tbuckley/cabot-search huggingface dataset:
Unraveling the Molecular Pathogenesis of Isolated Proximal Renal Tubular Acidosis
Authors: Takashi Igarashi, Takashi Sekine, Jun Inatomi, George Seki
Journal: Journal of the American Society of Nephrology (2002)

Proximal renal tubular acidosis (pRTA) results from an impairment of bicarbonate (HCO3−) reabsorption in the renal proximal tubules and is characterized by a decreased renal HCO3− threshold. Proximal RTA most commonly occurs in association with multiple defects of proximal tubular transport (renal Fanconi syndrome). Although much more rare, pRTA may occur without other functional defects in proximal tubules (isolated pRTA). The presenting clinical symptom of isolated pRTA is usually growth retardation in infancy or early childhood. Three categories of isolated pRTA have been identified: ( 1 ) autosomal dominant pRTA; ( 2 ) autosomal recessive pRTA with ocular abnormalities; and ( 3 ) sporadic isolated pRTA. Autosomal dominant and autosomal recessive pRTA are usually permanent; life-long alkali therapy is needed. In contrast, sporadic isolated pRTA is transient; alkali therapy can be discontinued after several years without reappearance of symptoms. Recent genetic studies have begun to elucidate the molecular pathogenesis of inherited isolated pRTA. Studies in knockout mice have identified a candidate gene for autosomal dominant pRTA, SLC9A3 , a gene encoding one of the five plasma membrane Na+/H+ exchangers (NHE3). Patients with autosomal recessive pRTA and ocular abnormalities have recently been found to have mutations in the kidney type Na+/HCO3− cotransporter gene ( SLC4A4 ). Identification of these gene mutations provides new insights into the molecular pathogenesis of pRTA.
Erythrodermic cutaneous T-cell lymphoma with CD8+CD56+ leukaemic T cells in a young woman
Authors: A. Ohshima, Y. Tokura, J. Misawa, H. Yagi, M. Takigawa
Journal: British Journal of Dermatology (2003)

Journal Article Erythrodermic cutaneous T‐cell lymphoma with CD8+CD56+ leukaemic T cells in a young woman Get access A. Ohshima, A. Ohshima Department of Dermatology, Numazu Municipal Hospital, 550 Higashishiji‐Harunoki, Numazu 410‐0302, Japan, Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Tokura, Y. Tokura Department of Dermatology, Numazu Municipal Hospital, 550 Higashishiji‐Harunoki, Numazu 410‐0302, Japan, Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Search for other works by this author on: Oxford Academic Google Scholar J. Misawa, J. Misawa Department of Dermatology, Seirei‐Mikatabara Hospital, Hamamatsu, Japan E‐mail: akohshima@mac.com Search for other works by this author on: Oxford Academic Google Scholar H. Yagi, H. Yagi Department of Dermatology, Numazu Municipal Hospital, 550 Higashishiji‐Harunoki, Numazu 410‐0302, Japan, Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Takigawa M. Takigawa Department of Dermatology, Numazu Municipal Hospital, 550 Higashishiji‐Harunoki, Numazu 410‐0302, Japan, Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 4, 1 October 2003, Pages 891–893, https://doi.org/10.1046/j.1365-2133.2003.05533.x Published: 01 October 2003
Sex Differences in Clinical Characteristics and Prognosis in a Broad Spectrum of Patients With Heart Failure
Authors: Eileen O’Meara, Tim Clayton, Margaret B. McEntegart, John J.V. McMurray, Ileana L. Piña, Christopher B. Granger, Jan Östergren, Eric L. Michelson, Scott D. Solomon, Stuart Pocock, Salim Yusuf, Karl Swedberg, Marc A. Pfeffer
Journal: Circulation (2007)

