tbuckley/cabot-search huggingface dataset:
Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas.
Authors: J L Jameson, A Klibanski, P M Black, N T Zervas, C M Lindell, D W Hsu, E C Ridgway, J F Habener
Journal: Journal of Clinical Investigation (1987)

Approximately 25% of patients with pituitary adenomas have no clinical or biochemical evidence for excess hormone secretion and are classified as having null cell or nonfunctioning adenomas. To characterize the cell type of these tumors, we analyzed pituitary hormone gene expression in clinically nonfunctioning pituitary adenomas using specific oligonucleotide probes for the messenger (m)RNAs encoding growth hormone, prolactin, ACTH, and the glycoprotein hormone subunits, alpha, luteinizing hormone (LH)beta, follicle-stimulating hormone (FSH)beta, and thyroid-stimulating hormone (TSH)beta. Expression of one or more of the anterior pituitary hormone genes was found in 12/14 (86%) of the patients with clinically classified nonfunctioning adenomas. Expression of one or more of the glycoprotein hormone genes (alpha, LH beta, FSH beta, TSH beta) was identified most commonly (79%) with expression of multiple beta-subunit genes in many cases. Expression of alpha-subunit mRNA was found in each of the adenomas from patients expressing one of the beta-subunit mRNAs and in three patients with no detectable beta-subunit mRNA. Although FSH beta and LH beta mRNAs were found with similar frequencies in nonfunctioning adenomas, expression of FSH beta mRNA was generally much more abundant. TSH beta mRNA was detected in only one adenoma. The levels of glycoprotein hormone subunit mRNAs were variable in different adenomas, but the lengths of the mRNAs and transcriptional start sites for the alpha- and beta-subunit genes were the same in the pituitary adenomas and in normal pituitary. Growth hormone and prolactin gene expression were not observed in the nonfunctioning adenomas, but ACTH mRNA was found in a single case. Immunohistochemistry of the adenomas confirmed production of one or more pituitary hormones in 13/14 (93%) nonfunctioning tumors, with a distribution of hormone production similar to that of the hormone mRNAs. These data indicate that pituitary adenomas originating from cells producing glycoprotein hormones are common, but are difficult to recognize clinically because of the absence of characteristic endocrine syndromes and defective hormone biosynthesis and secretion.
Abstract 5: Frequent translocations and overexpression of multiple full-length ETV1 transcripts in prostate cancer
Authors: Delila Gasi, Hetty van der Korput, Jan Trapman
Journal: Cancer Research (2010)

Abstract In prostate cancer the fusion between TMPRSS2 and the ETS transcription factor gene ERG causes over-expression of truncated ERG. This gene fusion is found in up to 60% of clinical samples. We show that the related gene ETV1 is overexpressed in ∼10% of prostate cancer samples: not only as a fusion transcript with many different partners, but in approximately half of the samples as a full-length transcript. Primary tumors with over-expression of full length ETV1 tend to have a worse prognosis. We showed in a novel fusion event that the complete ETV1 gene is integrated adjacent to the first exon of the poorly characterized ncRNA gene EST14 on chromosome 14. Further characterization of the translocation revealed that not only EST14-ETV1 fusion transcripts were formed, but that also wild-type ETV1 transcripts were over-expressed. These transcripts started at four different alternative first exons and gave rise to production of slightly different ETV1 proteins. However, all proteins have essentially the same properties. Investigation by break-apart in situ hybridization of 7 prostate cancer samples overexpressing full-length ETV1 showed that in at least 5 samples the gene is translocated. This translocation is not to chromosome 14, which seems a hot spot of ETV1 translocations. Chromosome spreads from a xenograft derived from one clinical sample, locate the translocation of ETV1 to a novel site on chromosome 4. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5.
The Politics of Medicine in Britain and the United States
Authors: John Lister
Journal: New England Journal of Medicine (1986)

