tbuckley/cabot-search huggingface dataset:
Abstract LB-105: Single nucleotide polymorphisms (SNPs) in the CYP19A1 gene are strongly associated with CYP1A2 expression: First evidence for epistasis in the CYP superfamily
Authors: Xuemei Zhang, Susan Kadlubar, Kelly Mercer, Xinfeng Yu, Ishwori Dhakal, Marjorie Beggs, David Caldwell, Vineetha Koroth Edavana, Suzanne Williams, Fred F. Kadlubar
Journal: Cancer Research (2010)

Abstract CYP1A2 is a member of the cytochromes P450 enzymes responsible for the oxidative metabolism of a wide array of endo- and xenobiotics, and has been demonstrated to be the major isoform responsible for oxidation of estrone and estradiol. To date, SNPs identified in this gene do not adequately explain the 60-80-fold variation in activity observed in Caucasians. We hypothesized that CYP1A2 could be a target of epistatic regulation (i.e., gene-gene interactions where SNPs in one gene influence the expression of another). CYP1A2 and CYP19A1 both lie on chromosome 15, and since CYP19A1 (aromatase) is responsible for the production of estrogens, and CYP1A2 is the primary catabolic P450, we hypothesized that these genes could be coordinately regulated, and SNPs influencing levels of CYP19A1 could also be related to expression levels of CYP1A2. Two TagSNPs (rs749292 A&amp;lt;G and rs727479 A&amp;lt;C) in CYP19A1 were genotyped using Beckman Single Base Extension Kit and TaqMan MGB probe, respectively. Levels of CYP1A2 protein in human liver microsomes from 100 donors were assessed by Western blotting and correlations between CYP19A1 SNPs and CYP1A2 protein amounts were determined. CYP1A2 expression was significantly higher in specimens with CYP19A1 (rs727479) AA homozygous compared with CC genotype (P&amp;lt;0.001), a SNP associated with increased CYP19A1 activity. CYP1A2 expression also is related CYP19A1 (rs749292) polymorphism and AA genotype carriers have higher CYP1A2 expression compared with GG genotype carriers. Moreover, in silico analyses shows the presence of over 300 putative estrogen-responsive elements upstream of the CYP1A2 transcription start sit. SNPs in CYP19A1 are significantly associated with CYP1A2 protein expression. This is the first evidence of epistasis in the P450 enzymes and suggests a role of estrogens in the regulation of CYP1A2. 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 LB-105.
THU0204 Lumbar interspinous bursitis in active polymyalgia rheumatica
Authors: C. Salvarani, L. Barozzi, M.G. Catanoso, L. Boiardi, N. Pipitone, P. Macchioni, G. Pazzola, G. Bajocchi, O. Addimanda, F. Muratore
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the inflammatory involvement of lumbar interspinous bursitis in patients with polymyalgia rheumatica (PMR) using magnetic resonance imaging (MRI). <h3>Methods</h3> Ten consecutive, untreated new patients with PMR and pain in the shoulder and pelvic girdles were investigated. Seven patients with spondyloarthritis (4 with psoriatic spondyloarthrits, one with entheropatic spondyloarthritis, and 2 with primary ankylosing spondylitis), 2 patients with spine osteoarthritis, and 2 patients with rheumatoid arthritis with lumbar pain served as controls. MRI of lumbar spine was performed in all 10 PMR case patients and in 11 control patients. Nine patients (5 PMR case patients and 4 control patients) also had MRI of the dorsal spine. <h3>Results</h3> MRI evidence of interspinous lumbar bursitis was found in 9/10 patients with PMR and in 5 control patients. A moderate to marked (grade≥2 on a semiquantitative 0-3 scale) lumbar bursitis occurred significantly more frequently in patients with PMR than in control patients (60% compared to 9%, p=0.024). In most of the patients and controls with lumbar bursitis the involvement was found at L3-L5 lumbar interspaces, only 2 patients had a more extended involvement (one case patient showed L1-L5 bursitis, and one control patient L2-L4 bursitis). No evidence of interspinous bursitis was showed at MRI of dorsal spine in case patients and controls. <h3>Conclusions</h3> Inflammation of lumbar bursae may be responsible for the low back pain reported by patients with PMR and hip girdle involvement. The prominent inflammatory involvement of cervical and lumbar bursae supports the hypothesis that PMR may be a disorder affecting predominantly extra-articular synovial structures, in particular of bursae. <h3>Disclosure of Interest</h3> None Declared
Diagnostic Strategy — The Shotgun versus the Arrow
Authors: George E. Thibault
Journal: New England Journal of Medicine (1995)

A 72-year-old man came to the emergency room with recurrent shortness of breath and dizziness.The combination of shortness of breath and dizziness makes me think about a cardiac event, and the shortness of breath raises the possibility of heart failure. The dizziness suggests that the patient's cardiac output might be low. A disturbance of rhythm — either atrial or ventricular tachyarrhythmia — would be the first possibility I would be concerned about.The patient had a history of hypertension, non-insulin-dependent diabetes mellitus, and chest pain on exertion that was responsive to nitroglycerin and that occurred three . . .
