tbuckley/cabot-search huggingface dataset:
Abstract 1232: Antiproliferative, antioxidant and antiapoptotic effect of rhamnetin in human prostate cancer cells
Authors: Christine Oak, Natarajan Bhaskaran, Sanjay Gupta, Sanjeev Shukla
Journal: Cancer Research (2014)

Abstract Persistent oxidative stress due to generation of reactive oxygen species (ROS) has been associated with malignancy and cancer progression. Using a panel of human prostate cancer cells, we observed increased production of intracellular ROS, compared to normal human prostate epithelial cells, accompanied by elevated expression of antioxidant enzymes viz. superoxide dismutase, catalase, peroxiredoxin-1 and thioredoxin that may be a likely mechanism to endure increased oxidative stress. There is a need for novel antioxidant agent that can effectively suppress the generation of increased ROS in cancer cells. Rhamnetin (3,5,3,4-tetrahydroxy-7-methoxyflavone), remains highest on oxygen radical absorbance capacity scale, however its anti-proliferative activities has not been assessed. Rhamnetin is an O-methylated flavonol, abundantly present in cloves, sweet annie, annual wormwood, green vegetables and orchard grass. Previous studies (Shukla et al. Proc. Amer. Assoc. Cancer Res. 102: 5576, 2011) using androgen-responsive human prostate cancer LNCaP and androgen-refractory PC-3 cells, we have demonstrated that rhamnetin possess anticancer activity, induces apoptosis, and inhibits cancer cell growth. In the present study we assessed the antioxidant and anti-proliferative ability of rhmanetin in prostate cancer. Treatment of LNCaP and PC-3 cells with 100μM paraquat, an oxidative stress-inducing agent, induced cellular proliferation in both these cells. Treatment of cells with 5-80μM rhamnetin significantly decreased paraquat-induced ROS production and inhibited cell proliferation in dose-dependent manner. Similar effects were noted with the addition of recombinant Klotho protein to these cells, which is known to offer resistance to oxidative stress at the cellular level. Rhamnetin treatment also increased Klotho protein levels in both cell lines, along with increase in the expression of p53 and p21/waf1. Furthermore, rhamnetin treatment resulted in the increased expression of caspase-3, caspase-9 causing induction of apoptosis, which may be one of the protective mechanism(s) to decrease cell proliferation and enhance resistance to oxidative stress in cancer cells. Taken together, these results demonstrate that rhamnetin acts as a potent antioxidant agent, reduces intracellular ROS levels, increases Klotho protein expression, induces apoptosis in prostate cancer cells, which may have a significant role in the inhibition of prostate cancer progression. Citation Format: Christine Oak, Natarajan Bhaskaran, Sanjay Gupta, Sanjeev Shukla. Antiproliferative, antioxidant and antiapoptotic effect of rhamnetin in human prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1232. doi:10.1158/1538-7445.AM2014-1232
Resuscitation of Drowned Children
Authors: J. Burke
Journal: BMJ (1971)

Save the Children Fund. Mental Health ResearchWith inflation at its present rate, says the Annual Report of the Mental Health Re- search Fund, each year 20% more money must be raised just to continue the support of a constant volume of research.Projects of high scientific merit are being turned down for lack of funds.Among research currenly receiving support is a study of the biochemistry of schizophrenia at Edinburgh; investigation of infant behaviour at Cam- bridge; and work on psychogenic amenorr- hoea.
Double Popliteal Aneurism: The Left Aneurism Developed after Haemorrhage Consequent on Ligature of the Right Femoral Artery: Pulsation Returning after Ligature of Artery, Arrested by Extension of Limb: Recovery: Subsequent Aneurism of Superior Mesenteric Artery
Authors: G. M. Humphry
Journal: BMJ (1876)
Effect of Chlorothiazide Therapy on Serum Uric Acid and Uric Acid Excretion
Authors: K. E. Monroe, L. H. Grant, A. A. Sasahara, D. Littmann
Journal: New England Journal of Medicine (1959)

