tbuckley/cabot-search huggingface dataset:
Cholic Acid Amelioration of Light and Electron Microscopic Hepatic Lesions in Experimental Protoporphyria
Authors: Jay H. Lefkowitch, Kuo-Ching Feng-Chen, Jeffrey A. Sklar, Maureen B. Poh-Fitzpatrick
Journal: Hepatology (2007)

We studied the effects of cholic acid treatment on hepatic histology and ultrastructure in mice with griseofulvin-induced protoporphyria. After 5 weeks of feeding griseofulvin alone, control mice developed darkly pigmented livers which by light microscopy showed birefringent, brown pigment deposits in bile ducts and ductules, sinusoidal Kupffer cell aggregates, and occasionally in hepatocytes and bile canaliculi. Electron microscopy demonstrated aggregated protoporphyrin crystals at these sites as well as membrane blebs and reduction of microvilli in bile canaliculi. In contrast, experimental mice that were concomitantly fed cholic acid and griseofulvin developed no detectable pigment on light microscopy, only rare protoporphyrin crystals on electron microscopy and minimal bile canalicular abnormalities. This study suggests that protoporphyrin transport into bile is enhanced by cholic acid treatment and results in a significant reduction in hepatic protoporphyrin deposition and associated abnormalities of liver morphology.
Proarrhythmic Potential of Mesenchymal Stem Cell Transplantation Revealed in an In Vitro Coculture Model
Authors: Marvin G. Chang, Leslie Tung, Rajesh B. Sekar, Connie Y. Chang, Josh Cysyk, Peihong Dong, Eduardo Marbán, M. Roselle Abraham
Journal: Circulation (2006)

Background— Mesenchymal stem cells (MSCs) are bone marrow stromal cells that are in phase 1 clinical studies of cellular cardiomyoplasty. However, the electrophysiological effects of MSC transplantation have not been studied. Although improvement of ventricular function would represent a positive outcome of MSC transplantation, focal application of stem cells has the potential downside of creating inhomogeneities that may predispose the heart to reentrant arrhythmias. In the present study we use an MSC and neonatal rat ventricular myocyte (NRVM) coculture system to investigate potential proarrhythmic consequences of MSC transplantation into the heart. Methods and Results— Human MSCs were cocultured with NRVMs in ratios of 1:99, 1:9, and 1:4 and optically mapped. We found that conduction velocity was decreased in cocultures compared with controls, but action potential duration (APD 80 ) was not affected. Reentrant arrhythmias were induced in 86% of cocultures containing 10% and 20% MSCs (n=36) but not in controls (n=7) or cocultures containing only 1% MSCs (n=4). Immunostaining, Western blot, and dye transfer revealed the presence of functional gap junctions involving MSCs. Conclusions— Our results suggest that mixtures of MSCs and NRVMs can produce an arrhythmogenic substrate. The mechanism of reentry is probably increased tissue heterogeneity resulting from electric coupling of inexcitable MSCs with myocytes.
Cases Illustrating the Family History of Syphilis: With Remarks
Authors: R. J. Lee
Journal: BMJ (1878)

8X9the pulse.Fig. vi, obtained from a patient under the care of Dr. Habershon, shows the effect of an aneurism, entirely confined to the innominate, on the pulse.In this case, the aorta was quite unaffected; the left pulse is, therefore, perfectly normal, while the right is highly aneurismal.The percussion-wave, well marked in the left, is entirely absent from the right, and the dicrotic is also less distinct.These tracings, showing the freedom of the aorta from disease, were of the highest value from a diagnostic point of view, especially with regard to the treatment to be recommended.Fig. vii, obtained from a patient
Case reopens against cardiologist facing charges of sexual abuse
Authors: C. Dyer
Journal: BMJ (2012)

The General Medical Council is to reopen a hearing into sexual abuse allegations against Philipp Bonhoeffer, former head of cardiology at Great Ormond Street Hospital in London, nearly two years after the original hearing was stayed.

The case, alleging misconduct by Bonhoeffer with boys in Kenya, which he visited often while doing humanitarian work for the Circle of Hope charity, was halted in October 2010 pending an application by the cardiologist to the High Court.

