tbuckley/cabot-search huggingface dataset:
Two Cases of Pemphigus Vegetans With IgG Anti–Desmocollin 3 Antibodies
Authors: Hiroshi Saruta, Norito Ishii, Kwesi Teye, Fumitake Ono, Bungo Ohyama, Hiroshi Koga, Chika Ohata, Minao Furumura, Daisuke Tsuruta, Takashi Hashimoto
Journal: JAMA Dermatology (2013)

Pemphigus vegetans shows clinically vegetating and/or pustular skin lesions mainly on the intertriginous areas and histopathologically neutrophilic and eosinophilic pustules in the epidermis. Pemphigus vegetans shows IgG reactivity mainly with desmoglein (Dsg) 3, but also with other autoantigens, including Dsg1 and desmocollins (Dscs).We examined antigen profiles in 2 cases of pemphigus vegetans. (1) A women in her 80s presented with typical vegetating skin lesions on the right inguinal region with typical histopathological features. Immunoblotting using normal human epidermal extracts detected IgG antibodies to Dsg1 and Dscs. Enzyme-linked immunosorbent assays (ELISAs) revealed IgG antibodies to Dsg1 but not to Dsg3. Complementary DNA (cDNA) transfection method to COS-7 cells and novel ELISAs using eukaryotic recombinant proteins of human Dsc1, Dsc2, and Dsc3 confirmed specific IgG reactivity with Dsc3. (2) A women in her 70s presented with pustular skin lesions on the left fingers with typical histopathological features. Immunoblotting and ELISAs did not detect antibodies to either Dsg1 or Dsg3. Conversely, immunoblotting detected IgG antibodies to Dscs, cDNA transfection method revealed IgG reactivity only with Dsc3, and findings from ELISAs showed that IgG reacted weakly with Dsc2 and strongly with Dsc3.Autoantibodies to Dscs, particularly to Dsc3, may play a pathogenic role in some cases of pemphigus vegetans.
Systemic treatment of psoriatic patients with bexarotene decreases epidermal proliferation and parameters for inflammation, and improves differentiation in lesional skin
Authors: Jürgen V Smit, Elke M.G.J de Jong, Candida A.E.M van Hooijdonk, Marisol E Otero, Jan B.M Boezeman, Peter C.M van de Kerkhof
Journal: Journal of the American Academy of Dermatology (2004)
Septic abortion and IUCDs.
Authors: R A Sparks, A T Letchworth
Journal: BMJ (1978)

could be evaluated as even better.As the possibility for iatrogenic damage after intra- articular cortisone injections has been reported2-'i to be higher than was observed after intra-articular or especially intra- muscular glycosaminoglycan polysulphate therapy it seems justified to suggest this treatment in cases of painful knee joints after sports trauma and strenuous exercise.
Docking Protein Gab1 Is an Essential Component of Postnatal Angiogenesis After Ischemia via HGF/c-Met Signaling
Authors: Wataru Shioyama, Yoshikazu Nakaoka, Kaori Higuchi, Takashi Minami, Yoshiaki Taniyama, Keigo Nishida, Hiroyasu Kidoya, Takashi Sonobe, Hisamichi Naito, Yoh Arita, Takahiro Hashimoto, Tadashi Kuroda, Yasushi Fujio, Mikiyasu Shirai, Nobuyuki Takakura, Ryuichi Morishita, Keiko Yamauchi-Takihara, Tatsuhiko Kodama, Toshio Hirano, Naoki Mochizuki, Issei Komuro
Journal: Circulation Research (2011)

