tbuckley/cabot-search huggingface dataset:
Direct Transcriptional Reprogramming of Adult Cells to Embryonic Nephron Progenitors
Authors: Caroline E. Hendry, Jessica M. Vanslambrouck, Jessica Ineson, Norseha Suhaimi, Minoru Takasato, Fiona Rae, Melissa H. Little
Journal: Journal of the American Society of Nephrology (2013)

Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population of the embryonic kidney gives rise to all cells within the nephron other than the collecting duct through a mesenchyme-to-epithelial transition, but this population is exhausted around the time of birth. Here, we sought to identify the conditions under which adult proximal tubule cells could be directly transcriptionally reprogrammed to nephron progenitors. Using a combinatorial screen for lineage-instructive transcription factors, we identified a pool of six genes (SIX1, SIX2, OSR1, EYA1, HOXA11, and SNAI2) that activated a network of genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule (HK2) cell line. Consistent with these reprogrammed cells being nephron progenitors, we observed differential contribution of the reprogrammed population into the Six2(+) nephron progenitor fields of an embryonic kidney explant. Dereplication of the pool suggested that SNAI2 can suppress E-CADHERIN, presumably assisting in the epithelial-to-mesenchymal transition (EMT) required to form nephron progenitors. However, neither TGFβ-induced EMT nor SNAI2 overexpression alone was sufficient to create this phenotype, suggesting that additional factors are required. In conclusion, these results suggest that reinitiation of kidney development from a population of adult cells by generating embryonic progenitors may be feasible, opening the way for additional cellular and bioengineering approaches to renal repair and regeneration.
Breast Implants and Connective-Tissue Disease
Authors: Jorge Litvak
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The article by Dr Hennekens and colleagues<sup>1</sup>is certainly a significant contribution to the controversial data on the association between breast implants and connectivetissue disease. The authors recognize that further research is still necessary before firm conclusions can be drawn, particularly because they targeted classic connective-tissue diseases and did not assess the occurrence of atypical connectivetissue disease causing symptoms that are common to many women with implants.<sup>2</sup> However, the purpose of this letter is not directly related to the results of this excellently designed retrospective cohort study, but to an ethical question that puzzled me after reading the sources of funding of the study. While research funding from private industry is to be commended, in this particular case, financial support was received from Dow Corning, one of the manufacturers of silicone breast implants. This company has been in litigation regularly in the last few years as defendants in
Trichothiodystrophy without associated neuroectodermal defects
Authors: None Peter, None Tomczok, None Hoting, None Behrendt
Journal: British Journal of Dermatology (1998)

Trichothiodystrophy leading to generalized trichorrhexis nodosa‐like hair changes with abnormal hair breakage is described in a 4‐year‐old girl. A marked deficiency of sulphur and the sulphur‐containing amino acid, cystine, was detected in the biochemical analysis of the hair. Further investigation of the hair showed the morphological criteria of trichothiodystrophy. Commonly related symptoms, such as mental retardation, ichthyosis and increased sensitivity to sunlight, were not present in our patient.
Health and Human Values: A Guide to Making Your Own Decisions
Authors: Mary-Carroll Sullivan
Journal: JAMA (1983)

With a modest disclaimer at the outset that their volume neither aspires to nor pretends to be an all-encompassing textbook of medical ethics, Harron, Burnside, and Beauchamp set out to produce what must be regarded as the model handbook of medical ethics. The authors have selected specific areas of ethical concern for physicians and other clinical practitioners: areas involving life's beginning and end and the area of individuals' rights of access to societally regulated health care. The volume begins with an introduction to moral theory that sets the groundwork for the kind of analysis that follows. Methods of ethical analysis differ from the rigorous scientific method in which most clinicians are educated. The data and conclusions are not always or even necessarily objective, verifiable, and reproducible. Indeed, often the "stuff" of ethical dilemmas is subjective and does not reproduce itself even in other, nearly identical, situations. Therefore, the chapter that
Metastatic potential severely altered by changes in tumor cell adhesiveness and cell-surface sialylation.
Authors: M Fogel, P Altevogt, V Schirrmacher
Journal: The Journal of Experimental Medicine (1983)

