tbuckley/cabot-search huggingface dataset:
Unique genome-wide map of TCF4 and STAT3 targets using ChIP-seq reveals their association with new molecular subtypes of glioblastoma
Authors: Jun-Xia Zhang, Jing Zhang, Wei Yan, Ying-Yi Wang, Lei Han, Xiao Yue, Ning Liu, Yong-Ping You, Tao Jiang, Pei-Yu Pu, Chun-Sheng Kang
Journal: Neuro-Oncology (2013)

Aberrant activation of beta-catenin/TCF4 and STAT3 signaling in glioblastoma multiforme (GBM) has been reported. However, the molecular mechanisms related to this process are still poorly understood.Genome-wide screening of the binding characteristics of the transcription factors TCF4 and STAT3 in GBM cells was performed by chromatin immunoprecipitation sequencing (ChIP-seq) assay. Hierarchical clustering was used to analyze the association of TCF4 and STAT3 coregulated genes with The Cancer Genome Atlas (TCGA) GBM subtypes (classical, mesenchymal, neural, and proneural). New molecular classification of GBM was proposed and validated in Western and Asian populations.We identified 1250 overlapping putative target genes that were coregulated by TCF4 and STAT3. Further, the coregulated genes had the potential to guide TCGA GBM subtypes. Finally, we proposed a new molecular classification of GBM into 2 subtypes (proneural-like and mesenchymal-like) and showed that the new classification could be applied to both Western and Asian populations. In addition, the GBM response to temozolomide therapy differed depending on its subtype; mesenchymal-like GBM benefited, while there was no benefit for proneural-like GBM.This is the first comprehensive study to combine a ChIP-seq assay of TCF4 and STAT3 and data mining of patient cohorts to derive molecular subtypes of GBM.
ACIDOSIS AND SEBORRHOEA
Authors: J. T. Ingram, F. S. Fowweather
Journal: BMJ (1931)

While it is undoubtedly true that certain portions of the cerebral cortex seem to specialize in particular functions, the conception of brain centres.obtained from most textbooks of medicine is extremely misleading; and Broca's area, still'unhappily described as the speech centre, forms an example of the persistence of an antiquated ignorance of cerebral function.Speech probably involves many portions of the cortex and myriads of cells in all layers.Notwithstanding this, certain portions of brain cortex do have specialized functions, as is proved by the findings of cyto-architectonics.Brodman, Campbell, Marinesco, Betz, and many others, divide the cortex, from thC known arrangement of its cells, into as many as upwards of a hundred areas.It suffices to say, with von Economo, that there are at least five main structural types of cortical cell construction and lamination.Thus the area known generally as the Rolandic motor area is largely devoid of granule cells, which it does not need, because it is concerned with outgoing cerebral impulses.This comparative absence of granule cells enables us to recognize such portions of the cerebral cortex under the microscope with considerable facility, and von Economo calls t-hese -areas the agranular cortex.Areas, on the other hand, which are primarily concerned with the receipt of impulses -from the chief exteroceptive senses, such as sight, hearing, taste, and touch in all its forms, will be particularly rich in granule cells, thus forming easily recognizable cortical areas, termed granular cortex.With these exceptions, the rest of the cortex is mainly made up of slight, but recognizable, variants of the five or six cellular layers.Correlating these facts with clinical conditions the Viennese and other Continental schools find that mental disorder is rarely associated with area lesions, but shows a predilection for certain laminae in one or other of the five types of cortex.
Glycemic Control, Complications, and Death in Older Diabetic Patients
Authors: Elbert S. Huang, Jennifer Y. Liu, Howard H. Moffet, Priya M. John, Andrew J. Karter
Journal: Diabetes Care (2011)

To identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients.We conducted a retrospective cohort study (2004-2008) of 71,092 patients with type 2 diabetes, aged ≥60 years, enrolled in Kaiser Permanente Northern California. We specified Cox proportional hazards models to evaluate the relationships between baseline glycated hemoglobin (A1C) and subsequent outcomes (nonfatal complications [acute metabolic, microvascular, and cardiovascular events] and mortality).The cohort (aged 71.0 ± 7.4 years [means ± SD]) had a mean A1C of 7.0 ± 1.2%. The risk of any nonfatal complication rose monotonically for levels of A1C >6.0% (e.g., adjusted hazard ratio 1.09 [95% CI 1.02-1.16] for A1C 6.0-6.9% and 1.86 [1.63-2.13] for A1C ≥11.0%). Mortality had a U-shaped relationship with A1C. Compared with the risk with A1C <6.0%, mortality risk was lower for A1C levels between 6.0 and 9.0% (e.g., 0.83 [0.76-0.90] for A1C 7.0-7.9%) and higher at A1C ≥11.0% (1.31 [1.09-1.57]). Risk of any end point (complication or death) became significantly higher at A1C ≥8.0%. Patterns generally were consistent across age-groups (60-69, 70-79, and ≥80 years).Observed relationships between A1C and combined end points support setting a target of A1C <8.0% for older patients, with the caution that A1Cs <6.0% were associated with increased mortality risk. Additional research is needed to evaluate the low A1C-mortality relationship, as well as protocols for individualizing diabetes care.
Onconephrology
Authors: Abdulla K. Salahudeen, Joseph V. Bonventre
Journal: Journal of the American Society of Nephrology (2012)

Renal diseases in patients with cancer have many unique features, and often these diseases require specialized approaches. Newer cancer therapy has increased cancer cure rate and survival time, but such benefit is not fully realized, partly because of therapy-associated toxicities. Fluid and electrolyte abnormalities are very common in patients with cancer, as are acute and chronic kidney injury. With the evolving complexities of newer cancer therapies, a comprehensive team approach is becoming necessary. It is essential for nephrologists to be informed and involved in cancer care. Many nephrologists caring for patients with cancer in the United States have recently met and formed a focus group, the OncoNephrology Forum, under the American Society of Nephrology. This update addresses what is clinically unique about onconephrology, the objectives and functions of the newly formed forum, and the potential of onconephrology becoming a subspecialty in nephrology.
Increased peak flow variability in children with asymptomatic hyperresponsiveness
Authors: PG Gibson, S Mattoli, MR Sears, J Dolovich, FE Hargreave
Journal: European Respiratory Journal (1995)

The relevance of increased methacholine airway responsiveness detected in children with no current or past symptoms of asthma is not known. We wished to determine whether the presence of airway hyperresponsiveness in asymptomatic children is also associated with abnormal variability of peak expiratory flow (PEF). In 12 asymptomatic children with methacholine hyperresponsiveness, we examined the diurnal variation of peak expiratory flow (PEF) and response to inhaled bronchodilator. Twelve asthmatic children with a comparable range of methacholine hyperresponsiveness, and 12 normal children without methacholine responsiveness, were used as positive and negative controls. The children were aged 11 (range 9-14) yrs. The mean diurnal variation of PEF in those children with asymptomatic hyperresponsiveness was increased at 9.3%, to a degree comparable to the symptomatic asthmatic children (10.7%), and greater than the normal children (5.7%). Methacholine stimulated airway constriction was associated with symptoms in subjects from each group, indicating that the children were capable of perceiving airway constriction. We conclude that asymptomatic children with methacholine airway hyperresponsiveness have other evidence of mild variable airflow obstruction with increased diurnal PEF variability, and can perceive airflow limitation. The lack of symptoms in the children with airway hyperresponsiveness could be due to an insufficient stimulus to cause symptomatic obstruction, or the absence of eosinophilic airway inflammation, which may be a requirement for the development of symptomatic airway hyperresponsiveness.
Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees.
Authors: K Tamura, M Nei
Journal: Molecular Biology and Evolution (1993)

Examining the pattern of nucleotide substitution for the control region of mitochondrial DNA (mtDNA) in humans and chimpanzees, we developed a new mathematical method for estimating the number of transitional and transversional substitutions per site, as well as the total number of nucleotide substitutions. In this method, excess transitions, unequal nucleotide frequencies, and variation of substitution rate among different sites are all taken into account. Application of this method to human and chimpanzee data suggested that the transition/transversion ratio for the entire control region was approximately 15 and nearly the same for the two species. The 95% confidence interval of the age of the common ancestral mtDNA was estimated to be 80,000-480,000 years in humans and 0.57-2.72 Myr in common chimpanzees.
NO forms an adduct with serum albumin that has endothelium-derived relaxing factor-like properties.
Authors: J F Keaney, D I Simon, J S Stamler, O Jaraki, J Scharfstein, J A Vita, J Loscalzo
Journal: Journal of Clinical Investigation (1993)