Background— We wished to test previous hypotheses that sex-related differences in mortality and morbidity may be due to differences in the cause of heart failure or in left ventricular ejection fraction (LVEF) by comparing fatal and nonfatal outcomes in women and men with heart failure and a broad spectrum of left ventricular ejection fraction. Methods and Results— We compared outcomes in 2400 women and 5199 men randomized in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program using multivariable regression analyses. A total of 1188 women (50%) had a low LVEF (≤0.40), and 1212 had a preserved LVEF (&gt;0.40). Among the men, 3388 (65%) had a low LVEF, and 1811 had a preserved LVEF. A total of 1216 women (51%) and 3465 men (67%) had an ischemic cause of their heart failure. All-cause mortality was 21.5% in women and 25.3% in men (adjusted hazard ratio [HR], 0.77; 95% CI, 0.69 to 0.86; P &lt;0.001). Fewer women (30.4%) than men (33.3%) experienced cardiovascular death or heart failure hospitalization (adjusted HR, 0.83; 95% CI, 0.76 to 0.91; P &lt;0.001). The risks of sudden death (HR, 0.70; 95% CI, 0.58 to 0.85) and death due to worsening heart failure (HR, 0.72; 95% CI, 0.58 to 0.89) were reduced to a comparable extent. The adjusted risk of cardiovascular hospitalization was also lower in women (HR, 0.88; 95% CI, 0.82 to 0.95), mainly because of a reduced risk of heart failure hospitalization (HR, 0.87; 95% CI, 0.78 to 0.97). Women had a lower risk of death irrespective of cause of heart failure or LVEF. Conclusions— Among patients with heart failure, women have lower risks of most fatal and nonfatal outcomes that are not explained, as previously suggested, by LVEF or origin of the heart failure.
A NEW NON-PATHOGENIC TETRAGENOUS AMEBA. I
Authors: Sohei Shimura
Journal: The Journal of Experimental Medicine (1918)

The non-pathogenic tetragenous ameba described here multiplies in the intestine of man, without producing any noticeable symptoms of dysentery. This non-pathogenic ameba is distinguished morphologically and biologically from Entamoeba tetragena Viereck and Entamoeba coli Lösch emend. Schaudinn. The vegetative forms of the non-pathogenic tetragenous ameba may be divided into two groups, large and small. The large vegetative form is found in the normally evacuated or the diarrheal stools obtained after purgation. The small form is found in the soft stools. This form may be transformed into cysts, or may reproduce itself by binary fission. Cysts are found in relatively large numbers in the soft and formed stools. Experimentally, the new tetragenous ameba may be readily distinguished from the pathogenic variety. The vegetative forms of the dysentery ameba produced the disease in 91 per cent of cases when introduced per anum, and in 50 per cent where the cysts were introduced per os. Similar infection experiments undertaken on twenty-three young cats, i.e. ten experiments with the vegetative form of the non-pathogenic tetragenous ameba per anum, and thirteen experiments with the cysts per os, failed to produce pathological conditions. The intestines of the animals macroscopically and histologically failed to show any of the changes of dysentery. Hence we may conclude that the new type of tetragenous ameba described here is non-pathogenic for man and for young cats.
Mect1-Maml2 Fusion Oncogene Linked to the Aberrant Activation of Cyclic AMP/CREB Regulated Genes
Authors: Amy Coxon, Ester Rozenblum, Yoon-Soo Park, Nina Joshi, Junji Tsurutani, Phillip A. Dennis, Ilan R. Kirsch, Frederic J. Kaye
Journal: Cancer Research (2005)

Malignant salivary gland tumors can arise from a t(11;19) translocation that fuses 42 residues from Mect1/Torc1, a cyclic AMP (cAMP)/cAMP-responsive element binding protein (CREB)-dependent transcriptional coactivator, with 982 residues from Maml2, a NOTCH receptor coactivator. To determine if the Mect1-Maml2 fusion oncogene mediates tumorigenicity by disrupting cAMP/CREB signaling, we have generated in-frame deletions within the CREB-binding domain of Mect1/Torc1 for testing transformation activity and have also developed a doxycycline-regulated Mect1-Maml2 mammalian expression vector for global gene expression profiling. We observed that small deletions within the CREB-binding domain completely abolished transforming activity in RK3E epithelial cells. Further, we have shown that the ectopic induction of Mect1-Maml2 in HeLa cells strongly activated the expression of a group of known cAMP/CREB-regulated genes. In addition, we detected candidate cAMP-responsive element sites within 100 nucleotides of the transcriptional start sites of other genes activated by Mect1-Maml2 expression. In contrast, we did not observe alterations of known Notch-regulated target genes in these expression array profile experiments. We validated the results by reverse transcription-PCR in transfected HeLa, RK3E, and H2009 lung tumor cells and in mucoepidermoid cancer cells that endogenously express the fusion oncopeptide. Whereas overexpression of components of the cAMP pathway has been associated with a subset of human carcinomas, these data provide a direct genetic link between deregulation of cAMP/CREB pathways and epithelial tumorigenesis and suggest future therapeutic strategies for this group of salivary gland tumors.
Normal erythrocyte sedimentation rate and age.
Authors: L. E. Bottiger, C. A. Svedberg
Journal: BMJ (1967)

