tbuckley/cabot-search huggingface dataset:
Antimicrobial Therapy of Vitamin B_6-Dependent Streptococcal Endocarditis
Authors: ROBERTA B. CAREY
Journal: Annals of Internal Medicine (1977)

Vitamin B6-dependent viridans streptococci were isolated from two patients with microbial endocarditis. Because of their unique requirement for pyridoxal hydrochloride, these organisms did not grow normally in the media usually used in diagnostic laboratories. When tested in supplemented media, both strains were resistant to penicillin G and relatively sensitive to streptomycin. Penicillin-streptomycin synergy was demonstrated in vitro as well as in experimental endocarditis. These laboratory findings confirmed the clinical observation in these two patients that penicillin-streptomycin therapy should be used in vitamin B6-dependent streptococcal endocarditis. Nutritionally variant streptococci may be important pathogens in microbial endocarditis and must be considered in patients with suggestive clinical findings but negative blood cultures.
Music Therapy: An Art Beyond Words
Authors: A. Storr
Journal: BMJ (1994)

Leslie Bunt Routledge, pounds sterling 14.99, pp 213 ISBN 0-415-08703-1

Music therapy is both very old and very new. Five hundred years before Christ, the followers of Pythagoras developed a science of musical psychotherapy. A daily programme of songs and pieces for the lyre made them feel bright and energetic on rising, and another set of pieces relieved them of the cares of the day and prepared them for agreeable dreams when they retired to sleep.

Plato believed that musical training was a more potent instrument than any other, …
Development is also experienced by a personal self who is shaped by culture
Authors: Michel Ferrari
Journal: Behavioral and Brain Sciences (2002)

I agree with Thomas &amp; Karmiloff-Smith (T&amp;K-S) in their critique of Residual Normality. However, first-person data must be integrated into their account of neurobiological development of disabilities. Furthermore, psychological development itself is not only about an individual’ brain and how it interacts with the world; rather, development depends crucially on the sociocultural context in which (normal and abnormal) children develop.
Smad4 Regulates Claudin-1 Expression in a Transforming Growth Factor-β–Independent Manner in Colon Cancer Cells
Authors: Sheng-Ru Shiou, Amar B. Singh, Krishnan Moorthy, Pran K. Datta, M. Kay Washington, R. Daniel Beauchamp, Punita Dhawan
Journal: Cancer Research (2007)

Abstract We have recently reported that the expression of a tight junction protein, claudin-1, is increased during colon carcinogenesis and particularly metastatic colorectal cancer. Manipulation of claudin-1 levels in colon cancer cells showed a positive correlation between claudin-1 expression and tumor growth and metastasis. However, the mechanisms underlying the increased claudin-1 expression in colorectal cancer remains unknown. The tumor suppressor Smad4 is a central intracellular signal transduction component of the transforming growth factor-β (TGF-β) family of cytokines. Loss of Smad4 protein expression is correlated with poor prognosis and is frequently observed in invasive and metastatic colorectal carcinoma. In the present study, we report an inverse relationship between Smad4 and claudin-1 expression in human colorectal carcinoma tumor samples and in human colon cancer cell lines. We found that the expression of Smad4 in Smad4-deficient but claudin-1–positive SW480 or HT29 colon cancer cell lines down-regulates claudin-1 expression through transcriptional repression by modulating β-catenin/T-cell factor/lymphocyte enhancer factor activity. Furthermore, this Smad4-dependent inhibition of claudin-1 expression is independent of TGF-β signaling because Smad4 expression alone is insufficient to restore TGF-β signaling in the SW480 cells, and the selective TGF-β receptor kinase inhibitor LY364947 did not prevent the Smad4 suppression of claudin-1 protein expression in either SW480 or HT29 cells. Taken together, these findings suggest a novel mechanism underlying Smad4 tumor–suppressive function through regulation of a potential metastatic modulator, claudin-1, in a TGF-β–independent manner. [Cancer Res 2007;67(4):1571–9]
Abstract 1933: Visfatin promotes malignant breast cancer behavior through activation of STAT3.
Authors: Shyng-Shiou F. Yuan, Yun-Ju Chen, Yi-Chen Lee, Ming-Feng Hou
Journal: Cancer Research (2013)

