tbuckley/cabot-search huggingface dataset:
Comparison of the Potential for Therapeutic Utilities with Gonadotropin-Releasing Hormone Agonists and Antagonists
Authors: BRIAN H. VICKERY
Journal: Endocrine Reviews (1986)

THE SUCCESS in synthesis of very potent agonistic analogs of GnRH was at first expected to lead to a low cost profertility therapy. Early findings of gonadal suppressive effects with these agents, however, led to the discovery of pituitary receptor desensitization and downregulation caused by continuous presence of GnRH and its analogs. It was then established that GnRH must be secreted in a pulsatile manner to exert its physiological effect of activating the reproductive cascade from gonadotropin release to gonadal steroidogenesis and gametogenesis. Only after application of this knowledge has GnRH become a valuable therapeutic agent in hypogonadotropic hypogonadism (1). A number of highly potent agonistic analogs have now been described and are in various stages of clinical evaluation (see Table 1). The increases in potency over the native hormone are related to increased binding affinity and consequent retardation in dissociation rate from the receptors (3). In addition, some of the analogs have a prolonged circulatory half-life in vivo (4, 5). As these changes would be expected to favor down-regulation and desensitization of receptors, it has been widely concluded that the high potency agonist analogs will be of no use as profertility agents. This conclusion may have been premature because the use of very low doses of such agents has not been fully explored. In specific instances where this approach has been taken, such as therapy for cryptorchidism (6) and some veterinary indications (7), success has been achieved with agonist analogs of GnRH (also see below). In addition, although such an analog has not been reported, a highly potent but short lived analog of GnRH would have direct application to therapy in hypogonadism of hypothalamic origin.
Molecular Cytogenetic Aberrations in Autosomal Dominant Polycystic Kidney Disease Tissue
Authors: Jean Gogusev, Ichiro Murakami, Mireille Doussau, Louise Telvi, Alexandre Stojkoski, Philippe Lesavre, Dominique Droz
Journal: Journal of the American Society of Nephrology (2003)

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder characterized by focal cyst formation from any part of the nephron. The molecular bases include germinal mutation of either PKD1 or PKD2 genes, enhanced expression of several protooncogenes, alteration of the TGF-alpha/EGF/EGF receptor (EGFR) axis, and disturbed regulation of proliferative/apoptosis pathways. To identify new locations of ADPKD related oncogenes and/or tumor suppressor genes (TSG), comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analyses were performed for a series of individual cysts (n = 24) from eight polycystic kidneys. By CGH, imbalances were detected predominantly on chromosomes 1p, 9q, 16p, 19, and 22q in all tissues. DNA copy number gain was seen on chromosomes 3q and 4q in five samples. The CGH data were supplemented by LOH analysis using 83 polymorphic microsatellite markers distributed along chromosomes 1, 9, 16, 19, and 22. The highest frequency of LOH was found on the 1p35-36 and 16p13.3 segments in cysts from seven samples. Allelic losses on 9q were detected in six, whereas deletions at 19p13 and 22q11 bands were observed in three polycystic kidneys. These results indicate that the deleted chromosomal regions may contain genes important in ADPKD initiation and progression.
Pornography: An Experimental Study of Effects
Authors: CLIFFORD B. REIFLER, JAMES HOWARD, MORRIS A. LIPTON, MYRON B. LIPTZIN, DONALD E. WIDMANN
Journal: American Journal of Psychiatry (1971)

The authors studied the effect of repeated exposure to pornographic material on young men. The 23 experimental subjects spent 90 minutes a day for three weeks viewing pornographic films and reading pornographic materials. Before-and-after measurements on these subjects and a control group of nine men included penile circumference changes and acid phosphatase activity in response to pornographic films. The data support the hypothesis that repeated exposure to pornography results in decreased interest in it and responsiveness to it. A variety of psychological tests and scales discerned no lasting effects on the subjects' feelings or behavior other than feeling bored by pornography, both immediately following the study and eight weeks later.
RELATION OF IRON SALTS TO INHIBITION OF GLYCOLYSIS BY THEILER FA VIRUS OF MOUSE ENCEPHALOMYELITIS
Authors: E. Racker, I. Krimsky
Journal: The Journal of Experimental Medicine (1947)

