bluuebunny/crossref_metadata_2025 huggingface dataset:
Src promotes delta opioid receptor (DOR) desensitization by interfering with receptor recycling
Authors: Archer‐Lahlou Elodie , Audet Nicolas , Amraei Mohammad Gholi , Huard Karine , Paquin‐Gobeil Mélanie , Pineyro Graciela
Published: March 2008

An important limitation in the clinical use of opiates is progressive loss of analgesic efficacy over time. Development of analgesic tolerance is tightly linked to receptor desensitization. In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the membrane. In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. A first series of experiments demonstrated that agonist binding activates Src and destabilizes a constitutive complex formed by the spontaneous association of DORs with the kinase. Src contribution to DOR desensitization was then established by showing that pre‐treatment with Src inhibitor PP2 (20 μM; 1 hr) or transfection of a dominant negative Src mutant preserved DOR signalling following sustained exposure to an agonist. This protection was afforded without interfering with endocytosis, but suboptimal internalization interfered with PP2 ability to preserve DOR signalling, suggesting a post‐endocytic site of action for the kinase. This assumption was confirmed by demonstrating that Src inhibition by PP2 or its silencing by siRNA increased membrane recovery of internalized DORs and was further corroborated by showing that inhibition of recycling by monensin or dominant negative Rab11 (Rab11S25N) abolished the ability of Src blockers to prevent desensitization. Finally, Src inhibitors accelerated recovery of DOR‐Gαl3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors.
Chemical investigations of disperse dyes in patch test preparations
Authors: Ryberg Kristina , Gruvberger Birgitta , Zimerson Erik , Isaksson Marléne , Persson Lena , Sörensen ÖSten , Goossens An , Bruze Magnus
Published: March 2008

Background:  Contact allergy to textile dyes is not uncommon. The allergy is detected by patch testing patients with commercial patch test preparations.

Objective:  To investigate 8 disperse dyes (DDs) used for patch testing in the departments in Malmö and in Leuven and to compare them with test preparations used at various dermatology departments.

Materials/Methods:  The investigated DDs were Disperse Blue (DB) 35, 106, and 124, Disperse Yellow (DY) 3, Disperse Orange (DO) 1 and 3, and Disperse Red (DR) 1 and 17. From 13 clinics, 107 petrolatum preparations were analysed using high‐performance liquid chromatography and thin‐layer chromatography (TLC), and compared with reference substances obtained at the Malmö laboratory. Concerning DB 35, no reference substance could be identified.

Results:  TLC visualized impurities in all DDs. For each DD, except DB 35, the mean concentration in the preparations labelled to contain 1.0% (w/w) were DB 106: 0.30%, DB 124: 0.25%, DY 3: 0.44%, DO 1: 0.40%, DO 3: 0.68%, DR 1: 0.49%, and DR 17: 0.35%; there were variations between the samples also with regard to the number of impurities. DO 3 could not be demonstrated in 4/15 preparations labelled DO 3.

Conclusion:  The results may have implications for individual diagnosis and prevention and when comparing test results from various centres.
Clinical characteristics and consequences of hand eczema – an 8‐year follow‐up study of a population‐based twin cohort
Authors: Lerbaek Anne , Kyvik Kirsten Ohm , Ravn Henrik , Menné Torkil , Agner Tove
Published: March 2008

Background:  Few population‐based clinical follow‐up studies on hand eczema are reported.

Objectives:  The aim of this study was to characterize clinical symptoms and to examine occupational and medical consequences as well as persistence of hand eczema in a population‐based twin cohort.

Patients/Methods:  A total of 274 individuals with and without hand eczema were examined, patch tested, and interviewed in 1997–1998 and 2005–2006. Data on 188 individuals with hand eczema in 2005–2006 were analysed.

Results:  Erythema and scaling were the most frequent symptoms, and fingers and palms were most often affected. Mean hand eczema severity index score in individuals with clinical symptoms was 12.0. Sick leave was reported by 12.4%; job change by 8.5%. Being in the lowest socio‐economic group and atopic dermatitis were risk factors for sick leave [odds ratio (OR) = 5.6; 95% confidence interval (95% CI) 1.5–22.9 and OR = 2.9; 95% CI 1.0–8.1]. The majority (63.4%) had seen a doctor at least once, and atopic dermatitis was a risk factor for more than 1 visit (OR = 3.0; 95% CI 1.4–6.4). Duration of >10 years was a risk factor for persistence of symptoms, which was reported by 67.7%.

