tbuckley/cabot-search huggingface dataset:
Abstract 5508: Screening Of Novel Thymidylate Synthase Inhibitors
Authors: Jayanthi Repalli, Matthew R. Robinson, Giuseppe Gumina, Sondra H. Berger
Journal: Cancer Research (2010)

Abstract The nucleotide stress response (NSR) is defined as activation of nucleoside salvage pathways to rescue cells from the detrimental consequences caused by a deficiency of or increased demand for nucleotides. Thymidylate depletion due to loss of function of the enzyme, thymidylate synthase (TS) or exposure to TS inhibitors disrupts the balance in nucleotide pools and damages DNA leading to stress-induced cell death. In order to replete nucleotide pools, cells activate nucleoside (ENT 1) transporters to increase the influx of extracellular nucleosides. TS catalyzes the de-novo synthesis of thymidylate for DNA replication. The enzyme in humans undergoes conformational switching between active and inactive forms. We are testing the hypothesis that stabilization of the inactive conformation will not induce the resistance mechanisms that are observed after exposure to active site-targeted TS inhibitors. To identify lead compounds that bind to the inactive conformation, a NSR assay has been developed, which measures a stress response to TMP depletion. TS inhibitors that bind to either the active or inactive conformations will induce TMP stress which is measured as induction of uptake of a fluorescent probe, N2, N3-etheno-6-thiomethylpurine riboside (ETMPR). In order to differentiate TS inhibitors that are selective for active and inactive conformations, we conducted an experiment on paired isogenic cell lines that express either wild-type hTS (undergoes conformational switching) or a mutant hTS (R163K - stabilized in the active conformation). Cells exposed to the potent active site TS inhibitor, raltitrexed (RTX) exhibited a similar level of uptake of ETMPR. When cells are exposed to glutarate (inactive site inhibitor predicted by structure-based drug design), fluorescent nucleoside uptake was preferentially induced in cells expressing wild-type hTS, consistent with the prediction that glutarate is an inactive site targeted drug. Protein turnover studies revealed that glutarate decreases TS expression, which is opposite to the effect of active TS inhibitors, which stabilize TS to degradation. Collectively, the data indicate that the NSR assay will be useful in identifying lead inactive site-targeted drugs and that these drugs will not stabilize TS, a mechanism thought to cause resistance to active state TS inhibitors. 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 5508.
Neonatal Copper Deficiency
Authors: Rashid A. Al-Rashid, John Spangler
Journal: New England Journal of Medicine (1971)

PURE copper deficiency in man has probably never been observed. When it occurs other deficiencies complicate the picture. In infants, a disorder characterized by hypocupremia, hypoferremia, neutropenia, hypoproteinemia and anemia has been reported.1,2Recently, we had the opportunity to study a three-month-old, low-birth-weight infant with the clinical and laboratory picture of copper deficiency who was not marasmic and had been thriving rather well.Case ReportJ.P., a 3-month-old male Indian infant, was referred for evaluation of anemia and a Central-nervous-system disorder. He had been born at 34 weeks' gestation, with an Apgar score of 2 at birth and a weight . . .
Perfusion “Brain Death“ Scintigraphy in Traumatic and Hypoxic Cerebral Insults
Authors: Andrew Chae Kim, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2012)

In the United States, approximately 1.7 million patients are treated annually for traumatic brain injury, and cerebrovascular insults are the third leading cause of death. Although CT plays a central role in the initial assessment of suspected intracranial injury, planar brain scintigraphy provides valuable information regarding cerebral perfusion, function, and brain death. An understanding of the complexity of injuries is helpful in scintigraphic image interpretation. To illustrate potential scintigraphic confounders, we present 8 suspected brain death cases with correlative CT. Even with negative brain death studies, severe brain injury by CT portends grave outcomes.
Hepatitis A and B in the Family Unit
Authors: Thomas M. Vernon
Journal: JAMA (1976)

