tbuckley/cabot-search huggingface dataset:
Autosomal dominant multiple syringomas linked to chromosome 16q22
Authors: W.M. Wu, Y.S. Lee
Journal: British Journal of Dermatology (2010)

Background The condition of multiple syringomas is a common skin problem that begins in early adulthood and is characterized by the appearance of skin-coloured papules around the eyes. Previous reports have demonstrated that some cases of multiple syringomas are inherited in an autosomal dominant manner. Objective To identify the genetic factors involved in the development of multiple syringomas. Methods We recruited seven families including multiple family members with multiple syringomas. Our sample included 24 affected individuals and 11 unaffected individuals. We performed genome-wide single-nucleotide polymorphism screening for linkage analysis. Results Whole-genome screening and subsequent analysis revealed that all of the seven families were linked at a locus on chromosome 16q22. A significant logarithm of the odds score of 4·51 with θ of 0·00 confirmed the mapping result. The analysis of critical recombinants defined the locus as a 6·63 cM interval in which 143 genes could be identified. Conclusions We confirmed that the condition of multiple syringomas is an autosomal dominant disorder, and we determined the genomic location of the responsible gene.
Extent of RV Dysfunction and Myocardial Infarction Assessed by CMR Are Independent Outcome Predictors Early After STEMI Treated With Primary Angioplasty
Authors: Tomasz Miszalski-Jamka, Piotr Klimeczek, Marek Tomala, Maciej Krupiński, George Zawadowski, Jessica Noelting, Michał Lada, Katarzyna Sip, Robert Banyś, Wojciech Mazur, Dean J. Kereiakes, Krzysztof Żmudka, Mieczysław Pasowicz
Journal: JACC. Cardiovascular imaging (2010)
Abstract 1319: Regulation of AR transcriptional activity and prostate cancer cellular proliferation by DACH1/Eya1/Six1 pathway.
Authors: Jing Wang, Shaoxin Cai, Ke Chen, Sean Li, Richard Pestell, Kongming Wu
Journal: Cancer Research (2013)

Abstract Prostate cancer progression from androgen responsive to androgen-depletion therapy resistance is a major cause of treatment failures. Novel therapies targeting this patient are a major clinical challenge. We previously reported that the cell fate determination factor DACH1 inhibits androgen signaling though binding the AR and enhancing co-repressor recruitment in the context of local chromatin at AR responsive genes. The repression of AR function of by DACH1 was partly rescued by the co-activators p300 and SRC. The repression was enhanced by ectopic expression of HDACs. We had previously shown that DACH1 inhibited proliferation of androgen-dependent LnCAP cells. To further explore the significance of DACH1 in human prostate cancer, we established stable cell lines expressing DACH1 or its DS domain deleted mutant (ΔDS) in androgen-independent C4-2 cells and AR-negative PC-3 cells by retrovirus infection. Stable expression of DACH1 inhibited cellular proliferation in both cell lines, requiring the DS domain. Ectopic expression of DACH1 inhibited colony formation of the androgen-independent 22RV1 cells. DACH1 inhibited migration, invasion and tumor growth of AR-negative PC-3 cells. Since DACH1, Eya1 and Six1 function together as a network to control cellular differentiation and organ formation during development, we examined whether other components of RDGN pathway, could regulate androgen signaling. In hormone responsive LnCAP cells, ligand stimulation (DHT, 50nM) induced 17 folds activation of MMTV Luc, co-expression of Eya1 reduced AR transactivation, and the repression required the EYA phophatase domain. Expressions of the AR co-repressors, HDAC1, HDAC3 or SirT1 inhibited the ligand-induced AR activity. Eya1 enhanced co-repressor function at the PSA and MMTV promoters. Consistent with our previous publication, DACH1 repressed ligand-induced activity &amp;gt;70%, Eya1 modified DACH1 repression of AR activity. Together, our studies demonstrated that the RDGN regulates both androgen dependent and independent prostate cancer cellular proliferation and tumorigenesis. Citation Format: Jing Wang, Shaoxin Cai, Ke Chen, Sean Li, Richard Pestell, Kongming Wu. Regulation of AR transcriptional activity and prostate cancer cellular proliferation by DACH1/Eya1/Six1 pathway. [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 1319. doi:10.1158/1538-7445.AM2013-1319
Can the Electronic Nose Really Sniff out Lung Cancer?
Authors: Serpil C. Erzurum, Timothy Burch, Daniel Laskowski, Peter J. Mazzone, Tarek Mekhail, Constance Jennings, James K. Stoller, Roberto F. Machado, Jacqueline Pyle, Olivia Deffenderfer, Raed A. Dweik
Journal: American Journal of Respiratory and Critical Care Medicine (2005)
Ambulatory blood pressure, microalbuminuria, and autonomic neuropathy in adolescents with type 1 diabetes.
Authors: A R Lafferty, G A Werther, C F Clarke
Journal: Diabetes Care (2000)

