. The critical roles of the mitochondria in both generating reactive oxygen species, and in initiating apoptosis are recognized, suggesting that maintaining mitochondrial function could be an important therapeutic goal, especially in post‐mitotic tissues. In contrast, the ability to eliminate unwanted, damaged and dysfunctional cells through apoptosis has anti‐aging implications in mitotic tissues.
Neither Caspase‐3 nor DNA Fragmentation Factor Is Required for High Molecular Weight DNA Degradation in Apoptosis
Authors: WALKER P. ROY , LEBLANC JULIE , CARSON CHRISTINE , RIBECCO MARIA , SIKORSKA MARIANNA
Published: July 2010

In this paper, we show that there is a two‐step process of DNA fragmentation in apoptosis; DNA is first cleaved to large fragments of 50–300 kb that are subsequently cleaved to smaller oligonucleosomes in some, but not all cells. Significantly, only the first stage is considered essential for cell death since some cells, for example human MCF7 breast carcinoma cells and human NT2 neuronal cells, do not show this behavior but still display normal nuclear morphological apoptotic changes. In cells that usually produce small fragments blocking the second (internucleosomal) stage of DNA fragmentation prevents neither nuclear condensation nor apoptosis. We are beginning to understand why the extent of DNA fragmentation during apoptosis varies enormously and why it appears to be a function of the cell type not the inducer. Presumably, this reflects the content of not only endonuclease activit(ies) but also on the ability of the cells to activate caspases, particularly caspase‐3, and other proteases that may be involved in endonuclease activation. Since NT2 cells activate caspase‐3, but do not correctly process DFF45, b other factors must also impinge on the inevitability of that process.
Regulation of Transglutaminases by Nitric Oxide
Authors: BERNASSOLA FRANCESCA , ROSSI ANTONELLO , MELINO GERRY
Published: July 2010

Nitric oxide (NO) is an inorganic diffusible molecular messenger that plays several central roles in pathophysiology. NO can affect the biological activity of proteins through the direct or indirect (via intermeidate S‐nitrosothiols) S‐nitrosylation of protein thiol groups. Transglutaminases (TGases), CA++‐dependent enzymes that modify proteins by cross‐linking reactions, require a cysteine residue in the active site as a prerequisite for their catalytic activity. Therefore, NO may regulate enzymatic activity of TGases and their biological effects, via S‐nitrosylation of their crucial thiol groups. We here review the effects of NO on coagulation factor XIII (fXIII, or plasma TGase) and Tgase 2 (or tissue transglutaminase). NO has an inhibitory effect on fXIII, thus suppressing the γ‐chain cross‐linking in fibrin gels, and subsequent clot formation. Tissue transglutaminase, an apoptotic effector molecule, also represents a molecular target for NO. Accordingly, the inhibition of tissue transglutaminase enzymatic activity by NO is able to prevent the induction of apoptosis.
Bone Morphogenetic Proteins Regulate Interdigital Cell Death in the Avian Embryo
Authors: MERINO RAMÓN , GAÑÁN YOLANDA , MACIAS DOMINGO , RODRÍGUEZ‐LEÓN JOAQUÍN , HURLE JUAN M.
Published: July 2010

The embryonic limb bud provides an excellent model for analyzing the mechanisms that regulate programmed cell death during development. At the time of digit formation in the developing autopod, the undifferentiated distal mesodermal cells may undergo or chondrogenic differentiation or apoptosis depending whether they are incorporated into the future digital rays or into the interdigital spaces. Both chondrogenesis or apoptosis are induced by local BMPS. However, whereas the chondrogenic‐promoting activity of BMPs appears to be regulated through the BMPR‐ 1b receptor, the mechanism by which the BMPs execute the death program remains unknown. The BMP proapoptotic activity requires the expression of members of the msx family of closely related homeobox‐containing genes and is finally mediated by caspase activation, but the nature of the caspase(s) directly responsible for the cell death is also unknown. Finally, other growth factors present in the developing autopod at the stages of digit formation such as members of the FGF and TGFβ families modulate the ability of BMPs to induce cell death or chondrogenesis.
The Immune Response to Apoptotic Cells
Authors: MEVORACH DROR
Published: July 2010