Investigation of an outbreak of hepatitis A among members of an adoption organization implicated recently arrived Vietnamese orphans as the source of infection. A serologic study disclosed a 27% prevalence of hepatitis B surface antigen among Vietnamese orphans and a 23.1% (6 of 26) prevalence of hepatitis B antibody among American children of adopting families. Five of the six antibody-positive American children were in families with HBsAg-positive orphans. Thus,healthy orphans from high hepatitis incidence areas may transmit hepatitis B, as well as hepatitis A, in the family unit.
Lifelong Curiosity: Frederick Novy and the Rat Virus
Authors: Powel Kazanjian
Journal: Annals of Internal Medicine (2012)

Frederick Novy (1864–1957) was a U.S. physician, medical researcher, and influential microbiologist of the early 20th century who devised culture techniques to visualize anaerobic bacteria, parasites, and spirochetes. In 1909 he began to investigate the cause of unexplained deaths in his laboratory rats, which he hypothesized were due to an “ultramicroscopic organism” or “filterable virus.” But in 1918, the test tubes he had been using for these experiments vanished from his laboratory. His dream of finding a virus as the likely cause of the mysterious deaths of his rats apparently was lost. Novy retired in 1935. Thirty-three years later, in 1951, a box containing the test tubes was discovered by chance during clean-up in preparation for a laboratory move. Novy's curiosity had not waned with time. Notified of the find, and 16 years into his retirement, he returned to his laboratory at the age of 88 to continue the experiments that he had begun more than 40 years earlier. He completed his investigations in 1953 and published his findings that a virus was indeed the unidentified organism that had swiftly killed his laboratory rats in 1909.
Why we need memetics
Authors: Susan Blackmore
Journal: Behavioral and Brain Sciences (2006)

Memes are not best understood as semantic information stored in brains, but rather, as whatever is imitated or copied in culture. Whereas other theories treat culture as an adaptation, for memetics it is a parasite turned symbiont that evolves for its own sake. Memetics is essential for understanding today's information explosion and the future evolution of culture.
Soluble HLA‐G and HLA‐A,‐B,‐C serum levels in patients with allergic rhinitis
Authors: G. Ciprandi, B. M. Colombo, P. Contini, P. Cagnati, A. Pistorio, F. Puppo, G. Murdaca
Journal: Allergy (2008)

Background: Allergic rhinitis (AR) is characterized by Th2‐polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. So far, however, no study investigated them in AR. Objective: The aim of this study was to evaluate sHLA‐G and sHLA‐A,‐B,‐C serum levels in AR patients with pollen allergy and in a group of healthy controls. Methods: Forty‐nine AR patients were enrolled. A group of healthy nonallergic subjects was considered as control. sHLA‐G and sHLA‐A,‐B,‐C serum levels were determined by immunoenzymatic method. The study was conducted during the winter, such as outside the pollen season. Results: Allergic patients had significantly higher levels of both sHLA‐G ( P &lt; 0.0001) and sHLA‐A,‐B,‐C ( P = 0.011) molecules than normal controls. Moreover, there was a significant relationship between these two soluble molecules ( r = 0.69) in allergic patients. Conclusion: The present study provides the first evidence that both sHLA‐G and sHLA‐A,‐B,‐C serum levels are significantly increased in AR patients with pollen allergy.
A 43-Year-Old Man With Angina, Elevated Troponin, and Lateral ST Depression
Authors: Duane S. Pinto
Journal: JAMA (2009)