Recent evidence suggests that sulfhydryl species can react with oxides of nitrogen under physiologic conditions and thereby stabilize endothelium-derived relaxing factor (EDRF) activity, but the presence of a specific in vivo thiol carrier for nitric oxide (NO) remains controversial. The single free sulfhydryl of serum albumin is the most abundant thiol species in plasma (approximately 0.5 mM) and is particularly reactive towards NO. To examine the potential role of serum albumin in endogenous nitric oxide metabolism, we synthesized S-nitroso-BSA (S-NO-BSA), a model S-nitroso-protein, and examined its effects on platelet function and coronary and systemic vascular tone in 16 mongrel dogs. Intravenous bolus S-NO-BSA markedly reduced mean arterial pressure in a dose-dependent manner and proved seven and a half-fold less potent than intravenous nitroglycerin and 10-fold less potent than intravenous S-nitroso-cysteine (half-maximal response of 75 nmol/kg compared to 10 and 7.5 nmol/kg, respectively; P < 0.05); when given by intravenous infusion (half-maximal response = 10 nmol/kg per min), however, S-NO-BSA and nitroglycerin were equipotent. Intravenous bolus S-NO-BSA had a greater duration of action than either nitroglycerin or S-nitroso-cysteine and produced marked prolongation of the template bleeding time associated with dose-dependent inhibition of ex vivo platelet aggregation (half-maximal response approximately 70 nmol/kg). Intracoronary S-NO-BSA increased coronary blood flow (mean +/- SEM) less effectively than nitroprusside, acetylcholine, or S-nitroso-cysteine (165% +/- 24% vs. 315% +/- 82%, 483% +/- 55%, or 475% +/- 66%, respectively; P < 0.05) although with much longer duration of action. On a molar basis, S-nitroso-cysteine proved more effective than S-nitroso-BSA, nitroprusside, or acetylcholine as an epicardial coronary vasodilator. Thus, serum albumin reacts with oxides of nitrogen to form a stable S-nitroso-thiol with properties reminiscent of authentic EDRF supporting the view that protein associated thiol may participate in the action and metabolism of EDRF.
T suppressor cell growth factor and anti-CD3 antibodies stimulate reciprocal subsets of T lymphocytes.
Authors: E J Fox, D E Lewis, K P Deemer, M N ElMasry, R R Rich
Journal: The Journal of Experimental Medicine (1987)

Because of the central role of IL-2 in clonal expansion of T cells, we have postulated that lymphocyte subpopulations with opposing regulatory functions might be independently regulated by differential requirements for expression of cell-surface IL-2-R. Purified CD4+ and CD8+ cells proliferated in an IL-2-dependent manner to crosslinked anti-T cell receptor antibodies (anti-CD3-Seph). Similarly, both CD4+ and CD8+ cells became IL-2 responsive after incubation in T suppressor cell growth factor (TsGF), a newly described approximately 8,000 Mr product of activated CD4+ cells. In support of our hypothesis, however, we observed that subpopulations of CD4+ and CD8+ cells, possessing distinct cell-surface antigens, showed differential responses to these stimuli. Those cells of suppressor-inducer or suppressor-effector phenotype failed to proliferate when cultured in anti-CD3-Seph plus IL-2, but did proliferate in an IL-2-dependent manner to TsGF. Furthermore, the suppressor-effector population was unresponsive to TsGF plus IL-2 when cocultured in anti-CD3-Seph, suggesting that functionally induced Ts may be refractory to growth stimuli. Conversely, cells with helper-inducer or cytolytic phenotype proliferated when incubated in anti-CD3-Seph and IL-2, while remaining essentially unresponsive to TsGF and IL-2. The results could not be explained by differences in the level of CD3 expression by the T cell subsets. Thus, cells within the helper and suppressor lineages appear to have distinct and reciprocal patterns for the induction of IL-2 responsiveness.
Changes in articular cartilage in experimentally induced patellar subluxation
Authors: J. Ryu, S. Saito, K. Yamamoto
Journal: Annals of the Rheumatic Diseases (1997)