Bonhoeffer objected to the GMC’s decision to rely on hearsay evidence from the main witness, “Witness A”—transcripts of police interviews, …
Laparoscopic Approach for Artificial Urinary Sphincter Implantation in Women with Intrinsic Sphincter Deficiency Incontinence: A Single-Centre Preliminary Experience
Authors: Morgan Rouprêt, Vincent Misraï, Christophe Vaessen, Vincent Cardot, Florence Cour, François Richard, Emmanuel Chartier-Kastler
Journal: European Urology (2009)
Abstract 2879: Proteome changes in mouse prostate induced by oral administration of penta-O-galloyl-beta-D-glucose (PGG) suggest targets for cancer chemoprevention
Authors: Jinhui Zhang, Ahamd Shaik, Katai Nhkata, Lei Wang, Kwan Hyun Kim, Joshua D. Liao, Chengguo Xing, Sung-Hoon Kim, Junxuan Lü
Journal: Cancer Research (2010)

Abstract 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose (PGG), a naturally occurring hydrolyzable gallotannin, has been shown by us and others to exhibit in vivo anti-cancer effects against prostate and breast cancer xenograft or lung cancer allograft when administrated by i.p injection or oral gavage. However, little is known of its safety for chronic chemoprevention use and virtually nothing is known of its in vivo target proteins. In the present study, we treated C57B6 mice with daily gavage of PGG from 7 weeks of age to 14 weeks of age with dosages of 1 and 2 mg per mouse (40-50 and 80-100mg/kg body weight). The dosage choices were made in reference to the efficacious anti-cancer dose of 20 mg/kg body weight. General health, body weights and food intake of mice were monitored. At necropsy, the organ weights were measured. Proteomic patterns in the prostate were profiled by 2D LC-MALDI-TOF/TOF analysis with iTRAQ labeling. Our results show that neither dose affected feed intake and body weight gain, but the 2 mg dose led to a statistically significant but very minor decrease of the weight of prostate and thymus. Proteome profiling by LC-MALDI-TOF/TOF identified 810 proteins from mouse prostates and 623 of them were identified with &amp;gt;95% confidence. Expression of 56 proteins was significantly modulated by either 1mg or 2mg PGG daily treatment, four different kinds of dose responses of proteins modulated by PGG were observed. Protein quantization results were validated by another mass spectrometry, ESI-Q-TOF. Selected proteins were further validated by Western blots and mRNA level by real-time PCR. The proteome profiles modulated by PGG include suppression of oncoproteins such as fatty acid synthase and induction of tumor suppressor proteins such as glutathione S-transferase M. Overall, the data show protein changes induced by tolerated dosages of PGG in the normal prostate are conducive for cancer chemoprevention. The chemopreventive efficacy of PGG is being evaluated in a primary carcinogenesis model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2879.
The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease
Authors: Kevin S. Eardley, Chandrashekhar Kubal, Daniel Zehnder, Marcus Quinkler, Julia Lepenies, Caroline O. Savage, Alec J. Howie, Kirrenjit Kaur, Mark S. Cooper, Dwomoa Adu, Paul Cockwell
Journal: Kidney International (2008)
Abstract 3211: PTTG1 attenuates drug-induced cellular senescence
Authors: Yunguang Tong, Weijiang Zhao, Kolja Wawrowsky, Shlomo Melmed
Journal: Cancer Research (2010)

