tbuckley/cabot-search huggingface dataset:
Antibodies to interleukin 12 abrogate established experimental colitis in mice.
Authors: M F Neurath, I Fuss, B L Kelsall, E Stüber, W Strober
Journal: The Journal of Experimental Medicine (1995)

In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c and SJL/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4+ T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4+ T cells from control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4+ T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease.
Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis
Authors: Justina McEvoy, Jacqueline Flores-Otero, Jiakun Zhang, Katie Nemeth, Rachel Brennan, Cori Bradley, Fred Krafcik, Carlos Rodriguez-Galindo, Matthew Wilson, Shunbin Xiong, Guillermina Lozano, Julien Sage, Ligia Fu, Lotfi Louhibi, Jeff Trimarchi, Amar Pani, Richard Smeyne, Dianna Johnson, Michael A. Dyer
Journal: Cancer Cell (2011)
Re: The sinoatrial node, connexin distribution patterns and specific immunodetection of connexin45
Authors: S Coppen
Journal: Cardiovascular Research (2002)

To the editor:

In a recent paper in Cardiovascular Research, Verheijck et al. [1] examine the important topic of the electrophysiological properties of the sinoatrial (SA) node in relation to the distribution of different connexin types. It is certainly pleasing to see that these authors' results and conclusions on connexin distribution in the mouse SA node in many respects parallel our earlier published findings in the rabbit [2]. Unfortunately, however, these parallels are largely concealed to the reader by the authors' confused representation of our work. Muddling up citations (as, for example, in their statement referring to our report of connective tissue between the atrium and nodal tissue; Ref. [2], not Ref. [3] as cited) would alone be too trivial a matter to merit comment. However, the authors go on to state that Coppen et al. [2] reported the rabbit SA node to be connexin43 (Cx43) positive when, in fact—just as in the study of Verheijck et al. [1] in the mouse—we found the central SA node to be Cx43 negative. The confusion is then compounded by a series of comments that appear to cast doubt on the reliability and specificity of the Cx45 antibody used in our work demonstrating the SA node to be connexin45 positive [2]. Such comments undermine the research effort we have devoted to re-appraising and advancing investigation of the spatial and temporal expression patterns of Cx45 in cardiovascular and other tissues [2–11]. From this perspective, we feel it imperative that the record be set straight.

The authors state that “Coppen et al. [3] showed that the Cx45 …
Endothelial Implants Inhibit Intimal Hyperplasia After Porcine Angioplasty
Authors: Helen M. Nugent, Campbell Rogers, Elazer R. Edelman
Journal: Circulation Research (1999)

Abstract —The perivascular implantation of tissue-engineered endothelial cells around injured arteries offers an opportunity to study fundamental vascular physiology as well as restore and improve tissue function. Cell source is an important issue because the ability to implant either xenogeneic or allogeneic cells would greatly enhance the clinical applications of tissue-engineered grafts. We investigated the biological and immunological responses to endothelial cell xenografts and allografts in pigs 4 weeks after angioplasty of the carotid arteries. Porcine or bovine aortic endothelial cells were cultured within Gelfoam matrices and implanted in the perivascular space of 42 injured arteries. Both porcine and bovine endothelial cell grafts reduced the restenosis index compared with control by 54% and 46%, respectively. Perivascular heparin release devices, formulated to release heparin at twice the rate of release of heparan sulfate proteoglycan from endothelial cell implants, produced no significant reduction in the restenosis index. Endothelial cell implants also reduced occlusive thrombosis compared with control and heparin release devices. Host immune responses to endothelial implants were investigated by immunohistochemical examination of explanted devices and by immunocytochemistry of serum samples. The bovine cell grafts displayed infiltration of leukocytes, consisting primarily of lymphocytes, and caused an increase in antibodies detected in serum samples. Reduced cellular infiltration and no humoral response were detected in animals that received allografts. Despite the difference in immune response, the biological effects of xenografts or allografts did not differ significantly.
Monitoring of Circulating Tumor DNA As Minimal Residual Disease in Diffuse Large B-Cell Lymphoma
Authors: Mark Roschewski, Kieron Dunleavy, Stefania Pittaluga, Katie Kong, Margaret Shovlin, Elaine S. Jaffe, Louis M. Staudt, Catherine Lai, Clara C. Chen, Jianbiao Zheng, Thomas D. Willis, Malek Faham, Wyndham H Wilson
Journal: Blood (2014)
THE SIGNIFICANCE OF THE BABINSKI SIGN DURING HYPOGLYCEMIC TREATMENT OF SCHIZOPHRENIA
Authors: MARCEL HEIMAN
Journal: American Journal of Psychiatry (1939)

