bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient‐based medicine
Authors: Dubertret L 
Published: October 2006

AbstractEvery day, we have to solve two questions:The first question is how to evaluate the severity of diseases affecting mainly the quality of life (psoriasis, acne, vitiligo, atopic dermatitis, genedermatosis …). This severity (the main information for selecting more appropriate treatments) is assessed by the patient but unfortunately the patient rarely has the expertise to make such assessments.The second question is to find a method to adjust the knowledge from the ‘evidence based medicine’, which is obtained by statistical population studies, to an individual patient, who will always be different and specific.The so‐called “Patient Based Medicine” is the association of clinical techniques which can make it possible to solve these two questions.Patient Based Medicine unfolds in four phases: questions, explanations, negotiation (the most important step) and prescription. The goal of these successive phases is to take into account in the therapeutic choice all the aspects of the patient's characteristics: way of life, co‐morbidities and associated treatments, previous experiences of the patient with different treatments, personal evaluation by the patient of his quality of life and of the impact on his quality of life of the disease and of the treatments. The goal of the negotiation is to involve the patient in the therapeutic choice. Patient Based Medicine is necessary for the efficient treatment of chronic diseases. Patient Based Medicine is a therapeutic revolution with a strong impact on patient/doctor relationships, medical education, and development of new drugs as well as on the awareness of the rights and the duty of patients.
Fluid inclusion constraints on the origin of the brines responsible for Pb–Zn mineralization at Pine Point and coarse non‐saddle and saddle dolomite formation in southern Northwest Territories
Authors: GLEESON S. A. , TURNER W. A. 
Published: October 2006

AbstractThe Pine Point region is a classic metallogenic mining camp that produced over 58 million short tons of Zn–Pb ore from approximately 40 base‐metal mineralized deposits hosted by Middle Devonian carbonates. The ore deposits are localized in paleokarstic features found in the epigenetic ‘Presqu'ile’ dolomite that preferentially replaced some of the upper barrier limestones. The main ore‐stage sulfides include galena, sphalerite, marcasite, and pyrite. A bulk fluid inclusion chemistry study was carried out on sulfide, coarse non‐saddle and saddle dolomite and calcite samples from the Pine Point and Great Slave Reef deposits, and unmineralized coarse non‐saddle and saddle dolomite samples from Hay West, Windy Point and Qito areas. Molar Cl/Br ratio data from Pine Point indicate the presence of four fluids at different stages of the paragenesis. The fluids trapped in sulfides and ore‐stage dolomites predominately consist of a Br‐rich fluid with a composition similar to that of evaporated seawater (fluid A), and a very Br‐enriched fluid of unknown origin (fluid B). Both these fluids are CaCl2–NaCl (Na to Ca ratios of 1:10)‐rich brines and have compositions unlike the modern formation waters in the Devonian aquifers in the basin today. A third, relatively Cl‐rich (or Br‐poor), fluid (fluid C) was identified in two samples and may have acquired some chlorinity by dissolving halide minerals. Mixing between the Br‐rich fluid A and a dilute fluid also occurred in the later stages of the paragenesis, resulting in the formation of calcite and native sulfur. Saddle and coarse dolomites not associated with significant sulfide mineralization have a narrow range of halogen compositions similar to fluid A. There is no evidence of fluid B or C in the unmineralized samples. Relative to a modern‐day seawater compositions all the fluids have had some modification of their cation compositions. There is some weak evidence for interactions with clastic units or crystalline basement rocks. It is also possible however, that the evaporative brines could have formed from a relatively CaCl2‐rich, NaCl‐depleted Devonian seawater, unlike the composition of modern‐day seawater.
Endoscopic investigation of the internal organs of a 15th‐century child mummy from Yangju, Korea
Authors: Kim Seok Bae , Shin Jeong Eun , Park Sung Sil , Bok Gi Dae , Chang Young Pyo , Kim Jaehyup , Chung Yoon Hee , Yi Yang Su , Shin Myung Ho , Chang Byung Soo , Shin Dong Hoon , Kim Myeung Ju 
Published: October 2006

