tbuckley/cabot-search huggingface dataset:
Rheumatoid involvement of the lumbar spine.
Authors: H Sims-Williams, M I Jayson, H Baddeley
Journal: Annals of the Rheumatic Diseases (1977)

On stereoscopic examination of the lumbar spines of 6 patients with rheumatoid arthritis and spinal disease we found typical rheumatoid erosions in the apophyseal joints. 2 also had severe asymmetrical disc destruction with associated involvement of the vertebral bodies and scoliosis. In one of these patients who developed Staphyloccocus aureus septicaemia, infection was localized in this part of the lumbar spine.
Abstract 4497: Therapeutic benefit of targeting ERK in mutant KRAS pancreatic ductal adenocarcinoma
Authors: Tikvah K. Hayes
Journal: Cancer Research (2014)

Abstract The limited success of anti-MEK and anti-RAF therapies with KRAS mutant cancers has been attributed, in part, to de novo or acquired resistance mechanisms that arise after prolonged treatment. A majority of resistance mechanisms involve kinome reprograming to reactivate ERK downstream of inhibitor activity. Therefore, we hypothesized that directly targeting ERK would be an effective method for overcoming these resistance mechanisms. To address this possibility, we evaluated the sensitivity of a panel of mutant KRAS pancreatic ductal adenocarcinoma (PDAC) cell lines to the highly selective SCH772984 ERK1/2 protein kinase inhibitor. First, we found that the anchorage-dependent growth of 6 of 12 cell lines were sensitive to SCH772984 treatment (IC50&amp;lt;2 uM). Some sensitive PDAC lines were resistant to the AZD6244 MEK1/2-selective inhibitor, indicating different mechanisms of action of these two inhibitors. Second, we identified phospho-AKT as a potential biomarker for PDAC SCH772984 sensitivity. Third, we assessed the molecular basis for anchorage-dependent growth inhibition. After 72 h treatment, flow cytometry analyses indicated impaired cell cycle progression through G1. Additionally, we found increased apoptosis as measured by formation of cleaved caspase-3. Together these observations suggest that sensitivity is a result of both impaired cell cycle progression and induction of apoptosis. Surprisingly prolonged SCH772984 treatment (2 weeks) resulted in senescence, as sensitive lines stained positive for senescence-associated beta-galactocidase. Furthermore, we found that senescent cells induced p16 and lost phospho-RB two common markers associated with induction of senescence. Onset of senescence was dependent on the loss of total MYC protein expression. Finally, we found that treatment with SCH772984 reduced tumorigenic growth in an in vivo xenograft mouse model. Our ongoing studies include determining the mechanisms of inhibitor resistance. In summary, our findings suggest that targeting ERK will be therapeutically beneficial for the treatment of KRAS mutant PDAC. Citation Format: Tikvah K. Hayes. Therapeutic benefit of targeting ERK in mutant KRAS pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4497. doi:10.1158/1538-7445.AM2014-4497
Disease progression in mothers of children enrolled in the Research Registry for Neonatal Lupus
Authors: T L Rivera, P M Izmirly, B K Birnbaum, P Byrne, J B Brauth, M Katholi, M Y Kim, J Fischer, R M Clancy, J P Buyon
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To evaluate autoimmune disease progression in asymptomatic and pauci-symptomatic mothers of children with neonatal lupus (NL). <h3>Methods:</h3> Clinical information on mothers enrolled in the Research Registry for NL (RRNL) was obtained from medical records. Genotyping was performed for −308A/G tumour necrosis factor (TNF)α, 869T/C transforming growth factor (TGF)β and −889C/T interleukin (IL)1α. <h3>Results:</h3> Of the 321 mothers enrolled, 229 had at least 6 months of follow-up. Of the 51 mothers who were asymptomatic at the NL child's birth, 26 progressed: 12 developed pauci-undifferentiated autoimmune syndrome (pauci-UAS), 2 poly-UAS, 7 SS, 4 SLE and 1 SLE/SS. The median time to develop any symptom was 3.15 years. Of the 37 mothers classified as pauci-UAS at the NL child's birth, 16 progressed: 5 developed poly-UAS, 6 Sjögren syndrome (SS), 4 systemic lupus erythematosus (SLE) and 1 SLE/SS. Of the pauci-UAS mothers enrolled within 1 year, the median time to progression was 6.7 years. Four mothers developed lupus nephritis (two asymptomatic, two pauci-UAS). The probability of an asymptomatic mother developing SLE by 10 years was 18.6%, and developing probable/definite SS was 27.9%. NL manifestations did not predict disease progression in an asymptomatic mother. Mothers with anti-Sjögren syndrome A antigen (SSA/)Ro and anti-Sjögren syndrome B antigen (SSB)/La were nearly twice as likely to develop an autoimmune disease as mothers with anti-SSA/Ro only. Only TGFβT/T was significantly higher in SLE mothers compared to asymptomatic mothers (p = 0.03). <h3>Conclusions:</h3> Continued follow-up of asymptomatic NL mothers is warranted since nearly half progress, albeit few develop SLE. While the anti-SSB/La antibodies may be a risk factor for progression, further work is needed to determine reliable biomarkers in otherwise healthy women with anti-SSA/Ro antibodies identified solely because of an NL child.
Effect of left ventricular volume on right ventricular end-systolic pressure-volume relation. Resetting of regional preload in right ventricular free wall.
Authors: S Yamaguchi, K Tsuiki, H Miyawaki, Y Tamada, I Ohta, H Sukekawa, M Watanabe, T Kobayashi, S Yasui
Journal: Circulation Research (1989)

