tbuckley/cabot-search huggingface dataset:
Eosinophil-derived neurotoxin in urine may predict the development of bronchopulmonary dysplasia in preterm infants
Authors: Sun Hee Choi, Yeong Ho Rha, Chong Woo Bae, Ji Young Chang
Journal: European Respiratory Journal (2013)

Rationale: Bronchopulmonary dysplasia (BPD) is the consequence of disturbed lung development and inflammation due to perinatal factors related to respiratory distress syndrome (RDS). Eosinophil-derived neurotoxin (EDN) is not the only marker of eosinophil activation, but also acts as an alarm protein. Very few studies have examined the potential role of eosinophil in development of BPD. This study aims to address the roles of eosinophil and EDN in the early phase of BPD development. Methods: Study patients were preterm neonates with RDS born at 36 weeks of gestation or lesser (RDS group). Control patients were preterm babies with only minor respiratory problems or none at all. Blood and urine samples were collected to measure total eosinophil count in the blood, serum eosinophil cationic protein (ECP), serum EDN and urinary EDN during the first week of life. Comparisons were made between the RDS group and the non-RDS group and between the BPD group and the non-BPD group.  Results: A total of 43 neonates were recruited and 10 patients were excluded. There were no differences between RDS and non-RDS group in total eosinophil count, serum ECP, serum EDN, or urinary EDN, except when compared by gestational age, birth weight, and prenatal dexamethasone use. Urinary EDN was increased significantly in the BPD group compared to the non-BPD group.  Conclusion: We demonstrated the roles of eosinophil and EDN in the development of BPD and urinary EDN may be utilized as a non-invasive tool in predicting development of BPD.
Molecular Evidence for the Independent Origin of Extra-ovarian Papillary Serous Tumors of Low Malignant Potential
Authors: J. Gu, L. M. Roth, C. Younger, H. Michael, F. W. Abdul-Karim, S. Zhang, T. M. Ulbright, J. N. Eble, L. Cheng
Journal: JNCI Journal of the National Cancer Institute (2001)

Molecular data suggest that peritoneal tumors in women with advanced-stage ovarian papillary serous adenocarcinoma are monoclonal in origin. Whether the same is true for ovarian tumors of low malignant potential is not known. We compared peritoneal and ovarian tumors from women with advanced-stage ovarian papillary serous tumors of low malignant potential to determine whether the peritoneal tumors arose from the same clone as the ovarian tumors.We studied the clonality of 73 peritoneal and ovarian tumors from 18 women with advanced-stage ovarian papillary serous tumors of low malignant potential. Formalin-fixed, paraffin-embedded tumors and representative normal tissues were sectioned and stained with hematoxylin-eosin, representative sections from separate tumors were manually microdissected, genomic DNA was extracted from the microdissected tumors, and the polymerase chain reaction was used to amplify a CAG polymorphic site in the human androgen receptor locus on the X chromosome to determine the inactivation pattern of the X chromosome and the clonality of the tumors.The pattern of X-chromosome inactivation could be determined from the tumors of 13 of 18 patients. Of the 13 patients, seven (54%) had nonrandom inactivation of the X chromosome, and six of the seven had different inactivation patterns in the peritoneal and ovarian tumors. Three of these patients also had different patterns of nonrandom X-chromosome inactivation in tumors from each ovary. The remaining six patients had random patterns of X-chromosome inactivation in the peritoneal and ovarian tumors.Our data suggest that peritoneal and ovarian tumors of low malignant potential arise independently.
Do X‐linked diseases affect periodontal health?
Authors: Hua‐Hong Chien, Thomas C. Hart
Journal: Periodontology 2000 (2012)

