tbuckley/cabot-search huggingface dataset:
Genotype-phenotype correlation of xeroderma pigmentosum in a Chinese Han population
Authors: Z. Sun, J. Zhang, Y. Guo, C. Ni, J. Liang, R. Cheng, M. Li, Z. Yao
Journal: British Journal of Dermatology (2014)

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to sunlight, freckle-like pigmentation and a greatly increased incidence of skin cancers. Genetic mutation detection and genotype-phenotype analysis of XP are rarely reported in the Chinese Han population.To investigate the mutational spectrum of XP in a Chinese Han population, to discover any genotype-phenotype correlation and, consequently, to propose a simple and effective tool for the molecular diagnosis of XP.This study was carried out on 12 unrelated Chinese families that included 13 patients with clinically suspected XP. Genomic DNA was extracted from peripheral blood samples. Mutation screening was performed by direct sequencing of exons and flanking intron-exon boundaries for the entire coding region of eight XP genes.In 12 patients, direct sequencing of the whole coding region of eight XP genes revealed pathogenic mutations, including seven compound heterozygous mutations, three homozygous mutations and a Japanese founder mutation. Thirteen mutations have not been previously identified. This cohort was composed of four patients with XP-C (XPC), two with XP-G (ERCC5), three with XP-A (XPA) and three with XP-V (POLH).This study identified 13 novel mutations and extended the mutation spectrum of XP in the Chinese Han population. In this cohort, we found that patients with XP-G have no neurological symptoms, and patients with XP-A and XP-V have a high incidence of malignancy. Furthermore, lack of stringent protection against sunlight, late diagnosis and long duration of disease play an important role.
Small-Community–Based Surveys
Authors: Ralph R Frerichs, Magda A Shaheen
Journal: Annual Review of Public Health (2001)

Rapid, small surveys are routinely done in much of the developing world but are less common in the United States. We present as an example a rapid survey of immunization status and other factors in a predominantly Hispanic region in Los Angeles. The survey united county employees, students, and community volunteers, first to enumerate the eligible population and then to conduct in-person interviews. Sampling was done in two stages in a downtown region of Los Angeles. Over the course of two weekends and during clean-up the following week, volunteers and others enumerated 718 eligible children in 30 clusters (i.e. groups of blocks). At the second stage, also in two weekends with midweek clean-up, we selected by simple random sample 10 children per cluster. The parents or legal guardians of 270 children were interviewed about vaccination issues, including home presence of an immunization card. Nearly one fourth of the respondents did not have a home telephone number and thus would have been underrepresented in a telephone survey. Information from such rapid surveys is important for local program planning and evaluation.
The epidemiology of injuries in English youth community rugby union
Authors: Christine M Haseler, Michael R Carmont, Michael England
Journal: British Journal of Sports Medicine (2010)

Recent studies report the incidence and epidemiology of injury in professional rugby union; however, there is limited research in amateur and youth rugby. Injuries in youth rugby may have consequences for sports participation and physical development. The authors performed a prospective cohort study of injuries during youth community rugby.An injury surveillance programme was established for the 2008-2009 season (9 months, 1636 player-hours) of an English community rugby club. The study included 210 players, all males, in Under 9 to Under 17 (U9-U17) age groups. These were categorised into mini, junior, pubertal and school participation age groupings. Injuries were defined according to the International Rugby Board consensus statements.There were 39 injuries reported (overall injury rate 24/1000 player-hours). Injury rates ranged from 0 to 49.3/1000 player-hours. More injuries occurred in junior (34.2/1000 player-hours) than in minis (11.9/1000 player-hours) (p<0.025). Higher numbers of moderate (20.6/1000 player-hours, p<0.005) and severe (9.5/1000 player-hours, p<0.05) injuries occurred in the U16-U17 age groups compared with younger age groups (U9-U10) where only minor injuries were reported. Most injuries occurred in the tackle (59%). The knee (4.9/1000 player-hours), shoulder (4.9/1000 player-hours) and head (4.3/1000 player-hours) were the most commonly affected areas. Concussion (1.8/1000 player-hours) affected half of the head injuries.Injuries in youth rugby occur infrequently and are lower than in adult series. The risk of injury and severity of injury increases with age. This study highlights the need for further research into injury risk factors around puberty and the need for first aid provision.
A Nonprofessional Discusses Her Role in Mental Health
Authors: LAURA HINES
Journal: American Journal of Psychiatry (1970)

