tbuckley/cabot-search huggingface dataset:
Mutation Analysis of the Entire Replicated Portion of PKD1 Using Genomic DNA Samples
Authors: BUNYONG PHAKDEEKITCHAROEN, TERRY J. WATNICK, GREGORY G. GERMINO
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The replicated portion of PKD1 , which comprises nearly 70% of the length of the gene, is predicted to harbor at least 85% of the mutations present in affected autosomal dominant polycystic kidney disease type 1 pedigrees. The relative paucity of reported mutations involving this segment is attributable to the significant technical challenges posed by the genomic structure of the gene. Previous genomic DNA-based strategies were unable to evaluate exons 1 and 22 and relied on the use of 10- to 13-kb PCR products. In this report, a set of six novel primer pair combinations, which can be used with previously reported reagents to analyze all of the exons in the replicated region (exons 1 to 34), are described. No product is greater than 5.8 kb in length, and various primer combinations can be used to reduce this length in half. Using this approach, two new pathogenic mutations, four novel disease-associated missense substitutions, and six new normal variants were identified. These new reagents should prove useful to investigators interested in performing DNA testing for this disorder.
An Address ON SURGERY IN THE TREATMENT OF PULMONARY TUBERCULOSIS
Authors: H. M. Davies
Journal: BMJ (1924)

SO03E twelve to fifteen years ago, and less, remnarks on this subject were almost completely confined to pneumothorax.Even with this limitation the audience was apt to look askance at one, and a sound physician might show his soundness by asking, "What is the pneum-othorax treat- ment " or, "What are refillsTo have said at that time much about the further surgical possibilities when artificial pneumothorax failed was to run big risks of being thought so ultraheterodox (one might say mentally aberrant) that one's ilnfluence in the teaching of the simpler forms of treatment was likely to be seriously impaired.Nowadays artificial pneumothorax is referred to familiarly as A.P.; in my plaoe the slang term " gassing is used.Instead, moreover, of having elaborately to expound the principles to general practitioners, patients are sent to one definitely for this treatment.The other and, if I may use the expression, more definitely surgical methods of treatment are not yet so widely recognized.They aremo're serious; they are associated with greater risks; and they are still, in this country, far from being widely known, or, when known, appro'ved of.In respect of these operations one is still looked upon with suspicion and even with disapproval, and the making of converts is a slow but very interestinig process.Because of the general knowledge as regards artificial
Homeopathy for eczema: a systematic review of controlled clinical trials
Authors: E. Ernst
Journal: British Journal of Dermatology (2012)

Journal Article Homeopathy for eczema: a systematic review of controlled clinical trials Get access E. Ernst E. Ernst Complementary Medicine, Peninsula Medical School, Exeter EX2 4SG, U.K Edzard Ernst. E‐mail: edzard.ernst@pms.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 6, 1 June 2012, Pages 1170–1172, https://doi.org/10.1111/j.1365-2133.2012.10994.x Published: 01 June 2012 Article history Accepted: 20 March 2012 Published: 01 June 2012
Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues
Authors: Steffan D Bos, Judith V M G Bovée, Bouke J Duijnisveld, Emma V A Raine, Wouter J van Dalen, Yolande F M Ramos, Ruud van der Breggen, Rob G H H Nelissen, P Eline Slagboom, John Loughlin, Ingrid Meulenbelt
Journal: Annals of the Rheumatic Diseases (2012)

Genetic variation at the type II deiodinase (D2) gene (DIO2) was previously identified as osteoarthritis (OA) risk factor. To investigate mechanisms possibly underlying this association, we assessed D2 protein in healthy and OA-affected cartilage and investigated allelic balance of the OA risk polymorphism rs225014 at DIO2 in human OA joints.Immunohistochemical staining of healthy and OA-affected cartilage was performed for D2. We then assessed allelic balance of DIO2 mRNA within OA-affected cartilage both at and away from the lesion, ligaments and subchondral bone. Allelic balance was measured by the amount of alleles 'C' and 'T' of the intragenic OA risk polymorphism rs225014 in heterozygous carriers.A markedly higher amount of D2 positive cells and staining intensity was observed in OA cartilage. A significant, 1.3-fold higher presence was observed for the OA-associated rs225014 'C' allele relative to the 'T' allele of DIO2, which was significant in 28 of 31 donors.In OA cartilage, D2 protein presence is increased. The allelic imbalance of the DIO2 mRNA transcript, with the OA risk allele 'C' of rs225014 more abundant than the wild-type 'T' allele in heterozygote carriers provides a possible mechanism by which genetic variation at DIO2 confers OA risk.
Bilateral diaphragmatic paralysis and related respiratory complications in a patient with West Nile virus infection
Authors: A D Betensley
Journal: Thorax (2004)