Abstract SY21-03: Skin stem cells in morphogenesis and cancer.
Authors: Elaine Fuchs, Slobodan Beronja, Markus Schober
Journal: Cancer Research (2013)

Abstract Stem cells have the ability to self-renew long term and differentiate into one or more tissues. Typically, stem cells are used sparingly to replenish cells during normal homeostasis. This is particularly true of adult tissues that undergo relatively infrequent or periodic turnover. However, even stem cells that are quiescent must be able to respond quickly to injury in order to fuel rapid tissue regeneration. How stem cells balance self-renewal and differentiation is of fundamental importance to our understanding of normal tissue maintenance and wound repair. Moreover, increasing evidence suggests that the regulatory circuitry governing this balancing act is at the root of some types of tumors both in mice and in humans. We've been using skin as a paradigm to understand how stem cells function in normal tissue generation and how this process goes awry in cancer. We've elucidated many of the pathways involved in how extrinsic signaling mobilizes stem cells to make tissue. In so doing, we have revealed mechanisms which are also deregulated in a variety of different human cancers. This has led us to the realm of identifying cancer stem cells (tumor-initiating cells) of squamous cell carcinomas of the skin. The second most abundant form of cancer world-wide, skin squamous cell carcinomas also establish a paradigm for many life-threatening cancers of lung, esophagus, breast, cervix, prostate, throat and oral tissues. We've demonstrated that when purified and transplanted serially into the skins of host recipients, a single cancer stem cell from a skin squamous cell carcinoma can generate a new squamous cell carcinoma that is similar in properties to the parent tumor. We've also discovered that cancer stem cell numbers and aggressiveness are predicated on the tumor microenvironment and on the ability of cancer stem cells to respond to it. The striking differences between the microenvironments of cancer stem cells and their normal counterparts seems likely to contribute to why their expression profiles are also markedly distinct. These findings underscore the importance of dissecting the molecular mechanisms of tumor progression and growth in vivo. To this end, we've developed a non-invasive method to knockdown genes rapidly, efficiently and selectively in the skin epithelium. We've exploited this technology to carry out a whole genome-wide screen in mice for genes that are selectively involved in regulating oncogenic growth in the skin. Our findings have major implications for our understanding of tumor progression and cancer. [This work was supported by the HHMI and a grant from the National Institutes of Health] Citation Format: Elaine Fuchs, Slobodan Beronja, Markus Schober. Skin stem cells in morphogenesis and cancer. [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 SY21-03. doi:10.1158/1538-7445.AM2013-SY21-03
Effect of the Interval between Pregnancies on Perinatal Outcomes
Authors: Bao-Ping Zhu, Robert T. Rolfs, Barry E. Nangle, John M. Horan
Journal: New England Journal of Medicine (1999)

A short interval between pregnancies has been associated with adverse perinatal outcomes. Whether that association is due to confounding by other risk factors, such as maternal age, socioeconomic status, and reproductive history, is unknown.We evaluated the interpregnancy interval in relation to low birth weight, preterm birth, and small size for gestational age by analyzing data from the birth certificates of 173,205 singleton infants born alive to multiparous mothers in Utah from 1989 to 1996.Infants conceived 18 to 23 months after a previous live birth had the lowest risks of adverse perinatal outcomes; shorter and longer interpregnancy intervals were associated with higher risks. These associations persisted when the data were stratified according to and controlled for 16 biologic, sociodemographic, and behavioral risk factors. As compared with infants conceived 18 to 23 months after a live birth, infants conceived less than 6 months after a live birth had odds ratios of 1.4 (95 percent confidence interval, 1.3 to 1.6) for low birth weight, 1.4 (95 percent confidence interval, 1.3 to 1.5) for preterm birth, and 1.3 (95 percent confidence interval, 1.2 to 1.4) for small size for gestational age; infants conceived 120 months or more after a live birth had odds ratios of 2.0 (95 percent confidence interval, 1.7 to 2.4);1.5 (95 percent confidence interval, 1.3 to 1.7), and 1.8 (95 percent confidence interval, 1.6 to 2.0) for these three adverse outcomes, respectively, when we controlled for all 16 risk factors with logistic regression.The optimal interpregnancy interval for preventing adverse perinatal outcomes is 18 to 23 months.
