tbuckley/cabot-search huggingface dataset:
Abstract 5276: Phospholipase A/acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signal pathway
Authors: Fu-Ming Tsai, Chang-Chieh Wu, Chun-Hua Wang, Tzung-Chieh Tsai, Rong-Yaun Shyu, Shun-Yuan Jiang
Journal: Cancer Research (2014)

Abstract H-rev107, also called HRASLS3 or PLA2G16, is a member of the HREV107 type II tumor suppressor gene family that includes HREV107, Retinoid-inducible gene 1, and HRASLS. The HREV107 protein family contains an NC domain, with unknown function at the N-terminus, and a hydrophobic membrane-anchoring domain at the C-terminus. Previous study showed that the H-rev107 gene specifically expressed in H-ras resistant fibroblasts. However, the mode of action and the site of inhibition of H-rev107 are still unknown. Our results revealed that H-rev107 reduced the levels of activated RAS (RAS-GTP) or Elk1-mediated transactivation in epidermal growth factor stimulated HtTA cells that expressed H-RAS. Further, we found that H-rev107 reduced H-RAS palmitoylation determined by acyl-biotin exchange assay. Palmitoylation or S-acylation is the post-translational attachment of fatty acids to cysteine residues and continuous cycles of de- and reacylation reactions accounts for the specific subcellular distribution of RAS. H-rev107 was shown as a phospholipase A/Acyltransferase (PLA/AT) that involved in the phospholipid metabolism. We next determined whether H-rev107 affected H-RAS palmitoylation through deacylation/acylation by acyl-protein thioesterases (APT1) or PLA/AT using APT1 inhibitor (palmostatin B) or PLA/AT inhibitor (arachidonyl trifluoromethyl ketone, AACOCF3). Treating cells with AACOCF3 can increase H-rev107-induced acylated H-RAS suppression of HtTA cells. Also, AACOCF3 significantly increased the levels of activated RAS and Elk-mediated transactivation in H-rev107 expressed cells. However, treating cells with palmostatin B enhanced H-rev107-induced acylated H-RAS suppression in H-rev107 expressing cells. In conclusion, H-rev107 can inhibit H-RAS palmitoylation to reduce its GTP-form levels and further suppress the downstream signal pathway. Our study suggested that PLA/AT activity of H-rev107 might play an important role in H-rev107 mediated RAS suppression. Note: This abstract was not presented at the meeting. Citation Format: Fu-Ming Tsai, Chang-Chieh Wu, Chun-Hua Wang, Tzung-Chieh Tsai, Rong-Yaun Shyu, Shun-Yuan Jiang. Phospholipase A/acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signal pathway. [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 5276. doi:10.1158/1538-7445.AM2014-5276
Human Immunodeficiency Virus Infections in Teenagers
Authors: Donald S. Burke
Journal: JAMA (1990)

Between October 15, 1985, and March 31, 1989, serum specimens from 1 141 164 teenaged youths (aged &lt;20 years) who applied for entry into the US military were tested for antibodies to the human immunodeficiency virus. Overall, 393 teenaged applicants were found to be seropositive (prevalence, 0.34 per 1000). Prevalences varied markedly in different geographic locales: less than 0.1 per 1000 throughout the north-central states, compared with greater than 2 per 1000 in urban counties in Maryland, Texas, New York, and the District of Columbia. Overall, rates among teenaged males (345/991 445; prevalence, 0.35 per 1000) and teenaged females (48/150 013; prevalence, 0.32 per 1000) were comparable. The prevalence among black teenaged applicants (1.06 per 1000) was greater than that among white (0.18 per 1000) or Hispanic (0.31 per 1000) teenaged applicants. Infections with the human immunodeficiency virus are not rare among teenaged Americans. (<i>JAMA</i>. 1990;263:2074-2077)
A Novel Mouse Model for <i>De novo</i> Melanoma
Authors: Mayuko Y. Kumasaka, Ichiro Yajima, Khaled Hossain, Machiko Iida, Toyonori Tsuzuki, Tamio Ohno, Masahide Takahashi, Masashi Yanagisawa, Masashi Kato
Journal: Cancer Research (2010)

