tbuckley/cabot-search huggingface dataset:
A novel genetic variant in the transcription factor Islet‐1 exerts gain of function on myocyte enhancer factor 2C promoter activity
Authors: Felix W. Friedrich, Gilles Dilanian, Patricia Khattar, Denise Juhr, Lucie Gueneau, Philippe Charron, Véronique Fressart, Jean‐Thomas Vilquin, Richard Isnard, Laurent Gouya, Pascale Richard, Naima Hammoudi, Michel Komajda, Gisèle Bonne, Thomas Eschenhagen, Olivier Dubourg, Eric Villard, Lucie Carrier
Journal: European Journal of Heart Failure (2012)
Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2
Authors: David E. Saslowsky, Jin Ah Cho, Himani Chinnapen, Ramiro H. Massol, Daniel J.-F. Chinnapen, Jessica S. Wagner, Heidi E. De Luca, Wendy Kam, Barry H. Paw, Wayne I. Lencer
Journal: Journal of Clinical Investigation (2010)

Cholera toxin (CT) causes the massive secretory diarrhea associated with epidemic cholera. To induce disease, CT enters the cytosol of host cells by co-opting a lipid-based sorting pathway from the plasma membrane, through the trans-Golgi network (TGN), and into the endoplasmic reticulum (ER). In the ER, a portion of the toxin is unfolded and retro- translocated to the cytosol. Here, we established zebrafish as a genetic model of intoxication and examined the Derlin and flotillin proteins, which are thought to be usurped by CT for retro-translocation and lipid sorting, respectively. Using antisense morpholino oligomers and siRNA, we found that depletion of Derlin-1, a component of the Hrd-1 retro-translocation complex, was dispensable for CT-induced toxicity. In contrast, the lipid raft-associated proteins flotillin-1 and -2 were required. We found that in mammalian cells, CT intoxication was dependent on the flotillins for trafficking between plasma membrane/endosomes and two pathways into the ER, only one of which appears to intersect the TGN. These results revise current models for CT intoxication and implicate protein scaffolding of lipid rafts in the endo-somal sorting of the toxin-GM1 complex.
Influence of the macromolecular form of a B cell epitope on the expression of antibody variable and constant region structure.
Authors: S Fish, T Manser
Journal: The Journal of Experimental Medicine (1987)

We investigated the influence of the macromolecular form of an epitope on the structure of antibody variable and constant regions expressed by the B cell population participating in an immune response to that epitope. Hybridomas were constructed from strain A/J mice undergoing either primary or secondary immune responses to p-azophenylarsonate conjugated to Brucella abortus (Ars-Bruc). We determined the sequences of the V genes expressed by hybridomas selected on the basis of expression of a single VH gene segment known to encode a large family of anti-Ars antibodies. These sequences were compared with the sequences of V genes expressed by a previously characterized panel of hybridomas isolated in the same way during the primary and secondary responses of A/J mice to Ars-KLH. The repertoire of Ars-specific V domains expressed among primary and secondary hybridomas elicited with these two forms of Ars were similar, as were the differences between primary and secondary V region somatic mutational alteration and affinity for Ars. In contrast, predominant expression of IgG2 anti-Ars antibodies was elicited in the secondary Ars-Bruc response, whereas secondary anti-Ars antibodies elicited with Ars-KLH are predominantly IgG1. Thus, differences in the macromolecular form of Ars clearly influence the isotypic profile of the anti-Ars response, but the expression, diversification, and selection of V domains elicited with this hapten are not greatly affected by such differences. Our results suggest that while isotype regulation is highly perceptive of the macromolecular form of a B cell epitope, V region regulation is primarily influenced by the molecular structure of that epitope.
Tolerance to p53 by A2.1-restricted Cytotoxic T Lymphocytes
Authors: Matthias Theobald, Judith Biggs, Javier Hernández, Joseph Lustgarten, Colleen Labadie, Linda A. Sherman
Journal: The Journal of Experimental Medicine (1997)

