tbuckley/cabot-search huggingface dataset:
Homosexuality in men and number of older brothers
Authors: R Blanchard, A F Bogaert
Journal: American Journal of Psychiatry (1996)

This study investigated whether homosexual men have a higher mean birth order than heterosexual men primarily because they have more older brothers or because they have more older siblings of both sexes.For the main analyses, 302 heterosexual men were individually matched on year of birth with an equal number of heterosexual men. Each completed a self-administered, anonymous questionnaire concerning family background and other biodemographic information.Logistic regression analysis showed that homosexuality was positively correlated with the proband's number of older brothers but not with older sisters, younger brothers, younger sisters, or parental age at the time of the proband's birth. Each additional older brother increased the odds of homosexuality by 33%.These results restrict the range of possible theories of the birth order phenomenon to those that can explain not only why older brothers increase the probability of homosexuality in later-born males but also why older sisters neither enhance this effect nor counteract it.
Re: Robert J. van Soest, Ellen S. de Morrée, Charlotte F. Kweldam, et al. Targeting the Androgen Receptor Confers In Vivo Cross-resistance Between Enzalutamide and Docetaxel, But Not Cabazitaxel, in Castration-resistant Prostate Cancer. Eur Urol 2015;67:981–5
Authors: Masaki Shiota, Akira Yokomizo
Journal: European Urology (2015)
270. Treatment of CT26 Tumors with Dendritic Cells Transduced with a Recombinant SV40 Vector Expressing Interleukine 15
Authors: Maria Vera, Gloria G. Aseguinolaza, Nerea Razquin, Ignacio Melero, Jesus Prieto, Puri Fortes
Journal: Molecular Therapy (2004)

Tumors can be treated with cytokines that activate the immuno-response against tumor cells. Viral vectors have been used to direct cytokine expression to the tumor and surrounding tissues or to cells like dendritic cells (DCs). We decided to study the efficiency of recombinant vectors based on Simian Virus 40 virus (SV40) to deliver interleukine 12 (IL12) or interleukine 15 (IL15) to the tumor or to transduced DCs. We produced recombinant viruses expressing firefly luciferase (rSVLuc), murine IL12 (rSVIL12) and murine IL15 (rSVIL15). Expression, secretion and activity of recombinant SV40 expressed IL12 and IL15, was demonstrated by several means. Infection of the tumour cell line CT26 and of human DCs by rSVIL12 was determined by Elisaagainst murine IL12. In vitro pre-treatment of CT26 cells with rSVLuc, rSVIL12 or rSVIL15 before subcutaneous inoculation in BALB/C mice did not prevent tumor formation. Intratumoral treatment of CT26 subcutaneous tumours with rSVLuc, rSVIL12 or rSVIL15 had no effect in tumor growth, even when three intratumoral viral injections were performed. We also used these vectors to infect in vitro differentiated BALB/C mice DCs obtained from bone marrow. Infection of immature DCs with rSV40 vectors did not change the expression of cell surface markers CD80, CD86, CD11c, CD40, HLA-I and HLA-II, indicating that DCs tranduced by rSV40 vectors maintained immature after virus infection. We assayed the antitumoral efficiency of infected and maturated DCs injected intratumoraly or infected immature DCs injected intratumoraly or intravenously. The best result was obtained with immature DCs injected directly inside the tumor. 73% tumour remissions were obtained with DCs expressing IL15 and 40% remissions with DCs transduced by rSVIL12. An elispot and a cytotoxic assay indicated that mice treated with DCs expressing IL15 had the highest amount of INFg producing T cells and cytotoxic T cells. These results can be explained by the ability of IL15 to enhance the interaction between DCs and T cells. We conclude that DCs infected with rSVIL15 vectors could be a good alternative to activate the immuno-response against tumor cells.
Abstract P104: Socio-Emotional Stressors Increase Ventilation Rate During Advanced Cardial Life Support in a Manikin Model
Authors: Kjell I Overgard, Cato A Bjorkli, Conrad Bjorshol, Helge Myklebust, Thomas Hoff
Journal: Circulation (2008)

