tbuckley/cabot-search huggingface dataset:
The cyclin E regulator cullin 3 prevents mouse hepatic progenitor cells from becoming tumor-initiating cells
Authors: Uta Kossatz, Kai Breuhahn, Benita Wolf, Matthias Hardtke-Wolenski, Ludwig Wilkens, Doris Steinemann, Stephan Singer, Felicitas Brass, Stefan Kubicka, Brigitte Schlegelberger, Peter Schirmacher, Michael P. Manns, Jeffrey D. Singer, Nisar P. Malek
Journal: Journal of Clinical Investigation (2010)

Cyclin E is often overexpressed in cancer tissue, leading to genetic instability and aneuploidy. Cullin 3 (Cul3) is a component of the BTB-Cul3-Rbx1 (BCR) ubiquitin ligase that is involved in the turnover of cyclin E. Here we show that liver-specific ablation of Cul3 in mice results in the persistence and massive expansion of hepatic progenitor cells. Upon induction of differentiation, Cul3-deficient progenitor cells underwent substantial DNA damage in vivo and in vitro, thereby triggering the activation of a cellular senescence response that selectively blocked the expansion of the differentiated offspring. Positive selection of undifferentiated progenitor cells required the expression of the tumor suppressor protein p53. Simultaneous loss of Cul3 and p53 in hepatic progenitors turned these cells into highly malignant tumor-initiating cells that formed largely undifferentiated tumors in nude mice. In addition, loss of Cul3 and p53 led to the formation of primary hepatocellular carcinomas. Importantly, loss of Cul3 expression was also detected in a large series of human liver cancers and correlated directly with tumor de-differentiation. The expression of Cul3 during hepatic differentiation therefore safeguards against the formation of progenitor cells that carry a great potential for transformation into tumor-initiating cells.
Initial increase in the cryoglobulin level after rituximab therapy for type II cryoglobulinemia secondary to Waldenström macroglobulinemia does not indicate failure of response
Authors: Irene M. Ghobrial, Daniel Z. Uslan, Timothy G. Call, Thomas E. Witzig, Morie A. Gertz
Journal: American Journal of Hematology (2004)

Abstract Type II (mixed) cryoglobulinemia is a systemic vasculitis that may affect many organs, including the skin, leading to ulcerations secondary to immune complex deposition. We report a patient who presented with a large necrotic ulcerative lesion on the right ankle secondary to type II cryoglobulinemic vasculitis due to Waldenström macroglobulinemia that was resistant to multiple modalities of therapy. Amputation to prevent further necrosis and infections was almost performed. Treatment with rituximab was initiated and the patient had a dramatic response. This case report highlights the effectiveness and prompt response to rituximab when used in patients with small vessel vasculitis and skin ulceration. We describe a rise in the cryoglobulin level that may occur initially after rituximab therapy. Am. J. Hematol. 77:329–330, 2004. © 2004 Wiley‐Liss, Inc.
A man with transient ischaemic attack and thrombocytopenia
Authors: M. Mohamed, J. Tan
Journal: BMJ (2014)

A 51 year old man presented to the emergency department with sudden onset of right upper limb weakness and slurring of speech, associated with intermittent headaches. He had no medical history of note. He had smoked 10-15 cigarettes a day for 30 years and had no history of excessive alcohol intake. Neurological examination showed weakness of the upper motor neurones of the right upper limb and right side of the face, but no other neurological signs. Cardiac, respiratory, and abdominal examinations were normal. The neurological signs spontaneously recovered within four hours, and computed tomography of the brain showed no abnormalities. 

Full blood counts showed low haemoglobin (92 g/L; normal range 130-180), a low platelet count (28×109/L; 140-440), and a high neutrophil count (11×109/L; 2-8). A blood smear showed red blood cells with morphological abnormalities (fig 1⇓). His absolute reticulocyte count (235×109/L; 50-100) and serum lactate dehydrogenase (814 U/L; 125-243) were raised, and serum haptoglobin was undetectable; however, his bilirubin concentration was normal. A direct antiglobin test was negative. His prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were within normal limits. Serum creatinine, liver function tests, lipid profile, and iron studies were also within the normal ranges.



### 1. Describe the findings on the blood film?

#### Short answer

His blood film shows an abundance of schistocytes, a few spherocytes, polychromasia, and thrombocytopenia. These features are suggestive of microangiopathic haemolytic anaemia.

