tbuckley/cabot-search huggingface dataset:
Rosai-Dorfman disease: Presentation of a clinical case
Authors: Rubén Garrido, Elisa Barrera, Elías Abbud, Karla Cabada
Journal: European Respiratory Journal (2012)

Introduction: Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative process, infrequent and idiopathic, benign with painless cervical or systemic linfandenopathy, fever, leukocytosis, polyclonal hypergammaglobulinemia and accelerated erythrocyte sedimentation. In a low percentage, there are extranodal manifestations. The histological diagnosis consists of filling of sinusoids in ganglia with linfocytes, plasmatic cells and histiocytes positive for S100, CD68, absence of CD1a and emperipolesis.

Case report: 49-year-old female patient, who was a heavy smoker is presented with severe dyspnoea, three months evolution and chest oppression sensation, with edema of face, neck and arms. The erythro sedimentation was accelerated (90 mm/hr). Chest x-rays showed mediastinum widening and tumor in the pulmonary right hilum. The computerized tomography showed right hilum hyperdensity of 7 cm. The bronchoscopy with biopsy showed right bronchi infiltrate with tumoral aspect. The hysthopathological findings revealed hysthiocyte proliferation and others with eosinophilic cythoplasma with fibrosis and lymphoid cells. Emperipolesis and plasmatic cells where identified, with Russel bodies. With the diagnosis 120 mg a day of 'attack dose' was initiated, continuing with 40 mg/day during 6 months with favorable response reducing the size of the lesion.

Discussion: In this case, the manifestation of the disease was dyspnoea produced by the bronqueal obstruction and compression of the superior vena cava due to the hilum infiltrative histiocytic mass, so our initial probable diagnosis was a bronchogenic cancer. This extranodal manifestation is infrequent, but it is to be taken into account as part of the pulmonary and mediastinal pathology.
Superior Temporal Gyrus Volume Abnormalities and Thought Disorder in Left-Handed Schizophrenic Men
Authors: Dorothy P. Holinger, Martha E. Shenton, Cynthia G. Wible, Robert Donnino, Ron Kikinis, Ferenc A. Jolesz, Robert W. McCarley
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. METHOD: Left-handed male patients (N=8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N=10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. RESULTS: There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. CONCLUSIONS: These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance.
STUDIES ON X-RAY EFFECTS
Authors: Robert T. Hance, Harry Clark
Journal: The Journal of Experimental Medicine (1926)

Two races of paramecium were submitted for varying lengths of time to x-radiation and a large number of individuals were observed to determine the effect on the rate of division. The division rate of both races suffered a slight initial depression lasting for 2 to 5 days following the exposure. This depression is followed by complete recovery. Within rather wide limits the length of the exposure has, in these experiments, made no appreciable difference. Apparently the maximum effect of the x-rays is produced by relatively short exposures. Continued radiation produces little further change until exposures of 3 and 4 hours are used, when precisely the opposite results are obtained from those obtained with shorter exposures. Doses repeated at various intervals have in general failed to interfere more markedly with the division rate than a single dose. Repeated radiation causes the cells to become slightly swollen without apparent interference with their viability.
The Role of ThPOK in Control of CD4/CD8 Lineage Commitment
Authors: Xi He, Kyewon Park, Dietmar J. Kappes
Journal: Annual Review of Immunology (2010)

During αβ T cell development, cells diverge into alternate CD4 helper and CD8 + cytotoxic T cell lineages. The precise correlation between a T cell's CD8 and CD4 choice and its TCR specificity to class I or class II MHC was noted more than 20 years ago, and establishing the underlying mechanism has remained a focus of intense study since then. This review deals with three formerly discrete topics that are gradually becoming interconnected: the role of TCR signaling in lineage commitment, the regulation of expression of the CD4 and CD8 genes, and transcriptional regulation of lineage commitment. It is widely accepted that TCR signaling exerts a decisive influence on lineage choice, although the underlying mechanism remains intensely debated. Current evidence suggests that both duration and intensity of TCR signaling may control lineage choice, as proposed by the kinetic signaling and quantitative instructive models, respectively. Alternate expression of the CD4 and CD8 genes is the most visible manifestation of lineage choice, and much progress has been made in defining the responsible cis elements and transcription factors. Finally, important clues to the molecular basis of lineage commitment have been provided by the recent identification of the transcription factor ThPOK as a key regulator of lineage choice. ThPOK is selectively expressed in class II–restricted cells at the CD4 + 8 lo stage and is necessary and sufficient for development to the CD4 lineage. Given the central role of ThPOK in lineage commitment, understanding its upstream regulation and downstream gene targets is expected to reveal further important aspects of the molecular machinery underlying lineage commitment.
Late mortality and morbidity of patients with Hodgkin lymphoma treated in adulthood
Authors: M. J. Matasar, L. N. McCallen, E. R. Riedel, J. S. Ford, K. C. Oeffinger, D. J. Straus
Journal: Journal of Clinical Oncology (2009)