AbstractOur previous reports on medieval mummies in Korea have provided information on their preservation status. Because invasive techniques cannot easily be applied when investigating such mummies, the need for non‐invasive techniques incurring minimal damage has increased among researchers. Therefore, we wished to confirm whether endoscopy, which has been used in non‐invasive and minimally invasive studies of mummies around the world, is an effective tool for study of Korean mummies as well. In conducting an endoscopic investigation on a 15th‐century child mummy, we found that well‐preserved internal organs remained within the thoracic, abdominal and cranial cavities. The internal organs – including the brain, spinal cord, lung, muscles, liver, heart, intestine, diaphragm and mesentery – were easily investigated by endoscopy. Even the stool of the mummy, which accidentally leaked into the abdominal cavity during an endoscopic biopsy, was clearly observed. In addition, unusual nodules were found on the surface of the intestines and liver. Our current study therefore showed that endoscopic observation could provide an invaluable tool for the palaeo‐pathological study of Korean mummies. This technique will continue to be used in the study of medieval mummy cases in the future.
Micro‐anatomical response of cartilage‐on‐bone to compression: mechanisms of deformation within and beyond the directly loaded matrix
Authors: Thambyah Ashvin , Broom Neil 
Published: October 2006

AbstractThe biomechanical function of articular cartilage relies crucially on its integration with both the subchondral bone and the wider continuum of cartilage beyond the directly loaded contact region. This study was aimed at visualizing, at the microanatomical level, the deformation response of cartilage including that of the non‐directly loaded continuum. Cartilage‐on‐bone samples from bovine patellae were loaded in static compression until a near‐equilibrium deformation was achieved, and then chemically fixed in this deformed state. Full‐depth cartilage–bone sections, incorporating the indentation profile and beyond, were studied in their fully hydrated state using differential interference contrast microscopy. Morphometric measurements of the indented profile were used in combination with a force analysis of the tangential layer to investigate the extent to which the applied force is attenuated in moving away from the directly loaded region. This study provides microscopic evidence of a structure‐related response in the transitional zone of the cartilage matrix. It is manifested as an intense chevron‐type shear discontinuity arising from the constraints provided by both the strain‐limiting articular surface and the osteochondral attachment. The discontinuity persists well into the non‐directly loaded continuum of cartilage and is proposed as a force attenuation mechanism. The structural and biomechanical analyses presented in this study emphasize the important role of the complex microanatomy of cartilage, highlighting the interconnectivity and optimal recruitment of the load‐bearing elements throughout the zonally differentiated cartilage depth.
Spatial separation of endothelial small‐ and intermediate‐conductance calcium‐activated potassium channels (KCa) and connexins: possible relationship to vasodilator function?
Authors: Sandow Shaun L. , Neylon Craig B. , Chen Mao X. , Garland Christopher J. 
Published: October 2006

AbstractActivation of endothelial cell small‐ (S) and intermediate‐ (I) conductance calcium‐activated potassium channels (KCa) and current or molecular transfer via myoendothelial gap junctions underlies endothelium‐derived hyperpolarization leading to vasodilation. The mechanism underlying the KCa component of vasodilator activity and the characteristics of gap junctions are targets for the selective control of vascular function. In the rat mesenteric artery, where myoendothelial gap junctions and connexin (Cx) 40 are critical for the transmission of the endothelial cell hyperpolarization to the smooth muscle, SKCa and IKCa provide different facets of the endothelium‐derived hyperpolarization response, being critical for the hyperpolarization and repolarization phases, respectively. The present study addressed the question of whether this functional separation of responses may be related to the spatial localization of the associated channels? The distribution of endothelial SKCa and IKCa and Cx subtype(s) were examined in the rat mesenteric artery using conventional confocal and high‐resolution ultrastructural immunohistochemistry. At the internal elastic lamina–smooth muscle cell interface at internal elastic lamina holes (as potential myoendothelial gap junction sites), strong punctate IKCa, Cx37 and Cx40 expression was present. SKCa, Cx37, Cx40 and Cx43 were localized to adjacent endothelial cell gap junctions. High‐resolution immunohistochemistry demonstrated IKCa and Cx37‐conjugated gold to myoendothelial gap junction‐associated endothelial cell projections. Clear co‐localization of KCa and Cxs suggests a causal relationship between their activity and the previously described differential functional activation of SKCa and IKCa. Such precise localizations may represent a selective target for control of vasodilator function and vascular tone.
Keystones in lymph node development
Authors: Blum Katrin S. , Pabst Reinhard 
Published: October 2006