AB0115 Influence of mtorc2/akt on the cell viability in rheumatoid arthritis fibroblast-like synoviocytes
Authors: Y. Pan, X. Guo, L. Fang
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent studies have shown that Akt signaling is activative in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and plays an important role of anti-apoptosis in the pathogenesis of RA. Akt can be fully activated by phosphorylation at Ser473 by mTORC2 (mammalian target of rapamycin complex 2), one of whose key components is RICTOR (rapamycin-insensitive companion of mTOR). We assumed that mTORC2/Akt might involve in the pathological processes of RA-FLS. <h3>Objectives</h3> To investigate the influence of mTORC2/Akt on the cell viability in RA-FLS. <h3>Methods</h3> FLS were isolated from the primary synovial tissue obtained from three patients with RA. After being transfected with RICTOR siRNA by cationic liposome for 48h, RA-FLS was treated with or without 10ng/ml TNF-alpha for 24h and 48h. The expression of RICTOR and Akt and the level of phosphorylated Akt at Ser473 were evaluated by western blotting, and the cell viability was analyzed by methyl thiazol tetrazolium (MTT) assay. After treatment with Akt pathway blocker MK-2206 at the dose of 0uM, 1uM, 2uM, 4uM and 8uM for 24h and 48h, the expression of Akt and the level of phosphorylated Akt at Ser473 were detected by western blotting. RA-FLS was incubated with MK-2206 at the dose of 0uM, 4uM and 8uM, and the cell viability was analyzed by MTT after 1.5h, 3h, 6h, 12h, 24h and 48h. <h3>Results</h3> 1) After the silence of RICTOR, the level of phosphorylated Akt at Ser473 increased and the cell viability decreased in RA-FLS, no matter with or without TNF-alpha for 48h later. But the expression of Akt was not influenced by the transfection with RICTOR siRNA. 2) In comparison with the control group, treatment of RA-FLS with MK-2206 at doses of 4uM, 8uM for 48h inhibited the expression of Akt protein and the level of phosphorylated Akt at Ser473. 3) The effect of MK-2206 on the cell viability of RA-FLS was time- and dose-dependent, since the cell viability significantly decreased after the treatment with MK-2206 for more than 3h at the dose of 8uM. <h3>Image/graph</h3> <h3>Conclusions</h3> There is an unexpected result that silencing RICTOR (thus mTORC2) causes the increasing level of phosphorylated Akt at Ser473 of RA-FLS in vitro. But at the same time, inhibiting the activation of mTORC2 and Akt can both reduce the cell viability of RA-FLS. These results indicate that the abnormity of mTORC2/Akt may contribute to the stable activation of RA-FLS. <h3>References</h3> Nissim Hay, Nahum Sonenberg. Upstream and downstream of mTOR. Genes Dev. 2004,18: 1926-1945. <h3>Disclosure of Interest</h3> None Declared
Nuclear factor-erythroid 2 (NF-E2) expression in normal and malignant megakaryocytopoiesis
Authors: L Catani, N Vianelli, M Amabile, L Pattacini, L Valdrè, ME Fagioli, M Poli, L Gugliotta, P Moi, MG Marini, G Martinelli, S Tura, M Baccarani
Journal: Leukemia (2002)
The Long-Term Outcome of Microvascular Decompression for Trigeminal Neuralgia
Authors: Fred G. Barker, Peter J. Jannetta, David J. Bissonette, Mark V. Larkins, Hae Dong Jho
Journal: New England Journal of Medicine (1996)

Several surgical procedures to treat trigeminal neuralgia (tic douloureux) are available, but most reports provide only short-term follow-up information.
