tbuckley/cabot-search huggingface dataset:
Relaxin’s Physiological Roles and Other Diverse Actions
Authors: O. David Sherwood
Journal: Endocrine Reviews (2004)

Relaxin has vital physiological roles in pregnant rats, mice, and pigs. Relaxin promotes growth and softening of the cervix, thus facilitating rapid delivery of live young. Relaxin also promotes development of the mammary apparatus, thus enabling normal lactational performance. The actions of relaxin on the mammary apparatus vary among species. Whereas relaxin is required for development of the mammary nipples in rats and mice, it is essential for prepartum development of glandular parenchyma in pregnant pigs. During pregnancy relaxin also inhibits uterine contractility and promotes the osmoregulatory changes of pregnancy in rats. Recent studies with male and nonpregnant female rodents revealed diverse therapeutic actions of relaxin on nonreproductive tissues that have clinical implications. Relaxin has been reported to reduce fibrosis in the kidney, heart, lung, and liver and to promote wound healing. Also, probably through its vasodilatory actions, relaxin protects the heart from ischemia-induced injury. Finally, relaxin counteracts allergic reactions. Knowledge of the diverse physiological and therapeutic actions of relaxin, coupled with the recent identification of relaxin receptors, opens numerous avenues of investigation that will likely sustain a high level of research interest in relaxin for the foreseeable future.
Is CT scan still necessary for staging in Hodgkin and non-Hodgkin lymphoma patients in the PET/CT era?
Authors: P. Raanani, Y. Shasha, C. Perry, U. Metser, E. Naparstek, S. Apter, A. Nagler, A. Polliack, I. Ben-Bassat, E. Even-Sapir
Journal: Annals of Oncology (2005)
A FURTHER STUDY OF THE BACTERICIDAL ACTION OF ETHYLHYDROCUPREIN ON PNEUMOCOCCI
Authors: Henry F. Moore
Journal: The Journal of Experimental Medicine (1915)

1. The serum of rabbits which have been previously treated with a single dose of ethylhydrocuprein (optochin) exerts a bactericidal action on, and, later, inhibits the growth of pneumococci in the test-tube. 2. These actions are most evident in the serum of rabbits when the base (optochin base) is given in oil subcutaneously; somewhat less when the hydrochloride of the drug is given in water subcutaneously; slight when the base is given in oil intramuscularly; and least evident, or absent, when the hydrochloride in water is introduced directly into the stomach. To get these effects by the intravenous route, toxic doses must be given, and, even with toxic non-fatal doses, the effects do not last long. 3. In the case of the base given in oil subcutaneously to rabbits in a dosage of 0.1 gram per kilo of body weight, the bactericidal action of the serum is at its maximum about one hour after administration, and it passes into an inhibitory effect about four hours after the drug has been given. 4. In man the same inhibitory and bactericidal actions of the serum are present when a single dose of 0.5 gram of the hydrochloride of the drug is given by the mouth or subcutaneously, but the bactericidal action is not so marked as in rabbits. 5. When the optochin concentration in the serum has, apparently,. diminished to a certain point in relation to the number of pneumococci present, the pneumococci which have survived the bactericidal action for a few hours acquire the power of growing freely.
Neurocognitive Function and CNS Integrity in Adult Survivors of Childhood Hodgkin Lymphoma
Authors: Kevin R. Krull, Noah D. Sabin, Wilburn E. Reddick, Liang Zhu, Gregory T. Armstrong, Daniel M. Green, Alejandro R. Arevalo, Matthew J. Krasin, Deo Kumar Srivastava, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2012)

Purpose Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL. Patients and Methods In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (&lt; 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations. Results Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P &lt; .001), naming speed (P &lt; .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E′; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E′]; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [DL co corr ; P = .04), and leukoencephalopathy (P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency (P = .001). Working memory impairment was associated with E/E′, although impaired sustained attention and naming speed were associated with DL co corr . Neurocognitive performance was associated with academic and vocational functioning. Conclusion These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.
Arnold Bennett and medicine: with particular reference to his description of dressing apraxia.
Authors: G D Perkin
Journal: BMJ (1981)

