tbuckley/cabot-search huggingface dataset:
Total Serum IgE Concentrations in Adolescents and Adults Using the Phadebas IgE PRIST® Technique
Authors: Jean Bousquet, Yves Coulomb, Hans Arrendal, Michèle Robinet‐Levy, Franclois B. Michel
Journal: Allergy (1982)

Total serum IgE measured with the Phadebas PRIST® technique was titrated in 117 normal non‐allergic subjects, 237 allergic adolescents or adults and 89 non‐allergic patients who suffered from asthma, rhinitis, or conjunctivitis. All subjects were of Caucasian origin. In normal subjects, mean total serum IgE was 38±43 kU/l. This value is exactly the same as that found in a study of Caucasian New Zealanders and very similar to the values found in most U.S. studies. This suggests that the mean total serum IgE concentration is remarkably constant in normal non‐allergic Caucasians. The upper limit of the normal range is considered to be 150 kU/l. 38% of allergic patients have total IgE concentrations within the normal range Some pollen or hymenoptera venom‐sensitive patients have a total serum IgE concentration of 94±93 kU/I The non‐allergic patients had a mean IgE concentration below 20% kU/l. The non‐allergic patients had a mean IgE concentration of 94±93 kU/l, and 25% of them had a total serum IgE above the normal range. Asthmatic patients had higher mean IgE levels than those who were suffering from either rhinitis or conjunctivitis.
Comparative Efficacy and Safety of Atypical and Conventional Antipsychotic Drugs in First-Episode Psychosis: A Randomized, Double-Blind Trial of Olanzapine Versus Haloperidol
Authors: Jeffrey A. Lieberman, Gary Tollefson, Mauricio Tohen, Alan I. Green, Raquel E. Gur, Rene Kahn, Joseph McEvoy, Diana Perkins, Tonmoy Sharma, Robert Zipursky, Hank Wei, Robert M. Hamer
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. METHOD: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. RESULTS: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Åsberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). CONCLUSIONS: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.
Points: Underprivileged areas: validation and distribution scores
Authors: J. Williams
Journal: BMJ (1985)

ments committees, grant awarding bodies, etc, are more impressed by the quantity than by the quality of published work.Unfortunately, the medical profession can- not seek guidance in proper behaviour from the scientific community, whose morals are questioned because of duplication and fraud.2Among so called pure scientists the ethic of "publish or perish" seems even more revered.Only when it is agreed that scientific communications are intended to further knowledge, rather than careers or egos, will we reach the peak of the present, senseless, exponential
Erratum. Initial Combination of Empagliflozin and Linagliptin in Subjects With Type 2 Diabetes. Diabetes Care 2015;38:394–402
Authors: Andrew Lewin, Ralph A. DeFronzo, Sanjay Patel, Dacheng Liu, Renee Kaste, Hans J. Woerle, Uli C. Broedl
Journal: Diabetes Care (2015)
Genes for the mouse T cell alloantigens Tpre, Tthy, Tind, and Tsu are closely linked near Igh on chromosome 12.
Authors: F L Owen, R Riblet
Journal: The Journal of Experimental Medicine (1984)

Genes encoding the T cell alloantigens Tpre, Tthy, Tind, and Tsu have been mapped to a short segment of chromosome 12 using Igh recombinant strains of mice. These loci are located in a tightly linked cluster between the immunoglobulin heavy chain constant region gene cluster, Igh-C, and the serum prealbumin locus Pre-1, in this manner: centromere--Igh-C--(Tthy, Tind)-Tsu-Tpre--Pre-1.
Histological and morphometrical indicators for a biopsy diagnosis of well-differentiated hepatocellular carcinoma
Authors: Yoshinobu Nagato, Fukuo Kondo, Yoichiro Kondo, Masaaki Ebara, Masao Ohto
Journal: Hepatology (1991)

Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well-differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid-sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well-differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular tissue.
Preventive NPWT over closed incisions in general surgery: Does age matter?
Authors: Gianluca Pellino, Guido Sciaudone, Giuseppe Candilio, G. Serena De Fatico, Isabella Landino, Angela Della Corte, Raffaella Guerniero, Raffaella Benevento, Antonio Santoriello, Ferdinando Campitiello, Francesco Selvaggi, Silvestro Canonico
Journal: International Journal of Surgery (2014)
EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas
Authors: Hidenori Fukuoka, Odelia Cooper, Anat Ben-Shlomo, Adam Mamelak, Song-Guang Ren, Dave Bruyette, Shlomo Melmed
Journal: Journal of Clinical Investigation (2011)

