tbuckley/cabot-search huggingface dataset:
The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells
Authors: T.J. Stoof, J. Flier, S. Sampat, C. Nieboer, C.P. Tensen, D.M. Boorsma
Journal: British Journal of Dermatology (2001)

The effectiveness of systemic treatment of psoriasis with fumaric acid esters has been proven, but their mode of action at the cellular and molecular level has not yet been fully elucidated.To study the effect of dimethylfumarate (DMF) on the production of the chemokines CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11, formerly known as GROalpha, interleukin-8, Mig, IP-10 and IP-9/I-TAC, respectively, in human keratinocytes and peripheral blood mononuclear cells (PBMC).Cultured keratinocytes were stimulated with interferon (IFN) -gamma to produce CXCL9, CXCL10 and CXCL11 and with phorbol myristate acetate to produce CXCL1 and CXCL8 in the absence and presence of DMF (5, 15 and 45 micromol L(-1)). PBMC were stimulated with either IFN-gamma to produce CXCL9 and CXCL10 or lipopolysaccharide to produce CXCL8, in the absence and presence of DMF (5, 15 and 45 micromol L(-1)). RNA preparations from isolated keratinocytes were analysed by Northern blotting; protein production by keratinocytes and PBMC was monitored by an enzyme-linked immunosorbent assay.Northern blot analysis on isolated keratinocyte RNA preparations showed a dose-dependent inhibition of CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11 transcription by DMF. At 45 micromol L(-1) the inhibition was almost complete. In addition, keratinocytes and PBMC showed in the presence of DMF a dose-dependent inhibition of CXCL8, CXCL9 and CXCL10 protein production.These results show the ability of DMF to inhibit the production of chemokines that may be critically involved in the development and perpetuation of psoriatic lesions. This might explain, at least in part, the beneficial effects of treatment with fumaric acid esters in psoriasis patients.
A Medical Student Looks at Medical Books
Authors: Eugene P. Cassidy
Journal: JAMA (1964)

T HE most concentrated market for medical books is the medical student, and the factors which influence his choice are many. Perhaps the ideal way to select a book is to go to a book store or library, examine the appropriate volumes, compare their features, read some of each, and then decide. But obviously, the student, by the very fact that he is a student, has little ability to judge whether a book on a new subject is accurate, complete, and generally desirable. He needs help. Fortunately, help is never very far away. Sometimes the student is spared the task of decision. On the first day of class a professor may strongly recommend a book. The student, after purchasing this "best work available," may then have his teacher autograph it. But more commonly the professor, in the first session, distributes a list of 12 to 50 books with titles that
Assessment of Ventricular Function in Infants and Children
Authors: ROGER A. HURWITZ, ASLAM SIDDIQUI, RANDALL L. CALDWELL, ROBERT M. WEETMAN, DONALD A. GIROD
Journal: Clinical Nuclear Medicine (1990)

A method to assess ventricular functional reserve in infants and children unable to perform dynamic exercise was evaluated. Left ventricular ejection fraction was measured by radionuclide angiocardiography at rest and during infusion of dobutamine in 5-15 micrograms/kg/min dosages. The only side effects noted were arrhythmias in two patients, who had similar ectopy documented previously. Group left ventricular ejection fraction increased from 0.40 +/- 0.21 to a maximum of 0.49 +/- 0.24 (P less than 0.001). Left ventricular ejection fraction at 5 micrograms/kg/min (0.44 +/- 0.23) was not statistically different from that measured during infusion of dobutamine at 10 micrograms/kg/min (0.48 +/- 0.24). The six patients receiving anthracyclines, who had relatively low function at rest and increased function during dobutamine administration, were continued on their anticancer regimen without deteriorating in condition. Absolute values of left ventricular ejection fraction correlated best with the prognosis in patients with idiopathic dilated cardiomyopathy or structural abnormalities; six out of ten patients whose left ventricular ejection fraction never rose above 0.40 have either died or are in transplant protocols. Thus, study of left ventricular function can be performed easily during dobutamine infusion, generating valuable prognostic information.
Second-person neuroscience: Implications for Wittgensteinian and Vygotskyan approaches to psychology
Authors: Kevin Moore
Journal: Behavioral and Brain Sciences (2013)