BACKGROUND: Studies suggest that trained medical personnel deliver manual ventilations at excessive rates while performing advanced cardiac life support (ACLS). Excessive ventilation rates may cont...
Circumferential Strain Analysis Identifies Strata of Cardiomyopathy in Duchenne Muscular Dystrophy
Authors: Kan N. Hor, Janaka Wansapura, Larry W. Markham, Wojciech Mazur, Linda H. Cripe, Robert Fleck, D. Woodrow Benson, William M. Gottliebson
Journal: Journal of the American College of Cardiology (2009)
The Importance of Brown Adipose Tissue
Authors: James A Timmons, Bente K Pedersen
Journal: New England Journal of Medicine (2009)

Objective: To describe the clinical characteristics and outcomes in a population of dogs with negative-pressure pulmonary edema (NPPE) and to identify the main causes of the disease.To evaluate any associations with morbidity and mortality.Design: Retrospective study.Setting: Three university teaching hospitals and two private referral centers.Animals: Thirty-five client-owned dogs presented with NPPE. Interventions: NoneMeasurements and Main Results: Data collected included patient characteristics, clinical history, clinicopathological abnormalities, radiographic features, treatments and outcome.Median age was 4 months (range 2-90) and median weight was 7.1 kg (range 1.7-37.2).There were many causes of NPPE including leash tugs, near hanging, accidental choking, anatomical obstruction to airflow and purposeful airway obstruction by people.The most common cause of NPPE was accidental choking (40% of cases).Dogs with an anatomical obstruction were older than 24 months.Hypoxemia with an increased alveolar-arterial gradient was common on presentation.The majority of thoracic radiographs (65.7%) showed an alveolar or interstitial pattern in the caudodorsal area as previously described in the literature.Oxygen therapy was administered to 33 (94.3%) dogs.Furosemide was administered to 18 (51.4%)dogs.Median length of hospitalization was 2 days (range 0-14).Twenty-eight (80%) dogs survived to discharge.Seven dogs were mechanically ventilated and only 2 of them (28.6%)survived to discharge.Requirement for mechanical ventilation (p<0.001) was the only parameter associated with mortality.Conclusions: Most cases of NPPE occur in juvenile dogs.Different incidents associated with upper airway obstruction can produce an episode of NPPE.Choking on food or toys and near hanging have not been previously described in the veterinary literature as inciting causes of NPPE.The overall prognosis is good.
Blocking and suppressing effects of white tea, green tea, EGCG and caffeine in PhIP-treated rats
Authors: Orianna Carter, Rong Wang, Gayle A. Orner, Roderick H. Dashwood
Journal: Cancer Research (2005)

2477   We reported previously that white tea, the least processed form of tea, was an inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP)-induced colonic aberrant crypt foci (ACF) in the rat when administered before, during and after the carcinogen. To distinguish blocking from suppressing effects, rats were given white tea (2% wt/vol) either before and during PhIP treatment or after the carcinogen. Additional groups received green tea (2% wt/vol) or corresponding doses of epigallocatechin-3-gallate (EGCG) or caffeine in the drinking water. In the blocking study, white tea was more potent than green tea at inducing hepatic cytochromes P4501A1 and 1A2, glutathione S-transferase, and UDP-glucuronosyltransferase, based on enzyme assays and/or immunoblotting; however, white tea and green tea were equally effective as blocking agents against PhIP-induced ACF. In the suppression study, white tea, caffeine and EGCG inhibited PhIP-induced ACF, whereas green tea had no significant effect. Interestingly, the most potent suppression was seen in rats given EGCG (**P
Clostridium perfringens in London, July 2009: two weddings and an outbreak
Authors: J Eriksen, D Zenner, S R Anderson, K Grant, D Kumar
Journal: Eurosurveillance (2010)

