tbuckley/cabot-search huggingface dataset:
Severe thrombocytopenia in iron deficiency anemia
Authors: Mark Berger, Lawrence F. Brass
Journal: American Journal of Hematology (1987)

Abstract Mild‐to‐moderate thrombocytopenia has been reported as an occasional finding in patients with iron deficiency. The present case describes a multiparous woman who presented with increased menorrhagia, severe anemia (3.0 g/dl) and thrombocytopenia (9,000 platelets/mm 3 ). Her bone marrow examination showed iron deficiency, megakaryocytopenia, and erythroid hypoplasia but no other evidence of a primary marrow disorder. Her symptoms, the thrombocytopenia and the megakaryocytopenia, resolved with iron replacement. This case demonstrates the profound degree to which thrombopoiesis can be affected in iron deficiency.
Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses
Authors: Long Li, Qianqian Zhu, Xin He, Saurabh Sinha, Marc S Halfon
Journal: Genome biology (2007)

Abstract Background Transcriptional cis -regulatory modules (for example, enhancers) play a critical role in regulating gene expression. While many individual regulatory elements have been characterized, they have never been analyzed as a class. Results We have performed the first such large-scale study of cis -regulatory modules in order to determine whether they have common properties that might aid in their identification and contribute to our understanding of the mechanisms by which they function. A total of 280 individual, experimentally verified cis -regulatory modules from Drosophila were analyzed for a range of sequence-level and functional properties. We report here that regulatory modules do indeed share common properties, among them an elevated GC content, an increased level of interspecific sequence conservation, and a tendency to be transcribed into RNA. However, we find that dense clustering of transcription factor binding sites, especially homotypic clustering, which is commonly believed to be a general characteristic of regulatory modules, is rather a feature that belongs chiefly to a specific subclass. This has important implications for current computational approaches, many of which are biased toward this subset. We explore two new strategies to assess binding site clustering and gauge their performances with respect to their ability to detect all 280 modules and various functionally coherent subsets. Conclusion Our findings demonstrate that cis -regulatory modules share common features that help to define them as a class and that may lead to new insights into mechanisms of gene regulation. However, these properties alone may not be sufficient to reliably distinguish regulatory from non-regulatory sequences. We also demonstrate that there are distinct subclasses of cis -regulatory modules that are more amenable to in silico detection than others and that these differences must be taken into account when attempting genome-wide regulatory element discovery.
Influence of human leukocyte antigen and tumour necrosis factor genes on the development of pre-eclampsia
Authors: D. Kilpatrick
Journal: Human Reproduction Update (1999)

Pre-eclampsia is a syndrome with a strong familial component. Autosomal recessive inheritance acting only in the mother is not consistent with the epidemiological data, and a more complex genetic susceptibility, involving interactions between maternal and fetal genomes, seems likely. The human leukocyte antigen (HLA) system has been implicated, but many of the findings reported have been inconsistent or contradictory. Pre-eclampsia is unlikely to be the simple result of excessive HLA-class II antigen sharing between mother and fetus, as was first thought, but a more complex mechanism involving feto-maternal compatibility cannot be excluded. The reported increase in HLA-DR4 in mothers and babies from pre-eclamptic pregnancies has not been independently confirmed for mothers, and no further studies have been conducted with babies. Consequently, the allegedly stronger relationship with HLA-DR4 sharing between mother and fetus has neither been confirmed nor refuted. Certain (B44-DR7)-containing haplotypes appear to confer increased risk for pre-eclampsia on the basis of independent analyses of American and Scottish populations. HLA-DR53 may be associated with the antiphospholipid antibody syndrome, which is itself a strong risk factor for pre-eclampsia. The tumour necrosis factor (TNF)-alpha allele, TNF1, may be associated with pre-eclampsia and certainly elevated concentrations of the cytokine appear to be a feature of the disease. The inducibility of TNF-alpha is HLA-class II-dependent, and the relevance of HLA-class II genes might be entirely in relation to TNF-alpha synthesis and secretion.
The autoimmune regulator gene (<i>AIRE</i>) is strongly associated with vitiligo
Authors: R. Tazi-Ahnini, A.J.G. McDonagh, D.A. Wengraf, T.R.J. Lovewell, Y. Vasilopoulos, A.G. Messenger, M.J. Cork, D.J. Gawkrodger
Journal: British Journal of Dermatology (2008)