1. A positive Babinski was found in 92.3 per cent of cases after the onset of unconsciousness and in 74.2 per cent prior to the onset of unconsciousness in patients undergoing insulin treatment for schizophrenia. 2. The positive Babinski has no significance in determining a stage of coma during the insulin hypoglycemia. 3. The loss of corneal reflexes is suggested as a reliable sign for determining a deeper stage of coma. 4. [Dr. Max Sherman gave assistance in reading records and correcting the manuscript.]
Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia
Authors: Nidal M. Almasri, Ricardo E. Duque, Jose Iturraspe, Eric Everett, Raul C. Braylan
Journal: American Journal of Hematology (1992)

The surface antigens expressed by the cells of chronic lymphocytic leukemia (CLL) are well known. Most CLL are monoclonal B-cell lymphoproliferative disorders characterized by the coexpression of B-cell antigens and CD5, an antigen present predominantly on T cells. Very little attention, however, has been paid to the quantitative characteristics of the expression of B-cell antigens in CLL. In this study, we used flow cytometry to analyze the expression of CD20, a well-known B-cell-associated antigen, in lymphocytes from 42 cases of CLL and its tissue counterpart, small lymphocytic lymphoma (SLL), and compared the results with results obtained from the analysis of 21 follicular lymphomas, 20 hyperplastic reactive nodes, and 26 samples of normal peripheral blood. The intensity of CD20 expression in the CLL/SLL cells was significantly lower than that of B cells in the other categories. This antigen expression abnormality does not appear to be a universal phenomenon in CLL/SLL, since CD19, another pan-B antigen, was expressed in CLL/SLL at levels higher than those in follicular lymphomas and comparable to those in reactive lymph nodes. These results indicate that the low CD20 expression can be used as a marker for CLL/SLL. The few cases exhibiting intense CD20 expression may represent a biologically different disease. CLL/SLL cells faintly expressing CD20 also show concomitant low CD5 expression in a manner not observed in normal CD5-expressing B cells.
Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4
Authors: Kanjoormana Aryan Manu, Muthu K Shanmugam, Peramaiyan Rajendran, Feng Li, Lalitha Ramachandran, Hui Sin Hay, Radhamani Kannaiyan, Shivananju Nanjunda Swamy, Shireen Vali, Shweta Kapoor, Bhargavi Ramesh, Pradeep Bist, Evelyn S Koay, Lina HK Lim, Kwang Seok Ahn, Alan Prem Kumar, Gautam Sethi
Journal: Molecular Cancer (2011)

Abstract Background Increasing evidence indicates that the interaction between the CXC chemokine receptor-4 (CXCR4) and its ligand CXCL12 is critical in the process of metastasis that accounts for more than 90% of cancer-related deaths. Thus, novel agents that can downregulate the CXCR4/CXCL12 axis have therapeutic potential in inhibiting cancer metastasis. Methods In this report, we investigated the potential of an agent, plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), for its ability to modulate CXCR4 expression and function in various tumor cells using Western blot analysis, DNA binding assay, transient transfection, real time PCR analysis, chromatin immunoprecipitation, and cellular migration and invasion assays. Results We found that plumbagin downregulated the expression of CXCR4 in breast cancer cells irrespective of their HER2 status. The decrease in CXCR4 expression induced by plumbagin was not cell type-specific as the inhibition also occurred in gastric, lung, renal, oral, and hepatocellular tumor cell lines. Neither proteasome inhibition nor lysosomal stabilization had any effect on plumbagin-induced decrease in CXCR4 expression. Detailed study of the underlying molecular mechanism(s) revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, inhibition of NF-κB activation, and suppression of chromatin immunoprecipitation activity. In addition, using a virtual, predictive, functional proteomics-based tumor pathway platform, we tested the hypothesis that NF-κB inhibition by plumbagin causes the decrease in CXCR4 and other metastatic genes. Suppression of CXCR4 expression by plumbagin was found to correlate with the inhibition of CXCL12-induced migration and invasion of both breast and gastric cancer cells. Conclusions Overall, our results indicate, for the first time, that plumbagin is a novel blocker of CXCR4 expression and thus has the potential to suppress metastasis of cancer.
TREATMENT OF BENION FAMILIAL PEMPHIGUS (HAILEY-HAILEY) BY SKIN GRAFTING
Authors: A. BITAR, J.-M. GIROUX
Journal: British Journal of Dermatology (1970)

Journal Article TREATMENT OF BENION FAMILIAL PEMPHIGUS (HAILEY‐HAILEY) BY SKIN GRAFTING Get access A. BITAR, A. BITAR Section of Dermatology, Hôtel‐Dieu, Montreal, Canada Search for other works by this author on: Oxford Academic Google Scholar J.‐M. GIROUX J.‐M. GIROUX Section of Dermatology, Hôtel‐Dieu, Montreal, Canada Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 83, Issue 3, 1 September 1970, Pages 402–404, https://doi.org/10.1111/j.1365-2133.1970.tb15725.x Published: 01 September 1970 Article history Accepted: 02 March 1970 Published: 01 September 1970
Slow turnover of manganese in active rheumatoid arthritis accelerated by prednisone
Authors: George C. Cotzias, Paul S. Papavasiliou, Edwin R. Hughes, Lily Tang, Donald C. Borg
Journal: Journal of Clinical Investigation (1968)