Abstract Background. Obesity-associated adipocyte dysfunction and adipocytokine imbalance has become a major focus in breast cancer research. In this study, the role of circulating visfatin, a recently discovered adipocytokine, in breast cancer was explored. Methods. Serum visfatin was analyzed by enzyme-linked immunosorbent assay and correlated with clinicopathological characteristics and survival, while the expression of phosphorylated and activated STAT3 in breast cancer tissue was analyzed by immunohistochemistry. The biologic activity of visfatin as well as the underlying mechanisms was analyzed by using XTT cell proliferation assay, flow cytometry and immunoblotting analysis in human breast cancer cells. Results. Serum visfatin was substantially elevated in breast cancer patients. It was positively associated with tumor stage and lymph node metastasis, but negatively associated with estrogen receptor (ER) and progesterone receptor (PR) status. Breast cancer patients with high serum visfatin, especially in combination with ER− and PR− status, had a poor patient survival. On the other hand, patients with high serum visfatin had a lower incidence of disease recurrence and a better patient survival after adjuvant hormone therapy. Serum visfatin was positively associated with STAT3 tyrosine phosphorylation in breast cancer tissues. In agreement with the clinical observation, visfatin treatment in breast cancer cells activated JAK1 and SRC as well as their downstream molecule STAT3, followed by an enhanced G1/S progression and cell proliferation. Conclusion. Serum visfatin, through activation of STAT3, leads to a malignant cancer behavior and poor survival in breast cancer patients. Key words: visfatin, adipocytokine, breast cancer, STAT3 Citation Format: Shyng-Shiou F. Yuan, Yun-Ju Chen, Yi-Chen Lee, Ming-Feng Hou. Visfatin promotes malignant breast cancer behavior through activation of STAT3. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1933. doi:10.1158/1538-7445.AM2013-1933 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1545: Education of macrophages through modulation of NF-kappaB: an opportunity for targeted therapy.
Authors: Whitney Barham, Oleg Tikhomirov, Lianyi Chen, Ryan Ortega, Linda Gleaves, Halina Onishko, Taylor Sherrill, Linda Connelly, Timothy S. Blackwell, Fiona E. Yull
Journal: Cancer Research (2013)

Abstract Macrophages are a plastic cell type, capable of adapting to numerous signals within their environment. As part of the innate immune system, macrophages were traditionally considered anti-tumor (M1), but it has been well established that macrophages can also help to create a pro-tumor, pro-metastatic tumor niche (M2). NF-κB transcription factors can regulate both pro- (MMP's, VEGF) and anti-tumor (iNOS) downstream targets within macrophages, suggesting that modulation of NF-κB may play a role in the two different macrophage phenotypes. However, our understanding of NF-κB signaling specifically within macrophages during tumor progression is limited. To this end, we have developed murine transgenic models that enable us to induce expression of an activator or dominant inhibitor of NF-κB in macrophages by adding doxycycline to the drinking water of mice. We have combined these novel transgenics with the polyoma model of mammary cancer for our studies. We have recently shown that activation of NF-κB in macrophages significantly limits metastasis in a tail vein model of tumor progression. In this model, constitutive IKK2 activity within macrophages leads to an anti-tumor immune response including altered immune cell populations within the lung microenvironment, changes in chemokine and cytokine expression and rapid killing of tumor cells during the seeding phase mediated by reactive oxygen species. Our current work has extended these findings to an orthotopic mammary tumor model. Again, we find that activation of NF-κB in macrophages results in decreased primary tumor growth and decreased tumor seeding into the blood. To model this activation in vitro, we have utilized immortalized bone marrow derived macrophages from IκBα knock-out mice compared to a wild type line. IκBα KO macrophages display changes in morphology and adhesion relative to wild type macrophages. This correlates with increased cytotoxic behavior in co-culture with polyoma tumor cells, mirroring the in vivo phenotype of the cIKK2 expressing macrophages. Given these findings, we believe that targeted activation of NF-κB signaling in macrophages could be harnessed to overcome the education of macrophages by tumor cells, and could be exploited as a novel targeted therapy. Citation Format: Whitney Barham, Oleg Tikhomirov, Lianyi Chen, Ryan Ortega, Linda Gleaves, Halina Onishko, Taylor Sherrill, Linda Connelly, Timothy S. Blackwell, Fiona E. Yull. Education of macrophages through modulation of NF-kappaB: an opportunity for targeted therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1545. doi:10.1158/1538-7445.AM2013-1545
NEUTRALIZATION OF THE AGENT CAUSING LEUKOSIS AND SARCOMA OF FOWLS BY RABBIT ANTISERA
Authors: Elvin A. Kabat, Jacob Furth
Journal: The Journal of Experimental Medicine (1941)

