tbuckley/cabot-search huggingface dataset:
Role of p53 Up-regulated Modulator of Apoptosis and Phosphorylated Akt in Melanoma Cell Growth, Apoptosis, and Patient Survival
Authors: Alison M. Karst, Derek L. Dai, Jin Q. Cheng, Gang Li
Journal: Cancer Research (2006)

Abstract Malignant melanoma is an aggressive and chemoresistant form of skin cancer characterized by rapid metastasis and poor patient prognosis. The development of innovative therapies with improved efficacy is critical to treatment of this disease. Here, we show that aberrant expression of two proteins, p53 up-regulated modulator of apoptosis (PUMA) and phosphorylated Akt (p-Akt), is associated with poor patient survival. Using tissue microarray analysis, we found that patients exhibiting both weak PUMA expression and strong p-Akt expression in their melanoma tumor tissue had significantly worse 5-year survival than patients with either weak PUMA or strong p-Akt expression alone (P &amp;lt; 0.001). Strikingly, no patients exhibiting strong PUMA expression and weak p-Akt expression in primary tumor tissue died within 5 years of diagnosis. We propose a two-pronged therapeutic strategy of (a) boosting PUMA expression and (b) inhibiting Akt phosphorylation in melanoma tumor tissue. Here, we report that a recombinant adenovirus containing human PUMA cDNA (ad-PUMA) efficiently inhibits human melanoma cell survival in vitro, rapidly induces apoptosis, and dramatically suppresses human melanoma tumor growth in a severe combined immunodeficient mouse xenograft model. In melanoma cells strongly expressing p-Akt, we show that Akt/protein kinase B signaling inhibitor-2 (API-2; a small-molecule Akt inhibitor) reduces cell survival in a dose- and time-dependent manner and enhances ad-PUMA-mediated growth inhibition of melanoma cells. Finally, we show that, by combining ad-PUMA and API-2 treatments, human melanoma tumor growth can be inhibited by &amp;gt;80% in vivo compared with controls. Our results suggest that a strategy to correct dysregulated PUMA and p-Akt expression in malignant melanoma may be an effective therapeutic option. (Cancer Res 2006; 66(18): 9221-6)
Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia
Authors: Etan Orgel, Jonathan Tucci, Waseem Alhushki, Jemily Malvar, Richard Sposto, Cecilia H. Fu, David R. Freyer, Hisham Abdel-Azim, Steven D. Mittelman
Journal: Blood (2014)
Naevoid basal cell carcinoma syndrome with a palmar epidermoid cyst, milia and maxillary cysts.
Authors: K. Ogata, M. Ikeda, K. Miyoshi, Y. Yamamoto, T. Yamamoto, T. Osaki, E. Michimukai, Y. Tanaka, A. Sakamoto, T. Oakamoto, H. Kodama
Journal: British Journal of Dermatology (2001)
Abstract 707: MK1775-mediated gemcitabine sensitization correlates with prolonged DNA damage signaling in S-phase cells.
Authors: Leslie A. Parsels, Joshua D. Parsels, Meredith A. Morgan, Theodore S. Lawrence, Jonathan Maybaum
Journal: Cancer Research (2013)

