tbuckley/cabot-search huggingface dataset:
Intercellular adhesion molecule-1 (ICAM-1) is upregulated on alveolar macrophages from AIDS patients
Authors: S Bohnet, J Braun, K Dalhoff
Journal: European Respiratory Journal (1994)

In acquired immune deficiency syndrome (AIDS) patients, alveolar macrophages (AMs) have an increased ability to serve as accessory cells during the generation of an immune response. In addition to soluble mediators, like cytokines, molecules of the major histocompatibility complex (MHC) class II and adhesion molecules, like intercellular adhesion molecule-1 (ICAM-1), play a major role in the regulation of these cellular interactions. Using an enzyme-linked immunosorbent assay (ELISA) technique and immunocytochemical staining, we investigated ICAM-1 and human leucocyte antigen-DR (HLA-DR) expression on AMs from 20 AIDS (HIV+) patients in context with other parameters of macrophage activation, such as tumour necrosis factor-alpha (TNF-alpha) secretion and the release of superoxide anion, comparing the results to a group of healthy volunteers. In addition, we quantified soluble ICAM-1 in the bronchoalveolar lavage fluid (BALF) using a commercially available kit. We found a nearly twofold increase in ICAM-1 expression (0.81 +/- 0.30 (SD) versus 0.42 +/- 0.12 ELISA units (EU) (mean +/- SD)), whilst the number of HLA-DR+ AMs was slightly decreased in AIDS-patients (80 +/- 5 versus 89 +/- 3%). Furthermore, soluble ICAM-1 in the BALF of these patients was significantly increased (41.9 +/- 26.1 versus 19.1 +/- 5.1 ng.ml-1). ICAM-1 levels on AMs in the patient group correlated strongly with the sodium fluoride triggered release of superoxide anion (O2-) but not with the spontaneous secretion of TNF-alpha by AMs.(ABSTRACT TRUNCATED AT 250 WORDS)
Epicene Pronouns—Obliterate, Slash, or Pluralize?
Authors: Robert E. Schoen
Journal: JAMA (1988)

To the Editor.—  Legitimate concern over sex bias in JAMA was recently expressed by Ms Lorimer-Lundberg 1 when she assailed Dr Kellner 1 for the use of nongeneric masculine pronouns such as he to signify he or she . Nevertheless, I must agree with Dr Kellner that use of the nonsexist he/she or himself/herself is rather clumsy and choppy and disrupts a smooth writing style. I have found that a far more acceptable epicene pronoun is s/he or him/erself . These are eminently readable and flowing, and while they are still cause for pause, this should resolve with increased use.
Effect of Wine Consumption on Mortality—Reply
Authors: Richard D. Semba, Kai Sun, Cristina Andres-Lacueva
Journal: JAMA Internal Medicine (2015)

Sex-Specific Chest Pain CharacteristicsTo the Editor Rubini Gimenez et al 1 studied sex-specific chest pain characteristics (CPCs) with the objective of improving the management of women with suspected acute myocardial infarction (AMI).They collected an impressive number of baseline and chest pain characteristics in a large sample of patients with chest pain.Unfortunately, the prevalence of CPCs in women was only compared with the prevalence of CPCs in men.Whether the prevalence of CPCs in women with AMI differed from women without AMI (and men with and without AMI) was not evaluated, while such an analysis would demonstrate which symptoms are related to AMI in women and which in men.The knowledge that certain CPCs are more prevalent in women than in men is not that useful for a medical physician.In clinical practice either a man or a woman present themselves with certain symptoms, and therefore it is important to know which symptoms are predictive for a AMI in women and which in men.The choice to use likelihood ratio as statistical test is unfortunate because it only evaluates 1 symptom at a time, while the diagnosis of AMI is a multivariable process.Moreover, the likelihood ratio does not provide the diagnostic value of the combination of CPCs in women and men.The diagnostic value, expressed as the area under the curve or C statistic, shows in how many women and men an AMI can be diagnosed based on the CPCs present.This quantification combines the CPCs in 1 person as is done in clinical practice.In addition, it allows a direct comparison between sexes.
Post-vagotomy insulin test: improved predictability of ulcer recurrence after corrections for height and collection errors.
Authors: N K Maybury, R G Faber, M Hobsley
Journal: Gut (1977)

