tbuckley/cabot-search huggingface dataset:
Infiltration of Lynch Colorectal Cancers by Activated Immune Cells Associates with Early Staging of the Primary Tumor and Absence of Lymph Node Metastases
Authors: Noel F.C.C. de Miranda, Danny Goudkade, Ekaterina S. Jordanova, Carli M.J. Tops, Frederik J. Hes, Hans F.A. Vasen, Tom van Wezel, Hans Morreau
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Lynch syndrome colorectal cancers often lose human leukocyte antigen (HLA) class I expression. The outgrowth of clones with immune evasive phenotypes is thought to be positively selected by the action of cytotoxic T cells that target HLA class I–positive cancer cells. To investigate this hypothesis, we related the type and density of tumor lymphocytic infiltrate in Lynch colorectal cancers with their HLA class I phenotype and clinicopathologic stage. Experimental Design: HLA class I expression was assessed by means of immunohistochemistry. Characterization of tumor-infiltrating lymphocytes was carried out by using a triple immunofluorescence procedure that allowed the simultaneous detection of CD3-, CD8-, and granzyme B (GZMB)-positive cells. Additional markers were also used for further characterization of an elusive CD3−/CD8−/GZMB+ cell population. Results: We discovered that high tumor infiltration by activated CD8+ T cells correlated with aberrant HLA class I expression and associated with early tumor stages (P &amp;lt; 0.05). CD8+ T cells were most abundant in HLA class I heterogeneous tumors (P = 0.02) and frequent in HLA class I–negative cases (P = 0.04) when compared with HLA class I–positive carcinomas. An elusive immune cell population (CD45+/CD8−/CD56−/GZMB+) was characteristic for HLA class I–negative tumors lacking lymph node metastases (P &amp;lt; 0.01). Conclusions: The immune system assumes an important role in counteracting the progression of Lynch colorectal cancers and in selecting abnormal HLA class I phenotypes. Our findings support the development of clinical strategies that explore the natural antitumor immune responses occurring in Lynch syndrome carriers. Clin Cancer Res; 18(5); 1237–45. ©2012 AACR.
Far-Infrared Therapy
Authors: Chih-Ching Lin, Chao-Fu Chang, Ming-Yu Lai, Tzen-Wen Chen, Pui-Ching Lee, Wu-Chang Yang
Journal: Journal of the American Society of Nephrology (2007)

Vascular access malfunction, usually presenting with an inadequate access flow (Qa), is the leading cause of morbidity and hospitalization in hemodialysis (HD) patients. Many methods of thermal therapy have been tried for improving Qa but with limited effects. This randomized trial was designed to evaluate the effect of far-infrared (FIR) therapy on access flow and patency of the native arteriovenous fistula (AVF). A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group. A WS TY101 FIR emitter was used for 40 min, and hemodynamic parameters were measured by the Transonic HD(02) monitor during HD. The Qa(1)/Qa(2) and Qa(3)/Qa(4) were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study, respectively. The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy (13.2 +/- 114.7 versus -33.4 +/- 132.3 ml/min; P = 0.021). In comparison with control subjects, patients who received FIR therapy for 1 yr had (1) a lower incidence (12.5 versus 30.1%; P < 0.01) and relative incidence (one episode per 67.7 versus one episode per 26.7 patient-months; P = 0.03) of AVF malfunction; (2) higher values of the following parameters, including Delta(Qa(4) - Qa(3)) (36.2 +/- 82.4 versus -12.7 +/- 153.6 ml/min; P = 0.027), Delta(Qa(3) - Qa(1)) (36.3 +/- 166.2 versus -51.7 +/- 283.1 ml/min; P = 0.035), Delta(Qa(4) - Qa(2)) (99.2 +/- 144.4 versus -47.5 +/- 244.5 ml/min; P < 0.001), and Delta(Qa(4) - Qa(2)) - Delta(Qa(3) - Qa(1)) (62.9 +/- 111.6 versus 4.1 +/- 184.5 ml/min; P = 0.032); and (3) a better unassisted patency of AVF (85.9 versus 67.6%; P < 0.01). In conclusion, FIR therapy, a noninvasive and convenient therapeutic modality, can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects.
An Analytical Account of Fifty-Seven Cases of Puerperal Infection
Authors: W. E. Macharg
Journal: BMJ (1900)