Patellar subluxation was experimentally induced in young rabbits and the resulting cartilaginous changes were observed over a prolonged period of time to determine histological changes in the subluxated patellar cartilage.The tibial tuberosity in 12 week old rabbits was laterally displaced and fixed to the tibia with wire to induce lateral patellar subluxation. Pathological changes in patellar cartilage were examined for 120 weeks after surgery using computed tomography and stereoscopic microscopy.Eight weeks after surgery, changes in articular cartilage consisting of horizontal splitting of the matrix were observed in the intermediate zone and were presumed to have been caused by shearing stress applied to the patellar cartilage. The cartilaginous changes caused by patellar subluxation progressed very little over the 120 weeks. Very few rabbits presented with osteoarthritic changes in the patellofemoral joint, most probably because the stress resulting from the malalignment of the patellofemoral joint was mild enough to permit recovery.The mild, non-progressive pathological changes, in particular, basal degeneration, induced in this experiment in patellar cartilage were quite similar to the changes in articular cartilage seen in human chondromalacia patellae.
Inherited DNA mutations contributing to thrombotic complications in patients with Sickle cell disease
Authors: Sherri A. Zimmerman, Russell E. Ware
Journal: American Journal of Hematology (1998)

Thrombosis may play an important role in the pathophysiology of certain complications of sickle cell disease (SCD), including stroke and avascular necrosis (AVN). Currently there is no laboratory or clinical parameter that can identify patients who are at highest risk of developing these thrombotic complications. We hypothesized that some patients with SCD have an inherited hypercoagulable state that results in an increased risk of developing stroke or AVN. We examined the role of two common inherited thrombophilic mutations that, in other populations, have been associated with arterial and venous thrombosis and are amenable to screening with DNA restriction enzyme analysis. The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the C1565T mutation in the platelet glycoprotein IIIa (GPIIIa) gene were evaluated. We analyzed genomic DNA from 86 children and adults with SCD, including 16 patients with a history of a clinical stroke and 14 patients with AVN, for the presence of these mutations. The C677T MTHFR mutation was found in 19% of patients with stroke, 14% of patients with AVN, and 14% of patients with neither complication (P = NS). The C1565T GPIIIa mutation was found in 25% of patients with stroke, 14% of patients with AVN, and 18% of patients with neither complication (P = NS). Although each of these mutations is relatively common in patients with SCD, neither is independently associated with an increased risk of developing stroke or AVN. Am. J. Hematol. 59:267–272, 1998. © 1998 Wiley-Liss, Inc.
Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study
Authors: Pierre-Olivier Bridevaux, J-D Aubert, P M Soccal, J Mazza-Stalder, C Berutto, T Rochat, L Turin, S Van Belle, L Nicod, P Meylan, G Wagner, Laurent Kaiser
Journal: Thorax (2013)

<h3>Background</h3> The incidence and outcomes of respiratory viral infections in lung transplant recipients (LTR) are not well defined. The objective of this prospective study conducted from June 2008 to March 2011 was to characterise the incidence and outcomes of viral respiratory infections in LTR. <h3>Methods</h3> Patients were seen in three contexts: study-specific screenings covering all seasons; routine post-transplantation follow-up; and emergency visits. Nasopharyngeal specimens were collected systematically and bronchoalveolar lavage (BAL) was performed when clinically indicated. All specimens underwent testing with a wide panel of molecular assays targeting respiratory viruses. <h3>Results</h3> One hundred and twelve LTR had 903 encounters: 570 (63%) were screening visits, 124 (14%) were routine post-transplantation follow-up and 209 (23%) were emergency visits. Respiratory viruses were identified in 174 encounters, 34 of these via BAL. The incidence of infection was 0.83 per patient-year (95% CI 0.45 to 1.52). The viral infection rates upon screening, routine and emergency visits were 14%, 15% and 34%, respectively (p&lt;0.001). Picornavirus was identified most frequently in nasopharyngeal (85/140; 60.7%) and BAL specimens (20/34; 59%). Asymptomatic viral carriage, mainly of picornaviruses, was found at 10% of screening visits. Infections were associated with transient lung function loss and high calcineurin inhibitor blood levels. The hospitalisation rate was 50% (95% CI 30% to 70.9%) for influenza and parainfluenza and 16.9% (95% CI 11.2% to 23.9%) for other viruses. Acute rejection was not associated with viral infection (OR 0.4, 95% CI 0.1 to 1.3). <h3>Conclusions</h3> There is a high incidence of viral infection in LTR; asymptomatic carriage is rare. Viral infections contribute significantly to this population9s respiratory symptomatology. No temporal association was observed between infection and acute rejection.
Different CXCR4 Expression According to Various Histologic Subtype of Papillary Thyroid Carcinoma
Authors: Dong Yeob Shin, Kwang Joon Kim, Cheol Ryong Ku, Mi Kyung Lee, Soo Il Jee, Woong Youn Chung, Eun Jig Lee
Journal: Endocrine Pathology (2013)
In Vitro Immunomodulatory Effect Of ASHMI (Anti-asthma Herbal Medicine Intervention) On PBMCs From Asthmatics
Authors: S.P. Patil, W.J. Ji, A. Singha, D.E. Hendricks, P.J. Busse, H.A. Sampson, J.P. Wisnivesky, X. Li
Journal: Journal of Allergy and Clinical Immunology (2010)
Noneffect of Oral Urinary Copper Ascorbic Acid on Reduction Glucose Test
Authors: Milap C Nahata, Don C McLeod
Journal: Diabetes Care (1978)

