tbuckley/cabot-search huggingface dataset:
A Case of Congenital Word Blindness
Authors: W. P. Morgan
Journal: BMJ (1896)

irritative eczema, with exfoliated epidermis, and a profuse sero-purulent discharge.When the sore was cleaned it had a smooth, glazed, pink surface, quite level with the surround- ing skin, very sharply defined, scarcely a trace of inflammatory redness extending beyond its edge.It was painless and almost insensitive.There were no granulations, as apparently only the cuticular layer was lost, having a surface exactly like that seen when the cuticle is rubbed off a dissecting room subject, except that it was a bright pink colour.Almost everything that could be thought of, in the shape of lotions, creams, powders, was used to try to check the copious serous discharge and get it to heal, but they were absolutely of no avail, being literally washed or floated off by the discharge.However, in about ten days the exudation began to lessen: the epithelium began to grow in from the edge, exactly as in a burn, and it was soon seen to be creeping up from the bottom of the umbilical recess.I at once commenced skin grafting, but though from from six to ten grafts were put on almost every day, comparatively few " took;" w1fether this was due to the constant motion of the part from respira- tion or not I cannot say.None lived in the central part.Healing steadily progressed till the last week of July, when the sore was reduced to an irregular patch about 3 by 31 inches, lying just above the umbilicus.After the healing process commenced it, for the first time, becamepainful, and was very sensitive to various applications.boric lotion caused considerable burning, and even a very weak ointment of salicylic acid could not be borne at all.When healing ceased it remained very irritable, the surface became grey and gradually covered with a thick semi-translucent material that could not be washed off, and which almost exactly resembled boiled white fish skin.On August gth the whole sore was deeply cauterised with solid nitrate of silver, some days after a thick slough separated, but the surface under- neath was grey and showed no sign of granulations.It radually became covered with a thick false membrane, not rikwthe previous one but tough, yellow, and opaque, and there was no tendency to heal.On September 2nd the patient was
Congenital Stenosis of the Pulmonary Artery Branches
Authors: DAVID BAUM, GEORGE H. KHOURY, PATRICK A. ONGLEY, H. J. C. SWAN, OWINGS W. KINCAID
Journal: Circulation (1964)

Eighteen cases of stenosis of the branches of the pulmonary artery, seen at the Mayo Clinic, have been reviewed and subdivided into two main types: Type I, stenosis of the main branches of the pulmonary artery, 11 cases, and type II, stenosis of multiple peripheral branches of the pulmonary arteries, seven cases. Of special interest were two cases in which thrombosis occurred as a complication and one case in which surgical relief of multiple areas of stenosis in the peripheral branches of the pulmonary arteries was accomplished. Unexplained pulmonary hypertension necessitates further investigation, which includes cardiac catheterization for measurement of intracardiac pressure and frequently selective angiocardiography. Main branch or peripheral pulmonary artery stenosis should be suspected when a continuous murmur is heard or when poststenotic dilatations of the pulmonary artery branches or areas of decreased pulmonary vasculature can be perceived in the roentgenogram. Angiocardiography is the only technic that permits detailed anatomic evaluation of the entire pulmonary vasculature, especially in the cases associated with severe infundibular or valvular pulmonic stenosis. Stenosis of the branches of the pulmonary artery must be taken into account, when surgical repair of associated cardiovascular defects is considered. These lesions also might complicate anastomotic procedures involving the pulmonary artery in cyanotic patients.
Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma
Authors: William Busse, Jonathan Corren, Bobby Quentin Lanier, Margaret McAlary, Angel Fowler-Taylor, Giovanni Della Cioppa, Andre van As, Niroo Gupta
Journal: Journal of Allergy and Clinical Immunology (2001)
Incidence, prevalence, and mortality of diabetes in a large population. A report from the Skaraborg Diabetes Registry.
Authors: B Berger, G Stenström, G Sundkvist
Journal: Diabetes Care (1999)

