tbuckley/cabot-search huggingface dataset:
Incorrect diagnosis of hereditary hemochromatosis
Authors: Oksana Mirochnik, Natasha Halim-Kertanegara, Mark Hertzberg, David McDonald, Christopher Liddle
Journal: American Journal of Hematology (2000)

To the Editor: Semenzato et al. proposed new criteria for large granular lymphocyte (LGL) leukemia because patients with low levels of GL were similar to those with levels greater than 2,000 GL/l [1].LGL leukemia is a GL proliferative disease often accompanied by pure red cell aplasia (PRCA).T-cell LGL leukemia is a clonal disease, and the phenotype of leukemic cells is CD3 + 4 -8 + .PRCA with thymoma is often associated with peripheral T cell expansion.We previously reported a case of PRCA with thymoma in which the T-cell receptor ␤ of both the thymus and peripheral mononuclear cells was rearranged [2].Thymoma and PRCA may be caused by T-cell clonal expansion, leukemia.We examined four patients with PRCA and thymoma (Table I), one of which was previously reported.Three of the four showed CD3 + 4 -8 + lymphocytosis and two exhibited T-cell receptor ␤ rearrangement of peripheral mononuclear cells.Patient 2 showed low levels of lymphocytes and the mononuclear cell's CD4/8 ratio of patient 3 was greater than 1.Due to the low levels of abnormal cells and low sensitivity of Southern blot analysis, we could not confirm the clonality of these two cases.According to treatment of PRCA with thymoma, the response rate of thymectomy was 12% [3].This limited effectiveness of thymectomy indicated that thymoma did not play a causative role in PRCA.Loughran reported 129 patients with LGL leukemia [4] and Oshimi et al. examined 33 patients [5].Neither study noted a complication of thymoma.PRCA with thymoma had been considered a distinct clinical entity from LGL leukemia.The old diagnostic criteria for LGL leukemia was "greater than 2,000 GL/l."The normal value of GL is 223 ± 99 l [4].Three of the 4 patients with PRCA and thymoma demonstrated levels greater than the mean + 3 SD (Table I).However, it is unknown whether or not a distinction between 'PRCA with thymoma' and 'PRCA with LGL leukemia' exists.Patients with LGL leukemia showed an indolent clinical course, and immunosuppressive therapy with cyclosporin A or low-dose cyclophosphamide was effective for the clinical symptoms.In contrast, patients with PRCA with thymoma were treated with more aggressive therapy such as surgical resection, intensive chemotherapy, or radiation.As the effectiveness of surgical resection for PRCA with thymoma is limited, PRCA with thymoma should be initially treated with immunosuppressive therapy.
Abstract 5058: Effects of honokiol on UACC-62 malignant melanoma cell line
Authors: Ruth F. Guillermo, Jonathan Stevens, Radhey S. Kaushik, Alan Young, Chandradhar Dwivedi
Journal: Cancer Research (2011)

Abstract Studies from our laboratory have indicated the chemopreventive effects of honokiol on UVB-induced squamous cell carcinoma in mouse skin. The purpose of this study is to investigate the effects of honokiol on UACC-62 malignant melanoma cell and elucidate the mechanisms of action. UACC-62 cells were grown in RPMI media in cell culture conditions. The effects of honokiol on cell viability and cell proliferation were studied by the MTT and BrdU assays. To investigate the effects of honokiol on cell cycle, UACC-62 cells were treated with honokiol, stained with propidium iodide and analyzed by flow cytometry. Cell lysates were prepared in similar conditions as the previous experiments to assess how honokiol affected the expressions of proteins involved in different pathways. The MTT assay showed a significant decrease in cell viability starting at 75 μM honokiol at 24 hours. The BrdU assay results indicated decreased cell proliferation as early as 12 hours and 50 μM honokiol. The cell cycle analysis indicated that honokiol caused G0/G1 phase arrest in melanoma cells (p &amp;lt; 0.05) at 24h and 50 μM. Western blots of the cell lysates prepared showed that honokiol decreased the expressions of cyclin E, CDK4, cyclin D2, NF-kβ, and p-MEK starting at 50 μM honokiol at 24 hours. The expressions of apoptotic proteins cleaved caspase-3, cleaved caspase-9, caspase 8, and cleaved PARP were increased by honokiol treatments. This data indicated that honokiol decreases cell proliferation and induces apoptosis of UACC-62 cells thus could be a candidate for pre-clinical studies as an agent for treating or preventing melanoma skin cancer. Supported by Translational Cancer Research Center funded as a 2010 Research Initiative Center by the State of South Dakota. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5058. doi:10.1158/1538-7445.AM2011-5058
Prophylactic use of cephazolin against wound sepsis after cholecystectomy.
Authors: C J Strachan, J Black, S J Powis, T A Waterworth, R Wise, A R Wilkinson, D W Burdon, M Severn, B Mitra, H Norcott
Journal: BMJ (1977)

