tbuckley/cabot-search huggingface dataset:
Cellular Transformation and Activation of the Phosphoinositide-3-Kinase–Akt Cascade by the ETV6-NTRK3 Chimeric Tyrosine Kinase Requires c-Src
Authors: Wook Jin, Chohee Yun, Amy Hobbie, Matthew J. Martin, Poul H.B. Sorensen, Seong-Jin Kim
Journal: Cancer Research (2007)

Abstract The ETV6-NTRK3 (EN) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages, functions as a constitutively active protein-tyrosine kinase. ETV6-NTRK expression leads to the constitutive activation of two major effector pathways of wild-type NTRK3, namely, the Ras–mitogen-activated protein kinase (MAPK) mitogenic pathway and the phosphoinositide-3-kinase (PI3K)-Akt pathway mediating cell survival, and both are required for EN transformation. However, it remains unclear how ETV6-NTRK3 activates Ras-Erk1/2 and/or PI3K-Akt cascades. Here, we define some aspects of the molecular mechanisms regulating ETV6-NTRK–dependent Ras-Erk1/2 and PI3K-Akt activation. We show that ETV6-NTRK3 associates with c-Src, and that treatment with SU6656, a c-Src inhibitor, completely blocks ETV6-NTRK-transforming activity. Treatment of NIH3T3 cells expressing ETV6-NTRK3 with SU6656 attenuated the activation of Ras-Erk1/2 and PI3K-Akt. Suppression of c-Src by RNA interference in NIH3T3-ETV6-NTRK3 cells resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. However, in Src-deficient cells, the ETV6-NTRK3 failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. Therefore, these data indicate that ETV6-NTRK3 induces the PI3K-Akt cascade through the activation of c-Src. [Cancer Res 2007;67(7):3192–200]
Comparative study of pancreatic polypeptide (PP) secretion, endocrine and exocrine function, and structural damage in chronic alcohol induced pancreatitis (CAIP).
Authors: A S Mee, L J Klaff, A H Girdwood, M Paul, M Tyler, I N Marks
Journal: Gut (1983)

The serum pancreatic polypeptide response to intravenous Boots secretin (1.5 U/kg), glucose tolerance, and insulin responses have been studied in 25 patients with chronic alcohol induced pancreatitis of varying severity, and these results compared with a secretin-pancreozymin test, and the structural damage noted on pancreatography. For the pancreatic polypeptide response 16 healthy subjects acted as controls. There was a marked reduction in pancreatic polypeptide response in patients with advanced structural changes of chronic alcohol induced pancreatitis compared with patients with minimal/moderate changes (p less than 0.01) and with healthy controls (p less than 0.05) although there was no difference between the latter two groups. Similarly, while the ratio of peak to mean basal pancreatic polypeptide concentration was also significantly reduced in patients with advanced changes compared with healthy controls (p less than 0.05) there was a marked degree of overlap in patients with lesser degrees of structural damage and control subjects. For all patients with chronic alcohol induced pancreatitis, however, there was a significant correlation between the pancreatic polypeptide response and each parameter of the standard secretin-pancreozymin test and with glucose tolerance and the integrated insulin response. We conclude therefore that while the secretin stimulated pancreatic polypeptide response correlates significantly with accepted tests of pancreatic structure and function, there is a significant degree of overlap in the response obtained in patients who have minimal/moderate damage and healthy controls making the test insufficiently sensitive for routine diagnostic use.
Role of somatostatin and its analogues in the treatment of acute and chronic pancreatitis.
Authors: M W Buchler, M Binder, H Friess
Journal: Gut (1994)

