tbuckley/cabot-search huggingface dataset:
Abstract 2388: Targeted expression of BAG3 to the murine mammary gland (MMTV-hBAG3) reveals a role in mammary tumorigenesis
Authors: Giovanna Casagrande, Minshu Yu, Jaime Rodriguez-Canales, Elise C. Kohn, Victoria M. Virador
Journal: Cancer Research (2011)

Abstract We have previously shown that BAG3 is a pro-survival protein in human cancer lines subject to stress. BAG3 overexpression also mediates a decrease in migration and adhesion to matrix in MDA-435 breast cancer cells; this is reversed in a BAG3 mutant with a deleted proline-rich domain (PXXP). Additionally, BAG3 induces the secreted molecule CCN-1 to regulate in vitro invasion of HeLa cells. This led us to hypothesize that MMTV-driven human BAG3 would contribute to mammary tumorigenesis. This was examined through generation and analysis of a transgenic mouse model of human BAG3 ectopically expressed under the MMTV promoter in FVB/N mice. Five of 14 confirmed founder lines were selected for characterization to rule out integration effects. Each line was shown to express hBAG3 in mammary ductal epithelium, a typical feature of the MMTV-driven transgenes. We next applied chemical carcinogenesis with DMBA (7,12-dimethylbenzanthracene) to eight-week old virgin transgenic females and age-matched FVB/N wild-type females, by weekly orogastric gavage (1 mg DMBA) for 6 weeks. At study end (18 weeks post DMBA-treatment), 5/19 (26%) transgenic animals had pathologically proven atypical hyperplasia [1], and malignant tumors [adenocarcinoma, 1; myoepithelial tumor, 2; adenosquamous carcinoma, 1]. The age-matched non-transgenic controls did not develop premalignant or malignant breast lesions [0/12]. Luminal cell expression of hBAG3 was present in the atypical hyperplasia, but was not observed in highly proliferative, less differentiated regions of tumors where ductal structures are absent. Since the tumors we obtained were both of the myoepithelial and the epithelial lineages, we next investigated whether forced expression of hBAG3 in the ductal epithelium may dysregulate mammary gland development. We collected mammary glands at 5, 7, 10, and 13 weeks of age from transgenic and wild-type animals (n=4 each per time point) for two selected MMTV-hBAG3 transgenic lines. The terminal end buds, epithelial elongation, and glandular differentiation are currently being analyzed. Our preliminary data indicate that the mammary gland of MMTV-hBAG3 mice have a trend to increased epithelial elongation and more secondary acinar structures in the later pubertal stages. A complete analysis of the study cohort will be discussed. The effects of multiple pregnancies and post-lactation involution are under study. Together our findings point to a putative role of BAG3 as contributor to mammary remodeling during puberty and a promoting effect during chemical carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2388. doi:10.1158/1538-7445.AM2011-2388
The 'Nursing' in Nursing Homes
Authors: George C. Manning
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Dr Kane's<sup>1</sup>essay on long-term care states, in the abstract, "Nursing home care... has been neglected by physicians." And so it should be. The proper focus of physicians is on the treatment and prevention of illness. Debilitated elderly people should no more be considered ipso facto ill than should pregnant women, though anyone in either group may contract an illness. Equating age to illness is the medicalization of a social problem, and the cost of care should not come out of the nation's medical budget. Seventy-five years ago, many of the elderly died at home, indicating that people did not consider the demise of the elderly as a problem to be managed by physicians. The nursing care of the elderly is quite properly within the purview of the nursing profession. Nursing, by definition, consists of the physical and psychological care of persons who cannot care for
A meta-analysis of cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia versus general population controls
Authors: Davy Vancampfort, Martien Wampers, Alex J. Mitchell, Christoph U. Correll, Amber De Herdt, Michel Probst, Marc De Hert
Journal: World Psychiatry (2013)

