tbuckley/cabot-search huggingface dataset:
Acute Hypoglycemia Impairs Executive Cognitive Function in Adults With and Without Type 1 Diabetes
Authors: Alex J. Graveling, Ian J. Deary, Brian M. Frier
Journal: Diabetes Care (2013)

Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes.Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes).Compared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes.Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed.
Standardisation of synovial tissue infiltrate analysis: how far have we come? how much further do we need to go?
Authors: M D Smith
Journal: Annals of the Rheumatic Diseases (2005)

Changes in cellular infiltrate and expression of cytokines, chemokines, and cell adhesion molecules as a result of therapeutic interventions in rheumatoid arthritis can be demonstrated in the synovial membrane. However, before synovial tissue analysis can be used as an outcome measure in such studies, standardisation of the site and method of synovial tissue acquisition, methods of tissue processing, and appropriate methods of detection and measurement of cell lineage specific markers and relevant biological proteins is needed.
New treatments for Tuberculosis
Authors: William Martin Ricketts
Journal: Thorax (2012)

New treatments for TuberculosisDiacon et al report a promising advance in both the future management of tuberculosis (TB) and the future design of drug trials in this field. 1 The authors undertook a prospective, randomised study in uncomplicated, treatment naive patients with smear-positive pulmonary TB in South Africa.The study assessed the early bactericidal activity (EBA) of novel combinations of new and existing drugs, but avoiding rifampicin and isoniazid, over the first 14 days of treatment, using the novel outcome measure of daily fall in colony forming units (CFUs) of Mycobacterium tuberculosis per millilitres of sputum.This approach has the potential to expedite the assessment of new individual drugs and combination regimens.The regimen of PA-824-moxifloxacin-pyrazinamide demonstrated significantly higher EBA at day 14 than that of bedaquiline, bedaquiline-pyrazinamide and bedaquiline-PA-824, but not PA-824-pyrazinamide and, while underpowered to demonstrate a significant difference, comparable with the standard regimen of rifampicin, isoniazid, pyrazinamide and ethambutol.Additionally, this regimen appears to produce a more rapid fall in CFUs than the majority of the other regimens tested.This study should be interpreted with cautious optimism at this stage; this regimen requires further investigation over the full course of treatment to ensure the promising results at 14 days persist and to ascertain the optimum duration of treatment.Additionally, further assessment of the risk of adverse reactions is required.However, if the early promise of this regimen is confirmed, it would provide the first entirely new regimen for many years.The avoidance of rifampicin reduces the likelihood of drug interactions.However, the key advantage of this regimen is the current absence of resistance to these new drugs, but these drugs must be used judiciously to preserve this status.
Shoulder injuries in skeletally immature throwers: review and current thoughts
Authors: James Leonard, Mark R Hutchinson
Journal: British Journal of Sports Medicine (2010)

The incidence of shoulder injuries in the paediatric athletic population continues to increase with increased participation particularly in throwing and overhead sports. While soft tissue injuries can occur, the physis remains the weak link and site of injury in many cases. Injury prevention targets proper throwing mechanics and the avoidance of overuse injuries by monitoring the amount of training and number of throws these young athletes are exposed to.
Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke
Authors: Woei-Cherng Shyu, Demeral David Liu, Shinn-Zong Lin, Wen-Wen Li, Ching-Yuan Su, Ying-Chen Chang, Hsiao-Jung Wang, Hsing-Won Wang, Chang-Hai Tsai, Hung Li
Journal: Journal of Clinical Investigation (2008)

