tbuckley/cabot-search huggingface dataset:
Receptor analogs and monoclonal antibodies that inhibit adherence of Bordetella pertussis to human ciliated respiratory epithelial cells.
Authors: E Tuomanen, H Towbin, G Rosenfelder, D Braun, G Larson, G C Hansson, R Hill
Journal: The Journal of Experimental Medicine (1988)

The adherence of Bordetella pertussis to human respiratory cilia is critical to the pathogenesis of whooping cough. To explore the development of agents that could interrupt adherence, the structure of the receptor on the ciliary surface was investigated. Using an in vitro adherence assay to human ciliated epithelial cells, galactose, lactose, and complex carbohydrates containing lactose eliminated adherence when preincubated with the bacteria. 10(-2) M galactose eluted adherent bacteria from cilia. B. pertussis and its two purified adhesins bound specifically to natural lactose-containing glycolipids in a TLC assay. mAbs to eukaryotic glycoconjugates with specificity for substituted galactose-glucose moieties blocked adherence when preincubated with ciliated cells. The carbohydrates that serve as receptors for B. pertussis on human cilia are galactose-glucose-containing glycolipids. Receptor analogs and anti-receptor antibodies effectively block adherence of B. pertussis to cilia and thus should be considered candidates for therapeutic intervention against disease.
Insulin Action in Hyperthyroidism: A Focus on Muscle and Adipose Tissue
Authors: Panayota Mitrou, Sotirios A. Raptis, George Dimitriadis
Journal: Endocrine Reviews (2010)

Hyperthyroidism leads to an enhanced demand for glucose, which is primarily provided by increased rates of hepatic glucose production due to increased gluconeogenesis (in the fasting state) and increased Cori cycle activity (in the late postprandial and fasting state). Adipose tissue lipolysis is increased in the fasting state, resulting in increased production of glycerol and nonesterified fatty acids. Under these conditions, increased glycerol generated by lipolysis and increased amino acids generated by proteolysis are used as substrates for gluconeogenesis. Increased nonesterified fatty acid levels are necessary to stimulate gluconeogenesis and provide substrate for oxidation in other tissues (such as muscle). In the postprandial period, insulin-stimulated glucose uptake by the skeletal muscle has been found to be normal or increased, mainly due to increased blood flow. Under hyperthyroid conditions, insulin-stimulated rates of glycogen synthesis in skeletal muscle are decreased, whereas there is a preferential increase in the rates of lactate formation vs. glucose oxidation leading to increased Cori cycle activity. In hyperthyroidism, the Cori cycle could be considered as a large substrate cycle; by maintaining a high flux through it, a dynamic buffer of glucose and lactate is provided, which can be used by other tissues as required. Moreover, lipolysis is rapidly suppressed to normal after the meal to facilitate the disposal of glucose by the insulin-resistant muscle. This ensures the preferential use of glucose when available and helps to preserve fat stores.
Marc Struelens-President of the European Society of Clinical Microbiology and Infectious Diseases
Authors: Pam Das
Journal: The Lancet Infectious Diseases (2004)

Marc Struelens completed his medical degree from the Université Libre de Bruxelles (ULB) in 1980. After obtaining a Diploma of Tropical Medicine at the Prince Léopold Institute of Tropical Medicine in Antwerp, he worked for 3 years as a research associate doing clinical and laboratory research at the International Centre for Diarrhoeal Diseases Research in Bangladesh. He then returned to Brussels where he specialised at ULB Erasme Hospital and was later appointed assistant then associate professor in clinical pathology.
Halothane hepatitis patients have serum antibodies that react with protein disulfide isomerase
Authors: Jackie L. Martin, Gerald J. Kenna, Brian M. Martin, David Thomassen, George F. Reed, Lance R. Pohl
Journal: Hepatology (1993)