Vitiligo is an autoimmune disorder that occurs with greatly increased frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected an association between alopecia areata and single nucleotide polymorphisms (SNPs) in the AIRE gene.To report the findings of an extended study including haplotype analysis on six AIRE polymorphisms (AIRE C-103T, C4144G, T5238C, G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease.A case-control analysis was performed.Results showed a strong association between AIRE 7215C and vitiligo [P = 1.36 x 10(-5), odds ratio (OR) 3.12, 95% confidence interval (CI) 1.87-5.46]. We found no significant association with the other polymorphisms individually. However, haplotype analysis revealed that the AIRE haplotype CCTGCC showed a highly significant association with vitiligo (P = 4.14 x 10(-4), OR 3.00, 95% CI 1.70-5.28). To select the most informative minimal haplotypes, we tagged the polymorphisms using SNP tag software. Using AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, the haplotype AIRE CGCC was associated with vitiligo (P = 0.003, OR 2.49, 95% CI 1.45-4.26).The link between vitiligo and AIRE raises the possibility that defective skin peripheral antigen selection in the thymus is involved in the changes that result in melanocyte destruction in this disorder.
Exercise pretraining protects against cerebral ischaemia induced by heat stroke in rats
Authors: Yu-Wen Chen, Sheng-Hsien Chen, Willy Chou, Yi-Ming Lo, Ching-Hsia Hung, Mao-Tsun Lin
Journal: British Journal of Sports Medicine (2007)

In the rat brain, heat-stroke-induced damage to cerebral neurons is attenuated through heat-shock-induced overexpression of heat-shock protein 72 (HSP72).To ascertain whether progressive exercise preconditioning induces HSP72 expression in the rat brain and prevents heat-stroke-induced cerebral ischaemia and injury.Male Wistar rats were randomly assigned to either a sedentary group or an exercise group. Those in the exercise group progressively ran on a treadmill 5 days/week, for 30-60 min/day at an intensity of 20-30 m/min for 3 weeks. The effects of heat stroke on mean arterial pressure, cerebral blood flow, brain ischaemia markers (glutamate, lactate/pyruvate ratio and nitric oxide), a cerebral injury marker (glycerol) and brain neuronal damage score in the preconditioned animals were compared with effects in unexercised controls. Heat stroke was induced by exposing urethane-anaesthetised animals to a temperature of 43 degrees C for 55 min, which caused the body temperature to reach 42 degrees C.Three weeks of progressive exercise pretreatment induced HSP72 preconditioning in the brain and conferred significant protection against heat-stroke-induced hyperthermia, arterial hypotension, cerebral ischaemia and neuronal damage; it also prolonged survival.Exercise for 3 weeks can improve heat tolerance as well as attenuate heat-stroke-induced cerebral ischaemia in rats. The maintenance of mean arterial pressure and cerebral blood flow at appropriate levels in the rat brain may be related to overexpression of HSP72.
Signature polymorphisms in the internal transcribed spacer region relevant for the differentiation of zoophilic and anthropophilic strains of <i>Trichophyton interdigitale</i> and other species of <i>T. mentagrophytes sensu lato</i>
Authors: S. Heidemann, M. Monod, Y. Gräser
Journal: British Journal of Dermatology (2009)