Elevated levels of the p53 protein occur in ∼50% of human malignancies, which makes it an excellent target for a broad-spectrum T cell immunotherapy of cancer. A major barrier to the design of p53-specific immunotherapeutics and vaccines, however, is the possibility that T cells may be tolerant of antigens derived from wild-type p53 due to its low level of expression in normal thymus and lymphohemopoetic cells. The combination of p53 deficient (p53−/−) and p53+/+ HLA-A2.1/Kb transgenic mice was used as a model to explore the possibility that A2.1restricted cytotoxic T lymphocytes (CTL) are functionally tolerant of self peptides derived from the wild-type p53 tumor suppressor protein. A2.1-restricted CTL specific for a naturally processed p53 self-epitope spanning residues 187-197 were completely aborted in p53+/+ as opposed to p53−/− transgenic mice. In contrast, CTL specific for a second self-epitope spanning residues 261-269 of the murine p53 sequence were detected in both p53−/− and p53+/+ A2.1/Kb transgenic mice. However, the avidity of the CTL effectors obtained from p53+/+ mice was 10-fold lower than that obtained from p53−/− mice, again suggesting elimination of CTL with high avidity for the A2.1-peptide complex. The circumvention of functional tolerance of high avidity CTL may therefore be a necessary prerequisite for optimizing immunotherapy against A2.1-restricted wild-type p53 epitopes in humans.
Reduced Cardiac Autonomic Flexibility Associated with Medically Unexplained Somatic Complaints in the Context of Internalizing Symptoms in a Preadolescent Population Sample: The TRAILS Study
Authors: Andrea Dietrich, Kirstin Greaves-Lord, Nienke M. Bosch, Albertine J. Oldehinkel, Ruud B. Minderaa, Pieter J. Hoekstra, Monika Althaus
Journal: Psychotherapy and Psychosomatics (2010)
Raised Exhaled Nitric Oxide in Healthy Children Is Associated with Domestic Formaldehyde Levels
Authors: PETER FRANKLIN, PETER DINGLE, STEPHEN STICK
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Exposure to domestic levels of formaldehyde has been associated with adverse respiratory symptoms in both adults and children. The underlying mechanisms responsible for these findings have not been established. In order to investigate possible inflammatory effects of formaldehyde at levels typically found in the home, we measured exhaled nitric oxide (eNO) in 224 healthy children 6 to 13 yr of age (116 girls) and monitored formaldehyde levels in their homes. Formaldehyde was monitored using a passive sampling technique. Exhaled NO was measured directly into a fast response chemiluminescence nitric oxide analyzer. The children also undertook a lung function (spirometry) test. There was no effect of formaldehyde levels measured in homes on spirometric variables. However, eNO levels were significantly elevated in children living in homes with average formaldehyde levels >/= 50 ppb. Exhaled NO levels (geometric mean) were 15.5 ppb (95% CI: 10.5 to 22.9 ppb) for children from homes with formaldehyde concentrations >/= 50 ppb compared with 8.7 ppb (7.9 to 9.6) for children from homes with formaldehyde concentrations < 50 ppb (p < 0.05). These results suggest that exposure to formaldehyde in homes may invoke a subclinical inflammatory response in the airways of healthy children.
Colonic pseudo-obstruction: a new complication of jejunoileal bypass.
Authors: R E Barry, J R Benfield, P Nicell, G A Bray
Journal: Gut (1975)

Five female patients ranging in age from 25 to 44 years are reported in whom jejunoileal bypass (three end-to-side and two end-to end), performed for morbid obesity, was complicated 1 1/2 to three years later by symptoms of colonic pseudo-obstruction. In each size, the colon was markedly elongated, dilated, and atonic but with no demonstrate organic obstruction. The cause of this complication is not known. Full thickness rectal biopsy in one case showed normal intrinsic nervous plexuses and ganglia. Serum electrolytes were normal. Functional and defunctionalized small bowel were not involved. Symptoms varied from complete colonic paralysis to incapacitating crampy abdominal pain and distention. In the three patients with end-to-side bypass, dilatation affected the entire colon, while, in the two patients with end-to-end bypass, the dilatation was localized to colon distal to the anastomosis with the defunctionalized small bowel. Resection of the affected portion of colon in one case resulted in recurrence distal to the new site of drainage of defunctioned bowel. Treatment with anti-anaerobe antibiotics in two cases produced dramatic but temporary relief of symptoms.
Signs and Symptoms in Pulmonary Medicine
Authors: William R. Barclay
Journal: JAMA (1984)