#### Long answer

Schistocytes are fragmented red blood cells that are detected by microscopy in peripheral blood films stained by standard procedures. These abnormalities are caused by extrinsic mechanical damage to red cells within …
Systolic time intervals by echocardiography.
Authors: M A Stefadouros, A C Witham
Journal: Circulation (1975)

Technical difficulties in recording phonocardiogram or indirect carotid pulse occasionally preclude determination of the systolic time intervals. Accordingly, an alternative method was tested in 52 patients, using high-speed strip chart recording of the aortic valve echocardiogram. Satisfactory records were obtained in 36. The interval from opening to closing of the aortic valve (ejection time) was subtracted from the interval between the Q wave of the electrocardiogram and the closing of the aortic valve (total electromechanical systole) to provide the pre-ejection period. When these intervals and the pre-ejection period/ejection time ratio were compared to corresponding values obtained by conventional methods from the simultaneously recorded phonocardiograms and indirect carotid pulses, a high degree of correlation (r greater than 0.97) was found. Differences between the two methods for each interval were insignificant, being greatest in the case of the ejection time but never exceeding 16 msec. These findings indicate that the echocardiogram of the aortic valve provides an alternative, noninvasive method for determination of the systolic time intervals whenever the usual methods fail.
Endothelin-1 is involved in the pathogenesis of ischemia/reperfusion liver injury by hepatic microcirculatory disturbances
Authors: Moritaka Goto, Yoshiyuki Takei, Sunao Kawano, Kouichi Nagano, Shingo Tsuji, Eiji Masuda, Yoshiya Nishimura, Shigetoshi Okumura, Toru Kashiwagi, Hideyuki Fusamoto, Takenobu Kamada
Journal: Hepatology (1994)

Hepatic microcirculatory perturbation is observed after ischemia/reperfusion. Endothelin-1, a potent vasoconstrictive peptide, is known to modulate local circulation. This study was designed to examine whether endothelin-1 participates in the mechanism of microcirculatory disturbance and damage of the liver after ischemia/reperfusion. Ischemia in the median and left lateral lobes of the liver was induced for 60 min; it was followed by reperfusion for 24 hr. In some rats, endothelin-1 antiserum or control serum without endothelin-1-blocking activity was administered intravenously just before reperfusion. Rats were divided into three groups: an ischemia/reperfusion group that was injected with control serum, an endothelin-1 antiserum-treated group and a sham-operated group. Endothelin-1 concentrations in blood collected from the suprahepatic vena cava were measured before and after ischemia/reperfusion by use of a sandwich enzyme immunoassay. Index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue were assessed with an organ reflectance spectrophotometry system before and at 5 min and 1, 2, and 24 hr after reperfusion. The endothelin-1 concentration in the ischemia/reperfusion group started to rise immediately at onset of reperfusion from basal values around 1 pg/ml and reached a value of 5 to 6 pg/ml 5 min after reperfusion; it was maintained at significantly high levels during the reperfusion period compared with the sham-operated group. Hepatic microcirculatory disturbance indicated by lowered index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue levels was observed in the early phase of reperfusion in the ischemia/reperfusion group.(ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (&lt;5 cm) hepatocellular carcinomas
Authors: Rita Golfieri, Alberta Cappelli, Alessandro Cucchetti, Fabio Piscaglia, Maria Carpenzano, Eugenia Peri, Matteo Ravaioli, Antonia D'Errico-Grigioni, Antonio Daniele Pinna, Luigi Bolondi
Journal: Hepatology (2011)

