tbuckley/cabot-search huggingface dataset:
Cloning and expression of a Leishmania donovani gene instructed by a peptide isolated from major histocompatibility complex class II molecules of infected macrophages.
Authors: A Campos-Neto, L Soong, J L Cordova, D Sant'Angelo, Y A Skeiky, N H Ruddle, S G Reed, C Janeway, D McMahon-Pratt
Journal: The Journal of Experimental Medicine (1995)

The studies reported here describe the isolation of peptides from MHC class II molecules of murine macrophages infected with Leishmania donovani, and the use of the derived peptide sequences to rescue the pathogen peptide donor protein. The isolation of the peptides was carried out by comparing the RP HPLC profile of peptides extracted from infected macrophages with the peptides extracted from noninfected cells. Several distinct HPLC peaks unique to infected macrophages were sequenced. One of the peptides that was not homologous to any known protein was used to instruct the designing of an oligonucleotide sense primer that was used in combination with an oligo dT nucleotide (anti-sense primer) to amplify by PCR a DNA fragment from L. donovani cDNA. The amplified DNA fragment was cloned and used as a probe to screen a L. donovani cDNA library. The cloned gene (Ld peptide gene) has an open reading frame of 525 bp and has no homology with any known protein/gene sequence. Northern blot analyses indicated that the Ld peptide/gene is broadly distributed and expressed among species of the Leishmania genus, in both the amastigote and promastigote life cycle forms. Using the pGEX 2T vector, the gene was expressed and the relationship of the purified recombinant protein with L. donovani was confirmed using both antibody and T cell responses from immunized or infected animals. The gene encodes a 23-kD molecule (Ldp 23) associated with the cell surface of L. donovani promastigotes. In addition, T cells purified from the lymph nodes of BALB/c mice immunized with L. donovani or infected with L. major, and from CBA/J mice infected with L. amazonensis were stimulated to proliferate by the recombinant Ldp 23 and produced high levels of IFN-gamma and no IL 4. This observation suggests that the Ldp 23 is an interesting parasite molecule for the studies concerning the host/parasite interaction because the Th1 pattern of cytokine response that it induces is correlated with resistance to Leishmania infections. These results clearly point to an alternative strategy for the purification of proteins useful for the development of both vaccines and immunological diagnostic tools not only against leishmaniasis but also for other diseases caused by intracellular pathogens.
Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children
Authors: D.G. Peroni, G.L. Piacentini, E. Cametti, I. Chinellato, A.L. Boner
Journal: British Journal of Dermatology (2010)

Vitamin D deficiency could be associated with the prevalence of atopic dermatitis (AD).We carried out a study to see whether deficient/insufficient levels of vitamin D correlate with the severity of atopic skin disease.Using the SCORAD index, we evaluated the severity of disease in 37 children (17 girls and 20 boys) aged between 8 months and 12 years with AD, consecutively enrolled in the study. Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined by a chemiluminescent method. Specific IgE (sIgE) to Staphylococcus aureus enterotoxins and sIgE to Malassezia furfur were assayed by the ImmunoCAP system. anova and the Pearson correlation test were used for statistical evaluation.We found severe, moderate and mild AD in nine (24%), 13 (35%) and 15 (41%) children, respectively. Mean ± SD serum levels of 25(OH)D were significantly higher (P < 0·05) in patients with mild disease (36·9 ± 15·7 ng mL(-1)) compared with those with moderate (27·5 ± 8·3 ng mL(-1)) or severe AD (20·5 ± 5·9 ng mL(-1)). The prevalence of patients with sIgE to microbial antigens increased in relation to vitamin D deficiency and AD severity.These data suggest that vitamin D deficiency may be related to the severity of AD and advocate the need for studies evaluating the use of vitamin D as a potential treatment in patients with this disease.
Normal Glucose Values Are Associated With a Lower Risk of Mortality in Hospitalized Patients
Authors: Alberto Bruno, Dario Gregori, Antonio Caropreso, Fulvio Lazzarato, Michele Petrinco, Eva Pagano
Journal: Diabetes Care (2008)

