tbuckley/cabot-search huggingface dataset:
Bone fracture repair, but not fetal skeletal development is supported by syndecan-4
Authors: Jessica Bertrand, Richard Stange, Heriburg Hidding, Frank Echtermeyer, Giovanna Nalesso, Lars Godmann, Francesco Dell'Accio, Thomas Pap, Rita Dreier
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The heparan sulphate proteoglycan syndecan-4 (Sdc4) has been strongly associated with osteoarthritis, a disease that mimics key aspects of early cartilage remodelling during endochondral ossification. The role of Sdc4 in embryonic and adult bone formation, however, remains unclear. Therefore, the authors used <i>Sdc4</i><sup>−/−</sup> mice to analyse the distribution and functional role of Scd4 in endochondral ossification of mouse embryos and in adult fracture repair, which recapitulates endochondral ossification, but like osteoarthritis involves an inflammatory component. <h3>Methods</h3> In <i>Sdc4</i><sup>−/−</sup><i>/LacZ knock-in</i> animals, <i>Sdc4</i> promoter activity was anlysed using β-galactosidase stainings. E16.5 embyros were used for histological (alcian blue/alizarin red) and immunohistological (PCNA, Col10a1, ADAMTS-4, BC-3, Sdc2) stainings. Calcified bone area was quantified using whole mount stainings. Histological (Masson-Goldner, alcian blue) and immunohistological (Col10a1, Sdc2, PCNA) stainings at day 7, 14 and 28 fracture calli were performed. Callus size and cartilage area were quantified using image J. Chondrocytes were isolated from neonatal knee joints and embyronal cartilage. Proliferation was investigated using MTT assay. Gene expression analysis for Sdc-2, Sdc-4 with and without stimulation using tumour necrosis factor α and WNT3a was performed using quantitative RT-PCR. <h3>Results</h3> Sdc4 promoter activity was detectable in all stages of chondrocyte differentiation, and Sdc4 deficiency inhibited chondrocyte proliferation both in vivo and in vitro. Moreover, aggrecan turn over in the epiphysial cartilage was decreased transiently in vivo, but this did not lead to a growth phenotype at birth. In contrast, fracture healing in adult mice was markedly delayed in Sdc4<sup>−/−</sup> animals and accompanied by increased callus formation. Analysing the discrepancy between the mild embryonic and the severe adult phenotype, the authors found a compensatory upregulation of Sdc2 in the developing cartilage of Sdc4<sup>−/−</sup> mice that was absent in adult tissue. Stimulation of chondrocytes with Wnt3a in vitro, led to an increased expression of Sdc2, while stimulation with TNFα resulted in an upregulation of Sdc4 but a decreased expression of Sdc2. <h3>Conclusion</h3> The authors conclude that Sdc4 is functionally involved in endochondral ossification and that the loss of Sdc4 impairs adult fracture healing due to the inhibition of compensatory mechanisms under inflammatory conditions.
HEART-BLOCK IN JAUNDICE
Authors: R. D. Rudolf
Journal: BMJ (1916)

IN view of the conmparative rarity of this condition the following cases possess considerable interest.All three men were in the early stages of their military training and paraded sick owing to discoloration of tile urine, wlicih, coupled with a feeling of great exhaustion, caused them considerable alarm.CASE I. Private H., aged 18.No history of venereal disease.Woke nLp one morning after night operations feeling very weak and shivery, and noticed that his urine was red in colour.His temperature was 100.80; no physical signs could be detected, except that the spleen was-just palpable.The urine was dark brown and contained heavy deposits; it showed the presence of albumin, anid gave a positive reaction to the guaiacum test.On microscopic examiuation a few red corpuscles, a quantity of amorphous pigment, and some bladder epithelium were seen.S3pectroscope examination showed the absorption bands typical of methaemoglobin.The patient was put to bed with hot-water bottles and given warm dritnks.After twenty-four hours the uritie was clear, and lie felt quite well, though weak.He was given an iron and arsenic tonic, and returned to special duty in a few days.He had no recurrence while under my observation.
Data protection, informed consent, and research
Authors: Stewart Room
Journal: BMJ (2004)