ABSTRACT Many textbooks have described the art of physical diagnosis of pulmonary diseases, but this book is unique in its method and organization. Divided into three parts, the first describes 11 major symptoms of pulmonary diseases in 11 chapters, the second part describes ten signs in ten chapters, and the third, consisting of only one chapter, succinctly outlines the clinical and laboratory findings in 36 pulmonary diseases.All of the chapters in parts 1 and 2 are organized in an identical fashion. The symptom or sign is first defined, its mechanisms and pathophysiology are then described, finally, its clinical correlations are listed. Each chapter is summarized in a table of three columns, the first listing diseases in which the sign or symptom occurs, the second, the frequency or severity of the finding, and finally, a column of comments about the sign or symptom for each disease listed.The text is extremely
The Aging Global Population
Authors: Margaret A. Winker
Journal: JAMA (1996)

We meet the aging process with ambivalence. While our Success as a society is quantified by increasing life expectancy, how we care for isolated and impaired elders is not measured. Ads that promote youth and vigor target retirees with disposable income. The successful aging idealized by geriatricians will elude most of their patients. Even as the preservation of Medicare assumed center stage in the US election year, how it will be paid for in the next decade remains uncertain. The increasing numbers and proportion of older people in the population, a result of declining fertility rates and more people surviving into old age, has become a symbol of improved health and economic status. This trend is occurring throughout the developed nations, such that 20% of the US population<sup>1</sup>and 27% of the Japanese population<sup>2</sup>are expected to be aged 65 years or older by 2025. Similar trends exist
No proof of environmental ill effects on heart
Authors: Elizabeth Rasche González
Journal: JAMA (1980)

An exhaustive literature review has failed to reveal any clear link between most suspected "ecological risk factors" and cardiovascular disease. However, this probably more reflects a dearth of hard data than a surfeit of studies proving the environment safe. Addressing the recent American Heart Association (AHA) science writers' forum in Florida, William R. Harlan, MD, chairman of the Department of Postgraduate Medicine at the University of Michigan, Ann Arbor, and chairman of the AHA Task Force on Environment and the Cardiovascular System, summarized the task force's conclusions about the following environmental factors: <h3>Water Softness.—</h3> The prevalence of cardiovascular disease is higher in areas with soft water, but water softness cannot be isolated from other factors that also vary from place to place. <h3>Fluoride.—</h3> Despite its sometimes dubious reputation, this chemical may actually have a protective effect. In places where the natural fluoride content of water is high, Harlan said, there
Lichen Striatus
Authors: Sigfrid A. Muller
Journal: JAMA (1963)

LICHEN STRIATUS is a unique line of pathologic reaction on the skin. Participation of vascular, nervous, and lymphatic tissues has been suggested to explain its linear quality, but actually we do not know of any satisfactory reason for its distribution. The original communication of Senear and Caro<sup>1</sup>in 1941 may be summarized as a description of a nonspecific, polymorphous, inflammatory reaction occurring in a line on an extremity and healing spontaneously within a few months. Recent reviews by Staricco<sup>2</sup>and by Laugier and Worringer<sup>3</sup>emphasized how little is know of the clinical and histologic patterns. Although vesiculation occasionally has been noted clinically and microscopically in lichen striatus,<sup>2,4</sup>observers have not considered it important. The exception is Felix Pinkus,<sup>5</sup>who recorded vesicles and crusts in addition to papules during the course of this dermatosis. Recently we have studied 2 patients with lichen striatus in whom
Feeding Tube Perforation as a Complication of Percutaneous Endoscopic Gastrostomy
Authors: A. C. Pesarini, H. J. Dittler
Journal: Endoscopy (1992)