Murine olfactory ensheathing cells (OECs) promote central nervous system axonal regeneration in models of spinal cord injury. We investigated whether OECs could induce a neuroplastic effect to improve the neurological dysfunction caused by hypoxic/ischemic stress. In this study, human OECs/olfactory nerve fibroblasts (hOECs/ONFs) specifically secreted trophic factors including stromal cell–derived factor–1α (SDF-1α). Rats with intracerebral hOEC/ONF implantation showed more improvement on behavioral measures of neurological deficit following stroke than control rats. [18F]fluoro-2-deoxyglucose PET (FDG-PET) showed increased glucose metabolic activity in the hOEC/ONF-treated group compared with controls. In mice, transplanted hOECs/ONFs and endogenous homing stem cells including intrinsic neural progenitor cells and bone marrow stem cells colocalized with specific neural and vascular markers, indicating stem cell fusion. Both hOECs/ONFs and endogenous homing stem cells enhanced neuroplasticity in the rat and mouse ischemic brain. Upregulation of SDF-1α and CXCR4 in hOECs/ONFs promoted neurite outgrowth of cocultured primary cortical neurons under oxygen glucose deprivation conditions and in stroke animals through upregulation of cellular prion protein (PrPC) expression. Therefore, the upregulation of SDF-1α and the enhancement of CXCR4 and PrPC interaction induced by hOEC/ONF implantation mediated neuroplastic signals in response to hypoxia and ischemia.
Reply to W.A.A. Tjalma and J.S. Grossman
Authors: Bradley J. Monk, David S. Miller, Krishnansu S. Tewari
Journal: Journal of Clinical Oncology (2015)

We appreciate the insightful comments by Tjalma 1 and Grossman 2 regarding the reporting of our phase II trial of pemetrexed plus cisplatin 3 and the case-based discussion of recurrent and metastatic cancer. 4ndeed, pemetrexed has had a checkered past in squamous cell lung and head and neck cancers.We remind Dr Grossman that approximately 25% of cervical cancers have a component of glandular histology.With pemetrexed plus cisplatin, there were 14 responses (33%) seen in the 43 patients with squamous cell histology and three (27%) in the 11 patients with adenocarcinoma. 3In addition, cervical cancers share a different biology from almost all lung and most head and neck cancers as well as a different anatomic location, stage at presentation, and treatment algorithm.One of the most exciting recent therapeutic advances in treating cervical cancer is the US Food and Drug Administration approval of bevacizumab in combination with paclitaxel plus cisplatin or topotecan as a treatment for patients with persistent, recurrent, or metastatic cervical cancer, based on the extension of overall survival in the phase III Gynecologic Oncology Group 240 study. 5The near 4-month improvement in overall survival is clinically important.In the pivotal phase III trial, 6 there were no lethal (grade 5) hemorrhages (including pulmonary), although the protocol prohibited enrollment of those with "active bleeding or pathologic conditions that carry a high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels."Although they were not statistically different from those not receiving bevacizumab, 4.5% of patients receiving bevacizumab with chemotherapy experienced grade 3 or 4 intestinal or genitourinary bleeding.We agree with Dr Tjalma that the largest impact on cervical cancer morbidity and mortality is rooted in effective prevention and screening, particularly immunization against the human papillomavirus.However, that was not the topic of our articles.
Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance
Authors: Shu-Chen Liu, Ngan-Ming Tsang, Wen-Che Chiang, Kai-Ping Chang, Chuen Hsueh, Ying Liang, Jyh-Lyh Juang, Kai-Ping N. Chow, Yu-Sun Chang
Journal: Journal of Clinical Investigation (2013)