Abstract Pancreatic cancer remains among the most lethal cancers with an overall 5-year survival of &amp;lt;5%. Wee1 inhibition has emerged as a potential approach to sensitize pancreatic cancer to gemcitabine (Gem), the current standard therapy for both local control and metastatic disease. In this study, we first characterized the ability of MK1775, a small molecule Wee1 inhibitor now entering Phase II clinical trials, to sensitize pancreatic cancer cells to Gem. Using a clonogenic survival assay, we tested the effects of MK1775 in a panel of pancreatic cancer cells and found MK1775-mediated Gem sensitization ranged from 80-fold in MiaPaCa2 cells to 12-fold in Panc1 cells. This sensitization was associated with aberrant mitotic entry in MiaPaCa2 and Panc1 cells, but not in the other cells lines tested. In addition, MK1775 potentiated and prolonged Gem-induced DNA damage signaling (γ-H2AX) as determined by 2-parameter flow cytometry. For example, 48 h post-Gem, 35±12% of BxPC3 cells remain γ-H2AX-positive compared to 76±3.7% of cells treated with Gem + MK1775. Using immunofluorescent staining, we further determined that Wee1 inhibition with MK1775 qualitatively changed Gem-induced γ-H2AX nuclear foci to high intensity pan-nuclear γ-H2AX pan-staining. Finally, we tested the ability of the CDK inhibitor roscovitine (Ros) to attenuate MK1775-mediated chemosensitization. Ros not only prevented aberrant mitotic entry in MiaPaCa2 and Panc1 cells, but in each cell line sensitized to Gem by MK1775, Ros inhibited both high-intensity γ-H2AX staining after treatment with Gem + MK1775 and chemosensitization. These results suggest the effects of MK1775 on DNA repair in S-phase cells may be more important for Gem chemosensitization than the effects of MK1775 on the G2-M checkpoint. Citation Format: Leslie A. Parsels, Joshua D. Parsels, Meredith A. Morgan, Theodore S. Lawrence, Jonathan Maybaum. MK1775-mediated gemcitabine sensitization correlates with prolonged DNA damage signaling in S-phase cells. [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 707. doi:10.1158/1538-7445.AM2013-707
Differential expression in glioblastoma multiforme and cerebral hemangioblastoma of cytoplasmic proteins that bind two different domains within the 3'-untranslated region of the human glucose transporter 1 (GLUT1) messenger RNA.
Authors: H Tsukamoto, R J Boado, W M Pardridge
Journal: Journal of Clinical Investigation (1996)

The glucose transporter 1 (GLUT1) protein is underexpressed in human glioblastoma multiforme and is overexpressed in human cerebral hemangioblastoma. To gain in-sight into possible posttranscriptional mechanisms regulating the expression of the GLUT1 protein in human brain tumors, cytosolic proteins were prepared from these two tumors and used in RNase T1 protection assays that employed [32P]human GLUT1 synthetic RNA prepared from transcription plasmids. Gel shift mobility assays and ultra-violet light cross-linking studies demonstrated the formation of specific RNA/protein complexes that migrated with a mol mass of 120, 44, and 41 kD. RNase T1 mapping and oligodeoxynucleotide competition studies showed that the 120 kD complex was comprised of an RNA fragment that localized to nucleotides 2186-2203 of the GLUT1 mRNA. The 44 kD complex contained an adenosine-uridine-rich RNA fragment that localized to nucleotides 1885-1906 of the human GLUT1 mRNA, and the formation of this complex was inhibited by synthetic RNA enriched in adenosine-uridine sequences. The 44 kD complex was selectively downregulated in hemangioblastoma as compared to glioblastoma multiforme. These studies demonstrate that human brain tumors have differential regulation of cytosolic proteins that specifically interact with two different domains in the 3'-untranslated region of the GLUT1 mRNA, which may serve to mediate the posttranscriptional regulation of GLUT1 gene expression in these tumors.
Hypercalcemia Secondary to a Primary Hepatoma
Authors: Reed T. Keller
Journal: JAMA (1965)

THE DIAGNOSTIC spectrum of hypercalcemia<sup>1</sup>has become increasingly complex since 1956 when Connor and associates<sup>2</sup>reported the subsidence of hypercalcemia after the resection of bronchogenic carcinoma in two patients. Subsequently, a wide variety of malignancies without skeletal involvement has been associated with hypercalcemia.<sup>3,4</sup>In many cases, as illustrated by this case report, death has resulted from hypercalcemia rather than from the invasive effects of the tumor. The separation of such cases from primary hyperparathyroidism is frequently the most difficult diagnostic problem in the hypercalcemic patient. The following is apparently the first case report of hypercalcemia secondary to a localized primary hepatoma. <h3>Report of a Case</h3> A 23-year-old white male beautician (UH-794-312) was transferred from a psychiatric hospital for the evaluation of hepatomegaly and somnolence on April 9, 1964. The patient had a six-year history of immoderate alcoholic ingestion and drank up to two pints of whisky per
Dietary Carotenoids, Vitamins A, C, and E, and Macular Degeneration-Reply
Authors: Johanna M. Seddon
Journal: JAMA (1995)