8547 Background: Increased late mortality and morbidity have been observed among adult survivors of Hodgkin lymphoma (HL) treated in childhood, but are less well characterized for patients treated in adulthood. Methods: We investigated the late mortality and morbidity of adult patients treated at our center from 1975 to 2000. The study population consisted of all patients treated on one of 6 consecutive first-line trials of combined modality therapy (CMT), one of which included a chemotherapy-only arm. Cause-specific mortality was determined by chart review and National Death Index. Survival was estimated using the method of Kaplan-Meier, and cause-specific mortality using competing risk methodology. Self-report surveys were distributed to surviving patients to assess the prevalence of late morbidity; severity of morbidity was scored based on a published adaptation of the Common Terminology Criteria for Adverse Events. Results: 746 patients were eligible for assessment. At time of survey, 227 patients (30.4%) had died: 107 deaths from HL, 100 from causes other than HL, and 20 from unknown cause ( Table 1 ). 20-year OS for the cohort was 71%. Cumulative risk of death due to HL is surpassed by causes other than HL by 22 years post-treatment. Among the 521 survivors, survey data were available for 233 (44.7%), with a median follow-up of 21.6y. Late morbidity was common: 94% reported any morbidity, 48% reported at least one severe (grade 3/4) late morbidity and 22% reported two or more severe late morbidities. The most prevalent severe morbidities included second primary malignancy (SPM) (17%), cardiovascular (CV) (18%) and neurologic (18%) disease. Conclusions: Among adults treated on trials of CMT, by 22y post-treatment the risk of death due to HL is surpassed by risk of death due to other causes. Survivors of HL treated during adulthood experience substantial late morbidity. These findings underscore the importance of efforts directed at prevention of and early intervention for late morbidity in adult survivors of HL. [Table: see text] No significant financial relationships to disclose.
Localization of the cystic fibrosis transmembrane conductance regulator in pancreas.
Authors: C R Marino, L M Matovcik, F S Gorelick, J A Cohn
Journal: Journal of Clinical Investigation (1991)

Cystic fibrosis (CF) is characterized by an abnormality in cAMP-regulated chloride transport that results from a primary defect in the protein product of the CF gene, the CF transmembrane conductance regulator (CFTR). In this report, antibodies against CFTR peptides were used to localize the CFTR protein in human pancreas. An affinity purified antibody (alpha-1468) raised against a synthetic CFTR peptide identified a 155-170-kD protein on immunoblot. Cytochemical studies with alpha-1468 localized CFTR to small branching, tubular structures. The same structures were recognized by two other antibodies raised against different regions of the CFTR molecule. To identify the cells being stained, double-label immunofluorescence studies were performed using alpha-1468 and a monoclonal antibody which stains pancreatic centroacinar and intralobular duct cells. Both antibodies localized to the same population of cells, with alpha-1468 being confined to the apical domain of these cells. No conclusive staining of acinar cells was evident. These findings suggest that proximal duct epithelial cells play a key role in the early events leading to pancreatic insufficiency in CF, and imply that apical chloride transport by these cells is essential for normal pancreatic secretory function.
High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer
Authors: Maureen E. Mork, Y. Nancy You, Jun Ying, Sarah A. Bannon, Patrick M. Lynch, Miguel A. Rodriguez-Bigas, Eduardo Vilar
Journal: Journal of Clinical Oncology (2015)

Established guidelines recommend evaluation for hereditary cancer syndromes in patients younger than 50 years diagnosed with colorectal cancer (CRC). This group has been well described in the literature; however, patients diagnosed as adolescents and young adults are not well represented in CRC studies. Here, we define the clinical profile, including the extent of hereditary cancer syndromes and family history of cancer, in patients diagnosed with CRC at age 35 or younger.We reviewed patients who underwent genetic counseling at our institution during 5 years (2009 to 2013). Data were collected regarding demographics, clinicopathologic information, tumor and genetic testing, and family history. Patients with an identified hereditary cancer syndrome were compared with those without a syndrome.Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease.We conclude that patients diagnosed with CRC at age 35 years or younger should receive genetic counseling regardless of their family history and phenotype.
Predictors of Survival After Radiofrequency Thermal Ablation of Colorectal Cancer Metastases to the Liver: A Prospective Study
Authors: Eren Berber, Robert Pelley, Allan E. Siperstein
Journal: Journal of Clinical Oncology (2005)