Insulin stimulated gastric secretion was studied in 74 unoperated duodenal ulcer patients (DUs), (20 women and 54 men). Three indices of secretion were studied--observed volume, acid output, and volume of gastric juice corrected for pyloric loss and duodenal reflux (VG). These three measurements were expressed both as peak secretion and as secretion during the 1/2 to two hour period after insulin, and also both before and after standardisation for height, making 12 different indices in all. From the data a significant correlation between insulin-stimulated secretion and height in DUs was found. A method of standardising each patient9s secretion for height is described. We confirm a significantly higher insulin-stimulated secretion in men than in women and show that this difference can be explained by their difference in height. For each of the 12 indices of secretion, the range of secretion for the unoperated subjects was obtained. The same indices were measured in 155 postvagotomy patients, including 33 patients with recurrent DUs, and compared with the ranges of secretion established in the unoperated patients. Responses above the lower 95% tolerance limit of the preoperative range were designated positive and those below negative. The Hollander status was determined. It was found that the least satisfactory criterion was Hollander9s (7% false negative and 69% false positive). The best was 1/2-2 VG standardised for height (3% false negatives and 43% false positives). The improvement in predictably was significant at the 0-0005 level.
Abstract 3720: Rad51 is involved in PARP inhibitor resistance in triple-negative breast cancer stem cells (TNBCSCs).
Authors: Yajing Liu, Rachel Martin, Shoumin Bai, Max Wicha, Suling Liu
Journal: Cancer Research (2013)

Abstract Although the mortality rate in breast cancer (BC) has been reduced by the advancing technology, the outcome of patients with “triple-negative” (TN) BC (accounts for 10-17% of invasive BC) has achieved little progression. Recently, inhibitors of poly (adenosine-disposphate-ribose) polymerase (PARP) have been developed to target cells with defective DNA repair molecules such as BRCA1-deficient cells. Despite the tumor regression induced by these agents in a subset of BCs, their ability to effect patient outcome remains inconclusive. According to the CSC hypothesis, a hierarchical tumor organization exists whereby dysregulated self-renewing CSCs drive tumorigenesis. Our preliminary results showed that PARP inhibitor significantly decreased cell number in BRCA1-deficient SUM149 cells in a dose-dependent manner, whereas BRCA1 wild type SUM159 cells were relatively resistant. However, there was little change in absolute CSC number in SUM149 cells after PARP inhibitor treatment, suggesting PARP inhibitor only targets the non-CSC population in SUM149 cells. More interestingly, the resistant population expressed higher active Rad51 as measured for Rad51 foci formation. Our pervious study also showed that Rad51 mRNA level was significantly higher in ALDH+ cells of some breast cancer cell lines. Therefore, in this study, we established an inducible knock-down system using lentivirus and found that knocking down Rad51 sensitizes SUM159 (both CSC and non-CSC) as well as ALDH+ SUM149 cells to PARP inhibitor, suggesting the expression of Rad51 is associated with PARP inhibitor resistant population. This system was also tested in mouse model where cells carrying Rad51 shRNA were injected into the mammary fat pads of female NOD/SCID mice. Knock-down of Rad51 alone and combination treatment with PARP inhibitor dramatically inhibited tumor growth in the xenografts of both SUM149 and SUM159 cells, whereas, tumor grew back after Rad51 expression was restored. However the inhibitory effect remained in the combined treatment group after the treatment was terminated. Furthermore, the combination treatment decreased ALDH+ cells by IHC staining. It also showed a significant decrease in tumor-initiating cells in the combined treatment group by limiting dilution transplantation. Our results suggest that Rad51 plays an important role in resistance to PARP inhibitor in TNBCSCs thus Rad51 inhibitor may be a novel therapeutic approach in addition to PARP inhibition for treating TNBC patients. Citation Format: Yajing Liu, Rachel Martin, Shoumin Bai, Max Wicha, Suling Liu. Rad51 is involved in PARP inhibitor resistance in triple-negative breast cancer stem cells (TNBCSCs). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3720. doi:10.1158/1538-7445.AM2013-3720
Sumoylated HSP90 is a dominantly inherited plasma cell dyscrasias risk factor
Authors: Klaus-Dieter Preuss, Michael Pfreundschuh, Natalie Fadle, Evi Regitz, Boris Kubuschok
Journal: Journal of Clinical Investigation (2014)