Our objective was to analyze the prevalence, incidence, and mortality of diabetes in a population of 280,539 inhabitants.The incidence, prevalence, and deaths from diabetes at all ages of a population have been prospectively followed in the county of Skaraborg, Sweden, since 1991.The annual incidence of diabetes per 100,000 inhabitants in 1991-1995 was (mean +/- 95% CI) 14.7 +/- 3.2 for type 1 diabetes (diagnosed at 24.1 +/- 2.2 years of age) and 265.6 +/- 16.1 for type 2 diabetes (diagnosed at 66.6 +/- 0.6 years of age). The incidence of type 2 diabetes was significantly (P < 0.001) higher among men. There was no significant change in the age at diagnosis of diabetes. Although the incidence rate and the age at diagnosis were constant, the prevalence of diabetes increased by 6% each year. The relative mortality risk for diabetic patients was almost four times higher than expected. The median age at death, however, increased significantly, from 77.2 to 80.2 years (P < 0.05), during the study.The prevalence but not the incidence rate of diabetes increased during the years 1991-1995. Although diabetic patients showed a high relative mortality, increased survival apparently explains the increase in prevalence of diabetes in the country of Skaraborg.
Adhesion Molecules in the Nervous System: Structural Insights into Function and Diversity
Authors: Lawrence Shapiro, James Love, David R. Colman
Journal: Annual Review of Neuroscience (2007)

The unparalleled complexity of intercellular connections in the nervous system presents requirements for high levels of both specificity and diversity for the proteins that mediate cell adhesion. Here we describe recent advances toward understanding the molecular mechanisms that underlie adhesive binding, specificity, and diversity for several well-characterized families of adhesion molecules in the nervous system. Although many families of adhesion proteins, including cadherins and immunoglobulin superfamily members, are utilized in neural and nonneural contexts, nervous system-specific diversification mechanisms, such as precisely regulated alternative splicing, provide an important means to enable their function in the complex context of the nervous system.
C-Peptide Replacement Therapy and Sensory Nerve Function in Type 1 Diabetic Neuropathy
Authors: Karin Ekberg, Tom Brismar, Bo-Lennart Johansson, Per Lindström, Lisa Juntti-Berggren, Anders Norrby, Christian Berne, Hans J. Arnqvist, Jan Bolinder, John Wahren
Journal: Diabetes Care (2006)

OBJECTIVE—C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function. RESEARCH DESIGN AND METHODS—This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo. RESULTS—The age of the 139 patients who completed the protocol was 44.2 ± 0.6 (mean ± SE) years and their duration of diabetes was 30.6 ± 0.8 years. Clinical neurological impairment (NIA) (score &amp;gt;7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 ± 0.08 SD below body height–corrected normal values at baseline and improved similarly within the two C-peptide groups (P &amp;lt; 0.007). The number of patients responding with a SCV peak potential improvement &amp;gt;1.0 m/s was greater in C-peptide–treated patients than in those receiving placebo (P &amp;lt; 0.03). In the least severely affected patients (SCV &amp;lt; 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P &amp;lt; 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide–treated groups (P &amp;lt; 0.011 and P &amp;lt; 0.002). A1C levels (7.6 ± 0.1% at baseline) decreased slightly but similarly in C-peptide–and placebo-treated patients during the study. CONCLUSIONS—C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.
High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma
Authors: Wu ZL, Song YQ, Shi YF, J Zhu
Journal: Journal of Hematology & Oncology (2011)

Abstract Background The purpose of the study was to investigate the expression and prognostic value of STAT3 in diffuse large B-cell lymphoma (DLBCL). Methods Seventy-four DLBCL patients from 2001 to 2007 were reviewed in the study. The STAT3 expression in their tumor tissues was examined using the immunohistochemistry (IHC) method, and evaluated for its association with clinicopathological parameters. Results Strong nuclear staining of STAT3 and phosphorylated-STAT3 tyr705 (P-STAT3) were observed in 19 cases (25.7%) and 24 cases (32.4%), respectively, and the expression levels were highly consistent between them ( P = 0.001). The high nuclear expression of STAT3 was more frequent in the non-germinal center B cell-like (non-GCB) DLBCL than that in the GCB subtype, but not reaching significance ( P &lt; 0.061). The high nuclear expression of STAT3 was found to be correlated with poor overall survival (OS) ( P = 0.005). Multivariate Cox regression analysis showed that the STAT3 expression was an independent prognostic factor for DLBCL patients regardless of CHOP or R-CHOP regimen used as the first-line therapy. Conclusion STAT3 is more frequently expressed in non-GCB DLBCL than that in GCB subtype, and its strong nuclear expression is correlated with poor OS in DLBCL.
Ceramide Is Not a Signal for Tumor Necrosis Factor–Induced Gene Expression but Does Cause Programmed Cell Death in Human Vascular Endothelial Cells
Authors: Mark R. Slowik, Linda G. De Luca, Wang Min, Jordan S. Pober
Journal: Circulation Research (1996)

