tbuckley/cabot-search huggingface dataset:
Gemcitabine hepatic arterial chemoembolization (TACE) in the treatment of unresectable HCC
Authors: B. I. Carr
Journal: Journal of Clinical Oncology (2006)

4141 Background: Hepatocellular carcinoma (HCC) generally arises in the presence of cirrhosis and is typically multifocal and bilobar and thus not often resectable. A major limitation of chemotherapy is due to the damaged underlying liver as a result of cirrhosis. A non-hepatotoxic drug such as Gemcitabine is thus potentially useful in patient management. Methods: 57 patients with biopsy-proven HCC were evaluated for response, survival and toxicity after treatment with gemcitabine via hepatic arterial chemoembolization. Patients were treated with 1250 mg/m 2 , given in 150 ml of normal saline over 30 min to either the right or left hepatic artery at any one treatment session. Treatments were repeated every 8 to 10 weeks. Embospheres (Embogold, Biosphere Medical) 100–300 micron size were also injected to vascular slowing but not to occlusion of the same hepatic artery during the chemotherapy infusion. A CT scan was performed at baseline and just prior to each repeat treatment, which was continued until tumor progression. CBC, liver function tests and AFP were performed at baseline and monthly. Results: There were 19 partial responses (PR) (33%), 2 minor responses (4%), 24 patients with stable tumors (42%), 9 with tumor progression (16%) and 3 unevaluable (diffuse) (5%). Survival was: median 12 mo (range 1–36 mo). 23 patients survived 24 mo. There were no hepatotoxicities greater than grade 1 and no myelotoxicities greater than grade 2 (NCI common toxicity criteria). Conclusions: Gemcitabine chemoembolization (TACE) in unresectable HCC patients with normal bilirubin and without ascites appears to be entirely safe with a minimal clinical or laboratory toxicity and is associated with encouraging responses and survival. No significant financial relationships to disclose.
Complementation of reduced survival, hypotension, and renal abnormalities in angiotensinogen-deficient mice by the human renin and human angiotensinogen genes.
Authors: R L Davisson, H S Kim, J H Krege, D J Lager, O Smithies, C D Sigmund
Journal: Journal of Clinical Investigation (1997)

The aim of this study was to determine whether elements of the human renin-angiotensin system (RAS) could functionally replace elements of the mouse RAS by complementing the reduced survival and renal abnormalities observed in mice carrying a gene-targeted deletion of the mouse angiotensinogen gene (mAgt). Double transgenic mice containing the human renin (HREN) and human angiotensinogen (HAGT) genes were bred to mice heterozygous for the mAgt deletion and the compound heterozygotes were identified and intercrossed. The resulting progeny (n = 139) were genotyped at each locus and the population was stratified into two groups: the first containing both human transgenes (RA+) and the second containing zero or one, but not both human transgenes (RA-). Despite appropriate Mendelian ratios of RA- mice that were wildtype (+/+), heterozygous (+/-), and homozygous (-/-) for the deletion of mAgt at birth, there was reduced survival of RA- mAgt-/- mice to adulthood (P < 0.001 by chi2). In contrast, we observed appropriate Mendelian ratios of RA+ mAgt+/+, RA+ mAgt+/-, and RA+ mAgt-/- mice at birth and in adults (P > 0.05 by chi2). These results demonstrate that the presence of both human transgenes rescues the postnatal lethality in mAgt-/- mice. The renal histopathology exhibited by RA- mAgt-/- mice, including thickened arterial walls, severe fibrosis, lymphocytic infiltration, and atrophied parenchyma, was also rescued in the RA+ mAgt-/- mice. Direct arterial blood pressure recordings in conscious freely moving mice revealed that BP (in mmHg) varied proportionally to mAgt gene copy number in RA+ mice (approximately 20 mmHg per mAgt gene copy, P < 0.001). BP in RA+ mAgt-/- mice (132+/-3, n = 14) was intermediate between wild-type (RA- mAgt+/+, 105+/-2, n = 9) and RA+ mAgt+/+ (174+/-3, n = 10) mice. These studies establish that the human renin and angiotensinogen genes can functionally replace the mouse angiotensinogen gene, and provides proof in principle that we can examine the regulation of elements of the human RAS and test the significance of human RAS gene variants by a combined transgenic and gene targeting approach.
Is Botulinum Neurotoxin Type A (BoNT-A) a Novel Therapy for Lower Urinary Tract Symptoms Due to Benign Prostatic Enlargement? A Review of the Literature
Authors: Athanassios Oeconomou, Helmut Madersbacher, Gustav Kiss, Thomas J. Berger, Michael Melekos, Peter Rehder
Journal: European Urology (2008)
The secondary endosymbiont of the cryptomonad Guillardia theta contains alpha-, beta-, and gamma-tubulin genes
Authors: P. J. Keeling, J. A. Deane, C. Hink-Schauer, S. E. Douglas, U. G. Maier, G. I. McFadden
Journal: Molecular Biology and Evolution (1999)