Abstract PTTG1 (pituitary tumor transforming gene) is abundantly expressed in several cancers and levels correlate with invasiveness and clinical outcome. Here we show that colon cancer cells devoid of PTTG1 (PTTG1−/−) demonstrate enhanced sensitivity and development of senescence in response to anti-neoplastic drugs including doxorubicin and trichostatin A (TSA). Doxorubicin (0.005 uM) had no effect on WT HCT116 colon cancer cells but inhibited PTTG1−/− HCT116 cell BrdU incorporation by 37 % (p&amp;lt;0.001). β-Galactosidase staining demonstrated that 43 % of PTTG1−/− HCT116 cells were senescent compared to 3 % of WT cells treated with 0.005 uM doxorubicin. Up to 0.02 uM doxorubicin did not cause apoptosis as measured by Tunel assay and activated caspase 3 levels, suggesting that cell cycle arrest is responsible for enhanced drug sensitivity in PTTG1−/− cells. PTTG1−/− cells exhibit ∼3 fold induction of p21 upon doxorubicin or TSA treatment, while knock down of p21 abrogated senescent effects of these drugs. p21 expression in PTTG1−/− cells after doxorubicin and TSA treatment was increased by enhanced binding of Sp1, p53 and p300 at the p21 promoter. PTTG1−/− cells developed smaller tumors than WT (1.24 ± 0.41 vs 0.39 ± 0.15 g, p&amp;lt;0.001), and were also more sensitive to doxorubicin treatments, with tumor growth inhibition rate 50% and 75 % respectively (p&amp;lt;0.05). PTTG1−/− cells develop less metastatic foci compared to WT (29 ± 8 vs 46 ± 12, p&amp;lt;0.001). Doxorubicin treatment suppressed metastatic foci formation by 49 % in PTTG1−/− tumors, compared to 15 % in WT cell-derived tumors. β-Galactosidase staining indicated that cell senescence was more pronounced in doxorubicin-treated PTTG1−/− tumors than in WT (57 % vs 22 % in subcutaneous tumor, p&amp;lt;0.001, 70 % vs 18 % in metastatic foci, p&amp;lt;0.001,). As senescence is a determinant of the cell response to anti-neoplastic treatments, the results indicate that PTTG1 may decrease anti-neoplastic drug responsiveness through attenuating cell senescence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3211.
A2.22 Tyrosine Phosphorylation Pathways in Myeloid Cell-Mediated Inflammatory Diseases
Authors: M Kovács, T Németh, K Futosi, Z Jakus, C Sitaru, A Mócsai
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tyrosine kinases are major therapeutic targets in cancer but their role in immune-mediated disease pathogenesis is less understood. <h3>Methods</h3> Here we tested the role of tyrosine kinases and tyro sine kinase substrates in two autoantibody-mediated disease models, the K/BxN serum-transfer arthritis and anti-collagen VII autoantibody-induced blistering skin diseases. <h3>Results</h3> Mice genetically deficient of the Syk tyrosine kinase in the hematopoietic compartment were completely protected from autoantibody-induced arthritis and blistering skin disease. Mice lacking three myeloid-specific tyrosine kinases (Hck, Fgr and Lyn) or the tyrosine kinase substrate PLCγ 2 were also protected from autoantibody-induced diseases. In vitro, Src-family kinases were required for Syk activation by immune complexes and both were further required for activation of PLCγ 2. The Src-family–Syk–PLCγ 2 pathway mediated cytokine production by myeloid cells but not neutrophil or monocyte migration per se. Lineage-specific analyses revealed that during autoantibody-induced arhritis, this signalling pathway was required in myeloid cells (particular neutrophils) but not in mast cells or platelets. Finally, Src-family kinases were also required for activation of myeloid cells by monosodium urite crystals and their deficiency attenuated monosdium urate crystal-induced arthritis, indicating that the role of this signalling pathway is not restricted to autoantibody-mediated disease processes. <h3>Conclusions</h3> Taken together, the Src-family–Syk–PLCγ 2 pathway is an important component of both autoantibody-mediated and autoantibody-independent inflammatory disease processes.
Unilateral periorbital oedema due to sarcoid infiltration of the eyelid: an unusual presentation of sarcoidosis with facial nerve palsy and parotid gland enlargement
Authors: M. Yaosaka, R. Abe, H. Ujiie, Y. Abe, H. Shimizu
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Causes of unilateral eyelid swelling include cellulitis, angio‐oedema, granulomatous blepharitis and malignant lymphoma. However, cases of sarcoidosis that present with unilateral eyelid swelling are rare. We report a patient with sarcoidosis who had a remarkable, unilateral eyelid swelling. Interestingly, the patient also had facial nerve palsy in the first branches of the right trigeminal nerve resulting facial weakness, in just the same area as the skin involvement. A 54‐year‐old man was initially seen with a 5‐month history of persistent and asymptomatic eruptions on his right eyelid with low‐grade fever and malaise. Physical examination revealed remarkable swelling on the right eyelid with a brown‐coloured erythema but without heat, tenderness or pruritus (Fig. 1a). Wrinkling around the right side of the forehead was indistinct. In addition, he had a right parotid gland swelling. The initial clinical diagnosis was granulomatous blepharitis. Histopathological examination of his upper right eyelid showed numerous noncaseating granulomas in the dermis, composed of epithelioid cells with a few scattered lymphocytes and histiocytes surrounding the granulomas (Fig. 2a, b).
Disturbed Eating Behavior and Omission of Insulin in Adolescents Receiving Intensified Insulin Treatment
Authors: Line Wisting, Dag Helge Frøisland, Torild Skrivarhaug, Knut Dahl-Jørgensen, Øyvind Rø
Journal: Diabetes Care (2013)