Abstract Interactive approaches to development and social psychology may particularly benefit from the non-dualist features of a second-person neuroscience. In that context, I discuss the compatibility of a second-person neuroscience with a Wittgensteinian analysis of psychological concepts and its connections to a Vygotskyan approach to psychological development.
Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients
Authors: N Schmitz, P Dreger, D.C Linch, A.H Goldstone, M.A Boogaerts, H.M.S Demuynck, A Ferrant, A Zander, H Link, A Barge, K Borkett
Journal: The Lancet (1996)
Detection of type III collagen in skin fibroblasts from patients with Ehlers-Danlos syndrome type IV by immunofluorescence
Authors: ANNE S. TEMPLE, P. HINTON, P. NARCISI, F.M. POPE
Journal: British Journal of Dermatology (1988)

Immunofluorescence showed that cultured skin fibroblasts from 15 out of 17 patients with Ehlers-Danlos syndrome type IV retained abnormal amounts of type III collagen within the cytoplasm. This was not shown by fibroblasts from normal subjects or from patients with other inherited connective tissue diseases. The diagnosis of Ehlers-Danlos syndrome type IV may be facilitated by this finding.
The immune response against myelin basic protein in two strains of rat with different genetic capacity to develop experimental allergic encephalomyelitis.
Authors: D E McFarlin, S C Hsu, S B Slemenda, F C Chou, R F Kibler
Journal: The Journal of Experimental Medicine (1975)

After challenge with guiena pig basic protein (GPBP) Lewis (Le) rats, which are homozygous for the immune response experimental allergic encephalomyelitis (Ir-EAE) gene, developed positive delayed skin tests against GPBP and the 43 residue encephalitogenic fragment (EF); in addition, Le rat lymph node cells (LNC) were stimulated and produced migration inhibitory factor (MIF) when incubated in vitro with these antigens. In contrast Brown Norway (BN) rats, which lack the Ir-EAE gene, did not develop delayed skin tests to EF and their LNC were not stimulated and did not produce MIF when incubated in vitro with EF. These observations indicate that the Ir-EAE gene controls a T-cell response against the EF. Le rats produced measurable anti-BP antibody by radioimmunoassay after primary challenge. Although no antibody was detectable in BN rats by radioimmunoassay, radioimmunoelectrophoresis indicated that a small amount of antibody was formed after primary immunization. After boosting intraperitoneally, both strains of rat exhibited a rise in anti-BP antibody; which was greater in Le rats. In both strains of rat the anti-BP antibody reacted with a portion of the molecule other than the EF. Since EF primarily evokes a T cell response, it is suggested that the EF portion of the BP molecule may contain a helper determinant in antibody production.
Foot and mouth disease: the human consequences
Authors: H. Prempeh
Journal: BMJ (2001)

We investigated the feasibility of radioiodine therapy targeting hepatoma cells (MH3924A) by tissue-specific expression of the human sodium/iodide symporter (hNIS) gene directed by the murine albumin enhancer and promoter (mAlb). <b>Methods:</b> The cell-specific transcriptional activity of mAlb was examined by a luciferase assay in several transiently transfected cell lines. MH3924A cells were stably transfected with the recombinant retroviral vector, in which hNIS complementary DNA expression was driven by mAlb and coupled to hygromycin resistance gene using an internal ribosomal entry site (IRES). Functional hNIS expression in hepatoma cells was confirmed by an iodide uptake assay. In imaging studies, the tumor-bearing ACI rats were intravenously injected with <sup>131</sup>I and imaged with a γ-camera. Biodistribution was studied at 30 min and at 1, 3, 6, and 25 h after injection of <sup>131</sup>I. Toxic effects of <sup>131</sup>I on hepatoma cells were studied in vitro and in vivo. <b>Results:</b> Stably transfected MH3924A cells concentrated <sup>125</sup>I up to 240-fold higher than the wild-type cells. The iodide uptake in stably transfected cells was inhibited by ouabain and sodium perchlorate but increased by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid. An in vitro clonogenic assay revealed an 86% decrease in colony number in stably transfected cells after exposure to 3.7 MBq/mL of <sup>131</sup>I and only about 8% in hNIS-negative control cells. Furthermore, the in vivo study showed intense tracer accumulation in hNIS-expressing tumors after administration of <sup>131</sup>I. At 3 h after intraperitoneal injection, the transfected tumors accumulated <sup>131</sup>I 19.2-fold higher than the parental tumors in a biodistribution study. Moreover, administration of a therapeutic dose of <sup>131</sup>I resulted in an inhibition of hNIS-expressing tumor growth, whereas control tumors continued to increase in size. <b>Conclusion:</b> A therapeutic effect of <sup>131</sup>I on hepatoma cells in vitro and in vivo has been demonstrated after tumor-specific iodide uptake induced by mAlb-directed hNIS gene expression. Because a stable transformed cell line has been used in these experiments, the clinical potential of this strategy must be evaluated after in vivo transfection of hepatoma cells.
Risk Factors for Foot Infections in Individuals With Diabetes
Authors: Lawrence A. Lavery, David G. Armstrong, Robert P. Wunderlich, M. Jane Mohler, Christopher S. Wendel, Benjamin A. Lipsky
Journal: Diabetes Care (2006)