Conclusions:  The clinical picture and consequences of hand eczema vary; however, the majority experience chronic symptoms.
Polarized immune responses differentially regulate cancer development
Authors: Johansson Magnus , DeNardo David G. , Coussens Lisa M.
Published: March 2008

Summary: Tumor‐associated immune responses assert varied responses toward developing neoplasms that can either act to eradicate malignant cells via engagement of potent cytotoxic programs or alternatively enhance tumor growth through release of multifunctional pro‐tumor mediators. Seemingly paradoxical, these disparate activities reflect a continuum of polarization (or activation) states possible for distinct leukocyte subsets that demonstrate tissue, organ, and tumor selectivity. Herein, we review clinical and experimental studies investigating cellular and molecular mechanisms utilized by neoplastic tissues to alternatively polarize immune responses that favor either pro‐ or anti‐tumor immunity.
Engineering therapeutic monoclonal antibodies
Authors: Liu Xiao‐yun , Pop Laurentiu M. , Vitetta Ellen S.
Published: March 2008

Summary: During last two decades, the chimerization and humanization of monoclonal antibodies (mAbs) have led to the approval of several for the treatment of cancer, autoimmune diseases, and transplant rejection. Additional approaches have been used to further improve their in vivo activity. These include combining them with other modalities such as chemotherapy and redesigning them for improved pharmacokinetics, effector function, and signaling activity. The latter has taken advantage of new insights emerging from an increased understanding of the cellular and molecular mechanisms that are involved in the interaction of immunoglobulin G with Fc receptors and complement as well as the negative signaling resulting from the hypercrosslinking of their target antigens. Hence, mAbs have been redesigned to include mutations in their Fc portions, thereby endowing them with enhanced or decreased effector functions and more desirable pharmacokinetic properties. Their valency has been increased to decrease their dissociation rate from cells and enhance their ability to induce apoptosis and cell cycle arrest. In this review we discuss these redesigned mAbs and current data concerning their evaluation both in vitro and in vivo.
Immunotherapy of malignant brain tumors
Authors: Mitchell Duane A. , Fecci Peter E. , Sampson John H.
Published: March 2008

Summary: Despite aggressive multi‐modality therapy including surgery, radiation, and chemotherapy, the prognosis for patients with malignant primary brain tumors remains very poor. Moreover, the non‐specific nature of conventional therapy for brain tumors often results in incapacitating damage to surrounding normal brain and systemic tissues. Thus, there is an urgent need for the development of therapeutic strategies that precisely target tumor cells while minimizing collateral damage to neighboring eloquent cerebral cortex. The rationale for using the immune system to target brain tumors is based on the premise that the inherent specificity of immunologic reactivity could meet the clear need for more specific and precise therapy. The success of this modality is dependent on our ability to understand the mechanisms of immune regulation within the central nervous system (CNS), as well as counter the broad defects in host cell‐mediated immunity that malignant gliomas are known to elicit. Recent advances in our understanding of tumor‐induced and host‐mediated immunosuppressive mechanisms, the development of effective strategies to combat these suppressive effects, and a better understanding of how to deliver immunologic effector molecules more efficiently to CNS tumors have all facilitated significant progress toward the realization of true clinical benefit from immunotherapeutic treatment of malignant gliomas.
Twelve immunotherapy drugs that could cure cancers
Authors: ‘Mac’ Cheever Martin A.
Published: March 2008

Summary: Immune T cells can kill cancer cells. Cancer vaccines function by increasing the number of immune T cells. There are exceedingly strict biologic limits imposed on the immune system to prevent excessive T‐cell activation and expansion. The same biological restrictions limit cancer vaccines. Immunotherapeutic agents that circumvent the biological restrictions have been invented and formulated, including (i) dendritic cell activators and growth factors, (ii) vaccine adjuvants, (iii) T‐cell stimulators and growth factors, (iv) immune checkpoint inhibitors, and (v) agents to neutralize or inhibit suppressive cells, cytokines, and enzymes. Few of these agents are broadly available for the development of effective multiple component regimens. The major problem facing immunotherapy today is a lack of broad availability of agents already in existence. The National Cancer Institute has developed a well‐vetted ranked list of agents with high potential to serve as immunotherapeutic drugs. This review focuses on 12 of the agents, all with proven ability to augment T‐cell responses. Alone, each has little chance of making substantial inroads into cancer therapy. In combinations dictated by biology, the agents are overwhelmingly likely to have an impact. Future availability of these agents for development of innovative combination cancer therapy regimens will provide a benchmark for the resolve of the national cancer therapy translational research enterprise.
Signaling defects in anti‐tumor T cells
Authors: Frey Alan B. , Monu Ngozi
Published: March 2008

Summary: The immune response to cancer has been long recognized, including both innate and adaptive responses, showing that the immune system can recognize protein products of genetic and epigenetic changes in transformed cells. The accumulation of antigen‐specific T cells within the tumor, the draining lymph node, and the circulation, either in newly diagnosed patients or resultant from experimental immunotherapy, proves that tumors produce antigens and that priming occurs. Unfortunately, just as obviously, tumors grow, implying that anti‐tumor immune responses are either not sufficiently vigorous to eliminate the cancer or that anti‐tumor immunity is suppressed. Both possibilities are supported by current data. In experimental animal models of cancer and also in patients, systemic immunity is usually not dramatically suppressed, because tumor‐bearing animals and patients develop T‐cell‐dependent immune responses to microbes and to either model antigens or experimental cancer vaccines. However, inhibition of specific anti‐tumor immunity is common, and several possible explanations of tolerance to tumor antigens or tumor‐induced immunesuppression have been proposed. Inhibition of effective anti‐tumor immunity results from the tumor or the host response to tumor growth, inhibiting the activation, differentiation, or function of anti‐tumor immune cells. As a consequence, anti‐tumor T cells cannot respond productively to developmental, targeting, or activation cues. While able to enhance the number and phenotype of anti‐tumor T cells, the modest success of immunotherapy has shown the necessity to attempt to reverse tolerance in anti‐tumor T cells, and the vanguard of experimental therapy now focuses on vaccination in combination with blockade of immunosuppressive mechanisms. This review discusses several potential mechanisms by which anti‐tumor T cells may be inhibited in function.
Autoantibodies to tumor‐associated antigens: reporters from the immune system
Authors: Tan Eng M. , Zhang Jianying
Published: March 2008

