tbuckley/cabot-search huggingface dataset:
Validation and clinical implications of the IDSA/ATS minor criteria for severe community-acquired pneumonia
Authors: J Phua, K C See, Y H Chan, L S Widjaja, N W Aung, W J Ngerng, T K Lim
Journal: Thorax (2009)

The 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) guidelines defined severe community-acquired pneumonia (CAP) and recommended intensive care unit (ICU) admission when patients fulfilled three out of nine minor criteria. These criteria have not been validated.All patients admitted to our hospital from 2004 to 2007 for CAP were reviewed retrospectively. Patients who fulfilled any IDSA/ATS major criteria for severe CAP at the emergency department (ie, the need for mechanical ventilation or vasopressors) were excluded. The predictive characteristics of the IDSA/ATS minor criteria were compared with those of the Pneumonia Severity Index (PSI) and the CURB-65 score for hospital mortality and ICU admission.1242 patients were studied (mean age 65.7 years, hospital mortality 14.7%). The areas under the receiver operating characteristic curves for the IDSA/ATS minor criteria were 0.88 (95% CI 0.86 to 0.91) and 0.85 (95% CI 0.81 to 0.88) for predicting hospital mortality and ICU admission, respectively. These were greater than the corresponding areas for the PSI and the CURB-65 score (p < 0.05). The sensitivity, specificity, positive and negative predictive values of the minor criteria were 81.4%, 82.9%, 45.2% and 96.3%, respectively, for hospital mortality and 58.3%, 90.6%, 52.9% and 92.3%, respectively, for ICU admission. The minor criteria were more specific than the PSI and more sensitive than the CURB-65 score for both outcomes.These findings support the use of the IDSA/ATS minor criteria to predict hospital mortality and guide ICU admission in inpatients with CAP who do not require emergency mechanical ventilation or vasopressors.
Myogenic Nature of Increase in Intestinal Vascular Resistance with Venous Pressure Elevation
Authors: PAUL C. JOHNSON, L. STUART GRAHAM
Journal: Circulation Research (1959)

These studies attempted to distinguish between the various intrinsic mechanisms which might be responsible for the increase in vascular resistance seen in the intestine with venous pressure elevation (the venous-arteriolar response). Intra-arterial infusion of procaine did not block the response, indicating that a local reflex is not involved. However, the resistance increase was greatly modified during infusion of a smooth muscle relaxant (papaverine). Cyanide and ischemia were more effective than papaverine, resistance remaining unchanged as venous pressure was elevated. The tone of the intestinal wall was not increased with venous pressure elevation. In preparations perfused with an oil-kerosene mixture, resistance decreased as venous pressure was elevated, although intravascular and extravascular fluid accumulation was quantitatively the same as in the blood-perfused control. It is concluded that the venous-arteriolar response is not dependent upon neural mechanisms, nor is it due to purely physical factors. It is suggested that elevation of venous pressure causes sufficient increase of arteriolar pressure to induce a myogenic response of the resistance vessels.
Linear IgA disease with circulating IgA antibodies against the NC16A domain of BP180
Authors: E Schmidt, K Herzele, H Schumann, U Wesselmann, I Chimanovitch, L Bruckner-Tuderman, E B Bröcker, G J Giudice, D Zillikens
Journal: British Journal of Dermatology (1999)

Journal Article Linear IgA disease with circulating IgA antibodies against the NC16A domain of BP180 Get access E Schmidt, E Schmidt Department of Dermatology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany, Search for other works by this author on: Oxford Academic Google Scholar K Herzele, K Herzele Department of Dermatology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany, Search for other works by this author on: Oxford Academic Google Scholar H Schumann, H Schumann Department of Dermatology, University of Münster, Münster, Germany, Search for other works by this author on: Oxford Academic Google Scholar U Wesselmann, U Wesselmann Department of Dermatology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany, Search for other works by this author on: Oxford Academic Google Scholar I Chimanovitch, I Chimanovitch Department of Dermatology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany, Search for other works by this author on: Oxford Academic Google Scholar L Bruckner‐Tuderman, L Bruckner‐Tuderman Department of Dermatology, University of Münster, Münster, Germany, Search for other works by this author on: Oxford Academic Google Scholar E B Bröcker, E B Bröcker Department of Dermatology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany, Search for other works by this author on: Oxford Academic Google Scholar G J Giudice, G J Giudice Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA. E‐mail: zillikens‐d.derma@mail.uni‐wuerzburg.de Search for other works by this author on: Oxford Academic Google Scholar D Zillikens D Zillikens Department of Dermatology, University of Würzburg, Josef‐Schneider‐Str. 2, 97080 Würzburg, Germany, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 140, Issue 5, 1 May 1999, Pages 964–966, https://doi.org/10.1046/j.1365-2133.1999.02838.x Published: 01 May 1999
Ivermectin alone or in combination with benzyl benzoate in the treatment of human immunodeficiency virus-associated scabies
Authors: F. Alberici, L. Pagani, G. Ratti, P. Viale
Journal: British Journal of Dermatology (2000)

