tbuckley/cabot-search huggingface dataset:
THE GENETIC DEFECT IN ATAXIA-TELANGIECTASIA
Authors: Martin F. Lavin, Yosef Shiloh
Journal: Annual Review of Immunology (1997)

▪ Abstract The autosomal recessive human disorder ataxia-telangiectasia (A-T) was first described as a separate disease entity 40 years ago. It is a multisystem disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency, with defects in both cellular and humoral immunity. The pleiotropic nature of the clinical and cellular phenotype suggests that the gene product involved is important in maintaining stability of the genome but also plays a more general role in signal transduction. The chromosomal instability and radiosensitivity so characteristic of this disease appear to be related to defective activation of cell cycle checkpoints. Greater insight into the nature of the defect in A-T has been provided by the recent identification, by positional cloning, of the responsible gene, ATM. The ATM gene is related to a family of genes involved in cellular responses to DNA damage and/or cell cycle control. These genes encode large proteins containing a phosphatidylinositol 3-kinase domain, some of which have protein kinase activity. The mutations causing A-T completely inactivate or eliminate the ATM protein. This protein has been detected and localized to different subcellular compartments.
Comparison of Effect of Pioglitazone With Metformin or Sulfonylurea (Monotherapy and Combination Therapy) on Postload Glycemia and Composite Insulin Sensitivity Index During an Oral Glucose Tolerance Test in Patients With Type 2 Diabetes
Authors: Antonio Ceriello, Don Johns, Mario Widel, David J. Eckland, Kathryn J. Gilmore, Meng H. Tan
Journal: Diabetes Care (2005)

OBJECTIVE— Pioglitazone, metformin, and gliclazide lower HbA1c and fasting plasma glucose in patients with type 2 diabetes. We compared the effects of these three drugs, used as monotherapy and in combination, on postload glycemia and composite insulin sensitivity index (CISI) in these patients. RESEARCH DESIGN AND METHODS— Postload glycemia and CISI were analyzed for 940 patients who had oral glucose tolerance tests (OGTTs) in four multicenter, randomized, double-blind, double-dummy, parallel group clinical trials (pioglitazone versus metformin, pioglitazone versus gliclazide, pioglitazone plus sulfonylurea versus metformin plus sulfonylurea, and pioglitazone plus metformin versus gliclazide plus metformin). Plasma glucose and insulin were determined during the 3-h OGTT performed at baseline and after 1 year of therapy. Incremental area under the curve for glucose was the surrogate for postload glycemia. CISI was calculated using the formula {10,000/√ of [(fasting glucose × fasting insulin) × (mean glucose × mean insulin)]} during the OGTT. RESULTS— In monotherapy, pioglitazone reduced postload glycemia and enhanced CISI more than metformin and gliclazide. In combination therapy, pioglitazone plus sulfonylurea reduced postload glycemia and increased CISI more than metformin plus sulfonylurea. Pioglitazone plus metformin also decreased postload glycemia and increased CISI more than gliclazide plus metformin. CONCLUSIONS— Pioglitazone improves postload glycemia and CISI more than metformin or gliclazide when used as monotherapy or in combination therapy in patients with type 2 diabetes.
Complications following bronchoscopic lung volume reduction (BLVR) - A small case series
Authors: Jurgen Herre, Tom Dymond, Pasupathy Sivasothy, Ravi Mahadeva
Journal: European Respiratory Journal (2013)