A plastic adherent variant line (ESb-M) of a highly invasive and metastatic murine T cell lymphoma (ESb) was found to have lost its metastatic potential while still being tumorigenic in normal syngeneic hosts. The variant retained most of its ESb-derived antigenic and biochemical characteristics but differed at binding sites for certain lectins with specificity for terminal N-acetylgalactosamine residues. Whereas such sites were masked by sialic acid on metastatic ESb cells, they became unmasked on the adherent variant line. Metastatic revertants of ESb-M cells did not express the respective lectin receptor sites because these were again masked by sialic acid. It is suggested that the masking of specific lectin receptors sites on the tumor cell surface is of crucial importance for metastatis. If freely exposed, these sites may change adherence characteristics of the cells possibly not only in vitro (to plastic) but also in vivo.
Comparison of Short-term Outcomes in Laparoscopic vs Open Hepatectomy
Authors: Cara Franken, Briana Lau, Krishna Putchakayala, L. Andrew DiFronzo
Journal: JAMA Surgery (2014)

Despite the increasing role of laparoscopy in partial hepatic resection, its short-term benefit compared with traditional open surgery remains unclear.To compare short-term (30-day) outcomes between laparoscopic (LH) and open (OH) partial hepatectomies.Retrospective matched case-control study from April 1, 2004, to March 31, 2013, in a tertiary hepatobiliary referral center. Patients who underwent partial hepatic resection (OH or LH) for benign or malignant disease were matched first by extent of resection, then by pathological diagnosis, and finally by age and sex to the extent possible.Partial hepatectomy for liver disease.Thirty-day morbidity and mortality rates.After the matching process, we included 104 patients (52 undergoing LH and 52 undergoing OH) in the study. Patients were evenly matched with respect to age, sex, extent of resection, and diagnosis. Cirrhosis was present in 17 patients (33%) in each group. We found no difference in positive margin status (1 patient [2%] for LH vs 2 patients [4%] for OH; P > .99). Although the estimated blood loss differed significantly between groups (237 mL for LH vs 387 mL for OH; P = .049), we found no difference in the rate of perioperative blood transfusion (1 patient [2%] for LH vs 5 [10%] for OH; P = .20). Operative time (219 minutes for LH vs 198 minutes for OH; P = .16), hospital length of stay (5 days for LH vs 6 days for OH; P = .13), and readmission rate (4 patients [8%] for LH vs 5 [10%] for OH; P = .70) were similar in both groups. The rates of major complications (4 patients [8%] for LH vs 4 patients [8%] for OH; P = 10), overall 30-day morbidity (22 patients [42%] for LH vs 19 [37%] for OH; P = .70), and 30-day mortality (1 patient [2%] for LH vs 2 [4%] for OH; P > .99) were not significantly different.Patients who undergo LH have similar short-term outcomes when compared with those who undergo OH. Laparoscopic hepatectomy was associated with lower intraoperative blood loss, although the clinical significance of this finding is uncertain given the lack of difference in perioperative transfusion or morbidity rates. In addition, we found no difference in margin status between the 2 groups. Future studies are needed to define which patients derive benefit from LH and to determine oncologic equivalence to OH.
Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma
Authors: Roberta Rizzo, Cristina E. Mapp, Loredana Melchiorri, Piero Maestrelli, Annalisa Visentin, Stefano Ferretti, Ilaria Bononi, Deborah Miotto, Olavio R. Baricordi
Journal: Journal of Allergy and Clinical Immunology (2005)
TCT-526 A New Scoring System for Predicting Wound Healing in Critical Limb Ischemia with Tissue Loss following Endovascular Therapy
Authors: Norihiro Kobayashi, Toshiya Muramatsu, Reiko Tsukahara, Yoshiaki Ito, Hiroshi Ishimori, Keisuke Hirano, Masatsugu Nakano
Journal: Journal of the American College of Cardiology (2013)
Factors influencing death at home in terminally ill patients with cancer: systematic review
Authors: Barbara Gomes, Irene J Higginson
Journal: BMJ (2006)