The author describes her period of training as a mental health assistant and her current work with individual patients, home visiting, child and parent groups, and the homemaking service she is developing at the Temple University Community Mental Health Center. She concludes that although mental health centers cannot solve all of society's problems, they must expand their services to meet the needs of the total community, as well as its patients, if they are to be truly effective in the promotion of mental health.
Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases
Authors: F. Saad, J.E. Brown, C. Van Poznak, T. Ibrahim, S.M. Stemmer, A.T. Stopeck, I.J. Diel, S. Takahashi, N. Shore, D.H. Henry, C.H. Barrios, T. Facon, F. Senecal, K. Fizazi, L. Zhou, A. Daniels, P. Carrière, R. Dansey
Journal: Annals of Oncology (2011)
The Two-Period Crossover Design in Medical Research
Authors: John R. Woods
Journal: Annals of Internal Medicine (1989)

The crossover design has enjoyed popularity with many clinical researchers, but has been criticized by biostatisticians. The central problem is the inability to derive an unbiased estimate of the treatment effect when differences occur because of the different sequences in which treatments are applied. This problem can be traced to a deficiency of the logic of the crossover arrangement itself. Factors that can invalidate the findings of a crossover trial include nonuniform pharmacologic and psychologic carry-over effects, failure to return patients to their baseline state before the crossover, nonuniform changes in the patients over time, and the use of time-dependent response measures. When these problems can be anticipated, a parallel-groups design should be used instead of a crossover trial.
Multilocus Analysis of Nucleotide Variation and Speciation in Oryza officinalis and Its Close Relatives
Authors: L.-B. Zhang, S. Ge
Journal: Molecular Biology and Evolution (2006)

Nucleotide variation in 10 unlinked nuclear genes was investigated in species-wide samples of Oryza officinalis and its close relatives (Oryza eichingeri and Oryza rhizomatis). Average estimates of nucleotide diversity were the lowest in O. rhizomatis (θsil = 0.0038) and the highest in O. eichingeri (θsil = 0.0057) that is disjunctly distributed in Africa and Sri Lanka. These wild rice species appeared to harbor relatively low levels of nucleotide variation relative to other plant species because the diversity level of O. eichingeri is only 23–46% of those in Zea species and 35% of that in Arabidopsis thaliana. The lower nucleotide diversity in these Oryza species could be best explained by their smaller historic effective population sizes. The speciation model test indicated that O. officinalis and its close relatives might have undergone a process of population contraction since divergence from their ancestor. Incongruent topologies among 10 gene trees, particularly regarding the positions of O. eichingeri and O. rhizomatis accessions might be attributed to lineage sorting arising from ancient polymorphism and hybridization/introgression between the Sri Lankan O. eichingeri and O. rhizomatis. However, the null hypothesis of the isolation model was not rejected for any contrast between taxa, which suggested that no subsequent gene flow shaped the present patterns of nucleotide variation since their divergence and that introgression was not pervasive in this group of species. Our molecular dating provides an approximate divergence time of 0.37 Myr between 2 geographical races of O. eichingeri, much more recent compared with the times of other speciation events in this group (0.63–0.68 Myr). A long-distance dispersal from West Africa to Sri Lanka was more likely to play a role in the disjunct distribution of O. eichingeri.
Bronchial hyperresponsiveness to methacholine in patients with primary Sjogren's syndrome.
Authors: B Gudbjornsson, H Hedenstrom, G Stalenheim, R Hallgren
Journal: Annals of the Rheumatic Diseases (1991)