Cryptomonads have acquired photosynthesis through secondary endosymbiosis: they have engulfed and retained a photosynthetic eukaryote. The remnants of this autotrophic symbiont are severely reduced, but a small volume of cytoplasm surrounding the plastid persists, along with a residual nucleus (the nucleomorph) that encodes only a few hundred genes. We characterized tubulin genes from the cryptomonad Guillardia theta. Despite the apparent absence of microtubules in the endosymbiont, we recovered genes encoding alpha-, beta-, and gamma-tubulins from the nucleomorph genome of G. theta. The presence of tubulin genes in the nucleomorph indicates that some component of the cytoskeleton is still present in the cryptomonad symbiont despite the fact that very little cytoplasm remains, no mitosis is known in the nucleomorph, and microtubules have never been observed anywhere in the symbiont. Phylogenetic analyses with nucleomorph alpha- and beta-tubulins support the origin of the cryptomonad nucleomorph from a red alga. We also characterized alpha and beta-tubulins from the host nucleus of G. theta and compared these with tubulins we isolated from two flagellates, Goniomonas truncata and Cyanophora paradoxa, previously proposed to be related to the cryptomonad host. Phylogenetic analyses support a relationship between the cryptomonad host and Goniomonas but do not support any relationship between cryptomonads and Cyanophora.
Hyperbasophilic immunoblasts in circulating blood in chronic inflammatory rheumatic and collagen diseases.
Authors: F Delbarre, A Le Go, A Kahan
Journal: Annals of the Rheumatic Diseases (1975)

The number of large circulating hyperbasophilic mononuclear cells - referred to as hyperbasophilic immunoblasts (HBI)- is often increased in collagen disease and rheumatoid arthritis (RA) and grossly reflects the degree of disease activity. In contrast, in psoriatic arthropathy the percentage of (HBI) is within the normal range. HBI are mainly involved in immune reactions and may provide a valuable routine test for the assessment of the latter in disease states and for the predicition of relapse in chronic collagen diseases. Immunofluorescent techniques applied to samples from active autoimmune diseases have shown that a number of HBI are Ig-producing B-blasts. Moreover, in a few cases these intracytoplasmic immunoglobulins exhibited a rheumatoid factor-like activity, a finding which promises to yield additional information on the immunopathogenesis of RA.
The Implications of Marijuana Legalization in Colorado
Authors: Andrew A. Monte, Richard D. Zane, Kennon J. Heard
Journal: JAMA (2014)

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
Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells
Authors: Bhavik Desai, Michael J Rogers, Meenakshi A Chellaiah
Journal: Molecular Cancer (2007)

