tbuckley/cabot-search huggingface dataset:
Maternal Rh-immunization.
Authors: D. F. Hopkins
Journal: BMJ (1969)

some such as 1 7a-hydroxyprogesterone 17-npaproate and norethynodrel have been shown ,to be free of these unfortunate side-effects.I would have thought that progestins are best avoided in the treatment of pregnancy prurigo, and the simpler measures that you advocated are best adhered to.-I am, etc., J.
Significance of Increased Factor VIII in Early Glomerulonephritis
Authors: MATS R. EKBERG
Journal: Annals of Internal Medicine (1975)

One hundred sixteen patients with early glomerulonephritis had factor VIII without impairment of renal function. They also had other coagulation and fibrinolytic components and acute phase reactants. The patients were followed for up to 4 years with respect to both coagulation pattern and renal function. Patients who made a complete recovery during follow-up had normal initial factor VIII levels, while those who developed persistent renal damage had high factor VIII levels. The other coagulation factors and the acute phase reactants were of no prognostic significance. Factor VIII has been shown to be synthesized in the vessel intima. The initial factor VIII level in early glomerulonephritis may reflect the degree of vascular affection of the glomeruli. The high factor VIII levels may be of significance for the development of fibrin deposits in glomeruli.
Out-Patient Gastroscopy Risks
Authors: K. Andersen, N. Clausen
Journal: Endoscopy (1978)

Complications in out-patient gastroscopy were evaluated retrospectively in 995 examinations performed in 625 patients. At the examination seven complications were registered in the gastroscopy record. Two complications: perforation of the stomach and cardiac arrhythmia, required hospitalisation. None of the complications was lethal. Inquiries to the referring general practitioners revealed 5 cases where the gastroscopy had led to consultations because of minor complaints after the examination. Considering all complaints as complications the frequency of complications in out-patient gastroscopy was 1.2%.
Thiazolidinediones Inhibit Insulin-Like Growth Factor-I–Induced Activation of p70S6 Kinase and Suppress Insulin-Like Growth Factor-I Tumor-Promoting Activity
Authors: Guobin He, You Me Sung, John DiGiovanni, Susan M. Fischer
Journal: Cancer Research (2006)

Abstract Thiazolidinediones are a novel class of antidiabetic drugs that improve insulin sensitivity in type 2 diabetic patients. Recently, these compounds have also been shown to suppress tumor development in several animal models. The molecular basis for their antitumor action, however, is largely unknown. We report here that oral administration of thiazolidinediones (rosiglitazone and troglitazone) remarkably inhibited insulin-like growth factor-I (IGF-I)–promoted skin tumor development by 73% in BK5.IGF-1 transgenic mice, although they were previously found to be ineffective in inhibiting UV- or chemically induced mouse skin tumorigenesis. The anti-IGF-I effect of troglitazone in mouse skin keratinocytes was due to, at least partially, inhibition of IGF-I–induced phosphorylation of p70S6 kinase (p70S6K) at Thr389, a site specifically phosphorylated by mammalian target of rapamycin (mTOR). Troglitazone did not directly inhibit mTOR kinase activity as shown by mTOR in vitro kinase assay but rapidly activated AMP-activated protein kinase (AMPK) through a yet undefined peroxisome proliferator-activated receptor γ–independent mechanism. Expression of a dominant-negative AMPK reversed the inhibitory effect of troglitazone on IGF-I–induced phosphorylation of p70S6K, suggesting that troglitazone inhibited IGF-I and p70S6K signaling through activation of AMPK. Collectively, these data suggest that thiazolidinediones specifically inhibit IGF-I tumor-promoting activity in mouse skin through activation of AMPK and subsequent inhibition of p70S6K. (Cancer Res 2006; 66(3): 1872-8)
Endocannabinoids are implicated in the infarct size-reducing effect conferred by heat stress preconditioning in isolated rat hearts
Authors: Marie Joyeux, Claire Arnaud, Diane Godin-Ribuot, Pierre Demenge, Daniel Lamontagne, Christophe Ribuot
Journal: Cardiovascular Research (2002)