See also: Transgastric Perforation of a Percutaneous Endoscopic Feeding Tube with a Fatal OutcomeEndoscopy 1989; 21(01): 45-46DOI: 10.1055/s-2007-1012895
Opening and Closing Characteristics of the Aortic Valve After Different Types of Valve-Preserving Surgery
Authors: Rainer G. Leyh, Claudia Schmidtke, Hans-Hinrich Sievers, Magdi H. Yacoub
Journal: Circulation (1999)

The surgical approach to aortic root aneurysm and/or dissection remains controversial. The use of valve-sparing operations, which are thought to have many advantages, is increasing. We hypothesized that the particular technique and type of surgery could influence valve motion characteristics and function. Therefore, we studied the instantaneous opening and closing characteristics of the aortic valve after the main 2 types of valve-sparing surgery.In 20 patients (10 with tube replacement of the aortic root, group A; and 10 with separate replacement of the sinuses of Valsalva, group B) and 10 controls (group C), transthoracic and transesophageal studies on aortic valve dynamics were performed. Three distinct phases of aortic valve motion were identified. They were as follows: (1) a rapid opening, with a velocity of 20.9+/-4.2 cm/s in group C, 27.1+/-10.9 cm/s in group B (P=NS), and 58.3+/-18.4 cm/s in group A (group A versus group C, P<0. 001; group A versus group B, P=0.001); (2) a slow systolic closure, with 12.5+/-6.6% and 10.8+/-2.2% of maximal opening in groups C and B, respectively (P=NS), and 3.8+/-1.6% in group A (group A versus group C, P=0.001; group A versus group B, P<0.001); and (3) a rapid closing movement, with a velocity of 26.3+/-5.6 cm/s in group C, 32. 4+/-11.4 cm/s in group B (P=NS), and 21.8+/-3.5 cm/s in group A (group A versus group C, P=NS; group A versus group B, P=0.008). The pressure strain of the elastic modulus was different in groups C and B only at the commissures (682+/-145 g/cm(2) versus 1896+/-726 g/cm(2), respectively; P<0.001). At all root levels, the distensibility was reduced in group A (P<0.001). Systolic contact of aortic cusps and wall occurred only in group A.Near-normal opening and closing characteristics can be achieved by a technique that preserves the shape and independent mobility of the sinuses of Valsalva.
Serum osteoprotegerin and soluble receptor activator of nuclear factor κB ligand levels in patients with a history of differentiated thyroid carcinoma: a case-controlled cohort study
Authors: Massimo Giusti, Francesca Cecoli, Laura Fazzuoli, Vincenzina De Franchis, Enrica Ceresola, Diego Ferone, Michele Mussap, Francesco Minuto
Journal: Metabolism (2007)
CD: StatsDirect---Statistical Software for Medical Research in the 21st Century
Authors: N. Freemantle
Journal: BMJ (2000)

Iain E Buchan CamCode, £99 single user academic, £179 single user commercial, £49 students and developing world Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Clinicians involved in medical research are increasingly numerate and statistically sophisticated. Recently, two colleagues hounded me. They wanted to see confidence intervals for every number in a paper describing a randomised trial that we had worked on together. I found myself in a strange position—(1);the confidence intervals that they wanted were neither … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Tamoxifen in treatment of primary biliary cirrhosis
Authors: Pietro Invernizzi, Domenico Alvaro, Andrea Crosignani, Eugenio Gaudio, Mauro Podda
Journal: Hepatology (2004)