Abstract Transarterial chemoembolization (TACE) is commonly used as a bridge therapy for patients awaiting liver transplantation (LT) and for downstaging patients initially not meeting the Milan criteria. The primary aim of this study was to analyze whether a difference exists between selective/superselective and lobar TACE in determining tumor necrosis by a pathological analysis of the whole lesion at the time of LT. The secondary aim was to investigate the relationship between the tumor size and the capacity of TACE to induce necrosis. Data were extracted from a prospective database of 67 consecutive patients who underwent LT for hepatocellular carcinoma and cirrhosis from 2003 to 2009 and were treated exclusively with TACE as a bridging (n = 53) or downstaging therapy (n = 14). We identified 122 nodules; 53.3% were treated with selective/superselective TACE. The mean histological necrosis level was 64.7%; complete tumor necrosis was obtained in 42.6% of the nodules. In comparison with lobar TACE, selective/superselective TACE led to significantly higher mean levels of necrosis (75.1% versus 52.8%, P = 0.002) and a higher rate of complete necrosis (53.8% versus 29.8%, P = 0.013). A significant direct relationship was observed between the tumor diameter and the mean tumor necrosis level (59.6% for lesions &lt; 2 cm, 68.4% for lesions of 2.1–3 cm, and 76.2% for lesions &gt; 3 cm). Histological necrosis was maximal for tumors &gt; 3 cm: 91.8% after selective/superselective TACE and 66.5% after lobar procedures. Independent predictors of complete tumor necrosis were selective/superselective TACE ( P = 0.049) and the treatment of single nodules ( P = 0.008). Repeat sessions were more frequently needed for nodules treated with lobar TACE (31.6% versus 59.3%, P = 0.049). Conclusion: Selective/superselective TACE was more successful than lobar procedures in achieving complete histological necrosis, and TACE was more effective in 3- to 5-cm tumors than in smaller ones. (Hepatology 2011;)
Abstract 2466: Elafin, a serine protease inhibitor, is deregulated during breast cancer progression
Authors: Joseph A. Caruso, Cansu Karakas, Kelly Hunt, Khandan Keyomarsi
Journal: Cancer Research (2012)

Abstract Deregulated protease activity promotes diverse aspects of tumorigenesis, including tumor growth, invasion, inflammation, and angiogenesis. Elafin is an endogenous inhibitor of the serine protease, Neutrophil Elastase (NE). Imbalance between NE and its inhibitors is implicated in the pathogenesis of many chronic inflammatory diseases. We hypothesize that elafin is deregulated during breast cancer progression, resulting in increased NE activity, accelerated tumor progression, and overall poor patient outcome. To test this hypothesis, we examined elafin expression by immunohistochemistry (IHC) in normal breast tissue from reduction mammoplasty, pre-malignant Ductal Carcinoma In Situ (DCIS), and invasive breast carcinoma (n&amp;gt;1000, using Tissue Microarray [TMA]). We observed that elafin is intracellularly (predominate nuclear localization) expressed in normal breast tissue. In the majority (&amp;gt;80%) of DCIS cases, intracellular elafin is expressed in a manner consistent with normal breast tissue. However, in cases of invasive breast cancer, intracellular elafin is largely downregulated (&amp;gt;80% of cases) suggesting elafin loss may have a role in progression to invasive carcinoma. Interestingly, examination of elafin expression in invasive breast cancer also revealed a subset (10-20%) of tumors with robust cytoplasmic overexpression of elafin, correlating with poor outcome. Similar results were seen in TMAs of high-grade ovarian carcinoma (n&amp;gt;200). Examination of publically available microarray data (TCGA) demonstrates that elafin measured at the mRNA level is correlates with poor outcome in ovarian cancer, consistent with our IHC results, and good outcome in breast cancer, incompatible with our IHC results. To further investigate the expression of elafin in breast cancer we examined by IHC a patient cohort (&amp;gt;200 patients) for whom full sections (not TMA) were available. Using these patient samples we found a unique subset of breast cancer patients that demonstrate high-level secretion of elafin into the tumor stroma, significantly correlating with increased survival especially in ER negative patients. Collectively, these data suggest that the prognostic role of extracellular elafin is related to the well-characterized ability of elafin to modulate inflammation and immunity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2466. doi:1538-7445.AM2012-2466
Biochemical tests for acute pancreatitis
Authors: P E T Isaacs
Journal: BMJ (1986)

