tbuckley/cabot-search huggingface dataset:
Clinical, Biochemical, and Genetic Heterogeneity in Short-Chain Acyl-Coenzyme A Dehydrogenase Deficiency
Authors: Bianca T. van Maldegem, Marinus Duran, Ronald J. A. Wanders, Klary E. Niezen-Koning, Marije Hogeveen, Lodewijk Ijlst, Hans R. Waterham, Frits A. Wijburg
Journal: JAMA (2006)

ContextShort-chain acyl-coenzyme A (CoA) dehydrogenase (SCAD) deficiency (SCADD) is an autosomal recessive, clinically heterogeneous disorder with only 22 case reports published so far. Screening for SCADD is included in expanded newborn screening programs in most US and Australian states.ObjectivesTo describe the genetic, biochemical, and clinical characteristics of SCADD patients in the Netherlands and their SCADD relatives and to explore the genotype to phenotype relation.Design, Setting, and ParticipantsRetrospective study involving 31 Dutch SCADD patients diagnosed between January 1987 and January 2006 and 8 SCADD relatives. SCADD was defined by the presence of (1) increased butyrylcarnitine (C4-C) levels in plasma and/or increased ethylmalonic acid (EMA) levels in urine under nonstressed conditions on at least 2 occasions, in combination with (2) a mutation and/or the c.511C>T or c.625G>A susceptibility variants on each SCAD-encoding (ACADS) allele. Patients were included only if the SCAD-encoding (ACADS) was fully sequenced and if current clinical information could be obtained. Relatives were included when they carried the same ACADS genotype as the proband, and had increased C4-C and/or EMA.Main Outcome MeasuresPrevalence, genotype (mutation/mutation, mutation/variant, variant/variant), C4-C and EMA levels, clinical signs and symptoms, and clinical course.ResultsA birth-prevalence of at least 1:50 000 was calculated. Most patients presented before the age of 3 years, with nonspecific, generally uncomplicated, and often transient symptoms. Developmental delay, epilepsy, behavioral disturbances, and hypoglycemia were the most frequently reported symptoms. The ACADS genotype showed a statistically significant association with EMA and C4-C levels, but not with clinical characteristics. Seven out of 8 SCADD relatives were free of symptoms.ConclusionsSCADD is far more common than assumed previously, and clinical symptoms in SCADD are nonspecific, generally uncomplicated, often transient, and not correlated with specific ACADS genotypes. Because SCADD does not meet major newborn screening criteria, including a lack of clinical significance in many patients and that it is not possible to differentiate diseased and nondiseased individuals, it is not suited for inclusion in newborn screening programs at the present time.
Magnetic Resonance Imaging in Gastroenterology: Time to Say Good-bye to All That Endoscopy?
Authors: H. E. Adamek, H. Breer, T. Karschkes, J. Albert, J. F. Riemann
Journal: Endoscopy (2000)

Magnetic resonance imaging (MRI) has been described as the most important development in medical diagnosis since the discovery of the roentgen ray more than 100 years ago. The effectiveness of MRI has been extended to make it applicable in a wide variety of gastrointestinal disorders. The attention of gastroenterologists is currently focusing on pancreaticobiliary and bowel diseases. Magnetic resonance cholangiopancreatography (MRCP) has become a competitive alternative to diagnostic endoscopic retrograde cholangiopancreatography in a variety of hepatobiliary and pancreatic diseases. Magnetic resonance enteroscopy has the potential to become the preferable method for evaluating the entire small bowel; virtual colonoscopy, on the other hand, is far from the stage at which it could be promoted as a tool for general screening purposes in suspected colonic diseases. Its drawbacks include problems with standardization, implementation of the techniques in generalized settings, and patient acceptance.
THE EXTERNAL BONE CLAMP VERSUS THE INTERNAL BONE PLATE IN THE OPERATIVE TREATMENT OF FRACTURES
Authors: LEONARD FREEMAN
Journal: JAMA (1913)