Dermatophytes are the main cause of superficial mycoses in humans and animals. Molecular research has given useful insights into the phylogeny and taxonomy of the dermatophytes to overcome the difficulties with conventional diagnostics.The Trichophyton mentagrophytes complex consists of anthropophilic as well as zoophilic species. Although several molecular markers have been developed for the differentiation of strains belonging to T. mentagrophytes sensu lato, correct identification still remains problematic, especially concerning the delineation of anthropophilic and zoophilic strains of T. interdigitale. This differentiation is not academic but is essential for selection of the correct antimycotic therapy to treat infected patients.One hundred and thirty isolates identified by morphological characteristics as T. mentagrophytes sensu lato were investigated using restriction fragment length polymorphism (RFLP) and sequence analysis of the polymerase chain reaction-amplified internal transcribed spacer (ITS) region of the rDNA.Species of this complex produced individual RFLP patterns obtained by the restriction enzyme MvaI. Subsequent sequence analysis of the ITS1, 5.8S and ITS2 region of all strains, but of T. interdigitale in particular, revealed single unique polymorphisms in anthropophilic and zoophilic strains.Signature polymorphisms were observed to be useful for the differentiation of these strains and epidemiological data showed a host specificity among zoophilic strains of T. interdigitale/Arthroderma vanbreuseghemii compared with A. benhamiae as well as characteristic clinical pictures in humans when caused by zoophilic or anthropophilic strains. The delineation is relevant because it helps in determining the correct treatment and provides clues regarding the source of the infection.
Angiotensin II Directly Stimulates ENaC Activity in the Cortical Collecting Duct via AT1 Receptors
Authors: János Peti-Peterdi, David G. Warnock, P. Darwin Bell
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Angiotensin II (AngII) helps to regulate overall renal tubular reabsorption of salt and water, yet its effects in the distal nephron have not been well studied. The purpose of these studies was to determine whether AngII stimulates luminal Na + transport in the cortical collecting duct (CCD). Intracellular Na + concentration ([Na + ] i ), as a reflection of Na + transport across the apical membrane, was measured with fluorescence microscopy using sodium-binding benzofuran isophthalate (SBFI) in isolated, perfused CCD segments dissected from rabbit kidneys. Control [Na + ] i , during perfusion with 25 mM NaCl and a Na + -free solution in the bath containing the Na + -ionophore monensin (10 μM, to eliminate basolateral membrane Na + transport) averaged 19.3 ± 5.2 mM ( n = 16). Increasing luminal [NaCl] to 150 mM elevated [Na + ] i by 9.87 ± 1.5 mM ( n = 7; P &lt; 0.05). AngII (10 −9 M) added to the lumen significantly elevated baseline [Na + ] i by 6.3 ± 1.0 mM and increased the magnitude (Δ = 25.2 ± 3.7 mM) and initial rate (≈5 fold) of change in [Na + ] i to increased luminal [NaCl]. AngII when added to the bath had similar stimulatory effects; however, AngII was much more effective from the lumen. Thus, AngII significantly increased the apical entry of Na + in the CCD. To determine if this apical entry step occurred via the epithelial Na + channel (ENaC), studies were performed using the specific ENaC blocker, benzamil hydrochloride (10 −6 M). When added to the perfusate, benzamil almost completely inhibited the elevations in [Na + ] i to increased luminal [NaCl] in both the presence and absence of AngII. These results suggest that AngII directly stimulates Na + channel activity in the CCD. AT 1 receptor blockade with candesartan or losartan (10 −6 M) prevented the stimulatory effects of AngII. Regulation of ENaC activity by AngII may play an important role in distal Na + reabsorption in health and disease.
Biochemical and Genetic Aspects of Mental Retardation
Authors: J H Menkes, B R Migeon
Journal: Annual Review of Medicine (1966)

Mental retardation is a symptom common to a number of neurological disorders of infancy and childhood. Its definition is ultimately a social one, and implies a degree of intellectual malfunction incompatible with successful social independence at maturity. In the majority of patients, retardation is detected in the early years of life, but in others, intellectual deterioration appears only after a variable period of normal development. This review intends to summarize our knowledge regarding the disorders which have mental retardation as a prominent clinical feature, and result from a well-defined genetic defect. This may involve a single gene and, there­ fore, lead to an inborn enzymatic disorder or may be secondary to an anom­ alous chromosomal pattern. In the first group of diseases, the diagnosis rests on the detection of a biochemical abnormality, which may be the direct or indirect result of the failure in enzymatic function. In the second group, microscopically evident anomalies of chromosome structure confirm the diagnosis. It is perhaps a significant commentary on the status of our knowledge concerning cerebral functioning and intermediary metabolism that in none of these conditions has it been possible to state either how the enzymatic defect produces men­ tal retardation, or to define unequivocally an abnormality in any one of the numerous enzymes whose production must be controlled by genes located on the anomalous chromosome. .
Angiotensin-Converting Enzyme (ACE) Expression Defines the Earliest Primitive and Definitive Lympho-Hematopoietic Progenitors Derived from Human Embryonic Stem Cells.
Authors: Elias T. Zambidis, Venta J. Jokubaitis, Ada Tam, Lidia Sinka, Curt I. Civin, Manuela Tavian, Paul J. Simmons, Bruno Peault
Journal: Blood (2006)
The Effect of Lay Advertising on Breast-feeding Prevalence
Authors: K. Paul Duncan
Journal: JAMA (1990)

To the Editor. —  I was disappointed by the remarks of Dr Finberg, 1 unsupported by documentation, pertaining to direct public advertising of infant formula. Many of my colleagues are contributing to this free-market phobia, despite having been trained to require scientific evidence of virtually all causeand-effect assertions. To my knowledge, there is no such evidence that direct public advertising of infant formula will cause a decline in breast-feeding. Until some is found, we would be premature to ask Congress to treat formula advertising and tobacco advertising as analogous.
Early Compared With Late Radiotherapy in Combined Modality Treatment for Limited Disease Small-Cell Lung Cancer: A London Lung Cancer Group Multicenter Randomized Clinical Trial and Meta-Analysis
Authors: Stephen G. Spiro, Lindsay E. James, Robin M. Rudd, Colin W. Trask, Jeffrey S. Tobias, Michael Snee, David Gilligan, Philip A. Murray, Mary Carmen Ruiz de Elvira, Katy M. O'Donnell, Nicole H. Gower, Peter G. Harper, Allan K. Hackshaw
Journal: Journal of Clinical Oncology (2006)

