tbuckley/cabot-search huggingface dataset:
Persistence of Neutrophil Hypersegmentation During Recovery from Megaloblastic Granulopoiesis
Authors: BARBARA J. NATH
Journal: Annals of Internal Medicine (1979)

We studied the rate of disappearance of neutrophil hypersegmentation in 23 patients with megaloblastic anemia during therapy with vitamin B12 and folic acid. In 14 patients with uncomplicated megaloblastic anemia, the neutrophil lobe average began to fall towards normal 11.4 ± 0.3 (SEM) days after treatment was begun and became normal by 13.9 ± 0.6 days. In nine patients with associated inflammatory disorders, the lobe average returned to normal more rapidly. In six initially neutropenic patients, a five-fold increase in total granulocyte count occurred by the eighth day and a sevenfold increment in the total number of circulating hypersegmented neutrophils. Granulocyte folate concentrations in five folate-deficient patients rose to normal levels within 4 to 7 days of starting therapy. Hypersegmentation thus persists for many days after correction of neutropenia and restoration of normal granulocyte folate levels have occurred. We conclude that cobalamin and folate are needed at two different steps in granulopoiesis.
Ethanol interferes with regeneration-associated changes in biotransforming enzymes: A potential mechanism underlying ethanol's carcinogenicity?
Authors: Anna Mae Diehl, Hanna Cathrine Bisgaard, Betsy T. Kren, Clifford J. Steer
Journal: Hepatology (1991)

The effects of chronic ethanol consumption on enzyme systems involved in carcinogen activation and detoxification were studied in a rat model of liver regeneration. In control rats, steady-state messenger RNAs of cytochrome P450j decreased 12 to 24 hr after partial hepatectomy but were fully recovered by 48 to 72 hr. In contrast, messenger RNA levels of cytochrome P450b and P450d did not vary significantly during that period. Steady-state messenger RNA levels for the placental form of glutathione S-transferase decreased within 30 min after partial hepatectomy but fluctuated until levels returned to normal by 48 hr. Preliminary nuclear run-on analyses suggest that the regulation of cytochrome P450j and the placental form of glutathione S-transferase messenger RNA levels involves posttranscriptional control in these animals. In ethanol-fed rats, as in controls, expression of cytochrome P450j and the placental form of glutathione S-transferase decreased transiently after partial hepatectomy. However, compared with control values, messenger RNA levels for cytochrome P450j were greater in ethanol-fed rats at each time point. Similar results were noted for placental glutathione S-transferase levels from 12 to 48 hr after partial hepatectomy. Ethanol feeding had no apparent effect on steady-state messenger RNA levels of cytochrome P450d, P450b or the multidrug-resistant gene. In both ethanol and control rats, only prehepatectomy levels of cytochrome P450 transcripts correlated with levels of the respective P450 isoenzymes. These data indicate that liver regeneration selectively decreases the steady-state messenger RNA expression of certain isoenzymes of cytochrome P450 and glutathione S-transferase.(ABSTRACT TRUNCATED AT 250 WORDS)
The rationale for targeted therapies in medulloblastoma
Authors: Tobey J. MacDonald, Dolly Aguilera, Robert C. Castellino
Journal: Neuro-Oncology (2013)

Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Patients with MB who are classified as having high-risk disease or those with recurrent disease respond poorly to current therapies and have an increased risk of MB-related mortality. Preclinical studies and molecular profiling of MB tumors have revealed upregulation or activation of several key signaling pathways such as the sonic hedgehog and WNT pathways. Although the exact mechanisms underlying MB tumorigenesis remain poorly understood, inhibiting these key pathways with molecularly targeted therapies represents an important approach to improving MB outcomes. Several molecularly targeted therapies are already under clinical investigation in MB patients. We discuss current preclinical and clinical data, as well as data from clinical trials of targeted therapies that are either ongoing or in development for MB.
Novel Effect of Antihelminthic Niclosamide on S100A4-Mediated Metastatic Progression in Colon Cancer
Authors: U. Sack, W. Walther, D. Scudiero, M. Selby, D. Kobelt, M. Lemm, I. Fichtner, P. M. Schlag, R. H. Shoemaker, U. Stein
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundMetastasis formation in colon cancer severely reduces the survival rate in patients. S100A4, a calcium-binding protein, is implicated in promoting metastasis formation in colon cancer.
Influences of Physical Training on the Heart of Dogs
Authors: HORACE L WYATT, JERE H. MITCHELL
Journal: Circulation Research (1974)

