bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib
Authors: Mulligan George , Mitsiades Constantine , Bryant Barb , Zhan Fenghuang , Chng Wee J. , Roels Steven , Koenig Erik , Fergus Andrew , Huang Yongsheng , Richardson Paul , Trepicchio William L. , Broyl Annemiek , Sonneveld Pieter , Shaughnessy John D. , Leif Bergsagel P. , Schenkein David , Esseltine Dixie-Lee , Boral Anthony , Anderson Kenneth C.
Published: December 2006

The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents.
Domestic Violence in the Chinese and South Asian Immigrant Communities
Authors: MIDLARSKY ELIZABETH , VENKATARAMANI‐KOTHARI ANITHA , PLANTE MAURA
Published: December 2006

Abstract:  Although the Chinese and South Asian immigrant populations are largely silent on this issue, domestic violence is a fact of life in many families. In this article, we discuss cultural factors that may cause and prolong abuse in Asian immigrant homes, and review similarities and differences between the two Asian cultures in this regard. This article also addresses the psychological trauma experienced by abused Asian immigrant women and the coping strategies that they are likely to employ. Culturally sensitive intervention strategies are presented that may be appropriately used in working with Chinese and South Asian immigrant women for whom abuse is a terrifying and demeaning fact of life.
Cultural Beliefs and Domestic Violence
Authors: FERNÁNDEZ MADELINE
Published: December 2006

Abstract:  The role of cultural beliefs in domestic violence is examined within the context of the identification of more culturally viable options for women who are operating within diverse cultural frameworks and experiencing domestic violence worldwide. Domestic violence advocacy efforts are encouraged to incorporate more culturally informed strategies that complement the worldviews and cultural traditions of women from different backgrounds. The need for a more culturally sensitive definition of domestic violence that is inclusive of a range of domestic violence across cultures and also enhances communication among victims is identified. Points of relevant cultural reference are discussed and a cultural cost‐benefit analysis is recommended for culturally relevant domestic violence research and program implementation.
Violence against Pregnant Women in Northwestern Ontario
Authors: TAN JOSEPHINE C. H. , GREGOR KATHRYN V.
Published: December 2006

Abstract:  Violence against women during pregnancy is a global problem with adverse outcomes for the mothers and their children. This paper provides a discussion of the prevalence rates of pregnancy‐related violence, associated factors, and outcomes. Most of the outcome literature focuses on perinatal and postnatal outcomes, but little is known about the longer term psychological outcome of children born to women abused during pregnancy. Moreover, the question as to whether the abuse increases during pregnancy remains unanswered given the equivocal findings in the literature. Findings from a small study conducted with women in the region of northwestern Ontario, Canada, are presented. The pattern of abuse during pregnancy over the three trimesters was examined. The long‐term psychological outcomes of the children born to women abused during pregnancy were also investigated by comparing these children to a sex‐ and age‐matched cohort of children born to women who were not abused during pregnancy. Although key confounding variables were controlled in the study, the results still showed that children born to women abused during pregnancy had greater behavioral problems.
An Exploration of Female Genital Mutilation
Authors: BARON ERIKA M. , DENMARK FLORENCE L.
Published: December 2006

Abstract: Female genital mutilation (FGM) is a form of violence against women that has recently been labeled a public health issue. This article will define and describe the procedure as well as discuss its physical and psychological implications. An exploration of the cultural significance of the practice will shed light on its continued existence in underdeveloped and developed nations. In addition, an examination of suggested guidelines for creating and implementing effective interventions will ensue.
Getting axons onto the right path: the role of transcription factors in axon guidance
Authors: Butler Samantha J. , Tear Guy
Published: December 2006

The normal function of the nervous system requires that the constituent neurons are precisely `wired together'. During embryogenesis, each neuron extends an axonal process, which can navigate a considerable distance to its target. Although a number of the receptors and guidance signals that direct axonal growth have been identified, less is known about the transcription factors that regulate the expression of these molecules within the neuron and its environment. This review examines recent studies in vertebrates and Drosophila that address the identity of the transcription factors that either control the repertoire of guidance receptors and signals that permits an axon to take a particular trajectory or act themselves as novel extracellular guidance factors.
Human Plasma ATP Concentration
Authors: Gorman Mark W , Feigl Eric O , Buffington Charles W
Published: December 2006

Background: Human plasma ATP concentration is reported in many studies as roughly 1000 nmol/L. The present study tested the hypothesis that the measured plasma ATP concentration is lower if ATP release from formed blood elements is inhibited during blood sample processing. A second hypothesis was that pretreatment with aspirin to inhibit platelets would reduce the measured plasma concentration of ATP.

Methods: Blood was sampled from the antecubital vein in 20 healthy individuals 30 and 60 min after ingestion of aspirin (325 mg) or placebo. Aliquots of each blood sample were added to the usual EDTA/saline solution to inhibit ATP catabolism, or to a new stabilizing solution designed to both stop ATP catabolism and inhibit ATP release from blood elements. The stabilizing solution contained NaCl, EDTA, tricine buffer, KCl, nitrobenzylthioinosine, forskolin, and isobutylmethylxanthine. Plasma ATP was measured with the luciferin–luciferase assay with standard additions in each sample to determine ATP content. Hemoglobin concentration was used as an index of sample hemolysis, and the plasma ATP concentration was corrected for the hemolysis component.