In order to establish a safe and reliable treatment for human immunodeficiency virus (HIV)-associated scabies, we have treated 60 episodes of scabies in this setting, occurring in 39 patients, with one of the following regimens: (i) topical treatment with benzyl benzoate solution; (ii) single-dose oral treatment with ivermectin alone; and (iii) combination therapy with benzyl benzoate solution and oral ivermectin, employing the same regimens as single-agent therapy. Patients were stratified according to the severity score of the disease and the outcome (eradication, relapse, failure). We found that both benzyl benzoate and ivermectin alone were quite effective in mild to moderate scabies, but they were both associated with an unacceptable rate of relapse and failure in severe or crusted scabies. In contrast, combined treatment produced an optimal rate of success, without significant treatment-related side-effects. Therefore, we consider that combination treatment with benzyl benzoate solution and oral ivermectin is preferable to single-agent therapy in crusted scabies occurring in HIV/acquired immune deficiency syndrome patients.
Habituation of Arousal Responses after Intermittent Hypercapnic Hypoxia in Piglets
Authors: Karen A. Waters, Kellie D. Tinworth
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Clinical studies have demonstrated arousal deficits in infants suffering obstructive sleep apnea, and some infant deaths have been attributed to such an arousal deficit.To evaluate whether arousal deficits can be induced by intermittent asphyxia during normal development.Young piglets were exposed to intermittent hypercapnic hypoxia for 4 days from age 9.55 +/- 0.5 days. Arousal responses were compared between control animals and animals exposed to intermittent hypercapnic hypoxia. Outcome measures included time to arouse after onset of the respiratory stimulus and frequency of arousals during recovery.Arousal deficits emerged after successive exposures to hypercapnic hypoxia on Day 1, and were exacerbated on Day 4, although after overnight recovery, the deficit only became evident during the second and subsequent episode of hypercapnic hypoxia. On Day 1, time to arouse increased from 16.9 +/- 7.1 seconds in the first epoch to 41.7 +/- 28.6 seconds in the fourth epoch (p = 0.004 between cycles, one-way analysis of variance). In the recovery periods after hypercapnic hypoxia, there were 64% fewer arousals than baseline on Day 1 and 90% fewer arousals on Day 4. Respiratory effort, measured by VT across 10 breaths before the arousal, increased from 25.7 +/- 7.6 on Day 1 to 29.1 +/- 6.8 ml/kg on Day 4 (p < 0.001, two-way analysis of variance, Day 4 vs. Day 1, respectively).These studies demonstrate that acute and chronic arousal deficits can be induced by intermittent asphyxia, on a background of otherwise normal postnatal development.
Diffusion Magnetic Resonance Imaging: A Biomarker for Treatment Response in Oncology
Authors: Daniel A. Hamstra, Alnawaz Rehemtulla, Brian D. Ross
Journal: Journal of Clinical Oncology (2007)

Imaging of response to oncology treatments, either on clinical protocol or as part of standard practice, is a complicated process that has evolved during the last 10 years due to the improvement of existing imaging technologies and the introduction of newer modalities. Diffusion magnetic resonance imaging is a technique that measures the mobility of water within tissues and, as such, may function as a surrogate marker for both tissue cellularity and response to treatment that occur earlier than usual measures of tumor response. This review highlights the development of this technique and the state of current clinical understanding of its utility.
Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence
Authors: Ketan R. Patel, Catherine Andreadi, Robert G. Britton, Emma Horner-Glister, Ankur Karmokar, Stewart Sale, Victoria A. Brown, Dean E. Brenner, Rajinder Singh, William P. Steward, Andreas J. Gescher, Karen Brown
Journal: Science Translational Medicine (2013)