A trial of antibiotic prophylaxis with cephazolin against postoperative wound sepsis was carried out on 201 patients undergoing routine cholecystectomy. Wound sepsis occurred in 11 out of 65 controls (16.9%), who were not given the drug; two out of 63 patients (3.2%) given a single dose preoperatively; and four out of 73 patients (5.5%) given the single preoperative dose plus a five-day course postoperatively. The difference between the controls and patients given the single preoperative dose was significant.
Comparative Phylogenetic Analysis of Blcap/Nnat Reveals Eutherian-Specific Imprinted Gene
Authors: Heather K. Evans, Jennifer R. Weidman, Dale O. Cowley, Randy L. Jirtle
Journal: Molecular Biology and Evolution (2005)

Imprinted genes are parent-of-origin dependent, monoallelically expressed genes present in marsupials and eutherian mammals. Altered expression of imprinted genes plays a significant role in the etiology of a variety of human disorders and diseases. Nevertheless, the regulatory mechanisms of imprinting remain poorly defined. The imprinted gene Neuronatin (Nnat) is an excellent candidate for studying imprinting because it resides within the 8.5-kb intron of the nonimprinted gene Bladder Cancer-Associated Protein (Blcap) and is the only imprinted gene within the region. A phylogenetic comparison of this micro-imprinted domain in human, mouse, and rat revealed several candidates for imprint control, including tandem repeats and putative binding sites for trans- acting factors known to be involved in chromatin remodeling. Genome-wide phylogenetic comparisons of species from the three major extant mammalian clades failed, however, to show any evidence of Nnat outside the eutherian lineage. Thus, Nnat is the first identified eutherian-specific imprinted gene, demonstrating that imprinted genes did not arise at a single point during evolution. This finding also suggests that the complexity of imprinting regulation observed at other loci may, in part, be directly related to the amount of time they have been imprinted.
Letter: Experts and child abuse.
Authors: J Mathers
Journal: BMJ (1974)

SIR,-Your leading article (21 September, p. 701) highlights the problems of Negro patients who may have repeated screening tests for sickle-cell disease.Now that the existence of sickle-cell disease in Britain has been recognized and well publicized I feel that the need for screening should be put in the right per- spective on a par with other potentially dangerous problems associated with anaes- thesia and surgery.It is advisable to perform routine screening for haemoglobinopathies on hospital attendance, but should the absence of a sickle-cell test in fit and nonanaemic adults and older children of possible Negro descent be a contraindication to general anaesthesia?This is certainly not the practice anywhere in Africa.The sutgestion that medical cards be carried by these patients is the obvious solution, but logically medical cards should be advisable for most patients and should include not only haemoglobinopathies but other relevant information, such as blood group, drug allergy, therapy with steroids, anticoagulants, etc. for the same reasons as suggesved in the article.
<i>In vitro</i>production of Mallory bodies and intracellular hyaline bodies: The central role of sequestosome 1 / p62
Authors: Conny Stumptner, Andrea Fuchsbichler, Kurt Zatloukal, Helmut Denk
Journal: Hepatology (2007)