Results: Aspirin pretreatment had no effect on plasma ATP concentrations. However, use of the stabilizing solution resulted in mean (SD) ATP concentrations 8-fold lower than the use of EDTA alone [28 (16) vs 236 (201) nmol/L; P <0.001].

Conclusion: When precautions are taken to inhibit ATP release from blood elements during sample preparation, human venous plasma ATP concentration is much lower than previously reported.
Transcriptional Profiling of Human Cord Blood CD133+ and Cultured Bone Marrow Mesenchymal Stem Cells in Response to Hypoxia
Authors: Martin-Rendon Enca , Hale Sarah J.M. , Ryan Dacey , Baban Dilair , Forde Sinead P. , Roubelakis Maria , Sweeney Dominic , Moukayed Meis , Harris Adrian L. , Davies Kay , Watt Suzanne M.
Published: December 2006

Umbilical cord blood (UCB) and bone marrow (BM)-derived stem and progenitor cells possess two characteristics required for successful tissue regeneration: extensive proliferative capacity and the ability to differentiate into multiple cell lineages. Within the normal BM and in pathological conditions, areas of hypoxia may have a role in maintaining stem cell fate or determining the fine equilibrium between their proliferation and differentiation. In this study, the transcriptional profiles and proliferation and differentiation potential of UCB CD133+ cells and BM mesenchymal cells (BMMC) exposed to normoxia and hypoxia were analyzed and compared. Both progenitor cell populations responded to hypoxic stimuli by stabilizing the hypoxia inducible factor (HIF)-1α protein. Short exposures to hypoxia increased the clonogenic myeloid capacity of UCB CD133+ cells and promoted a significant increase in BMMC number. The differentiation potential of UCB CD133+ clonogenic myeloid cells was unaltered by short exposures to hypoxia. In contrast, the chondrogenic differentiation potential of BMMCs was enhanced by hypoxia, whereas adipogenesis and osteogenesis were unaltered. When their transcriptional profiles were compared, 183 genes in UCB CD133+ cells and 45 genes in BMMC were differentially regulated by hypoxia. These genes included known hypoxia-responsive targets such as BNIP3, PGK1, ENO2, and VEGFA, and other genes not previously described to be regulated by hypoxia. Several of these genes, namely CDTSPL, CCL20, LSP1, NEDD9, TMEM45A, EDG-1, and EPHA3 were confirmed to be regulated by hypoxia using quantitative reverse transcriptase polymerase chain reaction. These results, therefore, provide a global view of the signaling and regulatory network that controls oxygen sensing in human adult stem/progenitor cells derived from hematopoietic tissues.

Disclosure of potential conflicts of interest is found at the end of this article.
Spontaneous Fusion and Nonclonal Growth of Adult Neural Stem Cells
Authors: Jessberger Sebastian , Clemenson Gregory D. , Gage Fred H.
Published: December 2006

Multipotent neural stem cells (NSCs) can be isolated from various regions of the adult brain and propagated in vitro. Recent reports have suggested spontaneous fusion events among NSCs when grown as free-floating neurospheres that may affect the genetic composition of NSC cultures. We used adult NSCs expressing either red fluorescent protein (RFP) or green fluorescent protein (GFP) to analyze the fusion frequency of rat and mouse NSCs. Fluorescence-activated cell sorting (FACS) revealed that, under proliferating conditions, approximately 0.2% of rat and mouse NSCs coexpressed RFP and GFP irrespective of whether the cells were grown as neurospheres (mouse NSCs) or as attached monolayers (rat and mouse NSCs). Fused cells did not proliferate and could not be propagated, suggesting that aberrantly fused cells are not viable. Furthermore, we found that neither neurospheres nor monolayers grew clonally, because even very low-density cultures had spheres containing both GFP- and RFP-expressing cells and monolayer patches with GFP- and RFP-expressing cells in close proximity. The nonclonal growth between distinct NSC populations strongly suggests the use of careful and precise culture conditions, such as single-cell assays, to characterize potency and growth of NSCs in vitro.

Disclosure of potential conflicts of interest is found at the end of this article.
Widespread Distribution and Muscle Differentiation of Human Fetal Mesenchymal Stem Cells After Intrauterine Transplantation in Dystrophic mdx Mouse
Authors: Chan Jerry , Waddington Simon N. , O'Donoghue Keelin , Kurata Hitoshi , Guillot Pascale V. , Gotherstrom Cecilia , Themis Michael , Morgan Jennifer E. , Fisk Nicholas M.
Published: December 2006

Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the absence of dystrophin in muscle. Affected boys suffer from incurable progressive muscle weakness, leading to premature death. Stem cell transplantation may be curative, but is hampered by the need for systemic delivery and immune rejection. To address these barriers to stem cell therapy in DMD, we investigated a fetal-to-fetal transplantation strategy. We investigated intramuscular, intravascular, and intraperitoneal delivery of human fetal mesenchymal stem cells (hfMSCs) into embryonic day (E) 14–16 MF1 mice to determine the most appropriate route for systemic delivery. Intramuscular injections resulted in local engraftment, whereas both intraperitoneal and intravascular delivery led to systemic spread. However, intravascular delivery led to unexpected demise of transplanted mice. Transplantation of hfMSCs into E14–16 mdx mice resulted in widespread long-term engraftment (19 weeks) in multiple organs, with a predilection for muscle compared with nonmuscle tissues (0.71% vs. 0.15%, p < .01), and evidence of myogenic differentiation of hfMSCs in skeletal and myocardial muscle. This is the first report of intrauterine transplantation of ontologically relevant hfMSCs into fully immunocompetent dystrophic fetal mice, with systemic spread across endothelial barriers leading to widespread long-term engraftment in multiple organ compartments. Although the low-level of chimerism achieved is not curative for DMD, this approach may be useful in other severe mesenchymal or enzyme deficiency syndromes, where low-level protein expression may ameliorate disease pathology.

Disclosure of potential conflicts of interest is found at the end of this article.
Sjögren's Syndrome: Diagnosis and Management
Authors: Al-Hashimi Ibtisam
Published: December 2006

This article reviews current understanding of the clinical manifestations, diagnosis and treatment of Sjögren's syndrome. Sjögren's syndrome is a chronic inflammatory disorder of the exocrine glands with multiple nonexocrine features. It is found predominantly in middle-aged women but exists throughout the population. The diagnosis of Sjögren's syndrome can be challenging because the cardinal sicca symptoms may be subclinical or attributed to other causes, such as medications or aging. Differential diagnosis of Sjögren's syndrome can be confounded by the multiple exocrine manifestations in the mouth, eyes, ears, nose, skin, vagina, and respiratory and gastrointestinal tracts, as well as seemingly unrelated nonexocrine involvement in the thyroid, liver, kidneys and the musculoskeletal, vascular and nervous systems. This article concludes that early diagnosis of Sjögren's syndrome is crucial to prevent and/or minimize potentially life-threatening complications. Periodic follow-up of patients’ status and collaboration between the primary-care physician and the rheumatologist, dentist, ophthalmologist and other specialists are indispensable.
Clinical Considerations regarding Contralateral Prophylactic Mastectomy
Authors: McCready David R , Escallon Jaime
Published: December 2006

The risk factors and clinical features for contralateral breast cancer are reviewed. Prevention is afforded by adjuvant systemic treatments but the largest risk reduction (95%) occurs with prophylactic mastectomy. Satisfaction with this procedure is high in selected individuals and studies but the potential complications should not be taken lightly. For those with a high risk of contralateral disease and a primary tumor with relatively good prognosis, it is quite reasonable to discuss and perform contralateral mastectomy with or without breast reconstruction.
Pharmacotherapy of Interstitial Cystitis in Women
Authors: Amrute Kaytan V , Moldwin Robert M
Published: December 2006

Interstitial cystitis is a condition that affects the urinary bladder and may be more prevalent than commonly thought. Symptoms range widely in severity and typically include urinary urgency, frequency and pelvic pain. Therapies usually target the known pathophysiology of this condition. Oral agents commonly include bladder surface mucin analogues, antihistamines, narcotics, tricyclic antidepressants and anticonvulsants. Intravesical therapy is usually used as second-line treatment. Multiple forms of pharmacotherapy are often provided simultaneously to improve efficacy and time to response.
Update on the Cardiovascular Risks of Hormone Replacement Therapy
Authors: Lowe Gordon DO
Published: December 2006

Systematic reviews of randomized, controlled trials have shown that use of hormone replacement therapy in women increases the risk of total cardiovascular disease (venous thromboembolism, stroke and coronary heart disease; there may also be an increased risk of peripheral arterial disease). The relative increase in risk is similar to that for use of combined oral contraceptives, but the absolute increase in risk is higher owing to the higher age of hormone replacement therapy users. The increased risk appears confined to current users, increases with age and obesity, and may differ with type of preparation. Transdermal hormone replacement therapy may carry a lower risk of venous thromboembolism compared with oral hormone replacement therapy. The mechanism for the increased risk is probably activated blood coagulation. The risk of venous thromboembolism is higher in women with thrombophilias; however, the value of screening for thrombophilias is not established. Further research is required to establish the risks of cardiovascular (and other) diseases in different groups of women for different types of hormone replacement therapy, including an individual participant meta-analysis of reported randomized, controlled trials.
Sleep and Menopause
Authors: Polo-Kantola Päivi
Published: December 2006

Sleeping problems are a serious public health problem, imposing a substantial burden on individuals and society. Although sleeping problems occur throughout the lifespan, and in both sexes, menopause can be considered as one important milestone of increasing occurrence in sleeping problems. However, to determine whether sleeping problems are caused by the menopause or merely occur by coincidence during the menopause is not always easy because several, particularly age-related, changes take place at the same time. The most important factors are general diseases, medications, weight changes and mood symptoms. According to women's own judgment, hormone therapy significantly improves sleep quality. Hormone therapy can thus be considered as a first-line treatment for climacteric sleeping problems. If sleeping problems are accompanied by other disorders, hormone therapy should be kept in mind as an adjuvant therapy. According to worldwide consensus on hormone therapy, the main indication of hormone therapy is alleviation of climacteric symptoms, including climacteric sleeping problems. However, when choosing hormone therapy for a patient, contraindications and possible long-term side effects should be individually considered. This review illustrates the effect of menopause on sleep and evaluates different treatment options, especially hormone therapy, in alleviation of symptoms.
Metagenomic studies reveal the critical and wide‐ranging ecological importance of uncultivated archaea: the role of ammonia oxidizers
Authors: Cavicchioli Ricardo , DeMaere Matthew Z. , Thomas Torsten
Published: December 2006