The phytochemical resveratrol has been shown to exert numerous health benefits in preclinical studies, but its rapid metabolism and resulting poor bioavailability may limit translation of these effects to humans. Resveratrol metabolites might contribute to in vivo activity through regeneration of the parent compound. We present quantitation of sulfate and glucuronide conjugates of resveratrol in human plasma and tissue after repeated ingestion of resveratrol by volunteers and cancer patients, respectively. Subsequent pharmacokinetic characterization of a mixture of resveratrol-3-O-sulfate and resveratrol-4'-O-sulfate in mice showed that these metabolites are absorbed orally but have low bioavailabilities of ~14 and 3%, respectively. Sulfate hydrolysis in vivo liberated free resveratrol, which accounted for ~2% of the total resveratrol species present in mouse plasma. Monosulfate metabolites were also converted to the parent in human colorectal cells. The extent of cellular uptake was dependent on specific membrane transporters and dictated antiproliferative activity. Sulfate metabolites induced autophagy and senescence in human cancer cells; these effects were abrogated by inclusion of a sulfatase inhibitor, which reduced intracellular resveratrol. Together, our findings suggest that resveratrol is delivered to target tissues in a stable sulfate-conjugated form and that the parent compound is gradually regenerated in selected cells and may give rise to the beneficial effects in vivo. At doses considered to be safe in humans, resveratrol generated via this route may be of greater importance than the unmetabolized form.
A gene linked to the Igh-C locus controls the production of rheumatoid factor in the mouse.
Authors: J L Van Snick
Journal: The Journal of Experimental Medicine (1981)

In certain specific pathogen-free colonies, mice, upon aging, produce autoantibodies (RF) specific for the Fc portion of their IgG. In our colony, 129/Sv mice (H-2bvl; Igh-1a) have 10-20 times higher RF levels than C5BL/6 (h-2b; Igh-1b). In addition, the 129 have mainly IgA anti-IgG2a, and the B6 have mainly IgM anti-IgGl. We analyzed the genetic factors that control these differences. The high RF-producer phenotype of strain 129 was inherited as a recessive trait as indicated by the low RF levels of (129 X B6) F1 mice. About 1 of 4 129 X F1 (129 X B6) backcrosses and 1 of 10 (129 X B6) F2 mice had high RF levels, suggesting the involvement of two recessive genes in the control of this RF production. All F2 mice and all but one backcross with high IgA anti-IgG2a levels were homozygous for the Ihg-1a allele of the 129 mouse. In contrast, the B6-type RF was eight times more frequent in Igh-1bb than in Igh-1ab or Igh-1aa mice. High RF titers of either type were suppressed in Igh-1ab mice.
Establishment of a Model to Objectively Examine Maximal Nasal Decongestion Using a Clinically Available Antihistamine/decongestant
Authors: F ROMEROJR, P PHILLIPS, V NORRIS, K TURNER, K HUTCHINSON, R ALLAN, E TAN, J MISFELDT, J WARD, T CASALE
Journal: Journal of Allergy and Clinical Immunology (2008)
Predicting outcome in melanoma: where are we now?
Authors: L. Jennings, G.M. Murphy
Journal: British Journal of Dermatology (2009)

Melanoma incidence continues to rise in most countries. This is of grave concern, given the mortality rate in a relatively young population. Current staging tools are limited in their ability to predict accurately those at risk of metastatic disease, relapse and treatment failure. This overview comprehensively reviews relevant literature, with the focus on the last 5 years, and discusses the current state of traditional and emerging novel methods of staging for melanoma and their effect on prognosis in this population.
Association of Autophagy Defect with a Malignant Phenotype and Poor Prognosis of Hepatocellular Carcinoma
Authors: Zhen-Bin Ding, Ying-Hong Shi, Jian Zhou, Shuang-Jian Qiu, Yang Xu, Zhi Dai, Guo-Ming Shi, Xiao-Ying Wang, Ai-Wu Ke, Bin Wu, Jia Fan
Journal: Cancer Research (2008)

