tbuckley/cabot-search huggingface dataset:
Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.
Authors: D A Sanan, K H Weisgraber, S J Russell, R W Mahley, D Huang, A Saunders, D Schmechel, T Wisniewski, B Frangione, A D Roses
Journal: Journal of Clinical Investigation (1994)

Late-onset and sporadic Alzheimer's disease are associated with the apolipoprotein E (apoE) type 4 allele expressing the protein isoform apoE4. Apolipoprotein E binds avidly to beta amyloid (A beta) peptide, a major component of senile plaque of Alzheimer's disease, in an isoform-specific manner. The apoE4 isoform binds to A beta peptide more rapidly than apoE3. We observed that soluble SDS-stable complexes of apoE3 or apoE4, formed by coincubation with A beta peptide, precipitated after several days of incubation at 37 degrees C with apoE4 complexes precipitating more rapidly than apoE3 complexes. A beta(1-28) and A beta(1-40) peptides were incubated in the presence or absence of apoE3, apoE4, or bovine serum albumin for 4 d at 37 degrees C (pH 7.3). Negative stain electron microscopy revealed that the A beta peptide alone self-assembled into twisted ribbons containing two or three strands but occasionally into multistranded sheets. The apoE/A beta coincubates yielded monofibrils 7 nm in diameter. ApoE4/A beta coincubates yielded a denser matrix of monofibrils than apoE3/A beta coincubates. Unlike purely monofibrillar apoE4/A beta coincubates, apoE3/A beta coincubates also contained double- and triple-stranded structures. Both apoE isoforms were shown by immunogold labeling to be uniformly distributed along the A beta peptide monofibrils. Monofibrils appeared earlier in apoE4/A beta than in apoE3/A beta in time-course experiments. Thus apoE3 and apoE4 each interact with beta amyloid peptide to form novel monofibrillar structures, apoE4 more avidly, a finding consistent with the biochemical and genetic association between apoE4 and Alzheimer's disease.
Lithium Causes G2 Arrest of Renal Principal Cells
Authors: Theun de Groot, Mohammad Alsady, Marcel Jaklofsky, Irene Otte-Höller, Ruben Baumgarten, Rachel H. Giles, Peter M.T. Deen
Journal: Journal of the American Society of Nephrology (2014)

Vasopressin-regulated expression and insertion of aquaporin-2 channels in the luminal membrane of renal principal cells is essential for urine concentration. Lithium affects urine concentrating ability, and approximately 20% of patients treated with lithium develop nephrogenic diabetes insipidus (NDI), a disorder characterized by polyuria and polydipsia. Lithium-induced NDI is caused by aquaporin-2 downregulation and a reduced ratio of principal/intercalated cells, yet lithium induces principal cell proliferation. Here, we studied how lithium-induced principal cell proliferation can lead to a reduced ratio of principal/intercalated cells using two-dimensional and three-dimensional polarized cultures of mouse renal collecting duct cells and mice treated with clinically relevant lithium concentrations. DNA image cytometry and immunoblotting revealed that lithium initiated proliferation of mouse renal collecting duct cells but also increased the G2/S ratio, indicating G2/M phase arrest. In mice, treatment with lithium for 4, 7, 10, or 13 days led to features of NDI and an increase in the number of principal cells expressing PCNA in the papilla. Remarkably, 30%–40% of the PCNA-positive principal cells also expressed pHistone-H3, a late G2/M phase marker detected in approximately 20% of cells during undisturbed proliferation. Our data reveal that lithium treatment initiates proliferation of renal principal cells but that a significant percentage of these cells are arrested in the late G2 phase, which explains the reduced principal/intercalated cell ratio and may identify the molecular pathway underlying the development of lithium-induced renal fibrosis.
Effect of three different bronchodilators during an exacerbation of chronic obstructive pulmonary disease
Authors: P Lloberes, L Ramis, JM Montserrat, J Serra, J Campistol, C Picado, A Agusti-Vidal
Journal: European Respiratory Journal (1988)

This study evaluates the effect of three different bronchodilators (beta 2-adrenergic, anticholinergic and methylxanthine) alone and in randomized sequence, during an exacerbation in thirteen patients with chronic obstructive pulmonary disease. Dose-response curves were obtained for inhaled salbutamol and inhaled ipratropium bromide. The bronchodilator effect of a perfusion of aminophylline was also assessed. When a plateau of bronchodilatation was achieved with one agent, one dose of a second bronchodilator was administered to see whether additional bronchodilation could be achieved. The increments in FEV1 and FVC were similar with the three agents. The addition of a second bronchodilator did not result in significant increments in most of the patients. In at least half of the patients the doses of salbutamol and ipratropium that produced the maximal bronchodilatation were twice that currently employed.
Mercurial Diuresis in Edematous Individuals
Authors: G. T. LESSER, M. F. DUNNING, F. H. EPSTEIN, E. Y. BERGER
Journal: Circulation (1952)