The aim of this study was to determine the predictors of survival at the time of radiofrequency thermal ablation (RFA) in patients with colorectal liver metastasis.One hundred thirty-five patients with colorectal liver metastases who were not candidates for resection underwent laparoscopic RFA.The median Kaplan-Meier survival for all patients was 28.9 months after RFA treatment. Patients with a carcinoembryonic antigen (CEA) less than 200 ng/mL had improved survival compared with those with a CEA more than 200 (34 v 16 months; P = .01). Patients with the dominant lesion less than 3 cm in diameter had a median survival of 38 v 34 months for lesions 3 to 5 cm, and 21 months for lesions greater than 5 cm (P = .03). Survival approached significance for patients with one to three tumors versus more than three tumors (29 v 22 months; P = .09). The presence of extrahepatic disease did not affect survival. Only the largest liver tumor size more than 5 cm was found to be a significant predictor of mortality by Cox proportional hazards model, with a 2.5-fold increased risk of death versus the largest liver tumor size less than 3 cm (P = .05).This study determines which patients do best after RFA. Historical survival with chemotherapy alone is 11 to 14 months, suggesting RFA has a positive impact on overall survival. Limited amounts of extrahepatic disease do not appear to affect survival adversely. RFA is a useful adjunct to chemotherapy in those patients with liver-predominant disease.
Activation of Ribosomal RNA Transcription by Hepatitis C Virus Involves Upstream Binding Factor Phosphorylation via Induction of Cyclin D1
Authors: Santanu Raychaudhuri, Vanessa Fontanes, Bhaswati Barat, Asim Dasgupta
Journal: Cancer Research (2009)

Abstract Hepatitis C virus (HCV) causes chronic infection in humans leading to liver cirrhosis and hepatocellular carcinoma. rRNA transcription, catalyzed by RNA polymerase I (Pol I), plays a critical role in ribosome biogenesis, and changes in Pol I transcription rate are associated with profound alterations in the growth rate of the cell. Because rRNA synthesis is intimately linked to cell growth and frequently up-regulated in many cancers, we hypothesized that HCV might have the ability to activate rRNA synthesis in infected cells. We show here that rRNA promoter–mediated transcription is significantly (10- to 12-fold) activated in human liver–derived cells following infection with type 2 JFH-1 HCV or transfection with the subgenomic type 1 HCV replicon. Further analysis revealed that HCV nonstructural protein 5A (NS5A) was responsible for activation of rRNA transcription. Both the NH2-terminal amphipathic helix and the polyproline motifs of NS5A seem to be essential for rRNA transcription activation. The NS5A-dependent activation of rRNA transcription seems to be due to hyperphosphorylation and consequent activation of upstream binding factor (UBF), a Pol I DNA binding transcription factor. We further show that hyperphosphorylation of UBF occurs as a result of up-regulation of both cyclin D1 and cyclin-dependent kinase 4 by the HCV NS5A polypeptide. These results suggest that the endoplasmic reticulum–associated NS5A is able to transduce signals into the nucleoplasm via UBF hyperphosphorylation leading to rRNA transcription activation. These results could, at least in part, explain a mechanism by which HCV contributes to transformation of liver cells. [Cancer Res 2009;69(5):2057–64]
Combining the Endoplasmic Reticulum Stress–Inducing Agents Bortezomib and Fenretinide as a Novel Therapeutic Strategy for Metastatic Melanoma
Authors: David S. Hill, Shaun Martin, Jane L. Armstrong, Ross Flockhart, Joge J. Tonison, Dominic G. Simpson, Mark A. Birch-Machin, Christopher P.F. Redfern, Penny E. Lovat
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Single-agent chemotherapy is largely the treatment of choice for systemic therapy of metastatic melanoma, but survival rates are low, and novel adjuvant and systemic therapies are urgently required. Endoplasmic reticulum (ER) stress is a potential therapeutic target, and two relatively new drugs, fenretinide and bortezomib (Velcade), each acting via different cellular mechanisms, induce ER stress leading to apoptosis in melanoma cells. The aim of this study was to test the hypothesis that apoptosis of melanoma cells may be increased by combining clinically achievable concentrations of fenretinide and bortezomib. Experimental Design: Three human melanoma cell lines were used to assess changes in viability and the induction of apoptosis in response to fenretinide, bortezomib, or both drugs together. A s.c. xenograft model was used to test responses in vivo. Results: Fenretinide and bortezomib synergistically decreased viability and increased apoptosis in all three melanoma lines at clinically achievable concentrations. This was also reflected by increased expression of GADD153, a marker of ER stress-induced apoptosis. In vivo, fenretinide in combination with bortezomib gave a marked reduction in xenograft tumor volume and an increase in apoptosis compared with fenretinide or bortezomib alone. The cell cycle stage of tumor cells in vivo were similar to that predicted from the effects of each drug or the combination in vitro. Conclusions: These results suggest that fenretinide and bortezomib, both of which are available in clinical formulation, warrant clinical evaluation as a combination therapy for metastatic melanoma.
A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction
Authors: Cindy L Grines, Donald R Westerhausen, Lorelei L Grines, J.Timothy Hanlon, Timothy L Logemann, Matti Niemela, W.Douglas Weaver, Marianne Graham, Judith Boura, William W O’Neill, Carlos Balestrini
Journal: Journal of the American College of Cardiology (2002)
Importance of Atrial Flutter Isthmus in Postoperative Intra-Atrial Reentrant Tachycardia
Authors: David P. Chan, George F. Van Hare, Judith A. Mackall, MD Mark D. Carlson, Albert L. Waldo
Journal: Circulation (2000)