A meta-analysis was conducted to explore the risk for cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia and age- and gender- or cohort-matched general population controls. Our literature search generated 203 relevant studies, of which 136 were included. The final dataset comprised 185,606 unique patients with schizophrenia, and 28 studies provided data for age- and gender-matched or cohort-matched general population controls (n=3,898,739). We found that multi-episode patients with schizophrenia were at increased risk for abdominal obesity (OR=4.43; CI=2.52-7.82; p<0.001), hypertension (OR=1.36; CI=1.21-1.53; p<0.001), low high-density lipoprotein cholesterol (OR=2.35; CI=1.78-3.10; p<0.001), hypertriglyceridemia (OR=2.73; CI=1.95-3.83; p<0.001), metabolic syndrome (OR=2.35; CI=1.68-3.29; p<0.001), and diabetes (OR=1.99; CI=1.55-2.54; p<0.001), compared to controls. Multi-episode patients with schizophrenia were also at increased risk, compared to first-episode (p<0.001) and drug-naïve (p<0.001) patients, for the above abnormalities, with the exception of hypertension and diabetes. Our data provide further evidence supporting WPA recommendations on screening, follow-up, health education and lifestyle changes in people with schizophrenia.
Comment re: Nitrite Activates Estrogen Receptor-α
Authors: Eddie Weitzberg, Filip Larsen, Jon O. Lundberg
Journal: Cancer Research (2009)

To the Editor:We read with interest the article by Veselik and colleagues in the May issue of Cancer Research (1). Using human breast cancer cells, they show that inorganic nitrate and nitrite mimicked the effects of estradiol on cell growth and gene induction via activation of estrogen receptor-α. The findings add to the growing body of evidence now suggesting important physiologic roles for these supposedly inert anions (2).The observed effects are remarkable, especially when considering the extremely low concentrations that were used. In humans, normal plasma levels of nitrate are ∼20 to 40 μmol/L, and for nitrite, 50 to 500 nmol/L (2, 3). The authors report potent effects at concentrations far below these levels, and in many cases, lower than what is ever seen in vivo. Given the physiologic plasma levels of nitrate, nitrite, and estradiol, this study implies that the three compounds are equally important in regulating estrogen receptor-α in vivo, with a further shift after menopause. Surprisingly, nitrate and nitrite were equipotent, suggesting a complete conversion of nitrate to nitrite. A functional mammalian nitrate reductase activity was indeed described recently, although in that study, the rate of aerobic nitrate reduction was much lower (4).Of concern is that most cell culture media already contain nitrate and nitrite at fairly high concentrations. Using a highly sensitive chemiluminescence method (3, 5), we measured nitrate and nitrite in 10 different culture media with or without the addition of charcoal-stripped fetal bovine serum. Nitrate varied between 0.8 and 100 μmol/L, whereas nitrite levels were 50 and 400 nmol/L. Therefore, it is highly surprising to see significant effects after adding only 1 μmol/L of nitrate. Did the authors measure nitrate and nitrite levels in the medium?The authors suggest a possible endocrine-like role for nitrate and nitrite in breast cancer. Again, we find it hazardous to extrapolate the present results to a discussion regarding dietary nitrate in relation to breast cancer because the effect should already be close to maximal from the normal levels of nitrate and nitrite present in blood and tissues.No potential conflicts of interest were disclosed.
Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle cells.
Authors: J A Steele, N Stockbridge, G Maljkovic, B Weir
Journal: Circulation Research (1991)

Single smooth muscle cells were isolated from the basilar artery of the rat by enzymatic dispersion. The membrane properties of the cells were assessed using the patch-electrode voltage-clamp technique, and cell viability was monitored using fluorescein diacetate uptake. Exposure of the cells to oxyhemoglobin (5 microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an increase in the outward potassium currents, 4) a decrease in the membrane resistance, and 5) cell death. In contrast, no effect of oxyhemoglobin on cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl sulfoxide (0.5%) protected against the effects of oxyhemoglobin; superoxide dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10 units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward potassium currents without affecting membrane resistance. Generation of hydroxyl radicals by metal ions plus hydrogen peroxide caused the same effects as oxyhemoglobin, that is, an increase in the potassium currents, followed by a decrease in the membrane resistance and cell death. In conclusion, it appears that oxyhemoglobin exerts its effects on vascular smooth muscle cells by the generation of free radicals, chiefly hydroxyl radicals.
Metaiodobenzylguanidine [131I] scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure.
Authors: M A Rabinovitch, C P Rose, J L Rouleau, C Chartrand, D M Wieland, L Lepanto, F Legault, S Suissa, L Rosenthall, J H Burgess
Journal: Circulation Research (1987)

