tbuckley/cabot-search huggingface dataset:
Structure, Divergence, and Distribution of the CRR Centromeric Retrotransposon Family in Rice
Authors: K. Nagaki
Journal: Molecular Biology and Evolution (2004)

The centromeric retrotransposon (CR) family in the grass species is one of few Ty3-gypsy groups of retroelements that preferentially transpose into highly specialized chromosomal domains. It has been demonstrated in both rice and maize that CRR (CR of rice) and CRM (CR of maize) elements are intermingled with centromeric satellite DNA and are highly concentrated within cytologically defined centromeres. We collected all of the CRR elements from rice chromosomes 1, 4, 8, and 10 that have been sequenced to high quality. Phylogenetic analysis revealed that the CRR elements are structurally diverged into four subfamilies, including two autonomous subfamilies (CRR1 and CRR2) and two nonautonomous subfamilies (noaCRR1 and noaCRR2). The CRR1/CRR2 elements contain all characteristic protein domains required for retrotransposition. In contrast, the noaCRR elements have different structures, containing only a gag or gag-pro domain or no open reading frames. The CRR and noaCRR elements share substantial sequence similarity in regions required for DNA replication and for recognition by integrase during retrotransposition. These data, coupled with the presence of young noaCRR elements in the rice genome and similar chromosomal distribution patterns between noaCRR1 and CRR1/CRR2 elements, suggest that the noaCRR elements were likely mobilized through the retrotransposition machinery from the autonomous CRR elements. Mechanisms of the targeting specificity of the CRR elements, as well as their role in centromere function, are discussed.
A STUDY OF ACUTE MERCURIC CHLORIDE INTOXICATIONS IN THE DOG WITH SPECIAL REFERENCE TO THE KIDNEY INJURY
Authors: William deB. MacNider
Journal: The Journal of Experimental Medicine (1918)

A study of the experiments comprising the first group of animals permits the deduction that these animals succumb to the acute poisoning as a result of the shock which the poison induces through its corrosive action in the stomach and intestine. The animals die before the mercury, acting as such during its elimination by the kidney, can induce an acute nephropathy and before the mercury, by inducing an acid intoxication, can lead to an acute kidney injury. The remaining animals of the series, Groups II, III, and IV, have withstood the corrosive action of the poison. These animals have shown the same type of delayed intoxication from the poison. The intoxication, however, has varied in time of appearance, duration, and severity. The animals classified as Group II have developed during the stage of improvement from the gastroenteritis a rapid and severe type of acid intoxication, have become rapidly anuric, and have died either in a state of air-hunger or in convulsions. The animals of Group III, either during or after their recovery from the gastroenteritis, have developed a mild grade of acid intoxication. During the following days of the experiments the animals succeeded in reestablishing their normal acid-base equilibrium. All the animals of this group recovered. The animals of Group IV have shown a recovery from the mercury enteritis. Following a period during which there was an attempt on the part of the animals to return to normal, as indicated by an increase in the alkali reserve of the blood and by an increased output of phenolsulfonephthalein and urine, the members of the group developed a delayed acid intoxication, and, like the animals of Group II, became anuric.
Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues.
Authors: E Bandrés, E Cubedo, X Agirre, R Malumbres, R Zárate, N Ramirez, A Abajo, A Navarro, I Moreno, M Monzó, J García-Foncillas
Journal: Molecular Cancer (2006)

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. In our study, we examined by Real-Time PCR the expression of 156 mature miRNA in colorectal cancer. The analysis by several bioinformatics algorithms of colorectal tumours and adjacent non-neoplastic tissues from patients and colorectal cancer cell lines allowed identifying a group of 13 miRNA whose expression is significantly altered in this tumor. The most significantly deregulated miRNA being miR-31, miR-96, miR-133b, miR-135b, miR-145, and miR-183. In addition, the expression level of miR-31 was correlated with the stage of CRC tumor. Our results suggest that miRNA expression profile could have relevance to the biological and clinical behavior of colorectal neoplasia.
cis-acting sequences required for class II gene regulation by interferon gamma and tumor necrosis factor alpha in a murine macrophage cell line.
Authors: Y R Freund, R L Dedrick, P P Jones
Journal: The Journal of Experimental Medicine (1990)