The electrolyte and water losses in 75 instances of diuresis following Mercuhydrin were studied in 17 edematous patients.The loss of potassium was appreciable following exhibition of the drug to patients who retained their dietary sodium almost completely.Occurrence of such clinical symptoms as weakness, nausea, and ventricular premature contractions might be attributed to this loss of potassium.The fluid lcst by mercurial diuresis was isotonic with body fluids.The chloride concen- tration was fairly constant at 151 mEq.per liter.The concentrations of sodium and potassium were more variable, the average concentrations being 97 and 35 mEq.per liter, respectively.Lcss of water and electrolyte in these concentrations leaves the patient in relative alkalosis, with a loss of intracellular potassium and a gain in intracellular sodium.
Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle.
Authors: A H Henderson, M R Cattell
Journal: Circulation Research (1976)

The plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude equal to or less than 5% Lmax) was obtained. Isotonic oscillations were less damped than their isometric counterparts, implying positive feedback and thus a causal role of the perturbation in length. Oscillation frequency was 2-3 HZ at 29 degrees C (Q 10, 2-3); it could be increased by epinephrine or caffeine, independently of their effects on extent of shortening; it otherwise changed as a generally constant function of the length at which the oscillation occurred, whether this was altered by changes in extracellular [Sr], frequency of contraction, or load (independent of the direction and magnitude of the preceding load step). Similar oscillatory responses were induced during Sr- or Ca-mediated contractures. Cat muscles showed an additional slower component to the oscillatory response. Transient augmentation of the velocity-length relationship after abrupt reduction in load, previously described for twitch contractions under certain conditions, appears to be analogous to the first phase of the oscillatory response studied here. Our findings indicate that the oscillation is not attributable to any mechanism intrinsic to myofilament interaction, but rather that it involves length-induced changes in the level of activation, probably mediated by Ca2+ or Sr2+. We conclude that length influences the level of activation during contraction of heart muscle.
IN VITRO CULTIVATION AND IMMUNOFLUORESCENT STUDIES OF TRANSPLANTABLE CARCINOMAS Vx2 AND Vx7
Authors: Toyoro Osato, Yohei Ito
Journal: The Journal of Experimental Medicine (1967)

The Vx2 and Vx7 rabbit carcinomas, both of Shope papilloma derivation, were cultivated in vitro and studied for immunofluorescence indicative of the presence of viral antigen. The cultured Vx7 cells were characteristically pleomorphic, round or polygonal cells, and immunofluorescence was demonstrable in 5–20% of them as counted on cover slip cultures after exposure to rabbit sera containing anti-Shope papilloma virus antibody. The Vx2 cells in contrast to this were of almost uniform size and character, small and approximately round, and the specific fluorescence was found in less than 0.1% of the total number. These findings indicate that some antigenic derivation from the Shope papilloma virus is still persisting at least in some fractions of the cells, not only of Vx7 tumors but also of the Vx2 tumors, even after maintenance of the growths by transplantation for more than 20 yr. During the course of the study, two lines of the Vx7 were kept continually growing while the culture of Vx2 was discontinued at its tenth passage after an accident due to mechanical failure of the incubator. The neoplastic capacity of the Vx7 cells cultured in vitro was demonstrated by implanting these intradermally on the ears of domestic rabbits. The result was destructive carcinomas of the Vx7 sort.
S110 Pulmonary Rehabilitation Outcomes in Chronic Obstructive Pulmonary Disease (COPD) vs Matched Patients with Interstitial Lung Disease (ILD): Abstract S110 Table 1
Authors: MJ Hussain, V Sandrey, S Barr, DL Smith
Journal: Thorax (2012)