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [131I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [131I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [131I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [123I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.
Pediatric Clinical Gastroenterology
Authors: Thomas Self
Journal: JAMA (1972)

This book constitutes an important asset to the clinical practice of pediatrics, for it brings together into a single focus a broad and thoughtful coverage of gastrointestinal disorders in children. Writing primarily from the standpoint of clinicians, the authors have compiled a first-rate collection of photomicrographs, roentgenograms and selected clinical histories. The first part of the book describes the clinical and historical features of gastrointestinal disease and shows the interrelation between disorders in other organ systems and the presence of gastrointestinal symptoms. The coverage of each entity is brief but accurate. The second part lists and defines pathogenetically the usual groups of hepatic, pancreatic, and intestinal disorders. In addition, some emphasis is given to immunological and metabolic problems reflected in various forms of gastrointestinal malfunction. The final section of the text discusses superficially the common diagnostic tests, nutritional problems (including parenteral alimentation), and the procedure involved in performing liver and
Correlation of transfusion volume to change in hematocrit
Authors: Mark E. Elzik, Douglas R. Dirschl, Laurence E. Dahners
Journal: American Journal of Hematology (2006)

While it has generally been accepted that a 3% change in hematocrit is equivalent to a 1-"unit" loss of blood, few studies have been published to actually document this. A more complete understanding of this correlation would be helpful in estimating blood loss from changes in hematocrit in patients sustaining hemorrhage as well as in those receiving transfusions. In this retrospective study, we analyzed the post-transfusion alterations in hematocrit from 61 independent transfusions in 48 different pelvic fracture patients (age range, 16-62 years). Transfusion volumes were correlated with changes in hematocrit over 24-hr periods between the 5th and 12th hospital days, a time when there was no ongoing hemorrhage in these patients. The average increase in hematocrit per liter of packed red blood cells transfused was 6.4% +/- 4.1%. If 1 "unit" of packed red blood cells is approximately 300 mL, this becomes a change of hematocrit of 1.9% +/- 1.2% per "unit" of blood. The accepted correlation of about 1 "unit" of blood loss per 3% change in hematocrit would be valid for a 500-cc unit, but a typical unit of packed red blood cells is typically 300 cc. In addition, the variability is substantial as indicated by our standard deviation. Limitations of this study include hematocrit changes due to fluid resuscitation, dehydration, age, persistent hemorrhage, and the retrospective nature of the evaluation.
Diagnosis and management of anal intraepithelial neoplasia and anal cancer
Authors: J. A. D. Simpson, J. H. Scholefield
Journal: BMJ (2011)