Clinical and laboratory evidence suggests that the fulminant liver failure sometimes associated with the inhalation anesthetic halothane may be an immune-mediated toxicity. Most importantly, the vast majority of patients with a clinical diagnosis of halothane hepatitis have serum antibodies, which react with one or more specific liver microsomal proteins that have been covalently altered by the trifluoroacetyl chloride metabolite of halothane. The serum antibodies are specific to halothane hepatitis patients and are not seen in sera of patients with other types of liver pathology. In this study, a 57-kD trifluoroacetylated liver microsomal neoantigen associated with halothane hepatitis and native 57-kD protein were purified from liver microsomes of halothane-treated and -untreated rats, respectively. When the purified trifluoroacetylated 57-kD and native 57-kD proteins were used as test antigens in an enzyme-linked immunosorbent assay, serum antibodies from halothane hepatitis patients (n = 40) reacted with both of these proteins to a significantly greater extent than did serum antibodies from control patients (n = 32). On the basis of its apparent monomeric molecular mass, isoelectric point and NH2-terminal amino acid and tryptic peptide sequences, the 57-kD protein has been identified as rat liver protein disulfide isomerase. Antibodies raised against rat liver protein disulfide isomerase also reacted with a protein of approximately 58-kD in human liver microsomes. The results of this investigation suggest that trifluoroacetylated protein disulfide isomerase is one of the immunogens associated with halothane hepatitis. In certain patients it might lead either to specific antibodies or, possibly, to specific T cells, which could be responsible for halothane hepatitis.
Think globally, ask functionally
Authors: Erik M. Altmann
Journal: Behavioral and Brain Sciences (2003)

The notion of functionality is appropriately central to the Newell Test but is also critical at a lower level, in development of cognitive sub-theories. I illustrate, on one hand, how far this principle is from general acceptance among verbal theoreticians, and, on the other hand, how simulation models (here implemented within ACT-R) seem to drive the functional question automatically.
Effect of Shape, Size, and Aspect Ratio on Nanoparticle Penetration and Distribution inside Solid Tissues Using 3D Spheroid Models
Authors: Rachit Agarwal, Patrick Jurney, Mansi Raythatha, Vikramjit Singh, Sidlgata. V. Sreenivasan, Li Shi, Krishnendu Roy
Journal: Advanced Healthcare Materials (2015)

Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography‐fabricated, polyethylene‐glycol‐based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor‐like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk‐like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (&gt;50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast‐agent delivery.
Left Ventricular Support Systems for High-Risk Percutaneous Coronary Interventions
Authors: John P. Vavalle, E. Magnus Ohman
Journal: Circulation (2012)

H igh-risk percutaneous coronary interventions (PCI) are becoming more prevalent as the ability to perform complex coronary interventions continues to improve.Patients for whom high-risk interventions are considered generally have severe diffuse coronary artery disease, a single last patent conduit, or significant left main disease with large territories of myocardial ischemia.In addition, these patients also typically have reduced left ventricular function (ejection fraction <25%-35%) with comorbidities that make them high risk for standard coronary artery bypass grafting.Thus, PCI is increasingly used as a viable alternative for coronary revascularization, but it too is associated with a high degree of morbidity and mortality.
Decreased Blood Flow with Increased Metabolic Activity: A Novel Sign of Pancreatic Tumor Aggressiveness
Authors: Nghi C. Nguyen, Khaled Taalab, Medhat M. Osman
Journal: Clinical Cancer Research (2009)