Radioresistance of EBV-associated nasopharyngeal carcinoma (NPC) is associated with poor prognosis for patients with this form of cancer. Here, we found that NPC patients had increased serum levels of leukemia inhibitory factor (LIF) and that higher LIF levels correlated with local tumor recurrence. Furthermore, in vitro studies with NPC cells and in vivo xenograft mouse studies demonstrated that LIF critically contributes to NPC tumor growth and radioresistance. Using these model systems, we found that LIF treatment activated the mTORC1/p70S6K signaling pathway, enhanced tumor growth, inhibited DNA damage responses, and enhanced radioresistance. Treatment with either soluble LIF receptor (sLIFR), a LIF antagonist, or the mTOR inhibitor rapamycin reversed LIF-mediated effects, resulting in growth arrest and increased sensitivity to γ irradiation. Immunohistochemical (IHC) analyses of human NPC biopsies revealed that LIF and LIFR were overexpressed in tumor cells and that LIF expression correlated with the presence of the activated p-p70S6K. Finally, we found that the EBV-encoded protein latent membrane protein 1 (LMP1) enhances LIF production. Together, our findings indicate that LIF promotes NPC tumorigenesis and suggest that serum LIF levels may predict local recurrence and radiosensitivity in NPC patients.
Lung and Chest Wall Mechanics in Anesthetized Children
Authors: JONAS INGIMARSSON, ADALBJÖRN THORSTEINSSON, ANDERS LARSSON, OLOF WERNER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The mechanical behavior of the lung and chest wall has not been determined in preschool children. We therefore obtained static expiratory pressure-volume (P-V) curves of the respiratory system, partitioned into lung and chest wall components using esophageal (Pes) and airway pressure (Paw) registration in 17 anesthetized children (0.2 to 15.5 yr) in the supine and lateral position. From the P-V curves the inspiratory capacity (IC), the chest wall elastance (Ecw), and the maximal compliance of the respiratory system (Crs) and lungs (C(lung)) were calculated and related to growth. At IC (Paw = 30 cm H(2)O), Pes was the same in the two positions: 11 +/- 3 cm H(2)O. In contrast, at end-expiration (Paw = 0), Pes was close to zero in the lateral position, but markedly positive in the supine position (7 +/- 2 cm H(2)O). C(lung) was similar in both positions and increased with growth. Thus, C(lung) in the lateral position (ml/cm H(2)O) = 0.0017 x length(2.26) (cm), r(2) = 0.90. Crs and IC were approximately 20% greater (p </= 0.001) in the supine position than in the lateral, and correlated strongly (r(2) >/= 0.93) with power functions of length in both positions. Ecw expressed as a fraction of total respiratory system elastance (Ecw/Ers) was 33 +/- 12% in the lateral position and 12 +/- 16% supine (p < 0.001). We conclude that the respiratory mechanics in children correlated closely with body size and showed important differences between the supine and lateral positions.
A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate
Authors: Koonlawee Nademanee, John McKenzie, Erol Kosar, Mark Schwab, Buncha Sunsaneewitayakul, Thaveekiat Vasavakul, Chotikorn Khunnawat, Tachapong Ngarmukos
Journal: Journal of the American College of Cardiology (2004)
Disease-associated Bias in T Helper Type 1 (Th1)/Th2 CD4<b>+</b> T Cell Responses Against MAGE-6 in HLA-DRB10401<b>+</b> Patients With Renal Cell Carcinoma or Melanoma
Authors: Tomohide Tatsumi, Lisa S. Kierstead, Elena Ranieri, Loreto Gesualdo, Francesco P. Schena, James H. Finke, Ronald M. Bukowski, Jan Mueller-Berghaus, John M. Kirkwood, William W. Kwok, Walter J. Storkus
Journal: The Journal of Experimental Medicine (2002)

T helper type 1 (Th1)-type CD4+ antitumor T cell help appears critical to the induction and maintenance of antitumor cytotoxic T lymphocyte (CTL) responses in vivo. In contrast, Th2- or Th3/Tr-type CD4+ T cell responses may subvert Th1-type cell-mediated immunity, providing a microenvironment conducive to disease progression. We have recently identified helper T cell epitopes derived from the MAGE-6 gene product; a tumor-associated antigen expressed by most melanomas and renal cell carcinomas. In this study, we have assessed whether peripheral blood CD4+ T cells from human histocompatibility leukocyte antigens (HLA)-DRβ1*0401+ patients are Th1- or Th2-biased to MAGE-6 epitopes using interferon (IFN)-γ and interleukin (IL)-5 enzyme-linked immunospot assays, respectively. Strikingly, the vast majority of patients with active disease were highly-skewed toward Th2-type responses against MAGE-6–derived epitopes, regardless of their stage (stage I versus IV) of disease, but retained Th1-type responses against Epstein-Barr virus– or influenza-derived epitopes. In marked contrast, normal donors and cancer patients with no current evidence of disease tended to exhibit either mixed Th1/Th2 or strongly Th1-polarized responses to MAGE-6 peptides, respectively. CD4+ T cell secretion of IL-10 and transforming growth factor (TGF)-β1 against MAGE-6 peptides was not observed, suggesting that specific Th3/Tr-type CD4+ subsets were not common events in these patients. Our data suggest that immunotherapeutic approaches will likely have to overcome or complement systemic Th2-dominated, tumor-reactive CD4+ T cell responses to provide optimal clinical benefit.
Smoking-induced Skeletal Muscle Dysfunction. From Evidence to Mechanisms
Authors: Hans Degens, Ghislaine Gayan-Ramirez, Hieronymus W. H. van Hees
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). Patients with COPD commonly suffer from skeletal muscle dysfunction, and it has been suggested that cigarette smoke exposure contributes to the development of skeletal muscle dysfunction even before overt pulmonary pathology. This review summarizes the evidence that muscles of nonsymptomatic smokers are weaker and less fatigue resistant than those of nonsmokers. Although physical inactivity of many smokers contributes to some alterations observed in skeletal muscle, exposure to cigarette smoke per se can also induce skeletal muscle dysfunction. Cigarette smoke constituents and systemic inflammatory mediators enhance proteolysis and inhibit protein synthesis, leading to loss of muscle mass. Reduced skeletal muscle contractile endurance in smokers may result from impaired oxygen delivery to the mitochondria and ability of the mitochondria to generate ATP due to interaction of carbon monoxide with hemoglobin, myoglobin, and components of the respiratory chain. Besides hampering contractile function, smoking may have immediate beneficial effects on motor skills, which are attributable to nicotine. In contrast to pulmonary pathology, many of the effects of smoking on skeletal muscle are most likely reversible by smoking cessation.
Analysis of EPCAM Protein Expression in Diagnostics of Lynch Syndrome
Authors: Matthias Kloor, Anita Y. Voigt, Hans K. Schackert, Peter Schirmacher, Magnus von Knebel Doeberitz, Hendrik Bläker
Journal: Journal of Clinical Oncology (2010)