Microbial genome sequencing has entered a new phase, where DNA sequence information is gathered from entire microbial communities (metagenomics or environmental genomics) rather than from individual microorganisms. By providing access to the genetic material of vast numbers of organisms, most of which are organisms that have never been isolated or cultivated, a new level of insight is being gained into the diversity and extent of the microbial processes that are presently occuring in environmental communities. By extending metagenomic‐based approaches to the study of very complex and methodologically recalcitrant soil environments, a recent study has found that ammonia‐oxidizing archaea are more abundant in many soils than bacteria.1 These findings not only highlight the undoubtedly critical yet unknown roles that archaea play in global nutrient cycles but illustrate the importance of genomic studies for informing us about the functional capacity of life on Earth. BioEssays 29: 11–14, 2007. © 2006 Wiley Periodicals, Inc.
Invasive assessment of mitral regurgitation: Comparison of hemodynamic parameters
Authors: Freihage Jeffrey H. , Joyal Dominique , Arab Dinesh , Dieter Robert S. , Loeb Henry S. , Steen Lowell , Lewis Bruce , Liu Jayson C. , Leya Ferdinand
Published: December 2006

Objectives: We sought to analyze several new hemodynamic characteristics which address the interplay of left atrial (LA) and left ventricular (LV) pressures, as well as to re‐analyze several other V wave characteristics employed in the determination of mitral regurgitation (MR) severity in order to determine which, if any, had adequate correlation with grade of MR for clinical utility. Background: Invasive assessment of mitral regurgitation includes analysis of intracardiac pressures and LV angiography. The V wave, when obtained from the pulmonary capillary wedge position (PCWP), and its various characteristics are believed to be of limited value for prediction of MR severity. Method: We analyzed the transeptal pressure tracings of patients with various degrees of MR. Several relationships from the simuItaneous pressure‐time curves of the LA and LV were defined. Biplane left ventricular angiography was used to grade MR. Correlation between each parameter and MR grade was determined by calculating a Pearson correlation coefficient. Results: The ratio of the area under the V wave to the LV systolic area (Va/LVa) best correlates with the degree of MR with a Pearson correlation coefficient of 0.60. The Va/LVa was significantly lower in patients with 0−1+ MR compared to ≥2+ MR (0.14 vs. 0.23 p = 0.002). Conclusions: Invasive hemodynamic assessment of MR severity could be enhanced by calculating our new ratio, Va/LVa, due to its ability to account for LV work that is lost to the LA with a proportional decrease in forward or useful LV work with progressively increasing severity of MR. © 2006 Wiley‐Liss, Inc.
Growth and optical damage properties of In:Zn:LiNbO3 waveguide substrate
Authors: Nie Yiran , Wang Rui , Wang Biao
Published: December 2006

In:Zn:LiNbO3 crystals doped with different indium concentrations were grown by Czochralski technique. The optical damage threshold value and ultraviolet‐visible absorption spectra of the In:Zn:LiNbO3 crystals were measured. The In:Zn:LiNbO3 crystals were made into optical waveguide substrates using hexanedioic acid as proton exchange agent. The optical damage resistant ability of those optical waveguide substrates was investigated by the m‐line method. The optical damage threshold values of In(2mol.%):Zn(3mol.%):LiNbO3 crystal and optical waveguide substrate are two orders of magnitude higher than those of pure LiNbO3. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A novel metal‐organic coordination complex crystal: tris allylthiourea zinc bromide (ATZB) as a nonlinear optical material
Authors: Sun Haiqing , Yuan Duorong , Hou Xianqin , Wang Xinqiang , Liu Liqiang , Zhang Dajiang , Han Ye
Published: December 2006

A new second order nonlinear optical coordination complex crystal tris allylthiourea zinc bromide was synthesized and grown from ethanol for the first time. Elemental analyses, X‐ray powder diffraction and infrared spectroscopy confirmed the formation of the new material. The thermal characterization was determined by the differential thermal analysis and thermogravimetric analysis. The transmission spectrum of the crystal shows a wide transparent UV‐Vis‐NIR band. The powder SHG efficiency is higher than that of urea crystal. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
XRD, thermal, FTIR and SEM studies on gel grown γ‐glycine crystals
Authors: Ramachandran E. , Baskaran K. , Natarajan S.
Published: December 2006

Glycine is the smallest among amino acids. The polymorphs, α‐ and γ‐forms of glycine were crystallized in silica gel by reduction of solubility method. The grown crystals were characterized by single crystal X‐ray diffraction studies and density determination. Fourier transform infrared spectroscopic studies and thermogravimetric analysis of γ‐glycine were also conducted. Morphological and scanning electron microscopic (SEM) studies were also made and compared with the crystal packing. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Novel hepatic progenitor cell surface markers in the adult rat liver
Authors: Yovchev Mladen I. , Grozdanov Petar N. , Joseph Brigid , Gupta Sanjeev , Dabeva Mariana D.
Published: December 2006