The prevalence of bronchial hyperresponsiveness (BHR) to methacholine inhalation in a consecutive series of 21 patients with primary Sjögren9s syndrome was studied prospectively. Slight to severe BHR was seen in 12/20 (60%) of the patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing, or intermittent breathlessness. Bronchial hyperresponsiveness was more common in patients with extraglandular symptoms (10/14, 71%) than in those with only glandular symptoms (29%). Spirometrically 29% (6/21) of the patients had 9small airways9 disease9, and all those had BHR. Of 6/21 (29%) who had diffuse interstitial lung disease, two had BHR. Three of the four patients with obstructive lung function were challenged with methacholine and two of them had BHR. Only two patients with BHR had normal spirometry findings. The data showed that respiratory disease--mostly mild or moderate but even severe bronchial hyperresponsiveness--is commonly seen in patients with primary Sjögren9s syndrome.
MicroRNA miR-29 Modulates Expression of Immunoinhibitory Molecule B7-H3: Potential Implications for Immune Based Therapy of Human Solid Tumors
Authors: Hong Xu, Irene Y. Cheung, Hong-Fen Guo, Nai-Kong V. Cheung
Journal: Cancer Research (2009)

Abstract B7-H3, a surface immunomodulatory glycoprotein, inhibits natural killer cells and T cells. The monoclonal antibody (mAb) 8H9 is specific for 4Ig-B7-H3, the long and principal form of B7-H3. Early results from radioimmunotherapy using 8H9 have shown promise in patients with metastatic solid tumors to the central nervous system. Whereas B7-H3 transcript was ubiquitously expressed in a wide spectrum of human solid tumors as well as human normal tissues, B7-H3 protein was preferentially expressed only in tumor tissues. By quantitative reverse transcription-PCR, all three isoforms of microRNA miR-29 (a, b, and c) were highly expressed in normal tissues. However, they were down-regulated in a broad spectrum of solid tumors, including neuroblastoma, sarcomas, brain tumors, and tumor cell lines. B7-H3 protein expression was inversely correlated with miR-29 levels in both cell lines and tumor tissues tested. Using luciferase reporter assay, miR-29a was shown to directly target B7-H3 3′ untranslated region, and knock-in and knockdown of miR-29a led to down-regulation and up-regulation, respectively, of B7-H3 protein expression. The ability of miR-29 to control B7-H3 protein expression has implications in immune escape by solid tumors. Differential modulation of this key immunoinhibitory molecule in tumor versus normal tissues may advance both cell-mediated immunotherapy and antibody-based targeted strategies using the B7-H3–specific mAb 8H9. [Cancer Res 2009;69(15):6275–81]
Research pointers: Unexplained differences in sex ratios at birth in Europe and North America
Authors: V. Grech
Journal: BMJ (2002)

sent memorandums pointing out any errors and omissions every six months.In 1996-7, the failure rate for bodies from all sources was 10.2% (table).This figure fell in the study period to 2.9% in 1999-2000.The bodies received from the hospital accounted for most cases of failed documentation.When the failure rate was calculated for hospital deaths alone, it fell from 11.9% in 1996-7 to 4.0% in 1999-2000.
Cannabis and sport
Authors: M Saugy, L Avois, C Saudan, N Robinson, C Giroud, P Mangin, J Dvorak
Journal: British Journal of Sports Medicine (2006)

Background and objectives: Cannabis is on the list of prohibited substances in the practice of sport, although its performance enhancing effect has not yet been proved. Its popularity among the younger generations as a social drug puts cannabis at the top of the list of compounds detected by the anti-doping laboratories accredited by the World Anti-Doping Agency worldwide. The management of the results of urine analysis is quite difficult for the medical and disciplinary committees not only because of the social use of the substance, but also because of the interpretation of the analytical data from urine samples. This paper gives an overview of what is presently known about cannabis in relation with the practice of sport. Methods: Review of literature on the cannabis and exercise, its effect in the body, and the problems with interpretation of results when it is detected in urine. Results: The paper outlines the major effects of cannabis in the context of its social use and its use for sport activities. The difficulties in the interpretation of urine sample analysis results because of the protracted excretion time of the main metabolite, long after the intake, are described. Conclusions: There is an urgent need for sport authorities to take measures necessary to avoid players misusing cannabis.
In Vivo RNA Interference Screens Identify Regulators of Antiviral CD4+ and CD8+ T Cell Differentiation
Authors: Runqiang Chen, Simon Bélanger, Megan A. Frederick, Bin Li, Robert J. Johnston, Nengming Xiao, Yun-Cai Liu, Sonia Sharma, Bjoern Peters, Anjana Rao, Shane Crotty, Matthew E. Pipkin
Journal: Immunity (2014)
l-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophages<i>in vitro</i>
Authors: R.B.R. Muijsers, N.H.T. ten Hacken, I. Van Ark, G. Folkerts, F.P. Nijkamp, D.S. Postma
Journal: European Respiratory Journal (2001)

Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO) in vitro despite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesis in vitro is due to limited availability of the NOS substrate l-;arginine, and putative NOS inhibiting factors present in foetal serum preparations, both alveolar macrophages (AM) and monocyte derived macrophages (MDM) were incubated in various circumstances. Nitrite production measured using stimulated AM was typically &lt;5 pmol·min −1 ·10 −6 cells. A range of stimuli were tested, but without result. Furthermore, incubation of MDMs with normal human serum or purified bovine serum albumin instead of foetal calf serum failed to enhance NO production. Moreover, neither the use of arginase inhibitors nor the addition of surplus l-;arginine resulted in an increased NO synthesis. Interestingly, addition of the NOS intermediate N ω-;hydroxy-;l-;arginine (100 µM) to AM led to nitrite release, which was unaffected by the NOS inhibitor amino guanidine showing that this effect is NOS independent. It is concluded that the limited nitric oxide production of human macrophages in vitro can neither be explained by limited availability of l-;arginine, nor by nitric oxide synthase inhibiting substances in foetal serum. Furthermore, it is shown that nitrite release from N ω-;hydroxy-;l-;arginine by alveolar macrophages is nitric oxide synthase independent.
Pilot study of phenytoin in rheumatoid arthritis.
Authors: D G Macfarlane, B Clark, G S Panayi
Journal: Annals of the Rheumatic Diseases (1986)

The anticonvulsant drug phenytoin has several interesting immunological properties which could theoretically be of benefit in the treatment of rheumatoid arthritis. For this reason a pilot study has been carried out on 11 patients with active classical or definite disease. Seven patients completed a 20 week course of treatment and showed continuous improvement at 12 and 20 weeks and some deterioration eight weeks after the drug was stopped. Laboratory and clinical measurements of disease activity responded favourably during the treatment period, suggesting that phenytoin may have second line activity.
NF-κB Activity Regulates Mesenchymal Stem Cell Accumulation at Tumor Sites
Authors: Ryosuke Uchibori, Tomonori Tsukahara, Hiroyuki Mizuguchi, Yasushi Saga, Masashi Urabe, Hiroaki Mizukami, Akihiro Kume, Keiya Ozawa
Journal: Cancer Research (2012)

Abstract Mesenchymal stem cells (MSC) accumulate at tumor sites when injected into tumor-bearing mice, perhaps offering cellular vectors for cancer-targeted gene therapy. However, the molecular mechanisms involved in MSC targeting the tumors are presently little understood. We focused on MSC–endothelial cell (EC) adhesion following TNF-α stimulation in an attempt to elucidate these mechanisms. Interestingly, stimulation of MSCs with TNF-α enhanced the adhesion of MSCs to endothelial cells in vitro. This adhesion was partially inhibited by blocking antibodies against vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4). It is well known that TNF-α induces VCAM-1 expression via the NF-κB signaling pathway. Parthenolide has an anti-inflammatory activity and suppressed NF-κB activity by inhibition of IκBα phosphorylation after TNF-α stimulation and strongly inhibited TNF-α–induced VCAM-1 expression on MSCs. In vivo imaging using luciferase-expressing MSCs revealed that the bioluminescent signal gradually increased at tumor sites in mice injected with untreated MSCs. In contrast, we observed very weak signals at tumor sites in mice injected with parthenolide-treated MSCs. Our results suggest that NF-κB activity regulates MSC accumulation at tumors, by inducing VCAM-1 and thereby its interaction with tumor vessel endothelial cells. These findings have implications for the ongoing development of efficient MSC-based gene therapies for cancer treatment. Cancer Res; 73(1); 364–72. ©2012 AACR.
Hyperlipidemia-Triggered Neutrophilia Promotes Early Atherosclerosis
Authors: Maik Drechsler, Remco T.A. Megens, Marc van Zandvoort, Christian Weber, Oliver Soehnlein
Journal: Circulation (2010)