To determine the relative influence of different factors on place of death in patients with cancer.Four electronic databases-Medline (1966-2004), PsycINFO (1972-2004), CINAHL (1982-2004), and ASSIA (1987-2004); previous contacts with key experts; hand search of six relevant journals.We generated a conceptual model, against which studies were analysed. Included studies had original data on risk factors for place of death among patients, > 80% of whom had cancer. Strength of evidence was assigned according to the quantity and quality of studies and consistency of findings. Odds ratios for home death were plotted for factors with high strength evidence.58 studies were included, with over 1.5 million patients from 13 countries. There was high strength evidence for the effect of 17 factors on place of death, of which six were strongly associated with home death: patients' low functional status (odds ratios range 2.29-11.1), their preferences (2.19-8.38), home care (1.37-5.1) and its intensity (1.06-8.65), living with relatives (1.78-7.85), and extended family support (2.28-5.47). The risk factors covered all groups of the model: related to illness, the individual, and the environment (healthcare input and social support), the latter found to be the most important.The ne of factors that influence where patients with cancer die is complicated. Future policies and clinical practice should focus on ways of empowering families and public education, as well as intensifying home care, risk assessment, and training practitioners in end of life care.
COEXISTING ACTIVE SYPHILIS OF THE LARYNX WITH ACTIVE PULMONARY TUBERCULOSIS
Authors: David Louis Engelsher
Journal: JAMA (1927)

<h3>History.</h3> —F. R., a man, aged 55, single, born in Germany and twenty-three years in the United States, came to the medical clinic, May 29, 1925. His occupation for the past few years was that of a clothing cutter, before which he had been a butcher, commencing that pursuit when a boy. He had had a hard chancre twenty-five years before, for which he was treated intermittently. The Wassermann reaction had been negative twice and positive once. Twenty years before admission the patient acquired a gonorrheal urethritis, from which he recovered in four weeks. Nineteen years before admission he had an acute purulent otitis of the left ear, and the recovery was uneventful in about six weeks. Five years before admission he had a skin syphilid, proved by a positive Wassermann blood test at the time. For years the patient had had a slight cough and stated that a
Folate Deficiency after Anticonvulsant Drugs: An Effect of Hepatic Enzyme Induction?
Authors: J. D. Maxwell, J. Hunter, D. A. Stewart, S. Ardeman, R. Williams
Journal: BMJ (1972)

Serum and red cell folate levels were reduced in 59% and 58% respectively of 75 children with epilepsy attending a residential school. The degree of folate deficiency was significantly related to increased hepatic microsomal enzyme activity, assessed from increased urinary excretion of D-glucaric acid and also correlated with the daily dose of anticonvulsant taken. Anticonvulsant drugs are known to have inducing properties, and since folate is required as a cofactor in drug hydroxylations it is suggested that folate depletion results from increased demand for the cofactor after induction of drug-metabolizing enzymes. As folate deficiency may ultimately limit drug metabolism this hypothesis would explain why blood phenytoin levels decrease and fit control may worsen after correction of folate deficiency in epileptic patients.
Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirus-associated nephropathy
Authors: Christopher K. Buehrig, Donna J. Lager, Mark D. Stegall, Michelle A. Kreps, Walter K. Kremers, James M. Gloor, Thomas R. Schwab, Jorge A. Velosa, Mary E. Fidler, Timothy S. Larson, Matthew D. Griffin
Journal: Kidney International (2003)
Increased bone marrow delta‐aminolevulinic acid synthetase activity in the acute reversible sideroblastic anemia of alcoholics
Authors: M. B. Fraser, B. A. Schacter
Journal: American Journal of Hematology (1980)

Abstract In an effort to clarify the biochemical pathogenesis of the acute reversible siderblastic anemia of alcoholics, bone marrow delta‐aminolevulinic acid (ALA) synthetase activity was measured in anemic alcoholic patients with and without pathological ring sideroblasts in their marrows and compared with the activity of this enzyme in normal subjects and in patients with idiopathic sideroblastic anemia. Mean ALA‐synthetase activity measured (following addition of exogenous pyridoxal phosphate in three patients with the ring sideroblast morphologic abnormality) was 502 ± 147 (SE) pmoles ALA per 10 6 erythroblasts per 30 minutes, as compared with 201 ± 69 in the seven alcoholic patients without pathologic sideroblastic marrow abnormalities, 169 ± 32 in the six normal subjects, and 52 ± 4 pmoles ALA per 10 6 erythroblasts per 30 minutes in two patients with idiopathic sideroblastic anemia. Comparison of enzyme activity in the presence and absence of pyridoxal phosphate revealed that addition of this enzyme cofactor accentuated ALA‐synthetase activity by an average of only 24% in the alcoholic sideroblastic group, as compared with 42% accentuation in the normal group and 8% accentuation in the idiopathic sideroblastic group. These results suggest that abnormalities in pyridoxal phosphate metabolism in alcoholics may not be of importance in the inhibition of heme biosynthesis at the level of ALA synthetase but, rather, that an enzymatic or metabolic block should be sought at a more distal site in the heme biosynthetic pathway.
THE SERUM DIAGNOSIS OF TUBERCULOSIS.
Authors: L. M. LOEB
Journal: JAMA (1903)