DURING preliminary testing in 1957, chlorothiazide revealed its effectiveness as a diuretic for oral administration.1 It was observed some months later also to have an antihypertensive effect.2 The present study was undertaken because of the relation between chlorothiazide and salicylate as inhibitors of uric acid secretion first suggested by Yü and Gutman.3 Material and MethodsTen patients who had been receiving chlorothiazide up to ten months were asked to return to the hospital. During the first forty-eight-hour admission, they had two determinations each of blood urea nitrogen, serum uric acid (by Caraway's4 method) and electrolytes, and collected all urine in . . .
PATHOLOGY OF THE EPIDEMIC STREPTOCOCCAL BRONCHOPNEUMONIA IN THE ARMY CAMPS
Authors: W. G. MacCALLUM
Journal: JAMA (1918)

In a previous paper<sup>1</sup>a peculiar form of bronchopneumonia, caused by a hemolytic streptococcus and prevalent in some of the Army camps, was described. This was based on observations made during February and March at Fort Sam Houston, Texas. Since that time I have been able to study during May a quite similar epidemic at Camp Dodge, Iowa,<sup>2</sup>where, however, the surrounding conditions, climate, housing of troops, and organization and construction of the base hospital were very different. Another striking difference lay in the great prevalence of measles in the Texas camp, whereas at Camp. Dodge measles has not been very common. In the Texas camp we were greatly impressed with the importance of measles as a disease predisposing to secondary invasion of the streptococcus, although we realized the possibility that other diseases, such as scarlet fever or lobar pneumonia, might act as predisposing causes, and that the
Loss of CD44 attenuates aberrant GM-CSF signaling in Kras G12D hematopoietic progenitor/precursor cells and prolongs the survival of diseased animals
Authors: J Du, Y Liu, B Meline, G Kong, L X Tan, J C Lo, J Wang, E Ranheim, L Zhang, Y I Chang, M J Ryu, J F Zhang, J Zhang
Journal: Leukemia (2012)
Blood concentrations of acetaldehyde during chlorpropamide-alcohol flush.
Authors: A H Barnett, C Gonzalez-Auvert, D A Pyke, J B Saunders, R Williams, C J Dickenson, M D Rawlins
Journal: BMJ (1981)

To test the suggestion that chlorpropamide-alcohol flushing (CPAF) resembles the disulfiram effect and might be mediated by acetaldehyde, the initial metabolite of alcohol, blood concentrations of acetaldehyde were measured after a drink of alcohol in controls and diabetics positive and negative for CPAF. The CPAF-positive diabetics had significantly greater blood acetaldehyde concentrations after alcohol than the CPAF-negative diabetics both with a single dose of chlorpropamide and after two weeks9 chlorpropamide treatment. Concentrations in the CPAF-positive group after chlorpropamide were also significantly greater than after a placebo tablet. There was also a clear separation in the increase in facial temperature after two weeks of chlorpropamide between the CPAF-positive and CPAF-negative groups (although there was some overlap after a single tablet). There was no difference in plasma chlorpropamide or alcohol concentrations between CPAF-positive and CPAF-negative diabetics. These findings show that CPAF is distinct from alcohol flushing and that the acetaldehyde concentration in the blood provides an objective measure of CPAF. The difference between flushing and non-flushing diabetics cannot be accounted for by differences in blood concentrations of chlorpropamide or alcohol.
O139 ALCOHOLIC HEPATITIS RESISTANT TO MEDICAL THERAPY IS CHARACTERIZED BY AN ALTERED DIFFERENTIATION OF HEPATIC PROGENITORS UNDER THE INFLUENCE OF EXTRACELLULAR MATRIX
Authors: L. Dubuquov, A. Louvet, G. Lassailly, F. Artru, S. Truant, F. Maggiotto, E. Gantier, E. Boleslawski, D. Buob, A. Cannesson-Leroy, C. Moreno, S. Dharancy, P. Mathurin
Journal: Journal of Hepatology (2014)
Blunted increase in serum hepcidin as response to oral iron in HFE - hemochromatosis
Authors: A. Sangwaiya, V. Manglam, M. Busbridge, M. Thursz, J. Arnold
Journal: Gut (2011)