<h3>Objective</h3> Public knowledge of early onset symptoms and risk factors (RF) of acute myocardial infarction (AMI) is very important for prevention, recurrence and guide medical seeking behaviours. This study aimed to identify clusters of knowledge on symptoms and RFs of AMI, compare characteristics and the awareness of the need for prompt treatment. <h3>Design</h3> Multistage stratified sampling was used in this cross-sectional study. Latent GOLD Statistical Package was used to identify and classify the respondent subtypes of the knowledge on AMI symptoms or modifiable RFs. Multivariable logistic regression was performed to identify factors that predicted high knowledge membership. <h3>Participants</h3> A structured questionnaire was used to interview 4200 community residents aged over 35 in China. 4122 valid questionnaires were recovered. <h3>Results</h3> For AMI symptoms and RFs, the knowledge levels were classified into two or three distinct clusters, respectively. 62.7% (Symptom High Knowledge Cluster) and 39.5% (RF High Knowledge Cluster) of the respondents were able to identify most of the symptoms and modifiable RFs. Respondents who were highly educated, had higher monthly household income, were insured, had regular physical examinations, had a disease history of AMI RFs, had AMI history in immediate family member or acquaintance or had received public education on AMI were observed to have higher probability of knowledge on symptoms and RFs. There was significant difference in awareness of the prompt treatment in case of AMI occurs among different clusters. 'Calling an ambulance' was the most popular option in response of seeing others presenting symptoms of AMI. <h3>Conclusions</h3> A moderate or relatively low knowledge on AMI symptoms and modifiable RFs was observed in our study. Identification of Knowledge Clusters could be a way to detect specific targeted groups with low knowledge of AMI, which may facilitate health education, further reduce the prehospital delay in China and improve patient outcomes.
Aspergilloma of the Thoracic Wall Another Cold Spot Lesion on Bone Scanning
Authors: FRANK DE GEETER, ANNE-MARIE MALFAIT, ACHIEL VAN HOOF
Journal: Clinical Nuclear Medicine (1995)

The authors describe a large and sharply defined cold area on bone imaging due to a thoracic wall aspergilioma occurring in a patient treated for acute myelogenous leukemia. Aspergilioma should be added to the differential diagnosis of localized rib destruction with adjacent soft tissue mass.
Arthur I. Holleb, MD (1921-2006)
Authors: H. Eyre, J. Seffrin, T. Gansler
Journal: CA A Cancer Journal for Clinicians (2007)

We are deeply saddened to inform you that Arthur I. Holleb, MD, passed away on October 19, 2006. Dr. Holleb was National Senior Vice President for Medical Affairs and Chief Medical Officer of the American Cancer Society from 1968 to 1988 and Editor-in-Chief of this journal from 1970 to 1988. Arthur was well known as a skillful and compassionate surgical oncologist and an outstanding leader and served as Associate Clinician of the Sloan-Kettering Institute for Cancer Research and Associate Director of the MD Anderson Hospital and Tumor Institute. Some of his other leadership roles include President of the New York Cancer Society, President of the James Ewing Society, first Vice President of the American Radium Society, and membership on the Cancer Commissions of the American College of Surgeons and the American College of Radiology, the Governing Council of the International Union Against Cancer (UICC), and the Board of Directors of the New York City Division of the American Cancer Society. Among Dr. Holleb's most enduring legacies are his leadership in promoting early detection of cancer through implementation of the Papanicolaou test during the 1940s and 1950s and his support for mammography research and implementation during the 1970s and 1980s. We at the American Cancer Society will never forget Dr. Holleb and his many contributions to the prevention, early detection, and treatment of cancer.
Muscle cramps in the calf as presenting symptom of sarcoidosis.
Authors: M Janssen, B A Dijkmans, F Eulderink
Journal: Annals of the Rheumatic Diseases (1991)

A patient is described, who presented with pain in the calf due to a palpable nodule as the presenting symptom of sarcoidosis. The patient was treated with rest and diclofenac, followed by intralesional injections with triamcinolone hexacetonide and became free from pain.
IRG1 induced by heme oxygenase-1/carbon monoxide inhibits LPS-mediated sepsis and pro-inflammatory cytokine production
Authors: Md Jamal Uddin, Yeonsoo Joe, Seul-Ki Kim, Sun Oh Jeong, Stefan W Ryter, Hyun-Ock Pae, Hun Taeg Chung
Journal: Cellular and Molecular Immunology (2015)