<h3>Introduction</h3> Pulmonary rehabilitation is an effective intervention for patients with COPD. There is now also good evidence of benefit for patients with ILD We have compared the outcome of the same PR programme in patients with COPD and ILD. <h3>Methods</h3> Patients with various forms of ILD (predominantly IPF or UIP) were matched with the same number of COPD patients for baseline MRC grade and for age. All patients had completed the same 7 week, 14 visit hospital based out patient PR program. Outcome Measures and desaturation during exercise were compared between the two groups. <h3>Results</h3> 51 ILD patients, age range 34–85, mean initial MRC grade 3.5(0.94), 30 male were compared with 51 COPD patients, age range 47–85, mean baseline MRC grade 3.5(0.94), 31 male. <h3>Discussion</h3> Our PR program produced clinically important improvements in ISWT and all domains of the CRDQ for COPD patients. ILD patients produced a smaller mean change in ISWT although this was not statistically significant between the groups. ILD patients also showed smaller changes in all domains of the CRDQ although again this was not statistically significant between the groups. The improvement in ESWT was similar in both groups. Desaturation during the baseline ISWT was more severe in the ILD group regardless of oxygen usage and despite a marginally higher pre-exercise value. This may account for the lower ISWT value seen in these patients. PR produces measurable improvements in both groups of patients. Interpretation is hampered by a lack of defined MCID values for ILD patients.
Reproducibility of Insulin Dosage on Consecutive Days of Blood Glucose Control by an Artificial Beta-Cell in Brittle Diabetic Patients
Authors: Waldemar Bruns, Hans Bombor, Erich Jutzi, Klaus-Peter Ratzmann, Bernd Schulz, Peter Abel, Uwe Fischer
Journal: Diabetes Care (1983)

The profiles of blood glucose and of insulin dosage were compared between the first and second of 2 consecutive days of Biostator administration under constant conditions in 12 brittle type I diabetic inpatients. All blood glucose criteria and the daily insulin doses were reproducible between these 2 days for the entire group of patients. In nearly all patients, however, there were distinct but unsystematic differences between the 2 daysin the diurnal patterns of insulin dose distribution. These differences could be ascribedto some stress reaction or inherent metabolic lability. It is concluded that, in these extremely labile diabetic patients, due to the insufficient short-term reproducibility of the outcome of an extracorporal artificial beta-cell, caution must be used when constant profiles are to be predicted from these doses for open-loop insulin delivery systems or for conventional subcutaneous injection therapy.
CD69 surface expression on human lung eosinophils after segmental allergen provocation
Authors: P Julius, W Luttmann, B Knoechel, C Kroegel, H Matthys, None Virchow JC
Journal: European Respiratory Journal (1999)

CD69 expression on eosinophils is observed in asthma and has been proposed as a marker of eosinophil activation. The role of allergens in the in vivo regulation of CD69 expression on eosinophils, however, remains incompletely understood. It was therefore investigated whether CD69 expression on eosinophils can be induced by allergen provocation in vivo. Ten allergic asthmatics were studied by segmental allergen provocation. Two segments of the right and left lung were challenged with allergen or saline. CD69 expression was determined by flow cytometry and concentrations of interleukins were analysed by enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid. Expression of CD69 on BAL eosinophils in the segments lavaged 10 min following saline instillation (28.3+/-8.8 specific mean fluorescence (SMF)) was not significantly different to segments lavaged 10 min after allergen (80.2+/-21.8 SMF) and segments lavaged 18 h after saline challenge (87.2+/-23.3 SMF). However, CD69 expression on eosinophils increased significantly 18 h after allergen challenge (128.6+/-21.9 SMF, p&lt;0.03) which was accompanied by elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations (114.9+/-42.9 pg x mL(-1), p&lt;0.05). CD69 expression on eosinophils and GM-CSF concentrations correlated 18 h following allergen provocation (r = 0.7, p&lt;0.025). These results suggest that in allergic asthma there is an allergen dependent, endobronchial upregulation of eosinophil activation as assessed by CD69 expression on eosinophils.
Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis.
Authors: S D Griffiths, D T Goodhead, S J Marsden, E G Wright, S Krajewski, J C Reed, S J Korsmeyer, M Greaves
Journal: The Journal of Experimental Medicine (1994)

We have compared the sensitivity of clonogenic interleukin 7 (IL-7)-dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis-inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL-2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells.
Stromal biology and therapy in pancreatic cancer
Authors: A. Neesse, P. Michl, K. K. Frese, C. Feig, N. Cook, M. A. Jacobetz, M. P. Lolkema, M. Buchholz, K. P. Olive, T. M. Gress, D. A. Tuveson
Journal: Gut (2010)

Pancreatic ductal adenocarcinoma (PDA) is an almost uniformly lethal disease. One explanation for the devastating prognosis is the failure of many chemotherapies, including the current standard of care therapy gemcitabine. Although our knowledge of the molecular events underlying multistep carcinogenesis in PDA has steadily increased, translation into more effective therapeutic approaches has been inefficient over the last several decades. Evidence for this innate resistance to systemic therapies was recently provided in an accurate mouse model of PDA by the demonstration that chemotherapies are poorly delivered to PDA tissues because of a deficient vasculature. This vascular deficiency correlated with the presence of a dense stromal matrix that is a prominent histological hallmark of PDA tumours. Therapeutic targeting of stromal cells decreased the stroma from pancreatic tumours, resulting in increased intratumoral perfusion and therapeutic delivery of gemcitabine. Stromal cells contained within the PDA tumour microenvironment therefore represent an additional constituent to neoplastic cells that should be critically evaluated for optimal therapeutic development in preclinical models and early clinical trials.
Superior Vena Cava Syndrome with Malignant Causes
Authors: Lynn D. Wilson, Frank C. Detterbeck, Joachim Yahalom
Journal: New England Journal of Medicine (2007)