1. Brain homogenates of mice infected with the Theiler FA strain of mouse encephalomyelitis virus show marked inhibition of glucose phosphorylation. 2. A similar effect can be obtained by incubating normal brain homogenates with small amounts of ferrous sulfate. 3. Partially purified preparations of Theiler FA virus contain iron in amounts corresponding to their inhibitory effect on brain glycolysis. The virus preparations were purified by chemical fractionation and differential centrifugation and were dialyzed against potassium cyanide or pyrophosphate and potassium chloride for several days before they were analyzed for iron content. 4. The inhibitory effect of the virus preparations and of ferrous sulfate has been shown to be dependent on a heat-labile factor present in normal brain ("inactivating factor"). 5. The glycolytic activity of brain homogenates of mice infected with the Theiler FA virus can be restored by addition of a factor prepared from rabbit muscle extract. This "restoring factor" is non-dialyzable and is heat-labile. It has no hexokinase or phosphohexokinase activity. Its restoring activity is destroyed by the "inactivating factor" present in brain.
Logistic Regression Model to Distinguish Between the Benign and Malignant Adnexal Mass Before Surgery: A Multicenter Study by the International Ovarian Tumor Analysis Group
Authors: Dirk Timmerman, Antonia C. Testa, Tom Bourne, Enrico Ferrazzi, Lieveke Ameye, Maja L. Konstantinovic, Ben Van Calster, William P. Collins, Ignace Vergote, Sabine Van Huffel, Lil Valentin
Journal: Journal of Clinical Oncology (2005)

To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery.Patients had at least one persistent mass. More than 50 clinical and sonographic end points were defined and recorded for analysis. The outcome measure was the histologic classification of excised tissues as malignant or benign.Data from 1,066 patients recruited from nine European centers were included in the analysis; 800 patients (75%) had benign tumors and 266 (25%) had malignant tumors. The most useful independent prognostic variables for the logistic regression model were as follows: (1) personal history of ovarian cancer, (2) hormonal therapy, (3) age, (4) maximum diameter of lesion, (5) pain, (6) ascites, (7) blood flow within a solid papillary projection, (8) presence of an entirely solid tumor, (9) maximal diameter of solid component, (10) irregular internal cyst walls, (11) acoustic shadows, and (12) a color score of intratumoral blood flow. The model containing all 12 variables (M1) gave an area under the receiver operating characteristic curve of 0.95 for the development data set (n = 754 patients). The corresponding value for the test data set (n = 312 patients) was 0.94; and a probability cutoff value of .10 gave a sensitivity of 93% and a specificity of 76%.Because the model was constructed from multicenter data, it is more likely to be generally applicable. The effectiveness of the model will be tested prospectively at different centers.
Publication bias in clinical research
Authors: P.J Easterbrook, R Gopalan, J.A Berlin, D.R Matthews
Journal: The Lancet (1991)

In a retrospective survey, 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987, were studied for evidence of publication bias. As of May, 1990, 285 of the studies had been analysed by the investigators, and 52% of these had been published. Studies with statistically significant results were more likely to be published than those finding no difference between the study groups (adjusted odds ratio [OR] 2·32; 95% confidence interval [Cl] 1·25-4·28). Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor. An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results, and with increasing sample size. The tendency towards publication bias was greater with observational and laboratory-based experimental studies (OR=3·79; 95% CI=1·47-9·76) than with randomised clinical trials (OR=0·84; 95% CI=0·34-2·09). We have confirmed the presence of publication bias in a cohort of clinical research studies. These findings suggest that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies. Improved strategies are needed to identify the results of unpublished as well as published studies.
The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma
Authors: Arun K. Iyer, Yang Su, Jinjin Feng, Xiaoli Lan, Xiaodong Zhu, Yue Liu, Dongwei Gao, Youngho Seo, Henry F. VanBrocklin, V. Courtney Broaddus, Bin Liu, Jiang He
Journal: Biomaterials (2011)
A god for guts
Authors: J Walker-Smith
Journal: Gut (2002)

While attending the 15th National Conference on Advances in Perinatal and Paediatric Nutrition at the University of Stanford, California, July 2001, at an evening social event at the Cantor Center for Visual Arts, I chanced upon the small but remarkable collection of ancient Egyptian artefacts from the Stanford Family Collection.