<h3>Objective.</h3> To identify how patients perceive the broad effect of active rheumatoid arthritis (RA) on their daily lives and indicate how RA disease management could benefit from the inclusion of individual goal-setting strategies. <h3>Methods.</h3> Two multinational surveys were completed by patients with RA. The “Good Days Fast” survey was conducted to explore the effect of disease on the daily lives and relationships of women with RA. The “Getting to Your Destination Faster” survey examined RA patients’ treatment expectations and goal-setting practices. <h3>Results.</h3> Respondents from all countries agreed that RA had a substantial negative effect on many aspects of their lives (work productivity, daily routines, participation in social and leisure activities) and emotional well-being (loss of self-confidence, feelings of detachment, isolation). Daily pain was a paramount issue, and being pain- and fatigue-free was considered the main indicator of a “good day.” Setting personal, social, and treatment goals, as well as monitoring disease progress to achieve these, was considered very beneficial by patients with RA, but discussion of treatment goals seldom appeared to be a part of medical appointments. <h3>Conclusion.</h3> Many patients with RA feel unable to communicate their disease burden and treatment goals, which are critically important to them, to their healthcare provider (HCP). Insights gained from these 2 surveys should help to guide patients and HCP to better focus upon mutually defined goals for continued improvement of management and achievement of optimal care in RA.
Increase in IL-8, IL-10, IL-13, and RANTES mRNA levels (in situ hybridization) in the nasal mucosa after nasal allergen provocation
Authors: Alex KleinJan, Mariska D. Dijkstra, Simone S. Boksa, Lies-Anne W.F.M. Severijnen, Paul G.H. Mulder, Wytske J. Fokkens
Journal: Journal of Allergy and Clinical Immunology (1999)
Evaluation of Home versus Laboratory Polysomnography in the Diagnosis of Sleep Apnea Syndrome
Authors: FLORENCE PORTIER, ADRIANA PORTMANN, PIERRE CZERNICHOW, LIONEL VASCAUT, ETIENNE DEVIN, DANIEL BENHAMOU, ANTOINE CUVELIER, JEAN FRANÇOIS MUIR
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The aim of this study was to compare home polysomnography (HoPSG) with laboratory polysomnography (LabPSG) in the diagnosis of sleep apnea syndrome (SAS). A total of 103 patients referred for investigation of SAS underwent two full polysomnographies, using the portable Minisomno device at home and the Respisomnographe in the laboratory (both devices manufactured by the same company). Twenty percent of home-studied device polysomnography (HoSD-PSG) recordings and 5% of LabPSG recordings were excluded from analysis either because of lost data or poor quality data. Sleep stage distribution and subjective quality of sleep were similar by both methods. Using LabPSG, the mean ( ± SD) RDI was 25.7 ( ± 30.6) versus 22.8 ( ± 31.5) using HoSD-PSG (p > 0.05). Absolute differences between the home and laboratory respiratory disturbance index (RDI) were less than 10 for 65% of patients. Discordant RDIs (i.e., differences greater than 10) were observed for 63% of individuals with severe SAS (RDI > 30) versus 22% of those with normal or moderate SAS (RDI ⩽ 30) (p < 0.05). Higher RDI differences were associated with poor airflow signal at home. Forty-seven percent of patients preferred LabPSG. Our results suggest that HoSD-PSG was not feasible for 33% of patients; there was no evidence of a better quality of sleep and recording tolerance at home; the reliability of HoSD-PSG for SAS diagnosis depends on the quality of data obtained under unattended conditions.
Treatment of Essential Hypertension with Combined Vasodilation and Beta-Adrenergic Blockade
Authors: Rudolf Zacest, Edward Gilmore, Jan Koch-Weser
Journal: New England Journal of Medicine (1972)

Twenty-three patients with moderate or severe essential hypertension were treated with a combination of diuretic, propranolol and hydralazine. In 20 of these patients blood pressure had not been satisfactorily controlled by diuretics, methyldopa and guanethidine. Daily propranolol dosage was 80 to 160 mg (mean, 143), and that of hydralazine 40 to 400 mg (mean, 225). The mean blood-pressure reduction achieved by combined beta-adrenergic blockade and vasodilation was 46/30 mm of mercury in the lying and 42/32 mm of mercury in the standing position. Diastolic arterial pressure was reduced below 100 mm of mercury in 21 patients and to 90 mm or less in 17 patients. This effective antihypertensive action was not associated with postural hypotension, tachycardia, other hemodynamic disturbances, impairment of renal function or adverse symptoms in any patient. The absence of side effects caused strong patient preference for the combination of propranolol and hydralazine over sympathoplegic drugs.
Non-Invasive Cardiac Diagnosis
Authors: Arthur J. Moss
Journal: JAMA (1976)

This book, edited by Dr Chung, contains 16 multiauthored chapters covering diverse areas of cardiovascular interest from echocardiography to ballistocardiography, from routine to computer electrocardiography, and from physical examination of the cardiovascular system to the interpretation of digitalis and antiarrhythmic drug levels. Such a wide range of subjects in a 300-page book by 18 coauthors inevitably results in variable quality and redundant coverage of certain topics, especially heart sounds and systolic time intervals. The first chapter, on the examination of the cardiovascular system, is elementary, with outdated interpretations as to the etiology of heart sounds; the most recent reference date in this chapter is 1964. The reason for including chapters on electrocardiography and vectorcardiography by Chung is not clear in light of Chung's recent textbooks on these subjects. Such subject material and chapter presentations are too brief for the novice and too superficial for the experienced cardiologist. Excellent chapters, critically
Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics
Authors: H. Bergstrand, B. Hegardt, O. Löuwhagen, Ö. Strannegård, N. Svedmyr
Journal: Allergy (1985)