Introduction  BLVR with endobronchial valves (Pulmonx) is an emerging alternative to failing medical therapy for severe disabling emphysema and carries a much lower mortality than Surgical LVR. Common complications include exacerbations, bronchospasm, valve occlusion and dislodgement and pneumothorax, the latter usually due to ipsilateral non-target lobe re-expansion.  Aims and objectives  We report our experience of 5 patients who suffered significant complications following endobronchial valve (EBV) treatment and describe their subsequent management.  Methods  Retrospective analysis of 10 cases from 2009 – 2012 describing complication and remedial action, effects of valve removal and morbidity post removal.  Results  Over the first 3 months post procedure, BLVR patients experienced cumulatively 8 significant complications: 3 pneumothoraces within 1 month requiring underwater drain, additionally 1 required blood patch and valve removal, 1 intubation and valve removal. Others; 1 valve removed for post-obstructive pneumonia, 1 valve repositioning following cough dislodgement, 1 small pleural effusion and 2 mild COPD exacerbations. All survived, 7/10 still have valves in situ and PFT returned to baseline in the patients who had valves removed.  Conclusions:  Bronchoscopic EBV has predictable complications that, in light of the severity of the underlying emphysema, have the potential to be serious. Nevertheless, the potential benefits, which outstrip pharmacological therapy, make it important to counsel patients of these potential risks and ensure careful patient selection and follow-up by specialists. Reassuringly, all patients in our group recovered back to baseline following complications.
Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach
Authors: Silvio E. Inzucchi, Richard M. Bergenstal, John B. Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L. Peters, Apostolos Tsapas, Richard Wender, David R. Matthews
Journal: Diabetes Care (2012)

Table 1dProperties of currently available glucose-lowering agents that may guide treatment choice in individual patients with type 2 diabetes mellitus Class Compound(s) Cellular mechanism
Complex chromosomal rearrangements: origin and meiotic behavior
Authors: F. Pellestor, T. Anahory, G. Lefort, J. Puechberty, T. Liehr, B. Hedon, P. Sarda
Journal: Human Reproduction Update (2011)

BACKGROUNDComplex chromosomal rearrangements (CCRs) describe structural rearrangements, essentially translocations, involving at least three breakpoints on two or more chromosomes. Although they are rare in humans, their clinical identification is important since CCR carriers can display various phenotypes which include phenotypically normal subjects, infertile males and patients with mental retardation and/or congenital abnormalities. The rearrangement can be de novo or familial. The use of fluorescent in situ hybridization assays and molecular techniques for the characterization of CCRs have indicated that the rearrangements could be more complex than initially assumed. Accumulating data have revealed that the mechanisms underlying the genesis of CCRs remain elusive.
A peculiar squamous dysplastic lesion presenting as a ground-glass opacity: a case report
Authors: Jun Atsumi, Kimihiro Shimizu, Tetsuhiro Nakano, Seiichi Kakegawa, Takaaki Sano, Mio Katano, Kenzo Hiroshima, Izumi Takeyoshi
Journal: European Respiratory Journal (2013)

A peculiar squamous dysplastic lesion presenting as a ground-glass opacity: a case reportTo the Editor:We report a patient with a pulmonary squamous dysplastic lesion that appears as pure ground-glass opacity (GGO) on computed tomography (CT).An ill-defined, 15-mm nodular lesion in the left lower lung was noted on a radiograph during an annual health check-up of a 61-year-old female who had never smoked.A physical examination and laboratory study results were unremarkable.Chest CT demonstrated a well-demarcated pure GGO nodule in the inferior lobe of the left lung.The nodule, measuring 15613 mm, was located in the anteromedial basal segment (S8) (fig.1a).A positron emission tomography scan showed no accumulation of radioactivity in the lesion.The patient underwent S8 segmentectomy of the left lung with lymph node sampling.
E2F1 Responds to Ultraviolet Radiation by Directly Stimulating DNA Repair and Suppressing Carcinogenesis
Authors: Anup Kumar Biswas, David L. Mitchell, David G. Johnson
Journal: Cancer Research (2014)

In response to DNA damage, the E2F1 transcription factor is phosphorylated at serine 31 (serine 29 in mouse) by the ATM or ATR kinases, which promotes E2F1 protein stabilization. Phosphorylation of E2F1 also leads to the recruitment of E2F1 to sites of DNA damage, where it functions to enhance DNA repair. To study the role of this E2F1 phosphorylation event in vivo, a knock-in mouse model was generated, in which serine 29 was mutated to alanine. The S29A mutation impairs E2F1 stabilization in response to ultraviolet (UV) radiation and doxorubicin treatment, but has little effect on the expression of E2F target genes. The apoptotic and proliferative responses to acute UV radiation exposure are also similar between wild-type and E2f1(S29A/) (S29A) mice. As expected, the S29A mutation prevents E2F1 association with damaged DNA and reduces DNA repair efficiency. Moreover, E2f1(S29A/) (S29A) mice display increased sensitivity to UV-induced skin carcinogenesis. This knock-in mouse model thus links the ability of E2F1 to directly promote DNA repair with the suppression of tumor development.
Is the lung important as a privileged site for the human immunodeficiency virus?
Authors: J R Clarke, D M Mitchell, R J Coker, D Israel-Biet
Journal: Thorax (1998)