In one of those delightful essays in The Doctor's Saddle-Bag,1 a former editor of the New England Journal of Medicine, Dr. Joseph Garland, recalled the advice given by the "autocrat of the breakfast table" to the young practitioner: "Do not dabble in the muddy sewer of politics, nor linger by the enchanted stream of literature, nor dig in the far-off fields for hidden waters of alien sciences — the great practitioners are generally those who concentrate all their powers on their business."Such advice has some considerable attraction, and at the time it was given, it may have . . .
Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and cellular basis for hereditary protein C deficiency.
Authors: K Yamamoto, M Tanimoto, N Emi, T Matsushita, J Takamatsu, H Saito
Journal: Journal of Clinical Investigation (1992)

Genetic analysis of a heterozygous protein C-deficient patient revealed a novel deletion of a single guanine residue (8857G) among four consecutive guanine nucleotides [380Trp(TGG)-381Gly(GGT)] in exon IX, which encodes the carboxyl-terminal region of protein C. This deletion results in a frameshift mutation and substitution of the last 39 amino acids (381Gly-419Pro) with 81 abnormal amino acid residues, and we have designated this elongated variant as Protein C-Nagoya. A mutagenic primer was designed which replaced the third guanine residue upstream from the deletion with cytosine, thereby creating a new AvaI site in an otherwise normal allele. Analysis of the polymerase chain reaction products derived from this mutagenic primer showed that the abnormal allele has been inherited in this family. To elucidate how this molecular abnormality leads to protein C deficiency, an expression plasmid containing this mutation was transfected into COS 7, BHK, and psi-2 cells, and the secretory process of the expressed Protein C-Nagoya was analyzed. ELISA and immunoprecipitation analysis with [35S]methionine labeling indicated that the mutant protein C, which was larger in size than normal, was mostly retained within the cells, and only a small portion of it was secreted into the medium. These results suggest that most of Protein C-Nagoya undergoes degradation within the producing cells, and this frameshift mutation apparently leads to protein C deficiency by impairment of secretion of the elongated protein C into plasma.
Macroautophagy modulates cellular response to proteasome inhibitors in cancer therapy
Authors: William K.K. Wu, Kathleen M. Sakamoto, Manuela Milani, Grace Aldana-Masankgay, Daiming Fan, Kaichun Wu, Chung W. Lee, Chi H. Cho, Jun Yu, Joseph J.Y. Sung
Journal: Drug Resistance Updates (2010)
Conditions at Broadmoor come under attack from inspectors
Authors: O. Dyer
Journal: BMJ (2003)

The Commission for Health Improvement has published a damning report on conditions at the high security psychiatric hospital, Broadmoor. The commission's clinical governance review of the West London Mental Health NHS Trust, which oversees Broadmoor Hospital, confirms the widespread public impression that the facility, built in 1863, is more of a prison than a hospital.

“The overwhelming majority of ward areas at Broadmoor Hospital are totally unfit for purpose and cannot be considered an appropriate, humane environment for modern mental healthcare delivery,” says the report. “It is difficult to see, in spite of the endeavours of staff at all levels, how …
Ethics of Experimental Therapeutics
Authors: Maurice B. Strauss
Journal: New England Journal of Medicine (1973)

New medicines, and new methods of cure, always work miracles for a while. — William Heberden1 Every new method of treatment, medical, surgical, psychologic or environmental, requires in the final analysis, proof or disproof of its efficacy in man —human experimentation. Neither the soundness of a theoretic basis nor countless successful laboratory bench and animal studies preclude the final testing, which must be on man and which inevitably must involve some degree of risk, whether large or small. The question I wish to raise is whether it is ever ethical to employ a new therapy except under such conditions that . . .
Prevalence, Complications, and Hospital Charges Associated With Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures
Authors: Kevin S. Cahill
Journal: JAMA (2009)