AbstractNew molecular markers are constantly increasing our knowledge of developmental processes. In this review article we have attempted to summarize the keystones of lymphoid tissue development in embryonic and pathological conditions. During embryonic lymph node development in the mouse, cells from the anterior cardinal vein start to bud and sprout, forming a lymph sac at defined sites. The protrusion of mesenchymal tissue into the lymph sacs forms the environment, where so‐called ‘lymphoid tissue inducer cells’ and ‘mesenchymal organizer cells’ meet and interact. Defects of molecules involved in the recruitment and signalling cascades of these cells lead to primary immunodeficiency diseases. A comparison of molecules involved in the development of secondary lymphoid organs and tertiary lymphoid organs, e.g. in autoimmune diseases, shows that the same molecules are involved in both processes. This has led to the hypothesis that the development of tertiary lymphoid organs is a recapitulation of embryonic lymphoid tissue development at ectopic sites.
The prevalence of mental health problems in children 1½ years of age – the Copenhagen Child Cohort 2000
Authors: Skovgaard Anne Mette , Houmann Tine , Christiansen Eva , Landorph Susanne , Jørgensen Torben ,   CCC 2000 Study Team, Olsen E.M. , Heering K. , Kaas‐Nielsen S. , Samberg V. , Lichtenberg A. 
Published: October 2006

Background:  The Copenhagen Child Cohort, CCC 2000, was established to investigate developmental psychopathology prospectively from birth in a general population.Methods:  A random sample of 211 children from the CCC 2000 was investigated when the children were 1½ years of age. The prevalence and associates of mental health problems and psychopathology were studied by clinical and standardised strategies, including videotape recordings, parent interviews and the following instruments: The Child Behavior Check List 1½–5 (CBCL 1½–5), The Infant Toddler Symptom Check List (ITSCL), Checklist for Autism in Toddlers (CHAT), Bayley Scales of Infant Development II (BSID II), The Parent Child Early Relationship Assessment (PC ERA) and Parent Infant Relationship Global Assessment Scale (PIR‐GAS).Results:  Mental health problems according to International Classification of Diseases (ICD‐10) and Diagnostic Classification Zero to Three (DC 0–3) diagnoses were found in 16–18% of 1½‐year‐old children. Most common were disturbances of emotion, behaviour and eating and the DC 0–3 diagnosis of regulatory disorder. Parent–child relationship disturbances were found in 8%. High psychosocial risk was significantly associated with emotional and behavioural disorders (OR 3.1 95% (1.2–8.1)) and disturbed parent–child relationship (OR 5.0 95% (1.6–16.0)). The strongest association of risk was found between relationship disorders and emotional and behavioural disorders (OR 11.6 95% (3.8–37.5)).Conclusions:  The prevalence and distribution of psychopathology in 1½‐year‐old children seem to correspond to the distributions among older children. Disturbances in parent–child relationship have a key position in the risk mechanisms in early child psychopathology.
Is there an epidemic of child or adolescent depression?
Authors: Jane Costello E. , Erkanli Alaattin , Angold Adrian 
Published: October 2006

Background:  Both the professional and the general media have recently published concerns about an ‘epidemic’ of child and adolescent depression. Reasons for this concern include (1) increases in antidepressant prescriptions, (2) retrospective recall by successive birth cohorts of adults, (3) rising adolescent suicide rates until 1990, and (4) evidence of an increase in emotional problems across three cohorts of British adolescents.Methods:  Epidemiologic studies of children born between 1965 and 1996 were reviewed and a meta‐analysis conducted of all studies that used structured diagnostic interviews to make formal diagnoses of depression on representative population samples of participants up to age 18. The effect of year of birth on prevalence was estimated, controlling for age, sex, sample size, taxonomy (e.g., DSM vs. ICD), measurement instrument, and time‐frame of the interview (current, 3 months, 6 months, 12 months).Results:  Twenty‐six studies were identified, generating close to 60,000 observations on children born between 1965 and 1996 who had received at least one structured psychiatric interview capable of making a formal diagnosis of depression. Rates of depression showed no effect of year of birth. There was little effect of taxonomy, measurement instrument, or time‐frame of interview. The overall prevalence estimates were: under 13, 2.8% (standard error (SE) .5%); 13–18 5.6% (SE .3%); 13–18 girls: 5.9% (SE .3%); 13–18 boys: 4.6% (SE .3%).Conclusions:  When concurrent assessment rather than retrospective recall is used, there is no evidence for an increased prevalence of child or adolescent depression over the past 30 years. Public perception of an ‘epidemic’ may arise from heightened awareness of a disorder that was long under‐diagnosed by clinicians.
Chronic lithium administration to FTDP‐17 tau and GSK‐3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre‐formed neurofibrillary tangles do not revert
Authors: Engel Tobias , Goñi‐Oliver Paloma , Lucas José J. , Avila Jesús , Hernández Félix 
Published: October 2006