Summary: Although autoantibodies have been recognized as participants in pathogenesis of tissue injury, the collateral role of autoantibodies as reporters from the immune system identifying cellular participants in tumorigenesis has not been fully appreciated. The immune system appears to be capable of sensing aberrant structure, distribution, and function of certain cellular components involved in tumorigenesis and making autoantibody responses to the tumor‐associated antigens (TAAs). Autoantibodies to TAAs can report malignant transformation before standard clinical studies and may be useful as early detection biomarkers. The autoantibody response also provides insights into factors related to how cellular components may be rendered immunogenic. As diagnostic biomarkers, specific TAA miniarrays for identifying autoantibody profiles could have sufficient sensitivity in differentiating between types of tumors. Such anti‐TAA profiles could also be used to monitor response to therapy. The immune system of cancer patients reveals the immune interactive sites or the autoepitopes of participants in tumorigenesis, and this information should be used in the design of immunotherapy.
The impact of T‐cell immunity on ovarian cancer outcomes
Authors: Nelson Brad H.
Published: March 2008

Summary: Ovarian cancer remains a challenging disease for which improved treatments are urgently needed. Most patients present with advanced disease that is highly responsive to surgery combined with platinum‐ and taxane‐based chemotherapy, with a state of minimal residual disease being achieved in many cases. However, chemotherapy‐resistant recurrent tumors typically appear within 1–5 years and are ultimately fatal. Recently, several groups have shown that ovarian tumors are often infiltrated by activated T cells at the time of diagnosis, and patients with dense infiltrates of CD3+CD8+ T cells experience unexpectedly favorable progression‐free and overall survival. Other cell types in the immune infiltrate oppose anti‐tumor immunity, including CD4+CD25+FoxP3+ regulatory T cells, CD8+ regulatory T cells, macrophages, and dendritic cells. The composition of immune infiltrates is shaped by the expression of cytokines, chemokines, antigens, major histocompatibility complex molecules, and costimulatory molecules. The relationship between these various immunological factors is reviewed here with a strong emphasis on outcomes data so as to create a knowledge base that is well grounded in clinical reality. With improved understanding of the functional properties of natural CD8+ T‐cell responses to ovarian cancer, there is great potential to improve clinical outcomes by amplifying host immunity.
Is interleukin‐1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy?
Authors: Apte Ron N. , Voronov Elena
Published: March 2008

Summary: The interleukin‐1 (IL‐1) family consists of two major agonistic proteins, IL‐1α and IL‐1β, which are pleiotropic and affect mainly inflammation, immunity, and hemopoiesis. The IL‐1 receptor antagonist (IL‐1Ra) is a physiological inhibitor of pre‐formed IL‐1. In their secreted form, IL‐1α and IL‐1β bind to the same receptors and induce the same biological functions. However, the IL‐1 molecules differ in their compartmentalization within the producing cell or the microenvironment. Thus, IL‐1β is solely active in its secreted form, whereas IL‐1α is mainly active in cell‐associated forms (intracellular precursor and membrane‐bound IL‐1) and only rarely as a secreted cytokine, mainly by macrophages/monocytes. IL‐1 is abundant at tumor sites, being produced by cellular elements of the tumor microenvironment or by the malignant cells, and it affects not only various phases of the malignant process, such as carcinogenesis, tumor growth, and invasiveness, but also patterns of interactions between malignant cells and the host's immune system. Hence, the effects of the IL‐1 molecules on the malignant process are complex and are often of an opposing nature. Comparative studies on the differential roles of malignant cell‐ or host‐derived IL‐1α and IL‐1β in different stages of the malignant process can subsequently open new avenues for manipulation of IL‐1 expression and function in cancer immunotherapy.
Enhancing the clinical activity of granulocyte‐macrophage colony‐stimulating factor‐secreting tumor cell vaccines
Authors: Jinushi Masahisa , Hodi F. Stephen , Dranoff Glenn
Published: March 2008

