tbuckley/cabot-search huggingface dataset:
FOREIGN BODIES IN THE AIR AND FOOD PASSAGES: REMARKS ON FIVE CASES
Authors: C. A. S. Ridout
Journal: BMJ (1923)

THE following series of 5 cases of foreign bodies in the air and food passages form an interesting group illustrative of the value of modern treatment for these conditions, and of the necessity of having at hand the most up-to-date instruments for dealing withi them; this was shown especially by thle one failure to remove the foreign body by endoscopic metbods, recourse to thie older and cruder surgical method of external incision becoming a necessity.CASE i.-7oothplate Impacted in the RightBroncchuts.J. S., a mechanic aged 22, was referred t; the Eye and Ear Hospital by my colleague Mr. Bosworth Wright on October 25th, 1922, with the followinig history.On October 22th he lay downL about 6 p.m. snd fell asleep lh e woke ab ut an iour later, coughing, and felt pain in the right side of the chest.He then missed his lower toothplate, Which con- tained ten teethand had one holding lhook.Past history eLcited that on a few occasions he ha ad suffered from petit mal, becoming unconscious for a short periol.The cough andpain in the chestcontinued, and he went to the Roval Ports-
NONCODING RNAS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM
Authors: Xinwei Cao, Gene Yeo, Alysson R. Muotri, Tomoko Kuwabara, Fred H. Gage
Journal: Annual Review of Neuroscience (2006)

The central nervous system (CNS) is arguably one of the most complex systems in the universe. To understand the CNS, scientists have investigated a variety of molecules, including proteins, lipids, and various small molecules. However, one large class of molecules, noncoding RNAs (ncRNAs), has been relatively unexplored. ncRNAs function directly as structural, catalytic, or regulatory molecules rather than serving as templates for protein synthesis. The increasing variety of ncRNAs being identified in the CNS suggests a strong connection between the biogenesis, dynamics of action, and combinatorial regulatory potential of ncRNAs and the complexity of the CNS. In this review, we give an overview of the diversity and abundance of ncRNAs before delving into specific examples that illustrate their importance in the CNS. In particular, we cover recent evidence for the roles of microRNAs, small nucleolar RNAs, retrotransposons, the NRSE small modulatory RNA, and BC1/BC200 in the CNS. Finally, we speculate why ncRNAs are well adapted to improving organism-environment interactions.
Serum chemokine levels differentially regulated by vorinostat in a Sézary syndrome patient
Authors: T. Miyagaki, M. Sugaya, T. Oka, H. Fujita, S. Sato
Journal: British Journal of Dermatology (2015)

Funding sources: Grants from the Ministry of Education, Culture, Sports, Science and Technology (Japan). Conflicts of interest: none. Dear Editor, Vorinostat is the first histone deacetylase inhibitor approved for cutaneous T‐cell lymphoma (CTCL).1 Although in vitro effects of this drug on various types of cells have been studied,2 3 4 5 little is known about how this drug exerts its clinical effects on patients with CTCL. As many chemokines are reported to reflect disease activity of CTCL, suggesting their important roles in disease progression,6 we investigated the variation of serum chemokine levels during oral vorinostat therapy in a Sézary syndrome (SS) patient. A 64‐year‐old Japanese woman visited our hospital in search of management of erythroderma and leukocytosis in 2008. On admission, she was found to have generalized erythroderma (Fig. 1a). Biopsy specimens showed infiltration of small, atypical lymphocytes in the superficial dermis with mild epidermotropism (Fig. 1b). Laboratory tests showed a leukocyte count of 2·29 × 1010 cells L−1with 80% atypical lymphocytes (Sézary cells; Fig. 1c). Her CD4/CD8 ratio was 32·0 (normal range 0·6–2·9), and serum soluble IL‐2 receptor (sIL‐2R) level was 1881 U mL−1 (normal range 167–497). The same rearranged bands of T‐cell receptor Jγ were detected from peripheral blood and from lesional skin. Systemic examination revealed multiple peripheral lymphadenopathy. She was diagnosed with SS. She was first treated with topical steroid and narrowband ultra‐violet B phototherapy. Her skin lesions cleared and Sézary cells in peripheral blood and serum sIL‐2R levels decreased (time point I in Fig. 1d). During the first half of 2012, her skin lesions deteriorated with high serum sIL‐2R levels (time point II). Oral vorinostat therapy (starting with 400 mg daily and maintaining with 200–300 mg per day, 5 days a week due to adverse effects) was started in July 2012. Her skin lesions improved temporarily (time point III). Her skin condition became worse in July 2013 (time point IV). In November 2013, sIL‐2R level reached 5929 U mL−1 (time point V). Oral vorinostat therapy was stopped and oral prednisolone therapy (20 mg daily) was started the following month. Her general condition continued to get worse with a high sIL‐2R level (12 657 U mL−1; time point VI). She died due to pancytopenia caused by deterioration of SS on February 2014.
Hepatocarcinogenesis in Mice with β-Catenin and Ha-Ras Gene Mutations
Authors: Naomoto Harada, Hiroko Oshima, Masahiro Katoh, Yositaka Tamai, Masanobu Oshima, Makoto M. Taketo
Journal: Cancer Research (2004)