Abstract Genetic factors play an important etiologic role in destructive periodontal diseases. There have been reports that sex chromosomes, especially disorders associated with the X chromosome, affect periodontal health. Although numerous X‐linked diseases have been reported to be associated with various periodontal diseases, the association of gingivitis and/or periodontitis with these genetic syndromes should be considered tenuous and raises the question of whether the periodontal manifestation truly arises from an underlying X‐linked genetic etiology. A brief overview of genetics in relation to sex chromosomes and putative X‐linked genetic periodontal diseases is given.
Secreted CXCL1 Is a Potential Mediator and Marker of the Tumor Invasion of Bladder Cancer
Authors: Hiroaki Kawanishi, Yoshiyuki Matsui, Masaaki Ito, Jun Watanabe, Takeshi Takahashi, Koji Nishizawa, Hiroyuki Nishiyama, Toshiyuki Kamoto, Yoshiki Mikami, Yoshinori Tanaka, Giman Jung, Hideo Akiyama, Hitoshi Nobumasa, Parry Guilford, Anthony Reeve, Yasushi Okuno, Gozoh Tsujimoto, Eijiro Nakamura, Osamu Ogawa
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The purpose of this study was to identify proteins that are potentially involved in the tumor invasion of bladder cancer. Experimental Design: We searched for the candidate proteins by comparing the profiles of secreted proteins among the poorly invasive human bladder carcinoma cell line RT112 and the highly invasive cell line T24. The proteins isolated from cell culture supernatants were identified by shotgun proteomics. We found that CXCL1 is related to the tumor invasion of bladder cancer cells. We also evaluated whether the amount of the chemokine CXCL1 in the urine would be a potential marker for predicting the existence of invasive bladder tumors. Results: Higher amount of CXCL1 was secreted from highly invasive bladder carcinoma cell lines and this chemokine modulated the invasive ability of those cells in vitro. It was revealed that CXCL1 regulated the expression of matrix metalloproteinase-13 in vitro and higher expression of CXCL1 was associated with higher pathologic stages in bladder cancer in vivo. We also showed that urinary CXCL1 levels were significantly higher in patients with invasive bladder cancer (pT1-4) than those with noninvasive pTa tumors (P = 0.0028) and normal control (P &amp;lt; 0.0001). Finally, it was shown that CXCL1 was an independent factor for predicting the bladder cancer with invasive phenotype. Conclusions: Our results suggest that CXCL1 modulates the invasive abilities of bladder cancer cells and this chemokine may be a potential candidate of urinary biomarker for invasive bladder cancer and a possible therapeutic target for preventing tumor invasion.
Detection of nonmelanoma skin cancer micrometastases in lymph nodes by using reverse transcriptase-polymerase chain reaction for keratin 19 mRNA
Authors: M. Kamiya, Y. Ichiki, H. Kamiya, A. Yamamoto, Y. Kitajima
Journal: British Journal of Dermatology (2003)

A new sensitive method for the detection of skin cancer micrometastases in lymph nodes is based on amplification of keratin 19 (K19) mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).To compare results of RT-PCR with those of histological examination in terms of the detection rate of skin cancer micrometastases.Twenty-six lymph nodes obtained from 13 patients with squamous cell carcinoma (SCC), eccrine porocarcinoma and Paget's disease were investigated by histological examination (haematoxylin and eosin sections) and RT-PCR. RT-PCR was performed on extracted RNA by using K19 primer pairs. RT-PCR products were visualized by ethidium bromide staining and confirmed by non-radioactive hybridization with K19-specific probes.All of 10 histologically positive lymph nodes yielded the expected 460-bp band. Of the 16 histologically negative lymph nodes, one (6%) was found by RT-PCR to express K19 mRNA, indicating the presence of micrometastases which could not be detected by histological examination. A serial dilution study using RNA extracted from SCC cells mixed with RNA extracted from normal lymph node cells showed a detection sensitivity of K19 RT-PCR of 10-5 micro g cancer cell RNA in 1 micro g lymph node RNA. Nested RT-PCR showed a detection sensitivity of one tumour cell in 106 lymphocytes.These results demonstrate the usefulness of K19 RT-PCR for the detection of skin cancer micrometastases in lymph nodes.
Ionotropic Glutamate Receptor Binding and Subunit mRNA Expression in Thalamic Nuclei in Schizophrenia
Authors: Hisham M. Ibrahim, Alan J. Hogg, Daniel J. Healy, Vahram Haroutunian, Kenneth L. Davis, James H. Meador-Woodruff
Journal: American Journal of Psychiatry (2000)