Neutralizing antibodies against fowl tumor agents can be produced in rabbits by injection of heavy materials obtained from chicken tumor. Similar sediments from normal chicken spleen produce no neutralizing antibodies. The complement-fixing antibodies produced by both materials are unrelated to the neutralizing antibodies.
Connexin 30 sets synaptic strength by controlling astroglial synapse invasion
Authors: Ulrike Pannasch, Dominik Freche, Glenn Dallérac, Grégory Ghézali, Carole Escartin, Pascal Ezan, Martine Cohen-Salmon, Karim Benchenane, Veronica Abudara, Amandine Dufour, Joachim H R Lübke, Nicole Déglon, Graham Knott, David Holcman, Nathalie Rouach
Journal: Nature Neuroscience (2014)
Imatinib Mesylate in Treatment of Advanced GIST – Single Institution Experience
Authors: Nikolić Vladimir, Nikolic Neda, Zorica Tomašević, Radosavljevic Davorin, Ristic Marija, Spasic Jelena, Stevanovic Jasna, Nikolic Srdjan, Zegarac Milan
Journal: Annals of Oncology (2014)
Abdur Rashid Choudhury
Authors: R. Choudhury
Journal: BMJ (2010)

Abdur Rashid Choudhury (“Rashid”) was born in Hailakandi, Assam. Coming from a humble background in a remote village, he had to work particularly hard to achieve his goal of becoming a surgeon. After qualifying, he did an MS in general surgery in 1965 and worked in Assam Medical …
Biliary cannulation can be facilitated by pancreatic stent insertion
Authors: J. Addley, R. Mitchell
Journal: Endoscopy (2009)

Biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) remains challenging in 1 %–10 % of cases [1]. A variety of sphincterotomes and cannulation techniques have been developed. Complications including pancreatitis remain a significant concern, particularly if repeated instrumentation or pancreatic duct injection or precut techniques are used.
Lung Cancer in Women — Five Years Later, Situation Worse
Authors: Paul D. Stolley
Journal: New England Journal of Medicine (1983)

IN October 1977, Lewis and Lewis presented data in the Journal on the health status of women in the United States. They wondered whether the fuller participation of women in the work force would alter their health, leading them to "die like men" as they increasingly lived like them.1 An accompanying editorial, entitled "Lung Cancer: Unwanted Equality for Women," pointed to the rapidly increasing death rates from lung cancer in women, predicted a continued rise in these rates if trends in smoking patterns in women persisted, and advocated more vigorous antismoking efforts, such as a ban on cigarette advertising.2 What . . .
Foreign Particle Embolism in Drug Addicts: Respiratory Pathophysiology
Authors: F. G. DOUGLAS
Journal: Annals of Internal Medicine (1971)

Three of seven intravenous-drug addicts had radiological, pathological, and functional manifestations of pulmonary foreign body emboli and granulomas; three others had abnormal pulmonary function without clinical or radiological evidence of respiratory disease. In the seventh case there was necropsy evidence of foreign body granulomas in the lungs. The first six patients had reduced diffusing capacities, and the three with proved granulomas also had increased elastic recoil of lungs. Thus, the ultimate effect of foreign body embolism on lung function is reduction in diffusion and compliance, presumably caused by the extravascular, interstitial spread of granulomas. Although embolic and granulomatous foreign body disease has not been proved in three cases, their diminished diffusing capacities may be early evidence of its presence. Early detection may prevent progression to chronic respiratory disease.
Grass Pollen Allergoids Coupled to Mannan Are Novel Vaccines with Enhanced Capacity to be Captured By Dendritic Cells Promoting Th1 Immune Responses and High Levels of IL-10
Authors: Oscar Palomares, Sofia Sirvent, Irene Soria, Barbara Cases, Carmen Díez, Pedro Reche, Juan López-Relaño, Eduardo Martínez-Naves, Enrique Fernandez-Caldas, Jose Luis Subiza
Journal: Journal of Allergy and Clinical Immunology (2014)
Pattern of Malformations in the Children of Women Treated with Carbamazepine during Pregnancy
Authors: Kenneth Lyons Jones, Ronald V. Lacro, Kathleen A. Johnson, Jane Adams
Journal: New England Journal of Medicine (1989)