18 Imance of infection of alveolar leucocytes by HIV-1 remains controversial. portantly, not all the virus was cleared and low levels of virus growth could still be detected within macrophages. Molecular techniques have shown that HIV-1 is present in the lung of some individuals early in HIV disease. 3 It is Of note, the few molecular studies that have compared HIV-1 genotypes in peripheral blood and lung have conknown that, in patients with AIDS, most have HIV-1 detectable in leucocytes from bronchoalveolar lavage centrated on comparisons between viruses in blood monocytes and alveolar macrophages. 19 One study reported (BAL). 45 HIV isolated from BAL fluid can usually be grown in cell cultures and is not defective. 67 This means genetic diVerences in HIV-1 virus detected in blood leucocytes compared with lung cells. 20 This finding underlines that the virus is in the lung in a form allowing replication under appropriate conditions. Analysis of the cells in BAL thepotentialimportanceofthelunginHIV-1induceddisease in view of the strong evidence that the virus is evolving fluid has shown that CD4+ alveolar lymphocytes are the predominant HIV-1 infected cells in patients with AIDS. 78 separatelyandinisolationinthelungcomparedwiththeother body compartments. Mathematical modelling has estimated Alveolar macrophages have also been shown to be an important reservoir for HIV. 7‐10 As HIV-1 is found pre- that it may take completely inhibitory treatment with potent antiretroviral therapy for over three years to eliminate HIV dominantly in alveolar lymphocytes, it has been suggested that virus is transported to the lung within infected lympho- from bodily compartments such as the lung. 21
Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy.
Authors: Melvin H. Freedman, Mary Ann Bonilla, Carol Fier, Audrey Anna Bolyard, Debra Scarlata, Laurence A. Boxer, Sherri Brown, Bonnie Cham, George Kannourakis, Sally E. Kinsey, Pier Georgio Mori, Tammy Cottle, Karl Welte, David C. Dale
Journal: Blood (2000)
THE EFFECT OF VARYING QUANTITIES OF INORGANIC IODIDE (CARRIER) ON THE URINARY EXCRETION AND THYROIDAL ACCUMULATION OF RADIOIODINE IN EXOPHTHALMIC GOITER 1
Authors: Donald S. Childs, F. Raymond Keating, J. Edward Rall, Marvin M. D. Williams, Marschelle H. Power
Journal: Journal of Clinical Investigation (1950)
Proliferation Kinetics Associated with T Cell Receptor-β Chain Selection of Fetal Murine Thymocytes
Authors: Ingrid Falk, Judit Biro, Hubertus Kohler, Klaus Eichmann
Journal: The Journal of Experimental Medicine (1996)