Programmed cell death (PCD) can be divided into two distinct but linked sequential processes, killing of the cells and removal of the dead cells, which may be a neighboring cell or a professional phagocyte. Following internalization of the apoptotic cell, the phagocyte typically triggers neither the development of a pro‐inflammatory response not the production of autoantibodies directed against apoptotic self antigens. Since apoptotic cells are characterized by translocation of autoantigens such as nucleosomes to the surface of the cell, we tested the hypothesis that excess or abnormally processed apoptotic cells can generate autoantibodies. We have found that syngeneic apoptotic load can induce transient hypergammaglobulinemia, anti‐DNA, anticardiolipin, and glomerular depositions in normal mice. Furthermore, we also found that one of the important mechanisms of uptake of apoptotic cells involves opsonization by the complement system, suggesting that deficient states could lead to aberrant handling of apoptotic cells. Therefore, conditions in which apoptotic cells become immunogenic may explain antigen selection in inflammatory and autoimmune conditions, such as in systemic lupus erythematosus (SLE).
The Pituitary‐Skin Connection in Amphibians: Reciprocal Regulation of Melanotrope Cells and Dermal Melanocytes
Authors: VAUDRY H. , CHARTREL N. , DESRUES L. , GALAS L. , KIKUYAMA S. , MOR A. , NICOLAS P. , TONON M. C.
Published: July 2010

ABSTRACT: In amphibians, α‐MSH secreted by the pars intermedia of the pituitary plays a pivotal role in the process of skin color adaptation. Reciprocally, the skin of amphibians contains a number of regulatory peptides, some of which have been found to regulate the activity of pituitary melanotrope cells. In particular, the skin of certain species of amphibians harbours considerable amounts of thyrotropin‐releasing hormone, a highly potent stimulator of α‐MSH release. Recently, we have isolated and sequenced from the skin of the frog Phyllomedusa bicolor‐a novel peptide named skin peptide tyrosine tyrosine (SPYY), which exhibits 94% similarity with PYY from the frog Rana ridibunda. For concentrations ranging from 5 × 10−10 to 10−7 M, SPYY induces a dose‐related inhibition of α‐MSH secretion. At a dose of 10−7 M, SPYY totally abolished α‐MSH release. These data strongly suggest the existence of a regulatory loop between the pars intermedia of the pituitary and the skin in amphibians.
The Subtilisin/Kexin Family of Precursor Convertases: Emphasis on PC1, PC2/7B2, POMC and the Novel Enzyme SKI‐1
Authors: SEIDAH NABIL G. , BENJANNET SUZANNE , HAMELIN JOSÉE , MAMARBACHI AIDA M. , BASAK AJOY , MARCINKIEWICZ JADWIGA , MBIKAY MAJAMBU , CHRÉTIEN MICHEL , MARCINKIEWICZ MIECZYSLAW
Published: July 2010

ABSTRACT: Proopiomelanocortin (POMC) is a precursor to various, bioactive peptides including ACTH, βLPH, αMSH, and βendorphin (βEND). Processing of POMC at dibasic residues is tissue‐specific and is performed by either PC1 alone (resulting in ACTH and βLPH, anterior pituitary corticotrophes) or by a combination of PC1 and PC2 (yielding αMSH and βEND, pituitary neurointermediate lobe and hypothalamus). The PC2‐specific binding protein 7B2 is intimately involved in the zymogen activation of proPC2 into PC2. Structure‐function studies of these enzymes demonstrated the presence of N‐ and C‐terminal domains, as well as specific amino acids within the catalytic segment that influence the degree of activity of each enzyme and the interaction of PC2 with 7B2. The tissue distribution, plasticity of expression, and the multiple precursors that are differentially cleaved by PC1 and/or PC2, predict a wide array of combinatorial activities of these convertases within the endocrine and neuroendocrine system. The phenotypic consequences of the absence of genetic expression of either PC1 or PC2 are now explored using knockout mice and in human patients suffering from obesity and diabetes.
Genetic Studies of the Human Melanocortin‐1 Receptor
Authors: REES JONATHAN L. , BIRCH‐MACHIN MARK , FLANAGAN NIAMH , HEALY EUGENE , PHILLIPS SION , TODD CAROLE
Published: July 2010