In this report, we have demonstrated that IFN-gamma and TNF-alpha increase expression of both the I-A and I-E region gene products on the surface of the myelomonocytic cell line WEHI-3, and that they mediate this increase via an increase in A alpha transcription. Constructs containing 5' deletion mutations of the A alpha promoter attached to the bacterial chloramphenicol acetyl transferase gene were used to delineate the minimum 5' flanking sequences required for promoter activity, and for inducibility by IFN-gamma and TNF-alpha. Approximately 115 bp of 5' sequences are required for minimum induction by IFN-gamma or TNF-alpha when the cytokines are present separately. This includes the three conserved promoter elements, the X, Y, and H boxes. Nested linker-scanner mutations demonstrated that additional regions were also critical for optimal induction by IFN-gamma or TNF-alpha. These include the kappa B-like enhancer and a TNF-alpha-specific sequence that we have tentatively called the T box. The T box sequence was also found in the promoter regions of the human HLA-DQ alpha and rat RT1.B alpha genes. Although the entire T box sequence element was not found in the other mouse class II genes, all class II alpha genes contained the SV40 core enhancer element in the regions included by the T box. Mouse class II beta genes appear to contain neither the T box nor the core enhancer element in this region, suggesting differential regulation of class II alpha and beta genes by TNF-alpha.
The bronchial epithelium promotes B cell survival and immunoglobulin production in a coculture system
Authors: Maha Zohra Ladjemi, Bruno Detry, Yves Sibille, Charles Pilette
Journal: European Respiratory Journal (2011)

Background:  Chronic obstructive pulmonary disease (COPD) is associated with chronic airway inflammation and structural remodelling, in particular of the epithelium, which is impaired in its capacity to transport immunoglobulin (Ig) A. Although peribronchial lymphoid follicles have been described in severe COPD, it remains unknown whether B-cell conditioning (e.g. for IgA production) is altered in this disease.   Objectives:  In this study, we report on preliminary data using a model of coculture of B cells with human primary bronchial epithelium (re)differentiated in vitro in air-liquid interface.   Methods:  IgA synthesis was studied in CD19+ B cells (purified by immunomagnetic sorting from healthy blood donors) following co-culture for 13 days with a bronchial epithelium. B cells were also assessed by flow cytometry for cell activation and survival (annexinV/propidium iodine staining).   Results:  In two independent experiments, we observed that Ig production was upregulated in B cells cocultured with the bronchial epithelium, as compared to B cells cultured alone (2.2 fold increase in IgG, and modest 1.4 fold increase in IgA), whereas IgM was decreased (0.8 fold). In contrast to expression of CD69, CD80 and CD86 which did not change, B-cell survival also increased (55.3% vs 20.8% for B cells alone) following epithelial coculture.   Conclusion:  These preliminary data using this model of coculture, which should reveal useful to investigate crosstalks between the epithelium and B cells with respect to COPD, confirm that the airway epithelium provides B cells with signals promoting both survival and Ig synthesis.
Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors
Authors: Catherine De Angelis, Jeffrey M. Drazen, Frank A. Frizelle, Charlotte Haug, John Hoey, Richard Horton, Sheldon Kotzin, Christine Laine, Ana Marusic, A. John P.M. Overbeke, Torben V. Schroeder, Hal C. Sox, Martin B. Van Der Weyden
Journal: New England Journal of Medicine (2004)