Abstract Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The role of autophagy and the prognostic value of autophagic genes are largely unknown in HCC. Here, we showed decreased expression of autophagic genes and their corresponding autophagic activity and increased expression of the antiapoptotic gene Bcl-xL in HCC cell lines compared with a normal hepatic cell line. We also found decreased expression of the autophagic gene Beclin 1 in 44 HCC tissue samples compared with adjacent nontumor tissues. In addition, we found that the most aggressive malignant HCC cell lines and HCC tissues with recurrent disease displayed much lower autophagic levels, especially when Bcl-xL was overexpressed. Interestingly, in a tissue microarray study consisting of 300 HCC patients who underwent curative resection, the expression of Beclin 1 was only significantly correlated with disease-free survival (DFS; P &amp;lt; 0.0001) and overall survival (OS; P &amp;lt; 0.0001) in the Bcl-xL+ group. Multivariate and univariate analyses also revealed that Beclin 1 expression was an independent predictor for DFS and OS in Bcl-xL+ patients. In addition, we found a significant correlation between Beclin 1 expression and tumor differentiation in Bcl-xL+ but not in Bcl-xL− HCC patients. In conclusion, our data showed expression of autophagic genes and their corresponding autophagic activities were suppressed in HCC. The autophagy defects synergized with altered apoptotic activity might facilitate tumor malignant differentiation, which results in a more aggressive cancer cell phenotype and poor prognosis of HCC. [Cancer Res 2008;68(22):9167–75]
Effect of albendazole on recurrent and residual alveolar echinococcosis of the liver after surgery
Authors: H Ishizu, J Uchino, N Sato, S Aoki, K Suzuki, H Kuribayashi
Journal: Hepatology (1997)

Patients with alveolar echinococcosis of the liver (AEL) can be cured by complete excision of the lesions; however, it is not always completely resectable in advanced cases. Recently, benzimidazole–type drugs have been reported to be effective in nonresectable AEL. One hundred fifty–two patients with AEL have been surgically treated in our institution since 1937. Our clinical trial with albendazole, one of the benzimidazole carbamates, has included 26 cases of AE since September 1988, each of whom had undergone an operation. Complete resection was performed in only six cases. Evaluation of response to the treatment was possible in 20 cases. A favorable response to albendazole, such as decreases in the size of the lesions, changes in cyst morphology, and amelioration in clinical symptoms or signs, was achieved in 11 (55%) cases. These favorable responses were also seen in cases of noncurative resection and palliative operation. The cumulative survival rate of the patients was 87%, 15 years after the operation. A complete response was achieved in one case; the residual lesion in the liver completely disappeared on the computed tomography image 3.5 years after noncurative surgery. Palliative or mass reduction surgery combined with albendazole therapy may be a strategy for advanced disease, especially when complete resection might result in significant morbidity or mortality.
THE MOLECULAR BASIS OF X-LINKED SEVERE COMBINED IMMUNODEFICIENCY: Defective Cytokine Receptor Signaling
Authors: Warren J. Leonard, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract X-linked severe combined immunodeficiency (XSCID) is an inherited disease characterized by profoundly diminished cell-mediated and humoral immunity. XSCID was found to result from mutations in the interleukin-2 (IL-2) receptor γchain. Knowledge of the genetic defect has important implications for prenatal and postnatal diagnosis, carrier female identification, and the possibility of gene therapy. The fact that the phenotype and clinical manifestations in XSCID are more severe than the abnormalities found in humans or mice deficient in IL-2 led to the speculation and subsequent confirmation that the IL-2 receptor is not the only receptor to contain the γ chain. Instead, the γ chain is also a component of the receptors for IL-4, IL-7, IL- 9, and IL-15 and is now denoted as the common cytokine receptor γ chain, γ c . The role of γ c in signaling and lymphoid development and the implications of a shared receptor component are discussed.
The Spermatozoa Protein, SLLP1, Is a Novel Cancer–Testis Antigen in Hematologic Malignancies
Authors: Zhiqing Wang, Yana Zhang, Arabinda Mandal, Jian Zhang, Francis J. Giles, John C. Herr, Seah H. Lim
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Neoplastic cells often aberrantly express normal testicular proteins. Because these proteins have a very restricted normal tissue expression, they may be suitable targets for immunotherapy. SLLP1 is an intra-acrosomal, nonbacteriolytic, c lysozyme–like protein recently isolated from human spermatozoa. In this study, we determined whether SLLP1 is a novel cancer–testis antigen in hematologic malignancies Experimental Design: SLLP1 expression in hematologic tumor cells and normal tissues was determined using a combination of reverse transcription-PCR, real-time PCR, and Western blot analysis. The presence of antibodies against SLLP1 was determined by ELISA analysis. Results: SLLP1 was aberrantly expressed in the tumor cells from 2 of 9 acute myeloid leukemia, 3 of 11 chronic lymphocytic leukemia, 4 of 14 chronic myeloid leukemia, and 6 of 17 multiple myeloma. In contrast, they were not detected in corresponding specimens from any healthy donors. SLLP1 exhibited a very restricted normal tissue expression, being found only in testis/spermatozoa. SLLP1 was expressed in some tumor cells at a level of &amp;gt;25%. High titer IgG antibodies against SLLP1 were also detected in the sera of some of these patients. Conclusions: SLLP1 is a novel cancer–testis antigen in hematologic malignancies and is capable of eliciting B-cell immune responses in vivo in cancer-bearing individuals. Our results, therefore, support SLLP1 as a protein target appropriate for additional in vitro study to define its suitability for immunotherapy.
TGF-β signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development
Authors: Juan Juan Yin, Katri Selander, John M. Chirgwin, Mark Dallas, Barry G. Grubbs, Rotraud Wieser, Joan Massagué, Gregory R. Mundy, Theresa A. Guise
Journal: Journal of Clinical Investigation (1999)

