tbuckley/cabot-search huggingface dataset:
Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: A clinicopathological study
Authors: M. Voulgarelis, S. Giannouli, A. Tasidou, D. Anagnostou, P.D. Ziakas, A.G. Tzioufas
Journal: American Journal of Hematology (2006)

Background: The histopathologic features characterizing the involvement of the bone marrow (BM) in systemic lupus erythematosus (SLE) have not been systematically analyzed to date. Objectives: The aim of this study was to assess morphologic and immunohistochemical characteristics of BM involvement in SLE. Patients and methods: Clinical and serological data of 40 SLE patients with unexplained cytopenias were studied. Ten patients with myelodysplasia of refractory anemia (RA) were used as controls. BM aspiration, BM biopsy (BMB), and immunohistochemistry were carried out in patients and controls. BM fibrosis, BM necrosis, stromal edema, and abnormal localization of immature precursors (ALIP) were assessed according to standard criteria. Results: Dyserythropoiesis and megakaryocytic atypias were uniform findings in SLE patients. The disruption of the normal BM architecture was a predominant SLE BM feature affecting cells of all three hemopoietic lineages, with both erythroid and megakaryocytic precursors tending to assume paratrabecular locations and ALIP aggregates being present in 27 cases. In addition, BM was hypocellular in 23 cases. BM necrotic alterations were evident in 90% of the cases. The density of reticulin content was generally increased. Vascular changes including dilatation of sinuses were manifest and were associated with the presence of necrotic alterations (P = 0.008). Hemoglobin levels correlated inversely with the presence of ALIP (P = 0.016). Upon comparing BMB features between SLE and RA controls there were striking similarities. Conclusions: BMB in patients with SLE and unexplained cytopenias presents a variety of histopathologic findings including BM necrosis, stromal alterations, hypocellularity, dyspoiesis, and distortion of normal BM architecture, characterized primarily by the presence of ALIP aggregates. Am. J. Hematol. 81:590–597, 2006. © 2006 Wiley-Liss, Inc.
Turnover rate of anti-D IgG injected during pregnancy.
Authors: J Eklund, M Hermann, H Kjellman, P Pohja
Journal: BMJ (1982)

Anti-D IgG was injected into 15 Rh-negative women in the 28th week of gestation and into three non-pregnant women. The uptake of anti-D after the intramuscular injections was calculated by measuring the concentration of antibody in the plasma with an autoanalyser. The biological half life and the catabolic rate of anti-D IgG were calculated according to a compartmental model. The recovery in vivo of anti-D was an average 24% in the non-pregnant women and 21% in the pregnant women. The half life of anti-D were 24 and 21 days, respectively. With a dose of 125 micrograms the plasma anti-D concentration was less than 1 ng/ml at about 10 weeks after the injection. With double the dose the concentration at delivery was at least 1 ng/ml. Although 250 micrograms of anti-D IgG seems to be effective when given in the 28th weeks of gestation, the great individual variations in uptake and recovery rates will lead to occasional cases of Rh-immunisation during pregnancy despite all routine regimens.
Novel and recurrent keratin 6A (<i>KRT6A</i>) mutations in Chinese patients with pachyonychia congenita type 1
Authors: Y.M. Lv, S. Yang, Z. Zhang, Y. Cui, C. Quan, F.S. Zhou, Q.Y. Fang, W.H. Du, F.R. Zhang, J.M. Chang, X.P. Tao, A.L. Zhang, R.H. Kang, W.D. Du, X.J. Zhang
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Pachyonychia congenita (PC) is a rare autosomal dominant disorder caused by keratin gene mutations. PC clinically presents with hypertrophic nail dystrophy, hyponychial keratosis, painful palmoplantar keratoderma and other ectodermal features.1 The PC classification accepted worldwide includes two clinical subtypes: the Jadassohn–Lewandowsky or PC type 1 (PC‐1; OMIM 167200) and the Jackson–Lawler or PC‐2 variant (OMIM 167210). PC‐1 is characterized by nail dystrophy associated with painful, focal, palmoplantar keratoderma, follicular keratoses and oral leucokeratosis.2 Steatocystomas and natal teeth are findings associated with PC‐2 but not typically with PC‐1.1 It is known that keratin proteins share a similar structural motif consisting of a highly conserved central helical rod domain. Each keratin polypeptide possesses an amino acid sequence of 310 residues and an α‐helical rod domain composed of four helical segments named 1A, 1B, 2A and 2B, respectively.3 It has been reported that all the known keratin mutations in patients with PC‐1 are limited to within the conserved helix boundary motifs of either the beginning of 1A or the end of the 2B domain which are encoded by exons 1 and 6 of the keratin 16 gene (KRT16) and exons 1 and 7 of the keratin 6A gene (KRT6A), respectively.3 4–5 So far, over 33 mutations in KRT6A/KRT16 have been identified in independently ascertained families with PC‐1 (http://www.interfil.org). Here we report three novel mutations and four recurrent missense mutations within the hotspot regions of KRT6A detected in Chinese patients with PC‐1.
Abstract 953: Benzyl isothiocyanate suppresses pancreatic cancer angiogenesis and invasion by inhibiting Akt and MMP-2
Authors: Srinivas Reddy Boreddy, Kartick C. Pramanik, Prabodh K. Kandala, Sanjay K. Srivastava
Journal: Cancer Research (2010)