Mallory bodies (MBs) and intracellular hyaline bodies (IHBs) are characteristic hepatocellular inclusions. MBs are hallmarks of steatohepatitis, whereas IHBs have first been detected in hepatocellular carcinoma. MBs and IHBs contain ubiquitin and sequestosome 1/p62 (p62), a stress-inducible adapter protein with affinity to polyubiquitinated proteins. MBs differ from IHBs by their keratin content and morphology. In vitro transfections were undertaken to study under defined conditions MB and IHB formation, their pathogenesis, and relationship. CHO-K1, TIB73, and HeLa cells were transfected with keratin 8, keratin 18, ubiquitin, p62, and p62 lacking the ubiquitin binding domain (p62DeltaUBA) and analyzed by immunofluorescence, immunoelectron microscopy, and immunoblotting. Transfection of p62 complementary deoxyribonucleic acid (cDNA) alone led to cytoplasmic aggregates consisting of filaments mostly arranged in parallel arrays resembling amyloid and type 1 MBs. Transfection of p62 and ubiquitin resulted in globular cytoplasmic aggregates with indistinct fibrillar ultrastructure resembling IHBs. Cotransfection of p62, keratin 8, and ubiquitin was necessary to produce in vitro type 2 MBs-like aggregates consisting of randomly oriented 10- to 15-nm filaments. A similar result was obtained when keratin 8 was replaced by keratin 18. After cotransfection of p62DeltaUBA, keratin 8, and ubiquitin, keratin formed irregular aggregates with electron-dense granular-amorphous ultrastructure (resembling type 3 MBs), whereas p62DeltaUBA remained in diffuse cytoplasmic distribution.Our studies show that in vitro development of classical type 2 MBs requires overexpression of keratin 8 (or keratin 18), ubiquitin, and p62 containing the ubiquitin binding domain, whereas IHBs result from overexpression of p62 together with ubiquitin without keratin involvement.
Genetics in Clinical Cancer Care — The Future is Now
Authors: Olufunmilayo I. Olopade
Journal: New England Journal of Medicine (1996)

The identification of BRCA1 as the first gene for susceptibility to breast and ovarian cancer was an important step toward a better understanding of the biology of these cancers.1 This advance should lead to new therapies, but for now it provides a unique opportunity to develop new strategies for early detection and prevention. The intense attention in the media to this breakthrough has caused many highly motivated women with family histories of cancer to seek counseling about their risks and options for prevention. It is no longer unusual for women with newly diagnosed breast cancer to seek genetic testing before . . .
Bilateral Sampling of the Internal Jugular Vein To Distinguish between Mechanisms of Adrenocorticotropic Hormone-Dependent Cushing Syndrome
Authors: John L. Doppman
Journal: Annals of Internal Medicine (1998)

Background: Bilateral sampling of the petrosal sinuses to distinguish Cushing disease from the ectopic adrenocorticotropic hormone (ACTH) syndrome is accurate but technically demanding and risky. Bilateral sampling of the internal jugular vein is simpler and safer. Objective: To compare bilateral internal jugular vein sampling with bilateral inferior petrosal sinus sampling for distinguishing patients with Cushing disease from those with the ectopic ACTH syndrome. Setting: Tertiary referral hospital. Patients: 20 patients with surgically proven Cushing disease and 1 patient with proven ectopic ACTH syndrome. Intervention: All patients underwent petrosal sinus sampling and jugular vein sampling before and after administration of corticotropin-releasing hormone (CRH) on separate days. Measurements: Ratios of central ACTH to peripheral ACTH in petrosal sinus samples and jugular vein samples were calculated before and after administration of CRH. Results: Ratios of central to peripheral ACTH were diagnostic for Cushing disease (>2 before administration of CRH and >3 after administration of CRH) in jugular vein samples from 16 of 20 patients with surgically proven Cushing disease (sensitivity, 80% [95% CI, 56% to 96%]). Ten of these 16 patients (63%) had diagnostic results only after CRH was administered. The average ratio of central to peripheral ACTH in jugular vein samples was 2.7 before CRH and 7.7 after CRH. Ratios of central to peripheral ACTH were diagnostic in petrosal sinus samples from 19 of 20 patients with surgically proven Cushing disease (sensitivity, 95% [CI, 75% to 99%]). Samples from all 19 patients had diagnostic ratios before and after administration of CRH. The average ratio of central to peripheral ACTH in petrosal sinus samples was 17.7 before CRH and 90.0 after CRH. In the patient with the ectopic ACTH syndrome, ratios of central to peripheral ACTH were negative in jugular vein samples and petrosal sinus samples before and after CRH (<2 and <3, respectively). Conclusions: Jugular vein sampling correctly identified ACTH-secreting pituitary adenomas in 80% of patients with proven Cushing disease. Administration of CRH was essential for diagnostic results in 63% of the patients. Jugular vein sampling is less invasive than petrosal sinus sampling. Negative results on jugular vein sampling should be confirmed by petrosal sinus sampling.
Medical Records That Guide and Teach
Authors: Lawrence L. Weed
Journal: New England Journal of Medicine (1968)