Hyperglycemia is a common condition in hospitalized patients. The aim of this study was to investigate the relationships between glycemia upon admission and mortality in a heterogeneous group of adult patients.The 3-year records released from a general hospital were associated with a plasma glucose dataset of its general laboratory. A matched case-control study was implemented (3,338 case-control subject pairs). All-patient refined diagnosis-related groups and the relative risk of death were the matching criteria. A multivariate conditional logistic regression model was used to evaluate the associations between death and glycemia.Higher in-hospital mortality was associated with hyperglycemia or hypoglycemia, whereas lower risk was observed for values between 78 and 101 mg/dl.Our data confirm the relation between glycemia upon admission and mortality and suggest that slightly increased or decreased plasma glucose can be linked with increased mortality risk.
Targeted Therapy With Imatinib: Hits and Misses?
Authors: Margaret von Mehren
Journal: Journal of Clinical Oncology (2004)

Targeted therapeutics are highly specific inhibitors of particular molecules and are, therefore, not broadly effective in diverse malignancies. Extensive preclinical and clinicalstudiesprovidebothclearexamplesoftheirefficacyand resounding examples of their shortcomings. Targeted therapies will require that we use them in a markedly different fashionthanweuseconventionaldrugsandwillbesuccessful only when they are used against biologically relevant targets in specific disease contexts. Imatinib mesylate (imatinib) is a success of targeted therapy. It is active against a number of related tyrosine kinases, namely ABL, BCR-ABL, KIT, PFGFR, and TEL. Imatinib has significant clinical efficacy in chronic myelogenous leukemia (CML) 1 and gastrointestinal stromal tumors (GISTs). 2 The reason that CML and GIST are effectively treated with imatinib is that they each contain a geneticchangeinvolvingthetargetedkinasesthatisintegral to the biology of the malignancy. CML contains a translocation between the breakpoint cluster region and the ABL genethatleadstoaconstitutivelyactivekinase.GISTscommonly express mutated KIT that is constitutively activated; some contain a wild-type KIT and/or a mutated plateletderivedgrowthfactorreceptoralpha(PDGFRA).Theactivityofthesekinasesprovidesthemalignantcellswithgrowth and survival signals. However, it is this activity that is so very effectively turned off by imatinib. The significant responses in patients with CML and GIST earned the agent rapidapprovalbytheUnitedStatesFoodandDrugAdministration,aswellassignificantnotorietyinboththemedical and lay press. Many have sought to use the drug in hopes of having similar dramatic responses in other cancers.
Analysis of the c-kit gene in patients with slow transit constipation
Authors: W-D Tong
Journal: Gut (2005)

Intestinal microbiota have become the subject of intense investigation in inflammatory bowel disease (IBD) over the past years after some groups demonstrated that significant alterations of the composition of enteric bacteria might be related to the underlying inflammatory process ( Gut 2006; 55 :205–11).1–4 However, the complexity of the intestinal microbiota and the availability of a variety of different experimental approaches generated sometimes conflicting and inconsistent data. Manichanh et al ( Gut 2006; 55 :205–11) recently published an extensive study using metagenomic libraries, a novel molecular technique allowing the recruitment of …
Oral administration of K-11706 inhibits GATA binding activity, enhances hypoxia-inducible factor 1 binding activity, and restores indicators in an in vivo mouse model of anemia of chronic disease
Authors: Yoko Nakano, Shigehiko Imagawa, Ken Matsumoto, Christian Stockmann, Naoshi Obara, Norio Suzuki, Takeshi Doi, Tatsuhiko Kodama, Satoru Takahashi, Toshiro Nagasawa, Masayuki Yamamoto
Journal: Blood (2004)
Mitoxantrone, Etoposide, and Cytarabine With or Without Valspodar in Patients With Relapsed or Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome: A Phase III Trial (E2995)
Authors: Peter L. Greenberg, Sandra J. Lee, Ranjana Advani, Martin S. Tallman, Branimir I. Sikic, Louis Letendre, Kathleen Dugan, Bert Lum, David L. Chin, Gordon Dewald, Elisabeth Paietta, John M. Bennett, Jacob M. Rowe
Journal: Journal of Clinical Oncology (2004)

To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator valspodar (PSC 833; Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).
Transgenic Mice for cGMP Imaging
Authors: Martin Thunemann, Lai Wen, Matthias Hillenbrand, Angelos Vachaviolos, Susanne Feil, Thomas Ott, Xiaoxing Han, Dai Fukumura, Rakesh K. Jain, Michael Russwurm, Cor de Wit, Robert Feil
Journal: Circulation Research (2013)