The immunoresponsive gene 1 (IRG1) protein has crucial functions in embryonic implantation and neurodegeneration. IRG1 promotes endotoxin tolerance by increasing A20 expression in macrophages through reactive oxygen species (ROS). The cytoprotective protein heme oxygenase-1 (HO-1), which generates endogenous carbon monoxide (CO), is expressed in the lung during Lipopolysaccharide (LPS) tolerance and cross tolerance. However, the detailed molecular mechanisms and functional links between IRG1 and HO-1 in the innate immune system remain unknown. In the present study, we found that the CO releasing molecule-2 (CORM-2) and chemical inducers of HO-1 increased IRG1 expression in a time- and dose-dependent fashion in RAW264.7 cells. Furthermore, inhibition of HO-1 activity by zinc protoporphyrin IX (ZnPP) and HO-1 siRNA significantly reduced expression of IRG1 under these conditions. In addition, treatment with CO and HO-1 induction significantly increased A20 expression, which was reversed by ZnPP and HO-1 siRNA. LPS-stimulated TNF-α was significantly decreased, whereas IRG1 and A20 were increased by CORM-2 application and HO-1 induction, which in turn were abrogated by ZnPP. Interestingly, siRNA against IRG1 and A20 reversed the effects of CO and HO-1 on LPS-stimulated TNF-α production. Additionally, CO and HO-1 inducers significantly increased IRG1 and A20 expression and downregulated TNF-α production in a LPS-stimulated sepsis mice model. Furthermore, the effects of CO and HO-1 on TNF-α production were significantly reversed when ZnPP was administered. In conclusion, CO and HO-1 induction regulates IRG1 and A20 expression, leading to inhibition of inflammation in vitro and in an in vivo mice model.
Fatal intestinal atony in myxoedema.
Authors: J. S. Chadha, D. W. Ashby, W. K. Cowan
Journal: BMJ (1969)

the platelet counts weekly and the knowledge that a cyclical variation may occur are important in assessing the severity of the thrombocytopenia, the response to treatment, and the timing of surgical procedures.The documented case in which a patient with clinical thyrotoxicosis and cyclic thrombocytopenia was found to have platelet, thyroid, and mitochondrial antibodies-the latter thought to be suggestive of primary biiary cirrhosis (Doniach et al., 1966)-and a positive antinuclear test (speckled variety) with clinical response to steroids, lends support to the concept that thrombocytopenia may be attributed to disorders of the unological system.
Therapy of hepatitis C: Patients with cirrhosis
Authors: S W Schalm, G Fattovich, J T Brouwer
Journal: Hepatology (1997)

The management of both compensated and decompensated cirrhosis caused by hepatitis C must be viewed in the context of the natural history of the disease. The prognosis of compensated cirrhosis caused by hepatitis C is relatively good. In a recent retrospective study, after 5 years of follow-up evaluation, 18% of patients had developed hepatic decompensation and 7% hepatocellular carcinoma. Overall 5-year survival rate was 91%. Treatment with α interferon appears to decrease the incidence of hepatocellular carcinoma in patients who achieve a sustained remission. However, on an intention-to-treat basis and after adjustment for differences in clinical and serological features at entry, interferon therapy does not correlate with a reduced incidence of liver cancer or improved survival. Combined analysis of multiple large studies on patients with cirrhosis caused by hepatitis C indicates that current regimens of α interferon (3 to 6 million units three times weekly for 6 to 12 months) result in a sustained biochemical response in 9% of patients. The rates of sustained virological responses are less well documented. Virological measurements during therapy show that only 22% of patients become hepatitis C virus (HCV) RNA negative by 4 weeks and, thereafter, there is a high rate of breakthrough. In small studies, the combination of interferon and ribavirin leads to sustained biochemical and virological response rates of 21%, more than twice the rates achieved with interferon alone. The prognosis of decompensated cirrhosis caused by hepatitis C is poor, with a 5-year survival rate of only 50%. The efficacy of interferon in patients with decompensated cirrhosis is not well documented and its use cannot be recommended. In contrast, 5-year survival rates after liver transplantation for cirrhosis caused by hepatitis C is excellent, in the range of 70% to 80%. Recurrence of HCV infection occurs in more than 95% of patients, but in short-term follow- up studies, recurrence of cirrhosis and graft failure occurs in only 10% of patients.