Tumor necrosis factor (TNF) activates transcription of endothelial leukocyte adhesion molecule-1 (CD62E) in endothelial cells (ECs) through the binding to the gene promoter of the p50/p65 heterodimeric form of nuclear factor-kappa B (NF-kappa B) and of the N-terminal phosphorylated form of the ATF2/c-Jun transcription factor, which is phosphorylated by Jun N-terminal kinase (JNK). However, the intracellular signaling pathways that activate endothelial NF-kappa B and JNK in TNF-induced responses are unknown. In this study we have examined the role of a recently described TNF signaling pathway involving sphingomyelin activation to generate ceramide, a potential intracellular mediator. We find that concentrations of TNF that strongly activate NF-kappa B and JNK within 15 minutes do not produce either a measurable decline in sphingomyelin or a measurable generation of ceramide in cultured human umbilical vein ECs at any time examined. Stimulation of ECs with purified sphingomyelinase (SMase) enzyme causes a rapid 60% to 80% decrease in cellular sphingomyelin content and a large increase in ceramide. However, SMase treatment only minimally activates NF-kappa B, achieving levels that are insufficient to initiate gene transcription. Extracellular SMase does not have access to intracellular sphingomyelin, but treatment of ECs with membrane-permeant ceramide analogues still completely fails to activate NF-kappa B and only activates JNK at late times. Neither SMase nor ceramide analogues induce gene transcription or surface expression of endothelial leukocyte adhesion molecules that are readily induced by TNF. Strikingly, low concentrations of membrane-permeant ceramide cause programmed cell death in ECs, a finding not observed at any concentrations of TNF tested. We conclude that ceramide is not an important second messenger for TNF signaling of gene transcription in ECs but may be a second messenger for cell death in response to as-yet-unidentified signals.
The genetic epidemiology of neurodegenerative disease
Authors: L. Bertram
Journal: Journal of Clinical Investigation (2005)

Gene defects play a major role in the pathogenesis of degenerative disorders of the nervous system. In fact, it has been the very knowledge gained from genetic studies that has allowed the elucidation of the molecular mechanisms underlying the etiology and pathogenesis of many neurodegenerative disorders. In this review, we discuss the current status of genetic epidemiology of the most common neurodegenerative diseases: Alzheimer disease, Parkinson disease, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease, and prion diseases, with a particular focus on similarities and differences among these syndromes.
HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies.
Authors: J F Carlquist, R L Menlove, M B Murray, J B O'Connell, J L Anderson
Journal: Circulation (1991)

We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p less than 0.007). A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination. For the combined studies, DR4 was elevated (51% versus 27% in controls, p less than 0.001), and DRw6 was decreased (9% versus 24% in controls, p less than 0.01). The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33.(ABSTRACT TRUNCATED AT 250 WORDS)
RSK Isoforms in Cancer Cell Invasion and Metastasis
Authors: Florian J. Sulzmaier, Joe W. Ramos
Journal: Cancer Research (2013)

Metastasis, the spreading of cancer cells from a primary tumor to secondary sites throughout the body, is the primary cause of death for patients with cancer. New therapies that prevent invasion and metastasis in combination with current treatments could therefore significantly reduce cancer recurrence and morbidity. Metastasis is driven by altered signaling pathways that induce changes in cell-cell adhesion, the cytoskeleton, integrin function, protease expression, epithelial-to-mesenchymal transition and cell survival. The ribosomal S6 kinase (RSK) family of kinases is a group of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) effectors that can regulate these steps of metastasis by phosphorylating both nuclear and cytoplasmic targets. However, our understanding of RSK function in metastasis remains incomplete and is complicated by the fact that the four RSK isoforms perform nonredundant, sometimes opposing functions. Although some isoforms promote cell motility and invasion by altering transcription and integrin activity, others impair cell motility and invasion through effects on the actin cytoskeleton. The mechanism of RSK action depends both on the isoform and the cancer type. However, despite the variance in RSK-mediated outcomes, chemical inhibition of this group of kinases has proven effective in blocking invasion and metastasis of several solid tumors in preclinical models. RSKs are therefore a promising drug target for antimetastatic cancer treatments that could supplement and improve current therapeutic approaches. This review highlights contradiction and agreement in the current data on the function of RSK isoforms in metastasis and suggests ways forward in developing RSK inhibitors as new antimetastasis drugs.
Cervical Length at Mid-Pregnancy and the Risk of Primary Cesarean Delivery
Authors: Gordon C.S. Smith, Ebru Celik, Meekai To, Olga Khouri, Kypros H. Nicolaides
Journal: New England Journal of Medicine (2008)