Stimulation of Growth by Both Androgen and Estrogen of the EMP-K1 Transplantable Tumor With Androgen and Estrogen Receptors From Human Extramammary Paget's Disease in Nude Mice
Authors: M. Nishi, M. Tashiro, H. Yoshida
Journal: JNCI Journal of the National Cancer Institute (1992)

Background: Experimental approaches using transplantable human tumors in nude mice have greatly improved studies on their pathogenesis and treatment. Purpose: We studied the establishment of a transplantable tumor, EMP-K1, derived from extramammary Paget's disease and the morphology and unique hormone dependence of this tumor. Methods: Tissue fragments from a metastatic skin tumor of an 80-year-old man with primary genital extramammary Paget's disease were implanted into male nude BALB/c mice. Tissue fragments of the established tumor were implanted into 50 castrated male 8-week-old nude mice, which were given injections of 100μg testosterone propionate (TP), 100 μg 5α-dihydrotestosterone (DHT), 10 μg diethylstilbestrol (DES), or 1, 10, or 100μg 17β-estradiol (E 2 ). All injections were administered intramuscularly once daily, starting from the day of transplantation. The established tumors were examined immunohisto-chemically and biochemically. Results: A transplantable tumor (EMP-K1) was established in the nude mouse. EMP-K1 tumor cells expressed antigens such as carcinoembryonic antigen and epithelial membrane antigen, cytokeratin, and c-erbB-2 protein and contained androgen, estrogen, and progesterone receptors. The growth of the EMP-K1 tumor was stimulated by TP, DHT, DES, and E 2 . Conclusions: These results suggest that both androgen and estrogen may stimulate the growth of the same tumor by both androgen receptor and estrogen receptor pathways. Implications: The EMP-K1 tumor is a useful tool for studies on the biology of extramammary Paget's disease, and further studies using these tumors will provide useful information concerning proper hormone therapy. [J Natl Cancer Inst 84: 519–523, 1992]
Staging and Response of Sternal Histoplasmosis by 18F-FDG PET/CT
Authors: Sellam Karunanithi, Ganesh Kumar, S K Sharma, Deepali Jain, Aashish Gupta, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2014)

Histoplasmosis, a granulomatous mycosis caused by the fungus Histoplasma capsulatum, is known to primarily affect the lungs and the immune system, with involvement of skeletal system as a rare manifestation, in which case the disease usually assumes multifocality. We present a singular case of a young man diagnosed to have an isolated skeletal histoplasmosis involving the body of sternum where 18F-FDG PET/CT played major role in both diagnosis and in response evaluation to antifungal therapy.
Correlation of Nonspecific Antiviral Activity with the Ability to Isolate Infectious Hiv-1 from Saliva
Authors: Dorian H. Coppenhaver, Pat Sriyuktasuth-Woo, Samuel Baron, Charles E. Barr, M. Nasar Qureshi
Journal: New England Journal of Medicine (1994)

To the Editor: Despite evidence of HIV in the saliva of HIV-positive persons, oral transmission of the virus appears to be a rare event. Researchers have isolated infectious virus from only a small percentage of saliva samples from HIV-infected patients, even when virus can be isolated from peripheral-blood samples from the same persons1,2 or when HIV DNA is detected in saliva by the polymerase chain reaction3. Components of saliva can inhibit HIV4 and other viruses5. Can the presence of salivary viral inhibitors explain the low rate of recovery of HIV from oral fluids? Recently, we tested saliva . . .