Cushing disease is a condition in which the pituitary gland releases excessive adrenocorticotropic hormone (ACTH) as a result of an adenoma arising from the ACTH-secreting cells in the anterior pituitary. ACTH-secreting pituitary adenomas lead to hypercortisolemia and cause significant morbidity and mortality. Pituitary-directed medications are mostly ineffective, and new treatment options are needed. As these tumors express EGFR, we tested whether EGFR might provide a therapeutic target for Cushing disease. Here, we show that in surgically resected human and canine corticotroph cultured tumors, blocking EGFR suppressed expression of proopiomelanocortin (POMC), the ACTH precursor. In mouse corticotroph EGFR transfectants, ACTH secretion was enhanced, and EGF increased Pomc promoter activity, an effect that was dependent on MAPK. Blocking EGFR activity with gefitinib, an EGFR tyrosine kinase inhibitor, attenuated Pomc expression, inhibited corticotroph tumor cell proliferation, and induced apoptosis. As predominantly nuclear EGFR expression was observed in canine and human corticotroph tumors, we preferentially targeted EGFR to mouse corticotroph cell nuclei, which resulted in higher Pomc expression and ACTH secretion, both of which were inhibited by gefitinib. In athymic nude mice, EGFR overexpression enhanced the growth of explanted ACTH-secreting tumors and further elevated serum corticosterone levels. Gefitinib treatment decreased both tumor size and corticosterone levels; it also reversed signs of hypercortisolemia, including elevated glucose levels and excess omental fat. These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease.
Pimecrolimus 1% cream for the treatment of steroid-induced rosacea: an 8-week split-face clinical trial
Authors: D.H. Lee, K. Li, D.H. Suh
Journal: British Journal of Dermatology (2008)

Steroid-induced rosacea is a relatively common dermatosis that is caused by the prolonged application of topical steroid to the face.The purpose of this investigator-blind, split-face study was to evaluate the efficacy and safety of pimecrolimus 1% cream for the treatment of steroid-induced rosacea.Patients were instructed to apply pimecrolimus 1% cream twice daily to the involved areas of a randomly allocated half side for the first 2 weeks, and to follow this by applying pimecrolimus 1% cream to both sides for a further 6 weeks.Fifteen of the 18 patients completed the 8-week study. After 1 week of application, a statistically significant improvement was observed for investigator's global assessments of erythema and papules on prior-treated sides (P-side). Later-treated sides (L-side) showed subsequent improvement after use of pimecrolimus on the L-side. Likewise, a statistically significant improvement was also observed for numbers of papules/pustules on P-sides after 1 week, and L-sides showed a significant improvement after application of pimecrolimus on the L-side. Comparative reflectance colorimetric assessments revealed that DeltaL*, Deltaa* and Deltab* tended to converge to zero during the first 4 weeks. A statistically significant improvement was observed for percentage area affected on P-sides after 1 week of application. The L-side showed a significant improvement after use of pimecrolimus cream on that side. The visual analogue scale of P-sides decreased more rapidly than those of L-sides. Cutaneous side-effects were mild and transient.This study suggests that pimecrolimus 1% cream is an effective and well-tolerated treatment for steroid-induced rosacea.
Inflammation, Oxidative Stress, and Repair Capacity of the Vascular Endothelium in Obstructive Sleep Apnea
Authors: Sanja Jelic, Margherita Padeletti, Steven M. Kawut, Christopher Higgins, Stephen M. Canfield, Duygu Onat, Paolo C. Colombo, Robert C. Basner, Phillip Factor, Thierry H. LeJemtel
Journal: Circulation (2008)

Background— Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea (OSA). We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA. The effects of continuous positive airway pressure (CPAP) therapy on endothelial function and repair capacity were assessed. Methods and Results— Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied. Proteins that regulate basal endothelial nitric oxide (NO) production (endothelial NO synthase [eNOS] and phosphorylated eNOS) and inflammation (cyclooxygenase-2 and inducible NOS) and markers of oxidative stress (nitrotyrosine) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy. Vascular reactivity was measured by flow-mediated dilation. Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity. Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59% and 94%, respectively, in patients with OSA compared with control subjects. Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects, whereas inducible NOS expression was 56% greater. Expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine, cyclooxygenase-2, and inducible NOS significantly decreased in patients who adhered to CPAP ≥4 hours daily. Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects, and both significantly increased in patients who adhered to CPAP ≥4 hours daily. Conclusions— OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity. Effective CPAP therapy is associated with the reversal of these alterations.
Gene Expression Patterns in Mismatch Repair-Deficient Colorectal Cancers Highlight the Potential Therapeutic Role of Inhibitors of the Phosphatidylinositol 3-Kinase-AKT-Mammalian Target of Rapamycin Pathway
Authors: Eduardo Vilar, Bhramar Mukherjee, Rork Kuick, Leon Raskin, David E. Misek, Jeremy M.G. Taylor, Thomas J. Giordano, Samir M. Hanash, Eric R. Fearon, Gad Rennert, Stephen B. Gruber
Journal: Clinical Cancer Research (2009)