ABSTRACT: Genetic approaches have suggested a critical role for the melanocortin‐1 receptor in the control of pigmentation. We showed that this gene is unusually polymorphic in European populations and that, of the many variants, three in particular appear to be associated with red hair or fair skin. Family studies suggest these are inherited as an autosomal recessive trait (or at least approximate to this in many families). To date all individuals with two of these three changes (homozygote or compound heterozygote) have red hair. Early functional studies are in keeping with defective signalling through MC1R. An interested and perhaps unexpected question relates to the evolutionary factors that have given rise to such variants. Two models can be proposed, that are based on multiple alleles with minor changes in function or genetic hitch‐hicking.
α‐MSH in Systemic Inflammation: Central and Peripheral Actions
Authors: CATANIA ANNA , DELGADO RENÉ , AIRAGHI LORENA , CUTULI MARIAGRAZIA , GAROFALO LETIZIA , CARLIN ANDREA , DEMITRI MARIA TERESA , LIPTON JAMES M.
Published: July 2010

ABSTRACT: Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on α‐melanocyte stimulating hormone (α‐MSH). Increases in circulating TNF‐α and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, were modulated by central injection of a small concentration of α‐MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central α‐MSH. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central α‐MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central α‐MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by α‐MSH could be used to treat systemic inflammation. In addition to its central influences, α‐MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. α‐MSH reduces chemotaxis of human neutrophils and production of TNF‐α, neopterin, and NO by monocytes. In research on septic patients, α‐MSH inhibited release of TNF‐α, interleukin‐1β (IL‐1β), and interleukin‐8 (IL‐8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.
Mechanisms of the Antiinflammatory Effects of α‐MSH: Role of Transcription Factor NF‐κB and Adhesion Molecule Expression
Authors: KALDEN D.‐H. , SCHOLZEN T. , BRZOSKA T. , LUGER T. A.
Published: July 2010

ABSTRACT: The recruitment of leukocytes from the circulation to inflamed tissue is regulated by the expression of adhesion molecules on both leukocytes and endothelial cells. The proopiomelanocortin‐derived peptide α‐melanocyte stimulating hormone (α‐MSH) is known to modulate inflammation. Thus, we investigated the influence of α‐MSH on the LPS‐induced expression of the adhesion molecules E‐selectin and VCAM‐1 on endothelial cells. Human microvascular endothelial cells (HMEC‐1) were treated with LPS (100 ng/ml) alone or in the presence of α‐MSH (10−8 to 10−16 M). RT‐PCR analysis showed that α‐MSH significantly reduced LPS‐induced expression of VCAM‐1 and E‐selectin. Since many adhesion molecules contain regulatory NF‐κB sites in their promoter region, the role of α‐MSH in the activation of the transcription factor NF‐αB was also investigated. α‐MSH significantly downregulated the LPS‐mediated activation of NF‐κB, in a dose‐dependent manner. These findings indicate that modulation of the transcription factor NF‐κB is a crucial molecular event, one that seems to be responsible for the antiinflammatory effects of α‐MSH.
Cutaneous Expression of CRH and CRH‐R: Is There a “Skin Stress Response System?”
Authors: SLOMINSKI ANDRZEJ T. , BOTCHKAREV VLADIMIR , CHOUDHRY MASHKOOR , FAZAL NADEEM , FECHNER KLAUS , FURKERT JENS , KRAUSE EBERHART , ROLOFF BIRGIT , SAYEED MOHAMMAD , WEI EDWARD , ZBYTEK BLAZEJ , ZIPPER JOSEF , WORTSMAN JACOBO , PAUS RALF
Published: July 2010