Altruism and trust lie at the heart of research on human subjects. Altruistic individuals volunteer for research because they trust that their participation will contribute to improved health for others and that researchers will minimize risks to participants. In return for the altruism and trust that make clinical research possible, the research enterprise has an obligation to conduct research ethically and to report it honestly. Honest reporting begins with revealing the existence of all clinical studies, even those that reflect unfavorably on a research sponsor's product. Unfortunately, selective reporting of trials does occur, and it distorts the body of evidence . . .
Effects of triiodothyronine-induced hypermetabolism on factor VIII and fibrinogen in man
Authors: John C. Hoak, William R. Wilson, Emory D. Warner, Ernest O. Theilen, Glenna L. Fry, Fred L. Benoit
Journal: Journal of Clinical Investigation (1969)

Triiodothyronine (liothyronine sodium) (400-500 mug/day for 14 days) was given to six normal subjects. Factor VIII (antihemophilic globulin) activity increased from 109 to 167% (P < 0.05); fibrinogen increased from 344 to 581 mg/100 ml (P < 0.01). To test whether the increases in factor VIII activity and fibrinogen were mediated by beta adrenergic receptors, propranolol (20 mg every 6 hr) was given orally to four other normal subjects in addition to triiodothyronine for 14 days. Factor VIII increased from 100 to 161%; fibrinogen increased from 374 to 564% (P < 0.01). Factor VIII activity did not change in a severe classical hemophiliac made hypermetabolic with triiodothyronine, but it increased from 39 to 82% in a patient with von Willebrand's disease. Triiodothyronine-induced hypermetabolism increased the incorporation of selenomethionine-(75)Se into plasma fibrinogen. These results suggest that the increases in clotting factor activity during triiodothyronine-induced hypermetabolism reflect an effect of increased protein synthesis rather than enhanced stimulation of beta adrenergic receptors.
Hemoglobin J Guantanamo [α<sub>2</sub>β<sub>2</sub> 128 (H6) Ala→Asp] in association with hemoglobin C and α‐thalassemia in a family from Benin
Authors: H. Wajcman, V. Baudin‐Chich, J. Kister, C. Feo, G. Gombaud‐Saintonge, B. Bohn, M. Marden, J. Pagnier, C. Poyart, C. Dodé, F. Galacteros, Y. Blouquit, T. Cynober, G. Tchernia
Journal: American Journal of Hematology (1988)

Abstract Hemoglobin J (HbJ), Guantanamo, which had been described but once in the literature, was found in a tamily originating from Benin; this second case was found to be in association with hemoglobin C (HbC) and α‐thalassemia. High‐performance liquid chromatography (HPLC) procedures and microsequencing were used for characterization of the aminoacid substitution. The main hematological disorder, in relation with the instability of Hb J Guantanamo, seems to be a worsening of the rheological properties of the red blood cells (RBC), as demonstrated by ektacytometric studies. Oxygen‐binding properties of the RBC were almost normal, but a slight decrease in cooperativity and lowered Bohr and 2,3‐diphosphoglycerate (DPG) effects were observed for pure stripped Hb J Guantanamo. The expression of the electrophoretic charge difference was partly masked, as is often observed when the structural abnormality is situated in or near a contact area.
Extrapulmonary lymphangioleiomyomatosis: a wolf in sheep's clothing
Authors: Aurélie Maria Derweduwen, Erik Verbeken, Marguerite Stas, Johny Verschakelen, Johan Coolen, Geert Verleden, Wim Wuyts
Journal: Thorax (2012)

We present a case of a 32-year-old woman who was diagnosed with lymphangioleiomyomatosis (LAM) after detecting a mass in the upper anterior mediastinum. Two years after presentation another metastatic localisation of LAM occurred in the cervical region. With this article we would like to highlight the fact that there are still a lot of unanswered questions, especially regarding the best management of extrapulmonary LAM.
CELL SURFACE IMMUNOGLOBULIN
Authors: Charles J. Sherr, Sonia Baur, Inge Grundke, Joseph Zeligs, Barbara Zeligs, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1972)