In an attempt to determine whether and to what extent carbamazepine is teratogenic, we evaluated eight children whom we identified retrospectively as having had prenatal exposure to carbamazepine alone or in combination with a variety of anticonvulsants other than phenytoin. In addition, in a prospective study, we documented the outcome of the pregnancies of 72 women who contacted us early in pregnancy because they were concerned about the potential teratogenicity of carbamazepine. A pattern of malformation, the principal features of which are minor craniofacial defects and fingernail hypoplasia, and of developmental delay was identified in the eight children retrospectively ascertained to have been exposed to carbamazepine in utero; this pattern was subsequently confirmed through the evaluation of 48 children born alive to the women in the prospective study. That carbamazepine itself is teratogenic is indicated by the incidence of craniofacial defects (11 percent), fingernail hypoplasia (26 percent), and developmental delay (20 percent) in the 35 live-born children of the women in the prospective study who were exposed prenatally to carbamazepine alone. The similarity between the children exposed prenatally to carbamazepine and those with the fetal hydantoin syndrome is probably related to the fact that both drugs are metabolized through the arene oxide pathway and raises the possibility that it is the epoxide intermediate rather than the specific drug itself that is the teratogenic agent. (N Engl J Med 1989; 320:1661–6.)
Intramuscular scAAV9-SMN Injection Mediates Widespread Gene Delivery to the Spinal Cord and Decreases Disease Severity in SMA Mice
Authors: Sofia Benkhelifa-Ziyyat, Aurore Besse, Marianne Roda, Sandra Duque, Stéphanie Astord, Romain Carcenac, Thibaut Marais, Martine Barkats
Journal: Molecular Therapy (2013)

We have recently demonstrated the remarkable efficiency of self-complementary (sc) AAV9 vectors for central nervous system (CNS) gene transfer following intravenous delivery in mice and larger animals. Here, we investigated whether gene delivery to motor neurons (MNs) could also be achieved via intramuscular (i.m.) scAAV9 injection and subsequent retrograde transport along the MNs axons. Unexpectedly, we found that a single injection of scAAV9 into the adult mouse gastrocnemius (GA) mediated widespread MN transduction along the whole spinal cord, without limitation to the MNs connected to the injected muscle. Spinal cord astrocytes and peripheral organs were also transduced, indicating vector spread from the injected muscle to both the CNS and the periphery through release into the blood circulation. Moreover, we showed that i.m. injection of scAAV9 vectors expressing "survival of motor neuron" (Smn) in spinal muscular atrophy (SMA) mice mediated high survival motor neuron (SMN) expression levels at both the CNS and the periphery, and increased the median lifespan from 12 days to 163 days. These findings represent to date the longest extent in survival obtained in SMA mice following i.m. viral vector gene delivery, and might generate a renewed interest in the use of i.m. adeno-associated viruses (AAV) delivery for the development of gene therapy strategies for MN diseases. We have recently demonstrated the remarkable efficiency of self-complementary (sc) AAV9 vectors for central nervous system (CNS) gene transfer following intravenous delivery in mice and larger animals. Here, we investigated whether gene delivery to motor neurons (MNs) could also be achieved via intramuscular (i.m.) scAAV9 injection and subsequent retrograde transport along the MNs axons. Unexpectedly, we found that a single injection of scAAV9 into the adult mouse gastrocnemius (GA) mediated widespread MN transduction along the whole spinal cord, without limitation to the MNs connected to the injected muscle. Spinal cord astrocytes and peripheral organs were also transduced, indicating vector spread from the injected muscle to both the CNS and the periphery through release into the blood circulation. Moreover, we showed that i.m. injection of scAAV9 vectors expressing "survival of motor neuron" (Smn) in spinal muscular atrophy (SMA) mice mediated high survival motor neuron (SMN) expression levels at both the CNS and the periphery, and increased the median lifespan from 12 days to 163 days. These findings represent to date the longest extent in survival obtained in SMA mice following i.m. viral vector gene delivery, and might generate a renewed interest in the use of i.m. adeno-associated viruses (AAV) delivery for the development of gene therapy strategies for MN diseases.
Community water fluoridation, bone mineral density, and fractures: prospective study of effects in older women
Authors: K. R Phipps
Journal: BMJ (2000)