Objective: We have investigated the involvement of the endocannabinoid system in the delayed cardioprotection conferred by heat stress preconditioning in the isolated rat heart. Methods: Rats were divided into eight groups (n = 7 in each group), subjected to either heat stress (42 °C for 15 min, HS groups) or sham anaesthesia (Sham groups). Twenty-four hours later, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. Some hearts were perfused with either SR 141716 (a cannabinoid CB1 receptor antagonist, 1 μM), SR 144528 (a CB2 receptor antagonist, 1 μM) or l-NAME (a NOS inhibitor, 3 μM) 5 min before ischaemia and during the ischaemic period. Results: The infarct size-reducing effect conferred by heat stress (35.7±1.8% in Sham to 14.1±0.6% in HS groups) was not altered by the perfusion of SR 141716 (11.2±1.5%) but was abolished by both SR 144528 (36.6±1.6%) and l-NAME (32.0±4.4%). In hearts from non-heat-stressed rats, perfusion with SR 141716 (32.8±1.6%), SR 144528 (33.4±2.2%) and l-NAME (31.6±2.9%) had no effect on infarct size. Conclusion: These results suggest an involvement of endocannabinoids, acting through CB2 receptors, and NO in the cardioprotection conferred by heat stress against myocardial ischaemia. The possible interaction between both mediators of the heat stress response remains to be determined.
p120-Catenin regulates leukocyte transmigration through an effect on VE-cadherin phosphorylation
Authors: Pilar Alcaide, Gail Newton, Scott Auerbach, Seema Sehrawat, Tanya N. Mayadas, David E. Golan, Patrick Yacono, Peter Vincent, Andrew Kowalczyk, Francis W. Luscinskas
Journal: Blood (2008)
Banti's Disease
Authors: D. B. Williams
Journal: BMJ (1952)

Previous results demonstrating homotropic activation of human UDP-glucuronosyltransferase (UGT) 1A1-catalyzed estradiol-3-glucuronidation led us to investigate the effects of 16 compounds on estradiol glucuronidation by human liver microsomes (HLM). In confirmation of previous work using alamethicin-treated HLM pooled from four livers, UGT1A1-catalyzed estradiol-3-glucuronidation demonstrated homotropic activation kinetics (S<sub>50</sub> = 22 μM, Hill coefficient, <i>n</i> = 1.9) whereas estradiol-17-glucuronidation (catalyzed by other UGT enzymes) followed Michaelis-Menten kinetics (<i>K</i><sub>m</sub> = 7 μM). Modulatory effects of the following compounds were investigated: bilirubin, eight flavonoids, 17α-ethynylestradiol (17α-EE), estriol, 2-amino-1-methyl-6-phenylimidazo [4,5-<i>b</i>]pyridine (PhIP), anthraflavic acid, retinoic acid, morphine, and ibuprofen. Although the classic UGT1A1 substrate bilirubin was a weak competitive inhibitor of estradiol-3-glucuronidation, the estrogens and anthraflavic acid activated or inhibited estradiol-3-glucuronidation dependent on substrate and effector concentrations. For example, at substrate concentrations of 5 and 10 μM, estradiol-3-glucuronidation activity was stimulated by as much as 80% by low concentrations of 17α-EE but was unaltered by flavanone. However, at higher substrate concentrations (25–100 μM) estradiol-3-glucuronidation was inhibited by about 55% by both compounds. Anthraflavic acid and PhIP were also stimulators of estradiol 3-glucuronidation at low substrate concentrations. The most potent inhibitor of estradiol 3-glucuronidation was the flavonoid tangeretin. The UGT2B7 substrates morphine and ibuprofen had no effect on estradiol 3-glucuronidation, whereas retinoic acid was slightly inhibitory. Estradiol-17-glucuronidation was inhibited by 17α-EE, estriol, and naringenin but was not activated by any compound. This study demonstrates that the interactions of substrates and inhibitors at the active site of UGT1A1 are complex, yielding both activation and competitive inhibition kinetics.
CTLA-4+ Regulatory T Cells Increased in Cetuximab-Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor Prognosis
Authors: Hyun-Bae Jie, Patrick J. Schuler, Steve C. Lee, Raghvendra M. Srivastava, Athanassios Argiris, Soldano Ferrone, Theresa L. Whiteside, Robert L. Ferris
Journal: Cancer Research (2015)