Background —In survivors of congenital heart surgery, intra-atrial reentrant tachycardia (IART) often develops. Previous reports have emphasized the atriotomy scar as the central barrier around which a reentrant circuit may rotate but have not systematically evaluated the atrial flutter isthmus in such patients. We sought to determine the role of the atrial flutter isthmus in supporting IART in a group of postoperative patients with congenital heart disease. Methods and Results —Nineteen postoperative patients with IART underwent electrophysiological studies with entrainment mapping of the atrial flutter isthmus for determining postpacing intervals. Radiofrequency ablation was performed at the identified isthmus in an effort to create a complete line of block. Twenty-one IARTs were identified in 19 patients, with a mean tachycardia cycle length of 293±73 ms. The atrial flutter isthmus was part of the circuit in 15 of 21 (71.4%). In the remaining 6 of 21, the ablation target zone was at sites near atrial incisions or suture lines. Ablation was successful in 19 of 21 (90.4%) IARTs and in 14 of 15 (93.3%) cases at the atrial flutter isthmus. Conclusions —In most of our postoperative patients, the atrial flutter isthmus was part of the reentrant circuit. The fact that the atrial flutter isthmus is vulnerable to ablation suggests that whenever IART occurs late after repair of a congenital heart defect, the atrial flutter isthmus should be evaluated. These data support the theory that some form of conduction block between the vena cava is essential for the establishment of a stable substrate for the atrial flutter reentrant circuit.
A Central Role for Heme Iron in Colon Carcinogenesis Associated with Red Meat Intake
Authors: Nadia M. Bastide, Fatima Chenni, Marc Audebert, Raphaelle L. Santarelli, Sylviane Taché, Nathalie Naud, Maryse Baradat, Isabelle Jouanin, Reggie Surya, Ditte A. Hobbs, Gunter G. Kuhnle, Isabelle Raymond-Letron, Françoise Gueraud, Denis E. Corpet, Fabrice H.F. Pierre
Journal: Cancer Research (2015)

Epidemiology shows that red and processed meat intake is associated with an increased risk of colorectal cancer. Heme iron, heterocyclic amines, and endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but their relative contribution is unknown. Our study aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat. The relative part of heme iron (1% in diet), heterocyclic amines (PhIP + MeIQx, 50 + 25 μg/kg in diet), and NOC (induced by NaNO₂+ NaNO₂; 0.17 + 0.23 g/L of drinking water) was determined by a factorial design and preneoplastic endpoints in chemically induced rats and validated on tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were analyzed in vitro in normal and Apc-deficient cell lines and confirmed on colon mucosa. Heme iron increased the number of preneoplastic lesions, but dietary heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary hemoglobin increased tumor load in Min mice (control diet: 67 ± 39 mm²; 2.5% hemoglobin diet: 114 ± 47 mm², P = 0.004). In vitro, fecal water from rats given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were more toxic to normal versus mutated cells and were only genotoxic to normal cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin. These results highlight the role of heme iron in the promotion of colon cancer by red meat and suggest that heme iron could initiate carcinogenesis through lipid peroxidation. .