So much has been said recently about Lane's internal bone plates that there is danger of losing sight of the advantages of the external bone clamp. Hence a brief comparison of the two should be of interest. In operating on fractures it is often necessary to employ some artificial means for holding the fragments in position. According to circumstances this may be done with chromic catgut, wire, bone or ivory ferrules or medullary plugs, autogenous or foreign bone grafts, staples, internal bone plates, or external clamps of various patterns. The ideal method would consist in the use of something which, while holding the bones firmly and not irritating the tissues, would rapidly undergo absorption, thus leaving no foreign body to cause delayed union and late infection. It should also be easy of application, with the least traumatism, and should not interfere with the process of repair. Unfortunately none of the procedures in use fulfil all
Urinary Phenylpyruvic Acid in Phenylketonuria
Authors: Richard J. Allen, James L. Wilson
Journal: JAMA (1964)

The simplest way to diagnose phenylketonuria, a ferric chloride test on urine samples, is still of great usefulness even in the newborn period when babies are most available for testing. Twenty-two of our 60 patients were less than 1 year old at the time of the diagnosis, but ten infants in particular who were less than 60 days of age also had "typical" biochemical findings. The proper collection of urine samples to avoid bacterial contamination resulted in a positive ferric chloride test in seven of these 10 infants who had been examined by 3 weeks of age. Several infants tested earlier were positive on the second, fifth, and eighth days of life. This method then may be employed to make an early diagnosis or to confirm a suspected diagnosis when only an elevated blood phenylalanine is available.
Sorafenib inhibits macrophage-induced growth of hepatoma cells by interference with insulin-like growth factor-1 secretion
Authors: Martin Franz Sprinzl, Andreas Puschnik, Anna Melissa Schlitter, Arno Schad, Kerstin Ackermann, Irene Esposito, Hauke Lang, Peter Robert Galle, Arndt Weinmann, Mathias Heikenwälder, Ulrike Protzer
Journal: Journal of Hepatology (2014)
Nonlaboratory-Based Risk Assessment Algorithm for Undiagnosed Type 2 Diabetes Developed on a Nation-Wide Diabetes Survey
Authors: Xianghai Zhou, Qing Qiao, Linong Ji, Feng Ning, Wenying Yang, Jianping Weng, Zhongyan Shan, Haoming Tian, Qiuhe Ji, Lixiang Lin, Qiang Li, Jianzhong Xiao, Weiguo Gao, Zengchang Pang, Jianping Sun
Journal: Diabetes Care (2013)

To develop a New Chinese Diabetes Risk Score for screening undiagnosed type 2 diabetes in China.Data from the China National Diabetes and Metabolic Disorders Study conducted from June 2007 to May 2008 comprising 16,525 men and 25,284 women aged 20-74 years were analyzed. Undiagnosed type 2 diabetes was detected based on fasting plasma glucose ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L in people without a prior history of diabetes. β-Coefficients derived from a multiple logistic regression model predicting the presence of undiagnosed type 2 diabetes were used to calculate the New Chinese Diabetes Risk Score. The performance of the New Chinese Diabetes Risk Score was externally validated in two studies in Qingdao: one is prospective with follow-up from 2006 to 2009 (validation 1) and another cross-sectional conducted in 2009 (validation 2).The New Chinese Diabetes Risk Score includes age, sex, waist circumference, BMI, systolic blood pressure, and family history of diabetes. The score ranges from 0 to 51. The area under the receiver operating curve of the score for undiagnosed type 2 diabetes was 0.748 (0.739-0.756) in the exploratory population, 0.725 (0.683-0.767) in validation 1, and 0.702 (0.680-0.724) in validation 2. At the optimal cutoff value of 25, the sensitivity and specificity of the score for predicting undiagnosed type 2 diabetes were 92.3 and 35.5%, respectively, in validation 1 and 86.8 and 38.8% in validation 2.The New Chinese Diabetes Risk Score based on nonlaboratory data appears to be a reliable screening tool to detect undiagnosed type 2 diabetes in Chinese population.
Abstract B10: Inactivation of androgen-induced coactivator ARD1 inhibits androgen receptor acetylation and prostate tumorigenesis
Authors: Zehua Wang, Zemin Wang, Jianhui Guo, Wanguo Liu
Journal: Cancer Research (2012)