Effect of left ventricular (LV) volume on right ventricular (RV) end-systolic pressure-volume relation (ESPVR) was investigated, and the mechanism was examined from a standpoint of the alteration of RV free wall mean fiber length. Twelve cross-circulated isovolumically contracting canine hearts in which both ventricular volumes were controlled independently were used, and RV-ESPVR was determined at three different LV volume levels. At small (10.2 +/- 0.6 ml), middle (15.3 +/- 1.0 ml), and large (20.5 +/- 1.4 ml) LV volume, the slope of the RV-ESPVR was 2.63 +/- 0.13, 2.74 +/- 0.13, and 2.89 +/- 0.12 mm Hg/ml, respectively, and each value was significantly different from the others (p less than 0.01). The volume intercept (V0) of the relation (RV-V0) was significantly decreased with the increment of LV volume (RV-V0 in small, middle, and large LV volume; 3.92 +/- 0.68, 3.39 +/- 0.67, and 2.87 +/- 0.71 ml, respectively; p less than 0.01). In nine hearts, RV free wall lengths in latitudinal and meridional direction were measured at three LV volume levels when RV volume was held constant (16.1 +/- 1.1 ml). RV latitudinal end-diastolic length was significantly augmented with increasing LV volume (latitudinal length in small, middle, and large LV volume; 9.68 +/- 0.55, 9.81 +/- 0.56, and 9.92 +/- 0.55 mm, respectively). RV meridional end-diastolic length also increased significantly with increasing LV volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Eosinophil, Mast Cell, and Basophil Siglec-8 Expression on Human Cell Lines and Hematologic Malignancies
Authors: A.N. Salicru, H. Hermann, S. Hudson, J. Steinke, L. Borish, P. Valent, B.S. Bochner
Journal: Journal of Allergy and Clinical Immunology (2012)
NI-17 * MULTIMODAL NAVIGATED SKULL BASE TUMOR RESECTION USING IMAGE-BASED VASCULAR AND CRANIAL NERVE SEGMENTATION: A PROSPECTIVE VALIDATION STUDY
Authors: P. Dolati, A. Gokoglu, A. Golby, O. Al-Mefty
Journal: Neuro-Oncology (2014)

INTRODUCTION: Skull base tumors frequently encase or invade adjacent normal neural and vascular structures. Preoperative segmentation and planning to identify these anatomical landmarks are essentially important in complex skull base tumor resection for minimizing surgical morbidities. METHODS: Ten patients with skull base tumors underwent preoperative 3TMRI, which included thin sectioned 3D space T2, 3D Time of Flight and MPRAGE sequences. Images were reviewed by an expert independent neuroradiologist. Imaging sequences were loaded in BrainLab iPlanNet (8/10) and Stryker (2/10) for segmentation and pre-operative planning. After patient registration to the intra-op neuronavigation system and surgical exposure, each segmented neural or vascular element was validated by manual placement of the navigation probe. RESULTS: Perfect correspondence between image-based segmentation and microscopic view was found at the surface of the tumor and tumor-normal brain interfaces in all cases. Pre-operative segmentation of the major arteries, veins, and venous sinuses matched with the intra-operative microscopic findings in all cases (Dice-coefficient =1). This information reassured the surgeon and prevented vascular tearing during different stages of tumor resection. This also helped in preventing major intra-operative arterial or venous bleeding. Preoperative segmentation of the related cranial nerves was technically possible in only 80% of cases. However, Image-guidance helped the surgeon to localize the involved cranial nerves in all cases. CONCLUSION: Image-based pre-operative vascular and neural element segmentation, especially with 3D reconstruction, is highly informative preoperatively and could increase the vigilance of neurosurgeons for preventing vascular and neural injury during skull base surgeries. This novel preliminary study is encouraging for future prospective intraoperative validation with larger numbers of patients.
Type 2 alveolar cells are stem cells in adult lung
Authors: Christina E. Barkauskas, Michael J. Cronce, Craig R. Rackley, Emily J. Bowie, Douglas R. Keene, Barry R. Stripp, Scott H. Randell, Paul W. Noble, Brigid L.M. Hogan
Journal: Journal of Clinical Investigation (2013)

Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations to obtain new information about the contribution of AEC2s to alveolar maintenance and repair. Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-term alveolar stem cells. Moreover, if many AEC2s were specifically ablated, high-resolution imaging of intact lungs showed that individual survivors undergo rapid clonal expansion and daughter cell dispersal. Individual lineage-labeled AEC2s placed into 3D culture gave rise to self-renewing "alveolospheres," which contained both AEC2s and cells expressing multiple AEC1 markers, including HOPX, a new marker for AEC1s. Growth and differentiation of the alveolospheres occurred most readily when cocultured with primary PDGFRα⁺ lung stromal cells. This population included lipofibroblasts that normally reside close to AEC2s and may therefore contribute to a stem cell niche in the murine lung. Results suggest that a similar dynamic exists between AEC2s and mesenchymal cells in the human lung.
Assessment of the performance of the Stanford online calculator for the prediction of non-sentinel lymph node metastasis in sentinel node positive breast cancer patients.
Authors: JS Scow, AC Degnim, TL Hoskin, C Reynolds, JC Boughey
Journal: Cancer Research (2009)

Abstract Abstract #1005 Background: Several models for the prediction of non-sentinel lymph node metastasis (+NSLN) in sentinel lymph node positive (+SLN) breast cancer patients have been published. Multiple variables have been shown to be important in prediction of +NSLN. To this date, models that utilize 7-8 variables have been significantly more discriminatory than models using only 2-3 variables. In this study, we evaluate the performance of the newly created Stanford online calculator (SOC) to predict the likelihood of +NSLN. The SOC uses 3 variables: primary tumor size, sentinel lymph node metastasis size, and presence/absence of lymphovascular invasion.&amp;#x2028; Methods: From 1997-2004, 465 breast cancer patients with clinically negative axillae were found to have a +SLN and underwent completion axillary lymph node dissection (ALND) at the Mayo Clinic. Using the SOC the probability of having +NSLN was determined for each patient. Complete variable data was available for 464 patients which make up the cohort reported here. A receiver-operating characteristic (ROC) curve was created and the area-under-the-curve (AUC) was calculated. Mean probabilities of patients with and without +NSLN were compared. Additionally, patients with a low Stanford probability were examined to determine the model's accuracy in discriminating patients who could potentially be spared ALND. These results were compared to the results of the Mayo Clinic and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms which have been previously applied to this same cohort of patients.&amp;#x2028; Results: The AUC of the Stanford model was 0.72 (95% CI 0.67-0.77). The mean Stanford probabilities for patients with and without NSLN disease were 0.75 (range 0.06 to 1.0) and 0.50 (range 0.05 to 1.0), respectively (p &amp;lt; 0.0001). Examining patients with a Stanford probability &amp;lt;= 10%, we found that 47 patients met this criterion; 6 had +NSLN and 41 did not, for a false negative (FN) prediction rate of 13%. There was only 1 patient with Stanford probability &amp;lt;= 5%, and this patient did not have +NSLN. The AUC of the MSKCC and Mayo nomograms in this same patient population was 0.74 and 0.77, respectively. The AUCs did not differ significantly (p = 0.13) among the 3 models.&amp;#x2028; &amp;#x2028; Conclusion: Despite using only three variables, the Stanford nomogram appears to perform as well as, but not better than the MSKCC and Mayo nomograms in our patient cohort. Further validation in other patient populations is needed prior to widespread utilization of this nomogram. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1005.
Management and diagnostic guidelines for urticaria and angio-oedema
Authors: C. Grattan, S. Powell, F. Humphreys
Journal: British Journal of Dermatology (2001)