To investigate the effects of physical training on cardiac dimensions and function, eight dogs were exercised for 12 weeks by treadmill running 1 hour/ day, 5 days/week. Five dogs were confined in cages as controls for an 8-week period. Heart rates were monitored by telemetry during rest and exercise. Maximum QRS spatial magnitudes were calculated from records of McFee lead electrocardiograms. Left ventricular end-diastolic dimensions were determined radiographically by the bead and clip technique. No statistically significant changes occurred during the control period. Training produced statistically significant decreases in heart rate at rest (72 beats/min to 49 beats/min, P &lt; 0.005) and at a standard work load of 6.1 mph on a level treadmill (205 beats/ min to 158 beats/min, P &lt; 0.005) and statistically significant increases in work load (5.4 mph to 9.1 mph, P &lt; 0.005) at a standard heart rate of 194 beats/min. Improvements were rapid during the first 4 weeks of training but gradual during the remaining 8 weeks. Training caused small but statistically significant increases in left ventricular end-diastolic wall thickness (8.7 mm to 9.3 mm, P &lt; 0.0025), estimated left ventricular mass (83.6 g to 91.2 g, P &lt; 0.01), and maximum (McFee) QRS spatial magnitude (4.0 mv to 4.8 mv, P &lt; 0.05).
Drugs and Investigations
Authors: S. L. H. Smith
Journal: BMJ (1964)

after the last delivery.On 15 June 1964 she began to take oral contraceptive tablets Volidan (containing ethinyloestradiol 0.05 mg. and meg- estrolacetate 4 mg.).On the sixth day she felt nausea and on the tenth day severe itching.Around the same time the urine became dark and the stools grey.She continued the medica- tion until the 15th day, when menstruation began, and she discontinued the drug intake.A week later she was admitted to hospital; she was markedly icteric and the laboratory examina- tions showed the following findings.Blood: Serum bilirubin 8.15 mg./100 ml., alkaline phosphatase 3.25 BL-units, serum iron 49 jig./ 100 ml., serum glutamic oxaloacetic transaminase 40 Wroblewski units, and thrombo- test value 100%.Urinalysis showed marked bilirubinuria and urobilinogen.During the first week of observation the jaundice became more intense and the serum bilirubin and alkaline phosphatase showed marked elevation: serum bilirubin 14.6 mg./100 ml., alkaline phosphatase 6.5 BL-units, while the values for serum glutamic oxaloacetic transamin- ase remained within normal range.Because of the severe obstructive jaundice exploratory laparotomy was decided upon.The liver was of normal size with smooth surface and slightly greenish colour.At operative cholangiography the extrahepatic and main intrahepatic ducts were patent.A liver-biopsy specimen showed severe cholestasis in the central parts of the lobuli which was manifested as "bile emboli" in the ducts and as aggregations in Kupffer cells.No inflammatory changes were encountered, nor manifest cellular degeneration, nor necrosis.These findings corresponded closely with intra- hepatic cholestasis.After the laparotomy the jaundice gradually disappeared and the laboratory values became normal.The duration of the disease was seven weeks.
CORRELATION BETWEEN CIRCULATING ANGIOGENIC CELL MOBILIZATIONS AND RECOVERY OF CORONARY FLOW RESERVE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Han Saem Jeong, Soon Jun Hong, Jae Hyoung Park, Jong-Ho Kim, Seung-Cheol Choi, Chul Min Ahn, Jesang Kim, Do-Sun Lim
Journal: Journal of the American College of Cardiology (2012)
Molecular Analysis of Colorectal Tumors within a Diverse Patient Cohort at a Single Institution
Authors: Brooke E. Sylvester, Dezheng Huo, Andrey Khramtsov, Jing Zhang, Rana V. Smalling, Sope Olugbile, Blase N. Polite, Olufunmilayo I. Olopade
Journal: Clinical Cancer Research (2011)