The case report is presented of a patient with West Nile virus infection and ventilator dependent respiratory failure in whom bilateral diaphragmatic paralysis developed. If the prevalence of West Nile virus infection continues to rise, recognition of diaphragmatic paralysis and related respiratory complications will become increasingly important to the pulmonary/critical care physician.
Overexpression of Aurora-A Contributes to Malignant Development of Human Esophageal Squamous Cell Carcinoma
Authors: Tong Tong, Yali Zhong, Jianping Kong, Lijia Dong, Yongmei Song, Ming Fu, Zhihua Liu, Mingrong Wang, Liping Guo, Shixin Lu, Ming Wu, Qimin Zhan
Journal: Clinical Cancer Research (2004)

Aurora-A/STK15/BTAK, a centrosome-associated oncogenic protein, is implicated in the control of mitosis. Overexpression of Aurora-A has been shown to result in chromosomal aberration and genomic instability. Multiple lines of evidence indicate that Aurora-A induces cell malignant transformation. In the current study, we are interested in investigating the expression of Aurora-A in human esophageal squamous cell carcinoma (ESCC) and characterizing the association of Aurora-A with ESCCmalignant progression.Aurora-A protein expression was examined in 84 ESCC tissues and 81 paired normal adjacent tissues by either immunohistochemistry or Western blot analysis. In addition, a gene-knockdown small interfering RNA technique was used in ESCC cells to investigate whether Aurora-A contributes to the ability of a tumor to grow invasively.The amount of Aurora-A protein in ESCC was considerably higher than that in normal adjacent tissues. Overexpression of Aurora-A was observed in 57 of 84 (67.5%) ESCC samples. In contrast, <2% of normal adjacent tissue displayed high expression of Aurora-A. Interestingly, overexpression of Aurora-A seemed to correlate with the invasive malignancy of ESCC. Disruption of endogenous Aurora-A using small interfering RNA technique substantially suppressed cell migrating ability.The findings presented in this report show that Aurora-A expression is elevated in human esophageal squamous cell carcinoma and is possibly associated with tumor invasion, indicating that overexpression of Aurora-A may contribute to ESCC occurrence and progression.
Early clinical response as a predictor of subsequent response to ixekizumab treatment: results from a phase II study of patients with moderate-to-severe plaque psoriasis
Authors: B. Zhu, E. Edson-Heredia, G.S. Cameron, W. Shen, J. Erickson, D. Shrom, P. Wang, S. Banerjee, K.B. Gordon
Journal: British Journal of Dermatology (2013)

Early identification of responsiveness to biologic treatments in psoriasis has significant clinical and economic implications.To evaluate whether early clinical improvements in Psoriasis Area and Severity Index (PASI) scores could predict subsequent clinical responses in patients treated with ixekizumab, an anti-interleukin-17 monoclonal antibody.This post hoc analysis was derived from a phase II study in patients with moderate-to-severe plaque psoriasis (n = 114) who received multiple doses of ixekizumab 10, 25, 75 or 150 mg subcutaneously over 20 weeks. PASI score improvements from baseline to weeks 2, 4 and 6 were evaluated to determine the optimal threshold for predicting subsequent PASI responses at week 12.Early clinical improvement in disease symptoms at weeks 4 and 6 was predictive of ≥ 75% improvement in PASI score (PASI 75) at week 12 with ≥ 90% predictability. A 40-50% improvement in PASI (PASI 40 to PASI 50) from baseline to weeks 4 and 6 was the optimum range for predicting PASI 75 response at week 12. For all doses combined, achieving PASI 40 at week 4 or week 6 was associated with high negative predictive values (NPVs) (80% and 95%, respectively) and positive predictive values (PPVs) (89% and 84%, respectively). For all doses combined, achieving PASI 50 at week 4 or week 6 was associated with NPVs of 71% and 89% and PPVs of 94% and 89%, respectively. Sensitivity analysis with the high-dose group (75 and 150 mg) results confirmed these findings.Early clinical responses (and nonresponse) may help predict later clinical responses in patients treated with ixekizumab.
Renal findings in patients with short-term type 2 diabetes.
Authors: C K Keller, K H Bergis, D Fliser, E Ritz
Journal: Journal of the American Society of Nephrology (1996)