Journal Article Management and diagnostic guidelines for urticaria and angio‐oedema Get access C. Grattan, C. Grattan Departments of Dermatology, West Norwich Hospital, Norwich, U.K. *The Churchill, Headington, Oxford, U.K. †Warwick Hospital, Warwick, U.K. Dr Clive Grattan. Search for other works by this author on: Oxford Academic Google Scholar S. Powell, S. Powell Departments of Dermatology, West Norwich Hospital, Norwich, U.K. *The Churchill, Headington, Oxford, U.K. †Warwick Hospital, Warwick, U.K. Search for other works by this author on: Oxford Academic Google Scholar F. Humphreys F. Humphreys Departments of Dermatology, West Norwich Hospital, Norwich, U.K. *The Churchill, Headington, Oxford, U.K. †Warwick Hospital, Warwick, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 4, 1 April 2001, Pages 708–714, https://doi.org/10.1046/j.1365-2133.2001.04175.x Published: 01 April 2001
Physiologic Age and the Recent Heart Disease Mortality
Authors: D. S. MCLAREN
Journal: Annals of Internal Medicine (1980)

Letters1 March 1980Physiologic Age and the Recent Heart Disease MortalityD. S. MCLAREN, M.D., PH.D.D. S. MCLAREN, M.D., PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-92-3-442_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Stern (1) in his thorough account of the decline in coronary heart disease mortality and its possible causes suggests that changes in life style and better medical care are partly responsible. If this were so, one would not expect to find the trend greater in nonwhites than whites, greater for stroke, notably resistant to preventive measures (2), and occurring also for all causes of death (3).More than 20 years ago Jones (4) in a largely forgotten paper showed that childhood disease experience played a very important part in determining life expectancy. In Sweden and the...References1. STERN M. The recent decline in ischemic heart disease mortality. Ann Intern Med. 1979;91:630-40. LinkGoogle Scholar2. OSTFELD A. Nutritional aspects of stroke, particularly in the elderly. In: ROCKSTEIN M. SUSSMAN ML, eds. Nutrition, Longevity and Aging. New York: Academic Press, 1976:197-227. CrossrefGoogle Scholar3. STAMLER J. Lifestyles, major risk factors, proof and public policy. Circulation. 1978;58:3-19. CrossrefMedlineGoogle Scholar4. JONES H. A special consideration of the aging process, disease and life expectancy. Adv Biol Med Physics. 1956;4:281-333. CrossrefMedlineGoogle Scholar5. STREHLER B. Implications of aging research for society. Fed Proc. 1975;34:5-8. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: D. S. MCLAREN, M.D., PH.D.Affiliations: Department of Physiology University of Edinburgh Medical School Edinburgh Scotland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1980Volume 92, Issue 3Page: 442-442KeywordsCardiovascular therapyCoronary heart diseaseLife expectancyMortalityStroke ePublished: 1 December 2008 Issue Published: 1 March 1980 PDF downloadLoading ...
Dose-Dependent Effects of Glyburide on Insulin Secretion and Glucose Uptake in Humans
Authors: Leif C Groop, Nir Barzilai, Klaus Ratheiser, Livio Luzi, Elisabeth Wåhlin-Boll, Arne Melander, Ralph A DeFronzo
Journal: Diabetes Care (1991)

Objective To examine the relationship between plasma glyburide concentrations (0, 50, 100, 200, 400, and 800 nM) and the insulin response and glucose metabolism during euglycemic (4.6 ± 0.1 mM) and hyperglycemic (11.6 ± 0.2 mM) conditions. Research Design and Methods Nine healthy subjects participated in the study. Steady-state plasma glyburide concentrations were achieved by primed continuous intravenous infusion of glyburide. Results During both euglycemia and hyperglycemia, glyburide enhanced insulin secretion and glucose disposal only to drug levels of 100–200 nM corresponding to an oral dose ≤ 10 mg. Conclusions The data suggest that glyburide (and probably other sulfonylureas), operates within a narrow range of plasma concentrations (50–200 nM), which can be achieved with very low doses of the drug. It remains to be shown whether the threshold of maximal effect also in clinical practice is achieved with lower sulfonylurea doses than that currently used.
Direct Measurement of Osteolysis in Man
Authors: James W. Hansen, Gilbert S. Gordan, Stanley G. Prussin
Journal: Journal of Clinical Investigation (1973)