To establish the prevalence of disturbed eating behavior (DEB) and insulin omission among adolescents with type 1 diabetes using intensive insulin treatment in a nationwide population-based study.The Diabetes Eating Problem Survey-Revised (DEPS-R) is a diabetes-specific screening tool for DEB. Clinical data and HbA1c were obtained from the Norwegian Childhood Diabetes Registry.A total of 770 children and adolescents 11-19 years of age with type 1 diabetes completed the DEPS-R. A total of 27.7% of the females and 8.6% of the males scored above the DEPS-R cutoff. Participants scoring above the cutoff had significantly higher HbA1c (9.2% [77 mmol/mol]; SD, 1.6) than participants scoring below the cutoff (8.4% [68 mmol/mol]; SD, 1.3; P < 0.001). The prevalence of DEB increased significantly with age and weight, from 7.2% in the underweight group to 32.7% in the obese group, and from 8.1% in the youngest age-group (11-13 years) to 38.1% in the oldest age-group (17-19 years). A total of 31.6% of the participants reported insulin restriction and 6.9% reported insulin omission after overeating. Patients reporting insulin restriction had significantly higher HbA1c (9.0% [75 mmol/mol]; SD, 1.7) than nonrestrictors (8.3% [67 mmol/mol]; SD, 1.2; P < 0.001).One-fourth of girls with type 1 diabetes scored above the cutoff for DEB and one-third reported skipping their insulin dose entirely at least occasionally after overeating. Both DEB and insulin restriction were associated with poorer metabolic control, which may increase the risk of serious late diabetes complications.
Clinical Lecture on a Case of Gun-Shot Injury of the Chest
Authors: J. E. Erichsen
Journal: BMJ (1867)

I WISH to-day, Gentlemen, to direct your attention to a case of as great interest professionally as it has been socially, and one which involves several questions connected with penetrating wounds of the chest in a very instructive and interesting manner.I mean the case of that unfor- tunate man McDonnell, who was shot in so barbarous and cowardly a manner last Saturday week in the neighbourhood of Bloomsbury.The particulars of this case are, in all probability, tolerably fresh in your re- collection; but I will just remind you of its main features, by reading to you a short abstract of the case, taken from the more copious notes which you will find in the case-book.Edwin McDonnell, aged 23, was admitted into the Hospital a little before two on the morning of September 28th, having been shot in the chest about half an hour before.On admission, he was cold and pale; countenance somewhat anxious; pulse I36, weak and small.On examination by the House-Surgeon, a small circular wound, about one-third of an inch in diameter, was found close by the edge of the sternum, and just below the fifth costal cartilage.The wound was cleanly cut; the edges were very slightly depressed.A second wound was also found at the back of his chest on the same side, somewhat higher than the one in front and further out, being just outside the inferior angle of the scapula.The size of this wound was slightly larger than that in front, and its edges were a little everted.His clothes were found perforated in front, but not behind; and, during their removal, the bullet fell to the ground.It was conical in shape, and about one-third of an inch in diameter.There was no haemorrhage; and, from the condition of the man's clothes, not more than an ounce of blood had escaped externally.He was placed on the injured side, and covered with blankets.Mr. Heath (who was summoned in the absence of Mr. Erichsen) in- serted a probe into the anterior wound, to ascertain that the track of the ball was not subcutaneous.Soon afterwards, some air was seen to bubble out of the wound.The patient complained of pain on movement and on drawing his breath.There was no cough, nor expectoration.The injured side was resonant on percussion; the breath-sounds were weak.
Permanent Cardiac Pacing in Children: Choosing the Optimal Pacing Site
Authors: Jan Janoušek, Irene E. van Geldorp, Sylvia Krupičková, Eric Rosenthal, Kelly Nugent, Maren Tomaske, Andreas Früh, Jan Elders, Anita Hiippala, Gunter Kerst, Roman A. Gebauer, Peter Kubuš, Patrick Frias, Fulvio Gabbarini, Sally-Ann Clur, Bert Nagel, Javier Ganame, John Papagiannis, Jan Marek, Svjetlana Tisma-Dupanovic, Sabrina Tsao, Jan-Hendrik Nürnberg, Christopher Wren, Mark Friedberg, Maxime de Guillebon, Julia Volaufova, Frits W. Prinzen, Tammo Delhaas
Journal: Circulation (2012)