The EGFR-targeted antibody cetuximab is effective against head and neck cancer (HNSCC), but in only 15% to 20% of patients, and the variability and extent of cetuximab-mediated cellular immunity is not fully understood. We hypothesized that regulatory T cells (Treg) may exert a functional and clinical impact on antitumor immunity in cetuximab-treated individuals. The frequency, immunosuppressive phenotype, and activation status of Treg and natural killer (NK) cells were analyzed in the circulation and tumor microenvironment of cetuximab-treated patients with HNSCC enrolled in a novel neoadjuvant, single-agent cetuximab clinical trial. Notably, cetuximab treatment increased the frequency of CD4(+)FOXP3(+) intratumoral Treg expressing CTLA-4, CD39, and TGFβ. These Treg suppressed cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and their presence correlated with poor clinical outcome in two prospective clinical trial cohorts. Cetuximab expanded CTLA-4(+)FOXP3(+) Treg in vitro, in part, by inducing dendritic cell maturation, in combination with TGFβ and T-cell receptor triggering. Importantly, cetuximab-activated NK cells selectively eliminated intratumoral Treg but preserved effector T cells. In ex vivo assays, ipilimumab targeted CTLA-4(+) Treg and restored cytolytic functions of NK cells mediating ADCC. Taken together, our results argue that differences in Treg-mediated suppression contribute to the clinical response to cetuximab treatment, suggesting its improvement by adding ipilimumab or other strategies of Treg ablation to promote antitumor immunity.
Environmental Factors in Childhood IDDM: A population-based, case-control study
Authors: Charles F Verge, Neville J Howard, Les Irwig, Judy M Simpson, Dorothy Mackerras, Martin Silink
Journal: Diabetes Care (1994)

To identify environmental factors involved in the etiology of insulin-dependent diabetes mellitus (IDDM).An estimated 90% of all incident cases of IDDM in patients 0-14 years of age in New South Wales, Australia, were ascertained over 18 months. For each IDDM patient, two age- and sex-matched control subjects were randomly selected from the population. Past environmental exposures were determined with a questionnaire completed by the parents. Response rates were 92% for the IDDM patients (217 of 235) and 55% for the control subjects (258 of 470). The relative risk associated with each exposure was estimated with the odds ratio (OR) adjusted for confounding factors using multiple logistic regression.The introduction of cow's milk-based infant formula into the diet before 3 months of age was associated with an increased risk (OR 1.52, 95% confidence interval [CI] 1.04-2.24). Exclusive breast-feeding for > or = 3 months was associated with a protective effect (OR 0.66, 95% CI 0.45-0.97). High dietary intake of cow's milk protein in the 12 months before the onset of diabetic symptoms was also associated with an increased risk (OR 1.84, 95% CI 1.12-3.00). A recent infection (during the 3 months before onset of diabetic symptoms) was more common in the patients than the control subjects (OR 2.92, 95% CI 1.96-4.35), as was day care attendance before the age of 3 (OR 1.73, 95% CI 1.00-3.00). When two age-groups, defined by the median age at onset of diabetes, were compared, the associations with early infant-feeding were stronger among the younger group (< 9.2 years), and associations with recent diet and recent infection were stronger among the older group (> or = 9.2 years).These results indicate an increased risk of IDDM associated with early dietary exposure to cow's milk-containing formula, short duration of exclusive breast-feeding, high intake of cow's milk protein in the recent diet, recent infection, and early attendance at day care.
P215 Referral Patterns For Mediastinal Staging With Ebus Across A Lung Cancer Network A Report From The Manchester Cancer Ebus Sub-group
Authors: M. Evison, P. Crosbie, J. Morris, J. Martin, R. Shah, H. Doran, J. Hoyle, S. Bailey, D. Rana, R. Sundar, R. Booton
Journal: Thorax (2014)

<h3>Introduction</h3> Manchester Cancer is a large Cancer Network in the North West of England, consisting of ten NHS Trusts. There is known variability in lung cancer outcomes across the ten trusts, including resection rates. We have examined the referral patterns of each individual trust for EBUS mediastinal staging and compared this with the trust’s lung cancer resection rates. <h3>Methods</h3> The Manchester Cancer EBUS sub-group has data for all EBUS referrals from each of the ten NHS trusts in our Network in 2012. The National Lung Cancer Audit Report 2013 provides the number of lung cancer patients diagnosed at each trust for the same time period. From this data we could estimate the proportion of lung cancer patients from each trust that were referred for mediastinal staging with EBUS. <h3>Results</h3> In 2012, 2302 patients were diagnosed with lung cancer in this Network. In the same period, 193 patients were referred for EBUS mediastinal staging (8.4%). The proportion of lung cancer patients referred for mediastinal staging with EBUS varied significantly across the ten trusts ranging from 3.4% to 30.2% (p &lt; 0.0001). The spearman co-efficient was 0.60 (p = 0.07) suggesting a possible relationship between the proportion of patients referred for EBUS and surgical resection (Figure 1). However, this may be due to a very high rate of staging EBUS at one trust, which if excluded yields a spearman co-efficient of 0.45 (p = 0.22). <h3>Discussion</h3> It is highly concerning that only 8% of lung cancer patients underwent EBUS nodal staging in our network given 52% of UK patients with histologically confirmed NSCLC are stage I-III at the time of diagnosis. It is of note that the Trust with the highest proportion of patients undergoing EBUS nodal staging have the highest surgical resection rate and three of the four Trusts with the lowest resection rates refer &lt;5% of patients for EBUS nodal staging. Standardisation of referral practice across the Network is a key future goal for the EBUS Sub-group.
Haloacetonitriles: metabolism, genotoxicity, and tumor-initiating activity.
Authors: E L Lin, F B Daniel, S L Herren-Freund, M A Pereira
Journal: Environmental Health Perspectives (1986)