Although ursodeoxycholic acid may improve liver biochemistry and slow disease progression, primary biliary cirrhosis (PBC) remains without a definite cure, and the search for additional medications continues.1 Cholangiocytes are the primary target of damage in PBC, and the balance between proliferation and death of these cells may condition the progression of the disease.2-4 We have recently found that estrogen receptors (ER) are expressed in cholangiocytes of rats with bile duct ligation (an animal model of cholestasis) and that selective modulators of ER influences cholangiocyte proliferation and death.2, 3. Furthermore, the cholangiocytes of PBC patients but not normal subjects expressed ER, and the degree of expression was shown to correlate with cell proliferation and with disease progression.4 On the basis of these findings, we hypothesize that selective ER modulators might have an impact on the biochemical and clinical expression of PBC. We searched the database of the entire patient population who had been on regular follow-up in our Liver Unit for at least 18 months since 1974. Of 488 women with PBC, 3 had been treated for at least 18 months with tamoxifen (TMX), a selective ER modulator,5 for breast cancer. They received TMX (20 mg/day) for 18 months (case A), 60 months (case B), and 30 months (case C) Fig. 1 shows the effect of TMX on liver enzymes related with cholestasis in these patients. At the beginning of the observation period, the patients were 58, 49, and 49 years old, respectively. Case B had liver cirrhosis. Case C received TMX while on ursodeoxycholic acid (15 mg/kg/day). Biochemical effect of tamoxifen (TMX) alone or in association with ursodeoxycholic acid (UDCA) in 3 patients with primary biliary cirrhosis. Normal values: alkaline phosphatase <279 IU/L; γ-glutamyltransferase <32 IU/L. Serum bilirubin levels were normal and did not change throughout the observation period in all the three cases. In cases A and B there was a marked decrease of alkaline phosphatase (about 70% and 85%, respectively) levels and of γ-glutamyltransferase (about 60% and 75%, respectively) levels during the TMX therapy, with a complete reversal in case A after TMX withdrawal. A reduction of the liver enzymes was observed also in case C, who had concomitant treatment with ursodeoxycholic acid. During the observation period, none of these patients developed any complications of liver cirrhosis. In conclusion, this retrospective survey shows a biochemical benefit of TMX, a selective ER-β antagonist and mixed agonist/antagonist ER-α modulator, in patients with PBC. TMX could affect PBC progression by regulating cholangiocyte proliferation and death. Further studies are warranted to assess the safety andefficacy of TMX (alone or in combination with ursodeoxycholic acid) in the treatment of PBC.
Experts clash as committee debates reducing 24 week abortion limit
Authors: Clare Dyer
Journal: BMJ (2007)

Health experts clashed this week over the long term health risks for women who have terminations as the House of Commons science and technology committee launched its inquiry into whether the abortion laws in England and Wales need updating in the light of current knowledge.

Doctors who gave evidence at the committee's first session agreed that the research showed that women who have induced abortions are more likely to have premature births in future—and the more terminations they have, the greater the risk.

But …
Concordance for Dyslipidemic Hypertension in Male Twins
Authors: Joseph V. Selby
Journal: JAMA (1991)

Sixty cases of dyslipidemic hypertension were identified in the 1028 middleaged, white, male twin participants in the first examination of the National Heart, Lung, and Blood Institute Twin Study (1969 to 1973). The prevalence of dyslipidemic hypertension was similar by zygosity but proband concordance was three times greater in monozygotic than dizygotic twins (0.44 [seven concordant and 18 discordant pairs] vs 0.14 [two concordant and 24 discordant pairs]), suggesting a genetic effect on the condition. Low high-density lipoprotein cholesterol level was the most common lipid abnormality in concordant pairs. Mortality from ischemic heart disease was significantly higher in individuals with dyslipidemic hypertension. Obesity and glucose intolerance were closely associated with the syndrome. Moreover, within the 18 discordant monozygotic twin pairs, the twins with dyslipidemic hypertension had gained significantly more weight as adults and were significantly heavier than their unaffected cotwins. Thus, although genetic factors may influence development of dyslipidemic hypertension, nongenetic, potentially modifiable aspects of obesity are also closely related to expression of this clinically important syndrome. (<i>JAMA</i>. 1991;265:2079-2084)