Background— We evaluated the effects of the site of ventricular pacing on left ventricular (LV) synchrony and function in children requiring permanent pacing. Methods and Results— One hundred seventy-eight children (aged &lt;18 years) from 21 centers with atrioventricular block and a structurally normal heart undergoing permanent pacing were studied cross-sectionally. Median age at evaluation was 11.2 (interquartile range, 6.3–15.0) years. Median pacing duration was 5.4 (interquartile range, 3.1–8.8) years. Pacing sites were the free wall of the right ventricular (RV) outflow tract (n=8), lateral RV (n=44), RV apex (n=61), RV septum (n=29), LV apex (n=12), LV midlateral wall (n=17), and LV base (n=7). LV synchrony, pump function, and contraction efficiency were significantly affected by pacing site and were superior in children paced at the LV apex/LV midlateral wall. LV dyssynchrony correlated inversely with LV ejection fraction ( R =0.80, P =0.031). Pacing from the RV outflow tract/lateral RV predicted significantly decreased LV function (LV ejection fraction &lt;45%; odds ratio, 10.72; confidence interval, 2.07–55.60; P =0.005), whereas LV apex/LV midlateral wall pacing was associated with preserved LV function (LV ejection fraction ≥55%; odds ratio, 8.26; confidence interval, 1.46–47.62; P =0.018). Presence of maternal autoantibodies, gender, age at implantation, duration of pacing, DDD mode, and QRS duration had no significant impact on LV ejection fraction. Conclusions— The site of ventricular pacing has a major impact on LV mechanical synchrony, efficiency, and pump function in children who require lifelong pacing. Of the sites studied, LV apex/LV midlateral wall pacing has the greatest potential to prevent pacing-induced reduction of cardiac pump function.
Karyotypic patterns and their clinical significance in polycythemia vera
Authors: J. R. Testa, J. R. Kanofsky, J. D. Rowley, J. M. Baron, J. W. Vardiman
Journal: American Journal of Hematology (1981)

We studied a series of 34 polycythemia vera (PV) patients to determine the incidence of chromosome abnormalities and their relationship to leukemic transformation. Metaphase chromosomes from bone marrow or unstimulated peripheral blood were examined with conventional stain and, in 20 patients, also with banding techniques. The overall incidence of clonal abnormalities in first samples was 44% (15 of 34 patients), with a higher incidence in patients who had received prior therapy. The most frequent abnormalities were long-arm deletion of No. 5 (5q-; four patients), gain of all or most of a No. 8 (five patients), gain of all or most of a No. 9 (four patients), and long-arm deletion of No. 20 (three patients); these sometimes occurred in combination. Some of the PV patients who had cytogenetic abnormalities early in the disease have had long survivals without developing leukemia. For example, one patient has been 48,XX,+8,+9 in sequential samples obtained over the last 15 years. Five patients developed acute myeloblastic leukemia (AML); each had a complex chromosomal pattern. Two of these five patients were cytogenetically normal during the polycythemic phase; the change in karyotype occurred with the leukemic transformation. Three AML patients were studied only in the leukemic phase. Three AML patients had a 5q-, and a fourth showed loss of a B-group chromosome. Evolutionary changes in the karyotype during the disease course and the occurrence of a 5q- appear to be associated with a terminal phase of PV.