The expression level of osteopontin correlates with the metastatic potential of several tumors. Osteopontin is a well-characterized ligand for the alphavbeta3 integrin. The present study was undertaken to elucidate the possible role of osteopontin/alphavbeta3 signaling in prostate cancer cell migration.We generated stable prostate cancer cell (PC3) lines that over-express osteopontin (PC3/OPN), mutant OPN in the integrin binding-site (PC3/RGDDeltaRGA), and null for OPN (PC3/SiRNA). The following observations were made in PC3/OPN cells as compared with PC3 cells: 1) an increase in multinucleated giant cells and RANKL expression; 2) an increase in CD44 surface expression, interaction of CD44/MMP-9 on the cell surface, MMP-9 activity in the conditioned medium, and cell migration; 3) western blot analysis of concentrated conditioned medium exhibited equal levels of MMP-9 protein in all PC3 cells. However, zymography analysis demonstrated that the levels of MMP-9 activity in the conditioned media reflect the CD44 surface expression pattern of the PC3 cell lines; 4) although MMP-9 and MMP-2 are secreted by PC3 cells, only the secretion of MMP-9 is regulated by OPN expression. A strong down regulation of the above-mentioned processes was observed in PC3/OPN (RGA) and PC3/SiRNA cells. PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells.Rho signaling plays a crucial role in CD44 surface expression. BPs inhibits the mevalonate pathway, which in turn, prevents the prenylation of a number of small GTPases. Attenuation of Rho GTPase activation by BPs may have contributed to the down regulation of cell surface CD44/MMP-9 interaction, MMP-9 activation/secretion, and cell migration. Taken together, these observations suggest that CD44 surface expression is an important event in the activation of MMP-9 and migration of prostate cancer cells. The various steps involved in the above mentioned signaling pathway and/or the molecules regulating the activation of MMP-9 are potential therapeutic target.
Long-term Particulate and Other Air Pollutants and Lung Function in Nonsmokers
Authors: DAVID E. ABBEY, RAOUL J. BURCHETTE, SYNNØVE F. KNUTSEN, WILLIAM F. McDONNELL, MICHAEL D. LEBOWITZ, PAUL L. ENRIGHT
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The associations between lung function measures (spirometry and peak expiratory flow lability) and estimated 20-yr ambient concentrations of respirable particles, suspended sulfates, sulfur dioxide, ozone, and indoor particles were studied in a sample of 1,391 nonsmokers followed since 1977. Differences in air pollutants across the population were associated with decrements of lung function. An increase of 54 d/yr when particles < 10 μ m in diameter (PM10) exceeded 100 μ g/m3 was associated with a 7.2% decrement in FEV1, as percent of predicted, in males whose parents had asthma, bronchitis, emphysema, or hay fever and with increased peak expiratory flow lability of 0.8% for all females and 0.6% for all males. An increase in mean SO4 concentration of 1.6 μ g/m3 was associated with a 1.5% decrement in FEV1, as percent of predicted, in all males. An increase of 23 ppb of ozone as an 8-h average was associated with a 6.3% decrement in FEV1, as percent of predicted, in males whose parents had asthma, bronchitis, emphysema, or hay fever.
Costly efforts to widen access to medical profession are failing, says BMA
Authors: A. O'Dowd
Journal: BMJ (2009)

Efforts to widen access to the medical profession are failing, despite years of investment and initiatives aimed at opening the profession to people from all backgrounds.

Just over 15% of people entering medicine in the United Kingdom are from the four lowest socioeconomic groups, which make up just under half of the population, and that percentage has risen by only 1.7% over five years, says a new report published by the BMA.

Ministers are failing in their effort to make medicine an accessible career option for people from poorer backgrounds, says the report, which analyses the backgrounds of the UK’s 40 000 medical students.

Most …
Intracellular Patterns of Her-2/neu, ras, and Ploidy Abnormalities in Primary Human Breast Cancers Predict Postoperative Clinical Disease-Free Survival
Authors: Stanley E. Shackney, Charles A. Smith, Agnese Pollice, Kathryn Brown, Roger Day, Thomas Julian, Jan F. Silverman
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In an earlier study (S. E. Shackney et al., Cancer J. Sci. Am., 2: 106, 1996), the presence of aneuploidy, Her-2/neu overexpression, and ras overexpression in the same cells (triple-positive cells) was of prognostic significance (P &amp;lt; 0.015) in 91 patients with localized breast cancer (median follow up, 32 months). Here, we present results involving a larger group of patients with longer follow-up. Experimental Design: Fixed cell suspensions prepared from primary tumors of 189 patients with early breast cancer were studied prospectively by multiparameter flow cytometry. Correlated intracellular fluorescence-based measurements of cell DNA content and Her-2/neu and ras protein were obtained on each of &amp;gt;2000 cells in each tumor. Intracellular combinations of abnormalities in these measurements were correlated with subsequent patient disease-free survival (DFS). Median time on study was 54 months (range, 7–128 months). Results: DFS of patients with ≥5% triple-positive tumor cells was shorter than those who did not meet this criterion (P = 0.004). The difference remained statistically significant after accounting for nodal status, tumor size, and each of the component abnormalities (P = 0.006). Node-negative patients whose tumors had fewer than 2 abnormalities/cell had an especially favorable clinical course, with a 5-year DFS of 96% (lower confidence bound, 86%). Conclusions: Patterns of accumulated intracellular molecular abnormalities in cells of primary human breast cancers are predictive for subsequent DFS independently of the abnormalities themselves taken individually.
Survival and prediction of successful ventilator weaning in COPD patients requiring mechanical ventilation for more than 21 days
Authors: S Nava, F Rubini, E Zanotti, N Ambrosino, C Bruschi, M Vitacca, C Fracchia, C Rampulla
Journal: European Respiratory Journal (1994)