Examination of 400 Saxon, Romano-British, and mediaeval skeletons from seven archaeological excava- tions in the west of England showed an unexpectedly high incidence of osteoarthritis and osteophytosis.Three skeletons had evidence of an erosive peripheral arthritis-one with probable gout, one probable psoriatic arthropathy, and one with possible rheumatoid arthritis.The pattern and types of rheumatic disease, and the resultant disability, were apparently different.An exuberant form of large joint osteoarthritis was common and rheumatoid arthritis and similar diseases rare.
Different Cytokines Induce Surface Lymphotoxin-αβ on IL-7 Receptor-α Cells that Differentially Engender Lymph Nodes and Peyer's Patches
Authors: Hisahiro Yoshida, Asuka Naito, Jun-Ichiro Inoue, Mizuho Satoh, Sybil M Santee-Cooper, Carl F Ware, Atsushi Togawa, Satomi Nishikawa, Shin-Ichi Nishikawa
Journal: Immunity (2002)
Evidence based case report: Asymptomatic haematuria ... in the doctor
Authors: C. Del Mar
Journal: BMJ (2000)

The patient was waiting in the consulting room; everything was nearly ready. The occasion was the examination in general practice for fifth year medical students. We run an objective structured clinical examination. For this part, the student had to measure the patient's blood pressure (the “patient” was actually someone recruited from our general practice), test his urine using a dipstick, and report to the examiner within the five minutes between bells. Just one thing was missing—the midstream sample of normal urine for testing. Because I did not want to disturb the volunteer patient, I collected it from myself. I measured the patient's blood pressure again (this had to be done after every 10th student)—it was stable. And I tested the urine to check it was normal—it was not.

For the next two hours, students either told me (or, in the case of those less skilled at this technique, did not tell me) that there was a trace of blood in the urine. This was not a problem as far as the examination was concerned because the marking was not affected by the test result. But it was a problem for me. What should I do? I tested my urine again a week later, and when I found it was still positive I sent a specimen to the laboratory. The report stated that urine culture was negative but confirmed the presence of normal red cells (30/ml).

Conventional medical teaching had taught me that bleeding must come from somewhere. The model that sprang to mind first is summarised in the table. I then checked with a textbook of surgery.1 I had forgotten tuberculosis and schistosomiasis as causes of haematuria. A textbook of medicine2 suggested further …
Spontaneous oesophageal perforation: an unreported complication of lymphocytic oesophagitis
Authors: Peter J Hendy, Timothy HJ Florin
Journal: Gut (2013)

Lymphocytic oesophagitis, an only recently described pathological entity (Rubio et al 1 2006), was reviewed in Gut in 2012.2 Its histology is characterised by a predominantly peripapillary lymphocytic infiltrate in the oesophageal mucosa with the absence of significant granulocytes. Studies into over 200 patients with this condition2 ,3 including a recent letter by Ronkainen et al 4 2012, suggest that the clinical manifestations of this condition appear to be mild. Approximately half of patients with symptoms have gastro-oesophageal reflux, and two-thirds have dysphagia.3 

Here we describe a spontaneous oesophageal perforation associated with lymphocytic oesophagitis. A previously well 35-year-old woman presented to the emergency department …
Comment on: Hernandez et al. Patterns of Glycemia in Normal Pregnancy: Should the Current Therapeutic Targets Be Challenged? Diabetes Care 2011;34:1660–1668
Authors: Edmond A. Ryan
Journal: Diabetes Care (2011)

The article by Hernandez et al. (1) makes a useful contribution to documenting normoglycemia in pregnancy. Although the current target glucose levels in managing gestational diabetes (GDM) are for the most part based on case-control studies, the author's statement that macrosomia still occurs if these targets are met is belied by the Maternal-Fetal Medicine Units Network report of a 7.1% large-for-gestational-age (LGA) rate when these targets are attained (2). Two more important concerns exist: the veracity of the data and using 1 SD above a weighted mean as a proposed target for glycemic control in GDM.