In Reply.  —Randomized trials of beta carotene or any one vitamin will not be able to answer all questions about the role of all antioxidants in the development or progression of age-related eye disease. The Editorial 1 accompanying our article reminds us that the success of the clinical trials in finding an association depends on giving the appropriate nutrient, in the appropriate dose, for an appropriate period of time, to an appropriate population. Failing to meet any one of these requirements will reduce or eliminate the probability of finding an effect even if one exists. As we discussed in our article, observational studies and clinical trials both can contribute to our understanding of the relationship between antioxidants as well as other nutrients and risk of chronic eye disease.
Association of unstable hemoglobin variants and heterozygous ?-thalassemia: Example of a new variant Hb acharnes or [?53(D4) Ala ? Thr]
Authors: I. Papassotiriou, J. Traeger-Synodinos, D. Prom�, J. Kister, E. Stamou, T. Liakopoulou, A. Stamoulakatou, E. Kanavakis, H. Wajcman
Journal: American Journal of Hematology (1999)

We report here the functional and structural characterization of Hb Acharnes [β53(D4) Ala → Thr], an unstable and electrophoretically silent variant, that was found associated in trans with a β0-thalassemic mutation (IVSI-1 G → A), in a patient with thalassemia intermedia syndrome. This case is discussed in comparison with other sporadic cases that we have previously investigated, resulting from the co-inheritance of a β0-thalassemic mutation (CD39 C → T) with two other types of unstable hemoglobins, Hb Köln [β98(FG5) Val → Met], and Hb Arta [β45(CD4) Phe → Cys]. It may be concluded that, in these associated forms, both the degree of instability of the variant and the altered oxygen binding properties (affecting the degree of tissue hypoxia) are major determinants of their clinical expression. Am. J. Hematol. 62:186–192, 1999. © 1999 Wiley-Liss, Inc.
Lipoma and Sensory Neuropathy in Mitochondrial Diabetes Associated With tRNA Mutation at Position 3271
Authors: Yoshihiko Suzuki, Katsunori Tsukuda, Matsuo Taniyama, Yoshihito Atsumi, Kempei Matsuoka, Yositomo Oka
Journal: Diabetes Care (2002)

We previously reported the first identified case of mitochondrial diabetes caused by a T-to-C transition at position 3271 (1). At age 32 years, the patient had lower limb paresthesia. Since beginning diet therapy at age 33 years, his glycemic control has generally been good (HbA1c 6–7%) and the paresthesia has disappeared.

During 12 years of follow-up, we observed two important clinical features: 1 ) lower limb …
We all are Rembrandt experts – or, How task dissociations in school learning effects support the discontinuity hypothesis
Authors: Régine Kolinsky, José Morais
Journal: Behavioral and Brain Sciences (1999)

We argue that cognitive penetration in non-early vision extends beyond the special situations considered by Pylyshyn. Many situations which do not involve difficult stimuli or require expert skills nevertheless load on high-level cognitive processes. School learning effects illustrate this point: they provide a way to observe task dissociations which support the discontinuity hypothesis, but they show that the scope of visual cognition in our visual experience is often underestimated.
Endothelial Lu/BCAM glycoproteins are novel ligands for red blood cell α4β1integrin: role in adhesion of sickle red blood cells to endothelial cells
Authors: Wassim El Nemer, Marie-Paule Wautier, Cécile Rahuel, Pierre Gane, Patricia Hermand, Frédéric Galactéros, Jean-Luc Wautier, Jean-Pierre Cartron, Yves Colin, Caroline Le Van Kim
Journal: Blood (2006)
ABC of diseases of liver, pancreas, and biliary system: Portal hypertension---1: varices
Authors: J E J Krige
Journal: BMJ (2001)

The portal vein carries about 1500 ml/min of blood from the small and large bowel, spleen, and stomach to the liver at a pressure of 5-10 mm Hg. Any obstruction or increased resistance to flow or, rarely, pathological increases in portal blood flow may lead to portal hypertension with portal pressures over 12 mm Hg. Although the differential diagnosis is extensive, alcoholic and viral cirrhosis are the leading causes of portal hypertension in Western countries, whereas liver disease due to schistosomiasis is the main cause in other areas of the world. Portal vein thrombosis is the commonest cause in children.



Anatomical relations of portal vein and branches



Increases in portal pressure cause development of a portosystemic collateral circulation with resultant compensatory portosystemic shunting and disturbed intrahepatic circulation. These factors are partly responsible for the important complications of chronic liver disease, including variceal bleeding, hepatic encephalopathy, ascites, hepatorenal syndrome, recurrent infection, and abnormalities in coagulation. Variceal bleeding is the most serious complication and is an important cause of death in patients with cirrhotic liver disease.