SAT0589-HPR Benefits of Strengthening Exercises with the Aid of Swiss Ball in Patients with Fibromyalgia: a Randomized Controlled Trial
Authors: J. S. Arakaki, F. Jennings, G. Q. Estrela, V. da Cruz, J. Natour
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia isa painful syndrome that determines global reduction in physical capacity. Exercises are essential in the treatment of FM, and currently, muscle strengthening have shown promising results. <h3>Objectives</h3> To evaluate the effectiveness of strengthening exercises using a Swiss Ball in the treatment of FM. <h3>Methods</h3> Sixty patients with FM were selected and randomized into two groups: intervention group (IG) who performed strength training using a Swiss ball and control group (CG) who performed stretching exercises. The trainings were performed 3 times per week, lasting 40 minutes. The IG performed strengthening exercises with a Swiss ball with the aim of recruiting the major muscle groups: deltoid, biceps, triceps, pectoralis major, rhomboid, trapezius, latissimus dorsi, retus abdominal. The control group performed stretching exercises for the same muscle groups trained by IG. Measuring instruments: VAS (visual analogue scale) to evaluate pain; the 1 RM (1-repetition maximum) test to assess muscle strength; FIQ (fibromyalgia impact questionaire) to assess the impact of disease; and the SF-36 questionnaire to evaluate general quality of life. All participants underwent an evaluation at the beginning and at 6 (T6) and 12 (T12) weeks after randomization. <h3>Results</h3> At baseline, the two groups were homogeneous regarding demographic and clinical characteristics. The IG showed statistically significant improvement (p &lt;0.05) in VAS for pain and FIQ compared to GC at T6 and T12. IG showed significant improvement of muscle strength evaluated by the loads in most prescribed exercises compared to the control group over time. Both groups improved their overall quality of life, but without significant differences between groups. <h3>Conclusions</h3> The strengthening exercise program using a Swissball determined improvement in pain, health-related quality of life and muscle strength in patiemnts with FM compared with the stretching exercises, without deleterious effects. <h3>References</h3> Bellato. E; Marini. E; Castoldi. F; Barbasetti. N; Mattei. L; Bonasia. D. E; Blonda. D. Fibromialgya Syndrome: Etiologya, Pathogenesis, Diagnosis, and Treatment. <b>Pain Research and Treatment</b>. 2012. Busch, A. J; Webber. S. C; Brachaniec. M; Bidonde. J; Dal Bello-Hass. V; Danyliw. A; Overend. T. J; Richards. R. S. Exercise Therapy for Fibromialgya. <b>Current Pain and Headache Reports</b>. 15(5), p. 358-367, 2011. Lehman, G. J; Gordon, T; Langley, J; Pemrose, P; Tregaskis, S. Replacing a Swiss ball for an exercise bench causes variable changes in trunk muscle activity during upper limb strength exercises. <b>Dyn Med</b>. 3; 4:6, 2005. <h3>Disclosure of Interest</h3> None Declared
Somatization in cross-cultural perspective: a World Health Organization study in primary care
Authors: O Gureje, G E Simon, T B Ustun, D P Goldberg
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to examine the phenomenon of somatization in different cultures by determining its frequency and correlates in primary care settings in 14 countries.Consecutive primary care patients (N = 25,916) were screened with the 12-item General Health questionnaire, and a stratified sample (N = 5,438) was interviewed with the Composite International Diagnostic Interview. Interviewed patients were also assessed for physical disease burden, self-rated overall health, physician-rated physical health status, number of disability days, and interviewer-rated occupational role functioning. The authors determined center-specific associations with the use of logistic regression analyses in which confounding variables were controlled.ICD-10 defined somatization disorder was relatively uncommon in most primary care settings. A less restrictively defined form was more common. Symptom rates were much higher in South American sites. There was a modest association with low education. Otherwise, frequency of unexplained somatic symptoms did not clearly vary according to geography or level of economic development. Somatizing patients were at elevated risk for self-reported disease burden, negative perception of their health, and comorbid depression and generalized anxiety disorder. Somatization was also commonly associated with disability. Cultures did not differ markedly in the pattern of these associated features.Somatization is a common problem in primary care across cultures and is associated with significant problems and disability.