PUERPER&L INFECTION.EDIOLJOUEL 373 reformatory for men, but the London County Council is about to build an institution for the accommodation of 4o male inebriates at Charlwood, near Horley.A medical attendant has to be appointed to attend to the patients at the certified inebriate reformatory, and for his guidance certain rules have been, laid down.The most important of these are:x.He is responsible for the general care of the health of the inmates, and has to report to the managers and make known to the superintendent any circumstance connected with the reformatory or the treatment of the inmates which appears to him to require consideration on medical grounds.2. He must visit the reformatory once every day, and see every inmate at least twice a week, except in the case of inmates complaining of illness or who are under punishment or special discipline, and these must be visited every day.3. Every inmate must be examined on reception, and the state of his health and such facts as are connected therewith recorded.4. He must frequently examine the washing places, baths, etc., and inspect the food, provisions,,clothing, and bedding, reporting to the superintendent any deficiency or defect which he may find, not only with respect to the above-stated clothes, food, etc., but any other cause which may affect the health of the inmates.5.He has to keep forms which he must fill up, giving an account of the state of health or dlisease of each sick inmate, and the treatment which he orders as well as statistical records relative to the health and treatment of the inmates and the sanitary condition of the buildings.6.He must give notice to the superintendent when the illness of the inmate becomes dangerous in character, and in case of death inform the superintendent.7. He has to report in writing to the superintendent the case of any inmate to which he thinks it necessary to call attention, and give direc- tions in writing for separating from the other inmates those who are suffering from infectious, contagious, or mental diseases, and take steps to prevent the spread of any contagious or infectious disease.8.He must examine any inmate before he is placed in close confine- ment or subjected to dietary punishment to certify whether or not he is filt for punishment.
Patterns of Use and Short-Term Complications of Breast Brachytherapy in the National Medicare Population From 2008–2009
Authors: Carolyn J. Presley, Pamela R. Soulos, Jeph Herrin, Kenneth B. Roberts, James B. Yu, Brigid Killelea, Beth-Ann Lesnikoski, Jessica B. Long, Cary P. Gross
Journal: Journal of Clinical Oncology (2012)

Purpose Brachytherapy has disseminated into clinical practice as an alternative to whole-breast irradiation (WBI) for early-stage breast cancer; however, current national treatment patterns and associated complications remain unknown. Patients and Methods We constructed a national sample of Medicare beneficiaries ages 66 to 94 years who underwent breast-conserving surgery from 2008 to 2009 and were treated with brachytherapy or WBI. We used hospital referral regions (HRRs) to assess national treatment variation and an instrumental variable analysis to compare complication rates between treatment groups, adjusting for patient and clinical characteristics. We compared overall, wound and skin, and deep-tissue and bone complications between brachytherapy and WBI at 1 year of follow-up. Results Of 29,648 women in our sample, 4,671 (15.8%) received brachytherapy. The percent of patients receiving brachytherapy varied substantially across HRRs, ranging from 0% to over 70% (interquartile range, 7.5% to 23.3%). Of women treated with brachytherapy, 34.3% had a complication compared with 27.3% of women undergoing WBI (P &lt; .001). After adjusting for patient and clinical characteristics, 35.2% of women treated with brachytherapy (95% CI, 28.6 to 41.9) had a complication compared with 18.4% treated with WBI (95% CI, 15.5 to 21.3; P value for difference, &lt;.001). Brachytherapy was associated with a 16.9% higher rate of wound and skin complications compared with WBI (95% CI, 10.0 to 23.9; P &lt; .001), but there was no difference in deep-tissue and bone complications. Conclusion Brachytherapy is commonly used among Medicare beneficiaries and varies substantially across regions. After 1 year, wound and skin complications were significantly higher among women receiving brachytherapy compared with those receiving WBI.
The fickle finger of fate
Authors: Luis de la Fuente, Jill A. Helms
Journal: Journal of Clinical Investigation (2005)