To prospectively determine risk factors for foot infection in a cohort of people with diabetes.We evaluated then followed 1,666 consecutive diabetic patients enrolled in a managed care-based outpatient clinic in a 2-year longitudinal outcomes study. At enrollment, patients underwent a standardized general medical examination and detailed foot assessment and were educated about proper foot care. They were then rescreened at scheduled intervals and also seen promptly if they developed any foot problem.During the evaluation period, 151 (9.1%) patients developed 199 foot infections, all but one involving a wound or penetrating injury. Most patients had infections involving only the soft tissue, but 19.9% had bone culture-proven osteomyelitis. For those who developed a foot infection, compared with those who did not, the risk of hospitalization was 55.7 times greater (95% CI 30.3-102.2; P < 0.001) and the risk of amputation was 154.5 times greater (58.5-468.5; P < 0.001). Foot wounds preceded all but one infection. Significant (P < 0.05) independent risk factors for foot infection from a multivariate analysis included wounds that penetrated to bone (odds ratio 6.7), wounds with a duration >30 days (4.7), recurrent wounds (2.4), wounds with a traumatic etiology (2.4), and presence of peripheral vascular disease (1.9).Foot infections occur relatively frequently in individuals with diabetes, almost always follow trauma, and dramatically increase the risk of hospitalization and amputation. Efforts to prevent infections should be targeted at people with traumatic foot wounds, especially those that are chronic, deep, recurrent, or associated with peripheral vascular disease.
Optimal treatment of metastatic pancreatic cancer
Authors: D. Cunningham, I. Chong
Journal: Gut (2010)

Approximately 60% of patients with pancreatic cancer have metastatic disease at the time of diagnosis.1 Gemcitabine, which has been shown to improve overall survival (OS) and clinical response compared with 5-fluorouracil (5-FU), is standard treatment with a median survival of 6 months and a 1 year survival rate of only 20%.2 The addition of other drugs to gemcitabine to improve outcome has been generally unsuccessful with the exception of erlotinib, an oral human epidermal growth factor 1 receptor/epidermal growth factor receptor ( HER1/EGFR ) tyrosine kinase inhibitor. The combination of erlotinib with gemcitabine resulted in an improved 1 year survival compared with gemcitabine alone (23% vs 17%, p=0.023).3 Data from a phase III trial evaluating gemcitabine with capecitabine (GEM-CAP) showed an improvement in response and progression-free survival with GEM-CAP over single-agent gemcitabine, and pooling of these results with two other randomised controlled trials in a meta-analysis resulted in a survival advantage with GEM-CAP.4

At this year's American Society of Clinical Oncology annual meeting, the interim analysis from the randomised phase III PRODIGE 4/ACCORD 11 trial comparing FOLFIRINOX (5-FU/leucovorin, irinotecan and oxaliplatin) with gemcitabine as first-line treatment for fit patients with metastatic pancreatic adenocarcinoma was presented.5 These preliminary results were encouraging, with a significantly longer OS, progression-free survival and improved response rate associated with the experimental arm compared with gemcitabine alone. Although …
Determination of IgA- and IgM-rheumatoid factors in patients with rheumatoid arthritis with and without nephropathy.
Authors: M Nakano, M Ueno, S Nishi, S Suzuki, H Hasegawa, T Watanabe, T Kuroda, S Ito, M Arakawa
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To clarify the characteristics and pathogenesis of renal disorders in patients with rheumatoid arthritis (RA). METHODS: In this study, 143 patients with RA were included, from whom 43 with urinary abnormalities were biopsied. Serum rheumatoid factor (RF) concentrations of IgA and IgM isotypes were also measured in these patients by enzyme linked immunosorbent assay. RESULTS: Light microscopy of renal biopsy specimens showed minor glomerular abnormalities in six patients, mesangial proliferative glomerulonephritis (GN) in 21, membranous nephropathy in seven, renal amyloidosis in seven, and tubulointerstitial nephritis in two. Twelve patients with mesangial proliferative GN and one with minor glomerular abnormalities were found by immunofluorescence microscopy to have abnormalities consistent with IgA GN. Although the concentrations of IgA-RF in patients with IgA GN were slightly raised compared with those with glomerulopathy established by biopsy but not associated with IgA GN, the concentrations of IgA-RF were higher in patients with RA with vasculitis or interstitial pneumonia than those with RA complicated by IgA GN. CONCLUSIONS: Mesangial proliferative GN, including IgA GN, may be a frequent renal lesion in Japanese patients with RA. IgA-RF may play little pathogenetic part in the development of IgA GN in RA.
Hypertension in Obesity and NIDDM: Role of Insulin and Sympathetic Nervous System
Authors: Patricia A Daly, Lewis Landsberg
Journal: Diabetes Care (1991)