Abstract Nevus-associated melanomas arise from pre-existing benign lesions, but de novo melanomas can also develop in the absence of such lesions. Few studies have addressed the latter phenomenon because no animal models have been described in which melanomas clearly develop in a de novo manner. In this study, we have address this need in defining RFP-RET-transgenic mice (RET mice) as a mouse model for multi-step melanomagenesis that proceeds via tumor-free, benign, premalignant, and malignant stages. Melanomas from RET mice exhibited decreased expression levels of endothelin receptor B (Ednrb) compared with benign tumors. In RET mice that were heterozygous for Ednrb (Ednrb+/−;RET mice), &amp;gt;80% of the arising primary tumors were malignant. Life span after tumor development in the mice was significantly shorter than in RET mice. Lung metastasis after tumor development was significantly higher than in RET mice. The observed process of melanomagenesis in Ednrb+/−;RET mice, which proceeded without a pre-existing benign lesion, along with the emergent characteristics in the model after tumor development corresponded well with the formation of de novo melanoma in humans. Our findings define a novel transgenic mouse model for de novo melanoma and suggest that reduced expression of Ednrb might facilitate the development of de novo melanoma in humans. Cancer Res; 70(1); 24–9
Toxic Shock Syndrome Surveillance in the United States, 1980 to 1981
Authors: ARTHUR L. REINGOLD
Journal: Annals of Internal Medicine (1982)

Between 1 January 1980 and 18 October 1981, investigators from the Centers for Disease Control collected information on 1407 cases of toxic shock syndrome using a nationwide passive surveillance system. Ninety-two percent of the reported cases were associated with menstruation. Information available on the type of menstrual device used shows that 99% of the cases occurred in tampon users. Menstrual cases occurred predominantly in whites (98%) under the age of 25 (65%). The case/fatality ratio for menstrual toxic shock syndrome was 3.1% for cases with onset in 1981. The distribution of reported cases by date of onset showed a gradual increase in the number reported before the summer of 1980, a sharp increase during the summer and early fall of 1980, a marked decrease in the late fall of 1980, and a subsequent gradual decrease. Factors affecting the incidence and reporting of toxic shock syndrome during these periods include changes in the number of tampon users, changes in the availability and usage patterns of tampons, changes in the prevalence of toxin-producing strains of Staphylococcus aureus, improved recognition of the syndrome, and publicity.
Acetyl glyceryl ether phosphorylcholine-stimulated human platelets cause pulmonary hypertension and edema in isolated rabbit lungs. Role of thromboxane A2.
Authors: J E Heffner, S A Shoemaker, E M Canham, M Patel, I F McMurtry, H G Morris, J E Repine
Journal: Journal of Clinical Investigation (1983)

Macrophages, neutrophils, and platelets may play a role in acute edematous lung injury, such as that seen in the adult respiratory distress syndrome (ARDS), but their potential actions and interactions are unclear. Because stimulated human macrophages and neutrophils can release acetyl glyceryl ether phosphorylcholine (AGEPC), a potent platelet activator, we hypothesized that in ARDS, leukocyte release of AGEPC might stimulate platelets to release thromboxane A2 (TXA2), which then produces pulmonary hypertension and lung edema. In support of this premise, we found that pulmonary hypertension and edema occurred in isolated rabbit lungs perfused with human platelets and AGEPC, but not with platelets or AGEPC alone. Infusion of a vasodilator (nitroglycerin) to maintain base-line pulmonary artery pressures in lungs perfused with platelets and AGEPC prevented the development of lung edema suggesting that platelet and AGEPC-induced edema was hydrostatic in nature. Additional experiments suggested that the increased pressure was a result of TXA2 release from platelets stimulated by AGEPC. Specifically, preincubation of platelets with imidazole, a thromboxane synthetase blocker, prior to infusion with AGEPC significantly diminished pulmonary hypertension and prevented lung edema. Furthermore, pretreating lung preparations with 13-azaprostanoic acid, a TXA2 antagonist, before infusion of AGEPC and untreated platelets also reduced the pulmonary hypertension and blocked the lung edema. The role of TXA2 was further suggested when perfusates from lungs infused with platelets and AGEPC developed high levels of TXA2, whereas perfusates from controls did not. These results suggest that platelet aggregation induced by AGEPC may contribute to ARDS by releasing TXA2, which raises microvascular pressure and increases edema formation, especially when an underlying permeability defect is present.
A randomized controlled trial of interferon-alpha in patients with cirrhosis caused by 2a/2b genotype hepatitis C virus
Authors: Kenji Ikeda, Hiromitsu Kumada, Satoshi Saitoh, Yoshiyuki Suzuki, Masahiro Kobayashi, Akihito Tsubota, Isao Koida, Mizuho Fukuda, Yasuji Arase, Kazuaki Chayama, Naoya Murashima, Toshiro Tango
Journal: Journal of Hepatology (1998)
Aluminium accumulation and immunosuppression.
Authors: A. Davenport, A. M. Davison, E. J. Will, C. Toothill, K. E. Newton, G. R. Giles
Journal: BMJ (1989)