Food poisoning outbreaks caused by Clostridium perfringens enterotoxin occur occasionally in Europe but have become less common in recent years. This paper presents the microbiological and epidemiological results of a large C. perfringens outbreak occurring simultaneously at two weddings that used the same caterer. The outbreak involved several London locations and required coordination across multiple agencies. A case-control study (n=134) was carried out to analyse possible associations between the food consumed and becoming ill. Food, environmental and stool samples were tested for common causative agents, including enterotoxigenic C. perfringens. The clinical presentation and the epidemiological findings were compatible with C. perfringens food poisoning and C. perfringens enterotoxin was detected in stool samples from two cases. The case-control study found statistically significant associations between becoming ill and eating either a specific chicken or lamb dish prepared by the same food handler of the implicated catering company. A rapid outbreak investigation with preliminary real-time results and the successful collaboration between the agencies and the caterer led to timely identification and rectification of the failures in the food handling practices.
Human epidermal growth factor receptor 2 protein overexpression and gene amplification in extramammary Paget disease
Authors: R. Tanaka, Y. Sasajima, H. Tsuda, K. Namikawa, A. Tsutsumida, F. Otsuka, N. Yamazaki
Journal: British Journal of Dermatology (2013)

Background Several recent studies have reported on the overexpression of human epidermal growth factor receptor (HER)2 in extramammary Paget disease (EMPD). However, there are only a few cases in which both overexpression and gene amplification of HER2 have been examined. Objectives To evaluate the overexpression and gene amplification of HER2 using a standardized method with a large number of cases of EMPD. Methods Immunohistochemically, the overexpression of the HER2 protein was examined in 104 cases of EMPD, including 31 intraepithelial cases and 73 invasive cases (35 superficially invasive and 38 deeply invasive). When the HER2 protein was overexpressed or potentially overexpressed, further analysis of amplification of the gene encoding HER2, ERBB2, was undertaken using fluorescence in situ hybridization. Results The HER2 protein was overexpressed in 16 cases (15%) in total, and in 13 of 73 cases (18%) of invasive EMPD. The ERBB2 gene was amplified in all cases with a HER2 score of 3+. A HER2 score of 3+ or 2+, and ERBB2 amplification were significantly more frequent in the cases of deeply invasive EMPD than in intraepithelial/superficially invasive EMPD (24% vs. 6%/3%, P =0·012) and were correlated with a larger number of lymph‐node metastases (P =0·047). Log‐rank tests for survival curves showed that lymph‐node metastasis and ERBB2 amplification were significant prognostic factors (P =0·0001 and P =0·043, respectively). However, by a multivariate analysis, only lymph‐node status was a significant indicator of Paget‐disease‐specific survival (P = 0·0001). Conclusions A subset of EMPD, both intraepithelial and invasive, showed HER2 overexpression and gene amplification. These HER2 alterations were correlated with biologically aggressive EMPDs, i.e. those with deep invasion and lymph‐node metastasis. Clinical trials of HER2‐targeted therapy are awaited for improvement of the prognosis of patients with aggressive EMPD.
NK314, a novel antitumor agent, induces rapid double strand DNA breaks by specific inhibition of topoisomerase IIα.
Authors: Shigehide Kagaya, Eriko Toyoda, Kazuhiro Tokunaka, Akira Masuda, Hirofumi Yokoyama, Kazuya Okamoto, Kiyohiro Nishikawa
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5525 