OBJECTIVE: To examine the relationship between 24-h blood pressure (BP) measurements, urinary albumin excretion rates, and autonomic neuropathy (AN) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 31 patients with microalbuminuria (MA), 20 patients with intermittent MA (I-MA) and 11 patients with persistent MA (P-MA) were identified from the diabetes clinics at two major Australian tertiary care pediatric hospitals. Two control groups were used; one consisted of 19 age-, sex-, and diabetes duration-matched adolescents with normoalbuminuria (NA), and the other consisted of 46 age- and sex-matched nondiabetic control subjects. A medical history and physical examination were followed by a series of noninvasive tests of cardiovascular and pupillary autonomic function and then by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: ABPM showed an incremental increase in all BP parameters from nondiabetic control subjects through subjects with NA. A parallel incremental increase in diurnal and nocturnal ambulatory heart rates was also evident. Subjects with MA had significantly reduced pupillary adaptation to darkness compared with nondiabetic subjects and subjects with NA. The above results paralleled an incremental increase in HbAlc levels in adolescents with type 1 diabetes from subjects with NA to subjects with P-MA. CONCLUSIONS: Higher 24-h BP values and evidence of subclinical signs of AN are present before P-MA develops and may have important implications for timing the introduction of treatments designed to prevent or retard the microvascular complications of type 1 diabetes in adolescents.
Maryland's Hospital Cost Review Commission at 40
Authors: John A. Kastor, Eli Y. Adashi
Journal: JAMA (2011)

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
BMPR2 Preserves Mitochondrial Function and DNA during Reoxygenation to Promote Endothelial Cell Survival and Reverse Pulmonary Hypertension
Authors: Isabel Diebold, Jan K. Hennigs, Kazuya Miyagawa, Caiyun G. Li, Nils P. Nickel, Mark Kaschwich, Aiqin Cao, Lingli Wang, Sushma Reddy, Pin-I Chen, Kiichi Nakahira, Miguel A. Alejandre Alcazar, Rachel K. Hopper, Lijuan Ji, Brian J. Feldman, Marlene Rabinovitch
Journal: Cell Metabolism (2015)
The Right of Falling Ill
Authors: H. Musaph
Journal: Psychotherapy and Psychosomatics (1979)

There are people who never permit themselves to fall ill. This negative illness is called by the present author: counter-hypochondriasis. Several defense mechanisms in counter-hypochondriasis are described, especially in relation to infantile roots. Pathological health is considered as a neurotic symptom formation in which disorders in object relationship are all-important.
The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling
Authors: Michael W.-H. Wang, Shi Wei, Roberta Faccio, Sunao Takeshita, Pablo Tebas, William G. Powderly, Steven L. Teitelbaum, F. Patrick Ross
Journal: Journal of Clinical Investigation (2004)