A 58-year-old man presents with a 2-week history of progressive dyspnea on exertion, neck swelling, decreased appetite, and fatigue. There is no history of syncope or dysphagia. He smoked cigarettes until 5 years ago. The physical examination reveals a heart rate of 105 beats per minute, a respiratory rate of 20 breaths per minute, and superficial vascular distention over the neck, chest, and upper abdomen. Stridor is not present. How should his case be evaluated and managed?
Whole-Genome Sequencing and Social-Network Analysis of a Tuberculosis Outbreak
Authors: Jennifer L. Gardy, James C. Johnston, Shannan J. Ho Sui, Victoria J. Cook, Lena Shah, Elizabeth Brodkin, Shirley Rempel, Richard Moore, Yongjun Zhao, Robert Holt, Richard Varhol, Inanc Birol, Marcus Lem, Meenu K. Sharma, Kevin Elwood, Steven J.M. Jones, Fiona S.L. Brinkman, Robert C. Brunham, Patrick Tang
Journal: New England Journal of Medicine (2011)

An outbreak of tuberculosis occurred over a 3-year period in a medium-size community in British Columbia, Canada. The results of mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) genotyping suggested the outbreak was clonal. Traditional contact tracing did not identify a source. We used whole-genome sequencing and social-network analysis in an effort to describe the outbreak dynamics at a higher resolution.
Efficacy and Tolerability of Vardenafil in Men With Mild Depression and Erectile Dysfunction: The Depression-Related Improvement With Vardenafil for Erectile Response Study
Authors: Raymond Rosen, Ridwan Shabsigh, Mark Berber, Pierre Assalian, Mathew Menza, Luis Rodriguez-Vela, Robert Porto, Keith Bangerter, Monica Seger, Francesco Montorsi
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: Erectile dysfunction and depression are highly associated. Previous studies have shown benefits of phosphodiesterase-5 inhibitor treatment for erectile dysfunction associated with antidepressant therapy or subsyndromal depression. The present study assessed the safety and efficacy of vardenafil in men with erectile dysfunction and untreated mild depression. METHOD: In this 12-week, multicenter, randomized, flexible-dose, parallel-group, double-blind study, 280 men with erectile dysfunction for at least 6 months and untreated mild major depression received placebo or vardenafil, 10 mg/day, for 4 weeks, with the option to titrate to 5 mg/day or 20 mg/day after each of two consecutive 4-week intervals. Endpoints included International Index of Erectile Function erectile function domain and 17-item Hamilton Depression Rating Scale (HAM-D) scores. RESULTS: Vardenafil produced statistically significant and clinically meaningful improvement in all erectile function parameters. The International Index of Erectile Function erectile function domain score was 22.9 with vardenafil compared to 14.9 with placebo. The HAM-D score was lower in the vardenafil group (7.9) than in the placebo group (10.1). Treatment with vardenafil was the most important predictor for return to normal erectile function. Improvement in International Index of Erectile Function erectile function domain score was the most important predictor of remission in depressive symptoms. CONCLUSIONS: Vardenafil was well tolerated and highly efficacious in men with erectile dysfunction and untreated mild major depression. Significant improvements in erectile function and depression were observed in patients treated with vardenafil versus placebo. Erectile dysfunction treatment should be considered a component of therapy for men with depression and erectile dysfunction.
Crohn's disease in two married couples.
Authors: J M Rhodes, T Marshall, J D Hamer, R N Allan
Journal: Gut (1985)

Only two examples of married couples where both partners have developed Crohn9s disease have been reported previously from the United Kingdom. We describe two further examples; one where the index patient had developed Crohn9s disease before marriage, and the spouse subsequently developed Crohn9s disease and a second example in which both spouses developed Crohn9s disease after marriage.
Association of Obesity With DNA Mismatch Repair Status and Clinical Outcome in Patients With Stage II or III Colon Carcinoma Participating in NCCTG and NSABP Adjuvant Chemotherapy Trials
Authors: Frank A. Sinicrope, Nathan R. Foster, Harry H. Yoon, Thomas C. Smyrk, George P. Kim, Carmen J. Allegra, Greg Yothers, Daniel A. Nikcevich, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2011)

Although the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown.BMI (kg/m(2)) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively.Overall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m(2)). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients.Colon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.