Abstract Purpose: African American colorectal cancer patients have worse survival outcomes than Caucasian patients. To determine whether differences exist in the molecular mechanisms driving colorectal cancer between African Americans and Caucasians, we characterized patient tumors from a single institution by assessing genetic alterations involved in colorectal cancer progression and response to treatment. Experimental Design: We retrospectively examined 448 African Americans and Caucasians diagnosed with colorectal cancer at The University of Chicago Medical Center between 1992 and 2002. Microsatellite instability (MSI) status was determined by genotyping the BAT25, BAT26, BAT40, D5S346, and BAX loci. Mutations in KRAS codons 12 and 13 and BRAF codon 600 were identified by direct sequencing. MSI and detected mutations were correlated with clinicopathologic features. Results: Overall, no difference existed in MSI or BRAF mutation frequencies between African Americans and Caucasians. However, African Americans with microsatellite stable (MSS)/MSI-low (MSI-L) tumors had a higher proportion of KRAS mutations than Caucasians (34% vs. 23%, P = 0.048) that was isolated to proximal colon cancers and primarily driven by mutations in codon 13. There was no racial difference in receipt of chemotherapy, but African Americans with MSS/MSI-L tumors had a 73% increased risk of death over Caucasians that could not be explained by known prognostic factors. Conclusions: The significantly higher risk of death among African Americans with MSS/MSI-L tumors may be related to differences in the distribution of factors influencing response to standard therapies. These data underscore the need for further research into the molecular mechanisms driving colorectal cancer progression in underserved and understudied populations. Clin Cancer Res; 18(2); 350–9. ©2011 AACR.
Preoperative Paclitaxel and Concurrent Rapid-Fractionation Radiation for Resectable Pancreatic Adenocarcinoma: Toxicities, Histologic Response Rates, and Event-Free Outcome
Authors: Peter W. T. Pisters, Robert A. Wolff, Nora A. Janjan, Karen R. Cleary, Chusilp Charnsangavej, Christopher N. Crane, Renato Lenzi, J. Nicolas Vauthey, Jeffrey E. Lee, James L. Abbruzzese, Douglas B. Evans
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the toxicity of a preoperative regimen of paclitaxel and concurrent external-beam radiation therapy, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 30 Gy external-beam radiation therapy and concomitant weekly 3-hour infusions of paclitaxel (60 mg/m 2 ). Radiographic restaging was performed 4 to 6 weeks after chemoradiation, and patients with localized disease underwent pancreatectomy with EB-IORT. RESULTS: Thirty-five patients completed chemoradiation; 16 (46%) experienced grade 3 toxicity. Four patients (11%) required hospitalization for dehydration due to grade 3 nausea and vomiting. Twenty (80%) of 25 patients who underwent surgery underwent pancreatectomy; EB-IORT was used in 13 patients. There were no histologic complete responses to preoperative therapy; 21% of specimens demonstrated more than 50% nonviable cells (grade 2b treatment effect). With a median follow-up period of 46 months, the 3-year overall survival rate with chemoradiation and pancreatectomy was 28%. CONCLUSION: Preoperative paclitaxel-based concurrent chemoradiation is feasible. The toxicity of this regimen seems greater than that with fluorouracil. The histologic responses and survival are similar, suggesting no advantages to paclitaxel-based preoperative treatment.
Large Numbers of Novel miRNAs Originate from DNA Transposons and Are Coincident with a Large Species Radiation in Bats
Authors: Roy N. Platt, Michael W. Vandewege, Colin Kern, Carl J. Schmidt, Federico G. Hoffmann, David A. Ray
Journal: Molecular Biology and Evolution (2014)

Vesper bats (family Vespertilionidae) experienced a rapid adaptive radiation beginning around 36 Ma that resulted in the second most species-rich mammalian family (>400 species). Coincident with that radiation was an initial burst of DNA transposon activity that has continued into the present in some species. Such extensive and recent DNA transposon activity has not been seen in any other extant mammal. Indeed, retrotransposon activity is much more common in all other sequenced mammal genomes. Deep sequencing of the small RNA fraction from a vespertilionid bat, Eptesicus fuscus, as well as a dog and horse revealed large numbers of 17–24 bp putative miRNAs (p/miRNAs). Although the origination rate of p/miRNAs is similar in all three taxa, 61.1% of postdivergence p/miRNAs in Eptesicus are derived from transposable elements (TEs) compared with only 23.9% and 16.5% in the dog and horse, respectively. Not surprisingly, given the retrotransposon bias of dog and horse, the majority of TE-derived p/miRNAs are associated with retrotransposons. In Eptesicus, however, 58.7% of the TE-derived and 35.9% of the total p/miRNAs arose not from retrotransposons but from bat-specific DNA transposons. Notably, we observe that the timing of the DNA transposon expansion and the resulting introduction of novel p/miRNAs coincide with the rapid diversification of the family Vespertilionidae. Furthermore, potential targets of the DNA transposon-derived p/miRNAs are identifiable and enriched for genes that are important for regulation of transcription. We propose that lineage-specific DNA transposon activity lead to the rapid and repeated introduction of novel p/miRNAs. Some of these p/miRNAs are likely functional miRNAs and potentially influenced the diversification of Vespertilionidae. Our observations suggest a mechanism for introducing functional genomic variation rapidly through the expansion of DNA transposons that fits within the TE-thrust hypothesis.
Perioperative Outcomes of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy: Results From the Nationwide Inpatient Sample
Authors: Quoc-Dien Trinh, Jesse Sammon, Maxine Sun, Praful Ravi, Khurshid R. Ghani, Marco Bianchi, Wooju Jeong, Shahrokh F. Shariat, Jens Hansen, Jan Schmitges, Claudio Jeldres, Craig G. Rogers, James O. Peabody, Francesco Montorsi, Mani Menon, Pierre I. Karakiewicz
Journal: European Urology (2011)
Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice
Authors: Falk Hildebrand, Thi Loan Anh Nguyen, Brigitta Brinkman, Roberto Garcia Yunta, Benedicte Cauwe, Peter Vandenabeele, Adrian Liston, Jeroen Raes
Journal: Genome biology (2013)