Summary: A comparative analysis of vaccination with irradiated, murine tumor cells engineered to express a large number of immunostimulatory molecules established the superior ability of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) to evoke potent, specific, and long‐lasting anti‐tumor immunity. Early stage clinical testing of this vaccination strategy in patients with diverse solid and hematologic malignancies revealed the consistent induction of a coordinated humoral and cellular reaction that effectuated substantial tumor destruction. Nonetheless, most subjects eventually succumbed to progressive disease, implying that additional immune defects remained to be addressed. More detailed investigations of the mechanisms underlying protective immunity in murine systems together with the characterization of the anti‐tumor reactions of patients who achieved durable clinical benefits in response to immunotherapy uncovered several pathways that restrain the efficacy of GM‐CSF‐secreting tumor cell vaccines. These include milk fat globule epidermal growth factor protein‐8 expansion of forkhead box protein 3+ regulatory T cells, cytotoxic T‐lymphocyte antigen‐4‐mediated negative costimulation, and soluble major histocompatibility complex class I chain‐related protein A suppression of NKG2D‐dependent innate and adaptive anti‐tumor cytotoxicity. Together, these results define key regulatory circuits that attenuate immune‐mediated tumor destruction and suggest novel combinatorial therapies that might enhance the clinical activity of GM‐CSF‐secreting tumor cell vaccines.
The promise of 4‐1BB (CD137)‐mediated immunomodulation and the immunotherapy of cancer
Authors: Lynch David H.
Published: March 2008

Summary: The continuing efforts in biomedical research to develop new therapies for cancer are entering an exciting new phase. Research over the past two to three decades has yielded a much more detailed understanding of the complexities of the cellular and molecular interactions involved in the generation and regulation of immune responses. We are also gaining insights into the mechanisms by which tumors evade or escape immune recognition and by which they become resistant to various existing chemotherapeutic and/or radiotherapeutic strategies. A clear conclusion that can be drawn from these studies is that effective treatments of cancer will become much more multifaceted and will include immunotherapeutic approaches. The identification and molecular cloning of genes encoding the receptors and ligands that play crucial roles in the generation and regulation of immune responses provides exciting new opportunities to induce and enhance effective endogenous immune responses to cancer. In this regard, the genes that comprise the tumor necrosis factor and tumor necrosis factor receptor superfamilies show particular promise. One receptor:ligand pair (4‐1BB/CD137 and 4‐1BBL/CD137L) is emerging as a target with important potential in its ability to enhance the generation of effective tumor‐specific immune responses in situ. The results of the studies cited in this review highlight the potentials of 4‐1BB‐mediated immunotherapy.
Perceived social support in relation to work among Danish general dental practitioners in private practices
Authors: Berthelsen Hanne , Hjalmers Karin , Söderfeldt Björn
Published: March 2008

Social support is an important phenomenon in the psychosocial work environment. The aim of this study was to assess the extent to which Danish general dental practitioners perceived support from colleagues and to relate perceived support to demographic and work related background factors. A questionnaire was sent to a random sample of 300 Danish dentists. The response rate was 80% after one reminder. Factor analyses and multiple regression analyses were carried out. The results showed that clinic size was the overall most important variable explaining perceived support among dentists. Gender differences were found in perceived emotional and practical support, and women perceived more emotional support (e.g. discussing problematic patients with peers) than their male colleagues. A similar gender difference was not found for the perception of practical support, such as helping each other in the event of falling behind schedule. Dentists from small and large practices did not differ in the extent of peer contact outside the clinical environment. This study emphasized the importance of the organizational setting for a professional and personal supportive psychosocial working environment in dentistry.
Salivary trefoil factor 3 enhances migration of oral keratinocytes
Authors: Storesund Trond , Hayashi Katsuhiko , Kolltveit Kristin M. , Bryne Magne , Schenck Karl
Published: March 2008

Trefoil factor 3 (TFF3) is a member of the mammalian TFF family. Trefoil factors are secreted onto mucosal surfaces of the entire body and exert different effects according to tissue location. Trefoil factors may enhance mucosal healing by modulating motogenic activity, inhibiting apoptosis, and promoting angiogenesis. Trefoil factor 3 is secreted from the submandibular gland and is present in whole saliva. The aim of this study was to assess the migratory and proliferative effects of TFF3 on primary oral human keratinocytes and oral cancer cell lines. The addition of TFF3 increased the migration of both normal oral keratinocytes and the cancer cell line D12, as evaluated by a two‐dimensional scratch assay. By contrast, no increase in proliferation or energy metabolism was observed after stimulation with TFF3. Trefoil factor 3‐enhanced migration was found to be driven partly by the extracellular signal‐related kinase (Erk1/2) pathway, as shown by addition of the mitogen‐activated protein kinase (MAPK) inhibitor PD 98059. Previous functional studies on trefoil peptides have all been based on cells from monolayered epithelium like the intestinal mucosa; this is the first report to show that normal and cancerous keratinocytes from stratified epithelium respond to TFF stimuli. Taken together, salivary TFF3 is likely to contribute to oral wound healing.
Patient delay for potentially malignant oral symptoms
Authors: Scott Suzanne , McGurk Mark , Grunfeld Elizabeth
Published: March 2008