Posttranslationally modified proteins serve as autoimmunogenic targets in a wide spectrum of autoimmune diseases. Here, we identified a posttranslationally modified paraprotein target (paratargs) in monoclonal gammopathies of undetermined significance (MGUS), multiple myelomas (MM), and Waldenstrom's macroglobulinemias (WM) using protein macroarrays that were sumoylated and screened for reactivity with paraproteins from MGUS, MM, and WM patients. We found that paraproteins from a proportion of European, African-American, and Japanese patients specifically reacted with the sumoylated heat-shock protein 90 β isoform-α (HSP90-SUMO1, where SUMO indicates small ubiquitin-like modifier), while no reactivity with HSP90-SUMO1 was detected in over 800 controls. HSP90-SUMO1 was present in blood cells from all patients with HSP90-SUMO1-binding paraproteins. We determined that the HSP90-SUMO1 carrier state is autosomal-dominantly inherited and caused by the inability of SUMO peptidase sentrin/SUMO-specific protease 2 (SENP2) to desumoylate HSP90-SUMO1. HSP90-SUMO1 was detected in a small percentage of healthy individuals from all backgrounds; however, only MGUS, MM, and WM patients who were HSP90-SUMO1 carriers produced HSP90-SUMO1-specific paraproteins, suggesting that sumoylated HSP90 promotes pathogenesis of these diseases through chronic antigenic stimulation. This study demonstrates that harboring HSP90-SUMO1 identifies healthy individuals at risk for plasma cell dyscrasias and that dominant inheritance of posttranslationally modified autoantigenic paratargs is one of the strongest molecular defined risk factors for MGUS, MM, and WM.
Rains fail to bring relief in Zimbabwe
Authors: Peter Moszynski
Journal: BMJ (2006)

Recent heavy rainfall across much of southern Africa has brought little respite to millions of people facing chronic food shortages caused by years of drought. Cases of cholera and anthrax have increased in the wake of wide-spread flooding, and the region's health systems are struggling to cope.

Particularly badly affected is Zimbabwe. A statement issued on 6 January by the International Federation of the Red Cross warned: “The cholera outbreak in southeastern Zimbabwe that began …
It's hardly sport, but parachuting fire fighters may benefit from what sports medicine has learned
Authors: V. S. Cowart
Journal: JAMA (1988)

WILDFIRES around Yellowstone National Park and elsewhere in the Northwest have kept forest fire fighters in the headlines for weeks.  Among persons in this unique line of work, smokejumpers—the commandos of fire fighting—do the same dangerous work as all fire fighters, but add to the risks by going to work in a parachute. Efforts to reduce these risks have become the focus of some sports medicine physicians.  The US Forest Service created smokejumper units some years ago in the hope of reducing destruction from out-of-control forest fires by having a mobile force that could drop into a fire zone and be working on containment long before conventional fire fighters could reach the area. That philosophy once again was tested with the summer and fall already having been preceded by a lengthy drought in many areas (Wall Street Journal1988;69:1, July 29). And, there is the recent memory of the 1987
Alprazolam Abuse During Methadone Maintenance Therapy
Authors: Anne C. Carney
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Alprazolam (Xanax), a short-acting triazolobenzodiazepine, has been demonstrated to be a potent anxiolytic,<sup>1</sup>efficacious for panic disorder.<sup>2</sup>In two drug abuse clinics in Baltimore and Chicago, we have noted abuse of and dependency on alprazolam by opiate-dependent patients receiving methadone maintenance therapy. We have received reports that physicians in emergency departments and medical clinics are willing to prescribe alprazolam rather than other benzodiazepines to walk-in patients, particularly if the individual complains of "panic attacks" and anxiety. Taking 20 to 40 1.0-mg alprazolam tablets after ingesting methadone produces a high without pronounced sedation. Five patients receiving methadone maintenance therapy have required hospitalization for detoxification from alprazolam. Reportedly, alprazolam is also being used and abused by nonopiate-drug abusers, much as diazepam was abused prior to increased physician awareness. Unfortunately, it is now common knowledge on the street that the usual urine toxicology screens for benzodiazepines often give
AIDS Dementia May Be Linked to Metabolite of Tryptophan
Authors: Paul Cotton
Journal: JAMA (1990)