In the University of Stanford collection of ancient Egyptian artefacts are two alabaster canopic jars dating from the 18th dynasty (1539–1295 BC) at the time of the New Kingdom. One had a head stopper shaped like a falcon (fig 1) representing Kebeh-senu-ef, one of the four sons of Horus acting as a guardian god of the embalmed guts of the deceased. A very similar name is given at the British Museum for the same god, namely Qebhsenuef. These four sons of Horus were the genii who guarded the north, south, east, and west. Remarkably, the ancient Maya of central America also had four deities upholding heaven at the four points of the compass. The Maya also used funerary jars called after these gods.



 Figure 1  
Alabaster canopic jar: Egypt 18th dynasty (1539–1295 BC). The falcon head stopper represents Kebeh-senu-ef, son of Horus, guardian of the embalmed intestines (photographed by the author at University of Stanford, Cantor Center for Visual Arts).



Nunn,1 in his remarkable account of ancient Egyptian medicine, states that the embalmers showed great technical expertise …
A collaborative study of infant respiratory function testing
Authors: I Dundas, C Beardsmore, T Wellman, J Stocks
Journal: European Respiratory Journal (1998)

The aims of this study were to compare inter-observer variability within and between two specialized infant lung function testing centres and to develop a strategy for performing and analysing infant respiratory function tests to facilitate future collaborative trials. A protocol for data collection and analysis was developed using similar equipment and identical software. All raw data were exchanged on disk and analysed, blind to infant status. All data were cross-analysed by both centres to assess inter-observer variability. Outcome measures were functional residual capacity (FRCpleth), airway resistance (Raw) and maximal expiratory flow at FRC (V'max,FRC). Subjects were recruited from the multicentre UK extracorporeal membrane oxygenation (ECMO) Trial and measured at around 1 yr of age. Forty-two infants attended the Institute of Child Health, London and 36 attended the Leicester Royal Infirmary. The proportion of infants treated with ECMO or conventional management at each centre was similar. There were no significant differences between any of the outcome measures for infants tested at either centre. During a cross-analysis, the agreement between the two centres, within infant, was closer for V'max,FRC and FRCpleth (within 10%) than for the more variable measurements of Raw (within 20%). A collaborative approach to trials with infant respiratory function as an outcome measure appears feasible, providing that close attention is paid to study design, and participants in such trials maintain a standard approach to data collection and analysis.
G-protein-coupled receptor dimers in the lime light
Authors: Lakshmi A Devi
Journal: Trends in Pharmacological Sciences (2000)

It will be important to apply these optical resonance energy transfer techniques to examine the dimerization of other GPCRs in intact cells. GPCRs can be classified into three major subfamilies (rhodopsin, calcitonin and metabotropic receptor subfamilies) and members of all three subfamilies have been shown to exist as homodimers12xSee all References12. Several recent studies have also revealed heterodimerization of GPCRs (between closely related as well as distantly related members), which alters the functional properties of these receptors13xGABAB receptors – the first 7TM heterodimers. Marshall, F.H. et al. Trends Pharmacol. Sci. 1999; 20: 396–399Abstract | Full Text | Full Text PDF | PubMed | Scopus (245)See all References, 14xG-protein-coupled receptor hetero-dimerization modulates receptor function. Jordan, B.A. and Devi, L.A. Nature. 1999; 399: 697–700Crossref | PubMed | Scopus (833)See all References, 15xReceptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Rocheville, M. et al. Science. 2000; 288: 154–157Crossref | PubMed | Scopus (638)See all References. Biochemical analyses have shown that in some GPCRs, agonist treatment leads to stabilization and/or an increase in the level of dimers, whereas in others agonist treatment has no effect or leads to a decrease in the level of dimers12xSee all References12. These optical resonance energy transfer techniques provide a novel and clear protocol to examine both homodimerization and heterodimerization of GPCRs in living cells. These methods are free from the complications that arise from more traditional biochemical methods of identifying dimers, and we should expect to see more studies using BRET and FRET given their simplicity and straightforwardness.Dimerization of GPCRs is a novel mechanism for receptor activation. It remains to be established whether GPCR dimerization occurs in vivo (i.e. in a living organism). Recent studies using energy transfer techniques to demonstrate the existence of dimers in living cells is a major step in this direction.
Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U
Authors: Kuen-Jer Tsai, Chun-Hung Yang, Yen-Hsin Fang, Kuan-Hung Cho, Wei-Lin Chien, Wei-Ting Wang, Tzu-Wei Wu, Ching-Po Lin, Wen-Mei Fu, Che-Kun James Shen
Journal: The Journal of Experimental Medicine (2010)