Physiological and biochemical studies suggest that normal parturition at term is dependent on programmed development of the uterus in early pregnancy. It is recognized that a short cervix in mid-pregnancy is associated with an increased risk of spontaneous preterm birth. We hypothesized that a long cervix in mid-pregnancy would be associated with an increased risk of cesarean delivery during labor at term.
No Benefit of Endoscopic Sphincterotomy Before Biliary Placement of Self-Expandable Metal Stents for Unresectable Pancreatic Cancer
Authors: Tsuyoshi Hayashi, Hiroshi Kawakami, Manabu Osanai, Hirotoshi Ishiwatari, Hirohito Naruse, Hiroyuki Hisai, Nobuyuki Yanagawa, Hiroyuki Kaneto, Kazuya Koizumi, Tamaki Sakurai, Tomoko Sonoda
Journal: Clinical Gastroenterology and Hepatology (2015)
Pilot Study of Nelarabine in Combination With Intensive Chemotherapy in High-Risk T-Cell Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group
Authors: Kimberly P. Dunsmore, Meenakshi Devidas, Stephen B. Linda, Michael J. Borowitz, Naomi Winick, Stephen P. Hunger, William L. Carroll, Bruce M. Camitta
Journal: Journal of Clinical Oncology (2012)

Children's Oncology Group study AALL00P2 was designed to assess the feasibility and safety of adding nelarabine to a BFM 86-based chemotherapy regimen in children with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL).In stage one of the study, eight patients with a slow early response (SER) by prednisone poor response (PPR; ≥ 1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus six courses of nelarabine 400 mg/m(2) once per day; four patients with SER by high minimal residual disease (MRD; ≥ 1% at day 36 of induction) received chemotherapy plus five courses of nelarabine; 16 patients with a rapid early response (RER) received chemotherapy without nelarabine. In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m(2) once per day (10 SER patients [one by MRD, nine by PPR]) or 400 mg/m(2) once per day (38 RER patients; 12 SER patients [three by MRD, nine by PPR]).The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine (42% with v 81% without nelarabine). Five-year event-free survival (EFS) rates were 73% for 11 stage one SER patients and 67% for 22 stage two SER patients treated with nelarabine versus 69% for 16 stage one RER patients treated without nelarabine and 74% for 38 stage two RER patients treated with nelarabine. Five-year EFS for all patients receiving nelarabine (n = 70) was 73% versus 69% for those treated without nelarabine (n = 16).Addition of nelarabine to a BFM 86-based chemotherapy regimen was well tolerated and produced encouraging results in pediatric patients with T-ALL, particularly those with a SER, who have historically fared poorly.
Molecular Pathways of Frontotemporal Lobar Degeneration
Authors: Kristel Sleegers, Marc Cruts, Christine Van Broeckhoven
Journal: Annual Review of Neuroscience (2010)

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative condition that predominantly affects behavior, social awareness, and language. It is characterized by extensive heterogeneity at the clinical, pathological, and genetic levels. Recognition of these levels of heterogeneity is important for proper disease management. The identification of progranulin and TDP-43 as key proteins in a significant proportion of FTLD patients has provided the impetus for a wealth of studies probing their role in neurodegeneration. This review highlights the most recent developments and future directions in this field and puts them in perspective of the novel insights into the neurodegenerative process, which have been gained from related disorders, e.g., the role of FUS in amyotrophic lateral sclerosis.
An ongoing search for potential targets and therapies for lethal sepsis
Authors: Guo-Qiang Bao, Li He, David Lee, John D'Angelo, Hai-Chao Wang
Journal: Military Medical Research (2015)

Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that are sequentially released early (e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ)) and late (e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.