Abstract We have established previously a mouse strain containing a mutant β-catenin allele of which exon 3 was sandwiched by loxP sequences [Catnblox(ex3)]. In this mouse strain, a Wnt-activating β-catenin mutation alone is insufficient for hepatocarcinogenesis, but additional mutations or epigenetic changes may be required. Here we report that hepatocellular carcinoma develops at the 100% incidence in mice with simultaneous mutations in the β-catenin and H-ras genes that are introduced by adenovirus-mediated Cre expression. Although H-ras mutation alone rapidly causes large cell dysplasia in the hepatocytes, these cells show no autonomous growth within 1 week after infection of the Cre-adenovirus. However, simultaneous induction of an additional mutation in the β-catenin gene causes a clonal expansion of such dysplastic cells, followed by nodular formation and development of hepatocellular carcinoma. These results indicate that β-catenin mutations play a critical role in hepatocarcinogenesis in cooperation with another oncogene and that these mice provide a convenient model to investigate early steps of hepatocarcinogenesis.
Innovative schedule of oral idarubicin in elderly patients with metastatic breast cancer: comprehensive results of a phase II multi-institutional study with pharmacokinetic drug monitoring
Authors: D. Crivellari, D. Lombardi, G. Corona, C. Massacesi, R. Talamini, R. Sorio, M.D. Magri, C. Lestuzzi, A. Lucenti, A. Veronesi, G. Toffoli
Journal: Annals of Oncology (2006)
Evidence against the hypothesis that prostaglandins are the vasodepressor agents of pregnancy. Serial studies in chronically instrumented, conscious rats.
Authors: K P Conrad, M C Colpoys
Journal: Journal of Clinical Investigation (1986)

Renal hemodynamics increase dramatically during pregnancy, and pressor responsiveness to exogenous administration of vasoconstrictors is attenuated. We investigated whether or not vasodilatory prostaglandins mediate these phenomena. Trained, chronically instrumented, conscious pregnant rats were used. Control values of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were elevated at midgestation (P less than 0.01 and P = 0.05 from prepregnant means, respectively), and effective renal vascular resistance was decreased (P = 0.05). Indomethacin (4.5-6.5 mg/kg body weight [BW]) failed to decrease renal hemodynamics at this stage of pregnancy; in fact, it raised GFR somewhat further (P less than 0.05). Systemic pressor responsiveness to bolus administration of norepinephrine and angiotensin II (AII) was significantly attenuated by at least gestational day 20. Neither indomethacin (7 mg/kg BW) or meclofenamate (6 mg/kg BW) affected the refractory response. The renal vasculature was also relatively unresponsive to an intravenous infusion of AII (5 ng X kg-1 X min-1) during late gestation (day 19); in particular, the fall in ERPF in response to AII (16 +/- 3%) was markedly less than that observed in the prepregnant condition (34 +/- 3%; P less than 0.05). Indomethacin (6 mg/kg BW) failed to restore this blunted response, and further attenuation was evident, despite the presence of the inhibitor (gestational day 21). We conclude that vasodilatory prostaglandins do not appear to mediate the rise in renal hemodynamics, and the attenuation of the systemic and renal pressor responsiveness observed during pregnancy, insofar as these phenomena were unaffected by acute cyclooxygenase inhibition in unstressed, conscious rats.
Sex Hormone–Binding Globulin and Testosterone in Individuals With Childhood Diabetes
Authors: Kirstie K. Danielson, Melinda L. Drum, Rebecca B. Lipton
Journal: Diabetes Care (2008)