#### Causes of portal hypertension

##### Increased resistance to flow

###### Prehepatic (portal vein obstruction)

###### Hepatic

###### Posthepatic

##### Increased portal blood flow

In Western countries variceal bleeding accounts for about 7% of episodes of gastrointestinal bleeding, although this varies according to the prevalence of alcohol related liver disease (11% in the United States, 5% in the United Kingdom). Patients with varices have a 30% lifetime risk of bleeding, and a third of those who bleed will die. Patients who have bled once from oesophageal varices have a 70% chance of bleeding again, and about a third of further bleeding episodes are fatal.

Several important considerations influence choice …
The rational clinical examination. Does this patient have a goiter?
Authors: K. Siminoski
Journal: JAMA (1995)

<h3>CLINICAL SCENARIOS— HOW LARGE ARE THESE THYROID GLANDS?</h3> For each of the following patients, assessment of thyroid size is an important part of the clinical examination. In case 1, a 32-year-old woman presents with symptoms and findings consistent with hyperthyroidism, but she has no exophthalmos and has always been anxious. In case 2, a 55-year-old man has a diagnosis of Graves' disease, and the choice is made for radioactive iodine ablation therapy. In case 3, a 64-year-old man has a goiter that causes discomfort on swallowing, and thyroxine is to be administered in an attempt to shrink the thyroid gland. <h3>WHY ASSESS THE THYROID GLAND FOR SIZE?</h3> A goiter is simply an enlargement of the thyroid gland and may result from hormonal or immunological stimulation of gland growth or the presence of inflammatory, proliferative, infiltrative, or metabolic disorders (Table 1). A common error among those first learning about the thyroid
Mandatory National Health Service
Authors: Peter H. Kurtz
Journal: JAMA (1993)

To the Editor.  —I had to write a response to the article concerning mandatory national health service by Dr Johns.1  Ideas concerning future medical delivery systems have been expressed well by authors of various articles inJAMAover the last few years. I am beginning to tire of articles emphatically pushing the right to medical care, the  that universal access will solve all our medical problems, and the fact that specialists are always high-priced, do inappropriate procedures, and are now concerned about their financial bottom line. Now, to paraphrase Johns, public service physicians would insure society's goal of competent, compassionate, and dedicated physicians.  I have spent time in Haiti, Romania, and Mexico donating medical time, equipment, and service. In all situations I've found that I have most enjoyed giving medical care when my efforts have been received with gratitude, even when all I had to offer was compassion.
How Odd, That All These Things Are Happening
Authors: Mel Belin
Journal: JAMA (2007)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
The medial dorsal nucleus of the thalamus is not part of a hippocampal-thalamic memory system
Authors: Menno P. Witter, Ysbrand D. Van der Werf
Journal: Behavioral and Brain Sciences (1999)

Aggleton &amp; Brown propose that familiarity-based recognition depends on a perirhinal-medial dorsal thalamic system. However, connections between these structures are sparse or absent. In contrast, the perirhinal cortex is connected to midline/intralaminar nuclei. In a human, a lesion in this thalamic domain, sparing the medial dorsal nucleus, impaired familiarity-based recognition while sparing recollective-based recognition. It is thus more likely that the intralaminar/midline nuclei are involved in recognition.
Spironolactone Reduces Cardiovascular and Cerebrovascular Morbidity and Mortality in Hemodialysis Patients
Authors: Yoshihiro Matsumoto, Yasuo Mori, Shinji Kageyama, Kazuo Arihara, Toshikazu Sugiyama, Hiromichi Ohmura, Toru Yakushigawa, Hatsumi Sugiyama, Yasushi Shimada, Youichi Nojima, Nobuo Shio
Journal: Journal of the American College of Cardiology (2013)
Scientists plead for right to create interspecies embryos
Authors: Andrew Cole
Journal: BMJ (2007)

UK NEWS Scientists plead for right to create interspecies embryos, p1238 World NEWS US gro�p highlights symptoms of early o�arian cancer, p 12�� US gro�p highlights symptoms of early o�arian cancer, p 12�� bmj.com �itamin d from s�n e�pos�re may protect against solid cancers �itamin d from s�n e�pos�re may protect against solid cancers
Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data.
Authors: J T Salonen, R Salonen, R Lappetelainen, P H Maenpaa, G Alfthan, P Puska
Journal: BMJ (1985)