TDP-43 is a multifunctional DNA/RNA-binding factor that has been implicated in the regulation of neuronal plasticity. TDP-43 has also been identified as the major constituent of the neuronal cytoplasmic inclusions (NCIs) that are characteristic of a range of neurodegenerative diseases, including the frontotemporal lobar degeneration with ubiquitin+ inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). We have generated a FTLD-U mouse model (CaMKII-TDP-43 Tg) in which TDP-43 is transgenically overexpressed in the forebrain resulting in phenotypic characteristics mimicking those of FTLD-U. In particular, the transgenic (Tg) mice exhibit impaired learning/memory, progressive motor dysfunction, and hippocampal atrophy. The cognitive and motor impairments are accompanied by reduced levels of the neuronal regulators phospho–extracellular signal-regulated kinase and phosphorylated cAMP response element-binding protein and increased levels of gliosis in the brains of the Tg mice. Moreover, cells with TDP-43+, ubiquitin+ NCIs and TDP-43–deleted nuclei appear in the Tg mouse brains in an age-dependent manner. Our data provide direct evidence that increased levels of TDP-43 protein in the forebrain is sufficient to lead to the formation of TDP-43+, ubiquitin+ NCIs and neurodegeneration. This FTLD-U mouse model should be valuable for the mechanistic analysis of the role of TDP-43 in the pathogenesis of FTLD-U and for the design of effective therapeutic approaches of the disease.
Toxic Shock Syndrome in Menstruating Women
Authors: RAY F. FISHER
Journal: Annals of Internal Medicine (1981)

Eight adult women became severely ill with an acute, toxic erythroderma during menses. The syndrome was characterized by fever, generalized erythema, profound shock, multiple organ dysfunction, and desquamation occurring several days after the rash had faded. Gastrointestinal and cardiovascular abnormalities were present in all patients; three patients required ventilatory support; dialysis was performed on two; and one patient died. Mild relapse occurred in two patients during subsequent menses; the other patients have recovered without sequelae during follow-up of 6 to 42 months. Cervical colonization or local infection with Staphylococcus aureus is associated with this syndrome.
Chronic diarrhoea in an elderly woman
Authors: J. K. Simpson, A. L. Timmis, S. Siddiqi
Journal: BMJ (2011)

An 89 year old woman was admitted with a six week history of severe watery brown diarrhoea. She had not travelled recently or changed her diet, but she had lost half a stone (3 kg) in weight. She had a history of diverticulosis, recurrent urinary tract infections, and hypertension but no family history of cancer. She was a non-smoker who lived alone and was independently mobile with a frame, requiring no package of care. On examination she was afebrile, her pulse was 95 beats/min, and her blood pressure was 150/88 mm Hg. Her abdomen was soft and non-tender. Per rectal examination and a plain abdominal film were unremarkable. Bloods on admission showed raised inflammatory markers, and within days of admission her electrolytes became deranged, with hypernatraemia (sodium 158 mmol/L) and hypokalaemia (potassium 2.5 mmol/L). Blood gas results showed a metabolic alkalosis (pH 7.52, pCO2 37 mm Hg, bicarbonate 31 mmol/L) and hyperchloraemia (chloride 116 mmol/L). Cloudy urine, which was positive for Escherichia coli , was collected after insertion of a urinary catheter. Stool culture and Clostridium difficile toxin were negative. Flexible sigmoidoscopy showed sigmoid diverticulosis, and a random biopsy showed a mild increase in chronic inflammatory cells. Figures 1⇓ and 2⇓ show axial and sagittal computed tomograms of the abdomen Fig 1 Axial computed tomogram of the abdomen Fig 2 Sagittal computed tomogram of the abdomen
Silica exposure and risk of lung cancer.
Authors: W. K. Morgan, R. B. Reger
Journal: Thorax (1996)