The detection of oral cancer at an early stage is the most effective means to improve survival and reduce morbidity, disfigurement, duration of treatment, and hospital costs associated with this disease. However, approximately 30% of patients delay seeking help for more than 3 months following the self‐discovery of symptoms of oral cancer. This study aimed to increase our understanding of patient delay for potentially malignant oral symptoms in order to inform the development of interventions to encourage early presentation of oral cancer. Newly referred patients (n = 80) with potentially malignant oral symptoms completed a questionnaire to determine influences on the timing of their decision to seek help. Logistic regression analyses were conducted to determine factors associated with patient delay. The analysis indicated that the gravity of patients’ initial symptom interpretation, the level of deprivation, knowledge of oral cancer, severity of life events in the patient delay period, and perceived ability to seek help for oral symptoms were significantly related to the duration of patient delay, with the latter three variables being independent predictors. The results are discussed with reference to their implications for interventions aimed at reducing patient delay for symptoms of oral cancer.
Cutaneous differences between Black, African or Caribbean Mixed‐race and Caucasian women: biometrological approach of the hydrolipidic film
Authors: Fotoh Corinne , Elkhyat Ahmed , Mac Sophie , Sainthillier Jean Marie , Humbert Philippe
Published: March 2008

Background/purpose: Studies about the adaptation of ethnic types of skin to an environment radically different from their original environment are rarely found in the literature. We have evaluated the differences in the skin surface properties of three ethnic groups: Black, African or Caribbean Mixed‐race and Caucasian women living in defined climatic conditions.

Methods: Biometrological evaluations of barrier function were made by measurements of transepidermal water loss (TEWL), skin hydration and skin dryness. To approach the skin protective coating we evaluated cutaneous lipid index (LI), cutaneous pH, skin frictional properties and skin wettability.

Results: The TEWL, cutaneous hydration, dryness and LI show no significant difference. Volunteers were given a self‐assessment questionnaire regarding their hygiene and cosmetic practices. The results show that 100% of Black and 92% of African or Caribbean Mixed‐race women use a hydrating product daily vs. only 16% of Caucasian women. They justify this practice by the ‘dry skin’ sensation that they feel if they do not use a moisturizer. We tried to assess objectively to the protective coating surface of the human skin: the hydrolipidic cutaneous film, by measurements of pH, frictional properties and wettability which show significant differences. We may suppose that the hydrophilic/lipophilic balance of the skin in these three ethnic groups is different.

Conclusion: To interpret these results as accurately as possible, it would be interesting, in future investigations on the ethnic types of skin, to evaluate the sweat secretion, and to analyse each element of the sebaceous secretions quantitatively as well as qualitatively.
Machine‐learning classification of non‐melanoma skin cancers from image features obtained by optical coherence tomography
Authors: Jørgensen Thomas Martini , Tycho Andreas , Mogensen Mette , Bjerring Peter , Jemec Gregor B.E.
Published: March 2008

Background/purpose: A number of publications have suggested that optical coherence tomography (OCT) has the potential for non‐invasive diagnosis of skin cancer. Currently, individual diagnostic features do not appear sufficiently discriminatory. The combined use of several features may however be useful.

Methods: OCT is based on infrared light, photonics and fibre optics. The system used has an axial resolution of 10 μm, lateral 20 μm. We investigated the combined use of several OCT features from basal cell carcinomas (BCC) and actinic keratosis (AK). We studied BCC (41) and AK (37) lesions in 34 consecutive patients. The diagnostic accuracy of the combined features was assessed using a machine‐learning tool.

Results: OCT images of normal skin typically exhibit a layered structure, not present in the lesions imaged. BCCs showed dark globules corresponding to basaloid islands and AKs showed white dots and streaks corresponding to hyperkeratosis. Differences in OCT morphology were not sufficient to differentiate BCC from AK by the naked eye. Machine‐learning analysis suggests that when a multiplicity of features is used, correct classification accuracies of 73% (AK) and 81% (BCC) are achieved.

Conclusion: The data extracted from individual OCT scans included both quantitative and qualitative measures, and at the current level of resolution, these single factors appear insufficient for diagnosis. Our approach suggests that it may be possible to extract diagnostic data from the overall architecture of the OCT images with a reasonable diagnostic accuracy when used in combination.
Dynamic indentation on human skin in vivo: ageing effects
Authors: Boyer G. , Laquièze L. , Le Bot A. , Laquièze S. , Zahouani H.
Published: March 2008

Background/purpose: Knowledge of the mechanical properties of the human skin is very important for cosmetic and clinical research. Objective and quantitative measurements are essential to compare studies performed by different experimenters in different centres. The aim of this paper is to present a method to measure the viscoelastic properties of human skin in vivo using dynamic indentation.

Methods: A complete device to assess the stiffness and damping of skin has been developed. The frequency and strain amplitude range from 10 to 60 Hz and from 1 to 10 μm. Tests on pure elastic inert materials have been performed to validate the device. An in vivo study including dynamic indentation, suction test, hydration measurement and topographic analysis has been performed on 46 subjects aged from 18 to 70 years, divided into three groups.

Results: Results on inert materials show the validity of the device developed. The mechanical behaviour of the skin can be described by a Kelvin–Voight model under dynamic indentation. A comparison with a suction test, hydration and topographic measurements shows that the stiffness and the damping measured by dynamic indentation correspond mainly to the natural tense state of the skin on the body due to the dermis. A weak correlation has been found between dynamic indentation and suction parameters. The complex modulus measured by dynamic indentation at 10 Hz frequency stress ranges from 7.2 ± 2.1 kPa for the oldest group to 10.7 ± 2.6 kPa for the youngest group.