To the Editor: Nghi Nguyen, Khalid Taalab, Medhat Osman.We read with great interest the recent article by Komar et al. (1), in which the authors evaluated blood flow (BF) using oxygen-15–labeled water and standardized uptake values (SUV) using 18F-fluorodeoxyglucose positron emission tomography in patients with pancreatic tumors, and correlated these findings with patient survival.Ten patients with pancreatic cancer were divided into two subgroups, using survival at 12 months as the cutoff. Because of the very small sample size (5 patients in each patient subgroup), the unpaired Student's t test applied in the study was inappropriate. Typically, unpaired Student's t test is used for samples with normal distribution. A nonparametric test such as the Mann-Whitney-Wilcoxon test would have been more appropriate because it would not require a normal distribution of the data (2). The P value, however, would have remained statistically significant when using the Mann-Whitney-Wilcoxon test (P = 0.015) instead of the unpaired Student's t test (P = 0.022).The prognosis in patients with pancreatic cancer depends largely on the extent of disease based on tumor-node-metastasis (TNM) staging. Therefore, it would be important to correlate the TNM staging with the SUV/BF ratio. Of the 10 pancreatic cancer patients evaluated, however, TNM staging was not provided in four of these patients because of insufficient data or other reasons. TNM staging was available in the remaining six patients, which, however, would be limited for a proper statistical analysis. It was not clear how much the SUV/BF ratio would correlate with the TNM staging in this study.The study contained pancreatic cancer lesions of 2.5 cm and greater. Therefore, it was not clear whether the prognostic marker of increased metabolism and associated decreased blood perfusion could be applicable for pancreatic lesions less than 2.5 cm in size.The authors suggested that decreased blood flow with associated increased fluorodeoxyglucose metabolism indicated a novel sign of pancreatic tumor aggressiveness. This statement was not convincing because the aforementioned insufficiencies that involved the very small sample size, the lack of lesions less than 2.5 cm in size, and the missing correlation between SUV/BF and TNM staging. Further studies are required to validate these findings.No potential conflicts of interest were disclosed.
Rearrangement of variable region T cell receptor gamma genes in acute lymphoblastic leukemia. V gamma gene usage differs in mature and immature T cells.
Authors: J Hara, S H Benedict, K Yumura, K Ha-Kawa, E W Gelfand
Journal: Journal of Clinical Investigation (1989)

Using probes recognizing variable regions (V gamma) and joining regions (J gamma) of the T cell receptor (TCR) gamma gene, we have analyzed the usage of V gamma genes in 24 patients with T cell acute lymphoblastic leukemia (ALL) and 36 patients with B-precursor ALL. In CD3- T-ALL derived from immature T cells, V gamma genes more proximal to J gamma were frequently rearranged; V gamma 8, V gamma 9, V gamma 10, and V gamma 11 were used in 19 of 24 rearrangements. In contrast, CD3+ T-ALL derived from a more mature stage of T cell ontogeny, showed a high frequency of rearrangements involving V gamma genes distal to J gamma; V gamma 2, V gamma 3, V gamma 4, and V gamma 5 were used in 17 of 25 rearrangements. In B-precursor ALL, no notable bias of V gamma gene usage was observed. This probably reflects the possibility that TCR genes may not rearrange according to a T cell hierarchy when under control of a B cell gene program. Furthermore, deletions of those V gamma genes located 3' to rearranged V gamma genes were observed in all patients analyzed. This supports the theory that loop deletion is a major mechanism for TCR-gamma gene rearrangement.
Prediction of Survival in Patients With Thin Melanoma: Results From a Multi-Institution Study
Authors: Andrea Maurichi, Rosalba Miceli, Tiziana Camerini, Luigi Mariani, Roberto Patuzzo, Roberta Ruggeri, Gianfranco Gallino, Elena Tolomio, Gabrina Tragni, Barbara Valeri, Andrea Anichini, Roberta Mortarini, Daniele Moglia, Giovanni Pellacani, Sara Bassoli, Caterina Longo, Pietro Quaglino, Nicola Pimpinelli, Lorenzo Borgognoni, Daniele Bergamaschi, Catherine Harwood, Odysseas Zoras, Mario Santinami
Journal: Journal of Clinical Oncology (2014)