Editor-The Data Protection Act 1998 does not prohibit the processing of personal information for medical research purposes.Indeed, it is clear from section 33 of the act that such processing is expressly permitted.If it were otherwise, then the act would be in direct conflict with the core aims of the laws that underpin it-namely, the Council of Europe Convention of 1981 and the European Union Directive of 1995.These laws seek to facilitate data processing activities, primarily "free flows" of information, rather than suppress data processing.The problems to which Peto et al refer in their editorial on data protection, informed consent, and research are not Data Protection Act problems but, rather, problems caused by ignorance and misunderstanding. 1 With basic training on the key mechanisms of the act the problems of which the authors complain can be easily overcome.Training need not be an expensive task either.Legal compliance can be achieved at comparatively modest cost.There are two additional points of note.Firstly, the Data Protection Act regulates the processing of personal information relating to living individuals.Thus, research following death is not regulated.Secondly, the act and case law make clear that information will not be "personal data" if it does not identify a living person or if it does not have the individual as its focus or is not significantly biographical.So, if medical researchers do not actually need or seek identification information the act should not be engaged.
One-time general consent for research on biological samples: Good idea, but will it happen?
Authors: Peter N Furness
Journal: BMJ (2006)

One-time general consent for research on biological samples Opt out system for patients is optimal and endorsed in many countriesEditor-Wendler's valuable overview of empirical studies of patients' preferences about the use of residual (leftover) tissue for research is not complete. 1 The discussion has already been settled by legislation in many countries.In 2004 the Danish act on patient rights was amended with an opt out system for using residual tissue for research.In 2004 the US Office for Human Research Protections (OHRP) issued guidance that research on residual tissue which is anonymous to the researcher is not human subject research and therefore the tissue can be used without consent. 2Earlier the Dutch Federation of Medical Research Societies' code of conduct on research with residual tissue drafted with patients' organisations had an opt out system for research on samples anonymous to the researcher. 3 In the recent UK Human Tissue Act no form of consent is needed for the use of fully anonymous or coded (or linked) residual tissue that is anonymous to the researcher, provided that an ethical review board has permitted the study.The more restrictive provisions in the original bill were amended also because of pressure from patient groups afraid that research to their benefit would be hampered by the proposed consent system.Wendler emphasises autonomy and argues that one-time consent protects the autonomy of individuals and protects them from serious risks.There are two major arguments against this.Firstly, autonomy should be balanced against other values such as the interests of patients who might benefit from this research. 4 Secondly, autonomy as such cannot protect individuals from risks but only from risks they do want to carry.Research on residual tissue, whether anonymous or anonymously used and being coded, does not carry any risks to individuals.Ethical review boards should oversee that sufficient measures have been taken to ensure that the samples used in research remain anonymously used.It should be possible to enrich data from tissue research with patient data.Fully anonymising samples, as suggested by Wendler, is a waste of valuable information.
Effect of trail design and grooming on the incidence of injuries at alpine ski areas
Authors: K A Bergstrøm, A Ekeland
Journal: British Journal of Sports Medicine (2004)

Objectives: To identify the conditions at certain sites on slopes known as black spots for injury. Method: In the Hafjell and Voss alpine ski areas in Norway, 1410 skiing injuries were recorded from December 1990 through the 1996 season. In Hafjell, 183 of these injuries were plotted on an area map during the two first seasons. Similarly, in Voss, 214 injuries were plotted on an area map for two seasons. During the last three seasons in Hafjell, 835 ski injuries were related to 6712 snow grooming hours and 6 829 084 lift journeys. Results: The mean injury rate was 2.2 injuries per 1000 skier days, and the mean injury severity score (ISS) was 3.1. Accumulations of injuries at three sites (black spots) were recorded on the Hafjell area map. These injuries represented 40% of all injuries in the alpine area (p&lt;0.05). Seven injury accumulation sites were recorded on the alpine area map of Voss, representing 22% of the total injuries (p&gt;0.05). Grooming of the slopes was rated poor for the 49% of injuries that occurred at the sites of injury concentration and significantly different (27%) from injuries that occurred at random in Hafjell. The corresponding values in Voss were 50% and 25% respectively. Grooming hours appeared to be inversely proportional to the number of injuries: R = −0.99 (p&lt;0.02). The mean ISS declined significantly in Hafjell over the observation period (p&lt;0.001). Conclusion: Inappropriate trail design and slope grooming seem to result in an accumulation of injuries at certain sites. Modification in construction and maintenance of the courses may reduce the number of injuries and mean ISS.
Analytical approaches to the study of the disposition of myelotoxic agents.
Authors: D E Rickert, T S Baker, J P Chism
Journal: Environmental Health Perspectives (1981)