References and texts in the fields of diabetes and clinical chemistry commonly report that ascorbic acid when given orally or parenterally gives a false-positive reaction to the copper reduction glucose test (Clinitest). This impression is based on a study in which ascorbic acid (250 mg./dl.) was added to urine in vitro, with a resultant positive-test reading in the absence of glucose. Ascorbic acid is a reducing agent, and theoretically it could interfere with the copper reduction method of glucose detection. In the current study 10 nondiabetic men were ingesting 4 and 6 gm. ascorbic acid per day. A total of 360 glucose detection tests with the copper reduction method were undertaken. In no instance was there a positive reaction to the glucose test.
Massive hepatic angiomyolipoma in a young woman with tuberous sclerosis complex: Significant clinical improvement during tamoxifen treatment
Authors: Ilaria Lenci, Mario Angelico, Giuseppe Tisone, Antonio Orlacchio, Giampiero Palmieri, Mariangela Pinci, Roberta Bombardieri, Paolo Curatolo
Journal: Journal of Hepatology (2008)

Background/AimsIsolated liver angiomyolipomas (AMLs) occur in about 40% of TSC patients. Because of their slow growth, these tumors are often asymptomatic. Since AMLs express estrogen and progesteron receptors we suggest the possible benefits of tamoxifen for the treatment of liver AMLs.MethodsWe report the case of a 26-year-old female affected by tuberous sclerosis (TSC2) with cerebral, renal and hepatic involvement admitted to the Liver Unit for severe malnutrition, anorexia and abdominal pain. MRI showed a grossly enlarged liver, causing severe gastric compression. The liver was entirely filled with multiple nodular lesions of different sizes. Liver biopsy showed tumoral tissue with microscopic and ultrastructural features of angiomyolipoma. All liver function tests were repeatedly normal. Prior to considering the patient for partial hepatectomy, she was administered tamoxifen (20 mg b.i.d).ResultsAfter 6 months of tamoxifen treatment a greatly improved quality of life and a significant weight gain were observed. After 12 months the clinical conditions further improved and the MRI showed a significant reduction of the largest lesion with a liquid central area and a diminished compression of the stomach.ConclusionsThis is to our knowledge the first report in which tamoxifen has been successfully used in a TSC patient with multiple liver angiomyolipomas. Isolated liver angiomyolipomas (AMLs) occur in about 40% of TSC patients. Because of their slow growth, these tumors are often asymptomatic. Since AMLs express estrogen and progesteron receptors we suggest the possible benefits of tamoxifen for the treatment of liver AMLs. We report the case of a 26-year-old female affected by tuberous sclerosis (TSC2) with cerebral, renal and hepatic involvement admitted to the Liver Unit for severe malnutrition, anorexia and abdominal pain. MRI showed a grossly enlarged liver, causing severe gastric compression. The liver was entirely filled with multiple nodular lesions of different sizes. Liver biopsy showed tumoral tissue with microscopic and ultrastructural features of angiomyolipoma. All liver function tests were repeatedly normal. Prior to considering the patient for partial hepatectomy, she was administered tamoxifen (20 mg b.i.d). After 6 months of tamoxifen treatment a greatly improved quality of life and a significant weight gain were observed. After 12 months the clinical conditions further improved and the MRI showed a significant reduction of the largest lesion with a liquid central area and a diminished compression of the stomach. This is to our knowledge the first report in which tamoxifen has been successfully used in a TSC patient with multiple liver angiomyolipomas.