Grb2-associated binder (Gab) docking proteins, consisting of Gab1, Gab2, and Gab3, have crucial roles in growth factor-dependent signaling. Various proangiogenic growth factors regulate angiogenesis and endothelial function. However, the roles of Gab proteins in angiogenesis remain elusive.To elucidate the role of Gab proteins in postnatal angiogenesis.Endothelium-specific Gab1 knockout (Gab1ECKO) mice were viable and showed no obvious defects in vascular development. Therefore, we analyzed a hindlimb ischemia (HLI) model of control, Gab1ECKO, or conventional Gab2 knockout (Gab2KO) mice. Intriguingly, impaired blood flow recovery and necrosis in the operated limb was observed in all of Gab1ECKO, but not in control or Gab2KO mice. Among several proangiogenic growth factors, hepatocyte growth factor (HGF) induced the most prominent tyrosine phosphorylation of Gab1 and subsequent complex formation of Gab1 with SHP2 (Src homology-2-containing protein tyrosine phosphatase 2) and phosphatidylinositol 3-kinase subunit p85 in human endothelial cells (ECs). Gab1-SHP2 complex was required for HGF-induced migration and proliferation of ECs via extracellular signal-regulated kinase (ERK)1/2 pathway and for HGF-induced stabilization of ECs via ERK5. In contrast, Gab1-p85 complex regulated activation of AKT and contributed partially to migration of ECs after HGF stimulation. Microarray analysis demonstrated that HGF upregulated angiogenesis-related genes such as KLF2 (Krüppel-like factor 2) and Egr1 (early growth response 1) via Gab1-SHP2 complex in human ECs. In Gab1ECKO mice, gene transfer of vascular endothelial growth factor, but not HGF, improved blood flow recovery and ameliorated limb necrosis after HLI.Gab1 is essential for postnatal angiogenesis after ischemia via HGF/c-Met signaling.
Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons
Authors: Yu-Jiao Zhang, Xiao-Wen Lu, Ning Song, Liang Kou, Min-Ke Wu, Fei Liu, Hang Wang, Jie-Fei Shen
Journal: International Journal of Oral Science (2014)

Chlorogenic acid (5-caffeoylquinic acid, CGA) is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer's disease and neuropathic pain disorders. However, its mechanism of action is unclear. Voltage-gated potassium channel (Kv) is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,A and IK,V channels. Trigeminal ganglion (TRG) neurons were acutely disassociated from the rat TRG, and two different doses of CGA (0.2 and 1 mmol⋅L−1) were applied to the cells. Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,A and IK,V channels. The results demonstrated that 0.2 mmol⋅L−1 CGA decreased the peak current density of IK,A. Both 0.2 mmol⋅L−1 and 1 mmol⋅L−1 CGA also caused a significant reduction in the activation and inactivation thresholds of IK,A and IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,A and IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects. A plant-derived compound with therapeutic potential may inhibit pain signals through its effects on specific nerve cell proteins. Scientists have recently begun exploring the anti-cancer, anti-inflammatory and neurological effects of chlorogenic acid (CGA), a molecule produced by bamboo and other plants. Jie-Fei Shen and colleagues at Sichuan University in China examined the effects of CGA on two 'potassium-gated voltage channel' (KV) proteins, which participate in nerve cell signaling. The researchers examined cells from the rat trigeminal ganglion, a nervous system structure that detects and responds to pain. CGA increased the activity of both KV proteins, and Shen and colleagues predict that the resulting response would gradually dampen trigeminal pain signaling. These findings could assist the development of drugs that block the severe discomfort associated with inflammatory and neuropathic pain.
Selective affinity fractionation of murine cytotoxic T lymphocytes (CTL). Unique lectin specific binding of the CTL associated surface glycoprotein, T 145.
Authors: A Kimura, H Wigzell, G Holmquist, B Ersson, P Carlsson
Journal: The Journal of Experimental Medicine (1979)

We have analyzed the lectin binding characteristics of cytotoxic T lymphocyte (CTL)-derived surface labeled glycoproteins by affinity chromatography of the labeled glycoproteins on a panel of immobilized lectin adsorbents. Evidence is presented for the specific interaction of the CTL-associated glycoprotein T 145 with a lectin derived from Vicia villosa seeds. Conditions are described for the preparation and use of lectin affinity adsorbents for the rapid isolation of T 145 bearing cytotoxic T lymphocytes. Direct proof is given to show that T 145-positive cells arising from a variety of T-cell activations constitute the only subpopulation of cells with ability to perform cell-mediated T-cell cytotoxicity. Specific depletion of the CTLs by adherence to V. villosa adsorbents is shown by their depletion in the nonbound cell fraction and correspondingly enriched recovery in the sugar eluted cell fraction. Specific affinity fractionation of CTLs has occurred in every strain combination tested and irrespective of the actual antigen specificity of the effector cell population.
Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia.
Authors: R J Newman
Journal: BMJ (1976)

Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus.
A Variant of Sufferdom?
Authors: Samuel Vaisrub
Journal: JAMA (1977)

<h3>To the Editor. —</h3> "Crippledom" (Vaisrub, 237:2636, 1977), the newly-designated variety of sufferdom, is ingenious and quite possibly an improvement on "crippling." However, would the editors ofThe Journalhold still for an exhibition of similar daredom in a manuscript submitted to them for publication? <h3>Editors' Note.—</h3> The suffix "-dom" designates a domain as in "kingdom" or status as in "serfdom." In the latter context, "crippledom" is appropriate. As to "daredom," it could be an asset in a submitted manuscript if combined with wisdom.
Death and Injury by Firearms: Who Cares?
Authors: Joseph M. Miller
Journal: JAMA (1986)

To the Editor.—  Who cares about death and injury by firearms? Ask the families of firearms victims. And ask about the repeated, defeated efforts of these people to convince legislators to enact a satisfactory gun-control law. Our present session of Congress has avoided such legislation, presumably due to intense lobbying by the National Rifle Association.  The creation of a special center to study injuries from firearms is reminiscent of the Crusade Against Cancer that was legislated into being in 1970. The allocation of great sums of money has not brought us much closer to successful therapy for the neoplastic diseases.  Jagger and Dietz 1 have suggested a method to gather information that, in the end, would generate some interesting articles but would not really help to solve our problem. We know that the manufacture, distribution, and sale of handguns must be curtailed. Why not get on with the job and
Gefitinib Therapy in Advanced Bronchioloalveolar Carcinoma: Southwest Oncology Group Study S0126
Authors: Howard L. West, Wilbur A. Franklin, Jason McCoy, Paul H. Gumerlock, Ralph Vance, Derick H.M. Lau, Kari Chansky, John J. Crowley, David R. Gandara
Journal: Journal of Clinical Oncology (2006)

Purpose Advanced bronchioloalveolar carcinoma (BAC) is a distinct subtype of non–small-cell lung cancer (NSCLC) for which there is currently no optimal therapy. Based on preclinical and clinical data suggesting relevance of the epidermal growth factor receptor (EGFR) axis in BAC, the Southwest Oncology Group initiated a phase II trial (S0126) to evaluate the EGFR tyrosine kinase inhibitor gefitinib in chemotherapy-naïve and chemotherapy-pretreated patients with advanced BAC. Methods A total of 136 eligible and assessable patients (101 untreated, 35 previously treated) received gefitinib 500 mg daily until progression or prohibitive toxicity. Results The median age was 68.0 years (range, 34.3 to 88.6); 51% were female; 89% had a performance status (PS) of 0% or 1% and 11% had a PS of 2. The Response Evaluation Criteria in Solid Tumors response rate was 17%, with 6% complete responses (CRs) among 69 previously untreated patients with measurable disease, and 9% with no CRs among 22 pretreated patients. Median survival was 13 months for both chemo-naïve (95% CI, 8 to 18) and previously treated patients (95% CI, 6 to 17). Overall survival at 3 years was 23% (95% CI, 14% to 32%). Toxicity consisted mainly of rash and diarrhea, but 2% of patients died of presumed interstitial lung disease. Exploratory subset analyses revealed improved survival among women (P = .031), patients developing a rash (P = .003), never-smokers (P = .061), and patients with a PS of 0 or 1 (P = .015). Conclusion Gefitinib is an active agent in advanced stage BAC. Several subsets demonstrate significantly improved clinical outcomes.
Rethinking transparency and accountability in medicines regulation in the United Kingdom
Authors: J. Abraham, J. Sheppard, T. Reed
Journal: BMJ (1999)