Breast cancer frequently metastasizes to the skeleton, and the associated bone destruction is mediated by the osteoclast. Growth factors, including transforming growth factor-β (TGF-β), released from bone matrix by the action of osteoclasts, may foster metastatic growth. Because TGF-β inhibits growth of epithelial cells, and carcinoma cells are often defective in TGF-β responses, any role of TGF-β in metastasis is likely to be mediated by effects on the surrounding normal tissue. However, we present evidence that TGF-β promotes breast cancer metastasis by acting directly on the tumor cells. Expression of a dominant–negative mutant (TβRIIΔcyt) of the TGF-β type II receptor rendered the human breast cancer cell line MDA-MB-231 unresponsive to TGF-β. In a murine model of bone metastases, expression of TβRIIΔcyt by MDA-MB-231 resulted in less bone destruction, less tumor with fewer associated osteoclasts, and prolonged survival compared with controls. Reversal of the dominant–negative signaling blockade by expression of a constitutively active TGF-β type I receptor in the breast cancer cells increased tumor production of parathyroid hormone–related protein (PTHrP), enhanced osteolytic bone metastasis, and decreased survival. Transfection of MDA-MB-231 cells that expressed the dominant–negative TβRIIΔcyt with the cDNA for PTHrP resulted in constitutive tumor PTHrP production and accelerated bone metastases. These data demonstrate an important role for TGF-β in the development of breast cancer metastasis to bone, via the TGF-β receptor–mediated signaling pathway in tumor cells, and suggest that the bone destruction is mediated by PTHrP.
Free fatty acids: potential proinflammatory mediators in rheumatic diseases
Authors: Klaus W Frommer, Andreas Schäffler, Stefan Rehart, Angela Lehr, Ulf Müller-Ladner, Elena Neumann
Journal: Annals of the Rheumatic Diseases (2013)

Objectives Due to their role in inflammatory metabolic diseases, we hypothesised that free fatty acids (FFA) are also involved in inflammatory joint diseases. To test this hypothesis, we analysed the effect of FFA on synovial fibroblasts (SF), human chondrocytes and endothelial cells. We also investigated whether the toll-like receptor 4 (TLR4), which can contribute to driving arthritis, is involved in FFA signalling. Methods Rheumatoid arthritis SF, osteoarthritis SF, psoriatic arthritis SF, human chondrocytes and endothelial cells were stimulated in vitro with different FFA. Immunoassays were used to quantify FFA-induced protein secretion. TLR4 signalling was inhibited extracellularly and intracellularly. Fatty acid translocase (CD36), responsible for transporting long-chain FFA into the cell, was also inhibited. Results In rheumatoid arthritis synovial fibroblasts (RASF), FFA dose-dependently enhanced the secretion of the proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, as well as the matrix-degrading enzymes pro-MMP1 and MMP3. The intensity of the response was mainly dependent on the patient rather than on the type of disease. Both saturated and unsaturated FFA showed similar effects on RASF, while responses to the different FFA varied for human chondrocytes and endothelial cells. Extracellular and intracellular TLR4 inhibition as well as fatty acid transport inhibition blocked the palmitic acid-induced IL-6 secretion of RASF. Conclusions The data show that FFA are not only metabolic substrates but may also directly contribute to articular inflammation and degradation in inflammatory joint diseases. Moreover, the data suggest that, in RASF, FFA exert their effects via TLR4 and require extracellular and intracellular access to the TLR4 receptor complex.