<h3>Introduction</h3> Majority of patients with <i>HFE</i> hemochromatosis (<i>HFE</i>-H) are homozygote for C282Y mutation. Studies suggest iron accumulation in most types of hemochromatosis is due to hepcidin deficiency. The precise link between hepcidin levels and iron absorption in <i>HFE</i>-H patients has been poorly understood. We measured hepcidin response to oral iron challenge (200 mg ferrous sulphate), in <i>HFE</i>-H (C282Y/C282Y) patients and compare to healthy controls (HC). <h3>Methods</h3> Nine patients with C282Y/C282Y <i>HFE</i>-H along with 15 HC were recruited for the study. All <i>HFE</i>-H were iron depleted and studied at a time distant to phlebotomy. Hepcidin was measured using a published immunoassay method. Serum iron, ferritin and transferrin saturation (%TSAT) were measured using standard methods. The area under the curve (AUC) was calculated and compared between the two groups. <h3>Results</h3> The basal serum hepcidin levels in patients with <i>HFE</i>-H were significantly low as compared to HC (p=0.0002) (table 1). Incremental serum hepcidin response seen in HC reached significance at 4 h post iron challenge (p=0.0085). There was no significant hepcidin response in <i>HFE</i>-H at 4 h (p=0.294) (figure 1). The overall hepcidin response was significantly lower in <i>HFE</i>-H as compared to HC (AUC: p=0.0127). <h3>Conclusion</h3> Failure to mount a rapid hepcidin response to an oral iron challenge is one of the key mechanisms of iron accumulation in spite of prevailing excess body iron in <i>HFE</i>-H patients with C282Y/C282Y mutation.
Wishful thinking about primary care in 2015
Authors: Robert D Walker
Journal: BMJ (2006)

Editor—With regard to the five visions of primary care,1–5 my heart hopes that the aspirations of Lakhani and Baker prevail, but my head suggests that the alternative scenarios outlined by Meldrum reflect the future.

I have had two contrasting careers—17 years as a general practitioner principal and then 13 years in medical …
Enhanced Antitumor Effects of an Engineered Measles Virus Edmonston Strain Expressing the Wild-type N, P, L Genes on Human Renal Cell Carcinoma
Authors: Xin Meng, Takafumi Nakamura, Toshihiko Okazaki, Hiroyuki Inoue, Atsushi Takahashi, Shohei Miyamoto, Gaku Sakaguchi, Masatoshi Eto, Seiji Naito, Makoto Takeda, Yusuke Yanagi, Kenzaburo Tani
Journal: Molecular Therapy (2010)