Abstract We have shown in our previous studies that benzyl isothiocyante (BITC) suppress the growth of pancreatic cancer cells by inhibiting the activation of NF-kB and STAT-3 without affecting the viability of normal HPDE cells. Further, we demonstrated that oral administration of BITC significantly blocked the growth of pancreatic tumor xenografts in vivo. In the present study, we examined the effect of BITC on pancreatic cancer angiogenisis and invasion. Our results demonstrate that 5-10µM BITC almost completely blocked neovasculture formation in an ex vivo chick chorio-allantoic membrane (CAM) model. In agreement with these results, in vivo matrigel plug assay in athymic nude mice also reveal that the hemoglobin content in the implanted matrigel plug was reduced by 70% in the mice which were orally fed 12µmol BITC for 7 days as compared to controls, suggesting reduced blood vessel formation. In a matrigel tube formation assay using mouse brain endothelial cells, BITC treatment significantly inhibited VEGF-induced tube formation. As compared to controls, 5µM BITC treatment for 36h caused a drastic reduction in the number of cells that migrated into the wounding area in a wound healing assay. Our results also showed that the tumor cell invasion was effectively (p&amp;lt;0.001) inhibited by 50% in the BxPC-3 cells treated with 10 µM BITC for 24h in a transwell cell invasion assay. Since PI3K, Akt and MMP-2 are critically involved in tumor cell invasion, angiogenesis and metastasis we next evaluated the effect of BITC on these key signaling molecules. As expected, BITC treatment significantly reduced the expression as well as phosphorylation of PI3K at Tyr-458 and Akt at Ser-473 in BxPC-3 cells in a dose-dependent manner. In addition, the expression and mRNA level of MMP-2 was significantly down-regulated by BITC treatment in BxPC-3 cells. Furthermore, tissue inhibitor of metalloproteinases-2 (TIMP-2) level was also reduced by BITC. Taken together, our data strongly suggests the anti-angiogenic and anti-metastatic role of BITC in pancreatic cancer cells and warrants further clinical investigation. [Supported in part by RO1 grants CA 106953 and CA129038 (to SKS) awarded by National Cancer Institute]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 953.
Abstract 4174: Variation in UDP glucouronyltransferase (UGT) genes associated with prostate cancer mortality
Authors: Manish Kohli, Douglas Mahoney, High Chai, David Hillman, David Rider, Brian Costello, James Cerhan
Journal: Cancer Research (2011)

Abstract Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of &amp;gt;5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS&amp;lt;7. After a median follow up of 1.8 years (IQ range: 0.8-3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table. Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4174. doi:10.1158/1538-7445.AM2011-4174
Risk of Multiple Sclerosis After Optic Neuritis
Authors: Leonard A. Levin
Journal: JAMA (2003)