Total body and area counts of intravenously injected (54)Mn were measured periodically in 29 in-patients. A heterogeneous group of 19 control patients showed fair reproducibility in the immediate distribution, and considerable individual variance in the subsequent loss of the isotope. Eight studies of the effects of feeding excesses of manganous sulfate to five patients showed acceleration of the rate of loss of the radioisotope from the whole body and the liver. These findings seem compatible with the presence of control mechanisms in man, operating to vary the metal's excretion, while tending to preserve constancy of its concentration in tissues. Slow turnover rates of the metal were demonstrated in seven out of eight patients with active rheumatoid arthritis, in one with hydralazine disease, but not in one arthritic undergoing an impressive, spontaneous remission. Statistically significant differences were encountered in the measurements of (54)Mn turnover of the total body, the thyroid, and the liver. Administration of prednisone induced clinical improvement and significant acceleration of these turnovers. Slow turnovers are characteristic of nutritional manganese deficiency. Therefore, serum and blood manganese determinations were performed by neutron activation analysis on 14 control patients, and on six patients with active rheumatoid arthritis. A statistically significant elevation of the red cell manganese concentration was encountered in patients with rheumatoid arthritis. This argued against the presence of classical tracemetal deficiency and called for an alternative explanation of these findings.
Identifying failure of empirical treatment for pneumonia: vigilance and common sense
Authors: W-S Lim
Journal: Thorax (2004)

Some progress in identifying the risk factors associated with treatment failure in CAP

In patients with community acquired pneumonia (CAP), clinical and radiological features at the time of presentation do not predict the microbiological aetiology with any certainty.1 Initial treatment is therefore usually empirical and directed by the severity of the illness at the time of presentation. A large number of studies have been conducted over the last 10 years to determine prognostic factors in CAP. In turn, clinical prediction rules based on a number of key prognostic factors have been developed, such as the pneumonia severity index (PSI) and the CURB-65 score, and incorporated into CAP management guidelines.2–6 Most of these CAP severity studies, and the resulting prediction rules, use mortality as the main outcome measure. However, mortality is not the only clinically important outcome. In this issue of Thorax , Menendez and colleagues report on a large observational study of the risk factors related to failure of initial empirical treatment for CAP.7

The definition of treatment failure adopted was complex and based on (a) the time from admission (less than or more than 72 hours corresponding to “early” and “late” treatment failure) and (b) the occurrence of clinical features such as “haemodynamic instability”, “the appearance or impairment of respiratory failure”, and “radiographic progression”. While pragmatic, these features were not rigorously defined, thus making it difficult …
THE VARIOUS FACTORS OF RESPIRATION IN PERSONS WITH PNEUMOTHORAX
Authors: J. H. Means, G. M. Balboni
Journal: The Journal of Experimental Medicine (1916)

It may be said that at rest all the factors of respiration, gaseous exchange, carbon dioxide tension, and the mechanical factors, are normal in persons with a collapsed lung, that the reaction to carbon dioxide is normal up to the point at which the respiration is trebled, or sometimes quadrupled, but that beyond that point a limit may be reached. The ventilation of the lungs can be accomplished in an entirely normal manner in spite of a greatly reduced vital capacity. The only difference between normal persons and persons with a collapsed lung is that the latter when called upon to increase their ventilation reach their limit a little sooner than the former. From these findings we might deduce that there will be no dyspnea except after moderate exertion. And this deduction is borne out by the histories of the patients. In other words, in the lungs, as in other organs, there is a large factor of safety, one lung being as efficient as two, except when the work done calls for more than a threefold increase in the normal ventilation.
Stroke As a Late Treatment Effect of Hodgkin's Disease: A Report From the Childhood Cancer Survivor Study
Authors: Daniel C. Bowers, D. Elizabeth McNeil, Yan Liu, Yutaka Yasui, Marilyn Stovall, James G. Gurney, Melissa M. Hudson, Sarah S. Donaldson, Roger J. Packer, Pauline A. Mitby, Catherine E. Kasper, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2005)

Purpose The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. Patients and Methods The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. Results Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P &lt; .0001). Conclusion Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.
Factors modifying the early nondiuretic vascular effects of furosemide in man. The possible role of renal prostaglandins.
Authors: G D Johnston, W R Hiatt, A S Nies, N A Payne, R C Murphy, J G Gerber
Journal: Circulation Research (1983)