Based on their review of data from 255 …
IL-37 requires IL-18Rα and SIGIRR/IL-1R8 to diminish allergic airway inflammation in mice
Authors: L. Lunding, S. Webering, C. Vock, A. Schröder, D. Raedler, B. Schaub, H. Fehrenbach, M. Wegmann
Journal: Allergy (2015)

Interleukin (IL) 37 has been described as a negative regulator of innate immunity, as it reduces the activation and cytokine production of different innate immune cells. Recently, results from the CLARA childhood asthma cohort suggested an implication of IL-37 for human asthma pathogenesis. This study aimed to investigate the effects of IL-37 on allergic airway inflammation in a mouse model of experimental asthma.Peripheral blood mononuclear cells (PBMCs) of children were cultured for 48 h (anti-CD3/anti-CD28 stimulation or unstimulated), and IL-37 concentrations in supernatants were determined. Wild-type, IL-18Rα-deficient ((-/-) ), and SIGIRR(-/-) C57BL/6 mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol to induce acute experimental asthma, and IL-37 was applied intranasally prior to each OVA challenge. Airway hyper-responsiveness (AHR), airway inflammation, cytokine levels in broncho-alveolar lavage fluid, and mucus production were determined.IL-37 production of human PBMCs was significantly lower in allergic asthmatics vs healthy children. In wild-type mice, intranasal administration of IL-37 ablated allergic airway inflammation as well as cytokine production and subsequently diminished the hallmarks of experimental asthma including mucus hyperproduction and AHR. In contrast, local application of IL-37 produced none of these effects in mice lacking either IL18Rα or SIGIRR/IL-1R8.This study demonstrates that IL-37 is able to ablate a TH2 cell-directed allergic inflammatory response and the hallmarks of experimental asthma in mice, suggesting that IL-37 may be critical for asthma pathogenesis. Furthermore, these data suggest a mode of action of IL-37 that involves IL18Rα as well as the orphan receptor SIGIRR/IL-1R8.
Mechanisms underlying the increase in mycobacterial infections in cystic fibrosis patients on azithromycin
Authors: Gareth Jones
Journal: Thorax (2011)

This study investigated the increased incidence of non-tuberculous mycobacterium (NTM) infections in cystic fibrosis (CF) patients on azithromycin. The authors were particularly interested in autophagia, a process whereby intracellular material is isolated into phagosomes and then destroyed by being fused with acid-rich lysosomes. It is disrupted by other macrolides and is crucial for the clearance of intracellular …
Chromatin Remodeling Is Required for Gene Reactivation after Decitabine-Mediated DNA Hypomethylation
Authors: Jiali Si, Yanis A. Boumber, Jingmin Shu, Taichun Qin, Saira Ahmed, Rong He, Jaroslav Jelinek, Jean-Pierre J. Issa
Journal: Cancer Research (2010)

Abstract The DNA hypomethylating drug decitabine (DAC) reactivates silenced gene expression in cancer and is approved for the treatment of the myelodysplastic syndrome. Gene reactivation after DAC is variable and incompletely understood. Here, we established a cell line system (YB5) derived from the SW48 colon cancer cell line to study DAC-induced reactivation. YB5 contains a hypermethylated cytomegalovirus promoter driving green fluorescent protein (GFP), and the locus is transcriptionally silent. GFP reexpression can be achieved by DAC treatment, but the expression level of individual cells is heterogeneous. DAC-treated YB5 cells were separated into GFP-positive and GFP-negative subpopulations. By comparing DAC-treated sorted GFP-positive and GFP-negative cells, we found that their methylation levels were similarly decreased but that histone modifications and histone H3 densities were remarkably different. Despite a similar degree of (incomplete) DNA hypomethylation, GFP-positive cells reverted to an active chromatin structure marked by higher H3K9 acetylation, lower H3K27 trimethylation, and lower promoter nucleosome density. GFP-negative cells had histone modifications and promoter nucleosome density, similar to parental cells. On DAC withdrawal, gradual resilencing and remethylation occurred in both GFP-positive and GFP-negative cells, and the resilencing correlated with a gradual increase in nucleosome occupancy in GFP-positive cells. These data show that hypomethylation alone after DAC is insufficient for gene expression induction, and that chromatin resetting to an active state including nucleosome eviction is required for activation of protein expression. Our findings suggest that gene expression is the key in optimizing DAC treatment strategies in the clinic. Cancer Res; 70(17); 6968–77. ©2010 AACR.
Neuropsychological Near Normality and Brain Structure Abnormality in Schizophrenia
Authors: Bruce E. Wexler, Hongtu Zhu, Morris D. Bell, Sarah S. Nicholls, Robert K. Fulbright, John C. Gore, Tiziano Colibazzi, Jose Amat, Ravi Bansal, Bradley S. Peterson
Journal: American Journal of Psychiatry (2008)