ObjectiveTo identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis.MethodsThree hundred eighty-eight patients who experienced acute optic neuritis between July 1, 1988, and June 30, 1991, were followed up prospectively for the development of multiple sclerosis. Consenting patients were reassessed after 10 to 13 years.ResultsThe 10-year risk of multiple sclerosis was 38% (95% confidence interval, 33%-43%). Patients (160) who had 1 or more typical lesions on the baseline magnetic resonance imaging (MRI) scan of the brain had a 56% risk; those with no lesions (191) had a 22% risk (P&lt;.001, log rank test). Among the patients who had no lesions on MRI, male gender and opticdisc swelling were associated with a lower risk of multiple sclerosis, as was the presence of the following atypical features for optic neuritis: no light perception vision; absence ofpain; and ophthalmoscopic findings of severe optic disc edema, peripapillary hemorrhages, or retinal exudates.ConclusionsThe 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion; higher numbers of lesions do not appreciably increase that risk. However, even when brain lesions are seen on MRI, more than 40% of the patients will not develop clinical multiple sclerosis after 10 years. In the absence of MRI lesions, certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis. This natural history information is a critical input for estimating a patient's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system.
Abstract 3311: IL6-Stat3 signaling promotes glioma stem cell (GSC) survival under hypoxia environment through inhibition of cell-death inducing gene Bnip3
Authors: Hui Wang, Xiao-Fan Wang, Jeremy Rich, Qinhong Wang, Anita Hjelmeland
Journal: Cancer Research (2011)

Abstract Glioblastomas (GBMs) are the most common and lethal brain tumor in adults. In rapid-growing tumors like malignant glioma, hypoxia is an unavoidable condition even with aggressive angiogenesis. Recent studies implicate an important role for a restricted population of neoplastic cells (glioma stem cells, GSCs) in glioma maintenance and recurrence. However, how these glioma stem cells survive and escape from harsh conditions like hypoxia is barely known. Our previous study and others’ have shown that GSCs preferentially express the interleukin 6 (IL6) receptors and Stat3 signaling is preferentially activated in GSCs. We further found that perturbation of IL6 signaling in GSCs reduced Stat3 activation, and small molecule inhibitors of Stat3 potently induced GSC cell death partially through induction of a BCL2 family member Bnip3. Despite its controversial role in cell survival, massive expression of Bnip3 is a well-studied mediator of cell death in hypoxic tumor cells. Furthermore, we found that enhanced IL6-Stat3 signaling in GSCs could counter the induction of Bnip3 under hypoxia, which provided an extra survival advantage for these glioma stem cells under severe hypoxic condition. These data indicated that Stat3 is a downstream mediator of pro-survival IL6 signals in GSCs partially through suppressing Bnip3 expression, especially under hypoxia condition. Together, our data indicate that IL6-Stat3 signaling contributes to glioma malignancy through the promotion of GSC survival under harsh conditions like hypoxia, and that targeting IL6-Stat3 signaling pathway may offer benefit for glioma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3311. doi:10.1158/1538-7445.AM2011-3311
Mechanism of the decrease in coronary blood flow after beta-blockade in conscious dogs
Authors: G. MARCHETTI, L. MERLO, V. NOSEDA
Journal: Cardiovascular Research (1972)

In order to gain further information on the mechanism responsible for the reduction in coronary blood flow produced by β-blockade, the responses of the coronary vascular bed to Butidrine and its stereoisomers and phenylephrine, were studied in 10 conscious dogs with electromagnetic flowmeters chronically implanted around the ascending aorta and the circumflex branch of the left coronary artery. The results confirmed that β-blockade decreases cardiac work and thus, since the metabolic requirements of the myocardium are reduced, coronary blood flow falls in proportion. After-blockade coronary vessels can, however, respond normally to a transient occlusion with a reactive hyperaemia. This indicates that the coronary vessels do not lose their ability to dilate. The reduction in coronary blood flow and cardiac work was elicited both by d-1 Butidrine and its isomer provided with-blocking activity as well as by that lacking in this activity. Alpha-receptors seem to be involved very little in reducing coronary blood flow. Although the increase in coronary resistance elicited by β-blockade can be eliminated by an α-blockade with phentolamine, the administration of an α-stimulating drug such as noradrenaline or phenylephrine further increases coronary resistance. This suggests that α-receptor activity is unmasked only to a very small extent by β-blockade.
CD69 Limits the Severity of Cardiomyopathy After Autoimmune Myocarditis
Authors: Aranzazu Cruz-Adalia, Luis Jesús Jiménez-Borreguero, Marta Ramírez-Huesca, Isabel Chico-Calero, Olga Barreiro, Erica López-Conesa, Manuel Fresno, Francisco Sánchez-Madrid, Pilar Martín
Journal: Circulation (2010)