Insulin downregulates hepatic production of sex hormone-binding globulin (SHBG), which in turn influences sex hormone bioavailability. The effects of childhood-onset diabetes and insulin resistance in nondiabetic individuals on SHBG and testosterone in children and young adults are poorly understood.Individuals with diabetes diagnosed at <18 years of age (n = 48) and their siblings without diabetes (n = 47) were recruited for the Chicago Childhood Diabetes Registry Family Study. SHBG and total and free testosterone were measured. Participants ranged in age from 10 to 32 years; 39% were non-Hispanic white. The majority of individuals with diabetes had the classic type 1 phenotype (75%), while the remainder exhibited features of type 2 or mixed diabetes; 96% were treated with insulin.SHBG and total testosterone were higher in male subjects with diabetes compared with those in male siblings. Elevated SHBG was associated with the absence of endogenous insulin independent of sex; elevated total testosterone was similarly associated with the absence of C-peptide for male subjects only. Diabetes type and treatment were unrelated. In those without diabetes, greater insulin resistance had a small, nonsignificant association with lower SHBG and higher free testosterone.SHBG and total testosterone appear to be higher in male children and young adults with diabetes compared with nondiabetic male siblings, which is apparently related to the absence of endogenous insulin. This may have implications for sex hormone-dependent processes across the lifespan in male individuals diagnosed with diabetes as children.
c-Met and NF-κB–Dependent Overexpression of Wnt7a and -7b and Pax2 Promotes Cystogenesis in Polycystic Kidney Disease
Authors: Shan Qin, Mary Taglienti, Lei Cai, Jing Zhou, Jordan A. Kreidberg
Journal: Journal of the American Society of Nephrology (2012)

The mechanisms of cystogenesis in autosomal dominant polycystic kidney disease (ADPKD) are not fully understood. Hyperactivation of the tyrosine kinase c-Met contributes to cyst formation, but we do not know the downstream mediators. Here, we found that hyperactivated c-Met led to increased NF-κB signaling, which in turn, drove de novo expression of Wnt7a and overexpression of Wnt7b in Pkd1−/− mouse kidneys. Hyperactivated Wnt signaling increased expression of the transcription factor Pax2 in the cells lining cysts. Furthermore, blocking Wnt signaling with DKK1 decreased cyst formation in an organ culture model of ADPKD. In summary, these results suggest that the c-Met/NF-κB/Wnt/Pax2 signaling transduction axis may provide pharmacological targets for the treatment of ADPKD.
The Forest and the Trees: Pathways and Proteins As Colorectal Cancer Biomarkers
Authors: Monica M. Bertagnolli
Journal: Journal of Clinical Oncology (2009)

tiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer. J Clin Oncol 26:4651-4658, 2008 17. Fiorentino L, McQuaid JR, Liu L, et al: Cognitive behavioral therapy for insomnia in breast cancer survivors: A randomized controlled crossover study. Sleep 31:A295, 2008 18. Berger AM, Kuhn BR, Farr LA, et al: One-year outcomes of a behavioral therapy intervention trial on sleep quality and cancer-related fatigue. J Clin Oncol 27:6033-6041, 2009
Rehabilitation of shoulder impingement syndrome and rotator cuff injuries: an evidence-based review
Authors: Todd S Ellenbecker, Ann Cools
Journal: British Journal of Sports Medicine (2010)

Rehabilitation of the patient with glenohumeral impingement requires a complete understanding of the structures involved and the underlying mechanism creating the impingement response. A detailed clinical examination and comprehensive treatment programme including specific interventions to address pain, scapular dysfunction and rotator cuff weakness are recommended. The inclusion of objective testing to quantify range of motion and both muscular strength and balance in addition to the manual orthopaedic clinical tests allows clinicians to design evidencebased rehabilitation programmes as well as measure progression and patient improvement.
Heteromultimeric TRPC6-TRPC7 Channels Contribute to Arginine Vasopressin-Induced Cation Current of A7r5 Vascular Smooth Muscle Cells
Authors: Yoshiaki Maruyama, Yuko Nakanishi, Emma J. Walsh, David P. Wilson, Donald G. Welsh, William C. Cole
Journal: Circulation Research (2006)