Cutaneous melanoma incidence is increasing. Most new cases are thin (≤ 1 mm) with favorable prognoses, but survival is nonetheless variable. Our aim was to investigate new prognostic factors and construct a nomogram for predicting survival in individual patients.Data from 2,243 patients with thin melanoma were retrieved from prospectively maintained databases at six centers. Kaplan-Meier survival and crude cumulative incidences of recurrence were estimated, and competing risks were taken into account. Multivariable Cox regression was used to investigate survival predictors.Median follow-up was 124 months (interquartile range, 106 to 157 months); 12-year overall survival was 85.3% (95% CI, 83.4% to 87.2%). Median times to local, regional, and distant recurrence were 79, 78, and 107 months, respectively. Relapse was significantly related to age, Breslow thickness, mitotic rate (MR), ulceration, lymphovascular invasion (LVI), and regression; incidence was lower and subgroup differences were less marked for distant metastasis than for regional relapse. The worst prognosis categories were age older than 60 years, Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, presence of LVI, and regression ≥ 50%. Breslow thickness more than 0.75 mm, MR ≥ 1, presence of ulceration, and LVI (all P = .001) were significantly associated with sentinel node positivity. Age, MR, ulceration, LVI, regression, and sentinel node status were independent predictors of survival and were used to construct a nomogram to predict 12-year overall survival. The nomogram was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.88).Our findings suggest including LVI and regression as new prognostic factors in the melanoma staging system. The nomogram appears useful for risk stratification in clinical management and for recruiting patients to clinical trials.
Impact of myocardial perfusion single-photon emission computed tomography on referral to catheterization of the very elderly Is there evidence of gender-related referral bias?
Authors: Aman M. Amanullah, Hosen Kiat, Rory Hachamovitch, J.Arthur Cabico, John D. Friedman, Daniel S. Berman
Journal: Journal of the American College of Cardiology (1996)
Congenital hypotrichosis due to short anagen
Authors: M.M. Barraud-Klenovsek, R.M. Trüeb
Journal: British Journal of Dermatology (2000)

Two children with congenital hypotrichosis are described. Both presented with persistent short, fine hair since birth. Evidence is provided that the short hair observed in these patients is due to a short anagen phase of the hair cycle, with a normal rate of hair growth. Shortening of the anagen phase of the scalp hair cycle leads to a decrease in the maximal hair length and an increase in the number of hairs in telogen, resulting in an increase in hair shedding. Scanning electron microscopy showed a widely spaced cuticular pattern, a finding typically seen in hair of thin calibre. One patient had affected family members with an apparently autosomal dominant mode of inheritance. The disorder appears to resolve spontaneously during puberty and adulthood.
Gene Transfer of Transforming Growth Factor-β1 to the Rat Peritoneum
Authors: PETER J. MARGETTS, MARTIN KOLB, TOM GALT, CATHERINE M. HOFF, TY R. SHOCKLEY, JACK GAULDIE
Journal: Journal of the American Society of Nephrology (2001)

Long-term peritoneal dialysis is limited by physiologic changes in the peritoneum that lead to ultrafiltration failure. To determine the role of profibrotic cytokines in the alteration of peritoneal transport, a rodent model of transforming growth factor-β (TGF-β)-mediated peritoneal fibrosis was established. An adenoviral vector driving the active form of TGF-β1 (AdTGFβ1) was administered intraperitoneally, and peritoneal structure and function were evaluated for 28 d after infection. Seven days after AdTGFβ1 infection, thickening of the peritoneum, with cellular proliferation and increased vascularization, was noted. By day 28, there was persistent thickening and extensive collagen deposition. The mesenteric collagen content was significantly elevated, compared with control adenovirus-treated animals, 21 d after infection (2.9 versus 1.8 mg hydroxyproline/g tissue, P = 0.006). Blood vessel density, as measured using factor VIII immunohistochemical analyses, was significantly increased from day 4 to day 21 but decreased by day 28. Animals infected with AdTGFβ1 demonstrated increased transport of solutes and decreased net ultrafiltration, which was maximal on day 7 and returned to baseline levels by day 28. It was demonstrated in vitro and in vivo that TGF-β1 induced production of vascular endothelial growth factor. Overexpression of TGF-β1 after adenovirus-mediated gene transfer causes peritoneal fibrosis, neoangiogenesis, and increased peritoneal membrane solute transport. This model should allow further delineation of the relative contributions of profibrotic and angiogenic cytokines to changes in peritoneal function and may lead to potential new interventions for peritoneal membrane failure.
A NEW AND RAPID METHOD FOR THE ISOLATION AND CULTIVATION OF TUBERCLE BACILLI DIRECTLY FROM THE SPUTUM AND FECES
Authors: S. A. Petroff
Journal: The Journal of Experimental Medicine (1915)