The independent and joint associations of serum selenium and vitamin A (retinol) and E (alpha tocopherol) concentrations with the risk of death from cancer were studied in 51 case-control pairs--that is, 51 patients with cancer, each paired with a control matched for age, sex, and smoking. Case-control pairs came from a random sample of some 12000 people aged 30-64 years resident in two provinces of eastern Finland who were followed up for four years. Patients who died of cancer during the follow up period had a 12% lower mean serum selenium concentration (p = 0.015) than the controls. The difference persisted when deaths from cancer in the first follow up year were excluded. The adjusted risk of fatal cancer was 5.8-fold (95% confidence interval 1.2-29.0) among subjects in the lowest tertile of selenium concentrations compared with those with higher values. Subjects with both low selenium and low alpha tocopherol concentrations in serum had an 11.4-fold adjusted risk. Among smoking men with cancer serum retinol concentrations were 26% lower than in smoking controls (p = 0.002). These data suggest that dietary selenium deficiency is associated with an increased risk of fatal cancer, that low vitamin E intake may enhance this effect, and that decreased vitamin or provitamin A intake contributes to the risk of lung cancer among smoking men with a low selenium intake.
Acute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo
Authors: Zhengyu Luo, Yasushi Fujio, Yasuko Kureishi, Radu Daniel Rudic, Geraldine Daumerie, David Fulton, William C. Sessa, Kenneth Walsh
Journal: Journal of Clinical Investigation (2000)

The serine/threonine protein kinase Akt (protein kinase B) phosphorylates endothelial cell nitric oxide synthase (eNOS) and enhances its ability to generate nitric oxide (NO). Because NO is an important regulator of vasomotor tone, we investigated whether Akt can regulate endothelium-dependent vasomotion in vivo using a rabbit femoral artery model of gene transfer. The endothelium of isolated femoral arteries was infected with replication-defective adenoviral constructs expressing β-galactosidase, constitutively-active Akt (myr-Akt), or dominant-negative Akt (dn-Akt). Femoral arteries transduced with myr-Akt showed a significant increase in resting diameter and blood flow, as assessed by angiography and Doppler flow measurements, respectively. L-NAME, an eNOS inhibitor, blocked myr-Akt–mediated vasodilatation. In contrast, endothelium-dependent vasodilatation in response to acetylcholine was attenuated in vessels transduced with dn-Akt, although these vessels showed normal responses to nitroglycerin, an endothelium-independent vasodilator. Similarly, relaxation of murine aorta ex vivo in response to acetylcholine, but not nitroglycerin, was inhibited by transduction of dn-Akt to the endothelium. These data provide evidence that Akt functions as key regulator of vasomotor tone in vivo.
Cytokine and chemokine expression in the skin from patients with maculopapular exanthema to drugs
Authors: T. D. Fernandez, C. Mayorga, M. J. Torres, J. A. Cornejo‐Garcia, S. López, P. Chaves, C. Rondon, M. Blanca
Journal: Allergy (2008)

Background: Maculopapular exanthema (MPE) is the most frequent clinical manifestation of nonimmediate allergic reactions to drugs and T helper 1 (Th1) cytokines and CD4 + T cells have been shown to play an important role in its pathogenesis. We assessed the role of cytokines and chemokines and their receptors in the pathogenesis of MPE. Methods: We evaluated skin biopsies and peripheral CD4 + and CD8 + T cells from 27 patients during the acute phase of the reaction and 26 exposed controls. Semiquantitative real‐time PCR was performed to determine the expression of cytokines and chemokines and their receptors and immunohistochemistry was used to determine the same chemokines and their receptor proteins in skin. Results: There was a high expression of the Th1 cytokines interferon‐γ ( P = 0.006) and tumor necrosis factor‐α ( P = 0.022) in skin and CD4 + T cells ( P = 0.007 and P = 0.005, respectively); and of the Th1 chemokines CXCL9 ( P = 0.005) and CXCL10 ( P = 0.028) in the skin, while their receptor CXCR3 was increased in skin ( P = 0.006) and CD4 + T cells ( P = 0.03). Homing chemokine receptors were also increased: CCR6 in skin ( P = 0.026) and CD4 + T cells ( P = 0.016), and CCR10 only in CD4 + T cells ( P = 0.016), as well as their ligands, CCL20 and CCL27, in skin alone. Immunohistochemistry confirmed these results. Conclusions: These data show significant differences in the expression of chemokines and chemokine receptors, related with a Th1 profile, in both skin biopsies and peripheral CD4 + T cells in patients with drug‐induced MPE.