Hepatic progenitor/oval cells appear in injured livers when hepatocyte proliferation is impaired. These cells can differentiate into hepatocytes and cholangiocytes and could be useful for cell and gene therapy applications. In this work, we studied progenitor/oval cell surface markers in the liver of rats subjected to 2-acetylaminofluorene treatment followed by partial hepatectomy (2-AAF/PH) by using rat genome 230 2.0 Array chips and subsequent RT-PCR, immunofluorescent (IF), immunohistochemical (IHC) and

in situ

hybridization (ISH) analyses. We also studied expression of the identified novel cell surface markers in fetal rat liver progenitor cells and FAO-1 hepatoma cells. Novel cell surface markers in adult progenitor cells included tight junction proteins, integrins, cadherins, cell adhesion molecules, receptors, membrane channels and other transmembrane proteins. From the panel of 21 cell surface markers, 9 were overexpressed in fetal progenitor cells, 6 in FAO-1 cells and 6 are unique for the adult progenitors (CD133, claudin-7, cadherin 22, mucin-1, ros-1, Gabrp). The specificity of progenitor/oval cell surface markers was confirmed by ISH and double IF analyses. Moreover, study of progenitor cells purified with Ep-CAM antibodies from D-galactosamine injured rat liver, a noncarcinogenic model of progenitor cell activation, verified that progenitor cells expressed these markers.

Conclusion

: We identified novel cell surface markers specific for hepatic progenitor/oval cells, which offers powerful tool for their identification, isolation and studies of their physiology and pathophysiology. Our studies also reveal the mesenchymal/epithelial phenotype of these cells and the existence of species diversity in the hepatic progenitor cell identity. (Hepatology 2007;45:139–149.)
Hepatic fibrosis 2006: Report of the third AASLD Single Topic Conference
Authors: Friedman Scott L. , Rockey Don C. , Bissell Montgomery D.
Published: December 2006

The third American Associated for the Study of Liver Diseases (AASLD)–sponsored Single Topic Conference on hepatic fibrosis was held in June 2006. The conference was both international, with 6 countries represented, and cross-disciplinary, linking the basic molecular and cellular biology of fibrogenic cells to clinical trial design for emerging antifibrotic therapies. The specific goals of the conference were: (1) to consolidate knowledge about the natural history of fibrosis; (2) to clarify potential endpoints and markers; (3) to emphasize new antifibrotic targets developed on the basis of advances in basic science; and (4) to understand current critical issues pertaining to clinical trial design. Given the tremendous growth of the field and the constraints of a 2-day format, the selection of speakers was a challenge. A number of topics not included in the oral presentations were featured at poster sessions, lending breadth and depth to the meeting as a whole. Surprising new themes emerged about molecular, clinical, and regulatory aspects of the field, and a consensus emerged that hepatic fibrosis has matured into an integrated discipline that promises to significantly improve the prognosis of patients with fibrosing liver disease. (Hepatology 2007;45:242–249.)
Effect of iron and ascorbate on uroporphyria in ascorbate-requiring mice as a model for porphyria cutanea tarda
Authors: Gorman Nadia , Zaharia Adrian , Trask Heidi S. , Szakacs Juliana G. , Jacobs Nicholas J. , Jacobs Judith M. , Balestra Dominic , Sinclair Jacqueline F. , Sinclair Peter R.
Published: December 2006

Excess hepatic iron is known to enhance both porphyria cutanea tarda (PCT) and experimental uroporphyria. Since previous studies have suggested a role for ascorbate (AA) in suppressing uroporphyria in AA-requiring rats (in the absence of excess iron), the present study investigated whether AA could suppress uroporphyria produced by excess hepatic iron. Hepatic URO accumulation was produced in AA-requiring

Gulo

(−/−) mice by treatment with 3,3′,4,4′,5-pentachlorbiphenyl, an inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered either sufficient AA (1000 ppm) in the drinking water to maintain near normal hepatic AA levels or a lower intake (75 ppm) that resulted in 70 % lower hepatic AA levels. The higher AA intake suppressed hepatic URO accumulation in the absence of administered iron, but not when iron dextran (300–500 mg Fe/kg) was administered. This effect of iron was not due to hepatic AA depletion since hepatic AA content was not decreased. The effect of iron to prevent AA suppression of hepatic URO accumulation was not observed until a high hepatic iron threshold was exceeded. At both low and high AA intakes, hepatic malondialdehyde (MDA), an indicator of oxidative stress, was increased three-fold by high doses of iron dextran. MDA was considerably increased even at low iron dextran doses, but without any increase in URO accumulation. The level of hepatic CYP1A2 was unaffected by either AA intake.