Cells from an established line of Burkitt lymphoma (Daudi) were enzymatically radioiodinated, and labeled Ig from the cell surface was isolated and studied. Subcellular fractionation of labeled cells confirmed that intracellular proteins from the cytoplasm are not iodinated by this method. Radioactive Ig was identified as monomeric (8S) IgM, and an average of 10(5) Ig molecules was found per cell. Ig molecules could be released from the plasma membrane by detergent lysis under nonreducing conditions indicating that attachment of Ig to the plasma membrane occurs via noncovalent interactions. The ratio of micro/L radioactivity in surface Ig was the same as that of total cellular Ig radioiodinated in solution suggesting that a large portion of the Fc fragment is not buried within the membrane. In contrast to the results obtained with cell surface Ig, most intracellular Ig was found as "free" micro- and L chains regardless of whether lysates were labeled with (125)I or cells were labeled with leucine-(3)H. The results indicate that only a small percentage of the total Ig of Daudi cells is associated with the cell surface and suggest that covalent assembly of Ig occurs at or near the time that the molecule becomes part of the plasma membrane. Similarities between cell surface Ig on normal splenic lymphocytes and Daudi cells suggest that the latter is a neoplasm of bone marrow-derived lymphocytes.
Roles of Ca2+ and Na+ on the modulation of antidiuretic hormone action on urea permeability in toad urinary bladder.
Authors: M A Hardy, H M Ware
Journal: Journal of Clinical Investigation (1985)

The present studies probe the role of Ca2+ and Na+ in the stimulation-permeability coupling sequences by which antidiuretic hormone (ADH) induces a cyclic AMP (cAMP)-mediated increase in urea permeability in toad urinary bladder. The following results were obtained: (a) Removal of mucosal Na+ or Ca2+ or deletion of serosal Ca2+ did not modify ADH action. (b) Reduction of the serosal Na+ concentration to less than 50 mM inhibited the effects of both ADH and cAMP. The minimal concentration of serosal Na+ needed for the hormone to elicit its maximal effect was reduced to approximately 10 mM if serosal Ca2+ was concomitantly deleted. (c) The Na+ ionophore monensin produced an inhibition of ADH and cAMP actions that was dependent on the presence of Na+ and Ca2+ in the serosa. (d) The Ca2+ ionophore A23187 produced a serosal Ca2+-dependent inhibition of ADH effect and did not modify cAMP action. (e) Carbachol, which increases Ca2+ uptake to the same extent that A23187 does, had no effect on ADH action. (f) Quinidine, which releases Ca2+ from intracellular stores, produced a large inhibition of the action of ADH but not that of cAMP; the inhibition was greatly reduced if serosal Ca2+ was deleted. (g) Dinitrophenol and iodoacetate, which also release Ca2+ from intracellular pools, had no effect on ADH action. (h) The Ca2+ channel blocker diltiazem had no effect on ADH action and did not modify the inhibitions produced by deletion of serosal Na+ or monensin. (i) The cyclooxygenase inhibitor indomethacin partially removed the inhibition produced by deletion of serosal Na+ and almost completely impeded the inhibitions produced by either monensin or A23187. It is concluded: (a) Extracellular Ca2+, Na+ transport rates, and serosal Na+, in concentrations between 10 and 110 mM, have no participation in modulating the increase in urea permeability produced by ADH. (b) Increases in cytosolic Ca2+ activity, which are capable of inhibiting the effect of ADH on urea permeability at pre- and/or post-cAMP steps, seem to be highly compartmentalized. (c) Endogenous prostaglandins might play a role in the inhibitions produced by absence of serosal Na+, monensin, or A23187.
Induction Chemotherapy for Larynx Preservation: Patient Selection or Therapeutic Effect?
Authors: David G. Pfister, John A. Ridge
Journal: Journal of Clinical Oncology (2005)