tive studies, in renal artery stenosis and stroke.In renal artery stenosis injudicious lowering of blood pressure long term can decrease renal perfusion pressure with a resulting loss of renal function" and possible death.'2Likewise, long term antihyper- tensive treatment in patients with cerebrovascular atheroma can cause a critical fall in cerebral blood flow," which may be accompanied by neurological symptoms and stroke." Raising the blood pressure in such cases can abolish transient ischaemic attacks," as occurred in the case reported by Dr Mark Oliver.'6It is difficult to understand why Dr Waller and colleagues and Drs Coope and Warrender are
"Super managers" to be sent into failing hospitals
Authors: J. Wise
Journal: BMJ (2013)

Senior doctors and top industry managers are to be recruited to a new fast track leadership programme as part of a plan to turn round failing NHS hospitals.

These “super managers” will be given a 10 month crash course in how to run hospital trusts and how the NHS works. As part of their training they will take a two month intensive business course at a leading institution, such as Harvard Business School. Graduates of the scheme will be expected to be rapidly promoted to NHS senior managers and chief executives.

England’s health secretary, Jeremy Hunt, made the announcement as part of a new plan to improve poorly performing NHS trusts. After the Keogh review which looked at 14 NHS trusts with high mortality rates, 11 have now been placed …
Clinical Effects of the Dichloro and Monochlorophenyl Analogues of Diamino Pyrimidine: Antagonists of Folic Acid12
Authors: M. Lois Murphy, Rose Ruth Ellison, David A. Karnofsky, Joseph H. Burchenal
Journal: Journal of Clinical Investigation (1954)

Hitchings, Elion, Vanderwerff, and Falco (1) demonstrated that certain 2,4-diamino-pyrimidines inhibited the growth of L. casei; this inhibition could be reversed by folic acid and citrovorum factor.The effects of these active pyrimidines are activity is associated with the presence of 2 and 4 amino groups in the pyriniidine nucleus, and a weighty substituent in the 5 position, suggesting a definite similarity in molecular configuration to the folic acid antagonists (Figure 1).FIGURE 1 N AMINOPTERIN Cl NH2 1/ Cl' HN S N CH: 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP)thus similar to those of the 4 amino derivatives of folic acid.But in contrast to the folic acid antagonists, the active pyrimidines are not pterins, and it appears unlikely that a rearrangement or structural alteration to a pterin ring system can occur.It is of interest, however, that high antagonist
Why are patients with acute stroke admitted to hospital?
Authors: B. Isaacs
Journal: BMJ (1986)

computed tomography2 but lacks the ability to provide a differential diagnosis.Recently interest has focused on radiopharmaceuticals which allow images to be made showing regional cerebral blood flow.Two agents in par- ticular have proved useful, '231 isopropylamphetamine (IMP)3 and, more recently, 99Tc hexamethyl propyleneamineoxime (HM-PAO).4These agents not only provide the ability to identify the presence of both tumours' and infarcts,6 although both appear as areas of reduced cerebral blood flow, but they also show distinctive patterns of perfusion for some types of dementia.78We have shown that, in particular, the pattern in Alzheimer's disease is ofa bilateral reduction in perfusion in the temporo- parieto-occipital regions while in multi-infarct dementia the uptake pattern varies from normal to that of gross focal defects.9Our recent work indicates that in Huntington's chorea there may be reduced perfusion in the head of the caudate nucleus.9'mTc HM-PAO, which offers several technical advantages over '23I IMP, should be available commercially in the near future, and the imaging equipment, a tomographic gammacamera, is avail- able in most hospitals.The study is simple to perform, requiring one intravenous injection of the radiopharmnaceutical and about 30 minutes' imagig tme.
An update on pachydermodactyly and a report of three additional cases
Authors: D. KOPERA, H.P. SOYER, H. KERL
Journal: British Journal of Dermatology (1995)

Pachydermodactyly is a benign condition characterized by symmetrical, painless, diffuse swelling of the skin on the lateral aspects of the proximal Interphalangeal joints of the lingers. Histopathological examination shows epidermal hyperplasia, an increase of dermal collagen bundles and a slightly increased number of fibroblasts. We report three adolescent males with pachydermodactyly. We also review 20 published cases, and discuss the differential diagnosis, clearly distinguishing pachydermodactyly from 'true' and 'false' knuckle pads.
Reorganisation problems in Powys
Authors: K C Harvey
Journal: BMJ (1982)

comitantly decrease end-diastolic volume and pressure, would, by Laplace's law, decrease oxygen consumption by decreasing the wall tension-related energy expenditure during pressure generation.There will also be the added beneficial effect in that coronary blood flow, which is maximal during diastole, would increase with the fall in end-diastolic pressure.An increase in arterial pressure may also reflexly decrease heart rate, another important determinant of myocardial oxygen consump- tion.
“Impending crisis” in journals provision requires radical solutions
Authors: Bruno Rushforth
Journal: BMJ (2004)

The House of Commons Science and Technology Committee has recommended that all UK higher education institutions establish electronic repositories where their published output can be stored and read, free of charge.