Under semiambulatory conditions, 85 consecutive patients with the diagnosis of Type 2 diabetes of short duration (excluding patients with islet cell antibodies or maturity onset diabetes of the young) were admitted to a self-control training program and were examined in this study. A comprehensive renal assessment was performed, including evaluation of albumin excretion rate (AER), renal hemodynamics, blood pressure (BP) profile, and indicators of genetic risk. AER > or = 30 mg/24 h was found in 13 (15%) of patients; in two of these patients, AER was > or = 300 mg/24 h. By logistic regression, high HbA1, current smoking, and BP parameters were significantly correlated with an increased risk of microalbuminuria (MA). In a multiple linear regression model, accounting for 57% of total variance, HbA1, ERPF, and current smoking were significantly correlated with AER. Median GFR (Cin(inulin clearance) 136 mL/min per 1.73m2; range, 94 to 194) and ERPF (Cpah(para-aminohippuric acid clearance) 733; range, 451 to 1328) were significantly higher in patients than in control subjects (upper 95th percentile, 131 and 706 mL/min per 1.73m2, respectively). In a multiple linear regression model, explaining 27% of total variance, age, AER, gender, and fasting blood glucose were significantly correlated to GFR. According to the criteria of average daytime BP > or = 135/85 mm Hg or 24-h BP > or = 130/80 mm Hg, 60% of patients were hypertensive (HT). Sixty-one percent of all patients (including 50% of the untreated normotensive patients) were "nondippers", i.e., < 15% nighttime decrease of mean arterial pressure. Either HT or nondipping was found in 79% of all patients, so that only 21% had a completely normal blood pressure profile. Ninety-four percent of untreated hypertensive patients had no MA. First-degree relatives of patients with MA compared with patients without MA had more frequent cardiovascular events (69% versus 31%). The risk of MA in diabetic patients with positive family history was amplified by poor glycemic control. MA, but not hypertension, was marginally related to K(m) of Na+/Li+ countertransport. It was concluded that (1) microalbuminuria is found in 15% of patients newly presenting with Type 2 diabetes; (2) a high proportion of patients exhibit hyperfiltration; (3) according to ambulatory BP only, 21% of patients have a completely normal circadian BP profile; (4) a family history of cardiovascular events interacts with glycemic control to increase the risk of MA.
Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor
Authors: Roberto Bellucci, Edwin P. Alyea, Sabina Chiaretti, Catherine J. Wu, Emmanuel Zorn, Edie Weller, Bingyan Wu, Christine Canning, Robert Schlossman, Nikhil C. Munshi, Kenneth C. Anderson, Jerome Ritz
Journal: Blood (2005)
A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma
Authors: A. Duffy, J. Kortmansky, G.K. Schwartz, M. Capanu, S. Puleio, B. Minsky, L. Saltz, E.M. O’Reilly, D.P. Kelsen
Journal: Annals of Oncology (2007)
Tumor-Specific Isoform Switch of the Fibroblast Growth Factor Receptor 2 Underlies the Mesenchymal and Malignant Phenotypes of Clear Cell Renal Cell Carcinomas
Authors: Qi Zhao, Otavia L. Caballero, Ian D. Davis, Eric Jonasch, Pheroze Tamboli, W.K. Alfred Yung, John N. Weinstein, Robert L. Strausberg, Jun Yao
Journal: Clinical Cancer Research (2013)

We aim to identify tumor-specific alternative splicing events having potential applications in the early detection, diagnosis, prognosis, and therapy for cancers.We analyzed RNA-seq data on 470 clear cell renal cell carcinomas (ccRCC) and 68 kidney tissues to identify tumor-specific alternative splicing events. We further focused on the fibroblast growth factor receptor 2 (FGFR2) isoform switch and characterized ccRCCs expressing different FGFR2 isoforms by integrated analyses using genomic data from multiple platforms and tumor types.We identified 113 top candidate alternatively spliced genes in ccRCC. Prominently, the FGFR2 gene transcript switched from the normal IIIb isoform ("epithelial") to IIIc isoform ("mesenchymal") in nearly 90% of ccRCCs. This switch is kidney specific as it was rarely observed in other cancers. The FGFR2-IIIb ccRCCs show a transcriptome and methylome resembling those from normal kidney, whereas FGFR2-IIIc ccRCCs possess elevated hypoxic and mesenchymal expression signatures. Clinically, FGFR2-IIIb ccRCCs are smaller in size, of lower tumor grade, and associated with longer patient survival. Gene set enrichment and DNA copy number analyses indicated that FGFR2-IIIb ccRCCs are closely associated with renal oncocytomas and chromophobe RCCs (chRCC). A reexamination of tumor histology by pathologists identified FGFR2-IIIb tumors as chRCCs and clear cell papillary RCCs (ccpRCC).FGFR2 IIIb RCCs represent misdiagnosed ccRCC cases, suggesting FGFR2 isoform testing can be used in the diagnosis of RCC subtypes. The finding of a prevalent isoform switch of FGFR2 in a tissue-specific manner holds promise for the future development of FGFR2-IIIc as a distinct early detection biomarker and therapeutic target for ccRCC.
Ventrolateral Prefrontal Cortex Activation and Attentional Bias in Response to Angry Faces in Adolescents With Generalized Anxiety Disorder
Authors: Christopher S. Monk, Eric E. Nelson, Erin B. McClure, Karin Mogg, Brendan P. Bradley, Ellen Leibenluft, R. James R. Blair, Gang Chen, Dennis S. Charney, Monique Ernst, Daniel S. Pine
Journal: American Journal of Psychiatry (2006)