Background— Inflammation and activation of immune cells are key mechanisms in the development of atherosclerosis. Previous data indicate important roles for monocytes and T lymphocytes in lesion formation, whereas the contribution of neutrophils remains to be firmly established. Here, we investigate the effect of hypercholesterolemia on peripheral neutrophil counts, neutrophil recruitment to atherosclerotic lesions, and the importance of neutrophils in atherosclerotic lesion formation in Apoe −/− mice. Methods and Results— Hypercholesterolemia induces neutrophilia, which was attributable to enhanced granulopoiesis and enhanced mobilization from the bone marrow. The degree of hypercholesterolemia-induced neutrophilia was positively correlated with the extent of early atherosclerotic lesion formation. In turn, neutropenic mice display reduced plaque sizes at early but not late stages of atherosclerotic lesion formation. Flow cytometry of enzymatically digested aortas further shows altered cellular plaque composition in neutropenic mice with reduced numbers of inflammatory monocytes and macrophages. Aortic neutrophil infiltration peaks 4 weeks after the start of a high-fat diet and decreases afterward. The recruitment of neutrophils to large arteries was found to depend on CCR1, CCR2, CCR5, and CXCR2, which contrasts to peripheral venous recruitment, which requires CCR2 and CXCR2 only. The involvement of CCR1 and CCR5 corresponded to the endothelial deposition of the platelet-derived chemokine CCL5 in arteries but not in veins. Conclusions— Our data provide evidence that hypercholesterolemia-induced neutrophilia is multifactorial and that neutrophils infiltrate arteries primarily during early stages of atherosclerosis. Collectively, these data suggest an important role of neutrophils in the initiation of atherosclerosis.
Metachronous occurrence of collagenous colitis and ulcerative colitis.
Authors: F M Giardiello, F W Jackson, A J Lazenby
Journal: Gut (1991)

Collagenous colitis and ulcerative colitis are distinct disorders. A 67 year old woman with clinical and histological evidence of collagenous colitis had an abrupt symptomatic exacerbation while taking anti-inflammatory treatment with sulphasalazine and prednisone. Repeat colorectal endoscopy showed active mucosal inflammation and colonic biopsy specimens were consistent with active ulcerative colitis. After bowel rest, total parenteral nutrition, intensification of the anti-inflammatory regimen, and withdrawal of non-steroidal anti-inflammatory drugs (which she had taken continuously for osteoarthritis) diarrhoea abated. Colorectal biopsy specimens obtained when the patient9s symptoms had improved showed inactive ulcerative colitis with no evidence of collagenous colitis. This may be the first case to be reported of the metachronous association of collagenous and ulcerative colitis.
The LINC complex is essential for hearing
Authors: Henning F. Horn, Zippora Brownstein, Danielle R. Lenz, Shaked Shivatzki, Amiel A. Dror, Orit Dagan-Rosenfeld, Lilach M. Friedman, Kyle J. Roux, Serguei Kozlov, Kuan-Teh Jeang, Moshe Frydman, Brian Burke, Colin L. Stewart, Karen B. Avraham
Journal: Journal of Clinical Investigation (2013)

Hereditary hearing loss is the most common sensory deficit. We determined that progressive high-frequency hearing loss in 2 families of Iraqi Jewish ancestry was due to homozygosity for the protein truncating mutation SYNE4 c.228delAT. SYNE4, a gene not previously associated with hearing loss, encodes nesprin-4 (NESP4), an outer nuclear membrane (ONM) protein expressed in the hair cells of the inner ear. The truncated NESP4 encoded by the families' mutation did not localize to the ONM. NESP4 and SUN domain–containing protein 1 (SUN1), which localizes to the inner nuclear membrane (INM), are part of the linker of nucleoskeleton and cytoskeleton (LINC) complex in the nuclear envelope. Mice lacking either Nesp4 or Sun1 were evaluated for hair cell defects and hearing loss. In both Nesp4–/– and Sun1–/– mice, OHCs formed normally, but degenerated as hearing matured, leading to progressive hearing loss. The nuclei of OHCs from mutant mice failed to maintain their basal localization, potentially affecting cell motility and hence the response to sound. These results demonstrate that the LINC complex is essential for viability and normal morphology of OHCs and suggest that the position of the nucleus in sensory epithelial cells is critical for maintenance of normal hearing.