Both thalamic and glutamatergic dysfunction have been implicated in the pathophysiology of schizophrenia. The authors examined ionotropic glutamate receptor expression in postmortem samples from patients with schizophrenia and comparison subjects, using the hypothesis that glutamate receptor expression differs in limbic nuclei of the thalamus in schizophrenia.N-Methyl-D-aspartate (NMDA), AMPA, and kainate receptor expression was determined in six thalamic nuclei from 12 subjects with DSM-III-R diagnoses of schizophrenia and eight psychiatrically normal individuals. The authors used in situ hybridization to determine NMDAR1, NMDAR2A-NMDAR2D, gluR1-gluR7, KA1, and KA2 subunit mRNA levels and receptor autoradiography to determine binding to glutamate binding sites of the three receptor subtypes and to the glycine, polyamine, and ion channel binding sites of the NMDA receptor.Glutamate receptor expression was lower at both transcriptional (NMDAR1, NMDAR2B, NMDAR2C, gluR1, gluR3, and KA2 subunit mRNAs) and posttranscriptional ([(3)H]ifenprodil and [(3)H]MDL105,519 binding to polyamine and glycine sites of the NMDA receptor) levels in the thalamus in patients with schizophrenia than in comparison subjects, but differences were most prominent in nuclei with reciprocal projections to limbic regions.Abnormalities in NMDA, AMPA, and kainate receptor expression in limbic thalamus are suggestive of the NMDA receptor hypoactivity hypothesis of schizophrenia and are consistent with diminished glutamatergic activity in the thalamus in schizophrenia. Alternatively, these results could suggest abnormal glutamatergic innervation in afferent and/or efferent regions, which are limbic structures that have been implicated in this illness. These results may provide a neurochemical anatomical substrate for antipsychotic therapies targeting ionotropic glutamate receptors.
Primary Cutaneous Follicular Lymphoma: An Assessment of Clinical, Histopathologic, Immunophenotypic, and Molecular Features
Authors: I. Mirza, N. Macpherson, S. Paproski, R. D. Gascoyne, B. Yang, W. G. Finn, E. D. Hsi
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Unlike nodal follicular lymphoma (NFL), Primary cutaneous follicular lymphomas (PCFLs) rarely express Bcl-2 protein or t(14;18)(q32;q21) (Bcl-2/IgH). The aim of this study was to further characterize PCFL in a large series from North America. PATIENTS AND METHODS: Clinical data and archival formalin-fixed, paraffin-embedded tissue were obtained from 32 patients. PCFL was defined as follicular lymphoma limited to the skin at the time of diagnosis and within the first 6 months after diagnosis. Specimens were analyzed for the expression of CD3, CD10, CD20, Bcl-2, and Bcl-6 proteins by immunohistochemistry as well as for the presence of t(14;18)(q32;q21) by polymerase chain reaction. RESULTS: The male-to-female ratio was 1.5:1, with a median age of 60 years. Twenty-four patients had lesions on the head and neck, five had lesions on the trunk, and three had lesions on both head and trunk. Follow-up data were available in all cases, with a mean length of 35.8 months. The majority of the patients were treated with radiation therapy. All patients were alive at last follow-up except one. Recurrence was noted in seven patients (22%), after a mean disease-free survival time of 17.7 months. CD10 and Bcl-6 expression were seen in 29 (91%) of 32 and 31 (97%) of 32 cases, respectively. Bcl-2 expression was noted in 13 (41%) of 32 cases. PCR results for t(14;18)(q32;q21) were positive in 11 (34%) of 32 patients and showed correlation with Bcl-2 protein expression. The sequencing of the t(14;18)(q32;q21) amplicons confirmed unique breakpoints in each of the seven tested cases. Comparison between the Bcl-2 and/or t(14;18)(q32;q21)-positive and t(14;18)(q32;q21)-negative cases revealed no significant difference in age, site, clinical course, or outcome. CONCLUSION: We demonstrated Bcl-2 protein expression and t(14;18)(q32;q21) in a significant minority of cases, suggesting a relationship with NFL. It remains to be seen whether, on longer follow-up, there is any clinical difference in cases with and without t(14;18)(q32;q21).
Comparative Evaluation of Radiation Treatments for Clinically Localized Prostate Cancer: An Updated Systematic Review
Authors: Raveendhara R. Bannuru, Tomas Dvorak, Ndidiamaka Obadan, Winifred W. Yu, Kamal Patel, Mei Chung, Stanley Ip
Journal: Annals of Internal Medicine (2011)