THE beginning clinical clerk, the house officer and the practicing physician are all confronted with conditions that are frustrating in every phase of medical action. The purpose of this article is to identify and discuss these conditions and point out solutions. To deal effectively with these frustrations it will be necessary to develop a more organized approach to the medical record, a more rational acceptance and use of paramedical personnel and a more positive attitude about the computer in medicine. Eventually, for every physician all three areas will be an obligatory part of his professional environment if he is to . . .
Acetylcholine reverses effects of beta-agonists on pacemaker current in canine cardiac Purkinje fibers but has no direct action. A difference between primary and secondary pacemakers.
Authors: F Chang, J Gao, C Tromba, I Cohen, D DiFrancesco
Journal: Circulation Research (1990)

We have investigated the actions of acetylcholine in the absence and presence of the beta-agonist isoproterenol in cardiac Purkinje fibers. beta-Agonists, like isoproterenol, increase the magnitude of the pacemaker current (If) in cardiac myocytes by shifting its activation voltage more positive on the voltage axis. We find that acetylcholine has no effect on If in the absence of isoproterenol. However, if If is first increased by beta-agonist stimulation, acetylcholine can then return If to control levels. This effect on If is exerted through muscarinic receptors since atropine prevents this action of acetylcholine. Functionally, this action of acetylcholine can guarantee the maintenance of ventricular pacemakers when there is high parasympathetic tone but can also prevent extra ventricular beats when sympathetic and parasympathetic tone are both high.
Postnatal depression: does no one care?
Authors: I. Swyer
Journal: BMJ (1980)

SIR,-With reference to the article "Postnatal depression: does no one care ?" (8 December, p 1487), I would like to point out that the subject of postpartum psychiatric disorders has been scrutinised and been the subject of a lot of time and energy of many researchers for over a century.'Needless to say, numerous papers and research projects have been published during this time.These concern many aspects of the whole spectrum of these disorders-from acute psychotic disorders2 to the "three-day blues syndrome,"'3 including postpartum depression.4With this history in mind I would like to reassure the author that the lack of "appropriate hormones" to treat people like his wife is not the result of people "not having a care" to answer the queries he poses but is much more likely to be a direct reflection of the complexity of the biochemical and endo- crinological state of the psychiatrically ill puerperal women.As far as the "lack of warning" that patients will be affected is concerned, epidemiological studies and research into the aetiology of these disorders are plentiful5 7 and concern in this respect is in an ever-evolving state.
Complete resolution of dermatitis herpetiformis with the Atkins' diet
Authors: M.J. Sladden, G.A. Johnston
Journal: British Journal of Dermatology (2006)

Journal Article Complete resolution of dermatitis herpetiformis with the Atkins' diet Get access M.J. Sladden, M.J. Sladden Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail: m.sladden@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar G.A. Johnston G.A. Johnston Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail: m.sladden@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 3, 1 March 2006, Pages 565–566, https://doi.org/10.1111/j.1365-2133.2005.07086.x Published: 01 March 2006
Distinct Roles for Cell-Autonomous Notch Signaling in Cardiomyocytes of the Embryonic and Adult Heart
Authors: Paschalis Kratsios, Catarina Catela, Ekaterina Salimova, Marion Huth, Valeria Berno, Nadia Rosenthal, Foteini Mourkioti
Journal: Circulation Research (2009)

Rationale : The Notch signaling pathway is important for cell–cell communication that controls tissue formation and homeostasis during embryonic and adult life, but the precise cell targets of Notch signaling in the mammalian heart remain poorly defined. Objective : To investigate the functional role of Notch signaling in the cardiomyocyte compartment of the embryonic and adult heart. Methods and Results : Here, we report that either conditional overexpression of Notch1 intracellular domain (NICD1) or selective silencing of Notch signaling in the embryonic cardiomyocyte compartment results in developmental defects and perinatal lethality. In contrast, augmentation of endogenous Notch reactivation after myocardial infarction in the adult, either by inducing cardiomyocyte-specific Notch1 transgene expression or by intramyocardial delivery of a Notch1 pseudoligand, increases survival rate, improves cardiac functional performance, and minimizes fibrosis, promoting antiapoptotic and angiogenic mechanisms. Conclusions : These results reveal a strict requirement for cell-autonomous modulation of Notch signaling during heart morphogenesis, and illustrate how the same signaling pathway that promotes congenital heart defects when perturbed in the embryo can be therapeutically redeployed for the treatment of adult myocardial damage.
Anhedonia: exclusion from the pleasure dome.
Authors: P. Snaith
Journal: BMJ (1992)