ABSTRACT:The classical neuroendocrine pathway for response to systemic stress is by hypothalamic release of corticotropin releasing hormone (CRH), subsequent activation of pituitary CRH receptors (CRH‐R), and production and release of proopiomelanocortin (POMC) derived peptides. It has been proposed that an equivalent to the hypothalamic‐pituitary‐adrenal axis functions in mammalian skin, in response to local stress (seeReference 1). To further define such system we used immunocytochemistry, RP‐HPLC separation, and RIA techniques, in rodent and human skin, and in cultured normal and malignant melanocytes and keratinocytes. Production of mRNA for CRH‐R1 was documented in mouse and human skin using RT‐PCR and Northern blot techniques; CRH binding sites and CRH‐R1 protein were also identified. Addition of CRH to immortalized human keratinocytes, and to rodent and human melanoma cells induced rapid, specific, and dose‐dependent increases in intracellular Ca2+. The latter were inhibited by the CRH antagonist α‐helical‐CRH(9–41) and by the depletion of extracellular calcium with EGTA. CRH production was enhanced by ultraviolet light radiation and forskolin (a stimulator for intracellular cAMP production), and inhibited by dexamethasone. Thus, evidence that skin cells, both produce CRH and express functional CRH‐R1, supports the existence of a local CRH/CRH‐R neuroendocrine pathway that may be activated within the context of askin stress response system.
Corticotropin Releasing Factor Receptors and Their Ligand Family
Authors: PERRIN MARILYN H. , VALE WYLIE W.
Published: July 2010

ABSTRACT:The CRF receptors belong to the VIP/GRF/PTH family of G‐protein coupled receptors whose actions are mediated through activation of adenylate cyclase. Two CRF receptors, encoded by distinct genes, CRF‐R1 and CRF‐R2, and that can exist in two alternatively spliced forms, have been cloned. The type‐1 receptor is expressed in many areas of the rodent brain, as well as in the pituitary, gonads, and skin. In the rodent, one splice variant of the type‐2 receptor, CRF‐R2α, is expressed mainly in the brain, whereas the other variant, CRF‐R2β, is found not only in the CNS, but also in cardiac and skeletal muscle, epididymis, and the gastrointestinal tract. The poor correlation between the sites of expression of CRF‐R2 and CRF, as well as the relatively low affinity of CRF for CRF‐R2, suggested the presence of another ligand, whose existence was confirmed in our cloning of urocortin. This CRF‐like peptide is found not only in brain, but also in peripheral sites, such as lymphocytes. The broad tissue distribution of CRF receptors and their ligands underscores the important role of this system in maintenance of homeostasis. Functional studies of the two receptor types reveal differences in the specificity for CRF and related ligands. On the basis of its greater affinity for urocortin, in comparison with CRF, as well as its brain distribution, CRF‐R2 may be the cognate receptor for urocortin. Mutagenesis studies of CRF receptors directed toward understanding the basis for their specificity, provide insight into the structural determinants for hormone‐receptor recognition and signal transduction.
Characterization of a Polyclonal Antibody Raised Against the Human Melanocortin‐1 Receptor
Authors: BÖHM MARKUS , BRZOSKA THOMAS , SCHULTE URSULA , SCHILLER MEINHARD , KUBITSCHECK ULRICH , LUGER THOMAS A.
Published: July 2010

ABSTRACT: We have generated a polyclonal antibody raised against a synthetic peptide corresponding to the amino acids 2–18 of the extracellular, N‐terminal domain of the human melanocortin‐1 receptor (MC‐1R). Specificity of the affinity‐purified anti‐MC‐1R antibody was confirmed by dot blot analysis with the an‐tigenic peptide. The antibody detected MC‐1R antigenicity on the surface of normal human melanocytes and WM35 melanoma cells, as shown by FACS and immunofluorescence analysis. The antibody was suitable for immunoperoxidase staining of deparaffinized skin sections, revealing prominent MC‐1R staining of a cutaneous melanoma as opposed to undiseased skin in which normal melanocytes were only occasionally immunoreactive. Distinct adnexal structures in normal skin also displayed MC‐1R immunostaining. Specificity of the MC‐1R immunoreactivity in each technique was confirmed by preabsorption with the immunogenic peptide, omission, or substitution of the primary antibody with preimmune serum. Our results provide a baseline for future studies on MC‐1R expression in diseased human skin.
Studies of Amphetamine or Methamphetamine Psychosis in Japan: Relation of Methamphetamine Psychosis to Schizophrenia
Authors: YUI KUNIO , IKEMOTO SHIGENORI , ISHIGURO TAKEO , GOTO KIMIHIKO
Published: July 2010