Highly active antiretroviral therapy (HAART), which includes HIV protease inhibitors (PIs), has been associated with bone demineralization. To determine if this complication reflects accelerated resorptive activity, we studied the impact of two common HIV PIs, ritonavir and indinavir, on osteoclast formation and function. Surprisingly, we find that ritonavir, but not indinavir, inhibits osteoclast differentiation in a reversible manner and also abrogates bone resorption by disrupting the osteoclast cytoskeleton, without affecting cell number. Ritonavir given in vivo completely blunts parathyroid hormone–induced osteoclastogenesis in mice, which confirms that the drug is bone sparing. In keeping with its antiresorptive properties, ritonavir impairs receptor activator of nuclear factor κB ligand–induced (RANKL-induced) activation of NF-κB and Akt signaling pathways, both critical to osteoclast formation and function. In particular, ritonavir is found to inhibit RANKL-induced Akt signaling by disrupting the recruitment of TNF receptor–associated factor 6/c-Src complex to lipid rafts. Thus, ritonavir may represent a bone-sparing PI capable of preventing development of osteopenia in patients currently on HAART.
Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells
Authors: Martina Lukasova, Camille Malaval, Andreas Gille, Jukka Kero, Stefan Offermanns
Journal: Journal of Clinical Investigation (2011)

Nicotinic acid (niacin) is a drug used to reduce the progression of atherosclerosis. Its antiatherosclerotic activity is believed to result from lipid-modifying effects, including its ability to decrease LDL cholesterol and increase HDL cholesterol levels in plasma. Here, we report that in a mouse model of atherosclerosis, we found that nicotinic acid inhibited disease progression under conditions that left total cholesterol and HDL cholesterol plasma levels unaffected. The antiatherosclerotic effect was not seen in mice lacking the receptor for nicotinic acid GPR109A. Surprisingly, transplantation of bone marrow from GPR109A-deficient mice into atherosclerosis-prone animals also abrogated the beneficial effect of nicotinic acid. We detected expression of GPR109A in macrophages in atherosclerotic plaques. In macrophages from WT mice, but not from GPR109A-deficient animals, nicotinic acid induced expression of the cholesterol transporter ABCG1 and promoted cholesterol efflux. Furthermore, activation of GPR109A by nicotinic acid inhibited MCP-1-induced recruitment of macrophages into the peritoneal cavity and impaired macrophage recruitment to atherosclerotic plaques. In contrast with current models, our data show that nicotinic acid can reduce the progression of atherosclerosis independently of its lipid-modifying effects through the activation of GPR109A on immune cells. We conclude therefore that GPR109A mediates antiinflammatory effects, which may be useful for treating atherosclerosis and other diseases.
Protein C and protein S. Vitamin K-dependent inhibitors of blood coagulation
Authors: M. E. Rick
Journal: JAMA (1990)

<h3>SELECTED CASE</h3> A 53-YEAR-OLD asymptomatic white man was evaluated for a possible thrombotic tendency after the death of his 19-year-old son from a pulmonary embolus. The father and his relatives had no history of venous thrombotic disease, but there was a history of coronary artery disease in the family. Physical examination of the father was normal. The deceased son had been athletic and was healthy until he sustained a knee injury that required surgery. His postoperative course had been uneventful for 8 weeks after the surgery, when he died suddenly. The postmortem examination revealed a massive pulmonary embolism. Testing performed on a postmortem blood sample was said to show low protein C levels. Laboratory tests showed that the father had a normal complete blood cell count and platelet count and normal results on screening coagulation tests (prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen). Immunologic assays for antithrombin
Abstract 1697: Pharmacological inhibition of ATM results in mitochondrial biogenesis in AMPK independent manner.
Authors: Hilal S. Khalil, Hemanth Tummala, Laura DeCaris, Nikolai Zhelev
Journal: Cancer Research (2013)