Objective: While adolescent anxiety disorders represent prevalent, debilitating conditions, few studies have explored their brain physiology. Using event-related functional magnetic resonance imaging (fMRI) and a behavioral measure of attention to angry faces, the authors evaluated differences in response between healthy adolescents and adolescents with generalized anxiety disorder. Method: In the primary trials of interest, 18 adolescents with generalized anxiety disorder and 15 comparison subjects of equivalent age/gender/IQ viewed angry/neutral face pairs during fMRI acquisition. Following the presentation of each face pair, subjects pressed a button to indicate whether a subsequent asterisk appeared on the same (congruent) or opposite (incongruent) side as the angry face. Reaction time differences between congruent and incongruent face trials provided a measure of attention bias to angry faces. Results: Relative to the comparison subjects, patients with generalized anxiety disorder manifested greater right ventrolateral prefrontal cortex activation to trials containing angry faces. Patients with generalized anxiety disorder also showed greater attention bias away from angry faces. Ventrolateral prefrontal cortex activation differences remained evident when differences in attention bias were covaried. Finally, in an examination among patients of the association between degree of anxiety and brain activation, the authors found that as ventrolateral prefrontal cortex activation increased, severity of anxiety symptoms diminished. Conclusions: Adolescents with generalized anxiety disorder show greater right ventrolateral prefrontal cortex activation and attentional bias away from angry faces than healthy adolescents. Among patients, increased ventrolateral prefrontal cortex activation is associated with less severe anxiety, suggesting that this activation may serve as a compensatory response.
Intensification of Therapy for Children With Lower-Risk Acute Lymphoblastic Leukemia: Long-Term Follow-Up of Patients Treated on Children’s Cancer Group Trial 1881
Authors: Raymond J. Hutchinson, Paul S. Gaynon, Harland Sather, Salvatore J. Bertolone, Herbert A. Cooper, Raymond Tannous, Linda M. Wells, Nyla A. Heerema, Scott Sailer, Michael E. Trigg
Journal: Journal of Clinical Oncology (2003)

From December 1988 through December 1992, the Children's Cancer Group (CCG) conducted a randomized trial (CCG-1881) designed to evaluate the impact of adding a single delayed intensification phase of therapy to standard therapy for patients with newly diagnosed low-risk acute lymphoblastic leukemia (ALL).Patients (n = 778) with newly diagnosed ALL, 2 to 9 years of age at diagnosis with an initial WBC count less than 10,000/microL, were eligible for this protocol. All patients received induction, consolidation, and interim maintenance phases of therapy over the first 16 weeks. At week 16, patients remaining in remission were randomly assigned to receive or not receive a single 7-week delayed intensification (DI) phase of therapy. Maintenance therapy was given in lieu of or after DI, with total duration of therapy approximately 3 years for boys and 2 years for girls.Patients randomized to receive DI experienced fewer relapse events in all categories. Kaplan-Meier life-table estimates for continuous complete remission (CCR) at 7 years for the randomized regimens were 77% (SE, 2.4%) for the standard regimen and 83% (SE, 2.7%) for the DI regimen (P =.072). The only prognostic factor of significance post-randomization in this selected low-risk population was the day 14 marrow response (P =.0001).The addition of a single DI phase of therapy was well tolerated and augmented 7-year CCR by 6% (SE of the difference, 3.3%), resulting in 26% fewer adverse events. Overall survival for eligible patients at 7 years is 90% (SE, 1.2%).
An Address ON ACUTE RHEUMATISM, ITS ALLIES AND ITS COUNTERFEITS
Authors: F. D. H. Hall
Journal: BMJ (1909)