Background— Experimental autoimmune myocarditis (EAM), a mouse model of post–infectious cardiomyopathy, reflects mechanisms of inflammatory cardiomyopathy in humans. EAM is characterized by an infiltration of inflammatory cells into the myocardium that can be followed by myocyte fibrosis, edema, and necrosis, leading to ventricular wall dysfunction and heart failure. Different data indicate that CD69 exerts an important immunoregulatory effect in vivo. However, the possible role of CD69 in autoimmune myocarditis has not been studied. Methods and Results— We have explored the role of the leukocyte regulatory molecule CD69 in the inflammation that leads to cardiac dysfunction after myocardial injury in EAM. We have found that after induction of EAM, the draining lymph nodes from CD69-deficient mice developed an exacerbated Th17 inflammatory response, resulting in increases in the numbers of infiltrating leukocytes in the myocardium. In the chronic phase of EAM, transthoracic echocardiography revealed a significantly reduced left ventricular fractional shortening and a decreased ejection fraction in CD69-deficient mice, indicative of an impaired cardiac contractility. This condition was accompanied by a greater extent of myocardial fibrosis, an elevated number of sinus pauses on ECG, and an enhanced ratio of heart weight to body weight in CD69 −/− mice. Moreover, both bone marrow transplantation and adoptive transfer of Th17 cells isolated from immunized CD69 −/− mice with EAM into naive wild-type recipients reproduced the severity of the disease, demonstrating that CD69 exerts its function within the lymphocyte compartment. Conclusion— Our findings indicate that CD69 negatively regulates heart-specific Th17 responses, cardiac inflammation, and heart failure progression in EAM.
A Phase II Study (FINDER 2) Comparing Three Dosing Regimens of Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Advanced Breast Cancer.
Authors: K. Pritchard, J. Rolski, Z. Pápai, L. Mauriac, F. Cardoso, K. Fukase, J. Lindemann, M. Macpherson, P. Neven
Journal: Cancer Research (2009)