Because of the wide range of plasma factor VIII concentrations found in normal donors, and the inaccuracy of assays on concentrated material, the best basis on which to calculate the appropriate dose of concentrate for a given situation is the factor VIII concentration of the original plasma from which the cryoprecipitate was prepared.If this is known the dose can be calculated without waiting for the result of an assay performed on the reconstituted material, applying a correction factor to account for the expected recovery, as described above.In practice, however, it may not always be possible to assay the original plasma, and in such a case the following formula may be used as a rough guide:No. of packs required= Factor VIII rise intended (%) x body wt.(kg.) x 4 1,000 This is based on the assumptions that a pack of fresh plasma contains 250 units of antihaemophilic globulin, and that the overall in-vivo recovery is not less than 50%, so that 1 unit of antihaemophilic globulin per kg.raises the patient's factor VIII concentration by not less than 1% (see Clinical Results).When the concentration to be achieved is critical, as in major bleeding episodes or to cover operative procedures, it is advisable to check the potency of the material by assaying the concentrate itself.We have found the use of supernatant plasma as the initial diluent for the cryoprecipitate to give more reproducible results in our assay system than other modifications which we have tested. SummaryAntihaemophilic globulin concentrate was prepared from 278 packs of fresh plasma by Pool's cryoprecipitation method, and from a further 103 packs by a modification of this method, involving more rapid thawing of the plasma.These concentrates were used for the treatment or prevention of bleeding on 59 occasions in 23 haemophilic patients, including two major surgical operations.224.
Thomas Goronwy (“T G”) Evans
Authors: Sue Smith
Journal: BMJ (2007)

Pioneered the first successful bone marrow transplants in children with primary immunodeficiency and became a fearless university administratorThe dreadful death of Roland Levinsky has shocked the world of paediatric oncology and genetics.He was an immunologist of international renown who performed the UK's first successful bone marrow transplant in children with primary immunodeficiency in 1979 at Great Ormond Street children's hospital.He went on to perform the UK's first successful attempts at gene therapy in children with fatal inherited diseases.He transformed the Institute of Child Health in London into a topclass research institution.Later, he did a similar makeover at Plymouth University, sending it soaring up the league tables.Levinsky was born in South Africa to a British-born mother and Polish/Lithuanian father.His father, died when Roland was 13.Two years later his mother returned to England with her three children.
Induction of Nitric Oxide Synthase in the Human Cardiac Allograft Is Associated With Contractile Dysfunction of the Left Ventricle
Authors: Neil P. Lewis, Philip S. Tsao, Peter R. Rickenbacher, Chun Xue, Roger A. Johns, Guy A. Haywood, Heiko von der Leyen, Pedro T. Trindade, John P. Cooke, Sharon A. Hunt, Margaret E. Billingham, Hannah A. Valantine, Michael B. Fowler
Journal: Circulation (1996)