It has also recommended encouraging further experimentation with “author pays” publishing models as one radical long term solution to help improve access to scientific, technical, and medical journals.

The committee's report into scientific publishing says that a combination of high journal …
Abstract P2-16-24: Folate targeted SMDC’s: A possible new treatment alternative for folate receptor expressing TNBC patients
Authors: CP Leamon, JA Reddy, M Nelson, A Bloomfield, R Dorton, M Vetzel
Journal: Cancer Research (2013)

Abstract Triple negative breast cancer (TNBC) is a subtype characterized by lack of gene expression for the estrogen receptor, progesterone receptor and the Her2/neu protein. Hence, the lack of hormonal or Her2 targeted therapy options makes TNBC difficult to treat, resulting in a death rate which is disproportionately higher than for other breast cancer subtypes. Recently, the folate receptor (FR) was shown to be highly expressed in TNBC, and expression significantly correlated with the higher grades of malignancy as well as poor outcomes. These observations suggest that TNBC patients may benefit from treatment with an FR-targeted therapy. To address this question, an established FR-positive subcutaneous TNBC pre-clinical model (MDA-MB-231) was chosen to evaluate a panel of FR-targeted small molecule drug conjugates (SMDC) with high potencies and varying mechanisms of action. Thus, EC1456 (folate-tubulysin B; IC50 ∼ 1 nM) and EC1744 (a folate-DNA cross-linking agent; IC50 ∼0.1 nM) were dosed intravenously at 2 μmol/kg following a three times per week, two week schedule in tumor-bearing mice. Both FR-targeted agents were found to be highly active against the MDA-MB-231 tumors, with 80-100% cure rates. In all cases, the observed anti-tumor activity was not accompanied by any significant weight loss in the test animals. These findings suggest that folate-targeted SMDCs may be active against TNBC and that further preclinical studies are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-24.
Landmark article July 10, 1937: The therapy of the Cook County Hospital. By Bernard Fantus
Authors: B. Fantus
Journal: JAMA (1984)

Edited by <h3>BLOOD PRESERVATION</h3> This preliminary report on the establishment of a "blood bank" at the Cook County Hospital is perhaps justified by the interest displayed in this development, the inquiries received from various parts of the country, and the importance of the promptest and most generous exchange of experience in a new field of life-saving endeavor. That blood can be preserved for weeks in condition fit for transfusion is now a well established fact, thanks most especially to Yudin's<sup>1</sup>work on cadaver blood. There is, however, something revolting to Anglo-Saxon susceptibilities in the proposal of using cadaver blood and it is not probable, even were this not the case, that enough blood could be secured in this manner to be of great practical importance. The "blood bank" proposition, on the other hand, seems susceptible of extensive development and it is to this, most especially, that we desire to
Corrigendum to “Impact of treatment on extra hepatic manifestations in patients with chronic hepatitis C” [J Hepatol 36 (2002) 812–818]
Authors: Patrice Cacoub, Vlad Ratziu, Robert P Myers, Pascale Ghillani, Jean Charles Piette, Joseph Moussalli, Thierry Poynard
Journal: Journal of Hepatology (2002)
Superficial Phlebitis and Phase 3.5 Trials
Authors: Lee Goldman, Jeffrey Ginsberg
Journal: New England Journal of Medicine (2010)

In this issue of the Journal, Decousus et al.1 report on the efficacy and safety of fondaparinux for the treatment of superficial-vein thrombosis in the legs. The results of their carefully conducted, placebo-controlled trial show that treatment with fondaparinux, at a dose of 2.5 mg once daily for 45 days, as compared with placebo, reduced the probability that superficial-vein thrombosis in the legs would progress to deep-vein thrombosis or pulmonary embolism (1.3% with placebo vs. 0.2% with fondaparinux), without an increase in bleeding or other serious adverse events. The probability that patients would undergo surgery for superficial-vein thrombosis was reduced . . .
Reproductive toxicity of di-n-butylphthalate in a continuous breeding protocol in Sprague-Dawley rats.
Authors: R N Wine, L H Li, L H Barnes, D K Gulati, R E Chapin
Journal: Environmental Health Perspectives (1997)