A correlation of myelotoxic effect with concentration or a foreign compound of its metabolite at the site of action may provide useful insights into the mechanism of toxic action and/or its amelioration. This correlation requires sensitive and specific assay methods. This communication describes useful methods for the study of benzene disposition in rodents. The assays are sensitive, specific, and rapid. They rely on gas chromatography-mass spectrometry and on high performance liquid chromatography. These methods have allowed measurement of catechol, phenol, and hydroquinone in samples of rodent bone marrow following inhalation exposure to benzene. Their application to the study of benzene metabolism in rat bone marrow in situ is also described.
T and B lymphocytes in contact and atopic dermatitis
Authors: LENA SECHER, ELSE SVEJGAARD, GRETE SΘNDERSTRUP HANSEN
Journal: British Journal of Dermatology (1977)

Twenty patients with contact dermatitis, eighteen with atopic dermatitis, two with mixed dermatitis, and 20 controls were examined for the number of T and B lymphocytes, and serum concentrations of IgD and IgE. Significantly higher counts of B lymphocytes bearing IgE and high serum IgE values were found in the atopic group. No other significant differences were found. In particular, we found a normal frequency of IgD bearing lymphocytes in contact dermatitis, and normal T lymphocyte counts in both groups of patients.
Modeling of Diffusion Transport through Oral Biofilms with the Inverse Problem Method
Authors: Rui Ma, Jie Liu, Yun‐tao Jiang, Zheng Liu, Zi‐sheng Tang, Dong‐xia Ye, Jin Zeng, Zheng‐wei Huang
Journal: International Journal of Oral Science (2010)

The purpose of this study was to develop a mathematical model to quantitatively describe the passive transport of macromolecules within dental biofilms. Fluorescently labeled dextrans with different molecular mass (3 kD, 10 kD, 40 kD, 70 kD, 2 000 kD) were used as a series of diffusion probes. Streptococcus mutans, Streptococcus sanguinis, Actinomyces naeslundii and Fusobacterium nucleatum were used as inocula for biofilm formation. The diffusion processes of different probes through the in vitro biofilm were recorded with a confocal laser microscope. Mathematical function of biofilm penetration was constructed on the basis of the inverse problem method. Based on this function, not only the relationship between average concentration of steady‐state and molecule weights can be analyzed, but also that between penetrative time and molecule weights. This can be used to predict the effective concentration and the penetrative time of anti‐biofilm medicines that can diffuse through oral biofilm. Furthermore, an improved model for large molecule is proposed by considering the exchange time at the upper boundary of the dental biofilm.
RADIOIMMUNODETECTION OF MELANOMA USING In-111???96.5 MONOCLONAL ANTIBODY (In-111???96.5 MoAb)
Authors: Samuel E. Halpern, Robert O. Dillman, Kathryn F. Witztum, Phillip L. Hagan, Jacquelyn B. Dillman, Maureen L. Clutter, John F. Shega, William M. Burrows, James M. Frincke, Richard M. Bartholomew, Gary S. David, Dennis J. Carlo
Journal: Clinical Nuclear Medicine (1984)