Sixty-nine positive cultures were obtained from sixty-nine specimens of sputum from practically all stages of tuberculosis. Six of these specimens were negative by direct microscopic examination, but the cultures gave positive findings. These six specimens have been positive for tubercle bacilli at some time. Nineteen positive cultures were isolated from thirty-two specimens of feces. All these thirty-two specimens, upon direct microscopical examination, gave positive findings, some showing only a few tubercle bacilli. Six specimens were not free from contaminating organisms, and the remaining seven were negative. The method presented in this paper has proved very simple and accurate for the isolation of tubercle bacilli from sputum. The partial success in isolating tubercle bacilli from feces may be due to the fact that many of the bacilli may be dead.
Development of Gene Silencing Pyrrole-Imidazole Polyamide Targeting the TGF-β1 Promoter for Treatment of Progressive Renal Diseases
Authors: Hiroyuki Matsuda, Noboru Fukuda, Takahiro Ueno, Yoshiko Tahira, Hirohito Ayame, Wen Zhang, Toshikazu Bando, Hiroshi Sugiyama, Satoshi Saito, Koichi Matsumoto, Hideo Mugishima, Kazuo Serie
Journal: Journal of the American Society of Nephrology (2005)

Pyrrole-imidazole (Py-Im) polyamides are nuclease-resistant novel compounds that inhibit gene expression by binding to the minor groove of DNA. A Py-Im polyamide that targets rat TGF-beta1 was designed as a gene-silencing agent for progressive renal diseases, and the distribution and the effects of this polyamide on renal injury were examined in Dahl-salt sensitive (Dahl-S) rats. For identification of transcription factor binding elements for activation of the rat TGF-beta1 gene, recombinant TGF-beta1 reporter plasmids were transfected into HEK-293 cells, and promoter activity was measured. Py-Im polyamide was designed to the activator protein-1 binding site of the rat TGF-beta1 promoter. This Py-Im polyamide showed strong, fast, and specific binding to the target DNA in gel mobility shift and Biacore assays. Py-Im polyamide significantly inhibited TGF-beta1 promoter activity and expression of TGF-beta1 mRNA and protein in rat mesangial cells. Intravenously administered fluorescein-labeled polyamide distributed to the kidney of rats. Py-Im polyamide significantly inhibited expression of TGF-beta1 mRNA and protein in the renal cortex of Dahl-S rats and reduced the increase in urinary protein and albumin in Dahl-S rats independent of changes in blood pressure. These results indicate that Py-Im polyamide that targets TGF-beta1 will be a novel gene-silencing agent for the TGF-beta1-associated diseases, including progressive renal diseases.
Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death
Authors: Minjian Chen, Maziar Divangahi, Huixian Gan, Daniel S.J. Shin, Song Hong, David M. Lee, Charles N. Serhan, Samuel M. Behar, Heinz G. Remold
Journal: The Journal of Experimental Medicine (2008)

Virulent Mycobacterium tuberculosis (Mtb) induces a maladaptive cytolytic death modality, necrosis, which is advantageous for the pathogen. We report that necrosis of macrophages infected with the virulent Mtb strains H37Rv and Erdmann depends on predominant LXA(4) production that is part of the antiinflammatory and inflammation-resolving action induced by Mtb. Infection of macrophages with the avirulent H37Ra triggers production of high levels of the prostanoid PGE(2), which promotes protection against mitochondrial inner membrane perturbation and necrosis. In contrast to H37Ra infection, PGE(2) production is significantly reduced in H37Rv-infected macrophages. PGE(2) acts by engaging the PGE(2) receptor EP2, which induces cyclic AMP production and protein kinase A activation. To verify a role for PGE(2) in control of bacterial growth, we show that infection of prostaglandin E synthase (PGES)(-/-) macrophages in vitro with H37Rv resulted in significantly higher bacterial burden compared with wild-type macrophages. More importantly, PGES(-/-) mice harbor significantly higher Mtb lung burden 5 wk after low-dose aerosol infection with virulent Mtb. These in vitro and in vivo data indicate that PGE(2) plays a critical role in inhibition of Mtb replication.