Animal experiments have suggested that salt-balance, prostaglandin synthesis, and renal function are important determinants of the nondiuretic vascular effects of furosemide. To investigate the influence of these factors in humans, we studied 10 normal volunteers and five anephric patients. The volunteers were studied on three occasions: when on a 10 mEq/day sodium diet, on a 250 mEq/day sodium diet, and on a 10 mEq/day sodium diet with indomethacin, 200 mg/day. The anephric patients were studied immediately after dialysis. Plethysmographic methods were used to measure venous capacitance and blood flow in the calf before, and at 5, 10, and 15 minutes after furosemide, 80 mg, iv. Blood was obtained before and 15 minutes after furosemide for determination of plasma renin activity by radioimmunoassay and of plasma 6-keto-prostaglandin F1 alpha by chromatography-mass spectrometry. We found that furosemide significantly increased venous capacitance in the calf of the normal volunteers on a low salt diet. Indomethacin, high salt intake, or lack of renal function was sufficient to inhibit this effect. Plasma renin activity increased only in the group that had the increase in venous capacitance. Limb blood flow decreased gradually in the 15 minutes following administration of furosemide in the normal volunteers, regardless of salt balance or indomethacin, but remained unchanged in the anephric patients. Plasma 6-keto-prostaglandin F1 alpha was less than 30 pg/ml in all samples. Indomethacin concentration averaged 1.3 micrograms/ml in volunteers on the drug. To determine whether indomethacin, salt intake or renal function affected another venodilator, we studied an additional group of normal and uremic volunteers who received 0.6 mg nitroglycerin sublingually.(ABSTRACT TRUNCATED AT 250 WORDS)
Naturally Occurring Anticarcinogenic Substances in Foodstuffs
Authors: E S Fiala, B S Reddy, J H Weisburger
Journal: Annual Review of Nutrition (1985)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Evidence From a Novel Human Cell Clone That Adult Vascular Smooth Muscle Cells Can Convert Reversibly Between Noncontractile and Contractile Phenotypes
Authors: Shaohua Li, Stephen Sims, Yang Jiao, Lawrence H. Chow, J. Geoffrey Pickering
Journal: Circulation Research (1999)

Abstract —Smooth muscle cells (SMCs) perform diverse functions that can be categorized as contractile and synthetic. A traditional model holds that these distinct functions are performed by the same cell, by virtue of its capacity for bidirectional modulation of phenotype. However, this model has been challenged, in part because there is no physiological evidence that an adult synthetic SMC can acquire the ability to contract. We sought evidence for this by cloning adult SMCs from human internal thoracic artery. One clone, HITB5, expressed smooth muscle α-actin, smooth myosin heavy chains, heavy caldesmon, and calponin and showed robust calcium transients in response to histamine and angiotensin II, which confirmed intact transmembrane signaling cascades. On serum withdrawal, these cells adopted an elongated and spindle-shaped morphology, random migration slowed, extracellular matrix protein production fell, and cell proliferation and [ 3 H]thymidine incorporation fell to near 0. Cell viability was not compromised, however; in fact, apoptosis rate fell significantly. In this state, agonist-induced elevation of cytoplasmic calcium was even more pronounced and was accompanied by SMC contraction. Readdition of 10% serum completely returned HITB5 cells to a noncontractile, proliferative phenotype. Contractile protein expression increased after serum withdrawal, although modestly, which suggested that the switch to contractile function involved reorganization or sensitization of existing contractile structures. To our knowledge, the physiological properties of HITB5 SMCs provide the first direct demonstration that cultured human adult SMCs can convert between a synthetic, noncontracting state and a contracting state. HITB5 cells should be valuable for characterizing the basis of this critical transition.
A bias-corrected estimate of heterozygosity for single-probe multilocus DNA fingerprints.
Authors: L Jin, R Chakraborty
Journal: Molecular Biology and Evolution (1993)

Stephens et al. ( 1992) proposed an estimate of average heterozygosity for loci detected by multilocus DNA probes used in DNA fingerprinting. This estimate is based on the DNA restriction-pattern matrices that are typical for fingerprinting studies. This effort is significant, since important genetic characteristics-such as the number of loci, as well as the distribution of alleles in those loci-are not directly available from DNA fingerprinting data. However, the estimate proposed has some statistical deficiencies. Contrary to the claim of Stephens et al., both the estimation of heterozygosity and the estimation of the number of loci are not truly unbiased. In this letter, we propose a bias-corrected estimate of heterozygosity for single-probe multilocus DNA fingerprinting data and demonstrate that the estimate proposed by Stephens et al. ( 1992) provides an underestimation of the average heterozygosity. The average heterozygosity (gene diversity), over L loci, in a population is defined (Nei 1973) as