No national data exist to examine use of bone-morphogenetic proteins (BMPs) in spinal fusion surgery.To determine the patterns of use and rates of complications and financial charges associated with BMP use in spinal fusion nationally.Retrospective cohort study of 328,468 patients undergoing spinal fusion procedures from 2002-2006 identified from the Nationwide Inpatient Sample database, a 20% sample of US community hospitals.The rates of use of BMP among patients undergoing spinal fusion procedures are examined along with complications, length of stay, and hospital charges associated with use of this fusion adjunct.The nationwide usage of BMP has increased from 0.69% of all fusions in 2002 to 24.89% of all fusions in 2006. Use of BMP varied by patient sex, race, and primary payer with increased use seen in women (56.26% with BMP vs 53.35% without BMP; odds ratio [OR], 1.12; 95% confidence interval, [CI], 1.09-1.16) and Medicare patients (29.62% with BMP vs 27.16% without BMP; OR, 1.43; 95% CI, 1.31-1.56) and decreased use in nonwhite patients (8.69% with BMP vs 10.23% without BMP; OR, 0.80; 95% CI, 0.75-0.85). When comparing immediate postoperative, in-hospital rates of complications for the year 2006 among patients undergoing spinal fusion by BMP use status, no differences were seen for lumbar, thoracic, or posterior cervical procedures. On univariate analysis and after multivariable adjustment, the use of BMP in anterior cervical fusion procedures was associated with a higher rate of complication occurrence (7.09% with BMP vs 4.68% without BMP; adjusted OR, 1.43; 95% CI, 1.12-1.70) with the primary increases seen in wound-related complications (1.22% with BMP vs 0.65% without BMP; adjusted OR, 1.67; 95% CI, 1.10- 2.53) and dysphagia or hoarseness (4.35% with BMP vs 2.45% without BMP; adjusted OR, 1.63; 95% CI, 1.30-2.05). Bone-morphogenetic protein use was associated with greater inpatient hospital charges across all categories of fusion. Increases between 11% and 41% of total hospital charges were reported, with the greatest percentage increase seen for anterior cervical fusion.Bone-morphogenetic protein was used in approximately 25% of all spinal fusions nationally in 2006, with use associated with more frequent complications for anterior cervical fusions and with greater hospital charges for all categories of fusions.
In the eye of the storm
Authors: Susan Mayor
Journal: BMJ (2006)

<i>As the New England Journal of Medicine carries the first account in a medical journal of the London drug trial that went wrong,</i><b><i>Susan Mayor</i></b><i>talks to one of the authors,</i><b><i>Ganesh Suntharalingam</i></b>, <i>whose unit had to cope with the crisis</i>
Measuring electrophysiological changes in transgenic mouse models of cardiovascular disease
Authors: C Eisenberg
Journal: Cardiovascular Research (2001)

See article by Eloff et al. [19] (pages 681–690) in this issue. 

The ability to remove selected genes within the mouse genome has proven to be an invaluable tool in the study of vertebrate biology. Many genetically modified ‘knockout’ mice possess significant morphological abnormalities that have provided substantial insights into the function of individual genes. However, the severity of the phenotype is often the drawback to using knockout mice as disease models, since many human diseases are due to subtle genetic defects. This is especially true for genetic alterations that manifest as electrophysiological disturbances in the heart, as cardiac conduction defects, substrates for arrhythmias, and susceptibility to sudden cardiac arrest may arise without any obvious morphological abnormalities.

Cardiac function requires the organized contractility of billions of myocytes. Propagation of electrical current from cell-to-cell is mediated by gap junctions, which are membrane channels that allow the transfer of ions, metabolites and other signaling molecules between neighboring cells [1–3]. In the heart, this chemical exchange permits the rapid conduction of action potentials [3–5]. The protein components of gap junctions are referred to as connexins. These proteins transverse the membrane four times and interact with connexins on adjacent cells by homophilic binding of the extracellular domains [1–3,6]. Three distinct connexin genes are known to be expressed within the adult myocardium: Connexin40 (Cx40), Cx43 and Cx45. Cx40 is preferentially exhibited in atrial tissue and the His-Purkinje system [7,8]. The distribution of Cx45 is restricted to the atrioventricular conduction system in a pattern that is similar, although not identical, to that of Cx40 [9]. The predominant connexin of the mammalian heart is Cx43, which is expressed at … 

*Corresponding author. Tel.: +1-843-792-6502; fax: +1-843-792-0664
Berylliosis: Report of Two Cases, With Special Reference to the Patch Test
Authors: G. F. Norris, M. C. Peard
Journal: BMJ (1963)