Cyclic GMP (cGMP) is an important intracellular signaling molecule in the cardiovascular system, but its spatiotemporal dynamics in vivo is largely unknown.To generate and characterize transgenic mice expressing the fluorescence resonance energy transfer-based ratiometric cGMP sensor, cGMP indicator with an EC50 of 500 nmol/L (cGi500), in cardiovascular tissues.Mouse lines with smooth muscle-specific or ubiquitous expression of cGi500 were generated by random transgenesis using an SM22α promoter fragment or by targeted integration of a Cre recombinase-activatable expression cassette driven by the cytomegalovirus early enhancer/chicken β-actin/β-globin promoter into the Rosa26 locus, respectively. Primary smooth muscle cells isolated from aorta, bladder, and colon of cGi500 mice showed strong sensor fluorescence. Basal cGMP concentrations were < 100 nmol/L, whereas stimulation with cGMP-elevating agents such as 2-(N,N-diethylamino)-diazenolate-2-oxide diethylammonium salt (DEA/NO) or the natriuretic peptides, atrial natriuretic peptide, and C-type natriuretic peptide evoked fluorescence resonance energy transfer changes corresponding to cGMP peak concentrations of ≈ 3 µmol/L. However, different types of smooth muscle cells had different sensitivities of their cGMP responses to DEA/NO, atrial natriuretic peptide, and C-type natriuretic peptide. Robust nitric oxide-induced cGMP transients with peak concentrations of ≈ 1 to > 3 µmol/L could also be monitored in blood vessels of the isolated retina and in the cremaster microcirculation of anesthetized mice. Moreover, with the use of a dorsal skinfold chamber model and multiphoton fluorescence resonance energy transfer microscopy, nitric oxide-stimulated vascular cGMP signals associated with vasodilation were detected in vivo in an acutely untouched preparation.These cGi500 transgenic mice permit the visualization of cardiovascular cGMP signals in live cells, tissues, and mice under normal and pathological conditions or during pharmacotherapy with cGMP-elevating drugs.
Effect of static stretching of muscles surrounding the knee on knee joint position sense
Authors: Farahnaz Ghaffarinejad, Shohreh Taghizadeh, Farshid Mohammadi
Journal: British Journal of Sports Medicine (2007)

Background: Muscle stretching is widely used in sport training and in rehabilitation. Considering the important contribution of joint position sense (JPS) to knee joint stability and function, it is legitimate to question if stretching might alter the knee JPS. Objective: To evaluate if a stretch regimen consisting of three 30 s stretches alters the knee JPS. Design and setting: A blinded, randomised design with a washout time of 24 h was used. Subjects: 39 healthy students (21 women, 18 men) volunteered to participate in this study. Methods and main outcome measures: JPS was estimated by the ability to reproduce the two target positions (20° and 45° of flexion) in the dominant knee. The absolute angular error (AAE) was defined as the absolute difference between the target angle and the subject perceived angle of knee flexion. AAE values were measured before and immediately after the static stretch. Measurements were repeated three times. The static stretch comprised a 30 s stretch followed by a 30 s pause, three times for each muscle. Results: The AAE decreased significantly after the stretching protocols for quadriceps (3.5 (1.3) vs 0.7 (2.4); p&lt;0.001), hamstring (3.6 (2.2) vs 1.6 (3.1); p = 0.016) and adductors (3.7 (2.8) vs 1.7 (2.4); p = 0.016) in 45° of flexion, but no differences were found for values of the gastrocnemius and popliteus muscles in this angle and for the values of all muscles in 20° of flexion (p&gt;0.05). Conclusion: The accuracy of the knee JPS in 45° of flexion is improved subsequent to a static stretch regimen of quadriceps, hamstring and adductors in healthy subjects.
Molecular characterization of two human autoantigens: unique cDNAs encoding 95- and 160-kD proteins of a putative family in the Golgi complex.
Authors: M J Fritzler, J C Hamel, R L Ochs, E K Chan
Journal: The Journal of Experimental Medicine (1993)