In this issue of the JCI, Niedermaier and colleagues demonstrate that a chromosomal inversion in mice results in dysregulation of Sonic hedgehog (Shh), such that Shh is ectopically expressed in a skeletogenic domain typically occupied by Indian hedgehog (Ihh). This molecular reversal eliminates phalangeal joint spaces, and consequently, Short digits (Dsh) heterozygotes (Dsh/+) have brachydactyly (shortened digits). Ihh is normally downregulated in regions that will become the joint space, but in Dsh/+ mice, Shh bypasses this regulatory control and persists; accordingly, cells maintain their chondrogenic fate and the developed digits are shorter than normal. The significance of these data extends far beyond the field of skeletal biology: they hint at the very real possibility that the endogenous Shh regulatory region contains a repressor designed to segregate the activity of Shh from Ihh. The existence of such a repressor provides a window into the distant past, revealing that Shh and Ihh must once have shared responsibilities in establishing tissue boundaries and orchestrating vertebrate tissue morphogenesis.
Hyperpolarized 13C magnetic resonance metabolic imaging: application to brain tumors
Authors: I. Park, P. E. Z. Larson, M. L. Zierhut, S. Hu, R. Bok, T. Ozawa, J. Kurhanewicz, D. B. Vigneron, S. R. VandenBerg, C. D. James, S. J. Nelson
Journal: Neuro-Oncology (2010)

In order to compare in vivo metabolism between malignant gliomas and normal brain, 13C magnetic resonance (MR) spectroscopic imaging data were acquired from rats with human glioblastoma xenografts (U-251 MG and U-87 MG) and normal rats, following injection of hyperpolarized [1-13C]-pyruvate. The median signal-to-noise ratio (SNR) of lactate, pyruvate, and total observed carbon-13 resonances, as well as their relative ratios, were calculated from voxels containing Gadolinium-enhanced tissue in T1 postcontrast images for rats with tumors and from normal brain tissue for control rats. [1-13C]-labeled pyruvate and its metabolic product, [1-13C]-lactate, demonstrated significantly higher SNR in the tumor compared with normal brain tissue. Statistical tests showed significant differences in all parameters (P < .0004) between the malignant glioma tissue and normal brain. The SNR of lactate, pyruvate, and total carbon was observed to be different between the U-251 MG and U-87 MG models, which is consistent with inherent differences in the molecular characteristics of these tumors. These results suggest that hyperpolarized MR metabolic imaging may be valuable for assessing prognosis and monitoring response to therapy for patients with brain tumors.
Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis
Authors: C Carlens, L Jacobsson, L Brandt, S Cnattingius, O Stephansson, J Askling
Journal: Annals of the Rheumatic Diseases (2008)

To investigate the importance of birth characteristics and early life infections on the risk of later rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA).A nationwide register-based case-control study was performed based on prospectively recorded data on individuals born in 1973 or later. Using the Swedish inpatient register and the early arthritis register, cases with RA aged 16 years or above (n = 333) and JIA (n = 3334) were identified. From the Swedish medical birth register (MBR), four controls per case, matched by sex, year and delivery unit were randomly selected. Through linkage to the MBR and to the Swedish inpatient register information on maternal, pregnancy and birth characteristics and infections during the first year of life was identified. Univariate and multivariate odds ratios (OR) were calculated using conditional logistic regression.Overall, infections during the first year of life were associated with increased risks for seronegative (OR 2.6, 95% CI 1.0 to 7.0) but not seropositive (OR 1.2) RA and for JIA (OR 1.9, 95% CI 1.7 to 2.1). Low birth weight (OR 0.7) and being small for gestational age (OR 0.5) were associated with reduced risks of RA of borderline statistical significance. Preterm birth (gestational age < or =258 days) was associated with a non-significantly decreased risk of RA (OR 0.6). Large for gestational age (OR 1.6) and having more than three older siblings (OR 1.4) were non-significantly associated with the risk of RA.Infections during the first year of life, and possibly also factors related to fetal growth and timing of birth, may be important in the aetiologies of adult RA and JIA.
Physicians and the First Amendment
Authors: Gregory D. Curfman, Stephen Morrissey, Michael F. Greene, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2008)

In the November elections, the citizens of three states resoundingly defeated initiatives aimed at curtailing reproductive rights. In Colorado, a proposed amendment to the state's Constitution would have given the same legal rights to fertilized eggs as to living persons. This amendment, which was rejected by a wide margin, would have had broad ramifications for abortion rights, the use of contraceptive agents, and stem-cell research. In California, a parental notification proposition backed by antiabortion forces was also rejected. In South Dakota, a ballot measure that would have effectively banned all abortions in the state was defeated, as was a similar . . .
Maleic acid-induced proximal tubulopathy
Authors: S K Mujais
Journal: Journal of the American Society of Nephrology (1993)