AbstractGlycogen synthase kinase‐3 (GSK‐3) has been proposed as the main kinase able to aberrantly phosphorylate tau in Alzheimer's disease (AD) and related tauopathies, raising the possibility of designing novel therapeutic interventions for AD based on GSK‐3 inhibition. Lithium, a widely used drug for affective disorders, inhibits GSK‐3 at therapeutically relevant concentrations. Therefore, it was of great interest to test the possible protective effects of lithium in an AD animal model based on GSK‐3 overexpression. We had previously generated a double transgenic model, overexpressing GSK‐3β in a conditional manner, using the Tet‐off system and tau protein carrying a triple FTDP‐17 (frontotemporal dementia and parkinsonism linked to chromosome 17) mutation. This transgenic line shows tau hyperphosphorylation in hippocampal neurones accompanied by neurofibrillary tangles (NFTs). We used this transgenic model to address two issues: first, whether chronic lithium treatment is able to prevent the formation of aberrant tau aggregates that result from the overexpression of FTDP‐17 tau and GSK‐3β; second, whether lithium is able to change back already formed NFTs in aged animals. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Furthermore, it is still possible to partially reverse tau pathology in advanced stages of the disease, although NFT‐like structures cannot be changed. The same results were obtained after shut‐down of GSK‐3β overexpression, supporting the possibility that GSK‐3 inhibition is not sufficient to reverse NFT‐like aggregates.
A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin
Authors: Omura Tomohiro , Kaneko Masayuki , Okuma Yasunobu , Orba Yasuko , Nagashima Kazuo , Takahashi Ryosuke , Fujitani Noboru , Matsumura Satoshi , Hata Akihisa , Kubota Kyoko , Murahashi Karin , Uehara Takashi , Nomura Yasuyuki 
Published: October 2006

AbstractIt has been proposed that in autosomal recessive juvenile parkinsonism (AR‐JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum‐associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin‐associated endothelin receptor‐like receptor (Pael‐R), a substrate of Parkin, leads to endoplasmic reticulum stress, causing neuronal death. We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress‐induced apoptosis. This study shows that HRD1 was expressed in substantia nigra pars compacta (SNC) dopaminergic neurons and interacted with Pael‐R through the HRD1 proline‐rich region, promoting the ubiquitylation and degradation of Pael‐R. Furthermore, the disruption of endogenous HRD1 by small interfering RNA (siRNA) induced Pael‐R accumulation and caspase‐3 activation. We also found that ATF6 overexpression, which induced HRD1, accelerated and caused Pael‐R degradation; the suppression of HRD1 expression by siRNA partially prevents this degradation. These results suggest that in addition to Parkin, HRD1 is also involved in the degradation of Pael‐R.
Glutamate pretreatment affects Ca2+ signaling in processes of astrocyte pairs
Authors: Padmashri Ragunathan , Sikdar Sujit Kumar 
Published: October 2006