Each year, approximately 2 million people in the United States experience acute coronary syndromes related to thrombosis and ulceration of atherosclerotic plaque within a coronary artery. The case of Mr C, a 43-year-old man with non–ST-segment elevation myocardial infarction, which is most often caused by subtotal thrombosis, illustrates the complex decision-making process involved in selecting treatment for each patient and in determining whether invasive procedures are warranted. Cardiac catheterization is performed in moderate- and high-risk individuals to define the extent of disease so the proper strategy—medications alone, percutaneous revascularization, or coronary artery bypass graft surgery—can be selected. Medications to disrupt platelet function as well as the coagulation system are used. Treatments are designed to minimize the extent of infarction and prevent reinfarction, thereby improving outcomes. The timing of cardiac catheterization, for whom catheterization is indicated, and the rationale for medication treatment are discussed.
Abstract 3868: Identification of PHLPP1 as a novel metastasis suppressor in melanoma .
Authors: Yanlin Yu, Andrew Lu, Meng Dai, Glenn Merlino
Journal: Cancer Research (2013)

Abstract Metastatic dissemination is the cause of nearly all melanoma-related deaths. Despite an improving understanding of genetic lesions present in human melanomas, how these alternations relate to the metastatic process is not well understood. Previously, we found that activation of the PI3K/Akt pathway is a driving force in metastatic melanomas. Here we identify PHLPP1 as a novel metastasis suppressor in melanoma. PHLPP1 was recently identified as a Ser/Thr-specific phosphatase, belonging to pleckstrin homology (PH) domain leucine-rich repeat protein phosphatase family. The two isoforms of this family, PHLPP1 and PHLPP2 control kinase signaling in the AKT family by catalyzing the dephosphorylation of the hydrophobic phosphorylation motif. PHLPP1 can specifically dephosphorylate AKT2 and AKT3, whereas PHLPP2 dephosphorylates AKT1 and AKT3. To study the role of PHLPPs in metastatic melanoma, we first examined the expression of PHLPPs in 30 melanoma metastases, 30 primary melanomas, and 9 normal skin tissues using tissue microarray analysis. We found that PHLPP1 was significantly downregulated or lost in metastatic melanoma samples, but not PHLPP2. Moreover, analysis of various human melanoma cell lines (12 highly metastatic, 14 poorly metastatic melanoma cell lines and 1 normal melanoctye cell line) demonstrated that PHLPP1 expression correlated with metastatic behavior, supporting the notion that PHLPP1 is involved in the metastatic regulation of melanoma. To confirm a functional role for PHLPP1 in metastasis, we forced the expression of PHLPP1 and PHLPP2 in B16 and A375sm melanoma cell lines. Overexpression of PHLPP1 dramatically inhibited metastasis in both cell lines. Unexpectedly, the PHLPP2 isoform had little influence on metastatic ability in both cell lines in vivo, despite the fact that both PHLPP1 and PHLPP2 were able to inhibit in vitro cell proliferation, motility, migration as well as colony formation in soft agar. Notably, introduction of PH mutant forms of PHLPP1 still blunted the metastatic potential of both cell lines, whereas a phosphatase-deficient C-terminal mutant did not affect metastasis. Interestingly, transfected AKT2 active form could rescue PHLPP1-mediaed inhibition of metastasis. Our data demonstrate at the first time that PHLPP1 plays a critical role in inhibiting metastasis through its phosphatase activity, and suggest that PHLPP1 could be a diagnostic marker and therapeutic target for metastatic melanoma. Citation Format: Yanlin Yu, Andrew Lu, Meng Dai, Glenn Merlino. Identification of PHLPP1 as a novel metastasis suppressor in melanoma . [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 3868. doi:10.1158/1538-7445.AM2013-3868
IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy
Authors: Vijayaprakash Suppiah, Max Moldovan, Golo Ahlenstiel, Thomas Berg, Martin Weltman, Maria Lorena Abate, Margaret Bassendine, Ulrich Spengler, Gregory J Dore, Elizabeth Powell, Stephen Riordan, David Sheridan, Antonina Smedile, Vincenzo Fragomeli, Tobias Müller, Melanie Bahlo, Graeme J Stewart, David R Booth, Jacob George
Journal: Nature Genetics (2009)
Peroxisome Proliferator-Activated Receptor γ Activators Inhibit Cardiac Hypertrophy in Cardiac Myocytes
Authors: Keiji Yamamoto, Ruri Ohki, Richard T. Lee, Uichi Ikeda, Kazuyuki Shimada
Journal: Circulation (2001)