Abstract Background: The Faslodex Investigation of Dose evaluation in Estrogen Receptor-positive (ER+) advanced breast cancer (FINDER) 2 study investigated the efficacy, safety, and pharmacokinetic (PK) profile of 3 fulvestrant dosing regimens in postmenopausal women with ER+ advanced breast cancer, recurring/progressing after prior endocrine therapy.Objectives: Primary: to evaluate the objective response rate (ORR). Secondary included assessment of: time to progression (TTP), clinical benefit rate (CBR), duration of response (DOR), tolerability, and PK parameters.Methods: This randomized, double-blind, parallel-group, multicenter, Phase II study, evaluated patients (pts) randomized 1:1:1 to different doses of fulvestrant: 250 mg (approved dose [AD]; given on Days 0, 28 and every 28 days thereafter), 250 mg plus loading dose (LD; 500 mg on Day 0, then 250 mg on Days 14, 28 and every 28 days thereafter), and 500 mg (high dose [HD]; Days 0, 14 and 28 and every 28 days thereafter). Treatment continued until disease progression, or until any other criterion for discontinuation was met.Results: In total, 144 pts were randomized from 34 centers in 8 countries and 143 received treatment: fulvestrant AD (n=47); LD (n=50); HD (n=46). ORRs were: 8.5% (95% confidence interval [CI] 2.4-20.4%), 5.9% (1.2-16.2%), and 15.2% (6.3-28.9%) in the AD, LD, and HD arms, respectively. CBRs were: 31.9% (95% CI 19.1-47.1%), 47.1% (32.9-61.5%), and 47.8% (32.9-63.1%) for the AD, LD, and HD arms, respectively. Median TTP was numerically longer for the HD (6.0 months) and LD (6.1 months) arms vs the AD arm (3.1 months). The low number of responders in all treatment arms prevented DOR assessment. The incidence of adverse events (AEs) was similar in all groups (76.6% AD, 72.0% LD, 69.6% HD); few pts experienced serious AEs (4 pts AD, 9 LD, 4 HD) with no clustering of event type. AEs with an incidence of ≥10% (in any arm) were back pain, arthralgia, fatigue, injection-site pain, nausea, dyspnea, cough, and hot flash. Concentrations in the AD arm approached steady state in the 3rd month of dosing and within the 1st month for LD and HD. Exposure (AUC, Cmin and Cmax) appeared to be linear across the dose range studied and, for the 250mg arms, similar to that previously reported in Western populations (Studies 9238IL/0020 &amp; 0021).Conclusion: No statistically significant differences in efficacy could be proven between AD, LD and HD given the widely overlapping CIs for median TTP. The tolerability profile was similar across the three dosing regimens. Steady-state concentrations were achieved earlier with LD and HD. A parallel study in Japanese pts will be used for comparisons of fulvestrant efficacy and tolerability in Japanese and non-Japanese pts. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4095.
Urothorax
Authors: H. Alan Hume, Lloyd W. Stevens, William H. Erb
Journal: New England Journal of Medicine (1962)

There are few reports of intrathoracic complications after renal trauma. We are reporting the following case to increase the awareness of this possibility among physicians who are called upon to manage patients with multiple injuries. In addition very little is known about the reaction of intrathoracic structures to urinary contamination, and we were afforded an opportunity to see the immediate result of the occurrence of this situation.Clinical AbstractS.W., a 10-year-old boy, was struck by an automobile on September 25, 1960, and admitted 15 minutes later to Taylor Hospital. He was unconscious for 2 minutes at the time of . . .
Cervical Spondylosis and Its Neurological Complications
Authors: Oscar Sugar
Journal: JAMA (1969)

For want of a better term, spondylosis is used to imply a chronic, commonly progressive degeneration of the joints of the neck, frequently with associated osteophytosis of adjacent vertebrae. This monograph is intended to gather facts concerning the relationship between spondylosis and neurological disorders, and to stress areas of ignorance; it cautions against facile acceptance of spondylosis as the cause of all neurological syndromes possibly related to the neck, and assesses various therapeutic measures claimed to be beneficial. The first third of the book deals with anatomy, physiology, and pathology of the spondylotic and related neurologic processes. The role of congenital variations in size and shape of the spinal canal is stressed; and the author discusses the importance of ligamentum flavum, dentate ligaments, and vascular supply of the spinal cord. The remaining pages deal with clinical aspects of spondylosis; radiculopathy, myelopathy, and associated vertebral artery disorders are illustrated with reproductions
DEA Physician Registration Numbers: A Need to Know-Reply
Authors: G. Thomas Gitchel
Journal: JAMA (1994)

In Reply.  —The concerns expressed by Dr Cooper regarding the inappropriate use of DEA registration numbers are legitimate. In many respects, his letter echoes the DEA's long-stated policy regarding this problem.  The insurance industry's policy of requiring the prescriber's DEA registration number as a condition for reimbursement is irresponsible. A significant portion of controlled substance diversion occurs through fraudulent prescriptions. Demanding that DEA numbers be furnished with all prescriptions, most of which do not otherwise require them, greatly increases the opportunities for misuse of DEA numbers. Despite the reservations expressed by the DEA, practitioners, pharmacists, and insurance firms continue the policy. They state, variously, that the DEA number is the only universal identifier available; there is no evidence that the requirement has increased diversion; or there is no law that prohibits the practice.  This inappropriate use of DEA registration numbers has compromised the closed system of distribution. The insurance industry