Background: Radiation therapy is one of many treatment options for patients with prostate cancer. Purpose: To update findings on the clinical and biochemical outcomes of radiation therapies for localized prostate cancer. Data Sources: MEDLINE (2007 through March 2011) and the Cochrane Central Register of Controlled Trials (2007 through March 2011). Study Selection: Published English-language comparative studies involving adults with localized prostate cancer who either had first-line radiation therapy or received no initial treatment. Data Extraction: 6 researchers extracted information on study design, potential bias, sample characteristics, interventions, and outcomes and rated the strength of overall evidence. Data for each study were extracted by 1 reviewer and confirmed by another. Data Synthesis: 75 studies (10 randomized, controlled trials [RCTs] and 65 nonrandomized studies) met the inclusion criteria. No RCTs compared radiation therapy with no treatment or no initial treatment. Among the 10 RCTs, 2 compared combinations of radiation therapies, 7 compared doses and fraction sizes of external-beam radiation therapy (EBRT), and 1 compared forms of low-dose rate radiation therapy. Heterogeneous outcomes were analyzed. Overall, moderate-strength evidence consistently showed that a higher EBRT dose was associated with increased rates of long-term biochemical control compared with lower EBRT dose. The body of evidence was rated as insufficient for all other comparisons. Limitations: Studies inconsistently defined and reported outcomes. Much of the available evidence comes from observational studies with treatment selection biases. Conclusion: A lack of high-quality comparative evidence precludes conclusions about the efficacy of radiation treatments compared with no treatments for localized prostate cancer. Primary Funding Source: Agency for Healthcare Research and Quality.
Chronic Kidney Disease Increases Risk for Venous Thromboembolism
Authors: Keattiyoat Wattanakit, Mary Cushman, Catherine Stehman-Breen, Susan R. Heckbert, Aaron R. Folsom
Journal: Journal of the American Society of Nephrology (2007)

Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95% confidence interval [CI] 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.
Lysis of measles virus-infected cells by the purified cytolytic alternative complement pathway and antibody.
Authors: J G Patrick Sissons, R D Schreiber, L H Perrin, N R Cooper, H J Müller-Eberhard, M B Oldstone
Journal: The Journal of Experimental Medicine (1979)

The dependence of antibody-and-complement-mediated lysis of virus-infected cells on the alternative pathway was examined utilizing the isolated cytolytic alternative pathway--a system consisting of the six purified proteins of the alternative pathway of activation (C3, factors B and D, beta 1H, C3b inactivator and properdin), and the five proteins of the membrane attack pathway (C5--9) of complement. HeLa cells acutely infected with measles virus were lysed by anti-viral IgG and the isolated cytolytic alternative pathway with an efficiency comparable to whole human serum. IgG and its F(ab')2 fragment were equally effective in inducing lysis by the isolated cytolytic alternative pathway, binding of approximately equal to 5 X 10(7) molecules per cell being required for 50% lysis; in contrast, no lysis occurred when equivalen or greater amounts of Fab' were bound to the virus-infected cell. Properdin was required for lysis. No lysis occurred if properdin was deleted from the isolated cytolytic alternative pathway, and lysis was diminished by 80% in properdin-depleted serum. Uptake of [125I]C3b from the isolated alternative pathway onto measles virus-infected cells occurred in the absence of properdin, but was accelerated in the presence of properdin. The 11 proteins of the isolated cytolytic alternative pathway are thus sufficient for lysis of measles virus-infected cells bearing anti-viral IgG or F(ab')2 without any other serum protein.
Naltrexone vs Placebo for the Treatment of Alcohol Dependence
Authors: David W. Oslin, Shirley H. Leong, Kevin G. Lynch, Wade Berrettini, Charles P. O’Brien, Adam J. Gordon, Margaret Rukstalis
Journal: JAMA Psychiatry (2015)