Haloacetonitriles (HAN) are drinking water contaminants produced during chlorine disinfection. This paper evaluates metabolism, genotoxicity, and tumor-initiating activity of these chemicals. The alkylating potential of the HAN to react with the electrophile-trapping agent, 4-(p-nitrobenzyl)pyridine, followed the order dibromoacetonitrile (DBAN) greater than bromochloroacetonitrile (BCAN) greater than chloroacetonitrile (CAN) greater than dichloroacetonitrile (DCAN) greater than trichloroacetonitrile (TCAN). When administered orally to rats, the HAN were metabolized to cyanide and excreted in the urine as thiocyanate. The extent of thiocyanate excretion was CAN greater than BCAN greater than DCAN greater than DBAN much greater than TCAN. Haloacetonitriles inhibited in vitro microsomal dimethylnitrosamine demethylase (DMN-DM) activity. The most potent inhibitors were DBAN and BCAN, with Ki = 3-4 X 10(-5) M; the next potent were DCAN and TCAN, with Ki = 2 X 10(-4) M; and the least potent inhibitor was CAN, with Ki = 9 X 10(-2) M. When administered orally, TCAN, but not DBAN, inhibited hepatic DMN-DM activity. The HAN produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells. TCAN was the most potent DNA strand breaker, and BCAN greater than DBAN greater than DCAN greater than CAN, which was only marginally active. DCAN reacted with polyadenylic acid and DNA to form adducts in a cell-free system; however, the oral administration of DBAN or DCAN to rats did not result in detectable adduct formation in liver DNA. None of the HAN initiated gamma-glutamyltranspeptidase (GGT) foci when assayed for tumor-initiating activity in rat liver foci bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 5194: Pim2 is required for maintaining Multiple Myeloma cell proliferation through modulating mTORC1 pathway.
Authors: Jing Lu, Tatiana Zavorotinskaya, Yumin Dai, Xiaohong Niu, Joseph Castillo, Janet Sim, Jianjun Yu, Kevin Shannon, Pablo Garcia
Journal: Cancer Research (2013)

Abstract Multiple Myeloma (MM) is the second most common hematological malignancy. Despite the advances of therapeutic regimens over the last decade, nearly all patients eventually relapse, highlighting the need for additional therapeutic agents. Pim kinases, a family of serine/threonine kinase, are reported to be oncogenic and required for the maintenance of hematological malignancies. Here, consistent with previous reports, we show that Pim2 kinase expression is most highly elevated in MM. Importantly, shRNA knockdown of Pim2 leads to a significant inhibition of MM cell growth, suggesting that Pim2 is critical in maintaining MM malignancy. We developed a potent and specific small molecule inhibitor for the Pim kinases. Inhibition of Pim2 by this molecule suppresses MM cell growth. We find that Pim inhibitor treatment results in the suppression of cell proliferation, but not induction of apoptosis, in all MM cell lines tested. Further, we identified mTORC1 signaling, which is critical for cell proliferation, as significantly repressed by Pim2 inhibition. The two major mTORC1 downstream effectors: P70S6K and 4EBP1 are rapidly dephosphorylated upon Pim inhibitor treatment of MM cells. We are currently investigating the potential signaling modules that may mediate Pim2’s regulation on mTORC1 pathway. Taken together, our findings strongly support Pim2 as a promising therapeutic target in MM, given its distinct expression in MM and essential role in maintaining proliferation. Citation Format: Jing Lu, Tatiana Zavorotinskaya, Yumin Dai, Xiaohong Niu, Joseph Castillo, Janet Sim, Jianjun Yu, Kevin Shannon, Pablo Garcia. Pim2 is required for maintaining Multiple Myeloma cell proliferation through modulating mTORC1 pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5194. doi:10.1158/1538-7445.AM2013-5194
610 Anti IL-6 therapy rescues transgenic mice with liver specific overexpression of TGF-β1 from death after LPS mediated liver injury
Authors: F.R. Thieringer, J.F. Garcia-Lazaro, P. Czochra, U. Schmitt, D. Friebe, E. Meyer, S. Luth, M. Schuchmann, P.R. Galle, A.W. Lohse
Journal: Journal of Hepatology (2004)
Ciprofloxacin and Loperamide in the Treatment of Bacillary Dysentery
Authors: Gerald S. Murphy
Journal: Annals of Internal Medicine (1993)