Abstract Androgen signaling through androgen receptor (AR) is critical for prostate tumorigenesis. Given that AR-mediated gene regulation is enhanced by AR coactivators, inactivation of those coactivators is emerging as a promising therapy for prostate cancer (PCa). Here, we show that the N-acetyltransferase Arrest-defect-1 protein (ARD1) functions as a novel AR coactivator in PCa cells. ARD1 is upregulated in human PCa cell lines, tumor biopsies, and in prostate tumor tissues of Pten null mouse. The expression of ARD1 was augmented by treatment with synthetic androgen (R1881) unless AR is deficient or is inhibited by AR-specific siRNA or androgen inhibitor bicalutamide (Casodex [CDX]). Depletion of ARD1 by shRNA suppressed PCa cell proliferation, anchorage-independent growth, and xenograft tumor formation in SCID mice, suggesting that AR-dependent ARD1 expression is biologically germane. Notably, ARD1 was necessary and sufficient to transcriptionally coactivate a number of AR-target genes that are involved in prostate tumorigenesis shown by qRT-PCR, reporter assay, and chromatin immunoprecipitation (ChIP) analysis. Furthermore, ARD1 but not ARD1-dead (acetylase activity null mutant) interacted physically with and acetylated the AR protein in vivo and in vitro. Moreover, the ARD1-mediated AR acetylating is p300 independent. Since ARD1-specific AR acetylation facilitated the AR binding to its targeted promoters for gene transcription, we propose that ARD1 functions as a unique AR coactivator and forms a positive feedback loop for AR-dependent prostate tumorigenesis. Disruption of AR-ARD1 interactions may be a potent intervention for androgen-dependent PCa therapy. Citation Format: Zehua Wang, Zemin Wang, Jianhui Guo, Wanguo Liu. Inactivation of androgen-induced coactivator ARD1 inhibits androgen receptor acetylation and prostate tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B10.
Faecal bacterial flora in cancer of the colon.
Authors: D Vargo, M Moskovitz, M H Floch
Journal: Gut (1980)

Selective aerobic and anaerobic plate media were employed to isolate the predominant faecal flora of patients with cancer of the colon (CC), cancer with non-gastrointestinal involvement (NGI), and with non-malignant diseases (N). The CC and N groups did not differ significantly in either total aerobic or anaerobic counts. The CC group did have a significantly lower anaerobic/aerobic ratio compared with the N group (2.42 vs. 2.96, P less than 0.05). This was the result of a greater predominance of aerobic bacteria and a decrease in anaerobic cocci, Eubacterium and Fusobacterium in the CC group. Previous studies report that aerobic organisms have a greater ability to produce amines than non-spore forming anaerobes. If the intestinal flora can produce carcinogenic nitrosamines in vivo from amines and nitrites, the aerobic bacterium in the faeces may be of importance in supplying the amine substrate for nitrosation. The comparison of the NGI group with the N group showed a significant variation in the total anaerobic count (11.02 vs. 11.41, P less than 0.05) and in the composition of the faecal flora. This indicates that discretion must be used in analysing the data obtained from cancer patients, as the presence of a carcinoma may be responsible for changes in bacterial flora.
Doctors call for an end to "malicious stories"
Authors: C Court
Journal: BMJ (1994)

A group of five women doctors, all of whom claim to have had false and damaging allegations made against them, is calling on the General Medical Council (GMC) - the doctors' regulatory body in Britain - to take action against doctors who harm colleagues' careers by spreading malicious stories.