Conclusion

: In this mouse model of PCT, AA suppresses hepatic URO accumulation at low, but not high hepatic iron levels. These results may have implications for the management of PCT. (Hepatology 2007;45:187–194.)
Thyroid hormone preconditioning: Protection against ischemia-reperfusion liver injury in the rat
Authors: Fernández Virginia , Castillo Iván , Tapia Gladys , Romanque Pamela , Uribe-Echevarría Sebastián , Uribe Mario , Cartier-Ugarte Denise , Santander Gonzalo , Vial María T. , Videla Luis A.
Published: December 2006

Recently, we reported that oxidative stress due to 3,3′,5-triiodothyronine (T3)-induced calorigenesis up-regulates the hepatic expression of mediators promoting cell protection. In this study, T3 administration in rats (single dose of 0.1 mg/kg intraperitoneally) induced significant depletion of reduced liver glutathione (GSH), with higher protein oxidation, O2 consumption, and Kupffer cell function (carbon phagocytosis and carbon-induced O2 uptake). These changes occurred within a period of 36 hours of T3 treatment in animals showing normal liver histology and lack of alteration in serum AST and ALT levels. Partial hepatic ischemia-reperfusion (IR) (1 h of ischemia via vascular clamping and 20 h reperfusion) led to 11-fold and 42-fold increases in serum AST and ALT levels, respectively, and significant changes in liver histology, with a 36% decrease in liver GSH content and a 133% increase in that of protein carbonyls. T3 administration in a time window of 48 hours was substantially protective against hepatic IR injury, with a net 60% and 90% reduction in liver GSH depletion and protein oxidation induced by IR, respectively. Liver IR led to decreased DNA binding of nuclear factor-κB (NF-κB) (54%) and signal transducer and activator of transcription 3 (STAT3) (53%) (electromobility shift assay), with 50% diminution in the protein expression of haptoglobin (Western blot), changes that were normalized by T3 preconditioning.

Conclusion:

T3 administration involving transient oxidative stress in the liver exerts significant protection against IR injury, a novel preconditioning maneuver that is associated with NF-κB and STAT3 activation and acute-phase response. (Hepatology 2007;45:170–177.)
Linkage between a new splicing site mutation in the MDR3 alias ABCB4 gene and intrahepatic cholestasis of pregnancy
Authors: Schneider Gudrun , Paus Teresa C. , Kullak-Ublick Gerd A. , Meier Peter J. , Wienker Thomas F. , Lang Thomas , van de Vondel Patricia , Sauerbruch Tilman , Reichel Christoph
Published: December 2006

Intrahepatic cholestasis of pregnancy (ICP) is defined as pruritus and elevated bile acid serum concentrations in late pregnancy. Splicing mutations have been described in the multidrug resistance p-glycoprotein 3 (

MDR3, ABCB4

) gene in up to 20% of ICP women. Pedigrees studied were not large enough for linkage analysis. Ninety-seven family members of a woman with proven ICP were asked about pruritus in earlier pregnancies, birth complications and symptomatic gallstone disease. The familial cholestasis type 1 (

FIC1, ATP8B1

) gene, bile salt export pump (

BSEP, ABCB11

) and

MDR3

gene were analyzed in 55 relatives. We identified a dominant mode of inheritance with female restricted expression and a new intronic

MDR3

mutation c.3486+5G>A resulting in a 54 bp (3465–3518) inframe deletion via cryptic splicing site activation. Linkage analysis of the ICP trait versus this intragenic

MDR3

variant yielded a LOD score of 2.48. A Bayesian analysis involving

MDR3

,

BSEP

,

FIC1

and an unknown locus gave a posterior probability of >0.9966 in favor of

MDR3

as causative ICP locus. During the episode of ICP the median γ-glutamyl transpeptidase (γ-GT) activity was 10 U/l (95% CI, 6.9 to 14.7 U/l) in the index woman. Four stillbirths were reported in seven heterozygous women (22 pregnancies) and none in five women (14 pregnancies) without

MDR3

mutation. Symptomatic gallstone disease was more prevalent in heterozygous relatives (7/21) than in relatives without the mutation (1/34), (

P

= 0.00341).

Conclusion:

This study demonstrates that splicing mutations in the

MDR3

gene can cause ICP with normal γ-GT and may be associated with stillbirths and gallstone disease. (Hepatology 2007;45:150–158.)
Developing an effective sell‐side strategy
Authors: Martin Dale R. , Wathen Michael M. , Smith Nigel W. H.
Published: December 2006

There's been a lot written about how to buy companies. But what about strategies to help the seller? Experts have paid very little attention to the best ways to sell a company. What can the seller do to get the most from the sale? © 2007 Wiley Periodicals, Inc.
Optimizing the quality control station configuration
Authors: Penn Michal , Raviv Tal
Published: December 2006

We study unreliable serial production lines with known failure probabilities for each operation. Such a production line consists of a series of stations, existing machines, and optional quality control stations (QCSs). Our aim is to decide on the allocation of the QCSs within the assembly line, so as to maximize the expected profit of the system. In such a problem, the designer has to determine the QCS configuration and the production rate simultaneously. The profit maximization problem is approximated assuming exponentially distributed processing times, Poisson arrival process of jobs into the system, and the existing of holding costs. The novel feature of our model is the incorporation of holding costs that significantly complicated the problem. Our approximation approach uses a branch and bound strategy that employs our fast dynamic programming algorithm for minimizing the expected operational costs for a given production rate as a subroutine. Extensive numerical experiments are conducted to demonstrate the efficiency of the branch and bound procedure for solving large scale instances of the problem and for obtaining some qualitative insights.