An important link exists between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension. Most patients with NIDDM are obese; the incidence of hypertension in obesity and NIDDM is substantial, approaching 50% in some studies. Furthermore, hypertension is known to contribute to the increased cardiovascular morbidity and mortality in patients with obesity and NIDDM. Despite the obvious clinical importance, the pathogenesis of hypertension in obesity and NIDDM remains poorly understood. Recent studies have identified hyperinsulinemia and insulin resistance as important threads that tie hypertension, obesity, and NIDDM together. The hypothesis is developed that insulin-mediated sympathetic stimulation contributes to blood pressure elevation in both obesity and NIDDM. Recruited as a mechanism to limit weight gain and restore energy balance, insulin resistance and sympathetic stimulation increase blood pressure by enhancing renal Na+ reabsorption and stimulating the cardiovascular system. In this article, we review the evidence on which this hypothesis is based.
Efficacy of adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device in adults with acute severe asthma
Authors: Yutaka Nakano, Noriyuki Enomoto, Akira Kawamoto, Ritsuko Hirai, Kingo Chida
Journal: Journal of Allergy and Clinical Immunology (2000)
Abstract 2814: Sonic hedgehog in gastric cancer metastasis; MAP Kinase/NFκB-dependent signaling pathway.
Authors: Myoung Hee Kang, Bo Ram Kim, Joo Sung Park, Jung Guk Jeon, Hyun Sook An, You Jin Jang, Sun Il Kim, Jun Suk Kim, Sang Cheul Oh
Journal: Cancer Research (2013)

Abstract Up-regulation of Sonic hedgehog and their receptors by tumor is an important hallmark in cancer progression, as it contributes through autocrine and paracrine mechanisms to tumor development, invasion, and metastasis, but the role and cellular mechanism in the invasive phenotype of gastric cancer cells is not known. Herein, we determined the roles of Mitogen-activated protein kinase (MAPK) signaling, nuclear factor (NF)-κB, and matrix metalloproteinase (MMP) expression in Shh-mediated metastatic function in gastric cancer. We found that stimulation of Shh in gastric cancer cells enhanced the phosphorylation of JNK and p38. Accompanying activation of JNK and p38 kinase, Shh also enhanced phosphorylation/degradation of IκBα and the nuclear translocation/activation of NF-κB. Interestingly, blockade of JNK and p38 signaling using SP600125 and SB202190, respectively, significantly inhibited Shh-induced motility and invasiveness in association with the activation of NF-κB. In addition, phosphorylation of JNK, p38 and of IκBα, IκBα degradation, and the nuclear translocation of NF-κB was enhanced by treatment with N-shh, but not cyclopamin or shh neutralization antibodies. Furthermore, Shh-induced MMP-9 expression and enzymatic activity was also significantly blocked by treatment with MAPK, JNK, or NF-κB inhibitors. Immunohistochemistry staining of 178 gastric tumor biopsies indicated that expression of shh and MMP-9 had a significant positive correlation with lymph node metastasis and a poor prognosis. These results indicate that the Shh signaling pathway enhances tumor metastasis in gastric cancer by sequential activation of the JNK or MAPK pathway followed by the induction of NF-κB and MMP-9 activity, indicating that shh has the potential to be a therapeutic molecular target to decrease metastasis. Overall, our studies suggest that Shh promote motility and invasion of gastric cancer cells by activating MAPK/ NF-κB signaling and that targeting for these signaling may provide therapeutic opportunities in preventing metastasis mediated by Shh. Citation Format: Myoung Hee Kang, Bo Ram Kim, Joo Sung Park, Jung Guk Jeon, Hyun Sook An, You Jin Jang, Sun Il Kim, Jun Suk Kim, Sang Cheul Oh. Sonic hedgehog in gastric cancer metastasis; MAP Kinase/NFκB-dependent signaling pathway. [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 2814. doi:10.1158/1538-7445.AM2013-2814
Histamine-releasing activity in supernatants of mononuclear cells: Contribution of monocyte chemotactic protein-1 activity compared with IgE-dependent activity
Authors: Suzanne G.M.A. Pasmans, Marja Aalbers, Mohamed R. Daha, Edward F. Knol, Henk M. Jansen, Rob C. Aalberse
Journal: Journal of Allergy and Clinical Immunology (1996)
Antihypertensive Treatment and Change in Blood Pressure Are Associated With the Progression of White Matter Lesion Volumes
Authors: Ophélia Godin, Christophe Tzourio, Pauline Maillard, Bernard Mazoyer, Carole Dufouil
Journal: Circulation (2011)