Acute pancreatitis is caused by the activation of digestive enzymes in the pancreas and a possible treatment, therefore, is the inhibition of enzyme secretion. This approach is somewhat controversial, however, as it is not clear whether pancreatic secretion continues to occur during the course of acute pancreatitis. Animal studies show an appreciable reduction of secretion in the inflamed pancreas, but studies in humans are not conclusive. The use of somatostatin or its analogue, octreotide, has been investigated in several clinical studies. A meta analysis of six individual studies in which somatostatin was given for acute pancreatitis showed that somatostatin significantly reduces mortality. A trial in patients with moderate to severe acute pancreatitis showed a lower rate (although not statistically significant) of complications in patients treated with 3 x 200 and 3 x 500 micrograms/day octreotide, compared with controls and patients receiving a lower dose of octreotide. A further study showed a significant reduction in patient controlled analgesics in patients treated with octreotide compared with controls. Pain is the important clinical symptom of chronic pancreatitis, possibly resulting from an increased intraductal pressure during secretion. The effect on pain of the inhibition of pancreatic secretion by octreotide has been investigated in two studies. One showed no significant reduction in pain after treatment with octreotide for three days. In the other, in which octreotide was used for three weeks, significantly less pain and analgesic use was recorded during octreotide treatment than during placebo. The most common complication of chronic pancreatitis is the formation of pseudocysts. There is some evidence that octreotide may be useful in their treatment.
GROWTH RETARDATION IN SICKLE-CELL DISEASE TREATED BY NUTRITIONAL SUPPORT
Authors: MelvinB. Heyman, Richard Katz, Deborah Hurst, Danny Chiu, ArthurJ. Ammann, Elliott Vichinsky, Barbara Gaffield, Ricardo Castillo, Klara Kleman, M.Michael Thaler, Bertram Lubin
Journal: The Lancet (1985)
Regulated protein aggregation: stress granules and neurodegeneration
Authors: Benjamin Wolozin
Journal: Molecular Neurodegeneration (2012)

The protein aggregation that occurs in neurodegenerative diseases is classically thought to occur as an undesirable, nonfunctional byproduct of protein misfolding. This model contrasts with the biology of RNA binding proteins, many of which are linked to neurodegenerative diseases. RNA binding proteins use protein aggregation as part of a normal regulated, physiological mechanism controlling protein synthesis. The process of regulated protein aggregation is most evident in formation of stress granules. Stress granules assemble when RNA binding proteins aggregate through their glycine rich domains. Stress granules function to sequester, silence and/or degrade RNA transcripts as part of a mechanism that adapts patterns of local RNA translation to facilitate the stress response. Aggregation of RNA binding proteins is reversible and is tightly regulated through pathways, such as phosphorylation of elongation initiation factor 2α. Microtubule associated protein tau also appears to regulate stress granule formation. Conversely, stress granule formation stimulates pathological changes associated with tau. In this review, I propose that the aggregation of many pathological, intracellular proteins, including TDP-43, FUS or tau, proceeds through the stress granule pathway. Mutations in genes coding for stress granule associated proteins or prolonged physiological stress, lead to enhanced stress granule formation, which accelerates the pathophysiology of protein aggregation in neurodegenerative diseases. Over-active stress granule formation could act to sequester functional RNA binding proteins and/or interfere with mRNA transport and translation, each of which might potentiate neurodegeneration. The reversibility of the stress granule pathway also offers novel opportunities to stimulate endogenous biochemical pathways to disaggregate these pathological stress granules, and perhaps delay the progression of disease.
Doxorubicin, vinblastine, and gemcitabine (CALGB 50203) for stage I/II nonbulky Hodgkin lymphoma: pretreatment prognostic factors and interim PET
Authors: David J. Straus, Jeffrey L. Johnson, Ann S. LaCasce, Nancy L. Bartlett, Lale Kostakoglu, Eric D. Hsi, Heiko Schöder, Nathan C. Hall, Sin-Ho Jung, George P. Canellos, Lawrence H. Schwartz, Ronald W. Takvorian, Malik E. Juweid, Bruce D. Cheson
Journal: Blood (2011)
ISOLATION OF B. TYPHOSUS FROM SEWAGE AND SHELLFISH
Authors: W. J. Wilson
Journal: BMJ (1928)

Surntinari.Three cases of frontal lobe tumLiour are described, in two of which the growths were bilateral.The onily observ-ed clinical signs which were common to all three cases were miiental changes and tremor.In two cases severe generalized convulsive attacks conistituted the first definite symptom.Attenttion is drawn to a peculiar exaggeration of the plantar reflexes encountered in two of the cases.
Carbolic Saturation in the Treatment of Certain Types of Streptococcal Blood Infection
Authors: T. S. Wilson
Journal: BMJ (1927)