Murine models are a crucial component of gut microbiome research. Unfortunately, a multitude of genetic backgrounds and experimental setups, together with inter-individual variation, complicates cross-study comparisons and a global understanding of the mouse microbiota landscape. Here, we investigate the variability of the healthy mouse microbiota of five common lab mouse strains using 16S rDNA pyrosequencing.We find initial evidence for richness-driven, strain-independent murine enterotypes that show a striking resemblance to those in human, and which associate with calprotectin levels, a marker for intestinal inflammation. After enterotype stratification, we find that genetic, caging and inter-individual variation contribute on average 19%, 31.7% and 45.5%, respectively, to the variance in the murine gut microbiota composition. Genetic distance correlates positively to microbiota distance, so that genetically similar strains have more similar microbiota than genetically distant ones. Specific mouse strains are enriched for specific operational taxonomic units and taxonomic groups, while the 'cage effect' can occur across mouse strain boundaries and is mainly driven by Helicobacter infections.The detection of enterotypes suggests a common ecological cause, possibly low-grade inflammation that might drive differences among gut microbiota composition in mammals. Furthermore, the observed environmental and genetic effects have important consequences for experimental design in mouse microbiome research.
Presence and Transmission of Mammary Tumor Virus and Leukemia Virus in the BALB/cfRIlI Mouse 2
Authors: Francesco Squartini, Emilio Bucciarelli, Giovanni B. Bolis
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Presence and Transmission of Mammary Tumor Virus and Leukemia Virus in the BALB/cfRIlI Mouse Get access Francesco Squartini, M.D, Francesco Squartini, M.D 3 3Institute of Pathological Anatomy and Histology, Medical School, University of Pisa, Via Roma Address reprint requests to Dr. Squartml. Search for other works by this author on: Oxford Academic PubMed Google Scholar Emilio Bucciarelli, M.D, Emilio Bucciarelli, M.D 4Division of Cancer Research, University of Perugia, 06100 Perugia, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar Giovanni B. Bolis, M.D Giovanni B. Bolis, M.D 4Division of Cancer Research, University of Perugia, 06100 Perugia, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 1, July 1974, Pages 137–150, https://doi.org/10.1093/jnci/53.1.137S Published: 01 July 1974 Article history Received: 23 October 1973 Accepted: 10 February 1974 Published: 01 July 1974
Circulating Immune Complexes in Hashimoto's Thyroiditis
Authors: E. Kappelgaard, H. Nielsen, K. Bech, H. Bliddal, U. Feldt‐Rasmussen, M. Thomsen
Journal: Allergy (1983)