High-frequency microsatellite-instable (MSI-H) tumors account for approximately 15% of colorectal cancers. Therapeutic decisions for colorectal cancer are empirically based and currently do not emphasize molecular subclassification despite an increasing collection of gene expression information. Our objective was to identify low molecular weight compounds with preferential activity against MSI colorectal cancers using combined gene expression data sets.Three expression/query signatures (discovery data set) characterizing MSI-H colorectal cancer were matched with information derived from changes induced in cell lines by 164 compounds using the systems biology tool "Connectivity Map." A series of sequential filtering and ranking algorithms were used to select the candidate compounds. Compounds were validated using two additional expression/query signatures (validation data set). Cytotoxic, cell cycle, and apoptosis effects of validated compounds were evaluated in a panel of cell lines.Fourteen of the 164 compounds were validated as targeting MSI-H cell lines using the bioinformatics approach; rapamycin, LY-294002, 17-(allylamino)-17-demethoxygeldanamycin, and trichostatin A were the most robust candidate compounds. In vitro results showed that MSI-H cell lines due to hypermethylation of MLH1 are preferentially targeted by rapamycin (18.3 versus 4.4 mumol/L; P = 0.0824) and LY-294002 (15.02 versus 10.37 mumol/L; P = 0.0385) when compared with microsatellite-stable cells. Preferential activity was also observed in MSH2 and MSH6 mutant cells.Our study shows that the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway is of special relevance in mismatch repair-deficient colorectal cancer. In addition, we show that amalgamation of gene expression information across studies provides a robust approach for selection of potential therapies corresponding to specific groups of patients.
<i>In vitro</i>model for penetration of sensory nerve fibres on a Matrigel basement membrane: implications for possible application to intractable pruritus
Authors: M. Tominaga, A. Kamo, S. Tengara, H. Ogawa, K. Takamori
Journal: British Journal of Dermatology (2009)

Epidermal hyperinnervation occurs in dermatoses with intractable pruritus, such as atopic dermatitis, suggesting that the hyperinnervation is partly responsible for abnormal itch perception.To investigate the mechanisms of penetration of sensory nerve fibres into the basement membrane of the skin.A rat dorsal root ganglion neurone culture system consisting of Matrigel and a Boyden chamber containing a nerve growth factor (NGF) concentration gradient was used. In some experiments, matrix metalloproteinase (MMP) blockers and semaphorin 3A (Sema3A) were added to the culture system. Matrigel-coated membranes were stained with anti-Tau antibody, and the number of nerve fibres that crossed the membrane was counted. Expression of MMPs in the cultured neurones was examined at mRNA and protein levels by quantitative reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. The activity was also examined by zymography.Nerve fibres penetrated into Matrigel in the presence of an NGF concentration gradient, which was dose-dependently inhibited by GM6001, a broad-spectrum MMP inhibitor. Transcripts for MMP2, but not MMP9, were increased in the cultured neurones, and the penetration was dose-dependently inhibited by MMP-2 blockers. MMP-2 and its activity were partially localized on the NGF-responsive growth cones. NGF also upregulated pro-MMP-2 activation molecules in the cultured neurones. Sema3A stimulation showed the opposite effects on these NGF-dependent events. Interestingly, MMP2 expression was modulated by extracellular matrix (ECM) substrates for this enzyme.Membrane-associated MMP-2 contributes to penetration of nerve fibres into Matrigel through modulation by axonal guidance molecules and/or ECM. These findings provide insight for understanding the development of intractable pruritus involving epidermal nerve density.
Calcitonin Gene-Related Peptide and Its Receptors: Molecular Genetics, Physiology, Pathophysiology, and Therapeutic Potentials
Authors: SUNIL J. WIMALAWANSA
Journal: Endocrine Reviews (1996)