QUINOLINIC ACID is intriguing researchers as a possible cause and marker of neurological damage in human immunodeficiency virus (HIV) disease. It is a neurotoxic convulsant metabolite of tryptophan that is activated by interferon gamma. It is elevated with any infection, from a common rhinovirus to the mysterious lentivirus linked to acquired immunodeficiency syndrome (AIDS). But quinolinic acid remains elevated for extended periods with HIV and increases as much as a 1000-fold over controls in patients with AIDS dementia complex, says Melvyn Heyes, PhD, a visiting scientist in the analytical biochemistry section at the National Institute for Mental Health in suburban Washington, DC (Maryland). It binds to and may down-regulate Nmethyl-D-aspartate receptors, which are involved in normal neurotransmission, neural regeneration, memory, and synaptic plasticity. It can also induce seizures and nerve cell death, says Heyes. "There is a wide spectrum of possible consequences known to occur in AIDS and other infectious
The Formation of the American Medical Profession: The Role of Institutions, 1780-1860
Authors: Lester S. King
Journal: JAMA (1968)

Most physicians who write medical history emphasize the scientific aspects and neglect the sociological interrelations. Mr. Kett, a professional historian and not a physician, attends particularly to the sociological and political aspects of medicine in the period before 1860. He is largely concerned with the problems of medical licensing and medical education and, consequently, the broader problem of the social control of medicine. The picture is not a particularly pretty one. Medicine was riddled with politics, and the problems of charters and licenses involved some of the less admirable qualities of both physicians and politicians, during this era. The relationships between orthodox medicine and the sects, such as thompsonianism and botanic medicine, or homeopathy, occupy a large part of the book. The volume is at its best where the author discusses the various sects as cultural expressions, and ties in political and social factors with the problems of unorthodox medicine.
Website of the week: Alcohol screening
Authors: C. Martyn
Journal: BMJ (2002)

A paper in this week's BMJ (p 870) describes some of the difficulties that doctors experienced when they tried to implement a screening programme to detect people who might have been drinking too much alcohol. One was discomfort with the inquisitorial and judgmental role that they had to play. Quite right, too. In the last analysis of occupational mortality in the United Kingdom, the medical profession was second only to publicans and veterinarians for deaths from cirrhosis of the liver.
Two cases of clear cell sarcoma with different clinical and genetic features: cutaneous type with<i>BRAF</i>mutation and subcutaneous type with<i>KIT</i>mutation
Authors: B.M. Park, S.A. Jin, Y.D. Choi, S.H. Shin, S.T. Jung, J.B. Lee, S.C. Lee, S.J. Yun
Journal: British Journal of Dermatology (2013)

Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a rare malignancy constituting approximately 1% of all soft-tissue sarcomas. It occurs predominantly in the lower extremities of young adults, manifesting as a deep, painless, slow-growing mass. CCS is sometimes confused with other types of melanoma because of its melanocytic differentiation. Although BRAF and KIT mutations are well-known melanocytic tumour-promoting mutations frequently found in cutaneous melanoma, they are rare or absent in CCS. We present two cases of CCS with different clinical and genetic features. Both female patients, aged 25 and 20 years, presented with a palpable nodule on a lower extremity. Biopsies of both tumours revealed features diagnostic of CCS. Each tumour cell was positive for S100 protein and HMB-45. However, one patient's tumour was localized to the dermis, with many multinucleated giant cells, whereas the other was located in the deep subcutaneous fat layer near bone. Fluorescence in situ hybridization demonstrated the presence of a characteristic Ewing sarcoma RNA-binding protein (EWSR)1 gene rearrangement in both cases. Reverse-transcription polymerase chain reaction (PCR) and sequencing of the PCR product revealed an EWSR1-activating transcription factor 1 type 1 fusion transcript in both cases. In addition, we detected BRAF mutation in the dermal type and KIT mutation in the subcutaneous type. It is of interest that the BRAF and KIT mutations are known to be very rare in CCS. On the basis of our observations, we suggest that mutation inhibitors may be useful in selected patients with mutated CCS lineages.
Health hazards from nuclear industry
Authors: M J Gaines
Journal: BMJ (1980)

had low toxicity and gave an overall response rate of 73%0.In the multicentre study in 153 patients there were no drug-related deaths.We conclude that intracavitary bleomycin is well tolerated and is effective as palliative treatment for malignant effusions, preventing the need for frequent aspiration of accumulated fluid.Because of its lack of haematological toxicity it may be used safely in the already leucopenic patient.
Studies without Internal Controls
Authors: John C. Bailar, Thomas A. Louis, Philip W. Lavori, Marcia Polansky
Journal: New England Journal of Medicine (1984)