After productive rearrangement of a TCR beta chain gene, CD4-8- double negative (DN) thymocytes express TCR beta polypeptide chains on the cell surface together with pre-T alpha and the CD3 complex forming the pre-TCR. Signals transmitted through the pre-TCR select TCR beta + DN thymocytes for further maturation to the CD4+8+ double positive stage, whereas DN cells that fail to generate a productive TCR beta gene rearrangement do not continue in development. This process is termed TCR beta chain selection. Although it is likely that differences between proliferation dynamics of TCR beta + and TCR beta-cells may play a role, the exact mechanisms of TCR beta chain selection have not been elucidated. We therefore studied the proliferation dynamics of TCR beta + and TCR beta-thymocytes during fetal development, i.e., when TCR beta chain selection takes place for the first time. We analyzed in situ accumulation of TCR beta + thymocytes by confocal microscopy, and determined cell cycle and division parameters of TCR beta + and TCR beta-populations by flow cytometry. About 600 TCR beta + cells/thymic lobe are generated by independent induction events between days of gestation (dg) 13.5, and 15.5. As of dg 14.5, most TCR beta + cells have entered S/G2 phase of cell cycle, followed by seven to eight rapid cell divisions in fetal thymic organ culture, suggesting a corresponding burst of nine cell divisions within 4 d in vivo. By dg 18.5, the division rate of TCR beta + cells has slowed down to less than 1/d. About three quarters of TCR beta-cells divide at a slow rate of 1/d on dg 14.5, the proportion of nondividing cells increasing to 50% within the following four d. From dg 16.5 onwards, TCR beta-cells, but not TCR beta + cells, contain a significant proportion of apoptotic cells. The results suggest that failure to become selected results in shutdown of proliferation and eventual programmed cell death of fetal TCR beta-cells. Positive selection of fetal TCR beta + cells is achieved by an increased rate of cell divisions lasting for approximately 4 d.
MouseCyc: a curated biochemical pathways database for the laboratory mouse
Authors: Alexei V Evsikov, Mary E Dolan, Michael P Genrich, Emily Patek, Carol J Bult
Journal: Genome biology (2009)

Linking biochemical genetic data to the reference genome for the laboratory mouse is important for comparative physiology and for developing mouse models of human biology and disease. We describe here a new database of curated metabolic pathways for the laboratory mouse called MouseCyc http://mousecyc.jax.org . MouseCyc has been integrated with genetic and genomic data for the laboratory mouse available from the Mouse Genome Informatics database and with pathway data from other organisms, including human.
Tax-Exempt Hospitals and Community Benefit: New Directions in Policy and Practice
Authors: Daniel B. Rubin, Simone R. Singh, Gary J. Young
Journal: Annual Review of Public Health (2015)

The current community benefit standard for nonprofit hospital tax exemption has been the subject of mounting criticism. Many different constituencies have advanced the view that in its present form it fails to ensure that nonprofit hospitals provide adequate benefits to their communities in exchange for their tax exemption. In contrast, hospitals have often expressed the concern that the community benefit standard in its current form is vague and therefore difficult to comply with. Various suggestions have been made regarding how the existing community benefit standard could be improved or even replaced. In this article, we first discuss the historical and legal development of the community benefit standard. We then present the key controversies that have emerged in recent years and the policy responses attempted thus far. Finally, we evaluate possible future policy directions, which reform efforts could follow.
Modifiable Predictors of Dementia in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis
Authors: Claudia Cooper, Andrew Sommerlad, Constantine G. Lyketsos, Gill Livingston
Journal: American Journal of Psychiatry (2015)

Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition.The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies.There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies.Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.
Challenge of culture, conscience, and contract to general practitioners' care of their own health: qualitative study
Authors: W. T Thompson, M. E Cupples, C. H Sibbett, D. I Skan, T. Bradley
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To explore general practitioners9 perceptions of the effects of their profession and training on their attitudes to illness in themselves and colleagues. <b>Design:</b> Qualitative study using focus groups and indepth interviews. <b>Setting:</b> Primary care in Northern Ireland. <b>Participants:</b> 27 general practitioners, including six recently appointed principals and six who also practised occupational medicine part time. <b>Main outcome measures:</b> Participants9 views about their own and colleagues9 health. <b>Results:</b> Participants were concerned about the current level of illness within the profession. They described their need to portray a healthy image to both patients and colleagues. This hindered acknowledgement of personal illness and engaging in health screening. Embarrassment in adopting the role of a patient and concerns about confidentiality also influenced their reactions to personal illness. Doctors9 attitudes can impede their access to appropriate health care for themselves, their families, and their colleagues. A sense of conscience towards patients and colleagues and the working arrangements of the practice were cited as reasons for working through illness and expecting colleagues to do likewise. <b>Conclusions:</b> General practitioners perceive that their professional position and training adversely influence their attitudes to illness in themselves and their colleagues. Organisational changes within general practice, including revalidation, must take account of barriers experienced by general practitioners in accessing health care. Medical education and culture should strive to promote appropriate self care among doctors. <h3>What is already known on this topic</h3> High levels of stress, psychological distress, and suicide have been reported among doctors Doctors are reluctant to seek help in the normal way when they become stressed or ill <h3>What this study adds</h3> The perceived need to portray an unrealistically healthy image is stressful and a barrier to appropriate self care The emotional response to personal illness can produce an oscillation between panic and denial The working arrangements of general practitioners reinforce a culture in which their own and colleagues9 distress is overlooked
Case of Anthrax in which the Infection Arose from a Hitherto Undescribed Source
Authors: J. C. Wilson
Journal: BMJ (1901)