CARBOLIC-SATUIRATION IN STREPTOCOCCAL INFECTION.rSD O=57-I~~~~~~~~~~~~~~~t wenty-five years.I have found that tuberculin has been able to produce just the effect-that Aschoff speakt of as being so desiirable.Children up to the age of 10 or 12 years respond readily to tuberculin, and even those
Acceptance of and Discontinuation Rate from Erectile Dysfunction Oral Treatment in Patients following Bilateral Nerve-Sparing Radical Prostatectomy
Authors: Andrea Salonia, Andrea Gallina, Giuseppe Zanni, Alberto Briganti, Federico Dehò, Antonino Saccà, Nazareno Suardi, Luigi Barbieri, Giorgio Guazzoni, Patrizio Rigatti, Francesco Montorsi
Journal: European Urology (2007)
Histopathology of Tumor Regression After Intralesional Injection of &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt;. II. Comparative Effects of Vaccinia Virus, Oxazolone, and Turpentine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. G. Hanna, Jr., B. Zbar, H. J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1972)

Treatment of transplanted syngeneic tumors in guinea pigs with a single sensitization by vaccinia virus, oxazolone, or turpentine was compared to therapy with Mycobacterium bovis strain bacillus Calmette-Guérin (BCG). Hepatocarcinoma cells, transplanted intradermally, had become established tumors with regional lymph node metastases before treatment. Except for topical painting of oxazolone, all other treatments were administered by intralesional injections. The established syngeneic tumor regressed in the skin site after a single injection of live BCG, and regional lymph node metastases were eliminated. The effective antitumor mechanism in the BCG-treated animals was a granulomatous reaction, both at the skin site and in the regional lymph node, characterized by an intense proliferation of stromal reticuloendothelial components and histiocytes. Cellular reactions in the regional lymph nodes draining tumors treated with vaccinia virus or oxazolone, which were characteristic of the development of delayed-type hypersensitivity, were not detrimental to the tumor and did not alter metastatic growth. The turpentine-induced inflammatory reaction at the tumor site was also ineffective in suppressing tumor growth. Both turpentine and oxazolone treatments, on the other hand, enhanced tumor growth in the skin.
Human Epidermal Growth Factor Receptor 2 Testing: Where Are We?
Authors: Pradip De, Brian R. Smith, Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2010)

In this issue of Journal of Clinical Oncology, Baehner et al have reported from a Kaiser Permanente case-control study that there is a high degree of concordance (97%) between quantitative reverse transcription polymerase chain reaction (qRT-PCR) and central laboratory fluorescent in situ hybridization (FISH) assessment of HER2 status. This provides us the opportunity to examine the status of human epidermal growth factor receptor 2 (HER2) testing today. For the most part, cancer is a genetic disease, and successful treatment of breast cancer is particularly dependent on a number of complex factors, including detection of the tumor early in the course of development, accurate assessment of the right biomarker, and the biology of the underlying disease. Amplification and overexpression of the HER2/ERBB2 oncogenes are observed in 15% to 25% of invasive breast cancers. HER2-positive tumors define a clinically important breast cancer subgroup that is generally associated with poor prognosis and variable response to conventional systemic cytotoxic therapy. HER2 testing is routinely performed in patients with a new diagnosis of invasive breast cancer. Accurate testing to identify HER2 status for patients with breast cancer who can benefit from anti-HER2 treatment (eg, trastuzumab, lapatinib) is a clinical and economic necessity (Fig 1). As a consequence, issues relating to accurate and reliable laboratory assessment of HER2 status in patients with breast cancer are a matter of significant concern to patients, pathologists, and oncologists.
B lymphocytes may escape tolerance by revising their antigen receptors.
Authors: M Z Radic, J Erikson, S Litwin, M Weigert
Journal: The Journal of Experimental Medicine (1993)