Precise, direct measurement of bone calcium release (v(o-)) has been accomplished using a continuous tracer administration (CTA) technique. Dietary calcium (96.97% (40)Ca) is replaced by (40)Ca (99.991% (40)Ca) and blood levels of the naturally occuring isotope (48)Ca are monitored by neutron activation analysis as a function of time. (48)Ca abundance falls as this isotope is excreted and only partially replaced by release from bone. After a suitable period, an asymptotic abundance of (48)Ca in serum, E, is approached which is the fraction of the turnover rate of the rapidly exchangeable calcium pools coming from the skeleton (E = v(o-)/v(t)). E is determined with a standard error of 2%, providing a precise, sensitive index of v(o-). 13 studies in three normal men and one postmenopausal woman receiving maintenance estrogen show large intersubject variations in parameters of calcium metabolism using both CTA and pulse tracer administration (PTA) plus balance techniques. Induced hypercalcemia results in a prolonged decrease in v(o-). Glucocorticoid therapy initially and consistently induces a marked hypercalciuria while effects on most other parameters of calcium kinetics are variable. In two men E fell when testosterone was added to glucocorticoid treatment, consistent with the known antiosteolytic effect of androgens, despite the short period of study.
Adenosine-Recruitable Flow Reserve Is Absent During Myocardial Ischemia in Unanesthetized Dogs Studied in the Basal State
Authors: John M. Canty, Thomas P. Smith
Journal: Circulation Research (1995)

Abstract We conducted the present study to determine if pharmacologically recruitable flow reserve was present during ischemia in unanesthetized dogs studied in the absence of adrenergic activation. Microsphere measurements of regional perfusion at reduced coronary pressures in a distal circumflex region subjected to intracoronary adenosine infusion (0.265 mg/min IC) were compared with measurements in a proximal circumflex region where pressure was reduced but flow was being autoregulated normally. Ischemia began when coronary pressure was reduced below 40 mm Hg. At a coronary pressure of 28±1 (mean±SEM) mm Hg, subendocardial flow with autoregulation intact was 0.59±0.05 mL · min · g −1 and similar to that in the region receiving adenosine, which averaged 0.61±0.05 mL · min −1 · g −1 ( P =NS). Although adenosine increased subepicardial flow from 0.81±0.05 to 1.16±0.09 mL · min −1 · g −1 ( P &lt;.001), the magnitude of the increase was minimal when coronary pressure fell to a level that caused subepicardial flow during autoregulation to be reduced below resting values. These results demonstrate that the substantially lower autoregulatory break point found in unanesthetized dogs studied in the basal state reflects the ability of intrinsic autoregulatory mechanisms to match local vasodilator reserve to that recruitable pharmacologically. This contrasts with the presence of pharmacologically recruitable subendocardial flow reserve in anesthetized animals and is most likely related to a low level of circulating catecholamines and lack of sympathetic activation in unanesthetized animals studied under basal conditions.
Case in which tubercular matter was evacuated by an opening made artificially into the lungs
Authors: M. Bricheteau
Journal: BMJ (1841)

ARTIFICIAL REMOVAL OF TUBERCU1IR MATTER.sulphur baths were employed, and effected a cure in fourteen days.There are few diseases in which so great a va- riety of remedial means has been tried as in chorea.Dr. Babington, in an interesting paper, contained in the last number (xiii.) of Guy's Hospital Reports, speaks very favourably of the sulphate of zinc.The French physicians prefer the oxide.Generally speaking, tonic remedies are those on which most reliance should be placed, but I am inclined to think that electricity and the sulphur baths wvill be found to be the most powerful means that we possess.
Immunotherapy of Malignant Melanoma
Authors: William D. Terry
Journal: New England Journal of Medicine (1980)

Publication of the results of a trial in which levamisole, a chemical that stimulates some components of the human immune system, had no effect on the clinical course of malignant melanoma (see the report of Spitler and Sagebiel in this issue) provides an opportunity to review the status of immunotherapy of melanoma and other cancers occurring in human beings.The available treatment for malignant melanoma is inadequate. Only 30 to 40 per cent of patients with a deeply penetrating primary lesion (Stage I) or with regional lymph-node metastases (Stage II) will survive for five years after diagnosis.1 The absence of . . .