The phthalate ester di-n-butylphthalate (DBP) is used extensively in the manufacture of plastics; its reproductive toxicity was tested in rats by the National Toxicology Program's Reproductive Assessment by Continuous Breeding protocol. Levels of 0.1, 0.5, and 1.0% DBP in the diet were selected, and this dosing design yielded average daily DBP intakes of 52, 256, and 509 mg/kg for males and 80, 385, and 794 mg/kg for females, respectively. DBP consumption by F0 rats reduced the total number of live pups per litter in all treated groups by 8-17% and live pup weights in the 0.5% and 1.0% dose groups by < 13%. In tests to determine the affected sex, the number of offspring was unchanged, but the weights of pups from treated females were significantly decreased and offspring from treated males were unchanged. At necropsy, high-dose F0 females had a 14% reduction in body weight, and both sexes had approximately 10-15% increased kidney and liver to body weight ratios compared to controls. Sperm parameters and estrous cyclicity were not affected. In the F1 mating trial, indices of mating, pregnancy, and fertility in the 1.0% dose group were all sharply decreased (one live litter was delivered out of 20 cohabited pairs), concomitant with a 13% decrease in dam body weight. Live F2 pup weights were 6-8% lower in all dose groups. F1 necropsy results revealed that epididymal sperm counts and testicular spermatid head counts were significantly decreased in the 1.0% dose group. Histopathologic investigation showed that 8 of 10 F1 males consuming 1.0% DBP had degenerated seminiferous tubules and 5 of 10 had underdeveloped or otherwise defective epididymides. No ovarian or uterine lesions were observed. In conclusion, this study showed that DBP is a reproductive/developmental toxicant in Sprague-Dawley rats exposed both as adults and during development; it also indicates that the adverse reproductive/developmental effects of DBP on the second generation were greater than on the first generation.
Suppression of Colorectal Cancer Liver Metastasis and Extension of Survival by Expression of Apolipoprotein(a) Kringles
Authors: Hyun-Kyung Yu, Jang-Seong Kim, Ho-Jeong Lee, Jin-Hyung Ahn, Suk-Keun Lee, Soon-Won Hong, Yeup Yoon
Journal: Cancer Research (2004)

Abstract The formation of hepatic metastases in colorectal cancer is the main cause of patient death. Current therapies directed at hepatic metastasis of colorectal cancer have had minimal impact on outcome. Therefore, alternative treatment strategies for liver metastasis require development. The present study was performed to evaluate the application of cDNA of LK68 encoding apolipoprotein(a) kringles IV-9, IV-10, and V as possible candidates for gene therapy treatment of this life-threatening disease. The murine colorectal cancer cell line CT26 was transduced ex vivo with LK68 cDNA via retroviral gene transfer, and an experimental model of hepatic metastasis was established by injecting LK68-expressing and control cells into the spleens of BALB/c mice. Expression of LK68 did not affect the growth characteristics and viability of transduced CT26 cells in vitro. LK68 produced from CT26 cells substantially inhibited the migration of endothelial cells in vitro. In vivo, substantial suppression of liver metastasis and prolonged survival were observed in mice bearing LK68-expressing CT26 cells, compared with controls. LK68-expressing liver metastases were restricted to smaller sizes and displayed decreased microvessel density and increased tumor cell apoptosis. Our data collectively indicate that LK68 suppresses angiogenesis-dependent progression of prevascular micrometastases to macroscopic tumors and their growth, which are clinically accessible and biologically relevant therapeutic targets. We propose that antiangiogenic gene therapy with LK68 is a promising strategy for the treatment of colorectal cancer liver metastasis.
Clinicians' Documentation of Gunshot Wounds
Authors: R. K. Wright
Journal: JAMA (1996)

<h3>To the Editor.</h3> —A Medical News &amp; Perspectives article by Ms Voelker entitled "New Program Targets Death Investigator Training"<sup>1</sup>has some inaccurate information concerning the presentation by Dr Fackler. The article states that Fackler reported "that clinicians inadequately documented the location in 38% of the wounds, size in 4%, and shape in 3%." My recollection of this presentation is that Fackler reported "that clinicians adequately document the location in 38%, size in 4%, and shape in 3%." This is an extremely significant error rate of over 90%. That was one of the purposes of the paper, to demonstrate what those of us who do forensic pathology know that clinicians do a ridiculously terrible job of documenting gunshot wounds.