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPARgamma mRNA is present in cardiac myocytes; however, whether PPARgamma affects cardiac hypertrophy remains unknown.We investigated the effects of PPARgamma activators on cardiac hypertrophy in neonatal rat cardiac myocytes. Cyclic 4% biaxial mechanical strain caused enlargement of cardiac myocytes (1.3-fold versus control, P<0.0001), but the PPARgamma activators troglitazone and 15-deoxy-Delta(12-14)-prostaglandin J(2) (15d-PGJ(2)) (10 micromol/L) inhibited this effect (troglitazone, -72%, P<0.0005; 15d-PGJ(2), -88%, P<0.0002). Total cell protein was increased by mechanical strain (control, 164.3 microgram/dish; strain, 265.5, P<0.0002), and this effect was inhibited by troglitazone and 15d-PGJ(2) (troglitazone, -61%, P<0.005; 15d-PGJ(2), -72%, P<0.001). [(3)H]Leucine uptake was also increased by mechanical strain (1.9-fold versus control, P<0.002), and this increase was inhibited by troglitazone and 15d-PGJ(2) (troglitazone, -52% at 10 micromol/L, P<0.01; 15d-PGJ(2), -70% at 10 micromol/L, P<0.005). An increase in [(3)H]leucine uptake induced by angiotensin II or phenylephrine was significantly inhibited by troglitazone and 15d-PGJ(2). Mechanical strain induced mRNA expression for brain natriuretic peptide, but PPARgamma activators inhibited this induction. Furthermore, PPARgamma activators inhibited mechanically induced activation of nuclear factor (NF)-kappaB. Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, inhibited strain-induced [(3)H]leucine uptake (-50% at 100 micromol/L, P<0.05).These results demonstrate that PPARgamma activators inhibit cardiac hypertrophy in cardiac myocytes and suggest that PPARgamma activators may regulate cardiomyocyte hypertrophy at least partially through the NF-kappaB pathway.
Pediatric Airway: Cry, Stridor, and Cough
Authors: Adam Frosh
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Skin Carcinoma Arising From Donor Cells in a Kidney Transplant Recipient
Authors: Sélim Aractingi, Jean Kanitakis, Sylvie Euvrard, Caroline Le Danff, Isabelle Peguillet, Kiarash Khosrotehrani, Olivier Lantz, Edgardo D. Carosella
Journal: Cancer Research (2005)

The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.
Rhabdomyosarcoma in Children
Authors: Donald Pinkel
Journal: JAMA (1961)

Sixteen children with rhabdomyosarcoma have been studied and treated in the past 3 1/2 years. The most common site of tumor origin was in the head and neck region, but some arose in the extremities, urogenital system, and trunk. The tumors grew rapidly, infiltrating locally and metastasizing to lung, bone, lymph nodes, and other organs. In 3 children tumor cells were found on routine bone marrow aspirations. Delay in correct medical diagnosis was common, and treatment was unsatisfactory in most instances. Radical surgical excision was possible in only 2 patients, in 1 of these only after reduction of tumor size by chemotherapy. Radiation therapy and an antitumor compound clinically known as actinomycin D produced temporary regressions in some patients; cyclophosphamide was effective in others.
Endothelium: from cellophane to orchestral maestro
Authors: Ralph L. Nachman
Journal: Journal of Clinical Investigation (2012)

Endothelial cells from human umbilical veins were first cultured nearly four decades ago, initiating explosive growth in research in vascular biology and leading to major insights into angiogenesis, vasculogenesis, and tumor biology. Recent studies now promise to open new horizons in regenerative medicine as well as organ engineering.
Diphtheria Epidemic at Akron—Use of Antitoxin.
Authors: A. P. Ohlmacher
Journal: JAMA (1895)