The role of chemotherapy as part of a larynx sparing treatment strategy for advanced laryngeal cancer has evolved considerably over the last 20 years. During the 1980s, no sort of chemotherapy—induction/neoadjuvant, concurrent, adjuvant, or any combination of these approaches— could be considered part of standard treatment. Partial laryngectomy and primary radiation were the recommended therapeutic options for patients hoping to avoid total laryngectomy. These approaches are still used in selected patients today. However, standard therapy for an advanced primary cancer of the larynx commonly entailed surgical removal of the voice box. The landmark Veterans Affairs’ (VA) laryngeal cancer study, 1 initially published in 1991, provided the best initial evidence to support cisplatin-based, induction chemotherapy as part of a larynx preserving treatment approach. The VA investigators randomized patients with stage III or IV laryngeal cancer to primary surgery and postoperative radiation versus three cycles of induction chemotherapy followed by radiation. Laryngectomy was reserved for patients with a less than major response after two cycles of chemotherapy, suspected disease persistence after radiation, or relapse. The chemotherapy/radiation arm yielded survival rates comparable to those achieved with primary surgical management. Two thirds of surviving patients retained their larynx. The similarly designed European Organisation for Research and Treatment of Cancer (EORTC) larynx preservation study, which focused on patients with advanced cancer of the hypopharynx, further supported the principles of the VA trial. 2 Induction chemotherapy followed by radiation with surgery reserved for salvage came to be considered a new standard treatment for patients with locally advanced cancer of the larynx. Subsequent studies, most prominently the Radiation Therapy
Early Predicted Time to Normalization of Tumor Markers Predicts Outcome in Poor-Prognosis Nonseminomatous Germ Cell Tumors
Authors: Karim Fizazi, Stéphane Culine, Andrew Kramar, Robert J. Amato, Jeannine Bouzy, Isan Chen, Jean-Pierre Droz, Christopher J. Logothetis
Journal: Journal of Clinical Oncology (2004)

The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification.Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values.The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis.Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.
Medical student debts could rise to more than 70 000 under new rules
Authors: A. O'Dowd
Journal: BMJ (2010)

The level of debt held by newly qualified doctors could rise sharply to between £70 000 (€80 000; $110 000) and £100 000 if the recommendations of a radical review of higher education funding in England are implemented.

In his independent review into funding of higher education and student finance, published on 12 October, the former BP chief executive John Browne called for the existing annual cap on the student tuition fee of £3290 to be abolished and for universities and colleges to be allowed to set their own fees up to a limit of around £12 000 a year.

The BMA has calculated that if universities were to set tuition fees for medicine courses to around £10 000, this would mean that a student would have an average debt of around £70 000 on qualifying—almost double the current average debt of £37 000. If tuition fees were set higher, it …
Impaired erythrocyte nad synthesis: A metabolic abnormality in thalassemia
Authors: Charles R. Zerez, Kouichi R. Tanaka
Journal: American Journal of Hematology (1989)

Abstract We have recently demonstrated that phosphoribosylpyrophosphate (PRPP) synthetase activity is decreased in RBC from individuals with thalassemia minor. Because NAD biosynthesis requires PRPP, the product of the PRPP synthetase reaction, we have investigated NAD synthesis in thalassemic RBC. NAD synthesis was measured in intact RBC both by following the accumulation of unlabeled NAD and by following the incorporation of 14 C‐nicotinic acid into NAD. Using both assay systems, we demonstrate that NAD synthesis is decreased significantly in thalassemic RBC compared to either normal or high reticulocyte red cells. Although this suggested that NAD content should be decreased in thalassemic RBC, no significant difference in NAD content was found among thalassemic, normal, or high reticulocyte red cells. Mechanisms for the lack of a significant decrease in NAD content in thalassemic RBC are discussed. These results indicate that NAD synthesis is impaired in thalassemic RBC possibly as a result of their decrease in PRPP synthetase activity. Our data provide evidence that thalassemic RBC have secondary metabolic abnormalities in addition to their primary defect in hemoglobin synthesis.