The women include Professor Wendy Savage, a senior lecturer in obstetrics and gynaecology who was suspended in 1985 on grounds of alleged incompetence and later reinstated after a six week inquiry, and Dr Bridget O'Connell, who has just received an apology form her health authority after being suspended for 12 years from her job as consultant …
Procarbazine associated alveolitis.
Authors: L D Lewis
Journal: Thorax (1984)

Drug induced pulmonary toxicity is a well documented complication of treatment with cytotoxic agents- bleomycin, methotrexate, cyclophosphamide, and busul- phan being most commonly implicated.'This report docu- ments a severe alveolitis associated with administration of procarbazine.
Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT) in DNA repair, apoptosis and necrosis after cisplatin
Authors: Janna Sand-Dejmek, Guillaume Adelmant, Bijan Sobhian, Anne S Calkins, Jarrod Marto, Dirk J Iglehart, Jean-Bernard Lazaro
Journal: Molecular Cancer (2011)

Abstract Background Platinum-containing chemotherapy produces specific DNA damage and is used to treat several human solid tumors. Tumors initially sensitive to platinum-based drugs frequently become resistant. Inhibition of DNA repair is a potential strategy to enhance cisplatin effectiveness. After cisplatin treatment, a balance between repair and apoptosis determines whether cancer cells proliferate or die. DNA-dependent protein kinase (DNA-PK) binds to DNA double strand breaks (DSBs) through its Ku subunits and initiates non-homologous end joining. Inhibition of DNA-PK sensitizes cancer cells to cisplatin killing. The goal of this study is to elucidate the mechanism underlying the effects of DNA-PK on cisplatin sensitivity. Results Silencing the expression of the catalytic subunit of DNA-PK (DNA-PKcs) increased sensitivity to cisplatin and decreased the appearance of γH2AX after cisplatin treatment. We purified DNA-PK by its Ku86 subunit and identified interactors by tandem mass spectrometry before and after cisplatin treatment. The structure specific recognition protein 1 (SSRP1), Spt16 and γH2AX appeared in the Ku86 complex 5 hours after cisplatin treatment. SSRP1 and Spt16 form the facilitator of chromatin transcription (FACT). The cisplatin-induced association of FACT with Ku86 and γH2AX was abrogated by DNase treatment. In living cells, SSRP1 and Ku86 were recruited at sites of DSBs induced by laser beams. Silencing SSRP1 expression increased sensitivity to cisplatin and decreased γH2AX appearance. However, while silencing SSRP1 in cisplatin-treated cells increased both apoptosis and necrosis, DNA-PKcs silencing, in contrast, favored necrosis over apoptosis. Conclusions DNA-PK and FACT both play roles in DNA repair. Therefore both are putative targets for therapeutic inhibition. Since DNA-PK regulates apoptosis, silencing DNA-PKcs redirects cells treated with cisplatin toward necrosis. Silencing FACT however, allows both apoptosis and necrosis. Targeting DNA repair in cancer patients may have different therapeutic effects depending upon the roles played by factors targeted.
Chronic Systemic Therapy With Low-dose Morpholino Oligomers Ameliorates the Pathology and Normalizes Locomotor Behavior in mdx Mice
Authors: Alberto Malerba, Paul S Sharp, Ian R Graham, Virginia Arechavala-Gomeza, Keith Foster, Francesco Muntoni, Dominic J Wells, George Dickson
Journal: Molecular Therapy (2010)

The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans. The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.
Amelioration of cerebral ischemia–reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin
Authors: Takayuki Ishii, Tomohiro Asai, Dai Oyama, Tatsuya Fukuta, Nodoka Yasuda, Kosuke Shimizu, Tetsuo Minamino, Naoto Oku
Journal: Journal of Controlled Release (2012)
Universal Grammar and second language acquisition: The null hypothesis
Authors: Samuel David Epstein, Suzanne Flynn, Gita Martohardjono
Journal: Behavioral and Brain Sciences (1996)

Abstract The target article advanced the null, unified and widely misinterpreted generative hypothesis regarding second language (L2) acquisition. Postulating that UG (Universal Grammar) constrains L2 knowledge growth does not entail identical developmental trajectories for L2 and first language (LI) acquisition; nor does it preclude a role for the L1. In embracing this hypothesis, we maintain a distinction between competence and performance. Those who conflate the two repeat fundamental and by no means unprecedented misconstruals of the generative enterprise, and more specifically, of the empirical content of the null hypothesis regarding L2 linguistic knowledge growth. We hope to have identified certain common goals, the adoption of which might constitute a firm foundation for continued productive interdisciplinary development of contemporary theoretical and experimental L2 acquisition research.
Relative Roles of Radionuclide Scanning and Radiographic Imaging in Eosinophilic Granuloma
Authors: RAJENDRA KUMAR, SUPPIAH BALACHANDRAN
Journal: Clinical Nuclear Medicine (1980)