The case for early administration of parenteral antibiotics to patients with suspected meningococcal disease is now stronger than ever.General practitioners and casualty officers should treat such patients immediately with parenteral (preferably intravenous) benzylpenicillin.(The dose is 1200 mg for adults and children aged 10 and above, 500 mg for children aged 1-9, and 300 mg for children under 1.) Before reconstitution both penicillin and chloramphenicol are stable for at least two years in an emergency bag.Frequent reminders of this simple, cheap measure are needed to reinforce the message.
Quantitative importance of biliary excretion to the turnover of hepatic lysosomal enzymes*1
Authors: A NAKANO
Journal: Hepatology (1995)

The turnover rate of an individual protein is a function of the rates of synthesis and loss of that protein. For most intracellular proteins, loss occurs through digestion by lysosomal or cytosolic proteases. Although a significant proportion of hepatic lysosomal enzymes is released from the hepatocyte by excretion into bile, the contribution of biliary excretion to the turnover of hepatic lysosomal enzymes has never been measured. Thus, we used in vivo pulse-labeling to determine the half-lives of two hepatic hydrolases, β-galactosidase (β-gal) and β-glucuronidase (β-glu). Each enzyme was purified by immunoisolation from hepatic lysosomes that were isolated at various times after injection of rats with 3H-labeled leucine. The decay curves for the specific radioactivities of β-gal and β-glu were used to calculate the half-lives of the proteins, which were 3.8 and 5.1 days, respectively. To determine the percent of total hepatic contents of each enzyme that was lost per day by biliary excretion, we collected bile from bile fistula rats for 24 hours and then used radioimmunoassays to quantitate the amounts of β-gal and β-glu in bile and liver samples of the same rats. We found that ∼4% of the total hepatic contents of both β-gal and β-glu was excreted into bile per day. Finally, we used these data to calculate that 31% and 41% of hepatic losses of β-gal and β-glu, respectively, were due to biliary excretion. These results suggest that extracellular release through biliary excretion is a major mechanism contributing to the turnover of lysosomal hydrolases.
Ventilation with Small Tidal Volumes
Authors: Arthur S Slutsky, Jeffrey M Drazen
Journal: New England Journal of Medicine (2002)

Human survival depends on the exchange of fresh air with carbon dioxide in the blood. Since this exchange takes place in the alveoli, one of the first concepts taught in respiratory physiology is that the size of each breath, the tidal volume, must exceed the volume of the conducting airways, also known as the dead space. However, this construct is not strictly accurate, since we know that adequate gas exchange can be achieved when tidal volumes smaller than that of the dead space are taken in at sufficiently high frequencies, a technique termed high-frequency ventilation.How can we survive if . . .
More Conflicts of Interest: Review Articles Sponsored by the Pharmaceutical Industry
Authors: Milap C. Nahata
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The recent article by Dr Witt and Mr Gostin<sup>1</sup>was interesting and informative. One subject missing from the article was payment of honoraria by the pharmaceutical industry to established investigators for publishing review articles. Some pharmaceutical companies may offer assistance in searching literature and writing a draft of the article either directly or through a contracted service. Even if the investigator writes the entire article, it is expected that the pharmaceutical company would review it and provide comments or suggestions for revision prior to its submission to a journal. This may give the pharmaceutical company an opportunity to include data on file and, more importantly, present its product most effectively in relation to competitive products since other companies would not have the same opportunity. Interestingly, the receipt of honoraria for review articles is rarely disclosed. Such disclosures to their readers should be required by all journals.
Phosphorylation of the Translation Initiation Factor eIF2α Increases BACE1 Levels and Promotes Amyloidogenesis
Authors: Tracy O'Connor, Katherine R. Sadleir, Erika Maus, Rodney A. Velliquette, Jie Zhao, Sarah L. Cole, William A. Eimer, Brian Hitt, Leslie A. Bembinster, Sven Lammich, Stefan F. Lichtenthaler, Sébastien S. Hébert, Bart De Strooper, Christian Haass, David A. Bennett, Robert Vassar
Journal: Neuron (2008)