Cleveland, Ohio, April 1,1895. <h3>To the Editor:</h3> —Permit me to submit for the columns of Public Health in the Journal the following item: An outbreak of diphtheria has recently occurred in the Summit County Children's Home at Akron, Ohio. Dr. L. S. Ebright, physician in charge of the Home, and Health Officer of Akron, diagnosed and isolated the first case March 21. This boy recovered after a severe illness of a week's duration. March 27 another boy was taken sick, and the next day the disease appeared in three girls. The Home contains sixty children varying in age from 2 years to 15 years, and fifteen attendants. March 30, after making a preliminary bacteriologic examination of one of the cases, I went to the Home with Dr. Ebright and administered the antitoxin obtained from our (Wooster Medical College) diphtheria-immune horse. The boy who had been sick three days was dying
The Natural History of Infectious Disease in a Boys' School, 1900–1956
Authors: Theodore H. Ingalls
Journal: New England Journal of Medicine (1956)

THE charts to be presented sketch in profile the natural history of measles, mumps, chicken pox, rubella, influenza, hepatitis and poliomyelitis in a universe of high-school boys throughout the twentieth century to date. Such information is, as far as I know, unique.Located in a small town about 25 miles from Boston, the St. Mark's School structure is an extended H-shaped building containing classrooms, dormitories, dining room, library, chapel and infirmary. An average annual enrollment of about 195 boarders, practically all of teen age, represents a gradual increase in population from 130 at the turn of the century. A pleasant . . .
Calcium dependency and free calcium concentrations during insulin secretion in a hamster beta cell line.
Authors: A E Boyd, R S Hill, J M Oberwetter, M Berg
Journal: Journal of Clinical Investigation (1986)

Using a glucose-responsive beta cell line, we tested the hypothesis that the free cytosolic Ca2+ concentration ([Ca2+]i) is the primary signal that couples a stimulus to insulin secretion, and examined the involvement of the extracellular Ca2+ pool in this process. Glucose or depolarization of the beta cell with 40 mM K+ stimulated a monophasic release of insulin directly proportional to the extracellular Ca2+ concentration. 40 mM K+ increased 45Ca2+ uptake and increased [Ca2+]i, which was measured with quin 2, 4.7-fold, from 56 +/- 3 to 238 +/- 17 nM. With high glucose, 45Ca2+ uptake did not increase, and [Ca2+]i was unchanged or fell slightly. There was a striking correlation between inhibitory effects of verapamil, the Ca2+ channel blocker, on insulin secretion and the rise in [Ca2+]i evoked by K+. Higher concentrations of verapamil were required to inhibit glucose- than K+-stimulated insulin secretion (dose giving half-maximal effect of 1.4 X 10(-4) M vs. 6.0 X 10(-7) M). Incubation in Ca2+-free, 1 mM EGTA buffer for 30 min lowered [Ca2+]i to 14 +/- 2 nM, and inhibited acute insulin release to both secretagogues. If high glucose was present in the Ca2+-free period, reintroduction of 2.5 mM Ca2+ in high glucose restored insulin secretion only to the basal rate. However, if low glucose was present during the Ca2+-free period, high glucose and 2.5 mM Ca2+ triggered a full first-phase insulin response. These data suggest that high glucose generates a non-Ca2+ signal that turns over rapidly and provide direct evidence that K+ triggers insulin release by drawing extracellular Ca2+ into the beta cell through verapamil-sensitive Ca2+ channels. However, an increase [Ca2+]i is not the primary signal that evokes glucose-stimulated insulin release in this beta cell line.
Book Review Nursing against the Odds: How Health Care Cost Cutting, Media Stereotypes, and Medical Hubris Undermine Nurses and Patient Care (The Culture and Politics of Health Care Work.) By Suzanne Gordon. 489 pp. Ithaca, N.Y., Cornell University Press, 2005. $29.95. 0-8014-3976-0
Authors: Jean Ann Seago
Journal: New England Journal of Medicine (2005)