(From the Pathological Laboratory of Rush Medical College,) In numerous journals at short intervals beginning in April, 1898, the Lyonese observers, Arloing and Courmont, have announced the discovery of a means for the diagnosis of early tuberculosis more certain and less harmful than any hitherto known. This naturally attracted great attention at once, although on account of the many difficulties in experimentation and control of results relatively few repeated the original measures. Many means and ways for the diagnosis of incipient tuberculosis have been suggested of late years, but all of them are either harmful or insufficient. By "incipient" tuberculosis is meant that period of the disease in which Koch's bacillus can not be clinically detected in the lesion it produces or in the products thereof. A few of the methods devised, with the objections to them, are the following: 1. The tuberculin test and its modifications by Koch and
Definitions and Methodology for the Grayscale and Radiofrequency Intravascular Ultrasound and Coronary Angiographic Analyses
Authors: Akiko Maehara, Ecaterina Cristea, Gary S. Mintz, Alexandra J. Lansky, Ovidiu Dressler, Sinan Biro, Barry Templin, Renu Virmani, Bernard de Bruyne, Patrick W. Serruys, Gregg W. Stone
Journal: JACC. Cardiovascular imaging (2012)
Abstract 3392: Thromboxane-A2 receptor β-isoform regulates the activity of the tumor suppressor FOXO3 via phosphorylation by ERK in urothelial cancer
Authors: Philip M. Sobolesky, Perry V. Halushka, Elizabeth Garrett-Mayer, Omar Moussa
Journal: Cancer Research (2014)

Abstract The tumor suppressor FOXO3 is a transcription factor whose activity and stability are regulated by phosphorylation on S294 via extracellular regulated kinases (ERK1/2). Previous data by our group has demonstrated overexpressing the thromboxane A2 isoform-β receptor (TPβ) increased ERK activation and induced malignant transformation of immortalized bladder cells. These data describe a novel mechanism of TPβ mediated regulation of FOXO3 via phosphorylation by ERK. Immunohistochemical studies revealed increased expression of nuclear pFOXO3-S294 in late stage bladder tumors, whereas total FOXO3 nuclear expression was reduced in high grade tumors. Both cytoplasmic and nuclear pFOXO3-S294 staining scores positively correlated with TPβ staining scores. Overexpressing TPβ in non-transformed urothelial cell lines, UROsta and SV-HUC, induced phosphorylation of FOXO3 at -S294. Knockdown of FOXO3 expression by shRNA increased cell migration and invasion. Conversely, overexpression of mutated FOXO3 that is resistant to ERK phosphorylation reduced the overall and TP agonist (U46619) mediated increase in malignant UMUC3 cell migration and invasion. Stimulation of UMUC3 cells with U46619 increased pFOXO3-S294 expression which could be attenuated with TP antagonist (PTXA2) pre-treatment. A dual luciferase assay demonstrated that U46619 stimulation decreased overall FOXO3 transcriptional activity. Additionally, U46619 stimulation initially caused nuclear accumulation of pFOXO3-S294, but prolonged stimulation increased FOXO3 cytoplasmic localization. In summary, the data describe a novel mechanism of TPβ signaling in bladder cancer that results in the ERK mediated regulation of FOXO3 activity, which could contribute to tumor progression. Citation Format: Philip M. Sobolesky, Perry V. Halushka, Elizabeth Garrett-Mayer, Omar Moussa. Thromboxane-A2 receptor β-isoform regulates the activity of the tumor suppressor FOXO3 via phosphorylation by ERK in urothelial cancer. [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 3392. doi:10.1158/1538-7445.AM2014-3392
Abstract LB-247: mTORC1 enhances bortezomib-induced death in TSC-null cells by a c-MYC-dependent induction of the unfolded protein response
Authors: Justin T. Babcock, Hoa B. Nguen, Yujun He, Ronald C. Wek, Lawrence A. Quilliam
Journal: Cancer Research (2012)