The molecular identity of receptor-operated, nonselective cation channels (ROCs) of vascular smooth muscle (VSM) cells is not known for certain. Mammalian homologues of the Drosophila canonical transient receptor potential channels (TRPCs) are possible candidates. This study tested the hypothesis that heteromultimeric TRPC channels contribute to ROC current of A7r5 VSM cells activated by [Arg 8 ]-vasopressin. A7r5 cells expressed transcripts encoding TRPC1, TRPC4β, TRPC6, and TRPC7. TRPC4, TRPC6, and TRPC7 protein expression was confirmed by immunoblotting and association of TRPC6 with TRPC7, but not TRPC4β, was detected by coimmunoprecipitation. The amplitude of arginine vasopressin (AVP)-induced ROC current was suppressed by dominant-negative mutant TRPC6 (TRPC6 DN ) but not TRPC5 (TRPC5 DN ) mutant subunit expression. These data indicate a role for TRPC6- and/or TRPC7-containing channels and rule a more complex subunit composition including TRPC1 and TRPC4. Increasing extracellular Ca 2+ concentration ([Ca 2+ ] o ) from 0.05 to 1 mmol/L suppressed currents owing to native, TRPC7, and heteromultimeric TRPC6-TRPC7 channels, but not TRPC6 current, which was slightly enhanced. The relative changes in native and heteromultimeric TRPC6-TRPC7 current amplitudes for [Ca 2+ ] o between ≈0.01 and 1 mmol/L were identical, but the changes in homomultimeric TRPC6 and TRPC7 currents were significantly less and greater, respectively, compared with the native channels. Taken together, the data provide biochemical and functional evidence supporting the view that heteromultimeric TRPC6-TRPC7 channels contribute to receptor-activated, nonselective cation channels of A7r5 VSM cells.
Vidarabine Monophosphate and Human Leukocyte Interferon in Chronic Hepatitis B Infection
Authors: Coleman I. Smith
Journal: JAMA (1982)

Ten young adult patients with chronic hepatitis B virus infection and positive hepatitis B e antigen and DNA polymerase (DNAP) levels were treated with alternating courses of seven to 28 days of 5 to 7.5 mg/kg of vidarabine monophosphate (adenine arabinoside monophosphate) and 28 days of human leukocyte interferon (IFN-alpha); three different regimens were given on an outpatient basis. All patients with a fall in their DNAP level, and the DNAP remained undetectable six months after treatment was stopped in one patient. The major side effect, which most often occurred in those patients receiving 7.5 mg/kg of vidarabine monophosphate, was severe muscular pains. This study demonstrated the feasibility of administering vidarabine monophosphate and interferon to outpatients. Based on data from this and other studies, it is now possible to use a relatively nontoxic regimen that includes 28 days of 5 mg/kg of vidarabine monophosphate in a larger controlled study to answer the question of efficacy.
The presence of metabolic syndrome is independently associated with elevated serum CD40 ligand and disease severity in patients with symptomatic coronary artery disease
Authors: Wen-Lieng Lee, Wen-Jane Lee, Ying-Tsung Chen, Tsun-Jui Liu, Kae-Woei Liang, Chih-Tai Ting, Wayne Huey-Herng Sheu
Journal: Metabolism (2006)
How Do I Perform a Lumbar Puncture and Analyze the Results to Diagnose Bacterial Meningitis?
Authors: Sharon E. Straus, Kevin E. Thorpe, Jayna Holroyd-Leduc
Journal: JAMA (2006)

Context Diagnostic lumbar punctures (LPs), commonly used to rule out meningitis, are associated with adverse events.Objective To systematically review the evidence about diagnostic LP techniques that may decrease the risk of adverse events and the evidence about test accuracy of cerebrospinal fluid (CSF) analysis in adult patients with suspected bacterial meningitis. Data SourcesWe searched the Cochrane Library, MEDLINE (using Ovid and PubMed) from 1966 to January 2006 and EMBASE from 1980 to January 2006 without language restrictions to identify relevant studies and identified others from the bibliographies of retrieved articles. Study SelectionWe included randomized trials of patients aged 18 years or older undergoing interventions to facilitate a successful diagnostic LP or to potentially reduce adverse events.Studies assessing the accuracy of biochemical analysis of the CSF for possible bacterial meningitis were also identified. Data ExtractionTwo investigators independently appraised study quality and extracted relevant data.For studies of the LP technique, data on the intervention and the outcome were extracted.For studies of the laboratory diagnosis of bacterial meningitis, data on the reference standard and test accuracy were extracted. Data SynthesisWe found 15 randomized trials.A random-effects model was used for quantitative synthesis.Five studies of 587 patients compared atraumatic needles with standard needles and found a nonsignificant decrease in the odds of headache with an atraumatic needle (absolute risk reduction [ARR], 12.3%; 95% confidence interval [CI], -1.72% to 26.2%).Reinsertion of the stylet before needle removal decreased the risk of headache (ARR, 11.3%; 95% CI, 6.50%-16.2%).The combined results from 4 studies of 717 patients showed a nonsignificant decrease in headache in patients who were mobilized after LP (ARR, 2.9%; 95% CI, -3.4 to 9.3%).Four studies on the accuracy of biochemical analysis of CSF in patients with suspected meningitis met inclusion criteria.A CSF-blood glucose ratio of 0.4 or less (likelihood ratio [LR], 18; 95% CI, 12-27]), CSF white blood cell count of 500/µL or higher (LR, 15; 95% CI, 10-22), and CSF lactate level of 31.53 mg/dL or more (Ն3.5 mmol/L; LR, 21; 95% CI, 14-32) accurately diagnosed bacterial meningitis.Conclusions These data suggest that small-gauge, atraumatic needles may decrease the risk of headache after diagnostic LP.Reinsertion of the stylet before needle removal should occur and patients do not require bed rest after the procedure.Future research should focus on evaluating interventions to optimize the success of a diagnostic LP and to enhance training in procedural skills.
Complete remission through blast cell differentiation inPLZF/RARα-positive acute promyelocytic leukemia: in vitro and in vivo studies
Authors: Maria C. Petti, Francesco Fazi, Massimo Gentile, Daniela Diverio, Paolo De Fabritiis, M. Stefania De Propris, Roberto Fiorini, Maria A. Aloe Spiriti, Fabrizio Padula, Pier Giuseppe Pelicci, Clara Nervi, Francesco Lo Coco
Journal: Blood (2002)
Monovalent Fab' immunoglobulin fragments from endemic pemphigus foliaceus autoantibodies reproduce the human disease in neonatal Balb/c mice.
Authors: B Rock, R S Labib, L A Diaz
Journal: Journal of Clinical Investigation (1990)