As the Labour government in the United Kingdom introduces its plans for British freedom of information legislation in a white paper, it is important to consider the issues raised by this for the regulation of medicines. In the United Kingdom, the regulation of medicines is governed currently by the 1911Official Secrets Act and 1968Medicines Act. These require all information on drug product licence applications to be treated with the utmost secrecy by the Department of Health's regulatory authority, the Medicines Control Agency, and all its expert advisory committees. Until May 1997,the official position of the British government was that confidentiality about regulation of medicines was needed to protect drug companies' commercially sensitive trade secrets so that the pharmaceutical industry continued to invest and to make medicines available in the United Kingdom.1

#### Summary points

The existing secrecy sits uneasily with the rhetoric of the Conservative government's 1993white paper on open government, which espoused the following principles:

> Open government is part of an effective democracy. Citizens must have adequate access to the information and analysis on which …
Oncostatin M Modulates the Mesenchymal–Epithelial Transition of Lung Adenocarcinoma Cells by a Mesenchymal Stem Cell-Mediated Paracrine Effect
Authors: Mong-Lien Wang, Chih-Ming Pan, Shih-Hwa Chiou, Wen-Hsin Chen, Hsiang-Yi Chang, Oscar Kuang-Sheng Lee, Han-Sui Hsu, Cheng-Wen Wu
Journal: Cancer Research (2012)

Mesenchymal stem cells (MSC) are strongly associated with tumor progression and have been used as novel cell-based agents to deliver anticancer drugs to tumors. However, controversies about the direct involvement of MSCs in tumor progression suggest that MSCs mediate tumor progression in a cancer type-dependent manner. In this report, we analyzed the functional interactions between human MSCs and lung adenocarcinoma (LAC) cells to determine the therapeutic potential of MSCs in lung cancer. We showed that MSCs effectively inhibited the migration, invasion, and cell-cycle progression of several LAC cell lines. MSCs also enhanced the mesenchymal-epithelial transition (MET) pathway, as evidenced by the reduction of several epithelial-mesenchymal transition-related markers in LAC cells cocultured with MSCs or in MSC-conditioned medium (MSC-CM). By cytokine array analysis, we determined that Oncostatin M (OSM), a differentiation-promoting cytokine, was elevated in the MSC-CM derived from primary MSC cultures. Furthermore, OSM treatment had the same effects as MSC-CM on LAC, whereas neutralizing antibodies to OSM reversed them. Notably, short hairpin RNAs against STAT1, an important downstream target of OSM, hindered the OSM-dependent induction of MET. In vivo xenograft tumor studies indicated that OSM inhibited tumor formation and metastasis of LAC cells, whereas neutralizing OSM in the MSC-CM hampered its inhibitory effects. In conclusion, this study showed that OSM is a paracrine mediator of MSC-dependent inhibition of tumorigenicity and activation of MET in LAC cells. These effects of OSM may serve as a basis for the development of new drugs and therapeutic interventions targeting cancer cells.
A Small Molecule for a Large Disease
Authors: Reed E. Pyeritz
Journal: New England Journal of Medicine (2008)

Almost three decades ago, Victor McKusick and I reviewed Marfan's syndrome in the Journal and advised traditional medical and surgical approaches to management.1 The holy grail at that time was the cause of this autosomal dominant condition, based on the common presumption that understanding the cause would lead directly to effective therapy. In fact, life expectancy improved dramatically in subsequent years for all but the most severely affected patients, despite a lack of understanding of the underlying connective-tissue defect.2 Dissection of the aorta was and remains the most common cause of death. However, the evolution of ever more effective surgical . . .
The world on tilt
Authors: Tony Delamothe
Journal: BMJ (2012)

> Man has been endowed with reason, with the power to create, so that he can add to what he’s been given. But up to now he hasn’t been a creator, only a destroyer. Forests keep disappearing, rivers dry up, wild life’s become extinct, the climate’s ruined, and the land grows poorer and uglier every day.

In the 115 years since Anton Chekhov put these words into the mouth of the doctor in his play Uncle Vanya , the planet has heated up by 1 degree Celsius and the atmospheric concentration of carbon dioxide has risen by one third. As every schoolchild knows, the two are closely linked; carbon dioxide makes up the bulk of greenhouse gases, which stop the sun’s heat radiating straight back out into space. More carbon dioxide equals a hotter planet.