To explore mechanisms that prevent autoreactivity in nonautoimmune mice, endogenous immunoglobulin (Ig) light (L) chains that associate with a transgenic anti-DNA heavy chain were analyzed. The antibodies from splenic B cell hybridomas of such mice did not bind double-stranded DNA (dsDNA) and their L chain sequences showed a biased use of V kappa and J kappa gene segments. The 44 L chains in this survey were coded for by just 18 germline genes. Six of the genes, each belonging to a different V kappa group, were used more than once and accounted for three fourths of all sequences. Based on the distribution of V kappa genes, the L chain repertoire in this line of transgenic mice was estimated at 37 V kappa genes. The most frequently observed gene, a member of the V kappa 12/13 group, was identified in 16 hybrids. In addition, the majority of V kappa genes used J kappa 5. We interpret the skewed representation of V kappa and J kappa gene segments to result from negative selection. Based on the data, we suggest that V kappa rearrangements giving rise to anti-dsDNA reactivity are removed from the repertoire by a corrective mechanism capable of editing self-reactive Ig.
Split Renal Function Outcome after Renal Angioplasty in Patients with Unilateral Renal Artery Stenosis
Authors: AGNE[Combining Grave Accent]S LA BATIDE-ALANORE, MICHEL AZIZI, MARC FROISSART, ALAIN RAYNAUD, PIERRE-FRANC[COMBINING CEDILLA]OIS PLOUIN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The general use of bilateral rather than separate renal function evaluation has led to the publication of conflicting results concerning the effect of percutaneous transluminal renal angioplasty (PTRA) on renal function, especially in patients with atherosclerotic renal artery stenosis. The aim of this study was to evaluate prospectively, in standardized conditions, split renal function (SRF) and GFR outcome after successful PTRA, by measuring single kidney GFR with synchronous inulin or 51Cr-ethylenediaminetetraacetic acid clearance and 99mTc-diethylenetriamine pentaacetic acid scintigraphy, in a well-defined population of patients with unilateral renal artery stenosis. Thirty-two consecutive hypertensive patients (18 with atherosclerotic and 14 with dysplastic disease) with significant unilateral stenosis of the main native renal artery (≥60%) and normal renal function were included in the study. Renal and angiographic follow-up evaluations were performed 6 mo after PTRA. PTRA alone or combined with stenting (n = 2) was technically successful in all patients. Repeat PTRA was necessary in two patients, evaluated 6 mo after the second PTRA. Six mo after PTRA, total GFR had increased slightly but significantly in the 29 patients with positive lateralization indices. SRF and single-kidney GFR of the stenotic kidney increased significantly, whereas concurrently the GFR and SRF of the nonstenotic kidney decreased significantly. Six mo after successful PTRA reducing renal ischemia, a reversal of both the hypoperfusion of the stenotic side and the hyperperfusion of the nonstenotic side was observed, which was accompanied by a slight increase in total GFR.
Asporin repeat polymorphism in rheumatoid arthritis
Authors: B Torres, G Orozco, J R Garcia-Lozano, J Oliver, O Fernandez, M A Gonzalez-Gay, A Balsa, A Garcia, D Pascual-Salcedo, M A Lopez-Nevot, A Nunez-Roldan, J Martin, M F Gonzalez-Escribano
Journal: Annals of the Rheumatic Diseases (2006)

Asporin belongs to a family of proteins associated with the cartilage matrix.To investigate the role of the functional polymorphism consisting of an aspartic acid (D) repeat polymorphism located in the ASPN gene in the susceptibility to and clinical outcome of rheumatoid arthritis.A total of 803 Spanish Caucasian patients with rheumatoid arthritis and 904 controls of the same ethnic origin and matched for age and sex were included in the study. The asporin D repeat polymorphism was genotyped using polymerase chain reaction with a fluorescent primer.No significant differences were detected in the distribution of the 10 alleles found in our population on comparing patients with rheumatoid arthritis with control groups. Nevertheless, individuals bearing D14 produced rheumatoid factor more often than the rest (85.7% v 72.1%, p = 0.006, odds ratio (OR) = 2.35, 95% confidence interval 1.21 to 4.50), and the mean (SD) onset age was higher in the group of individuals bearing D13 (50.09 (13.94)) compared with the rest (47.21 (14.31)), although the difference did not reach significance (p = 0.06).The results do not support a major role for asporin D repeat polymorphism in the susceptibility to rheumatoid arthritis. Nevertheless, they support the influence of this gene on the outcome of the disease.
Structural Brain MRI Abnormalities in Healthy Siblings of Patients With Childhood-Onset Schizophrenia
Authors: Nitin Gogtay, Alexandra Sporn, Liv S Clasen, Deanna Greenstein, Jay N Giedd, Marge Lenane, Peter A Gochman, Alex Zijdenbos, Judith L Rapoport
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Childhood-onset schizophrenia shows progressive brain magnetic resonance imaging (MRI) changes during adolescence, which follow a back-to-front "wave." The authors' goal was to examine whether healthy siblings of patients with childhood-onset schizophrenia show structural brain abnormalities and the age-related pattern of abnormalities seen in patients with childhood-onset schizophrenia. METHOD: Anatomic brain MRI scans were obtained from 15 psychiatrically healthy full siblings of 15 patients with childhood-onset schizophrenia and from 32 matched community volunteers. Automated measures were used to compare total and regional brain volumes of the siblings and volunteers. RESULTS: Siblings of patients with childhood-onset schizophrenia had smaller total cerebral volume and total, frontal, and parietal gray matter volumes than volunteers. When divided into younger and older groups, younger siblings had smaller parietal gray matter volumes and older siblings showed trends for smaller total and frontal gray matter volumes. CONCLUSIONS: Healthy siblings of patients with childhood-onset schizophrenia share brain MRI abnormalities with the patients that may follow a similar pattern of progression. Developmental brain abnormalities in childhood-onset schizophrenia may thus be genetic trait markers.
The Pim kinases control rapamycin-resistant T cell survival and activation
Authors: Casey J. Fox, Peter S. Hammerman, Craig B. Thompson
Journal: The Journal of Experimental Medicine (2005)