Background: NK314 is a synthetic benzo[c]phenanthridine analog and exhibits cytotoxic effect against various human tumor cell lines with low IC50 values ranging from 3 to 600ng/ml. As NK314 showed high efficacy on various human tumors xenografted in nude mice, phase I dose escalation study has been scheduled. In the last AACR meeting (#1368), we reported that NK314 induced rapid DNA double-strand breaks in cultured P388 leukemia cells. In order to elucidate the mechanism of DNA breakage, we examined the effect of NK314 on topoisomerase (Topo). Results: NK314 induced double strand breaks of cellular DNA very rapidly and strongly. This DNA fragmentation was detected even without protease treatment, which is necessary to detect DNA double strand breaks by known Topo inhibitors for degrading protein-DNA complex. However, NK314-induced DNA fragmentation was inhibited by Topo catalytic inhibitors, such as ICRF-193 and suramin. To examine how Topos are involved in NK314-induced DNA fragmentation and cytotoxicity, we examined the effect of NK314 on Topo-DNA cleavable complex formation by ICE bioassay. After blotting DNA from drug-treated cells onto the membrane, covalently bound Topo IIα and Topo IIβ were detected with specific antibodies. In NK314 (1 μM)-treated cells, only Topo IIα-DNA cleavable complex was detected, while in Etoposide (ETP) (100 μM)-treated cells, both Topo IIα- and Topo IIβ-cleavable complexes were detected. This stabilization of cleavable complex was stable even after NK314 was removed from culture medium, although ETP-induced cleavable complex was diminished rapidly. The potent anti-tumor activity of NK314 seems to be caused by this stable cleavable complex formation. Moreover, DNA fragmentation by NK314 in Topo IIβ -deficient HL-60/MX2 cells was affected very slightly compared to in HL-60 parental cells, although DNA fragmentation by ETP was largely decreased in HL-60/MX2 cells. In accordance with this, HL-60/MX2 cells showed higher resistance to ETP than NK314. Furthermore, effect of NK314 on DNA fragmentation and cytotoxicity was largely inhibited by Topo IIα siRNA, while Topo IIβ siRNA slightly inhibited NK314 cytotoxicity only when NK314 was treated at higher concentration. These results suggest that NK314 is a potent Topo IIα specific inhibitor, and the very stable cleavable complex formation causes rapid DNA double strand breaks and efficient anti-tumor activity.
Modeling cancer in the Zebrafish.
Authors: Leonard I. Zon
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

SY13-01 

The zebrafish is a powerful system for dissecting cancer genetics. We recently generated a melanoma model in zebrafish by overexpressing human BRAF V600E in melanocytes using an MITF promoter. Stable transgenics develop moles, and when crossed to the p53 mutant, develop melanoma. Our studies have demonstrated that the moles and melanoma are p53 dependent and the dose of BRAF alters the latency of disease. We also recently generated a model of NRAS induced melanoma. In the stable transgenics, the entire fish appears black and yet individual moles occur and ultimately melanoma arises. These tumors are labeled with green fluorescent protein (GFP) and can be transplanted. We are currently mating the BRAF transgenic and NRAS transgenic melanoma models to a variety of pigment pattern mutants in an effort to find modifiers of mole formation and melanoma. Our studies are providing new insight into the genesis of melanoma and are likely to provide therapeutic opportunities for chemical biology and genetics in the future.
Sequence specificity of aflatoxin B1-induced mutations in a plasmid replicated in xeroderma pigmentosum and DNA repair proficient human cells.
Authors: Dan D. Levy, John D. Groopman, Susan E. Lim, Michael M. Seidman, Kenneth H. Kraemer
Journal: Cancer Research (1992)

The mutagenic spectrum induced by aflatoxin-DNA lesions in DNA repair deficient and repair proficient human cells was investigated. The reactive metabolite aflatoxin B1-8,9-epoxide was synthesized and reacted in vitro with the shuttle vector plasmid pS189. Plasmids were transfected into human fibroblasts and allowed to replicate, and the recovered plasmids were screened in indicator bacteria for plasmid survival and mutations in the supF marker gene. Sequence data were obtained from 71 independently arising mutants recovered from DNA repair deficient xeroderma pigmentosum (XP) cells [XP12BE(SV40)] and 60 mutants recovered from a DNA repair proficient cell line (GM0637). Plasmid survival was lower and mutation frequency higher with the XP cells, and the mutation hotspots differed substantially for the 2 cell lines. Most mutations (> 90%) were base substitutions at G:C pairs, only about one-half of which were G:C-->T:A transversions, the expected predominant mutation. One-third of the mutations at GG sites and none of those at isolated Gs were G:C-->A:T transitions. Tandem base substitutions also occurred only at GG sites and were found only with XP cells. The location of mutation hotspots with either cell line did not correlate with the level of modification within the sequence as assessed by a DNA polymerase stop assay. These results suggest that the DNA repair deficiency associated with XP can influence not only the overall frequency of mutations but also the distribution of mutations within a gene. The finding of transition mutations exclusively at GG sites may be of predictive value in attempts to link dietary aflatoxin exposure to cancers associated with specific mutations in the c-ras oncogene and the p53 tumor suppressor gene.
Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism
Authors: Quinten Waisfisz, Neil V. Morgan, Maria Savino, Johan P. de Winter, Carola G.M. van Berkel, Maureen E. Hoatlin, Leonarda Ianzano, Rachel A. Gibson, Fre Arwert, Anna Savoia, Christopher G. Mathew, Jan C. Pronk, Hans Joenje
Journal: Nature Genetics (1999)
Adrenalectomy in Breast Cancer
Authors: R. D. Bulbrook, F. C. Greenwood, G. J. Hadfield, E. F. Scowen
Journal: BMJ (1958)