Cognitive deficits are prominent in schizophrenia. Patients have an average score one standard deviation below normal on a broad spectrum of cognitive tests. It has been repeatedly noted, however, that 20%-25% of patients differ from this general pattern and score close to normal on neuropsychological testing. This study used brain morphometry to 1) identify brain abnormalities associated with more severe cognitive deficits and 2) help determine whether cognitively relatively intact patients perform better because they have less severe illness or because they have a different illness.Patients were assigned to a neuropsychologically near normal (N=21) subgroup if they scored within 0.5 standard deviation of healthy comparison subjects (N=30) on four tests of attention and verbal and nonverbal working memory, and to a neuropsychologically impaired (N=54) group if they scored at least 1.0 standard deviation below that of comparison subjects. Subgroup assignments were confirmed with the California Verbal Learning Test and degraded-stimulus Continuous Performance Test. Volumes of ventricular compartments, hippocampus, amygdala, thalamus, cerebellum, and regional cortical gray and white matter were dependent variables. Differences among groups were evaluated by using linear mixed-model multivariate analyses with gender, age, and height as covariates.Both neuropsychologically near normal and neuropsychologically impaired patients had markedly smaller gray matter and larger third ventricle volumes than healthy comparison subjects. Only neuropsychologically impaired patients, however, had significantly smaller white matter and larger lateral ventricle volumes than healthy comparison subjects.Although both neuropsychologically impaired and neuropsychologically near normal patients have marked neuropathology in their gray matter, the relative absence of white matter pathology in the neuropsychologically near normal group suggests the possibility of differences in the disease process.
The ETA receptor antagonist, BMS-182874, reduces acute hypoxic pulmonary hypertension in pigs in vivo
Authors: P Holm
Journal: Cardiovascular Research (1998)

Objective: Elevated levels of the potent vasoactive peptide endothelin (ET), have been found in pathophysiological conditions associated with pulmonary hypertension. In this study, we have investigated the effects of the ETA receptor antagonist, BMS-182874, on hypoxic pulmonary hypertension in pigs. Methods: Pigs were subjected to acute, intermittent 15-min periods of hypoxia (FiO2 0.1). Following a first hypoxia establishing hypoxic baseline values, vehicle or BMS-182874 (10 or 30 mg/kg) was administered i.v. before a second hypoxic period. In separate groups of animals, the effects of the nitric oxide synthase inhibitor Nω-nitro-l-arginine (l-NNA) in combination with BMS-182874 (10 mg) during repeated hypoxia were investigated. The ET-1-blocking properties of BMS-182874 were studied in vivo by infusion of ET-1 during normoxia and in vitro using isolated porcine pulmonary arteries. Results: The hypoxia-evoked increase in mean pulmonary artery pressure was reduced by administration of BMS-182874 (10 mg/kg i.v.; from 42±8 to 34±4 mmHg, P<0.05 and 30 mg/kg i.v.; from 38±4 to 30±5 mmHg, P<0.05). In addition, BMS-182874 at 30 mg/kg reduced the pulmonary vascular resistance during hypoxia (from 7.4±1.5 to 5.3±1.1 mmHg·min·l−1P<0.05). The hemodynamic response to repeated hypoxia was reproducible in control animals and unaffected by the cyclo-oxygenase inhibitor diclophenac (3 mg/kg). Infusion of l-NNA alone resulted in an augmented pulmonary vasoconstriction during hypoxia; pulmonary arterial pressure from 35±6 to 43±9 mmHg; P<0.05 and vascular resistance from 7.2±1.1 to 9.9±1.8 mmHg·min·l−1; P<0.05. l-NNA in combination with BMS-182874 (10 mg/kg) resulted in a hypoxic pulmonary vasoconstriction of similar magnitude as hypoxic baseline. In addition, BMS-182874 reduced the hemodynamic response to ET-1 in normoxic pigs and competitively antagonized the vasoconstrictor effect of ET-1 in isolated porcine pulmonary arteries. Conclusions: The non-peptide, selective ETA receptor antagonist, BMS-182874, reduces hypoxic pulmonary vasoconstriction in pigs. The reduction in pulmonary vascular response to hypoxia following BMS-182874 is at least partly independent of nitric oxide.
Senior Adult Oncology
Authors: Arti Hurria, Ilene S. Browner, Harvey Jay Cohen, Crystal S. Denlinger, Mollie deShazo, Martine Extermann, Apar Kishor P. Ganti, Jimmie C. Holland, Holly M. Holmes, Mohana B. Karlekar, Nancy L. Keating, June McKoy, Bruno C. Medeiros, Ewa Mrozek, Tracey O’Connor, Stephen H. Petersdorf, Hope S. Rugo, Rebecca A. Silliman, William P. Tew, Louise C. Walter, Alva B. Weir, Tanya Wildes
Journal: Journal of the National Comprehensive Cancer Network (2012)