Although Pim-1 or Pim-2 can contribute to lymphoid transformation when overexpressed, the physiologic role of these kinases in the immune response is uncertain. We now report that T cells from Pim-1−/−Pim-2−/− animals display an unexpected sensitivity to the immunosuppressant rapamycin. Cytokine-induced Pim-1 and Pim-2 promote the rapamycin-resistant survival of lymphocytes. The endogenous function of the Pim kinases was not restricted to the regulation of cell survival. Like the rapamycin target TOR, the Pim kinases also contribute to the regulation of lymphocyte growth and proliferation. Although rapamycin has a minimal effect on wild-type T cell expansion in vitro and in vivo, it completely suppresses the response of Pim-1−/−Pim-2−/− cells. Thus, endogenous levels of the Pim kinases are required for T cells to mount an immune response in the presence of rapamycin. The existence of a rapamycin-insensitive pathway that regulates T cell growth and survival has important implications for understanding how rapamycin functions as an immunomodulatory drug and for the development of complementary immunotherapeutics.
An 8-Year Follow-up on the Effect of Subthalamic Nucleus Deep Brain Stimulation on Pain in Parkinson Disease
Authors: Yu Jin Jung, Han-Joon Kim, Beom S. Jeon, Hyeyoung Park, Woong-Woo Lee, Sun Ha Paek
Journal: JAMA Neurology (2015)

Pain is a common and distressing feature in Parkinson disease (PD). The major indication of subthalamic nucleus deep brain stimulation (STN DBS) is motor complications in advanced PD; however, pain reduction after STN DBS has been noted.To evaluate the long-term effect of STN DBS on pain in PD.Twenty-four patients who underwent STN DBS at the Movement Disorder Center at Seoul National University Hospital from June 1, 2005, through March 31, 2006, were studied. The assessments of pain were performed preoperatively and 8 years after surgery. Because 13 of the total 24 patients had additional 2-year postoperative data, the serial change between the preoperative and the 2- and 8-year follow-ups after surgery was also evaluated.Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr staging scale. The severity of pain was scored according to an ordinal scale ranging from 0 (absent) to 10 (maximal pain) in 7 parts of the body (head, neck, trunk, and the upper and lower extremities on each side of the body). For each body part, the quality of pain was grouped into 1 of 4 categories: dystonic, musculoskeletal, radiculoneuritic, and central.Sixteen of the 24 patients (67%) experienced pain at baseline when not taking medication (off-state). All off-state pain at baseline improved or disappeared at 8 years after surgery. The number of body parts with pain was 21 at baseline and decreased to 11 at 8 years after the surgery. The mean (SD) and median scores of the off-state pain were 6.2 (2.5) and 7.0 at baseline and improved to 3.5 (2.2) and 2.5 at 8 years after the surgery, respectively. However, new pain developed in 18 of 24 patients (75%) during the 8-year follow-up period. The number of body parts with newly developed pain was 47, and the mean (SD) and median scores for new pain were 4.4 (3.0) and 3.0, respectively. The types of new pain at 8 years were musculoskeletal in 11 patients, central in 4 patients, radiculoneuritic in 3 patients, and dystonic in 1 patient.Pain associated with PD is improved by STN DBS, and the beneficial effect persists after a long-term follow-up of 8 years. In addition, new pain, especially the musculoskeletal type, developed in most patients, becoming a long-term distressing problem.