Measles virus Edmonston strain (MV-Edm) is thought to have remarkable oncolytic activity that selectively destroys human tumor cells. The P/V/C protein of wild-type MV was shown to resist the antiviral effects of interferon (IFN)-α. Here, we engineered new MVs by arming MV-Edm tag strain (a V-defective vaccine-lineage strain, MV-Etag) with the P or N, P, and L genes of wild-type MV (MV-P and MV-NPL, respectively). The oncolytic activities of the MVs were determined in human renal cell carcinoma (RCC) cell lines and primary human RCC cells by the MTT assay. The antitumor efficacy of the MVs was evaluated in A-498 xenografts in nude mice. IFN-α effectively inhibited the replication of MV-Etag and MV-P, but not MV-NPL. MV-NPL more efficiently induced cytopathic effects (CPEs) in OS-RC-2 cells, even in the presence of human IFN-α. MV-NPL replicated more rapidly than MV-P and MV-Etag in A-498 cells. Apoptosis was induced earlier in A-498 cells by MV-NPL than MV-Etag and MV-P. MV-NPL showed more significant antitumoral effects and had prolonged replication compared to MV-Etag and MV-P. In this study, we demonstrated that the newly engineered MV-NPL has more effective oncolytic activity and may help establish an innovative cancer therapy. Measles virus Edmonston strain (MV-Edm) is thought to have remarkable oncolytic activity that selectively destroys human tumor cells. The P/V/C protein of wild-type MV was shown to resist the antiviral effects of interferon (IFN)-α. Here, we engineered new MVs by arming MV-Edm tag strain (a V-defective vaccine-lineage strain, MV-Etag) with the P or N, P, and L genes of wild-type MV (MV-P and MV-NPL, respectively). The oncolytic activities of the MVs were determined in human renal cell carcinoma (RCC) cell lines and primary human RCC cells by the MTT assay. The antitumor efficacy of the MVs was evaluated in A-498 xenografts in nude mice. IFN-α effectively inhibited the replication of MV-Etag and MV-P, but not MV-NPL. MV-NPL more efficiently induced cytopathic effects (CPEs) in OS-RC-2 cells, even in the presence of human IFN-α. MV-NPL replicated more rapidly than MV-P and MV-Etag in A-498 cells. Apoptosis was induced earlier in A-498 cells by MV-NPL than MV-Etag and MV-P. MV-NPL showed more significant antitumoral effects and had prolonged replication compared to MV-Etag and MV-P. In this study, we demonstrated that the newly engineered MV-NPL has more effective oncolytic activity and may help establish an innovative cancer therapy.
Introduction to nasal and pulmonary allergy cascade
Authors: G. W. Canonica
Journal: Allergy (2002)

The early phase of an IgE‐dependent allergic reaction is followed by the activation of a complex network of inflammatory phenomena – T lymphocytes, cytokines, mediators, and adhesion molecules – that mediate late and ongoing allergic symptoms. The kinetics of respiratory inflammation following allergen exposure involve the migration of inflammatory cells to the mucosa within about 30 min, increased inflammatory infiltration over the following hours, and then slow subsidence. A relationship between asthma and allergic rhinitis is supported by epidemiological, histological, physiological, and immunopathological data, and by the response of asthma symptoms in rhinitic patients to intranasal corticosteroids and antihistamines. For example, there is no morphological difference between the bronchial inflammatory response following allergen‐specific challenge in patients suffering from asthma alone or rhinitis alone. It is the allergen dose that makes the difference in the airway response to allergen in allergic rhinitis and asthma. Recognition of the relationship between asthma and allergic rhinitis has led to the introduction of new diagnostic terminology and treatment recommendations: 1) patients with persistent rhinitis should be evaluated for asthma; 2) patients with persistent asthma should be evaluated for rhinitis; and 3) a strategy should combine the treatment of upper and lower airways in terms of efficacy and safety.
Future diagnosis of sepsis
Authors: Juan Chen, Youxin Wang, Wei Wang
Journal: The Lancet (2010)

Päivi Tissari and colleagues1 present accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform (the Prove-it sepsis assay). This assay yielded a clinical sensitivity of 94·7% (95% CI 93·6–95·7) and specificity of 98·8% (98·1–99·2). However, the sensitivity and specificity were calculated with the combined data for all pathogens, not for each pathogen individually, and could be confusing for readers. For example, if a sample is diagnosed as Escherichia coli by blood culture analysis and as Staphylococcus epidermidis by the Prove-it assay, the real diagnosis should be E coli (false positivity for S epidermidis); however, it would be S epidermidis in Tissari and colleagues' study.
Hypoglycemia and Clinical Outcomes in Patients With Diabetes Hospitalized in the General Ward
Authors: Alexander Turchin, Michael E. Matheny, Maria Shubina, James V. Scanlon, Bonnie Greenwood, Merri L. Pendergrass
Journal: Diabetes Care (2009)