Sometimes questions of clinical interest can be addressed only by investigations without concurrent controls that are under the supervision of the investigator (internal controls). Such studies nearly always make use of other types of comparisons (external controls), such as historical controls. In this paper we examine studies of clinical treatments that have weak internal controls or lack internal controls, as illustrated by recent examples from the Journal. These studies have a small but important and unique role in clinical investigation. Five interrelated features can add to the strength of such studies: (1) an intent by the investigator, expressed before the study, that the treatment will affect the outcomes reported; (2) planning of the analysis before the data are generated; (3) articulation of a plausible hypothesis before the results are observed; (4) a likelihood that the results would still have been of interest if they had been "opposite" in some sense; and (5) reasonable grounds for generalizing the results from the study subjects to a substantially broader group of patients. In spite of potential pitfalls, carefully selected and reported studies without internal controls can play a substantial part in the acquisition of scientific knowledge.
A Facile Lentiviral Vector System for Expression of Doxycycline-Inducible shRNAs: Knockdown of the Pre-miRNA Processing Enzyme Drosha
Authors: Lars Aagaard, Mohammed Amarzguioui, Guihua Sun, Luis C Santos, Ali Ehsani, Hans Prydz, John J Rossi
Journal: Molecular Therapy (2007)

RNA interference (RNAi) is a powerful genetic tool for loss-of-function studies in mammalian cells and is also considered a potentially powerful therapeutic modality for the treatment of a variety of human diseases. During the past 3 years a number of systems for conditional RNAi have been developed that allow controlled expression of short hairpin RNA (shRNA) triggers of RNAi. The simplest strategy relies on tet-operable polymerase III-promoted shRNAs and co-expression of the tetracycline regulatory protein, TetR. In this study we have combined these features into a single lentiviral vector that upon delivery to target cells allows robust induction of shRNAs, even with low levels of doxycycline; importantly, we show minimal leakiness in the absence of inducer. We have exploited the regulatory properties of our system by targeting an essential cellular gene, the nuclear RNaseIII endonuclease Drosha. Drosha is the core catalytic component of the "microprocessor complex" and cleaves the primary microRNA (miRNA) transcripts into their pre-miRNA hairpin intermediates. We anticipate that our vector will facilitate functional studies of miRNA biogenesis.
716 EFFECTS OF YIN-CHEN-HAO-TANG (HERBAL MEDICINE, TJ-135) ON CIRCULATING ENDOTHELIAL PROGENITOR CELLS AND INFLAMMATORY MARKERS IN OBESITY MICE WITH HEPATIC STEATOSIS
Authors: T.-Y. Lee, Y.S. Chang, Y.C. Lo, F.Y. Chen, H.H. Chang
Journal: Journal of Hepatology (2009)
Effect of simvastatin in addition to chenodeoxycholic acid in patients with cerebrotendinous xanthomatosis
Authors: Aad Verrips, Ron A. Wevers, Baziel G.M. Van Engelen, Antoine Keyser, Bert G. Wolthers, Frederik Barkhof, Anton Stalenhoef, Ruurd De Graaf, Fokje Janssen-Zijlstra, Alwin Van Spreeken, Fons J.M. Gabreëls
Journal: Metabolism (1999)
Retinoic acid modulates rat Ito cell proliferation, collagen, and transforming growth factor beta production.
Authors: B H Davis, R T Kramer, N O Davidson
Journal: Journal of Clinical Investigation (1990)

Recent studies suggest that vitamin A plays an inhibitory role with respect to "activation" of the hepatic Ito cell, a likely effector of hepatic fibrogenesis. Ito cell "activation" during fibrogenesis is characterized by a decrease in intracellular vitamin A and an increase in cellular proliferation and collagen production. To explore the hypothesis that retinoids have the capacity to diminish Ito cell activation, cultured Ito cells were exposed to retinoic acid and its effects assessed on three key features: cell proliferation, collagen protein production and mRNA abundance, and transforming growth factor beta protein production. Retinoic acid was 100-1,000X more potent than retinol with respect to inhibition of Ito cell proliferation. Interstitial collagen and transforming growth factor beta production were also reduced by 10(-6) M retinoic acid. The relative abundance of type I collagen mRNA however, was not significantly altered. By contrast, retinoic acid administration to rats caused a marked reduction in the abundance of type I collagen mRNA in both total hepatic and purified Ito cell RNA. The relative abundance of rat hepatic fibronectin or apolipoprotein E mRNA was not significantly altered. These studies demonstrate that retinoic acid can differentially modulate several key features of hepatic fibrogenesis in vitro and in vivo.