Serum autoantibodies from a patient with autoantibodies directed against the Golgi complex were used to screen clones from a HepG2 lambda Zap cDNA library. Three related clones, designated SY2, SY10, and SY11, encoding two distinct polypeptides were purified for further analysis. Antibodies affinity purified by adsorption to the lambda Zap-cloned recombinant proteins and antibodies from NZW rabbits immunized with purified recombinant proteins reproduced Golgi staining and bound two different proteins, 95 and 160 kD, from whole cell extracts. The SY11 protein was provisionally named golgin-95 and the SY2/SY10 protein was named golgin-160. The deduced amino acid sequence of the cDNA clone of SY2 and SY11 represented 58.7- and 70-kD proteins of 568 and 620 amino acids. The in vitro translation products of SY2 and SY11 cDNAs migrated in SDS-PAGE at 65 and 95 kD, respectively. The in vitro translated proteins were immunoprecipitated by human anti-Golgi serum or immune rabbit serum, but not by normal human serum or preimmune rabbit serum. Features of the cDNA suggested that SY11 was a full-length clone encoding golgin-95 but SY2 and SY10 together encoded a partial sequence of golgin-160. Analysis of the SY11 recombinant protein identified a leucine zipper spanning positions 419-455, a glutamic acid-rich tract spanning positions 322-333, and a proline-rich tract spanning positions 67-73. A search of the SwissProt data bank indicated sequence similarity of SY11 to human restin, the heavy chain of kinesin, and the heavy chain of myosin. SY2 shared sequence similarity with the heavy chain of myosin, the USO1 transport protein from yeast, and the 150-kD cytoplasmic dynein-associated polypeptide. Sequence analysis demonstrated that golgin-95 and golgin-160 share 43% sequence similarity and, therefore, may be functionally related proteins.
NEUROPSYCHIATRY IN A GENERAL HOSPITAL
Authors: THOS. J. HELDT
Journal: American Journal of Psychiatry (1944)

The admission to, and the housing of an insane patient in a general hospital is not new. Complete and successful integration of the admission and the treatment of such a patient in a general hospital is new and requires not only patience and tact, but also all modern facilities for its satisfying achievement. The administrative demands and problems of conducting a division of neuropsychiatry as part and parcel of the department of medicine in a general hospital is a challenge that should be more liberally accepted. The associated difficulties are in no sense insurmountable. The advantages to the hospital, to its lay and professional personnel, and to the mentally ill patient far outweigh the disadvantages. [See for table VI in Source PDF] General hospitals, thoughtful of their facilities and with careful training of their personnel and the guidance of a qualified psychiatrist, can do much to meet the problems of the returning neuropsychiatric casualties of the present war. The results of caring for neuropsychiatric patients in a general hospital are highly gratifying. Such care does relieve our state hospitals and disseminates a more wholesome understanding of the neuropsychiatric patient among our professional colleagues, and most of all, among the people that constitute the general public. Morbid fears are reduced and references to "living death" are less frequent.
Inferring the Geographic Mode of Speciation by Contrasting Autosomal and Sex-Linked Genetic Diversity
Authors: Jui-Hua Chu, Daniel Wegmann, Chia-Fen Yeh, Rong-Chien Lin, Xiao-Jun Yang, Fu-Min Lei, Cheng-Te Yao, Fa-Sheng Zou, Shou-Hsien Li
Journal: Molecular Biology and Evolution (2013)

When geographic isolation drives speciation, concurrent termination of gene flow among genomic regions will occur immediately after the formation of the barrier between diverging populations. Alternatively, if speciation is driven by ecologically divergent selection, gene flow of selectively neutral genomic regions may go on between diverging populations until the completion of reproductive isolation. It may also lead to an unsynchronized termination of gene flow between genomic regions with different roles in the speciation process. Here, we developed a novel Approximate Bayesian Computation pipeline to infer the geographic mode of speciation by testing for a lack of postdivergence gene flow and a concurrent termination of gene flow in autosomal and sex-linked markers jointly. We applied this approach to infer the geographic mode of speciation for two allopatric highland rosefinches, the vinaceous rosefinch Carpodacus vinaceus and the Taiwan rosefinch C. formosanus from DNA polymorphisms of both autosomal and Z-linked loci. Our results suggest that the two rosefinch species diverged allopatrically approximately 0.5 Ma. Our approach allowed us further to infer that female effective population sizes are about five times larger than those of males, an estimate potentially useful when comparing the intensity of sexual selection across species.
Pulmonary nodules in the setting of an extrapulmonary tumor - 5 year review
Authors: Filipe Leite, Tiago Nogueira, João Bernando, Luis Eugénio, Manuel Antunes
Journal: European Respiratory Journal (2014)