The purpose of this study was to evaluate In-111–96.5 MoAb as a radiopharmaçeuticl (R) for the detection of melanoma (mel). The 96.5 MoAb targets a 97 kilodalton surface antigen on the mel cells. Labeling was by a bifunctional chelation technique, and resulted in 3–5 mCi of In-111 chelated to 1 mg of antibody (A). The R was administered (Ad) intravenously through a 30–120 minute period. Twenty-two studies were performed in 21 patients (PT), with one PT studied twice. In four PT, unlabeled A was Ad prior to the R. Other PT received from 2–19 mg of unlabeled A mixed with the R. Blood (B) was drawn at multiple times following the infusion to observe R kinetics, and to determine if serum chemistries indicated toxicity (tox). There was no evidence of tox from the R or carrier A. Increasing protein mass slowed the loss of In-111 from B, and appeared to improve lesion detection. 66% of the 73 lesions 1.5 cm or larger were detected. Eight metastases were detected which were not clinically suspected. Five metastases imaged were in the 0.5–1.0 cm size range. Two were scalp metastases, and three were lymph nodes in the anterior cervical triangle of the neck. Liver uptake was a major cause of failure of the R as lesions could not be resolved if they occurred in the liver. We conclude that In-111–96.5 MoAb shows promise as a R for the detection of mel, and warrants further study.
IS THE REALIZATION OF REASONABLE IDEALS IN DENTAL EDUCATION NEAR AT HAND?
Authors: CHAS. C. CHITTENDEN
Journal: JAMA (1903)

Reasonable ideals in dental education would seem to be defined by those standards as yet unattained and not yet in practical working, but which are admittedly possible and desirable in the estimation of the leading dental teachers, practitioners and examiners of this and foreign countries as expressed and promulgated by them personally and in the councils of the great national and international organizations. In no other country in the world is dentistry esteemed so truly a separate and distinct science and profession as in the United States of America. Most of our schools are independent of and free from domination by the medical profession and medical schools, which is a condition not at all to be found in the schools of Europe, where our beloved profession is held as a mechanical art tacked onto a background of medical didactics. Every enthusiastic lover of his profession probably has formed an ideal
Apixaban or Enoxaparin for Thromboprophylaxis after Knee Replacement
Authors: Michael Rud Lassen, Gary E Raskob, Alexander Gallus, Graham Pineo, Dalei Chen, Ronald J Portman
Journal: New England Journal of Medicine (2009)

ConclusionsAs compared with enoxaparin for efficacy of thromboprophylaxis after knee replacement, apixaban did not meet the prespecified statistical criteria for noninferiority, but its use was associated with lower rates of clinically relevant bleeding and it had a similar adverse-event profile.(ClinicalTrials.govnumber, NCT00371683.)
Metabolism of hemoglobin-vesicles (artificial oxygen carriers) and their influence on organ functions in a rat model
Authors: Hiromi Sakai, Hirohisa Horinouchi, Yohei Masada, Shinji Takeoka, Eiji Ikeda, Masuhiko Takaori, Koichi Kobayashi, Eishun Tsuchida
Journal: Biomaterials (2003)
773. Role of Lipid-Rafts in the Binding and Internalization of Dendriplexes and Lipoplexes
Authors: Peng H. Tan, Maria Manunta, Andrew J.T. George
Journal: Molecular Therapy (2005)

Top of pageAbstract
Understanding the cellular uptake and intracellular trafficking of non-viral vector complexes is an important prerequisite for improving the transfection efficiency. Synthetic branched polymers, such as dendrimers and liposomes are both vectors used for gene transfer. Although these cationic molecules show promise as versatile DNA carriers, very little is known about the mechanism of gene delivery. This report investigates how the uptake occurs and evaluates whether the internalization of dendriplexes and lipoplexes takes place randomly on the cell surface or at preferential sites, such as membrane rafts. Following extraction of plasma membrane cholesterol, the transfection efficiency of the gene delivered by dendrimer and liposomes was drastically decreased. Replenishment of membrane cholesterol restored the gene expression. The binding and especially internalization of dendriplexes and lipoplexes was strongly reduced by cholesterol depletion before transfection. However, cholesterol removal after transfection did not inhibit expression of the delivered gene. Fluorescent dendriplexes co-localize with the ganglioside GM1 present into membrane rafts both in immunoprecipitation assay and confocal microscopy studies. These data strongly suggest that membrane cholesterol and raft integrity are physiologically relevant for the cellular uptake of DNA-dendrimer or -lipid complexes. Hence, these findings provide evidence that membrane rafts are important for the internalization of non-viral vectors in gene therapy.
Progressive Esophagitis from Acyclovir-Resistant Herpes Simplex
Authors: Stephen L. Sacks
Journal: Annals of Internal Medicine (1989)