There exist clinical characteristics of methamphetamine (MAP) psychosis in the Japanese population. MAP psychosis involves paranoid‐hallucinatory states indistinguishable from paranoid schizophrenia, with residual volitional disturbances (e.g., loss of spontaneity and idleness). Paranoid‐hallucinatory states persist after the pharmacological effects of MAP have worn off and readily reappear upon a reinjection of MAP. Individuals with a history of MAP psychosis further undergo spontaneous recurrence of their paranoid‐hallucinatory states in response to stress. The development of MAP psychosis might therefore be related to persisting brain damage or changes in brain metabolism induced by repeated MAP use, and thus studies of the clinical course and neurological basis of MAP psychosis could provide insights into the pathophysiology of schizophrenia. Accordingly, psychiatrists have studied the clinical characteristics of MAP psychosis and examined the neurobiological basis of MAP‐induced behavioral sensitization, using animals. MAP‐induced behavioral sensitization might well be related to dopamine supersensitivity; however, the contribution of presynaptic autoreceptors remains controversial, and other hypotheses should be considered. Recently, the process that triggers spontaneous recurrence of MAP psychosis (flashbacks) and corresponding peripheral neurotransmitter functions has been studied. Stress sensitization associated with noradrenergic hyperactivity, involving increased dopamine release, appears to be crucial in the development of flashbacks. Overall, MAP‐induced susceptibility to paranoid‐hallucinatory states and to abnormal behavior (e.g., stereotyped behavior) in animals is examined as a model for predicting relapses of paranoid schizophrenia. Further extensive studies on the neurobiological and molecular mechanisms of this susceptibility are required.
Activation of an Effector Immediate‐early Genearcby Methampetamine
Authors: YAMAGATA KANATO , SUZUKI KYOKO , SUGIURA HIROKO , KAWASHIMA NAOYA , OKUYAMA SHIGERU
Published: July 2010

As immediate‐early genes (IEGs) are thought to play a critical role in mediating stimulus‐induced neural plasticity, IEG response induced by methamphetamine (METH) has been characterized to define the changes in gene expression that may underlie its long‐lasting behavioral effects. Although activation of several transcription factor IEGs has been described, little is known about effector IEGs. Here, we have examined whether METH administration affects expression of an effector IEGarc(activity‐regulated, cytoskeleton‐associated) that encodes a protein with homology to spectrin. Usingin situhybridization, we observed that METH caused a rapid and transient dose‐dependent increase inarcmRNA level in the striatum and cortex that was abolished by pretreatment with the specific dopamine D1 receptor antagonist SCH‐23390 but not by an atypical neuroleptic clozapine. METH inducedarcmRNA in layers IV and VI of the cortex which dopamine receptor are localized to. These results suggest that D1 receptors are coupled to activation ofarcgene, which may be involved in functional or structural alterations underlying neural plasticity triggered by METH.
Neuroprotective Role of Estrogen upon Methamphetamine and Related Neurotoxins within the Nigrostriatal Dopaminergic System
Authors: DLUZEN DEAN E. , McDERMOTT JANET L.
Published: July 2010

In this report we describe some of the data on the capacity for estrogen to function as a neuroprotectant of the nigrostriatal dopaminergic (NSDA) system. The data show that estrogen (E) can alter two different response characteristics to NSDA neurotoxins. The first being that striatal DA concentrations of ovariectomized rodents treated with E are consistently greater than non‐E‐treated animals in response to neurotoxins which produce degeneration of the NSDA system. The second being that E significantly reduces the amount of DA output upon initial exposure to the NSDA neurotoxin, 1‐methyl‐4‐phenylpyridium ion (MPP+). At present, it is not known whether these two response characteristics are related. An intriguing possibility is that the E‐dependent changes in initial DA output are related to the resultant neurotoxicity (attenuations in DA concentration reductions). So far our incipient findings do not seem to support this eventuality. However, additional testing on this topic is required. The present data suggest that one of the mechanisms by which E can exert these effects is through inhibition of DAT activity. This conclusion results from data which show that E produces: 1) an inhibition of [3H]DA uptake, 2) a reduction in DA clearance rates, and 3) an effect upon DA recovery that is similar to that observed to the putative DA uptake blocker, nomifensine. The capacity and significance for steroid hormones to modulate neurotransmitter transporters has been recently reviewed.