TUMOURS m OUN MWDIC.4LJOURNAL Recent studies have shown that these complements are viable and not altogether very uncommon in man, and the discrepancies observed in the tumours under consideration might be produced by one or more errors of mitosis such as non-disjunction or anaphase lagging of the sex chromosomes at the inception of the tumour or soon afterwards.In some cases the discrepancy between nuclear sex and inferred sex-chromosome complement of the tumour and of the patient may be more apparent than real.Both Carpentier et al. (1956) and Hienz (1961) have described dysgerminomata in chromatin-negative women with ovarian dysgenesis.Hunter and Lennox (1954) described the case of a boy with a chromatin-positive pineal teratoma who was later shown to have chromatin- positive Klinefelter's syndrome (Lennox, 1960), and W. M. Davidson (personal communication 1962) has recently seen a further patient with Klinefelter's syndrome and a chromatin-positive teratoma. SummarySex-chromatin discrepancies were found in 8 out of 50 teratomata and 4 out of 49 other embryonic tumours studied.It is suggested that sex-chromatin discrepancies in these tumours may be the expression of abnormal sex-chromosome complements such as XO, XXY, XY/ XXY, produced by one or more errors of mitosis such as non-disjunction or anaphase lagging at or soon after the inception of the tumour.The work referred to in this communication is part of a Ph.D. thesis
AB0793 Discordance between patients and physicians in their assessment of rheumatoid arthritis disease activity
Authors: T. Watanabe, T. Kojima, N. Takahashi, K. Funahashi, D. Kato, Y. Hattori, M. Hanabayashi, K. Terabe, Y. Yoshioka, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is important to evaluate disease activity accurately in Rheumatoid Arthritis (RA). Disease activity assessment is necessary for treatment decision and for achieving remission or low disease activity. A patient self-report, patient's global assessment (PGA), is one of the outcome measures. Though there is often discordance between patients and physicians in their assessment of RA disease activity. <h3>Objectives</h3> The aim of this study is to explore the reasons for this discordance. <h3>Methods</h3> 385 RA patients at Nagoya University Hospital were enrolled in this study. Patient global assessment (PGA) using visual analog scale, and physician's/evaluator's global assessment (EGA) were assessed independently. Painful joint count (PJC) and swollen joint count (SJC) by patients, and tenderness joint count (TJC) and SJC by physicians, were also assessed independently. Serum C-reactive protein (CRP) and Matrix Metalloproteinase-3 (MMP-3) levels, DAS28, SDAI, were collected. <h3>Results</h3> Patients were primarily women (82%), age 60.1±14.0 years. The correlation coefficient between PGA and EGA was 0.46. PGA and EGA were categorized into 3 groups, 10mm or less, 11mm to 50mm, 51mm or more. Comparing cases that PGA and EGA were the same category (226 cases) with cases that PGA was in the higher categories than EGA (117 cases), the average of the difference between TJC and PJC were the former 2.22, the latter 4.40, which showed a significant difference. There was significant difference in the average of CRP, the former 0.54mg/dl, the latter 0.31mg/dl, but not in MMP-3, DAS28, or SDAI. There were 190 cases which CRP, TJC and SJC by physicians are all 1 or less. Of those cases, the group of PGA was 10mm or less (87 cases) and the group of PGA was 11mm or more (103 cases), the average of the PJC was a significant difference in 1.01, 3.88, respectively. The average of CRP was the former 0.13mg/dl, the latter 0.20mg/dl, which also showed a significant difference, but not in MMP-3. <h3>Conclusions</h3> About 30% of RA patients assessed their disease activity higher than physicians do. Discordance between PJC and TJC affects the discordance between PGA and EGA. <h3>Disclosure of Interest</h3> T. Watanabe: None Declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers, N. Takahashi: None Declared, K. Funahashi: None Declared, D. Kato: None Declared, Y. Hattori: None Declared, M. Hanabayashi: None Declared, K. Terabe: None Declared, Y. Yoshioka: None Declared, N. Ishiguro Speakers bureau: Mitsubishi Tanabe Pharma Corporation, Takeda Pharma, Corporation, Eisai Pharma Corporation, Chugai Pharma Corporation, Abbott, Bristol-Myers Squibb and Pfizer
Hypoglycemia, functional brain failure, and brain death
Authors: Philip E. Cryer
Journal: Journal of Clinical Investigation (2007)