OverviewCancer is the leading cause of death in women and men aged 60 to 79 years. 1 More than 50% of all cancers and more than 70% of cancer-related deaths in the United States occur in patients aged 65 years or older. 2 By 2030, an estimated 70% of all cancers will be diagnosed in adults aged 65 years or older. 3Older individuals are more prone to develop cancer than younger individuals.Furthermore, the aging of the U.S. population and increased life expectancy of the elderly mean that cancer in older adults is becoming an increasingly common problem.Unique issues must be considered when caring for older adults with cancer.The biology of certain neoplasms and responsiveness to therapy changes
Sall1 Maintains Nephron Progenitors and Nascent Nephrons by Acting as Both an Activator and a Repressor
Authors: Shoichiro Kanda, Shunsuke Tanigawa, Tomoko Ohmori, Atsuhiro Taguchi, Kuniko Kudo, Yutaka Suzuki, Yuki Sato, Shinjiro Hino, Maike Sander, Alan O. Perantoni, Sumio Sugano, Mitsuyoshi Nakao, Ryuichi Nishinakamura
Journal: Journal of the American Society of Nephrology (2014)

The balanced self-renewal and differentiation of nephron progenitors are critical for kidney development and controlled, in part, by the transcription factor Six2, which antagonizes canonical Wnt signaling-mediated differentiation. A nuclear factor, Sall1, is expressed in Six2-positive progenitors as well as differentiating nascent nephrons, and it is essential for kidney formation. However, the molecular functions and targets of Sall1, especially the functions and targets in the nephron progenitors, remain unknown. Here, we report that Sall1 deletion in Six2-positive nephron progenitors results in severe progenitor depletion and apoptosis of the differentiating nephrons in mice. Analysis of mice with an inducible Sall1 deletion revealed that Sall1 activates genes expressed in progenitors while repressing genes expressed in differentiating nephrons. Sall1 and Six2 co-occupied many progenitor-related gene loci, and Sall1 bound to Six2 biochemically. In contrast, Sall1 did not bind to the Wnt4 locus suppressed by Six2. Sall1-mediated repression was also independent of its binding to DNA. Thus, Sall1 maintains nephron progenitors and their derivatives by a unique mechanism, which partly overlaps but is distinct from that of Six2: Sall1 activates progenitor-related genes in Six2-positive nephron progenitors and represses gene expression in Six2-negative differentiating nascent nephrons.
A New Family of Potent AB5 Cytotoxins Produced by Shiga Toxigenic <i>Escherichia coli </i>
Authors: Adrienne W. Paton, Potjanee Srimanote, Ursula M. Talbot, Hui Wang, James C. Paton
Journal: The Journal of Experimental Medicine (2004)

The Shiga toxigenic Escherichia coli (STEC) O113:H21 strain 98NK2, which was responsible for an outbreak of hemolytic uremic syndrome, secretes a highly potent and lethal subtilase cytotoxin that is unrelated to any bacterial toxin described to date. It is the prototype of a new family of AB5 toxins, comprising a single 35-kilodalton (kD) A subunit and a pentamer of 13-kD B subunits. The A subunit is a subtilase-like serine protease distantly related to the BA_2875 gene product of Bacillus anthracis. The B subunit is related to a putative exported protein from Yersinia pestis, and binds to a mimic of the ganglioside GM2. Subtilase cytotoxin is encoded by two closely linked, cotranscribed genes (subA and subB), which, in strain 98NK2, are located on a large, conjugative virulence plasmid. Homologues of the genes are present in 32 out of 68 other STEC strains tested. Intraperitoneal injection of purified subtilase cytotoxin was fatal for mice and resulted in extensive microvascular thrombosis, as well as necrosis in the brain, kidneys, and liver. Oral challenge of mice with E. coli K-12–expressing cloned subA and subB resulted in dramatic weight loss. These findings suggest that the toxin may contribute to the pathogenesis of human disease.