Conclusion: The device presented gives convincing results. The measurement of stiffness and damping complements the viscoelastic phenomenological parameters of the suction test.
Multiple crown‐root fractures in primary molars and a suspected subcondylar fracture following trauma: a report of a case
Authors: Tejani Zahra , Johnson Adèle , Mason Carol , Goodman Jane
Published: March 2008

Abstract –  Dental trauma is common and often more than one injury is found. Injuries to the primary dentition are usually luxations and mandibular fractures rarely occur. With trauma sustained to the chin, the posterior primary teeth are at increased risk of trauma and mandibular fractures can occur. The case discussed is of a 4‐year‐old female who presented 2 weeks following dental trauma with multiple primary molar fractures and a possible subcondylar fracture. The need for a detailed examination is emphasized and the management of the case under general anaesthesia is described.
Reduced anxiety‐like and depression‐related behavior in neuropeptide Y Y4 receptor knockout mice
Authors: Painsipp E. , Wultsch T. , Edelsbrunner M. E. , Tasan R. O. , Singewald N. , Herzog H. , Holzer P.
Published: March 2008

Neuropeptide Y (NPY) acting through Y1 receptors reduces anxiety‐ and depression‐like behavior in rodents, whereas Y2 receptor stimulation has the opposite effect. This study addressed the implication of Y4 receptors in emotional behavior by comparing female germ line Y4 knockout (Y4−/−) mice with control and germ line Y2−/− animals. Anxiety‐ and depression‐like behavior was assessed with the open field (OF), elevated plus maze (EPM), stress‐induced hyperthermia (SIH) and tail suspension tests (TST), respectively. Learning and memory were evaluated with the object recognition test (ORT). In the OF and EPM, both Y4−/− and Y2−/− mice exhibited reduced anxiety‐related behavior and enhanced locomotor activity relative to control animals. Locomotor activity in a familiar environment was unchanged in Y4−/− but reduced in Y2−/− mice. The basal rectal temperature exhibited diurnal and genotype‐related alterations. Control mice had temperature minima at noon and midnight, whereas Y4−/− and Y2−/− mice displayed only one temperature minimum at noon. The magnitude of SIH was related to time of the day and genotype in a complex manner. In the TST, the duration of immobility was significantly shorter in Y4−/− and Y2−/− mice than in controls. Object memory 6 h after initial exposure to the ORT was impaired in Y2−/− but not in Y4−/− mice, relative to control mice. These results show that genetic deletion of Y4 receptors, like that of Y2 receptors, reduces anxiety‐like and depression‐related behavior. Unlike Y2 receptor knockout, Y4 receptor knockout does not impair object memory. We propose that Y4 receptors play an important role in the regulation of behavioral homeostasis.
Magnetic resonance spectroscopy in anxiety disorders
Authors: Trzesniak Clarissa , Araújo David , Crippa José Alexandre S.
Published: March 2008

Objective:

Magnetic resonance spectroscopy (MRS) is a non-invasivein vivomethod used to quantify metabolites that are relevant to a wide range of brain processes. This paper briefly describes neuroimaging using MRS and provides a systematic review of its application to anxiety disorders.

Method:

A literature review was performed in the PubMed, Lilacs and Scielo databases using the keywords spectroscopy and anxiety disorder. References of selected articles were also hand-searched for additional citations.

Results:

Recent studies have shown that there are significant metabolic differences between patients with anxiety disorders and healthy controls in various regions of the brain. Changes were mainly found inN-acetylaspartate, which is associated with neuronal viability, but some of them were also seen in creatine, a substance that is thought to be relatively constant among individuals with different pathological conditions.

Conclusions:

MRS is a sophisticated neuroimaging technique that has provided useful insights into the biochemical and neurobiological basis of many anxiety disorders. Nevertheless, its utilization in some anxiety disorders is still modest, particularly social phobia and generalised anxiety. Although it is an extremely useful advance in neuroimaging, further research in other brain areas and patient populations is highly advisable.
Incidental brain MRI abnormalities in 60- to 64-year-old community-dwelling individuals: data from the Personality and Total Health Through Life study
Authors: Kumar Rajeev , Sachdev Perminder S. , Price Jeremy L. , Rosenman Stephen , Christensen Helen
Published: March 2008

Objective:

There have been limited data available on the prevalence of structural brain abnormalities in asymptomatic individuals and a growing interest in the various ethical issues related to reporting of such findings. This study evaluated the prevalence of incidental abnormalities on brain magnetic resonance imaging (MRI) in a random sample of 60- to 64-year-old community-dwelling individuals as well as successfully followed a referral pathway taking into account of the various ethical issues related to the referral process. The Personality and Total Health (PATH) Project was designed to study the risk and protection factors of normal ageing, dementia and other neuropsychiatric disorders.

Method:

MRI scans were performed in randomly selected 478 healthy, community-dwelling 60- to 64-year-old individuals. All scans were reported for abnormalities by a radiologist.