Book review lung pathology and cultures of respiratory secretions.Numerous studies have been performed in this area in recent years in an attempt to clarify the diagnostic approach to the socalled "ventilator-associated pneumonia".It would be unfortunate if such efforts were wasted simply because of misinterpretation.The practical issue for physicians who care for patients on mechanical ventilation is to learn how much they can rely on the sampling technique(s) they routinely use when pul- monary infection is suspected.Taken together, the studies by Torres et al and others simply suggest that tracheal aspirates are just as good as other more "sophisticated" techniques using quantitative cultures and/or protected specimens, with or without bron- choscopy.I have already mentioned the po- tential impact of this approach on antibiotic usage in intensive care units and its consequences.But are we 25 years behind with diagnostic techniques of pulmonary in- fection?
Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage
Authors: Alan B. Cantor, Hiromi Iwasaki, Yojiro Arinobu, Tyler B. Moran, Hirokazu Shigematsu, Matthew R. Sullivan, Koichi Akashi, Stuart H. Orkin
Journal: The Journal of Experimental Medicine (2008)

The zinc finger transcription factor GATA-1 requires direct physical interaction with the cofactor friend of GATA-1 (FOG-1) for its essential role in erythroid and megakaryocytic development. We show that in the mast cell lineage, GATA-1 functions completely independent of FOG proteins. Moreover, we demonstrate that FOG-1 antagonizes the fate choice of multipotential progenitor cells for the mast cell lineage, and that its down-regulation is a prerequisite for mast cell development. Remarkably, ectopic expression of FOG-1 in committed mast cell progenitors redirects them into the erythroid, megakaryocytic, and granulocytic lineages. These lineage switches correlate with transcriptional down-regulation of GATA-2, an essential mast cell GATA factor, via switching of GATA-1 for GATA-2 at a key enhancer element upstream of the GATA-2 gene. These findings illustrate combinatorial control of cell fate identity by a transcription factor and its cofactor, and highlight the role of transcriptional networks in lineage determination. They also provide evidence for lineage instability during early stages of hematopoietic lineage commitment.
Pulmonary alveolar proteinosis associated with Epstein-Barr virus infection
Authors: C. Edwards, R. Primhak, M.C. Cohen
Journal: European Respiratory Journal (2010)

To the Editors:

We report the case of a 3-yr-old male who became unwell over a period of months. He was found to have pulmonary alveolar proteinosis (PAP), confirmed by computed tomography (CT) scan, bronchoalveolar lavage fluid and lung biopsy. Histology from the lung biopsy also revealed a high load of Epstein–Barr virus (EBV). EBV DNA was also found in the blood samples by PCR. We believe this is the first case of PAP caused by EBV reported in the literature.

A 3-yr-old male, born at 34 weeks gestation, had transient infantile hypothyroidism. He had been discharged from an endocrinology clinic at 2 yrs of age, but re-presented with failure to thrive. He was the second twin of consanguineous Asian parents, who had lived in the UK for 15 yrs. They had three healthy older daughters. On examination, he was tachypnoeic and tachycardic with signs of respiratory distress. He had persistent hypoxaemia despite high-flow oxygen and was admitted to the Paediatric Intensive Care Unit (Sheffield Children’s Hospital, Sheffield, UK). Chest radiography showed bilateral air-space opacification, and he was administered i.v. cefuroxime. Within 12 h, his condition deteriorated and endotracheal mechanical ventilation was commenced. An initial diagnosis of pneumonia, possibly due to an atypical organism or tuberculosis, was made and the antibiotic spectrum was widened to include clarithromycin, cotrimoxazole, clindamycin, rifampicin, isoniazid, pyridoxine, pyrazonamide and fluconazole.

A blind tracheobronchial lavage was performed by the intensive-care staff. The aspirated fluid was reported to …