Abstract The ability of the proteasome inhibitor bortezomib to induce apoptosis of cancer cells is influenced by a variety of signaling pathways. We have found that control of c-MYC expression by the mammalian target of rapamycin complex-1 (mTORC1) plays a key role in determining drug sensitivity. Bortezomib treatment of Elt3 (rat TSC2-null leiomyoma) cells, that have high mTORC1 activity, activates the unfolded protein response (UPR) and apoptosis. Both effects were prevented by pretreatment of cells with the mTORC1 inhibitor, rapamycin, indicating mTORC1 dependence. Bortezomib also induced c-MYC expression in Elt3 cells in an mTORC1-dependent manner. c-MYC bound to the promoters of the UPR-induced transcription factors ATF4 and CHOP during bortezomib treatment. These data suggest direct involvement of an mTORC1/c-MYC-driven signaling pathway in the activation of the UPR. Consistent with this notion, overexpression of c-MYC in the presence of rapamycin was sufficient to rescue bortezomib induced CHOP and ATF4 expression, as well as apoptosis. These findings demonstrate that the induction ATF4/CHOP expression by mTORC1 via regulation of c-MYC is a major determinant in the ability of bortezomib to induce apoptosis of tumor cells. Since hypoxia and low nutrient levels in poorly vascularized tumors may contribute to down regulation of mTORC1, our data may help explain some of the difficulties in treating solid tumors with bortezomib and caution against the use of rapamycin in combination with proteasome inhibitors in cancer treatment. 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 LB-247. doi:1538-7445.AM2012-LB-247
Internal Arteriovenous Fistulae for Home Dialysis
Authors: Joel Chinitz
Journal: JAMA (1969)

In our home hemodialysis training program, we have tained family members of ten patients to perform venipunctures in arterialized veins of subcutaneous fistulae. Fistula venipuncture training time has not prolonged the total dialysis training period. No fistula has required surgical revision. Our current fistulae dialysis experience at home totals 56 patient months and 604 dialyses. The fistula venipuncture complication rate at home during this period has involved less than 1.5% of all venipunctures. Both the staff and the patients in our hemodialysis unit prefer the subcutaneous arteriovenous fistula to standard arteriovenous shunts.
Involvement of CD95/Apo1/Fas in Cell Death After Myocardial Ischemia
Authors: I. Jeremias, C. Kupatt, A. Martin-Villalba, H. Habazettl, J. Schenkel, P. Boekstegers, K. M. Debatin
Journal: Circulation (2000)

Background —The death of cardiac cells during ischemia and reperfusion is partially mediated by apoptosis, as seen, eg, in autopsy material of patients after acute myocardial infarction. Methods and Results —To study the role of CD95/Fas/Apo1 for induction of postischemic cell death, we used an ischemia/reperfusion model of isolated rat and mouse hearts in Langendorff perfusion. In this model, caspase-dependent apoptosis occurred during postischemic reperfusion. Moreover, soluble CD95 ligand/Fas ligand was released by the postischemic hearts early after the onset of reperfusion. In addition, this ligand was synthesized de novo under these circumstances. Similar findings were observed for other “death-inducing” ligands, such as tumor necrosis factor (TNF)-α and TNF-related apoptosis-inducing ligand. In primary adult rat myocyte culture, hypoxia and reoxygenation caused a marked increase in sensitivity to the apoptotic effects of CD95 ligand. Isolated hearts from mice lacking functional CD95 ( lpr ) display marked reduction in cell death after ischemia and reperfusion compared with wild-type controls. Conclusions —These data suggest that CD95/Apo1/Fas is directly involved in cell death after myocardial ischemia. The CD95 system might thus represent a novel target for therapeutic prevention of postischemic cell death in the heart.
Study shows what INR level is best for preventing stroke in patients with atrial fibrillation
Authors: J. H. Tanne
Journal: BMJ (2003)

Patients with atrial fibrillation who took warfarin in dosages to maintain an international normalised ratio (INR) in the recommended range had fewer ischaemic strokes, less severe strokes, and were less likely to die than patients who took lower doses of warfarin or who took aspirin or no treatment, reports a large study in the New England Journal of Medicine ( 2003; 349: 1019-26).

Atrial fibrillation can lead to the formation of clots that travel to the brain. It causes 80 000 strokes in the United States each …