Continued excretion of oestrogen produced by the adrenal cortex occurs after-oophorectomy in the majority of women with breast cancer.In 1945 Huggins and Scott performed bilateral adrenalectomy in four cases of advanced breast and prostatic cancer in an attempt to remove the second source of oestrogen pro- duction from the body.One patient survived for 116 days in a hypo-adrenal state, with some objective improvement in skeletal metastases.When cortisone became available the operation was carried out in 18 cases (Huggins and Bergenstal, 1952).Seven were women suffering from cancer of the breast, and clinical improvement was induced in all of them.The results stimulated great interest in the subject, and since 1952 many series of cases have been reported.It seems that bilateral adrenalectomy can play a definite and some- times valuable part in the palliative treatment of breast cancer.
Abstract 20591: A Simple Novel Classification of Left Atrial Appendage Morphology Predicts Stroke in Patients With Atrial Fibrillation
Authors: Madhu Reddy, Pramod Janga, Brandon Barnds, Arun Kanmanthareddy, Jayasree Pillarisetti, Sudharani Bommana, Donita Atkins, Dhanunjaya Lakkireddy
Journal: Circulation (2014)

Introduction:  Prior Left atrial appendage (LAA) morphology classification (cauliflower, windsock, cactus and chicken wing) have been made based on resemblance to “poorly defined” structures and may be difficult to replicate.   Hypothesis:  A more structured, easily replicable classification of LAA morphology would predict the risk of stroke in patients with atrial fibrillation (AF).   Methods:  Consecutive patients who underwent CT scan of the heart prior to AF ablation were included in this study. LAA morphology was classified into Class 1, Class 2 and Class 3 based on number of primary curvatures/bends on LAA (0, 1 and ≥2 bends respectively) by 2 independent observers. Patient variables including CHADS2 score, history of stroke, TEE determined LAA variables were collected and analyzed.   Results:  A total of 265 patients in whom CT was available with TEE findings were included in the current study. Mean age of the population was 60 ±9 years. Mean CHADS2 score was 1.18 ±0.9 and mean LA size was 4.3 ±0.6cm with a mean LVEF of 60 ±8. Twenty five (9.5%) patients had a history of stroke. Class 1, 2 and 3 groups comprised of 48 (18%), 95 (36%) and 122 (46%) patients respectively. The prevalence of stroke among these groups were 5.6%, 5.6% and 14% respectively. Class 3 LAA morphology (≥2 LAA bends) was much more likely to be associated with stroke when compared to the other 2 morphologies (14% vs 5.6%; p =0.021). This association was significant despite adjusting for baseline and TEE variables of LAA function. We also classified LAAs based on older classification. There was lesser inter-observer variability (6% vs 16%; p   Conclusions:  A novel classification of the LAA morphology is more reliable than the older classification. Patients with Class 3 LAA morphology (≥2 bends) are much more likely to have had a stroke compared to those with Class 1 or 2 morphology.
Lead Exposure and Cataract Risk in Men
Authors: David C. Beebe
Journal: JAMA (2005)

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Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis
Authors: Colin A. Flaveny, Kristine Griffett, Bahaa El-Dien M. El-Gendy, Melissa Kazantzis, Monideepa Sengupta, Antonio L. Amelio, Arindam Chatterjee, John Walker, Laura A. Solt, Theodore M. Kamenecka, Thomas P. Burris
Journal: Cancer Cell (2015)