We studied survival and failure or success of weaning from mechanical ventilation (MV) in 42 consecutive chronic obstructive pulmonary disease (COPD) patients requiring prolonged MV (more than 21 days) after an episode of acute respiratory failure requiring admission to our Intermediate Intensive Care Unit (IICU). Parameters including arterial blood gases, pulmonary function tests, respiratory muscle force, neuromuscular drive, and nutritional status were recorded during a phase of clinical stability, in order to identify the features related to survival and weaning. All the patients were submitted to a comprehensive rehabilitation programme. Successful weaning from MV was defined as complete respiratory autonomy for at least 48 h. Twenty three patients were successfully weaned from MV after an average period of 44 days (Group A), requiring no further MV during their stay in hospital, whilst the remaining 19 patients were not able to be disconnected from the ventilator (Group B). The discriminant analysis showed that weaning from MV was significantly associated with arterial carbon dioxide tension (PaCO2), neuromuscular drive (P0.1), maximal inspiratory pressure (MIP), arterial oxygen tension (PaO2), the ratio of respiratory frequency to tidal volume (f/VT) and the serum protein level. Other pulmonary function tests (forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), anthropometric data, nutritional status, number of pulmonary exacerbations during MV and evidence of cor pulmonale, were similar in the two groups. The discriminant equation considering PaCO2 and MIP could separate the two groups with an accuracy of 84%. The overall survival at 2 yrs was 40%; in Group B it was significantly lower than in Group A (22 vs 68%). Most of the deaths occurred within the first 120 days after intubation.(ABSTRACT TRUNCATED AT 250 WORDS)
Risk Factors for Plantar Foot Ulcer Recurrence in Neuropathic Diabetic Patients
Authors: Roelof Waaijman, Mirjam de Haart, Mark L.J. Arts, Daniel Wever, Anke J.W.E. Verlouw, Frans Nollet, Sicco A. Bus
Journal: Diabetes Care (2014)

OBJECTIVE Recurrence of plantar foot ulcers is a common and major problem in diabetes but not well understood. Foot biomechanics and patient behavior may be important. The aim was to identify risk factors for ulcer recurrence and to establish targets for ulcer prevention. RESEARCH DESIGN AND METHODS As part of a footwear trial, 171 neuropathic diabetic patients with a recently healed plantar foot ulcer and custom-made footwear were followed for 18 months or until ulceration. Demographic data, disease-related parameters, presence of minor lesions, barefoot and in-shoe plantar peak pressures, footwear adherence, and daily stride count were entered in a multivariate multilevel logistic regression model of plantar foot ulcer recurrence. RESULTS A total of 71 patients had a recurrent ulcer. Significant independent predictors were presence of minor lesions (odds ratio 9.06 [95% CI 2.98–27.57]), day-to-day variation in stride count (0.93 [0.89–0.99]), and cumulative duration of past foot ulcers (1.03 [1.00–1.06]). Significant independent predictors for those 41 recurrences suggested to be the result of unrecognized repetitive trauma were presence of minor lesions (10.95 [5.01–23.96]), in-shoe peak pressure &amp;lt;200 kPa with footwear adherence &amp;gt;80% (0.43 [0.20–0.94]), barefoot peak pressure (1.11 [1.00–1.22]), and day-to-day variation in stride count (0.91 [0.86–0.96]). CONCLUSIONS The presence of a minor lesion was clearly the strongest predictor, while recommended use of adequately offloading footwear was a strong protector against ulcer recurrence from unrecognized repetitive trauma. These outcomes define clear targets for diabetic foot screening and ulcer prevention.
Association of primary cutaneous amyloidosis with atopic dermatitis: a nationwide population-based study in Taiwan
Authors: D.D. Lee, C.K. Huang, P.C. Ko, Y.T. Chang, W.Z. Sun, Y.J. Oyang
Journal: British Journal of Dermatology (2010)