Abstract The gene mutated in Ataxia telangiectasia termed Ataxia Telangiectasia Mutated (ATM) encodes for a Serine/Threonine protein kinase which functions at the core of signalling network responsible for DNA damage recognition and repair. Recent evidence has supported the role of ATM beyond DNA repair and has been shown to function in metabolic regulation and cellular homeostasis. Here, we show that ATM regulates mitochondrial biogenesis in MCF-7 and A549 cancer cell lines. Inhibition of ATM kinase activity with its specific inhibitor KU55933 (KU) both with and without DNA damage by Doxorubicin or Bleomycin resulted in evoked cytosolic Ca2+ ions leading to rapid, but sustained induction of mitochondrial biogenesis in these cell lines. This induction was independent of AMPK, a kinase previously shown to be involved in mitochondrial biogenesis as KU treatment resulted in downregulation of phospho AMPK. Moreover siRNA mediated knockdown of AMPK could not prevent KU dependent induction of mitochondrial biogenesis. Interestingly, KU treatment resulted in induction of Extracellular signal-regulated kinase(ERK) and CREB phosphorylation. Inhibition of ERK signalling by using MEK inhibitor U0126 disrupted KU dependent induction of mitochondrial biogenesis demonstrating the involvement of ERK signalling cascade in mitochondrial biogenesis upon ATM or AMPK inhibition. These results demonstrate that ATM maintains cellular homeostasis by regulating AMPK mediated mitochondrial biogenesis and that perturbation in this pathway by KU treatment causes a switch in mitochondrial biogenesis in ERK dependent manner. This study indicates cancer cell's fail-safe mechanism in maintaining its homeostasis by up-regulating mitochondrial biogenesis upon inhibition of ATM. Citation Format: Hilal S. Khalil, Hemanth Tummala, Laura DeCaris, Nikolai Zhelev. Pharmacological inhibition of ATM results in mitochondrial biogenesis in AMPK independent manner. [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 1697. doi:10.1158/1538-7445.AM2013-1697
MS-12 * TEMOZOLOMIDE-BASED THERAPY FOR THE MANAGEMENT OF PROGRESSIVE PITUITARY CARCINOMA
Authors: C. Kamiya-Matsuoka, D. Cachia, S. G. Waguespack, I. E. McCutcheon, A. Mahajan, P. D. Brown, M. D. Groves, M. Penas-Prado
Journal: Neuro-Oncology (2014)

BACKGROUND: Pituitary carcinomas (PC) are very uncommon, accounting for only 0.1 % of all pituitary tumors and representing a treatment challenge. Diagnosis is based on presence of intra- and/or extracranial metastases. PC is resistant to current treatment regimens, with a median overall survival of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Temozolomide (TEM)-based regimens are being used in progressive PC, but its effectiveness and the schedule/duration of treatment have not been established. The aim of this study is to report our experience with TEM in patients with progressive PC. METHODS: Three adult patients with progressive PC who were treated with TEM at MDACC between 01/2010-06/2014 were identified. Clinical and radiographic data were extracted from medical records. RESULTS: All three cases had prior history of pituitary macroadenoma. Clinical presentation of PC included visual field deficits, headaches and/or Cushing syndrome. Pathology revealed a mean Ki67 index of 11.5 % (0.4-24.2%) with positive p53 staining in one case. Cavernous sinus invasion was common and metastases involved lymph nodes, liver, bone and leptomeninges. Case 1 received a combined regimen consisting of capecitabine and TEM (CAPTEM). Case 2 was treated with standard-dose TEM, CAPTEM, and chemoradiation with TEM followed by TEM. Case 3 with dissemination to the bone and leptomeninges was initially treated with standard-dose TEM, followed by dose-dense TEM at progression. In the two patients who received chemoradiation with TEM for extracranial disease, the progression-free survival (PFS) was 15 and 17 months, whereas the PFS after TEM-only was 13 months. The median overall survival was 41 months, with all the patients still alive. CONCLUSION: TEM-based therapy seems to be an appropriate initial treatment for PC, prolonging the PFS and leading to tumor-stabilization.
Preventing transmission of maternally inherited mitochondrial DNA diseases
Authors: J. Poulton, S. Kennedy, P. Oakeshott, D. Wells
Journal: BMJ (2009)

#### Summary points

#### Methods 

We used our personal archive of references, Medline searches, and consultation with other experts in the field to produce this review. It is derived from 22 years of research and 11 years of genetic counselling in mitochondrial DNA diseases.