Blood pressure (BP) is recognized as a major risk factor for white matter lesions (WMLs), but longitudinal data are scarce, and there is insufficient evidence for the benefit of antihypertensive therapy on WML progression. We studied the relationship between BP change and WML volume progression over time in a sample of 1319 elderly individuals who had 2 cerebral magnetic resonance imaging examinations 4 years apart. We also examined the impact of antihypertensive treatment on WML progression.Subjects were participants from the Three-City (3C)-Dijon Magnetic Resonance Imaging Study, a prospective population-based cohort of elderly ≥ 65 years of age. WML volumes and their progression were estimated with the use of a fully automatic procedure. We performed ANCOVA models first to assess the association between BP change and WML progression and second to estimate the relation between antihypertensive treatment and WML load progression. Baseline and change in BP were significant predictors of higher WML progression over time after controlling for potential confounders. Among subjects with high SBP (≥ 160 mm Hg) at baseline not treated by antihypertensive medication, antihypertensive treatment started within 2 years was related to a smaller increase in WML volume at a 4-year follow-up (0.24 cm³; SE=0.44 cm³) than no hypertensive treatment (1.60 cm³; SE = 0.26 cm³; P = 0.0008) on multivariable modeling.Our findings reinforce the hypothesis that hypertension is a strong predictor of WML and that adequate treatment may reduce the course of WML progression. Because WMLs are linked to both dementia and stroke risks, these results could have implications for future preventive trials.
Risks of Weight Lifting
Authors: Paul H. Langer
Journal: JAMA (1970)

<h3>To the Editor.—</h3> The answers given by your two consultants cover the orthopedic aspects but fail to consider the cardiovascular problems. Weight lifting by a 22-year-old man with a blood pressure of 160/100 leaves something to be desired from the cardiovascular standpoint. I agree with the benefits your consultants mention for people who are, or wish to become, muscle men or athletes. However, the presence of a hypertension of 160/100 in someone who is presumably not a professional athlete raises an entirely different group of problems. Weight lifting is principally a static form of exercise and it has been clearly shown that static exercise raises the blood pressure and does little or nothing to benefit the heart and cardiovascular system in general. Therefore, anyone with a tendency to hypertension should refrain from weight lifting and other forms of static exercise and should consider a rhythmic exercise such as swimming or
Fungus-Specific CD4<sup>+</sup> T Cells for Rapid Identification of Invasive Pulmonary Mold Infection
Authors: Petra Bacher, Angela Steinbach, Olaf Kniemeyer, Axel Hamprecht, Mario Assenmacher, Maria J. G. T. Vehreschild, Jörg J. Vehreschild, Axel A. Brakhage, Oliver A. Cornely, Alexander Scheffold
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Complications Following Closed-Chest Cardiac Massage
Authors: Dean T. Clark
Journal: JAMA (1962)

WITH THE ADVENT of closed-chest cardiac massage for cardiac arrest, there have appeared reports of complications of this procedure. Morgan has reported a ruptured liver, and Barin ger et al. have reported cases of fractured ribs, hemothorax, hemopericardium, liver injury, and bone-marrow emboli. This paper reports 19 cases of complications that were found at coroners' autopsies. None of these cases involved trauma as the cause of death, so the injuries found could only be complications of the closed-chest cardiac massage. Most of the following cases were dead on arrival at hospital emergency rooms. Report of Cases Case1.—A 67-year-old female was found comatose in bed at home. She died while being admitted to the hospital. A doctor performed closed-chest cardiac massage for approximately 20 minutes. Autopsy findings showed a large myoeardial infarction, and a hematoma around the hilus of the left kidney of 100 cc. of blood. Case2.—A 64-year-old