A CASE OF ANTHRAX.[DBC.2r, 190t, Very careful precautions were taken in examining microscopically and bacteriologically the pus from every source above described, as well as the sputum In all cases the apparently same organism the pneumo- coccus of Fraenkel was found-in pure culture.The man made a good recovery and is well to this day.I have no doubt that in this case prompt surgical interference saved his life.CASE II.-T.A., aged 52, was admitted on January 5th, 1900, with severe ipain in right side of chest and profuse dark expectoration.He had also pain and swelling of right ankle and swelling with great tenderness over ,the right sternoclavicular joint.Next day he was found to have definite pneumonia at the right apex, with effusion at the base.
Prognosis After Ipsilateral Breast Tumor Recurrence and Locoregional Recurrences in Five National Surgical Adjuvant Breast and Bowel Project Node-Positive Adjuvant Breast Cancer Trials
Authors: Irene L. Wapnir, Stewart J. Anderson, Eleftherios P. Mamounas, Charles E. Geyer, Jong-Hyeon Jeong, Elizabeth Tan-Chiu, Bernard Fisher, Norman Wolmark
Journal: Journal of Clinical Oncology (2006)

Locoregional failure after breast-conserving surgery is associated with increased risk of distant disease and death. The magnitude of this risk in patients receiving chemotherapy has not been adequately characterized.Our study population included 2,669 women randomly assigned onto five National Surgical Adjuvant Breast and Bowel Project node-positive protocols (B-15, B-16, B-18, B-22, and B-25), who were treated with lumpectomy, whole-breast irradiation, and adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated. Kaplan-Meier curves were used to estimate distant-disease-free survival (DDFS) and overall survival (OS) after IBTR or oLRR. Cox models were used to model survival using clinical and pathologic factors jointly with IBTR or oLRR as time-varying predictors.Four hundred twenty-four patients (15.9%) experienced locoregional failure; 259 (9.7%) experienced IBTR, and 165 (6.2%) experienced oLRR. The 10-year cumulative incidence of IBTR and oLRR was 8.7% and 6.0%, respectively. Most locoregional failures occurred within 5 years (62.2% for IBTR and 80.6% for oLRR). Age, tumor size, and estrogen receptor status were significantly associated with IBTR. Nodal status and estrogen and progesterone receptor status were significantly associated with oLRR. The 5-year DDFS rates after IBTR and oLRR were 51.4% and 18.8%, respectively. The 5-year OS rates after IBTR and oLRR were 59.9% and 24.1%, respectively. Hazard ratios for mortality associated with IBTR and oLRR were 2.58 (95% CI, 2.11 to 3.15) and 5.85 (95% CI, 4.80 to 7.13), respectively.Node-positive breast cancer patients who developed IBTR or oLRR had significantly poorer prognoses than patients who did not experience these events.
The 4th Asia-Pacific Primary Liver Cancer Expert Meeting
Authors: Kwang-Hyub Han, Masatoshi Kudo, Sheng-Long Ye
Journal: Liver Cancer (2013)

Recurrence following curative therapy for hepatocellular carcinoma (HCC) remains a major problem. Alfa-fetoprotein (AFP), des-a-carboxy prothrombin (DCP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) are biomarkers that have been shown to predict recurrence and overall survival in patients undergoing surgical resection, radiofrequency ablation (RFA) or liver transplantation (LT). Not only can they provide prognosis following curative therapy, but there is emerging evidence that AFP should be used in the selection process for LT. A better understanding of the genetics and molecular pathways involved in HCC will lead to the development of new molecular biomarkers; however, these tests are not yet routinely available.