Results:

Abnormalities were detected in 22 (4.8%) subjects, comprising 10 tumours (pituitary adenoma 4, meningioma 3, suprasellar tumour 1, cavernous haemangioma 1, subarachnoid lipoma 1), 6 infarct-like lesions, 2 arachnoid cysts, 1 possible normal pressure hydrocephalus, and 1 each of unconfirmed aneurysm and mesial temporal sclerosis. Further evaluation led to novel intervention in one case of pituitary adenoma, and adjustment of drug treatment to modify risk factors in two cases with subclinical infarction.

Conclusion:

While no case required immediate referral or urgent surgical intervention, the change in the outcome of treatment of some cases suggests that appropriate referral process should be in place when researchers study large number of subjects in the community using MRI of the brain.
Associations of several anthropometric indices with insulin resistance in children: The Children Study
Authors: Manios Yannis , Kourlaba Georgia , Kafatos Anthony , Cook Tina L , Spyridaki Aspasia , Fragiadakis George A
Published: March 2008

Aim: To compare the associations of several anthropometric indices (i.e. waist circumference [WC], waist‐to‐height ratio, body mass index (BMI) and waist‐to‐hip ratio) with the insulin resistance (IR) proxy measures in Greek schoolchildren.

Methods: A random sample of 248 children was used. Fasting plasma glucose and serum insulin levels were measured. IR was estimated through homeostasis model assessment (HOMA), glucose‐to‐insulin ratio and quantitative insulin sensitivity check index.

Results: Insulin levels and IR indices were significantly related to BMI, WC and waist‐to‐height ratio. Glucose‐to‐insulin ratio and quantitative insulin sensitivity check index were inversely correlated with all anthropometric indices, while insulin levels and HOMA were positively associated with these indices. Generally, all significant correlations were weak to moderate (0.217 ≤ r ≤ 0.513). BMI, WC and waist‐to‐height ratio displayed similar correlation with insulin levels (r = 0.431, r = 0.427 and r = 0.354, respectively) and IR indices. Similar results were found using multiple linear regression analysis.

Conclusion: Based on the current findings, BMI, waist‐to‐height ratio and WC are higher, associated with the IR proxy measures compared with waist‐to‐hip ratio, among Greek pupils. Therefore, all these simple adiposity‐related indices could be used, alternatively, in clinical practice as a simple tool for identification of children at risk for developing IR.
Increased Expression of Catalase in Human Hepatoma Cells by the Soy Isoflavone, Daidzein
Authors: Kampkötter Andreas , Wiegand Christian , Timpel Claudia , Röhrdanz Elke , Chovolou Yvonni , Kahl Regine , Wätjen Wim
Published: March 2008

Abstract:  The reduced incidence of cancer that has been observed in Asian population traditionally consuming soy‐based food has been linked to the antioxidant potential of soy isoflavones, in particular daidzein and genistein. The present study was undertaken in order to test the antioxidative potential of daidzein and to examine the effect of daidzein treatment on the expression of the antioxidant enzyme catalase in the human hepatoma cell lines Huh‐7 and HepG2. Daidzein itself did not display radical scavenging activity but it significantly increased the activity of the antioxidant enzyme catalase. Huh‐7 cells were much more susceptible to daidzein cytotoxicity than HepG2 cells and showed much lower basal activity in luciferase reporter gene assays with the 3.2 kb fragment of the human catalase promoter. However, treatment with daidzein at a non‐toxic concentration resulted in a similar induction of promoter activity in both cell lines. Reporter gene studies with different promoter constructs in HepG2 cells restrict the potential localization of the main regulatory elements for basal and inducible activity of the catalase promoter to a region approximately 120 bp to 300 bp upstream of the start codon of the catalase gene. From our results, we conclude that in human hepatoma cells daidzein at a non‐toxic concentration increases the activity of human catalase and induces the transcription of the catalase gene via interaction with the proximal part of the promoter.
Labiaplasty of the Labia Minora: Patients’ Indications for Pursuing Surgery
Authors: Miklos John R. , Moore Robert D.
Published: March 2008

Introduction

Limited information is available regarding patients’ indication for seeking labiaplasty of the labia minora.

Aim

The aim of this article is to investigate a patient's indications for seeking labiaplasty of the labia minora.

Methods

This is a retrospective review of the medical records of all patients undergoing labiaplasty at our clinic over a 27-month period.

Main Outcome Measures

Indications for surgery were assessed using standardized questionnaires during the patients’ initial history and physical. Patients were divided into three groups as based on the questionnaire, including: Group I—patients seeking the procedure strictly for aesthetic reasons; Group II—patients seeking the procedure strictly for functional impairment (i.e., pain and discomfort); and Group III—patients who feel they are having the surgery for both aesthetic and functional reasons. Patients undergoing the surgery for aesthetic reasons were also asked whether this was strictly a personal decision or was influenced by either another man or woman whether a friend, spouse, or partner.

Results

The review revealed 131 patients had undergone a labia reduction surgery: Group I—those who received labia reduction surgery for strictly aesthetic reasons equaled 37% (49/131); Group II—those seeking the surgery strictly for functional impairment equaled 32% (42/131); and Group III—those seeking the surgery for both functional and aesthetic reasons equaled 31% (40/131).