AbstractSimultaneous somatic patch‐pipette recording of a single astrocyte to evoke voltage‐gated calcium currents, and Ca2+ imaging, were used to study the spatial and temporal profiles of depolarization‐induced changes in intracellular Ca2+ ([Ca2+]i) in the processes of cultured rat cortical astrocytes existing as pairs. Transient Ca2+ changes locked to depolarization were observed as microdomains in the processes of the astrocyte pairs, and the responses were more pronounced in the adjoining astrocyte. Considering the functional significance of higher concentrations of glutamate observed in certain pathological conditions, Ca2+ transients were recorded following pretreatment of cells with glutamate (500 µm for 20 min). This showed distance‐dependent incremental scaling and attenuation in the presence of the metabotropic glutamate receptor (mGluR) antagonist, α‐methyl(4‐carboxy‐phenyl) glycine (MCPG). Estimation of local Ca2+ diffusion coefficients in the astrocytic processes indicated higher values in the adjoining astrocyte of the glutamate pretreated group. Intracellular heparin introduced into the depolarized astrocyte did not affect the Ca2+ transients in the heparin‐loaded astrocyte but attenuated the [Ca2+]i responses in the adjoining astrocyte, suggesting that inositol 1,4,5 triphosphate (IP3) may be the transfer signal. The uncoupling agent, 1‐octanol, attenuated the [Ca2+]i responses in both the control and glutamate pretreated astrocytes, indicating the role of gap junctional communication. Our studies indicate that individual astrocytes have distinct functional domains, and that the glutamate‐induced alterations in Ca2+ signaling involve a sequence of intra‐ and intercellular steps in which phospholipase C (PLC), IP3, internal Ca2+ stores, VGCC and gap junction channels appear to play an important role.
Ubiquitin–proteasome pathway mediates degradation of APH‐1
Authors: He Guiqiong , Qing Hong , Cai Fang , Kwok Clement , Xu Huaxi , Yu Gang , Bernstein Alan , Song Weihong 
Published: October 2006

Abstractγ‐Secretase catalyzes intramembraneous proteolysis of several type I transmembrane proteins, including β‐amyloid precursor protein (APP), to generate amyloid β protein (Aβ), a key player in the pathogenesis of Alzheimer's disease (AD). The critical components of the γ‐secretase complex include presenilin (PS), nicastrin (NCT), presenilin enhancer‐2 (PEN‐2) and anterior pharynx defective‐1 (APH‐1). Abnormalities of the ubiquitin–proteasome pathway have been implicated in the pathogenesis of AD; while PS and PEN‐2 turnover is regulated by this pathway, it is unknown whether the ubiquitin–proteasome pathway is also involved in the degradation of APH‐1 protein. In this study, we found that the expression of endogenous and exogenous APH‐1 significantly increased in cells treated with proteasome‐specific inhibitors. The effect of the proteasome inhibitors on APH‐1 was dose‐ and time‐dependent. APH‐1 protein was ubiquitinated. Pulse‐chase metabolic labeling experiments showed that the degradation of newly synthesized radiolabeled APH‐1 proteins was inhibited by lactacystin. Disruption of the PS1 and PS2 genes did not affect the degradation of APH‐1 by the ubiquitin–proteasome pathway. Furthermore, over‐expression of APH‐1 and inhibition of proteasomal APH‐1 degradation facilitated γ‐secretase cleavage of APP to generate Aβ. These results demonstrate that the degradation of APH‐1 protein is mediated by the ubiquitin–proteasome pathway.
Regulation of neurotrophin‐3 gene transcription by Sp3 and Sp4 in neurons
Authors: Ishimaru Naoki , Tabuchi Akiko , Hara Daichi , Hayashi Hiroyuki , Sugimoto Takayuki , Yasuhara Masahiro , Shiota Jun , Tsuda Masaaki 
Published: October 2006

AbstractNeurotrophin‐3 (NT‐3), a neurotrophin member, plays crucial roles in neuronal development, function and plasticity. Previous studies have demonstrated that NT‐3 gene transcription is driven by alternative promoters A and B, located upstream of exons 1A (EIA) and 1B (EIB), respectively. However, the transcription factors and DNA elements that drive NT‐3 gene transcription remain to be identified. Here, we analysed the promoter region of the NT‐3 gene and found that an NT‐3 transcript containing EIB is predominantly expressed in cortical neurons which preferentially utilize promoter B, and two tandemly repeated GC‐boxes, located between −100 and −60 base pairs within promoter B, are required for the transcription. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that both specificity protein (Sp)3 and Sp4 were able to bind to the Sp1 binding sequences within the GC boxes. Expression of dominant‐negative Sp3 and Sp4 small interfering RNA in cortical neurons reduced the activity of the NT‐3 gene promoter. Over‐expression of Sp1 family members, especially Sp4, resulted in an increase of the NT‐3 gene promoter. These findings indicate that the NT‐3 gene is a target gene for Sp4 that is abundantly expressed in the brain.