Clinically acquired acyclovir resistance in herpes simplex has usually been associated with a deficiency in viral thymidine kinase, which, in turn, has been linked with attenuated virulence in animal models. Diminished pathogenicity in thymidine kinase-deficient isolates has been partly responsible for controversies about the clinical significance of antiviral resistance. We report on a series of resistant virus isolates from a patient who had severe, progressive esophagitis. These isolates had various thymidine kinase activities, ranging from 2.8% to 130% when compared with the activity of the isolate obtained before treatment; the resistant isolate 615 retained enzyme activity as well as neurovirulence in an encephalitis model. Plaque purification showed a heterogeneous mixture containing at least one acyclovir-resistant, foscarnet-resistant plaque isolate (615.8) fully able to phosphorylate acyclovir. The 3.3-kbp BamHI fragment containing most of the DNA polymerase gene from isolate 615.8 was purified and used to successfully transfer both acyclovir and foscarnet resistance. Acquisition of in-vitro acyclovir resistance was associated with progression of clinical disease, as well as with maintenance of pathogenicity in an animal model and at least one mutation in viral DNA polymerase. Patients with herpes simplex infections that progress during acyclovir therapy should be observed for acquisition of resistance in the setting of antiviral chemotherapy; future studies should also consider the presence of heterogeneous virus populations in such patients.
The natural history of childhood eczema: observations from the British 1958 birth cohort study
Authors: None Williams, None Strachan
Journal: British Journal of Dermatology (1998)

The National Child Development Study (NCDS) is a birth cohort study whose longitudinal design makes it suitable for examining the natural history of common diseases in childhood such as atopic eczema. We have analysed the age of onset and clearance rates for examined and/or reported eczema in 6877 children born during the period 3-9 March 1958 for whom linked data were available at birth and at the ages of 7, 11, 16 and 23 years. Of the 870 cases with examined or reported eczema by the age of 16 years, 66% had age of onset by the age of 7 years. Of the 571 children with reported or examined eczema by the age of 7 years, the proportion of children who were clear in terms of examined eczema or reported eczema in the last year at ages 11 and 16 years was 65% and 74%, respectively. These 'apparent' or short-term clearance rates fell to 53% and 65%, respectively, after allowance for subsequent recurrences in adolescence and early adulthood. Age of onset of community-ascertained cases of atopic eczema may be later than that reported in hospital-based studies. The long-term prognosis of childhood eczema may be worse than some previous studies have suggested, especially when subsequent recurrences are taken into account.
Lung T-Helper Cells Expressing T-cell Receptor AV2S3 Associate with Clinical Features of Pulmonary Sarcoidosis
Authors: JOHAN GRUNEWALD, MARY BERLIN, OLLE OLERUP, ANDERS EKLUND
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In previous reports of studies of Scandinavian sarcoidosis patients, we have described a strong association between lung-restricted expansions of T cells expressing T-cell receptor (TCR) AV2S3 and the human leukocyte antigen (HLA)-DRB1*0301 (DR17) and -DRB3*0101 alleles, suggesting the presence of a specific antigen in sarcoidosis. In the present study, the degree of lung-accumulated TCR AV2S3+ T cells was related to clinical data in 51 HLA-DRB1*0301/DRB3*0101-positive Scandinavian patients with pulmonary sarcoidosis. Significantly more AV2S3+ lung T cells (median: 30.0% of CD4+ cells in bronchoalveolar lavage fluid [BALF]) were found accumulated in patients with a short ( < 2 yr) than with a long ( > 2 yr) (median: 18.6%) disease duration (p = 0.003). A strong positive association was also found between lung-restricted AV2S3+ T cells and both the CD4+-to-CD8+ cell ratio (p = 7 × 10− 6) in BALF and with an acute disease onset (p = 0.018). Negative associations were found between both the interval from disease onset to bronchoalveolar lavage (p = 0.0001) and the age of the patient (p = 0.002). Our findings strongly link lung-accumulated AV2S3+ T cells to the acute inflammatory response in sarcoidosis. Moreover, the association of these cells with a good prognosis indicates that AV2S3+ T cells may have a protective role against a presumed sarcoidosis antigen. Grunewald J, Berlin M, Olerup O, Eklund A. Lung T-helper cells expressing T-cell receptor AV2S3 associate with clinical features of pulmonary sarcoidosis.