I. IntroductionTHE calcitonin (CT) and calcitonin gene-related peptide (CGRP) are derived from the CT/CGRP gene, which is localized in chromosome 11. Alternative splicing of the primary RNA transcript leads to the translation of CGRP and CT peptides in a tissue-specific manner. This alternative tissue-specific processing of primary mRNA from the α-CT/CGRP gene in rats generates two distinct peptides, CT and CGRP (1, 2). CGRP is a 37-amino acid neuropeptide expressed predominantly in the nervous system and CT is expressed mainly in the thyroid gland. CGRP receptors, widely distributed in the body, are the most potent endogenous vasodilatory peptides that have been discovered. Derived from the C cells of the thyroid gland, CT is the most potent peptide inhibitor of osteoclast-mediated bone resorption and is involved primarily in protecting the skeleton during periods of "calcium stress" such as growth, pregnancy, and lactation (3).In 1961, Copp and colleagues (4) postulated the existence of the calcium-lowering peptide CT. Its sequence and structure were determined by Neher et al. in 1968 (5). Similar to CGRP and amylin, CT is a single-chain peptide hormone consisting of 32 amino acids. In humans, CT is secreted by the parafollicular cells (C cells) of the thyroid (6, 7), which are of neural crest origin (8). In addition, a minority of CT-producing cells are also in the bronchial Kulchitsky (K) cells in the lungs (9). These K cells have been shown to be the origin of bronchial carcinoid and small cell carcinoma of the lung, both of which secrete CT (10, 11). Therefore, even after total thyroidectomy, the complete absence of CT from the circulation is unlikely, and minute amounts of CT in the circulation may be sufficient to counteract the bone-resorbing effects of other hormones such as PTH (12).
Systemic Combination Virotherapy for Melanoma with Tumor Antigen-Expressing Vesicular Stomatitis Virus and Adoptive T-cell Transfer
Authors: Diana M. Rommelfanger, Phonphimon Wongthida, Rosa M. Diaz, Karen M. Kaluza, Jill M. Thompson, Timothy J. Kottke, Richard G. Vile
Journal: Cancer Research (2012)

Abstract Oncolytic virotherapy offers the potential to treat tumors both as a single agent and in combination with traditional modalities such as chemotherapy and radiotherapy. Here we describe an effective, fully systemic treatment regimen, which combines virotherapy, acting essentially as an adjuvant immunotherapy, with adoptive cell transfer (ACT). The combination of ACT with systemic administration of a vesicular stomatitis virus (VSV) engineered to express the endogenous melanocyte antigen glycoprotein 100 (gp100) resulted in regression of established melanomas and generation of antitumor immunity. Tumor response was associated with in vivo T-cell persistence and activation as well as treatment-related vitiligo. However, in a proportion of treated mice, initial tumor regressions were followed by recurrences. Therapy was further enhanced by targeting an additional tumor antigen with the VSV-antigen + ACT combination strategy, leading to sustained response in 100% of mice. Together, our findings suggest that systemic virotherapy combined with antigen-expressing VSV could be used to support and enhance clinical immunotherapy protocols with adoptive T-cell transfer, which are already used in the clinic. Cancer Res; 72(18); 4753–64. ©2012 AACR.
From basic research to clinical development of MEK1/2 inhibitors for cancer therapy
Authors: Christophe Frémin, Sylvain Meloche
Journal: Journal of Hematology & Oncology (2010)

The Ras-dependent Raf/MEK/ERK1/2 mitogen-activated protein (MAP) kinase signaling pathway is a major regulator of cell proliferation and survival. Not surprisingly, hyperactivation of this pathway is frequently observed in human malignancies as a result of aberrant activation of receptor tyrosine kinases or gain-of-function mutations in RAS or RAF genes. Components of the ERK1/2 pathway are therefore viewed as attractive candidates for the development of targeted therapies of cancer. In this article, we briefly review the basic research that has laid the groundwork for the clinical development of small molecules inhibitors of the ERK1/2 pathway. We then present the current state of clinical evaluation of MEK1/2 inhibitors in cancer and discuss challenges ahead.
Department of Health to cut two fifths of its staff
Authors: A. Elliot
Journal: BMJ (2003)

The health secretary, John Reid, has announced cuts that will see the number of staff at the Department of Health shrink by more than a third over the next 12 months.

Dr Reid said the plans to shed 1400 central staff–38% of the total–by October 2004 were the “most significant and ambitious ever undertaken by a Whitehall department.”

He told the House of Commons health select committee's inquiry into public expenditure last week that he wanted to redirect savings to the front line of the …