In our study of hypoglycemia in hospitalized patients with diabetes (1), we have found a strong association between the frequency and severity of hypoglycemia and clinical outcomes including mortality and length of hospital stay. In their comment, Ng et …
Multislice Computed Tomographic Characteristics of Coronary Lesions in Acute Coronary Syndromes
Authors: Sadako Motoyama, Takeshi Kondo, Masayoshi Sarai, Atsushi Sugiura, Hiroto Harigaya, Takahisa Sato, Kaori Inoue, Masanori Okumura, Junichi Ishii, Hirofumi Anno, Renu Virmani, Yukio Ozaki, Hitoshi Hishida, Jagat Narula
Journal: Journal of the American College of Cardiology (2007)
Identifying infants at high risk of peanut allergy: The Learning Early About Peanut Allergy (LEAP) screening study
Authors: George Du Toit, Graham Roberts, Peter H. Sayre, Marshall Plaut, Henry T. Bahnson, Herman Mitchell, Suzana Radulovic, Susan Chan, Adam Fox, Victor Turcanu, Gideon Lack
Journal: Journal of Allergy and Clinical Immunology (2012)
Is pregnancy in diabetic women associated with folate deficiency?
Authors: J S Kaplan, S Iqbal, B G England, C M Zawacki, W H Herman
Journal: Diabetes Care (1999)

OBJECTIVE: To determine whether folate metabolism in pregnant diabetic women is significantly different from that in pregnant nondiabetic women, thus predisposing them to having offspring with major congenital anomalies. RESEARCH DESIGN AND METHODS: A total of 31 pregnant diabetic women and 54 pregnant nondiabetic control subjects were studied at their first prenatal visits. Dietary folate intake, serum folate, red blood cell folate, urinary folate, and homocysteine were measured and compared after controlling for folate supplementation. Among diabetic women the relationships among parameters of folate metabolism and glycemic control were also assessed. RESULTS: There were no significant differences between the pregnant diabetic and non-diabetic women for any measures of folate metabolism after accounting for folate supplementation. In addition, among diabetic women, there were no associations among parameters of folate metabolism and glycemic control. CONCLUSIONS: Abnormal folate metabolism does not appear to occur in pregnant diabetic women. It is unlikely that deranged folate metabolism explains the higher incidence of major anomalies in infants of diabetic mothers. These results do not diminish the importance of periconception folate supplementation or preclude other possible scenarios that could restrict folate use by the embryo, leading to congenital anomalies.
Hemophilia in the Talmud and Rabbinic Writings
Authors: FRED ROSNER
Journal: Annals of Internal Medicine (1969)

A familial bleeding disorder, probably hemophilia, is described in the Talmud. The decree of Rabbi Judah that the sibling of two brothers who died of bleeding after circumcision may not be circumcised is codified by Jewish sages of the last 10 centuries. Such rulings are found in the works of Alfasi (eleventh century); Maimonides (twelfth century); Jacob ben Asher and Asher ben Yechiel (fourteenth century); Karo and Isserles (sixteenth century); Azulay, Reischer, and Landau (eighteenth century); and Epstein (nineteenth century), among others. Modern Rabbinic authority extends this ruling to any child, even the firstborn, in whom a diagnosis of hemophilia can be established by coagulation studies. This ruling was stated only in regard to siblings or maternal cousins as only the direct maternal transmission of the disease was recognized. Omitted from all the Jewish sources is a consideration of the child whose maternal uncles died of bleeding after circumcision.
Achieving a pathological diagnosis in biliary tract cancer
Authors: S. Bannoo, M. H. Chapman, N. S. Sandanayake, G. J. Webster, G. Johnson, S. OldeDamink, M. Malago, S. P. Pereira
Journal: Gut (2011)