Alcohol use disorder is one of the leading causes of disability worldwide. While effective pharmacological treatments exist, they are efficacious only in certain individuals, contributing to their limited use. Secondary analysis of clinical trial data suggests that a functional polymorphism (rs1799971, Asn40Asp) of the µ-opioid receptor gene (OPRM1) is associated with the risk of relapse to heavy drinking following treatment with the opioid antagonist naltrexone.To prospectively examine whether rs1799971 is predictive of naltrexone treatment response.We conducted a 12-week, double-blind, randomized clinical trial of naltrexone vs placebo in individuals with alcohol dependence (intent-to-treat analysis). Participants were randomly assigned to study treatment based on the presence of 1 or 2 copies of the Asp40 allele compared with those homozygous for the Asn40 allele (2 × 2 cell design). Recruitment occurred between January 2009 and September 2013. All participants were seen in an outpatient clinical setting. A convenience sample of participants (n = 221) was recruited from 5 sites. All participants met DSM-IV criteria for alcohol dependence, with no concurrent psychotic or manic symptoms, no use of concurrent psychotropic medications, and no current dependence on illicit substances.The study drug was naltrexone (50 mg) given once daily or corresponding placebo.The primary study outcome measure was relapse to heavy drinking measured using the timeline follow-back method.There was no evidence of a genotype × treatment interaction on the primary outcome of heavy drinking (P = .32). In the Asn40 group, the observed effect of naltrexone was similar to that in previous trials (odds ratio, 0.69; 95% CI, 0.41-1.18; P = .17), with a very small naltrexone effect in the Asp40 group (odds ratio, 1.10; 95% CI, 0.52-2.31; P = .80), contrary to the pattern expected a priori. A significant reduction in heavy drinking occurred across all groups (P = .001). Other drinking outcomes, and all secondary outcomes, demonstrated similar time effects, with no genotype × treatment interaction.The results of this study do not support the hypothesis that the Asp40 allele moderates the response to naltrexone treatment. It is premature to use the Asn40Asp polymorphism as a biomarker to predict the response to naltrexone treatment of alcohol dependence.clinicaltrials.gov Identifier: NCT00831272.
Can the Retinal Screening Interval Be Safely Increased to 2 Years for Type 2 Diabetic Patients Without Retinopathy?
Authors: Daniel Chalk, Martin Pitt, Bijay Vaidya, Ken Stein
Journal: Diabetes Care (2012)

In the U.K., people with diabetes are typically screened for retinopathy annually. However, diabetic retinopathy sometimes has a slow progression rate. We developed a simulation model to predict the likely impact of screening patients with type 2 diabetes, who have not been diagnosed with diabetic retinopathy, every 2 years rather than annually. We aimed to assess whether or not such a policy would increase the proportion of patients who developed retinopathy-mediated vision loss compared with the current policy, along with the potential cost savings that could be achieved.We developed a model that simulates the progression of retinopathy in type 2 diabetic patients, and the screening of these patients, to predict rates of retinopathy-mediated vision loss. We populated the model with data obtained from a National Health Service Foundation Trust. We generated comparative 15-year forecasts to assess the differences between the current and proposed screening policies. RESULTS The simulation model predicts that implementing a 2-year screening interval for type 2 diabetic patients without evidence of diabetic retinopathy does not increase their risk of vision loss. Furthermore, we predict that this policy could reduce screening costs by ~25%.Screening people with type 2 diabetes, who have not yet developed retinopathy, every 2 years, rather than annually, is a safe and cost-effective strategy. Our findings support those of other studies, and we therefore recommend a review of the current National Institute for Health and Clinical Excellence (NICE) guidelines for diabetic retinopathy screening implemented in the U.K.
Trak1 mutation disrupts GABAA receptor homeostasis in hypertonic mice
Authors: Sandra L Gilbert, Li Zhang, Michele L Forster, Tamaki Iwase, Betty Soliven, Leah Rae Donahue, Hope O Sweet, Roderick T Bronson, Muriel T Davisson, Robert L Wollmann, Bruce T Lahn
Journal: Nature Genetics (2005)