Conclusion

The majority of patients undergoing reduction of the labia minora do so for functional reasons with minimal outside influences affecting their decision for treatment.
Delivering the urban housing offer
Authors: Glossop Catherine , Harrison Ben
Published: March 2008

Housing is high on Gordon Brown's agenda, but with the remit to deliver three million new homes by 2020, he and his government face a major challenge, say Catherine Glossop and Ben Harrison.
The end of aspiration?
Authors: Edelstein Jean
Published: March 2008

Gordon Brown has claimed that encouraging individual aspiration is a key goal of his Government. But what does that mean? Here Jean Edelstein argues that, in a world in which achievement is measured largely in terms of acquisition and consumer culture, Brown's agenda needs to be rethought.
ONE ON ONE An Interview With Joseph A. Yacura
Authors: Schildhouse Jill
Published: March 2008

Joseph A. Yacura is chief strategist and co‐founder for Supply Chain Management, LLC, headquartered in New York, a consulting firm that specializes in providing “Total Cost and Supply Chain Management Solutions” to mid‐ and large‐scale companies. Yacura has held numerous senior executive management positions – including operations, manufacturing, production control, strategic planning, finance, and supply chain management – at IBM, Pacific Bell, American Express and Inter Continental Hotels Group. He is past chair of CAPS Research in Tempe, Arizona, and is involved with the advisory board for the State University of New York at Oswego Foundation Board. Yacura has appeared on “The Nightly Business Report” program. He earned an MBA in finance and an MS in accounting from Binghamton University, along with a master's degree in quality management from Loyola University. He has also completed the Senior Executive Program at Stanford University.
Public Sector Entrepreneurship: Evidence from Trade Policy
Authors: McClough David
Published: March 2008

This article argues that a sudden and sustained increase in Regional Trade Agreements (RTAs) notified to the General Agreement on Tariffs and Trade (GATT) and the World Trade Organization (WTO) during the 1990s may be reflective of innovation by political and policy making entrepreneurs seeking to overcome increasing costs associated with participation in multilateral trade negotiations conducted under the auspices of the GATT/WTO. Analysis of data from the WTO suggests that the increase in RTA notifications may reveal entrepreneurial innovation.
Use of a bottle warmer to increase 4% sodium hypochlorite tissue dissolution ability on bovine pulp
Authors: Rossi‐Fedele Giampiero , De Figueiredo Jose A. P.
Published: March 2008

The aim of this study was to evaluate the tissue dissolution ability of 4% sodium hypochlorite at increasing temperatures with the use of a baby bottle warmer. Twenty pieces of bovine pulp tissue from freshly extracted incisors and canines were weighted and randomly distributed among four groups in accordance to the exposure to 4% sodium hypochlorite at different temperatures: group C – room temperature (20.5°C – control); group T1 – 45°C; group T2 – 60°C; group T3 – 75°C. The samples were placed within test tubes when the solution reached the desired temperature. Time taken for the dissolution was recorded. One‐way anova with logarithmical transformation and Duncan post‐hoc was used (P = 0.05). There was a statistically significant increase in speed of pulp dissolution from group T1 to group C and from groups T2 and T3 to group T1; group T2 and T3 displayed similar dissolution speeds.
SYMPOSIUM: Clearance of Aβ from the Brain in Alzheimer's Disease: Aβ‐Degrading Enzymes in Alzheimer's Disease
Authors: Miners James Scott , Baig Shabnam , Palmer Jennifer , Palmer Laura E. , Kehoe Patrick G. , Love Seth
Published: March 2008

In Alzheimer's disease (AD) Aβ accumulates because of imbalance between the production of Aβ and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Aβ is partly, if not in some cases solely, because of defects in its removal—mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Aβ. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Aβ‐degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin‐degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Aβin vitro or in animal studies include plasmin; endothelin‐converting enzymes ECE‐1 and ‐2; matrix metalloproteinases MMP‐2, ‐3 and ‐9; and angiotensin‐converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE‐2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEε4. We found no change in the level or activity of MMP‐2, ‐3 or ‐9 in AD. The level and activity of ACE are increased, the level being directly related to Aβ plaque load. Up‐regulation of some Aβ‐degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Aβ‐clearance pathways, reductions in the activity of particular Aβ‐degrading enzymes may become critical, leading to the development of AD and CAA.
Suspected primary scapulohumeral osteoarthritis in two Miniature ponies
Authors: Parth RA , Svalbe LS , Hazard GH , Church S
Published: March 2008

Summary  Two cases of severe scapulohumeral osteoarthritis in Miniature ponies are described, one bilateral and the other unilateral. The condition is thought to occur in miniature breeds as a result of scapulohumeral dysplasia. The presentation in one of the ponies was unusal: it refused to pick up either fore limb, with progression to a uniquely bizarre gait with narrow forelimb placement, an arched back and widely placed hindlimbs camped well forward under the body. The other pony was presented for an acute unilateral non‐weight bearing forelimb lameness. Response to analgesia in both cases was poor and both ponies were euthanased. A pathological fracture was evident in one affected glenoid cavity.