<h3>Introduction</h3> Diagnosing BTC is challenging because of a lack of reliable tumour markers and radiological similarities with benign hepatobiliary disease. Current guidelines advise confirmatory histology and/or cytology should be sought for the diagnosis of biliary tract cancer (BTC) (Khan <i>et al</i>, <i>Gut</i> 2002;<b>51</b>(Suppl VI)). However, tissue sampling for pathological diagnosis is hampered by tumour site and morphology limiting access to diagnostic tissue, with success rates of only 60–70% (Connor S <i>et al,</i> 2005;<b>9</b>:476; Witzigmann <i>et al,</i> 2006;<b>244</b>:230). <h3>Methods</h3> All patients (n=256) with a final clinical diagnosis of BTC (229 cholangiocarcinoma, 27 gallbladder cancer) between January 2003 and September 2010 were included (135M, 121F; mean age 70 years, range 23–107 years). All cytology and tissue biopsy data, including number and technique, for each patient were recorded. <h3>Results</h3> 59/256 patients (23%) were referred with a tissue diagnosis. Of the 197/256 patients (77%) without a prior tissue diagnosis, 196 had attempted tissue sampling (median 1 procedure, range 1–6) at our hospital. Out of a total of 341 tissue samples, 127 were taken for biliary cytology and 54 for other cytology (pleural and ascitic fluid n=38; endoscopic ultrasound-guided fine needle aspiration (FNA) n=15; bile n=1), of which 43/127 (34%) and 11/54 (20%), respectively, were positive for cancer. 124 percutaneous and 36 endobiliary biopsies were taken, of which 70% and 44% respectively, were positive. 45 (13%) samples were reported as suspicious for malignancy and a further 15 (4%) had suboptimal specimens unsuitable for pathological diagnosis; all were classified negative for malignancy. Overall, 161/197 (82%) had a pathological confirmation of cancer at our hospital, giving a total positivity rate of 220/256 (86%). A clinical diagnosis of BTC, based on multidisciplinary review and evidence of disease progression, was made in the remaining 36 (14%) patients. <h3>Conclusion</h3> A pathological diagnosis of BTC can be achieved in 86% of patients, exceeding previous best published data. The sensitivity of biliary cytology in routine clinical practice is low, but a pathological diagnosis can be obtained with a combination of other endoscopic and percutaneous approaches, allowing alternative diagnoses to be excluded and appropriate treatment given.
PREDICTIVE VALUE OF ELEVATED URIC ACID IN PATIENTS UNDERGOING PRIMARY ANGIOPLASTY FOR STEMI
Authors: Özgür Akgül, Huseyin Uyarel, Hamdi Pusuroglu, Selahattin Turen, Ozgur Surgit, Mehmet Gul, Mehmet Erturk, Umit Bulut, Omer Faruk Baycan, Mustafa Cetin, Nevzat Uslu
Journal: Journal of the American College of Cardiology (2013)
Incidence and management of limb ischemia with percutaneous wire-guided intraaortic balloon catheters
Authors: James D. Alderman, Gregory I. Gabliani, Carolyn H. McCabe, Cynthia C. Brewer, Beverly H. Lorell, Richard C. Pasternak, John J. Skillman, Michael L. Steer, Donald S. Baim
Journal: Journal of the American College of Cardiology (1987)
Receptor-mediated regulation of superoxide production in human neutrophils stimulated by phorbol myristate acetate.
Authors: R I Lehrer, L Cohen
Journal: Journal of Clinical Investigation (1981)

Human neutrophils contain receptors for phorbol myristate acetate (PMA), a complex lipid that induces them to generate superoxide (O (2)). Binding of PMA to these receptors displays specificity, reversibility, and high affinity. The receptor's apparent KD was approximately 0.29 nM and multiple copies (approximately 2.1 +/- 0.6 x 10(5)) were present per neutrophil. We found that the timing and magnitude of the neutrophil's respiratory burst were set independently. The onset of O (2) production occurred after a lag that was inversely proportional to the initial concentration of added PMA. The extent (rate) of O (2) production was directly proportional to the fractional occupancy of the receptor by PMA. Dual regulatory controls, such as those we noted when neutrophils were stimulated by PMA, could afford metabolic stability in the face of transient or low intensity stimuli without compromising quick and powerful responses to larger disturbances.