Twenty-four skeletal lesions were studied in seven patients with eosinophilic granuloma by radiographic skeletal surveys and radionuclide bone imaging. The radiographs detected 22 (92%) of these lesions and missed only two, whereas the scintiscans identified only 16 (67%) of these lesions, and missed eight. Radiographic skeletal survey and radionuclide bone imaging are complementary procedures in detecting bone lesions in bone marrow disorders, including eosinophilic granuloma. Use of either method alone is fraught with the danger of missing bone lesions of eosinophilic granuloma.
Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice
Authors: Yanyan Zheng, Wen-ling Chen, Stan G. Louie, T. S. Benedict Yen, Jing-hsiung James Ou
Journal: Hepatology (2006)

HBV is a major risk factor for hepatocellular carcinoma (HCC). However, whether HBV can directly cause HCC or only indirectly via the induction of chronic liver inflammation has been controversial. By using transgenic mice carrying the entire HBV genome as a model, we now demonstrate that HBV by itself is an inefficient carcinogen. However, it can efficiently promote hepatocarcinogenesis initiated by the carcinogen diethylnitrosamine (DEN). This effect of HBV does not involve chronic liver inflammation, is apparently due to enhanced hepatocellular apoptosis and compensatory regeneration following DEN treatment, and does not require the HBV X protein. Conclusion: Our results demonstrate a direct role of HBV in a hepatocarcinogenesis pathway that involves the interaction between this virus and a dietary carcinogen. (HEPATOLOGY 2007;45:16–21.)
THE TEACHING OF ANESTHESIOLOGY IN THE ARMY
Authors: STEVENS J. MARTIN
Journal: JAMA (1942)

It is now a well established fact that inadequate anesthesia was responsible for much of the surgical morbidity and mortality of the last war. Such costly lessons must not and will not be repeated in the present conflict. Anesthesiology has progressed tremendously in the last two decades and has been recognized as an indispensable department in the organization of leading university<sup>1</sup>and other civilian<sup>2</sup>hospitals. Its recognition in army hospitals<sup>3</sup>has begun with the designation of a special section for anesthesiology. The organized didactic and clinical instruction by the Army of its personnel in the science of anesthesiology constitutes a further advance. The plan of instruction at Tilton General Hospital is now presented to the medical profession for the first time. Aside from the mobilization of combat units for the successful prosecution of this war, the various services of the Army have been augmented tremendously by specially
Adult Respiratory Distress Syndrome in Patients with Severe Neutropenia
Authors: Frederick P. Ognibene, Sue E. Martin, Margaret M. Parker, Terri Schlesinger, Patricia Roach, Cynthia Burch, James H. Shelhamer, Joseph E. Parrillo
Journal: New England Journal of Medicine (1986)

Most investigators believe that the pulmonary endothelial damage that is characteristic of the adult respiratory distress syndrome (ARDS) requires the action of neutrophils. In a retrospective review of patients with ARDS, we looked for cases that had developed in patients who already had neutropenia. Four clinical criteria were required for the diagnosis of ARDS: the occurrence of a precipitating event, diffuse bilateral pulmonary infiltrates on a chest x-ray film, a normal intravascular volume (as reflected by a wedge pressure of less than 18 mm Hg), and arterial hypoxemia. During 2 1/2 years, 11 patients fulfilled these clinical criteria, had severe neutropenia that antedated the onset of ARDS, and had pulmonary histologic specimens obtained during the early stages (less than seven days) of clinical respiratory distress. Five of these specimens showed diffuse alveolar damage without evidence of infectious pneumonitis (the histopathological finding characteristic of ARDS), and none had a neutrophil infiltrate. We conclude that ARDS can occur in the setting of severe neutropenia, without pulmonary neutrophil infiltration.