The MedicaI Examination for Life Asuwrance2 I have- laid down the following rules:An attack of acute rheumatism, sufficiently severe to keep the patient in bed two or three weeks and to incapacitate him from his occupation for six or seven weeks, would require the addition of an equivalent to seven years at the age of 30, and three years must have elapsed sin'ce the attack.If there has been more than one attack, the life would not be assurable until at least ten years after the last attack.An applicant with a rheumatic history had better not be accepted under the age of 25 years.
Outcomes After Stereotactic Lung Radiotherapy or Wedge Resection for Stage I Non–Small-Cell Lung Cancer
Authors: Inga S. Grills, Victor S. Mangona, Robert Welsh, Gary Chmielewski, Erika McInerney, Shannon Martin, Jennifer Wloch, Hong Ye, Larry L. Kestin
Journal: Journal of Clinical Oncology (2010)

PURPOSE To compare outcomes between lung stereotactic radiotherapy (SBRT) and wedge resection for stage I non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS One hundred twenty-four patients with T1-2N0 NSCLC underwent wedge resection (n = 69) or image-guided lung SBRT (n = 58) from February 2003 through August 2008. All were ineligible for anatomic lobectomy; of those receiving SBRT, 95% were medically inoperable, with 5% refusing surgery. Mean forced expiratory volume in 1 second and diffusing capacity of lung for carbon monoxide were 1.39 L and 12.0 mL/min/mmHg for wedge versus 1.31 L and 10.14 mL/min/mmHg for SBRT (P = not significant). Mean Charlson comorbidity index and median age were 3 and 74 years for wedge versus 4 and 78 years for SBRT (P < .01, P = .04). SBRT was volumetrically prescribed as 48 (T1) or 60 (T2) Gy in four to five fractions. Results Median potential follow-up is 2.5 years. At 30 months, no significant differences were identified in regional recurrence (RR), locoregional recurrence (LRR), distant metastasis (DM), or freedom from any failure (FFF) between the two groups (P > .16). SBRT reduced the risk of local recurrence (LR), 4% versus 20% for wedge (P = .07). Overall survival (OS) was higher with wedge but cause-specific survival (CSS) was identical. Results excluding synchronous primaries, nonbiopsied tumors, or pathologic T4 disease (wedge satellite lesion) showed reduced LR (5% v 24%, P = .05), RR (0% v 18%, P = .07), and LRR (5% v 29%, P = .03) with SBRT. There were no differences in DM, FFF, or CSS, but OS was higher with wedge. CONCLUSION Both lung SBRT and wedge resection are reasonable treatment options for stage I NSCLC patients ineligible for anatomic lobectomy. SBRT reduced LR, RR, and LRR. In this nonrandomized population of patients selected for surgery versus SBRT (medically inoperable) at physician discretion, OS was higher in surgical patients. SBRT and surgery, however, had identical CSS.
PTEN Loss Compromises Homologous Recombination Repair in Astrocytes: Implications for Glioblastoma Therapy with Temozolomide or Poly(ADP-Ribose) Polymerase Inhibitors
Authors: Brian McEllin, Cristel V. Camacho, Bipasha Mukherjee, Brandon Hahm, Nozomi Tomimatsu, Robert M. Bachoo, Sandeep Burma
Journal: Cancer Research (2010)

Glioblastomas (GBM) are lethal brain tumors that are highly resistant to therapy. The only meaningful improvement in therapeutic response came from use of the S(N)1-type alkylating agent temozolomide in combination with ionizing radiation. However, no genetic markers that might predict a better response to DNA alkylating agents have been identified in GBMs, except for loss of O(6-)methylguanine-DNA methyltransferase via promoter methylation. In this study, using genetically defined primary murine astrocytes as well as human glioma lines, we show that loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) confers sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a functional analogue of temozolomide. We find that MNNG induces replication-associated DNA double-strand breaks (DSB), which are inefficiently repaired in PTEN-deficient astrocytes and trigger apoptosis. Mechanistically, this is because PTEN-null astrocytes are compromised in homologous recombination (HR), which is important for the repair of replication-associated DSBs. Our results suggest that reduced levels of Rad51 paralogs in PTEN-null astrocytes might underlie the HR deficiency of these cells. Importantly, the HR deficiency of PTEN-null cells renders them sensitive to the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-888 due to synthetic lethality. In sum, our results tentatively suggest that patients with PTEN-null GBMs (about 36%) may especially benefit from treatment with DNA alkylating agents such as temozolomide. Significantly, our results also provide a rational basis for treating the subgroup of patients who are PTEN deficient with PARP inhibitors in addition to the current treatment regimen of radiation and temozolomide.