Twenty asymptomatic atopic asthmatics were treated with either cimetidine 100 mg orally (13 patients) or placebo (7 patients) once a day for 4 weeks. Bronchial challenges were performed with the pertinent allergen immediately before and 2 and 4 weeks after the initiation of treatment and, finally, 4 weeks after the cessation of treatment. Before each challenge blood was drawn for the determination of specific IgE antibody levels (RAST procedure) and total IgE (PRIST), allergen- and anti-IgE-induced basophil histamine release, and mitogen-induced lymphocyte (3H)-thymidine incorporation. Patients treated with cimetidine were found to be significantly (P less than 0.05) less responsive to bronchial allergen challenge during the treatment than before it; patients treated with placebo were more reactive (P less than 0.05) 14 days after the initiation of treatment. The difference in responsiveness to treatment between the placebo and the cimetidine groups was significant 14 days (P less than 0.01) and 4 weeks (P less than 0.05) after the initiation of treatment; no significant difference in allergen responsiveness was recorded between the groups 1 month after cessation of treatment. No clear-cut changes in specific IgE antibody or total IgE levels, histamine release capacity, or mitogen-induced lymphocyte responsiveness were observed in either group, except that lymphocytes from cimetidine-treated patients tended to show an increased ratio of PHA- to PMA-induced thymidine incorporation. Thus, it was found that the treatment of asymptomatic atopic asthmatics with low-dose cimetidine reduced their allergen sensitivity in bronchial provocation tests by a mechanism which remains to be elucidated.
IMPACT OF SUSTAINED ANEMIA ON LONG TERM CLINICAL OUTCOMES IN PATIENTS WHO UNDERWENT DRUG-ELUTING STENT
Authors: Tae Hoon Kim, Chan Joon Kim, Soo-Yeon Jung, Soe Hee Ann, Suk Min Seo, Youn Seok Koh, Youn Seok Choi, Dong Bin Kim, Jong Min Lee, Pum Joon Kim, Keon Woong Moon, Kiyuk Chang, Ki Dong Yoo, Hee Yeol Kim, Wook Sung Chung, Ki-Bae Seung
Journal: Journal of the American College of Cardiology (2011)
C-peptide and insulin secretion. Relationship between peripheral concentrations of C-peptide and insulin and their secretion rates in the dog.
Authors: K S Polonsky, W Pugh, J B Jaspan, D M Cohen, T Karrison, H S Tager, A H Rubenstein
Journal: Journal of Clinical Investigation (1984)

Estimation of the insulin secretory rate from peripheral C-peptide concentrations depends upon the following characteristics of C-peptide kinetics: (a) equimolar secretion of insulin and C-peptide by pancreatic beta cells; (b) negligible hepatic extraction of C-peptide; (c) constant metabolic clearance rate (MCR) of C-peptide over a physiological and pathophysiological range of plasma levels; and (d) proportional changes in the secretion rate of C-peptide and its peripheral concentrations under varying physiological conditions. In the present experiments, the relationship between a variable intraportal infusion of C-peptide and its concentration in the femoral artery was explored in 12 pancreatectomized dogs. As the infusion of C-peptide was rapidly increased, the magnitude of its peripheral concentration initially increased less than the infusion rate by 20-30%. After an equilibration period of approximately 30 min, however, further increases and decreases in the intraportal infusion were accompanied by nearly proportional changes in its peripheral concentration. Estimates of the amount of C-peptide infused during the experiment based on the steady state C-peptide MCR and its peripheral concentration were within 20% of the amount of C-peptide actually infused. These experiments demonstrate that the portal delivery rate of C-peptide can be calculated from its MCR and peripheral concentration in the dog. They also provide a basis for testing the validity of more complicated models of insulin secretion based on peripheral C-peptide concentrations in the dog as well as other species, including man. Finally, we have shown that the hepatic extraction of endogenously secreted C-peptide is negligible in the basal state (3.1 +/- 6.1%), and does not change after oral glucose ingestion. The MCR of exogenous dog C-peptide was similar whether measured by constant peripheral intravenous infusion (12.3 +/- 0.7 ml/kg per min), constant intraportal infusion (13.4 +/- 0.6 ml/kg per min), or analysis of the decay curve after a bolus injection (13.5 +/- 0.7 ml/kg per min).