“Ever increasing quality is mandatory—not only for corporate profitability—but also for corporate survival” Inman, Blumenfeld, Huang, and Li (Int J Prod Res 38(9) (2000), 1953–1976)

© 2006 Wiley Periodicals, Inc. Naval Research Logistics, 2007
Sonohysterography versus transvaginal sonography for screening of patients with abnormal uterine bleeding
Authors: Alborzi S. , Parsanezhad M.E. , Mahmoodian N. , Alborzi S. , Alborzi M.
Published: December 2006

Objectives: To compare the accuracy of saline infusion sonohysterography (SIS) with transvaginal sonography (TVS) for the screening of causes of abnormal uterine bleeding (AUB) in out‐patients. Methods: 81 patients with AUB were studied. All cases who were examined with TVS, were further investigated with SIS using saline as contrast medium, finally hysteroscopy was used as the gold standard. Results: TVS had sensitivity of 72%, specificity of 92%, positive predictive value of 94% and negative predictive value of 65%, while SIS had sensitivity of 94.1%, specificity of 95%, positive predictive value of 96% and negative predictive value of 90%. TVS had kappa measure of agreement of 0.60 while 0.86 was reported for SIS. Conclusions: In this study SIS was more sensitive and specific in diagnosing polyp, myoma and adenomyosis with high positive and negative predictive value. Furthermore, results obtained by SIS demonstrate more agreement with that obtained by hysteroscopy than TVS.
Gene flow in symbionts of Cladonia arbuscula
Authors: ROBERTSON Jason , PIERCEY-NORMORE Michele D.
Published: December 2006

Genetic diversity in symbionts of the lichen Cladonia arbuscula was investigated. Forty-eight specimens of Cladonia arbuscula located within a 2 km range at Payuk Lake in Manitoba were collected. Population structure and method of symbiont transmission in C. arbuscula were inferred by examining the presence or absence of introns in the nuclear small subunit (SSU) ribosomal DNA (rDNA) of the mycobiont and restriction fragment length polymorphism (RFLP) of the internal transcribed spacer (ITS) rDNA in the photobiont. The mycobiont showed a high level of genetic variation and the photobiont a low level of variation within the small geographic range studied. An analysis of molecular variance of fungal genotypes showed significant population subdivision for the mycobiont when the data were analysed at P=0·05. No population subdivision was detected when P=0·001. The photobiont also showed no population subdivision. Photobiont genotypes did not correlate with mycobiont genotypes suggesting the symbionts were not transmitted together in the same propagule. Multiple fungal genotypes were also detected in C. arbuscula and possible explanations were discussed.
Under-nutrition in old age: diagnosis and management
Authors: Watson L. , Leslie W. , Hankey C.
Published: December 2006

A recent international definition of under-nutrition or malnutrition has been given by the WHO. Mal-nutrition means ‘badly nourished’ but it is more than a measure of what we eat, or fail to eat. Clinically, malnutrition is characterized by inadequate intake of protein, energy, and micronutri-ents and by susceptibility to infection or disease. Nutritional status is the result of the complex interaction between the food we eat, our overall state of health, and the environment in which we live – in short, food, health and caring are the three ‘pillars of well-being’.
The relationship between social class and the use of health services in Britain
Authors: Waddington Ivan
Published: December 2006

There is considerable evidence to suggest that despite the availability of free medical services under the British National Health Service, there remains a clear social class bias in accessibility to a wide range of health care services. The literature on social class and the use of health services is examined and it is suggested that the greatest inequalities are to be found in the use of preventive services. In the second half of the paper, some tentative proposals, which might erve to reduce existing patterns of inequality, are examined.
Development of the undergraduate nursing course in the University of Manchester
Authors: Marsh Nora
Published: December 2006

The diploma in community nursing was set up in the University of Manchester in 1959 and was unique in the United Kingdom (UK) as an experimental course in nurse education in which nursing was taught as a university subject. It sought to provide a university education in nursing, demonstrating also that integration of hospital and community nursing was possible in the basic course. It was thought that this might prove a better preparation for health visiting than the conventional method of following nurse training by a special course in public health nursing. In 1964, at the end of the experimental period, the course was revised and better integration of practical experience was achieved. The student also had greater opportunity to participate in university activities, an essential aspect of university education. Recruitment to the course increased considerably over the years and it was evident that there were sufficient entrants of high calibre whose work was of a quality comparable to that in degree courses. The revised course therefore became the prototype for a degree course and, in 1969, the first group of students graduated bachelor of nursing.