Background The mechanisms underlying cardiac contractile dysfunction after transplantation remain poorly defined. Previous work has revealed that inducible nitric oxide synthase (iNOS) is expressed in the rat heterotopic cardiac allograft during rejection; resultant overproduction of nitric oxide (NO) might cause cardiac contractile dysfunction via the negative inotropic and cytotoxic actions of NO. In this investigation, we tested the hypothesis that induction of iNOS may occur and be associated with cardiac allograft contractile dysfunction in humans. Methods and Results We prospectively studied 16 patients in the first year after cardiac transplantation at the time of serial surveillance endomyocardial biopsy. Clinical data, the results of biopsy histology, and echocardiographic and Doppler evaluation of left ventricular systolic and diastolic function were recorded. Total RNA was extracted from biopsy specimens, and mRNA for β-actin, detected by reverse transcription–polymerase chain reaction (RT-PCR) using human specific primers, was used as a constitutive gene control; iNOS mRNA was similarly detected by RT-PCR using human specific primers. iNOS protein was detected in biopsy frozen sections by immunofluorescence. Myocardial cGMP was measured by radioimmunoassay, and serum nitrogen oxide levels (NO x =NO 2 +NO 3 ) were measured by chemiluminescence. iNOS mRNA was detected in allograft myocardium at some point in each patient and in 59 of 123 biopsies (48%) overall. In individual patients, iNOS mRNA expression was episodic and time dependent; the frequency of expression was highest during the first 180 days after transplant ( P =.0006). iNOS protein associated with iNOS mRNA was detected by immunofluorescence in cardiac myocytes. iNOS mRNA expression was not related to the ISHLT histological grade of rejection or to serum levels of NO x but was associated with increased levels of myocardial cGMP ( P =.01) and with both systolic ( P =.024) and diastolic ( P =.006) left ventricular contractile dysfunction measured by echocardiography and Doppler. Conclusions These data support a relation between iNOS mRNA expression and contractile dysfunction in the human cardiac allograft.
Melanoma-associated B cells are distinct from peripheral blood-derived B cells, and may serve as a source of tumor-targeting antibodies
Authors: Daniel Abate-Daga, Theresa A Alexander, Evgeny Arons, Mitchell Ho, Paul F Robbins, Steven A Rosenberg, Richard A Morgan
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The tumor microenvironment contains a complex mix of cell types that can modulate the anti-tumor immune response. In the present study we performed a characterization of tumor-associated B cells, aimed at understanding the biological implications of B cell infiltration in
Tertiary extracontractual referrals
Authors: M. Forsythe
Journal: BMJ (1993)

poor fit of the distribution of free ( human chorionic gonadotrophin to a Gaussian model in the upper range.More data are required to clarify this, but our present conclusion is that with appropriate allowance for the poor fit, the same parameters2 yield an estimated difference in detection that may be as little as 1-2%.
Review: Acute geriatric unit care reduces falls, delirium, and functional decline
Authors: Mary Tinetti
Journal: Annals of Internal Medicine (2013)

Source Citation Fox MT, Persaud M, Maimets I, et al. Effectiveness of acute geriatric unit care using Acute Care for Elders components: a systematic review and meta-analysis. J Am Geriatr Soc. 2012;60:2237-45. 23176020
STRANGULATED CONGENITAL UMBILICAL HERNIA
Authors: I. R. MAERCKLEIN
Journal: JAMA (1910)

As strangulated congenital umbilical hernia is rare, I report the following case: <h3>History.—</h3> July 7, 1910, I was called to attend Mrs. A. in confinement, but arrived twenty minutes too late, the call being nine miles in the country. I found that the baby had a congenital irreducible hernia. Having answered the call hurriedly I had forgotten my pocket case, so after ten minutes futile taxis, I instructed the parents to keep cloths wrung out of hot water on the hernia during the night and told them that I would return in the morning to operate on the child. <h3>Operation.—</h3> The next morning, after again trying taxis and failing to reduce the contents of the sac, I operated, opening the sac, which contained about one foot of cecum and ascending colon and eighteen inches of ileum. Being unable to reduce the contained intestine<i>en masse</i>, due to adhesions of bowel
Abstract 2831: Novel antibody-drug conjugates for selective tumor activation
Authors: Jocelyn R. Setter, Svetlana O. Doronina, Tim D. Bovee, Marti E. Anderson, Peter D. Senter, Dennis R. Benjamin, Robert P. Lyon
Journal: Cancer Research (2011)