Primary cutaneous amyloidosis (PCA) is a pruritic skin disorder most commonly seen in Southeast Asia and South America. Association of PCA with atopic dermatitis (AD) has been reported in the literature. However, no large-scale epidemiological study of PCA and its associations with other diseases has been conducted so far.We aimed to provide overall demographic data and comorbidities of patients with PCA based on a nationwide database in Taiwan.Cases of PCA were collected from records of National Health Insurance claims from 2000 to 2007. We analysed patients' gender, age when the diagnosis was first made, and the overall 8-year prevalence. We also investigated comorbidities.The overall 8-year prevalence of PCA was 7·87 per 10,000 persons. Although there was no significant gender difference in the prevalence of PCA, men and women showed a different peak age (men, 71-80 years; women, 41-50 years) and a different age distribution at diagnosis. The mean age at diagnosis of PCA was significantly younger for women than for men. Men sought medical assistance for PCA more frequently than women. There was a higher disease activity from May to September than during other months. PCA was strongly associated with AD (odds ratio 7·18). Patients with PCA had a higher comorbidity of hyperlipidaemia and diabetes mellitus.This is the first nationwide population-based epidemiological study of PCA. We demonstrate that PCA can be associated with other disorders, especially AD.
Monozygotic twins with stiff person syndrome and autoimmune thyroiditis: rituximab inefficacy in a double-blind, randomised, placebo controlled crossover study
Authors: N Venhoff, M Rizzi, U Salzer, L Bossaller, J Thoden, H Eibel, U A Walker
Journal: Annals of the Rheumatic Diseases (2009)

Autoimmune polyglandular syndromes result from the failure of multiple endocrine glands due to an autoimmune process. In autoimmune polyglandular syndrome type 3, autoimmune thyroiditis is associated with autoimmune diseases other than Addison’s disease and hypoparathyroidism.1

We report two identical twins with the rare combination of autoimmune thyroiditis with stiff person syndrome (SPS). SPS presents with progressive muscle rigidity and spasms of axial muscles and extremities.2 The majority of SPS patients have serum autoantibodies against glutamic acid decarboxylase (GAD)65,3 an enzyme responsible for the synthesis of γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the central nervous system (CNS). GAD65 antibodies probably play a direct pathogenetic role in SPS because they are found within the cerebrospinal fluid (CSF) and block the activity of …
Aberrant Expression of Collagen Triple Helix Repeat Containing 1 in Human Solid Cancers
Authors: Liren Tang, Derek L. Dai, Mingwan Su, Magdalena Martinka, Gang Li, Youwen Zhou
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The collagen triple helix repeat containing 1 (CTHRC1) is a promigratory protein first found to be expressed during rat tissue repair process. Recent preliminary results revealed CTHRC1 mRNA in melanoma and breast cancer. However, the full significance of CTHRC1 to human carcinogenesis remains unclear. This study is to further characterize the clinical and functional relevance of CTHRC1 in melanoma and other human solid cancers. Experimental Design: First, semiquantitative immunohistochemistry analysis was done on 304 clinically annotated, paraffin-embedded biopsies representing different stages of melanoma progression. Then, short interfering RNA was used to inhibit expression of CTHRC1 protein for migration analysis on cultured melanoma cells. Finally, the CTHRC1 expression was surveyed in 310 samples representing 19 types of human solid cancers. Results: In benign nevi and noninvasive melanoma biopsies, there was little CTHRC1 protein expression. In contrast, in invasive primary melanomas, there was a significant increase of CTHRC1 protein (P &amp;lt; 0.01, χ2 test). There was a further increase of CTHRC1 protein in metastatic melanoma specimens compared with nonmetastatic lesions (P &amp;lt; 0.01, χ2 test). In addition, inhibition of CTHRC1 expression resulted in decreased cell migration in vitro. Finally, transcription survey in 19 types of human solid cancers revealed aberrant CTHRC1 expression in 16 cancer types, especially cancers of the gastrointestinal tract, lung, breast, thyroid, ovarian, cervix, liver, and the pancreas. Conclusions: Aberrant expression of CTHRC1 is widely present in human solid cancers and seems to be associated with cancer tissue invasion and metastasis. It potentially plays important functional roles in cancer progression, perhaps by increasing cancer cell migration.