Miss Jean K. McFarlane was appointed head of nursing studies in 1971, becoming the first professor of nursing in England and Wales in 1974. Since 1972, the annual intake of students has been increased from 12 to 25, though this number has been exceeded (153 students in the years 1972–1976). Courses have also been developed for qualified and experienced nurses–a diploma in advanced nursing studies and a master of science degree course (nursing option). Since 1970, research fellows have also been appointed, firstly in the department of social and preventive medicine and secondly, since its inception, in the department of nursing.
Personality correlates in a sample of male nurses in the British Royal Air Force
Authors: Gumley C. J. G. , McKenzie J. , Ormerod M. B. , Keys Wendy
Published: December 2006

This descriptive study provides data relevant to two currently popular views of the male nursing image. Firstly, that male nurses tend to prefer the more technological or administrative aspects of nursing and secondly, that they exhibit to an unusually high degree what are commonly thought of as being amongst the more feminine personality traits. The sample consisted of 91 male RAF nurses working in RAF hospitals, and was of predominantly English nationality. Of the 39 SRNs in the sample 65‐8% preferred general nursing to the more technical areas such as intensive care, operating theatre, orthopaedic and renal. The preference for general nursing was even greater, 76‐1%, amongst the 30 SENs surveyed. The Eysenck Personality Questionnaire (EPQ) and a Level of Aspiration Test (LOA) were used to obtain measures of the personality traits of the sample. The scores obtained showed that the male RAF nurses were significantly less psychotic than male civilian nurses, male civilians or servicemen of similar age. They were also significantly less extraverted than servicemen as a whole and significantly more stable than the male civilian norm. A comparison of SRNs with SENs revealed only two significant differences. The SRNs were significantly less extraverted and had a significantly higher level of aspiration than the SENs.
The challenge of health education for nurses in the 1980s*
Authors: Smith James P.
Published: December 2006

As nurses are the largest group of health workers, it is argued that their potential for influence, so far as health education is concerned, is very great.

The health problems associated with demographic changes in British society, smoking, alcohol, road accidents, dental decay, mental health and the sexual revolution are focused on; and the health education contribution that nurses (and other health workers) can make to alleviate and prevent these problems is discussed. The important role of ‘significant others’ is also stressed.

Problems associated with general lack of basic biological and health information, and with the physically handicapped, and immigrant groups are also noted with concern and are considered to be particular challenges to nurses.

Nurses are urged to develop their social skills, to constantly update their knowledge about British society, and to commit themselves to the aims of health education. It is also argued that they need missionary zeal so that they will take health education to the people in the community at large.

The basic tenet of the paper is that health education is part and parcel of the nursing process and, therefore, greater involvement of nurses in health education is a logical and rational extension of their role.
Foreign nursing students in the USA: problems in their educational experiences
Authors: Abu‐Saad Huda , Kayser‐Jones Jeanie
Published: December 2006

With the increasing number of foreign nursing students enrolled in university nursing programmes in the United States and the paucity of relevant studies it would seem essential to assess the difficulties foreign nursing students encounter in their adjustment to university nursing programmes and to evaluate the mechanisms that facilitate their adaptation. Data from this study was based on the results of 82 questionnaires completed by foreign nursing students enrolled in university nursing programmes nationwide. Language difficulties, a faculty to a great extent unfamiliar with foreign cultures, rapid pace, insufficient clinical experience, and highly competitive programmes were found to cause the foreign nursing students problems in their educational experiences. In addition to identifying the difficulties foreign nursing students have in adjusting to a university nursing programme, this paper proposes and discusses changes that would help make the foreign nursing students’ experiences more meaningful and effective.
Factors related to the problems of long‐term catheterization
Authors: Kennedy Anne P. , Brocklehurst J. C. , Lye M. D. W.
Published: December 2006

A survey of 97 elderly catheterized patients revealed the catheter‐related problems of leaking, blocking, need for irrigation, odour and irritation. Details were taken of factors thought to be related to the problems and the data were analysed by using stepwise forward multiple regression. Hospital and community patients were found to have different problems. Females in both groups had more problems than males. For hospital patients, larger catheters were found to be associated with most problems, particularly leaking and blocking. For community patients, immobility and daily changing of drainage bags were major problem causers. The common nursing practice of changing to wider‐diameter catheters in an attempt to prevent bypassing is wrong.
The evolutionary history and tissue mapping of GPR123: specific CNS expression pattern predominantly in thalamic nuclei and regions containing large pyramidal cells
Authors: Lagerström Malin C. , Rabe Nadine , Haitina Tatjana , Kalnina Ineta , Hellström Anders R. , Klovins Janis , Kullander Klas , Schiöth Helgi B.
Published: December 2006

The Adhesion family of G protein‐coupled receptors (GPCRs) includes 33 receptors and is the second largest GPCR family. Most of these proteins are still orphans and fairly little is known of their tissue distribution and evolutionary context. We report the evolutionary history of the Adhesion family protein GPR123 as well as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization and real‐time PCR, respectively. GPR123 was found to be well conserved within the vertebrate lineage, especially within the transmembrane regions and in the distal part of the cytoplasmic tail, containing a potential PDZ binding domain. The real‐time PCR data indicates that GPR123 is predominantly expressed in CNS. The in situ data show high expression in thalamic nuclei and regions containing large pyramidal cells like cortex layers 5 and 6 and subiculum. Moreover, we found distinct expression in amygdala, hypothalamus, inferior olive and spinal cord. The CNS specific expression, together with the high sequence conservation between the vertebrate sequences investigated, indicate that GPR123 may have an important role in the regulation of neuronal signal transduction.