As can be seen from the graphs (figs 1⇓ and 2⇓ …
Evidence-Based Medicine in Surgery
Authors: Ryan P. Merkow, Clifford Y. Ko
Journal: JAMA (2011)

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Natural History of Obsessional States
Authors: J. Pollitt
Journal: BMJ (1957)

<h3>Abstract</h3> <h3>Objectives</h3> Studies have demonstrated that sex differences may play a crucial role in the alternations of brain structures in individuals with bipolar disorder, but findings are not consistent. The current study identified sex differences in brain structure and function among a large sample of individuals with bipolar I disorder (BD-I). <h3>Methods</h3> Structural and functional magnetic resonance imaging datasets were acquired from 105 individuals with BD-I (36 men and 69 women) and 210 healthy adults (72 men and 138 women). A general linear regression model was used for voxel-wise analysis of grey matter (GM) and functional connectivity. Age, sex, diagnosis, and sex-by-diagnosis interaction were defined as predictors. <h3>Results</h3> In GM, the left caudate (<i>p</i> &lt; .001), left thalamus (<i>p</i> &lt; .001), right caudate (<i>p</i> = .003), right thalamus (<i>p</i> &lt; .001), left anterior cingulate gyrus (<i>p</i> = .015), and left middle/posterior cingulate gyrus (<i>p</i> = .022) exhibited sex-by-diagnosis interaction. Furthermore, by using these six brain regions as seeds, we observed sex-by-diagnosis interaction in the alteration of functional connectivity between the left thalamus and right angular gyrus (<i>p</i> = .019). <h3>Conclusions</h3> Our data revealed a sex-by-diagnosis interaction associated with structure and function of the limbic system in individuals with BD-I. These findings may serve as reference for future studies on the pathophysiology of bipolar disorder.
Effect of Diabetes on Long-Term Mortality Following Contemporary Percutaneous Coronary Intervention
Authors: Sean R. Wilson, Babak A. Vakili, Warren Sherman, Timothy A. Sanborn, David L. Brown
Journal: Diabetes Care (2004)

OBJECTIVE—Diabetic patients are known to have reduced long-term survival following percutaneous transluminal coronary angioplasty compared with nondiabetic patients. However, it is unknown whether this survival disadvantage has persisted in the era of contemporary percutaneous coronary intervention (PCI) techniques, which include the widespread use of stents and the availability of platelet glycoprotein (GP) IIb/IIIa inhibitors. RESEARCH DESIGN AND METHODS—Three hospitals in New York City contributed prospectively defined data on 4,284 patients undergoing PCI. The primary end point was all-cause mortality following hospital discharge for PCI. RESULTS—Hypertension, renal insufficiency, and renal failure requiring dialysis were all more common in diabetic patients, whereas active smoking was less frequent. Congestive heart failure on admission was more common in diabetic than nondiabetic patients (7.7 vs. 4.0%, P &amp;lt; 0.001). Stents were placed in 78% of nondiabetic patients and 75% of diabetic patients (P = 0.045). Platelet GP IIb/IIIa antagonists were administered to 23% of nondiabetic and 24% of diabetic patients (P = NS). At a mean follow-up of 3 years, mortality was 8% among nondiabetic patients and 13% for diabetic patients (P &amp;lt; 0.001). After adjustment for differences in baseline characteristics between nondiabetic and diabetic patients, diabetes remained a significant independent hazard for late mortality (hazard ratio 1.462, 95% CI 1.169–1.828; P = 0.001). CONCLUSIONS—Following contemporary PCI, diabetic patients continue to have worse survival than nondiabetic patients.
Commission plans new controls on supply of genetic tests to the public
Authors: S. Mayor
Journal: BMJ (2003)

The Human Genetics Commission–the body that advises the UK government on genetic issues–has recommended the introduction of new controls on the direct provision of genetic tests to the public.

The government asked the commission in February 2002 to carry out a thorough review of genetic testing services provided directly to the public. At a meeting last week, members of the commission discussed the results of a public consultation on the issue.

Philip Webb, chairman of the commission's genetic services subgroup, commented: “The consultation showed how concerned the public are about this area.”

The consultation showed …