Abstract Auristatin based antibody-drug conjugates (ADCs) have demonstrated profound activites, both preclinically and clinically. Upon internalization, the active auristatin is released through proteolytic degradation of the linker, where it induces cell kill through the inhibition of tubulin polymerization. Once released from the antibody, clearance of the auristatin proceeds via the hepatobiliary route. This finding prompted us to explore new auristatin-peptide drug linkers that had the capacity to release the active form of the drug in tumors, but an inactive form in the liver. To this end, we designed a novel in vivo screen in which multiple ADCs were cassette dosed in mice. LC-MS/MS was used to determine which sequences amongst approximately 800 new auristatin-peptide derivatives allowed for differential drug activation. Sequences were identified that allowed for more selective intratumoral release of the active drug. 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 2831. doi:10.1158/1538-7445.AM2011-2831
Antimyeloperoxidase antibodies in individuals with occupational exposure to silica.
Authors: I Wichmann, J Sanchez-Roman, J Morales, M J Castillo, C Ocana, A Nunez-Roldan
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To determine the prevalence of autoantibodies to myeloperoxidase (MPO) in a series of patients exposed to silica. METHODS: The study included 52 patients with occupational exposure to silica (mean exposure time seven years) and a control group comprising seven patients with progressive systemic sclerosis (PSS), six patients with systemic lupus erythematosus (SLE), and 15 healthy individuals. Antibodies to MPO were detected using commercial enzyme linked immunosorbent assay (ELISA) plates coated with MPO. Indirect immunoflurescence studies for antineutrophil cytoplasmic antibodies were performed using ethanol and formol fixed neutrophils. Clinical and biological data of individuals exposed to silica were recorded (published previously). RESULTS: Antibodies to MPO were detected in 14 individuals exposed to silica (27%). There was a statistically significant difference in anti-MPO ELISA units between the healthy subjects and patients (SLE, PSS, silica exposed individuals) (p &lt; 0.01), but no difference between the different disease groups. CONCLUSIONS: Individuals chronically exposed to silica, whether or not they have a connective tissue disease, have levels of antibodies to MPO (as detected by ELISA) that are greater than those found in the normal population, but similar to those in patients with systemic diseases not induced by silica (SLE/PSS).
Exenatide (Exendin-4)–Induced Pancreatitis
Authors: Paul S. Denker, Paul E. Dimarco
Journal: Diabetes Care (2006)

Exenatide is a 39–amino acid peptide approved for the adjunctive treatment of type 2 diabetes. It is an incretin mimetic agent that is consistent in activity with the actions of glucagon-like peptide 1. Proposed mechanisms of action include enhanced glucose-dependent insulin secretion from pancreatic β-cells, restoration of first-phase insulin response, suppression of glucagon secretion, and delay of gastric emptying. Kendall et al. (1) found no evidence of cardiovascular, pulmonary, hepatic, or renal toxicities with exenatide. Nausea (39–48%) and hypoglycemia (19–27%) were the most common side effects reported.

A 69-year-old man with type 2 diabetes of 15 years’ duration presented for follow-up. He had known diabetic neuropathy and retinopathy. His medical history was remarkable for coronary artery disease, gastroesophageal reflux disease, rheumatoid arthritis, and …
Lenalidomide treatment promotes CD154 expression on CLL cells and enhances production of antibodies by normal B cells through a PI3-kinase–dependent pathway
Authors: Rosa Lapalombella, Leslie Andritsos, Qing Liu, Sarah E. May, Rebekah Browning, Lan V. Pham, Kristie A. Blum, William Blum, Asha Ramanunni, Chelsey A. Raymond, Lisa L. Smith, Amy Lehman, Xiaokui Mo, David Jarjoura, Ching-Shih Chen, Richard Ford, Christoph Rader, Natarajan Muthusamy, Amy J. Johnson, John C. Byrd
Journal: Blood (2009)
Why All of Medicine Should Care About &lt;emph type="ital"&gt;DSM-5&lt;/emph&gt;
Authors: David J. Kupfer
Journal: JAMA (2010)

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