Fogo selvagem (FS) is an autoimmune disease caused by IgG autoantibodies to desmoglein I (DG-I), a desmosomal glycoprotein. We have previously shown that the autoantibodies in these patients are pathogenic and restricted mainly to the IgG4 subclass. The purpose of this study was to determine if the Fc domain or the valence of FS autoantibodies were relevant in the induction of epidermal disease in neonatal mice. IgG4 was prepared from sera of FS patients by anion exchange chromatography, and digested with pepsin to yield F(ab')2 fragments. Monovalent FS Fab' were made by reduction and alkylation of FS F(ab')2. Intact FS IgG4, FS F(ab')2, and FS Fab' fragments were injected into neonatal mice. Intact FS IgG4 and both FS IgG fragments were pathogenic. The disease in the animals was dose dependent, and on the molar basis, FS Fab' fragments were more potent and efficient in producing disease than whole FS IgG. These results suggest: (a) simple binding of FS autoantibodies to DG-I may trigger keratinocyte detachment and epidermal disease; (b) DG-I may represent a keratinocyte cell adhesion molecule; and (c) complement activation and surface cross-linking may not be relevant in keratinocyte detachment.
Melatonin and Breast Cancer: A Prospective Study
Authors: R. C. Travis, D. S. Allen, I. S. Fentiman, T. J. Key
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Experimental data from animals suggest a protective role for the pineal hormone melatonin in the etiology of breast cancer, but results from the few retrospective case–control studies that examined the association in humans have been inconsistent. To determine whether low levels of endogenous melatonin are associated with an increased risk for developing breast cancer, we conducted a prospective nested case–control study among British women. Methods: Concentrations of 6-sulfatoxymelatonin, the main metabolite of melatonin in urine and a validated marker of circulating melatonin levels, were measured by radioimmunoassay in 24-hour urine samples collected from women shortly after enrollment in the prospective Guernsey III Study. Levels of 6-sulfatoxymelatonin were compared among 127 patients diagnosed with breast cancer during follow-up and among 353 control subjects, matched for age, recruitment date, menopausal status, and day of menstrual cycle for premenopausal women or number of years postmenopausal for postmenopausal women. Associations were examined by analyses of covariance and conditional logistic regression. All tests of statistical significance were two-sided. Results: No statistically significant differences in urinary 6-sulfatoxymelatonin concentrations were observed between women who developed breast cancer and control subjects among premenopausal or postmenopausal women (P= .8 and P= .9, respectively). When data from premenopausal and postmenopausal women were combined in a multivariable analysis adjusted for potential confounders and grouped into three categories defined by 6-sulfatoxymelatonin tertiles of control subjects, the level of 6-sulfatoxymelatonin excreted was not statistically significantly associated with the risk of breast cancer (odds ratio [OR] for breast cancer = 0.95, 95% confidence interval [CI] = 0.55 to 1.65, comparing the middle category with the lowest category of 6-sulfatoxymelatonin concentration, and OR = 0.99, 95% CI = 0.58 to 1.70, comparing the highest category with the lowest category). Conclusion: We found no evidence that the level of melatonin is strongly associated with the risk for breast cancer.