Lynch syndrome is an inherited tumor predisposition syndrome caused by germline mutations of DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Recently, germline deletions affecting the epithelial cell adhesion molecule (EPCAM) gene located upstream of MSH2 were identified as a novel mutational mechanism causing Lynch syndrome by epigenetic inactivation of the respective MSH2 allele. Immunohistochemical analysis of MMR protein expression is a hallmark of Lynch syndrome diagnostics, but it cannot distinguish between EPCAM deletion carriers and MSH2 mutation carriers. We hypothesized that EPCAM protein expression might be altered in tumors from patients with a germline EPCAM deletion.Immunohistochemistry was used to assess EPCAM expression in Lynch syndrome-associated MSH2-negative tumors (n = 26). Multiplex ligation-dependent probe amplification (MLPA) analysis was performed to detect germline deletions of the EPCAM and MSH2 gene loci.In four MSH2-negative tumors, a concomitant lack of EPCAM expression was detected. MLPA analysis revealed heterozygous EPCAM deletions in all patients with EPCAM-negative tumors. In contrast, EPCAM expression was positive in all cancers from patients with germline alterations affecting MSH2 but not EPCAM. Two EPCAM deletions were detected in patients with an EPCAM-positive tumor.These results indicate that loss of EPCAM protein expression is frequent in tumors from patients with EPCAM germline deletions. EPCAM immunohistochemistry therefore represents a promising novel tool for the identification of Lynch syndrome patients with EPCAM germline deletions.
Chromosomal location of human kappa and lambda immunoglobulin light chain constant region genes
Authors: OW McBride, PA Heiter, GF Hollis, D Swan, MC Otey, P Leder
Journal: The Journal of Experimental Medicine (1982)

The chromosomal location of human constant region light chain immunoglobulin (Ig) genes has been determined by analyzing a group of human fibroblast/rodent somatic cell hybrids with nucleic acid probes prepared from cloned human kappa and lambda constant region genes. Human chromosomes in each cell line were identified by isoenzyme analysis. The DNA from hybrid cells was digested with restriction endonucleases, size fractionated by gel electrophoresis, transferred to nitrocellulose or DBM paper, and hybridized with (32)P-labeled nucleic acid probes. The C(kappa) gene was assigned to human chromosome 2 and the C(lambda) genes to chromosome 22, based upon analysis of these hybrid cell lines, and these assignments were confirmed by analysis of subclones. A group of previously unassigned loci can be mapped to chromosome 2 by virtue of their close linkage to C(kappa). The lambda and kappa light chain and heavy chain Ig genes have now been assigned to all three human chromosomes that are involved in translocations with chromosome 8 in human B cell neoplasms. These techniques and probes provide a means to study the detailed arrangement of human Ig genes and their pseudogenes.
Delhi hospital’s call for special treatment for VIPs sparks criticism
Authors: Sanjeet Bagcchi
Journal: BMJ (2015)

A circular issued by New Delhi’s Ram Manohar Lohia Hospital has sparked a backlash across the country, with strong criticism from the Indian Medical Association and others who have called for the document to be withdrawn.