<h3>Abstract</h3> Clinical trials of SHP2 inhibitors (SHP2i) alone and in various combinations are ongoing for multiple tumors with over-activation of the RAS/ERK pathway. SHP2 plays critical roles in normal cell signaling; hence, SHP2is could influence the tumor microenvironment. We found that SHP2i treatment depleted alveolar and M2-like macrophages and promoted B and T lymphocyte infiltration in <i>Kras</i>- and <i>Egfr</i>-mutant non-small cell lung cancer (NSCLC). However, treatment also increased intratumor gMDSCs via tumor-intrinsic, NF-kB-dependent production of CXCR2 ligands. Other RAS/ERK pathway inhibitors also induced CXCR2 ligands and gMDSC influx in mice, and CXCR2 ligands were induced in tumors from patients on KRAS<sup>G12C</sup>-inhibitor trials. Combined SHP2(SHP099)/CXCR1/2(SX682) inhibition depleted a specific cluster of <i>S100a8/9</i><sup>high</sup> gMDSCs, generated <i>Klrg1</i>+ CD8+ effector T cells with a strong cytotoxic phenotype but expressing the checkpoint receptor NKG2A, and enhanced survival in <i>Kras-</i>and <i>Egfr</i>-mutant models. Our results argue for testing RAS/ERK pathway/CXCR1/2/NKG2A inhibitor combinations in NSCLC patients. <h3>Statement of Significance</h3> Our study shows that inhibiting the SHP2/RAS/ERK pathway triggers NF-kB-dependent up-regulation of CXCR2 ligands and recruitment of S100A8<sup>high</sup> gMDSCs, which suppress T cells in NSCLC. Combining SHP2 and CXCR2 inhibitors blocks this gMDSC immigration, resulting in enhanced Th1 polarization, induction of CD8+ KLRG1+ effector T cells with high cytotoxic activity and improved survival in multiple NSCLC models.
THE POSTPARTUM KIDNEY
Authors: HENRY W. E. WALTHER
Journal: JAMA (1933)

Renal infections complicating pregnancy are receiving an ever increasing degree of attention from both obstetricians and urologists. This unquestionably bespeaks a further reduction in the untoward situations arising out of the parturient state. Until recently, the major portion of care was devoted to the antepartum period, to the neglect of many postpartum sequelae. It can no longer be taken for granted that, following delivery, vigilance can be relaxed. Hospital records attest the fact that postpartum complications still occur and, in fair measure, the urinary tract shares in these unfortunate end results.  Because such cases have come under our observation, in private practice, it was considered that a report might be of interest. We include cases that were unrecognized prior to delivery, cases recognized before delivery but remaining untreated until after parturition, and cases recognized but presenting no complications until after childbirth.  The delay in detecting many of these conditions we
Acute Lymphoblastic Leukemia — On the Wings of IKAROS
Authors: Katia Georgopoulos
Journal: New England Journal of Medicine (2009)

Acute lymphoblastic leukemia (ALL) with an immature B-cell immunophenotype (B-cell–progenitor ALL) is a common cancer in children and adolescents, and it also occurs in adults. Cure rates of B-cell–progenitor ALL among children are very high, but they are not as high among adults. Approximately one fifth of children with B-cell–progenitor ALL have recurring disease, which is difficult to treat. Thus, this form of ALL varies with respect to the potential for relapse and resistance to chemotherapy.It is generally accepted that B-cell–progenitor ALL originates in B-cell–restricted progenitors that have accumulated critical genetic lesions. Cytogenetic studies of B-cell–progenitor ALL have revealed . . .
Investigational Exemption Procedures for New Drugs
Authors: Henry E. Simmons
Journal: JAMA (1970)

To the Editor.—  The QUESTIONS AND ANSWERS section ofThe Journal( 211 :1705, 1970) contained two statements which I fear may mislead some physicians.  They were included in responses by Betty Jane Anderson, of the AMA Law Division, and Dr. Thomas H. Hayes of the AMA Department of Drugs, to a question about nonapproved uses of drugs approved by the Food and Drug Administration.  Miss Anderson, in discussing approval of the FDA to market a drug, said:  Approval simply means that there has been a sufficient number of clinical trials to warrant making the drug available for use by all physicians.  The federal Food, Drug, and Cosmetic Act is much more specific in this regard. It requires adequate testing to demonstrate safety under the uses proposed in the labeling. And with regard to effectiveness, the law requires substantial evidence that the drug will have the effect it purports or is
More cases of polonium-210 contamination are uncovered in London
Authors: Owen Dyer
Journal: BMJ (2007)

The investigation into the death of the former Russian intelligence officer Alexander Litvinenko has uncovered further cases of contamination with the radioactive isotope polonium-210, and police believe that they are now close to identifying the suspected poisoners. But the chances of a criminal prosecution look slim in the face of a refusal from Russia to extradite any suspects named by British police. 

Traces of polonium-210 were last week found at the Pescatori restaurant in Mayfair, while two more people tested positive for contamination with the substance, bringing the total to 12. 

The UK Health Protection Agency, which is advising authorities on technical aspects of …