Introduction: In a patient with a known previous extrapulmonary tumor and a new pulmonary lesion, the hypothesis of a metastasis is put forth, often accepted and a wedge resection is performed. Still this remains empirical.  Objectives: To analyze patients with known previous tumors submitted to resection surgery due to pulmonary nodules. To establish a relation between the type of tumor, size, location, number and histology of the nodules.  Material and Methods: Search the center9s records for patients with the diagnosis of pulmonary lesion/nodule, from January 1st 2008 to December 31st 2012, excluding cases with no previous tumor.  Results: 279 patients (163 male / 116 female). 150 had an history of colorectal cancer, 23 breast, 23 ORL, 23 soft tissue, 20 renovesical, 7 prostatic and 5 uterine cancer. 232 patients presented with a single nodule (82%), 37 with 2 (13%) and 10 with 3 (4%). The average size was 22.2mm (SD 16.03). 171 patients had preoperative PET scan, 99 with PET positive nodules and 13 PET negative nodules. 218 wedge resections were performed, 27 lobectomies, 2 pneumonectomies and 18 enucleations. Comparing the preoperative hypothesis of the nodules being metastasis with the pathological diagnosis there was concordance in 199 cases (70%). In patients with a history of colorectal cancer the relative risk (RR) of the nodule being a primary lung cancer was 2.02 (1.365-2.99) (p  Conclusion: In patients with a history of colorectal cancer a new pulmonary nodule presented a significant risk of being primary lung cancer. Still the surgical approach remains dependent on the ability to distinguish between them in an extemporaneous examination.
Authors’ response: virus–host interactions in HBV-related hepatocellular carcinoma: more to be revealed?
Authors: Qian Cao, Sandrine Imbeaud, Shalini Datta, Jessica Zucman-Rossi
Journal: Gut (2014)

We acknowledge Cao et al 1 for being interested in our recent study on molecular features of hepatitis B related hepatocellular carcinoma (HBV-related HCC).2 As they suggested, we searched for the HBx-LINE1 chimerical transcript recently identified in a Chinese population of HBV-related HCC by Lau et al 3 in our series of HCC treated in France.2 To this aim, we have selected and analysed 50 HBV-related HCC tumours which were included in our last report.2 Total RNAs were extracted using Trizol (Invitrogen) from frozen tissues and converted into …
Oncolytic Efficacy and Enhanced Safety of Measles Virus Activated by Tumor-Secreted Matrix Metalloproteinases
Authors: Christoph Springfeld, Veronika von Messling, Marie Frenzke, Guy Ungerechts, Christian J. Buchholz, Roberto Cattaneo
Journal: Cancer Research (2006)

Abstract Cancer cells secrete matrix metalloproteinases (MMP) that degrade the extracellular matrix and are responsible for some hallmarks of malignant cancer. Many viruses, including a few currently used in oncolytic virotherapy clinical trials, depend on intracellular proteases to process their proteins and activate their particles. We show here for measles virus (MV) that particle activation can be made dependent of proteases secreted by cancer cells. The MV depends on the intracellular protease furin to process and activate its envelope fusion (F) protein. To make F protein activation cancer cell specific, we introduced hexameric sequences recognized by an MMP and identified the mutant proteins most effective in fusing MMP-expressing human fibrosarcoma cells (HT1080). We showed that an MMP inhibitor interferes with syncytia formation elicited by mutant F proteins and confirmed MMP-dependent cleavage by Edman degradation sequence analysis. We generated recombinant MVs expressing the modified F proteins in place of furin-activated F. These viruses spread only in cells secreting MMP. In nude mice, an MMP-activated MV retarded HT1080 xenograft growth as efficiently as the furin-activated MV vaccine strain. In MV-susceptible mice, the furin-activated virus caused lethal encephalitis upon intracerebral inoculation, whereas the MMP-activated did not. Thus, MV particle activation can be made dependent of proteases secreted by cancer cells, enhancing safety. This study opens the perspective of combining targeting at the particle activation, receptor recognition, and selective replication levels to improve the therapeutic index of MV and other viruses in ongoing clinical trials of oncolysis. (Cancer Res 2006; 66(15): 7694-700)