Purpose To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC). Patients and Methods Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-naïve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks. Results TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17). Conclusion This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.
Paravalvular Leak After Transcatheter Aortic Valve Replacement
Authors: Philippe Généreux, Stuart J. Head, Rebecca Hahn, Benoit Daneault, Susheel Kodali, Mathew R. Williams, Nicolas M. van Mieghem, Maria C. Alu, Patrick W. Serruys, A. Pieter Kappetein, Martin B. Leon
Journal: Journal of the American College of Cardiology (2013)
Palifermin Reduces the Incidence of Oral Mucositis in Patients With Metastatic Colorectal Cancer Treated With Fluorouracil-Based Chemotherapy
Authors: Lee S. Rosen, Ehtesham Abdi, Ian D. Davis, John Gutheil, Frederick M. Schnell, John Zalcberg, Alessandra Cesano, Urte Gayko, Mon-Gy Chen, Stephen Clarke
Journal: Journal of Clinical Oncology (2006)

To characterize the efficacy and safety of palifermin in reducing the incidence of oral mucositis (OM) and diarrhea when administered to patients with metastatic colorectal cancer (CRC) receiving fluorouracil/leucovorin (FU/LV) chemotherapy.Patients (N = 64) were randomly assigned to receive either placebo or palifermin (40 microg/kg for 3 consecutive days) before each of two consecutive cycles of chemotherapy with FU/LV. The incidence of OM and diarrhea, safety, disease progression, and survival were evaluated.Thirty-six patients received placebo and 28 patients received palifermin. The incidence of WHO grade 2 or higher OM was lower in patients who received palifermin compared with placebo (29% v 61% in cycle 1; 11% v 47% in cycle 2). FU dose reductions in the second chemotherapy cycle were more frequent in the placebo group (31%) than in the palifermin group (14%). Investigators reported lower mucositis scores and patients reported less severe symptoms with palifermin. There were no statistically significant differences in the incidence or severity of diarrhea or in overall survival between the groups. Overall, palifermin was safe and well tolerated.Palifermin administered at the indicated dosing regimen (40 microg/kg for 3 consecutive days) before chemotherapy was well tolerated and resulted in a statistically significant and clinically meaningful reduction in the incidence of WHO grade 2 or higher OM in patients with metastatic CRC.
We are better off without perfect perception
Authors: Eli Brenner, Jeroen B. J. Smeets
Journal: Behavioral and Brain Sciences (2001)

Stoffregen &amp; Bardy's target article is based on the assumption that our senses' ultimate purpose is to provide us with perfect information about the outside world. We argue that it is often more important that information be available quickly than that it be perfect. Consequently our nervous system processes different aspects of information about our surrounding as separately as possible. The separation is not between the senses, but between separate aspects of our surrounding. This results in inconsistencies between judgments: sometimes because different frames of reference are used. Such inconsistencies are fundamental to the way the information is picked up, however, and hence cannot be avoided with clearer instructions to the subjects.
Enhancement of Antibody-Dependent Mechanisms of Tumor Cell Lysis by a Targeted Activator of Complement
Authors: Masaki Imai, Rieko Ohta, Juan C. Varela, Hongbin Song, Stephen Tomlinson
Journal: Cancer Research (2007)

Complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies (mAb). We investigated a novel strategy to overwhelm complement inhibitor activity and amplify complement activation on tumor cells. The C3-binding domain of human complement receptor 2 (CR2; CD21) was linked to the complement-activating Fc region of human IgG1 (CR2-Fc), and the ability of the construct to target and amplify complement deposition on tumor cells was investigated. CR2 binds C3 activation fragments, and CR2-Fc targeted tumor cells by binding to C3 initially deposited by a tumor-specific antibody. Complement deposition on Du145 cells (human prostate cancer cell line) and anti-MUC1 mAb-mediated complement-dependent lysis of Du145 cells were significantly enhanced by CR2-Fc. Anti-MUC1 antibody-dependent cell-mediated cytotoxicity of Du145 by human peripheral blood mononuclear cells was also significantly enhanced by CR2-Fc in both the presence and the absence of complement. Radiolabeled CR2-Fc targeted to s.c. Du145 tumors in nude mice treated with anti-MUC1 mAb, validating the targeting strategy in vivo. A metastatic model was used to investigate the effect of CR2-Fc in a therapeutic paradigm. Administration of CR2-Fc together with mAb therapy significantly improved long-term survival of nude mice challenged with an i.v. injection of EL4 cells. The data show that CR2-Fc enhances the therapeutic efficacy of antibody therapy, and the construct may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density.