Objective: To compare the safety and efficacy of loperamide plus ciprofloxacin with those of ciprofloxacin alone in the treatment of bacillary dysentery. Design: Double-blind, placebo-controlled, randomized clinical trial. Setting: Hospital in Thailand. Participants: Eighty-eight adults with dysentery seeking medical care between November 1990 and February 1992. Patients who had received prior antibiotics or antimotility drugs were excluded. Intervention: All 88 patients with dysentery were treated with ciprofloxacin, 500 mg twice daily for 3 days. Forty-two of these patients were randomly assigned to receive loperamide, a 4-mg initial dose followed by 2 mg after every loose stool (as many as eight caplets [16 mg] daily), and 46 were randomly assigned to receive placebo. Measurements: Stools were collected daily until resolution of diarrhea and again after 10 days. The time to passage of the last unformed stool, number of unformed stools, and symptoms were recorded after treatment. Results: Shigella or enteroinvasive Escherichia coli (53%), Vibrio parahaemolyticus (16%), and Salmonella (7%) were the most common bacterial enteric pathogens identified in 88 patients with dysentery. In patients infected with Shigella or enteroinvasive E. coli, the median duration of diarrhea was 19 hours (25th to 75th percentiles, 6 to 42 hours) for those receiving loperamide plus ciprofloxacin compared with 42 hours (21 to 46 hours) for those receiving ciprofloxacin alone (P = 0.028). The median number of diarrheal stools for those receiving ciprofloxacin and loperamide was 2.0 (1 to 5 stools) compared with 6.5 (2 to 9 stools) for those receiving ciprofloxacin alone (P = 0.016). None of the participants had a temperature greater than 38 C after 24 hours of treatment. None of the patients was infected with the same bacterial enteric pathogen more than 1 day after receiving treatment. Conclusions: Loperamide decreases the number of unformed stools and shortens the duration of diarrhea in dysentery caused by Shigella in adults treated with ciprofloxacin.
Reversal of Meconium Inhibition of Pulmonary Surfactant by Ferric Chloride, Copper Chloride, and Acetic Acid
Authors: RUNAR ALMAAS, BENGT ROBERTSON, BIM LINDERHOLM, EVA LUNDBERG, OLA D. SAUGSTAD, ATLE MOEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Meconium inhibits pulmonary surfactant function. We investigated the in vitro effect of meconium on three different commercial surfactants. The dynamic surface properties of these surfactants were evaluated at the concentration of 5 mg/ml with a pulsating bubble system. The inhibitory effect of 2.75 mg/ml meconium was significantly less on Alveofact than on Curosurf and Survanta. Ferric chloride and copper chloride completely reversed the inhibitory effect of meconium. Meconium also prevented effective spreading of surfactant in a Wilhelmy balance system, and this inhibitory effect was counteracted by addition of ferric chloride. Image analysis of Curosurf demonstrated that meconium reduced the total number of microbubbles in 15 light-microscopic fields (4.35 mm2) from 1,748 ± 481 to 180 ± 166. Ferric chloride restored the number of microbubbles. Addition of ferric chloride or copper chloride to surfactant/meconium lowers pH, and pH adjustment by acetic acid also reversed the inhibitory effect of meconium. Together with the fact that the iron-chelator deferoxamine did not attenuate the effect of ferric chloride this suggests that the observed contrainhibition is caused by lowering of pH, and that meconium inhibition of surfactant is pH-dependent. Lowering pH from 6.2 to 5–5.5 abolished the inhibitory effects of meconium on surfactant. Inhibition of 2.5 mg/ml of Curosurf with plasma could also be reversed by increasing amounts of ferric chloride. We conclude that the inhibitory effect of meconium on surfactant in vitro can be abolished by addition of ferric chloride, copper chloride, or acetic acid.
Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model
Authors: R. Chugh, K.A. Griffith, E.J. Davis, D.G. Thomas, J.D. Zavala, G. Metko, B. Brockstein, S.D. Undevia, W.M. Stadler, S.M. Schuetze
Journal: Annals of Oncology (2015)
Action planning supplements mirror systems in language evolution
Authors: Bruce Bridgeman
Journal: Behavioral and Brain Sciences (2005)

Mirror systems must be supplemented by a planning capability to allow language to evolve. A capability for creating, storing, and executing plans for sequences of actions, having evolved in primates, was applied to sequences of communicatory acts. Language could exploit this already-existing capability. Further steps in language evolution may parallel steps seen in the development of modern children.