Circulating immune complexes (IC) were determined in sera from 41 patients with Hashimoto's thyroiditis by a polyclonal rheumatoid factor (pRF) assay based on the inhibition of the agglutination of IgG‐coated latex particles. Elevated levels of IC were found in 63% (26/41) of the sera. There was a significant correlation (Rho = 0.91, P &lt; 0.001) between results obtained before and after treatment of sera with dithiothreitol (DTT). By precipitation with 2.5% polyethylene glycol (PEG) before pRF inhibition assay, the activity of IC was found in only 7% (3/41) of the sera. Size chromatography studies of the sera showed the inhibitory activity predominantly in the intermediary region. When found in the IgM‐region the activity was not reduced by DTT. By use of a polyethylene glycol complement consumption test (PEG‐CC) the occurrence of IC was 10% (4/41). It was not possible to find any correlation between the detectable IC and the presence of microsomal, thyroglobulin, or thyroid‐stimulating antibodies. Based on our studies the sizes of IC seemed to be heterogeneously distributed and the majority were not precipitated by PEG (2.5%, final concentration). The antibodies involved in the formation of complexes seemed to be of IgG or IgA classes. HLA‐D typing of the patients showed a non‐significant association between HLA‐Dw5 and low levels of IC while the presence of HLA‐Dw4 was significantly associated with a high level of IC ( P &lt; 0.05).
Inflammasome Activation in Reperfusion Injury
Authors: Sebastian Grundmann, Christoph Bode, Martin Moser
Journal: Circulation (2011)

W ith the advances in percutaneous coronary intervention technology and accompanying medical therapy, the prognosis of patients with acute coronary syndromes has greatly improved over the last decades.Still, approximately 6% of admitted patients do not survive to hospital discharge, 1 and despite the implementation of rapid interventional protocols, loss of cardiac tissue, and a consecutive decrease in cardiac function is the frequent consequence of acute myocardial infarction.In addition, increasing experimental and clinical evidence demonstrates that revascularization itself triggers a harmful inflammatory response, termed ischemiareperfusion (I/R) injury, that might contribute up to 50% of the ultimate infarction area 2 and that can exert deleterious effects even beyond the initially affected perfusion territory.Since the first description of I/R injury by Jennings et al in the 1960s, 3,4 a large number of studies have aimed to unravel the basic mechanisms of this complex pathophysiological process.It became evident that I/R injury is an inflammatorydriven mechanism, in part depending on the infiltration of bone marrow-derived cells and the activation of classic inflammatory pathways. 5However, none of the experimental strategies has evolved into a clinically applicable adjuvant therapy for the treatment of acute coronary syndromepatients, demonstrating the complexity of I/R injury. Article see p 594Recently, different components of the innate immune system, the evolutionarily ancient defense mechanism against exogenous pathogens and endogenous danger signals, were implicated in this context. 6In this issue of Circulation, Kawaguchi and coworkers from the Shinshu School of Medicine and the Jichi Medical University in Japan present comprehensive experimental data that demonstrate a critical role of the inflammasome in cardiac fibroblasts for myocardial I/R injury.
Information from cochlear potentials and genetic mutations helps localize the lesion site in auditory neuropathy
Authors: Rosamaria Santarelli
Journal: Genome Medicine (2010)

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity resulting from lesions involving the auditory nerve (postsynaptic AN), inner hair cells and/or the synapses with auditory nerve terminals (presynaptic AN). Affected subjects show impairment of speech perception beyond that expected for the hearing loss, abnormality of auditory brainstem potentials and preserved outer hair-cell activities. Furthermore, AN can be identified either as an isolated disorder or as an associated disorder with multisystem involvement including peripheral and optic neuropathies (non-isolated AN). Mutations in several nuclear and mitochondrial genes have been identified as underlying these forms of AN. Recently, new genes have been identified as involved in both isolated (DIAPH3, OTOF) and non-isolated AN (OPA1). Moreover, abnormal cochlear potentials have been recorded from patients with specific gene mutations by using acoustic stimuli or electrical stimulation through cochlear implant. In this review, different types of genetically based auditory neuropathies are discussed and the proposed molecular mechanisms underlying AN are reviewed.
Impact of first- and second-line treatment for Hodgkin’s lymphoma on the incidence of AML/MDS and NHL—experience of the German Hodgkin’s Lymphoma Study Group analyzed by a parametric model of carcinogenesis
Authors: M. Scholz, A. Engert, J. Franklin, A. Josting, V. Diehl, D. Hasenclever, M. Loeffler
Journal: Annals of Oncology (2010)
Neuropilin 1 is important in NSCLC
Authors: Tim Jones
Journal: Thorax (2008)

Neuropilin 1 (NRP1) is a neuronal receptor that mediates angiogenesis and lung branching during embryonic development and promotes tumour angiogenesis. Its role in cancer progression is not clear. This study examined the role of NRP1 in cancer invasion and angiogenesis, its signalling pathways and prognostic significance in non-small cell lung cancer (NSCLC).

Sixty consecutive patients …