Hypoglycemia commonly causes brain fuel deprivation, resulting in functional brain failure, which can be corrected by raising plasma glucose concentrations. Rarely, profound hypoglycemia causes brain death that is not the result of fuel deprivation per se. In this issue of the JCI, Suh and colleagues use cell culture and in vivo rodent studies of glucose deprivation and marked hypoglycemia and provide evidence that hypoglycemic brain neuronal death is in fact increased by neuronal NADPH oxidase activation during glucose reperfusion (see the related article beginning on page 910). This finding suggests that, at least in the setting of profound hypoglycemia, therapeutic hyperglycemia should be avoided.
Predictive Value of Fetal Pulmonary Venous Flow Patterns in Identifying the Need for Atrial Septoplasty in the Newborn With Hypoplastic Left Ventricle
Authors: Erik Michelfelder, Carlen Gomez, William Border, William Gottliebson, Cheri Franklin
Journal: Circulation (2005)

Pulmonary venous Doppler (PVD) flow patterns in the fetus with hypoplastic left heart syndrome (HLHS) have been correlated with restrictive interatrial communication or intact atrial septum (RAS) postnatally; however, the ability of PVD to identify the neonate requiring emergent atrial septoplasty (EAS) for severe left atrial hypertension and hypoxemia has not been critically evaluated. It was the purpose of this study to determine the predictive power of fetal PVD in identifying the need for EAS in newborns with HLHS and RAS.Forty-one patients with fetal PVD flow analysis and postnatally confirmed HLHS were studied. Pulsed-wave assessment of PVD flow included S-, D-, and A-wave velocity, time-velocity integral (VTI) of forward and reverse flow, and S/D velocity and forward/reverse VTI ratio. Neonatal EAS was used as the primary clinical outcome variable. Receiver operating characteristic curves were used to determine cutpoints at which PVD indices best predicted EAS. Cutpoints were evaluated for clinical accuracy and usefulness by use of Bayesian analysis. Eight of 41 subjects underwent EAS. Need for EAS was most accurately predicted by forward/reverse VTI ratio <5 (sensitivity, 0.88, 95% CI, 0.49 to 0.99; specificity, 0.97, 95% CI, 0.82 to 0.99), which, when present, increases the posttest likelihood of EAS to 74%, assuming a pretest prevalence of 10%. Accuracy and usefulness of other PVD indices were affected by false-positive results.In the fetus with HLHS, a PVD forward/reverse VTI ratio of <5 is the strongest predictor of the need for EAS in the newborn period. These observations should improve our ability to identify and expectantly manage the fetus with HLHS and RAS.
Influence of pentachlorophenol on light emission from single barnacle muscle fibers preloaded with aequorin.
Authors: E E Bittar, J R Wu
Journal: Environmental Health Perspectives (1993)

Experiments show that the resting ouabain-insensitive sodium efflux in giant fibers from the barnacle Balanus nubilus is stimulated by external application of pentachlorophenol (PCP). This work has now been extended to include a study of muscle fibers preloaded with the Ca2+ indicator aequorin to determine whether PCP is able to increase light emission; and whether its potency depends on the number of chlorine atoms and external pH. The results obtained are as follows: 1) PCP causes a dose-dependent, multiphasic rise in light emission; the threshold concentration in fibers not poisoned with ouabain was in the low micromolar range. 2) The efficacy of PCP is considerably greater than that of less-chlorinated phenols and phenol. 3) The response to PCP is a sigmoidal function of external pH both in unpoisoned and ouabain-poisoned fibers. Reducing external pH potentiates its efficacy. 4) The response to PCP depends on the external Ca2+ concentration, and the requirement for Ca2+ is usually absolute.
Poetry and Medicine
Authors: Jack Coulehan
Journal: JAMA (1992)

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Carcinoma of the Esophagus and Long-term Sclerotherapy
Authors: P. A. McCormick, A. Sawyer, N. McIntyre, A. K. Burroughs
Journal: Endoscopy (1989)

We report a case where a chronic non-healing esophageal ulcer which developed following a course of endoscopic sclerotherapy proved to be an esophageal carcinoma. In view of 2 similar previous reports we discuss the possibility that sclerotherapy may act as a carcinogen, and suggest that all such non-healing esophageal ulcers should be biopsied.