Maternally inherited mutations of mitochondrial DNA can be asymptomatic or cause illnesses such as developmental regression, deafness, blindness, neuropathy, diabetes, cardiomyopathy, and liver failure. Families who have lost a child from a mitochondrial DNA disease (fig 1⇓) often seek genetic counselling before trying to conceive again. They may also need support from their general practitioner when deciding between treatments that could increase their chances of having a healthy baby, but some doctors have limited knowledge of current genetic advances. In February 2008, an important step towards nuclear transfer in humans was reported.1 The nucleus of a fertilised human egg was transplanted into an enucleated recipient egg (oocyte) from an unrelated donor, resulting in an embryo with “three genetic parents.” In future, this technique might help to prevent transmission of maternally inherited mitochondrial DNA diseases, a range of potentially devastating illnesses caused by defects in mitochondrial function. Meanwhile, other in vitro fertilisation related interventions have recently become available that should be offered more widely. Here, we explain why the management of mitochondrial DNA diseases has lagged behind the genetics …
Interaction between selenium and methylmercury.
Authors: S Skerfving
Journal: Environmental Health Perspectives (1978)

The available data on the influence of selenium on the toxicity of methylmercury and of methylmercury on selenium as a nutrient and toxic agent are reviewed. Selenium as selenite has a relative protective effect on acute and subacute toxicity of methylmercury in the rat and the quail. The protective mechanism is far from clear. Of special interest is the fact that selenium-treated animals may remain unaffected, even when they have attained tissue mercury levels otherwise associated with toxic effects. Selenite causes some increase of tissue mercury levels in methylmercury-exposed animals. On the other hand, methylmercury induces a remarkable enhancement of organ concentrations of selenium in animals given selenite. The interaction between selenium and methylmercury is in many ways different from that between selenium and inorganic mercury, and also from that between selenium and other metals. Due to the considerable interspecies differences in the toxicity of methylmercury, the available data do not allow conclusions on interactions in man. Practical implications of a possible protective effect of selenium on methylmercury toxicity in humans are discussed.
Demonstration of Rapid Onset Vascular Endothelial Dysfunction After Hyperhomocysteinemia
Authors: John C. Chambers, Andrew McGregor, Jeff Jean-Marie, Omar A. Obeid, Jaspal S. Kooner
Journal: Circulation (1999)

Hyperhomocysteinemia is a major and independent risk factor for vascular disease. The mechanisms by which homocysteine promotes atherosclerosis are not well understood. We hypothesized that elevated homocysteine concentrations are associated with rapid onset endothelial dysfunction, which is mediated through oxidant stress mechanisms and can be inhibited by the antioxidant vitamin C.We studied 17 healthy volunteers (10 male and 7 female) aged 33 (range 21 to 59) years. Brachial artery diameter responses to hyperemic flow (endothelium dependent), and glyceryltrinitrate (GTN, endothelium independent) were measured with high resolution ultrasound at 0 hours (fasting), 2 hours, and 4 hours after (1) oral methionine (L-methionine 100 mg/kg), (2) oral methionine preceded by vitamin C (1g/day, for 1 week), and (3) placebo, on separate days and in random order. Plasma homocysteine increased (0 hours, 12.8+/-1.4; 2 hours, 25.4+/-2.5; and 4 hours, 31. 2+/-3.1 micromol/l, P<0.001), and flow-mediated dilatation fell (0 hours, 4.3+/-0.7; 2 hours, 1.1+/-0.9; and 4 hours, -0.7+/-0.8%) after oral L-methionine. There was an inverse linear relationship between homocysteine concentration and flow-mediated dilatation (P<0. 001). Pretreatment with vitamin C did not affect the rise in homocysteine concentrations after methionine (0 hours, 13.6+/-1.6; 2 hours, 28.3+/-2.9; and 4 hours, 33.8+/-3.7 micromol/l, P=0.27), but did ameliorate the reduction in flow-mediated dilatation (0 hours, 4. 0+/-1.0; 2 hours, 3.5+/-1.2 and 4 hours, 2.8+/-0.7%, P=0.02). GTN-induced endothelium independent brachial artery dilatation was not affected after methionine or methionine preceded by vitamin C.We conclude that an elevation in homocysteine concentration is associated with an acute impairment of vascular endothelial function that can be prevented by pretreatment with vitamin C in healthy subjects. Our results support the hypothesis that the adverse effects of homocysteine on vascular endothelial cells are mediated through oxidative stress mechanisms.