The circular, which is signed by the hospital’s medical superintendent, was issued on 18 May, but widespread reports on social media have sent the story viral.

The circular warned doctors at the hospital of “action” if they took care of VIP patients in a “casual way.” It said, “It has been observed that VIP reference has not been attended properly and handled in a very casual way by the doctors on duty at trauma centre …
CHEMOTAXIS OF MONONUCLEAR CELLS
Authors: Peter A. Ward
Journal: The Journal of Experimental Medicine (1968)

Chemotaxis of rabbit mononuclear cells was studied by the micropore-filter technique. Mononuclear cells obtained from mineral oil-induced peritoneal exudates respond chemotactically to rabbit serum treated with immune complexes or with streptokinase and plasminogen, to soluble factors produced by bacteria, and to lysates obtained from rabbit neutrophils. The first chemotactic factor requires heat-labile factors in serum for its generation, but, once formed, the chemotactic factor is relatively heat stable. This factor has been compared with the complement-associated factor in serum, C'(5, 6, 7)a, that is chemotactic for neutrophils. The ability to generate the mononuclear cell chemotactic factor in serum that has been treated with potassium thiocyanate suggests that complement is not required. The position of the chemotactic factor in preparative electrophoresis and density-gradient ultracentrifugation indicates that on the basis of physical-chemical criteria, this factor is not C'(5, 6, 7)a. The mononuclear cell chemotactic factor present in lysates of neutrophils sediments slowly in the ultracentrifuge and may be related, at least in part, to cationic peptides of lysosomal granules. A study in the time course of the chemotactic response of mononuclear cells reveals that the response begins to level off after 4 or 5 hr. This is in sharp contrast to the time course for the chemotactic response of neutrophils, in which the reaction is complete within 1.5 hr. Rabbit mononuclear cells obtained from a starch-induced peritoneal exudate respond to serum treated with plasminogen and streptokinase and to the soluble factor produced by bacteria, but no chemotactic response is elicited to serum treated with immune complexes. This indicates a functional difference between two populations of mononuclear cells. Rabbit alveolar macrophages respond poorly to all agents tested, although a weak chemotactic response to bacterial factors was found. The requirement of a serine esterase in the mononuclear cell for the cell to respond chemotactically was defined by the use of organophosphorus inhibitors. Pretreatment of mononuclear cells with several series of phosphonates renders them unresponsive in the chemotactic system. The effect is similar for mononuclear cells responding chemotactically to activated serum and to the bacterial chemotactic factor. Several points of contrast with inhibition profiles obtained in the chemotactic system of the neutrophil suggest that, while the mononuclear cell requires a serine esterase for chemotactic responsiveness, this enzyme is different from the one previously defined in the neutrophil.
THE SIGNIFICANCE OF THE SYNOVIAL VILLUS AND THE CILIARY PROCESS AS FACTORS IN THE LOCALIZATION OF BACTERIA IN THE JOINTS AND EYES OF RABBITS
Authors: D. Murray Angevine, Sidney Rothbard
Journal: The Journal of Experimental Medicine (1940)

1. Histological examination of sections of the eyes and joints of large numbers of rabbits injected with hemolytic streptococci has clearly demonstrated that when arthritis or cyclitis occurs, the synovial villi and ciliary processes are the most frequent and usually the primary sites of inflammation. 2. By special methods for demonstration of bacteria, it has been shown that bacteria which found lodgement in either an eye or a joint were demonstrable first in the vessels of ciliary processes or synovial villi. 3. A localized synovitis or iridocyclitis is brought about by the localization of bacteria in the synovial villus and ciliary process. 4. These experiments, which give a clearer insight into the pathogenesis of infectious arthritis and iritis, explain why both may occur in association with certain infectious diseases.