Maleic acid (MA) administration to experimental animals induces a rapid, reversible, complex dysfunction of the renal tubule resembling Fanconi's syndrome. The intent of this work was to characterize the changes in the Na:K pump along the nephron during the development and recovery from MA injury to better define the site of damage and to correlate the observed changes in Na:K pump function with alterations in metabolic function. Male Sprague Dawley rats were studied before and 2 and 24 h after the injection of MA (100 mg/kg iv). MA induced an early and reversible decline in Na:K pump activity in the proximal convoluted tubule (PCT) from 2,324 +/- 61 to 1,446 +/- 55 pmol/mm.h (P < 0.001). This decrement was transient because enzyme activity returned to near baseline by 24 h after MA administration. The changes in Na:K pump activity were restricted to the PCT because no change in pars rectae, in medullary thick ascending limb, or in medullary collecting tubules was observed. PCT obtained from MA-treated rats 2 h after drug injection showed a decline in 14CO2 formation from radiolabeled glutamine, implying impaired oxidation of the carbon skeleton of the amino acid. This decline was transient with recovery of oxidative rates to normal 24 h after MA administration. It was concluded that a reversible, segment-specific impairment in PCT Na:K pump occurs early after the administration of MA. The decline in PCT Na:K pump activity is paralleled by a decrement in oxidative metabolism and may underlie the many consequences of this model of proximal tubulopathy that are reflections of impairment in sodium-dependent transport processes.
Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00
Authors: G. Fountzilas, U. Dafni, H. Gogas, H. Linardou, H.P. Kalofonos, E. Briasoulis, D. Pectasides, E. Samantas, D. Bafaloukos, G.P. Stathopoulos, M. Karina, C. Papadimitriou, D. Skarlos, N. Pisanidis, P. Papakostas, C. Markopoulos, E. Tzorakoeleftherakis, K. Dimitrakakis, P. Makrantonakis, N. Xiros, A. Polichronis, I. Varthalitis, C. Karanikiotis, A.M. Dimopoulos
Journal: Annals of Oncology (2007)
Unique DNA Methylation Loci Distinguish Anatomic Site and HPV Status in Head and Neck Squamous Cell Carcinoma
Authors: Roberto A. Lleras, Richard V. Smith, Leslie R. Adrien, Nicolas F. Schlecht, Robert D. Burk, Thomas M. Harris, Geoffrey Childs, Michael B. Prystowsky, Thomas J. Belbin
Journal: Clinical Cancer Research (2013)

We have used a genome-wide approach to identify novel differentially methylated CpG dinucleotides that are seen in different anatomic sites of head and neck squamous cell carcinoma (HNSCC), as well as those that might be related to HPV status in the oropharynx.We conducted genome-wide DNA methylation profiling of primary tumor samples and corresponding adjacent mucosa from 118 HNSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY, using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M-value).When datasets were individually analyzed by anatomic site of the primary tumor, we identified 293 differentially methylated CpG loci in oral cavity squamous cell carcinoma (SCC), 219 differentially methylated CpG loci in laryngeal SCC, and 460 differentially methylated in oropharyngeal SCC. A subset of these differentially methylated CpG loci was common across all anatomic sites of HNSCC. Stratification by HPV status revealed a significantly higher number of differentially methylated CpG loci in HPV+ patients.Novel epigenetic biomarkers derived from clinical HNSCC specimens can be used as molecular classifiers of this disease, revealing many new avenues of investigation for this disease.
Role of Glycogen Synthase Kinase-3β in Cardioprotection
Authors: Magdalena Juhaszova, Dmitry B. Zorov, Yael Yaniv, H. Bradley Nuss, Su Wang, Steven J. Sollott
Journal: Circulation Research (2009)

Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Increasing the ROS threshold for mPTP induction enhances the resistance of cardiomyocytes to oxidant stress and results in infarct size reduction. Here, we survey and synthesize the present knowledge about the role of glycogen synthase kinase (GSK)-3beta in cardioprotection, including pre- and postconditioning. Activation of a wide spectrum of cardioprotective signaling pathways is associated with phosphorylation and inhibition of a discrete pool of GSK-3beta relevant to mitochondrial signaling. Therefore, GSK-3beta has emerged as the integration point of many of these pathways and plays a central role in transferring protective signals downstream to target(s) that act at or in proximity to the mPTP. Bcl-2 family proteins and mPTP-regulatory elements, such as adenine nucleotide translocator and cyclophilin D (possibly voltage-dependent anion channel), may be the functional downstream target(s) of GSK-3beta. Gaining a better understanding of these interactions to control and prevent mPTP induction when appropriate will enable us to decrease the negative impact of the reperfusion-induced ROS burst on the fate of mitochondria and perhaps allow us to limit propagation of damage throughout and between cells and consequently, to better limit infarct size.
Impaired Airway Function and Wheezing in Infancy
Authors: C. DEZATEUX, J. STOCKS, I. DUNDAS, M. E. FLETCHER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

This prospective community-based study of infants born in inner London was undertaken to examine the association between premorbid airway function and subsequent wheezing in the first year of life and to explore the influence on this association of a family history of asthma and maternal smoking during pregnancy. Healthy Caucasian term infants were recruited shortly after birth, and physician-diagnosed wheezing episodes were identified retrospectively from medical records. Specific airway conductance was determined from plethysmographic measurements of lung volume and airway resistance, before 13 wk and prior to any respiratory illness, in 101 infants, 28 of whom experienced at least one episode of wheezing during the first year. Mean (SD) specific airway conductance was significantly diminished in infants who subsequently wheezed: 2.02 (1.07) s− 1 · kPa− 1 and 2.60 (0.93) s− 1 · kPa− 1, respectively (p < 0.05), and in those with a first-degree relative with asthma: 1.98 (0.83) s− 1 · kPa− 1 and 2.60 (1.0) s− 1 · kPa− 1, respectively (p < 0.05), but not in those whose mothers smoked during pregnancy, in whom airway resistance was, however, significantly elevated (p < 0.05). The odds ratio (95% confidence interval [CI]) for wheezing was 2.1 (1.1 to 3.8) for every unit (s− 1 · kPa− 1) decline in specific airway conductance (p = 0.02). After adjustment for premorbid airway function, the odds of wheezing were significantly increased in those with a family history of asthma (4.3; 95% CI, 1.3 to 13.8; p = 0.016) and those exposed to maternal smoking during pregnancy (4.9; 95% CI, 1.6 to 15.0; p = 0.005). Our findings confirm previous reports that impaired premorbid airway function precedes and predicts wheezing in the first year. Among those with a genetic predisposition to asthma, alterations in airway geometry or tone may increase susceptibility to wheezing. Maternal smoking has important and potentially preventable adverse effects on somatic growth and respiratory morbidity in early life.
Evidence for genetic drift in endosymbionts (Buchnera): analyses of protein-coding genes
Authors: J. J. Wernegreen, N. A. Moran
Journal: Molecular Biology and Evolution (1999)

Buchnera, the bacterial endosymbionts of aphids, undergo severe population bottlenecks during maternal transmission through their hosts. Previous studies suggest an increased effect of drift within these strictly asexual, small populations, resulting in an increased fixation of slightly deleterious mutations. This study further explores sequence evolution in Buchnera using three approaches. First, patterns of codon usage were compared across several homologous Escherichia coli and Buchnera loci, in order to test the prediction that selection for the use of optimal codons is less effective in small populations. A chi 2-based measure of codon bias was developed to adjust for the overall A + T richness of silent positions in the endosymbionts. In contrast to E. coli homologues, adaptive codon bias across Buchnera loci is markedly low, and patterns of codon usage lack a strong relationship with gene expression level. These data suggest that codon usage in Buchnera has been shaped largely by mutational pressure and drift rather than by selection for translational efficiency. One exception to the overall lack of bias is groEL, which is known to be constitutively overexpressed in Buchnera and other endosymbionts. Second, relative-rate tests show elevated rates of sequence evolution of numerous protein-coding loci across Buchnera, compared to E. coli. Finally, consistently higher ratios of nonsynonymous to synonymous substitutions in Buchnera loci relative to the enteric bacteria strongly suggest the accumulation of nonsynonymous substitutions in endosymbiont lineages. Combined, these results suggest a decreased effectiveness of purifying selection in purging endosymbiont populations of slightly deleterious mutations, particularly those affecting codon usage and amino acid identity.