tbuckley/cabot-search huggingface dataset:
Neurotrophin receptor p75NTR mediates Huntington’s disease–associated synaptic and memory dysfunction
Authors: Verónica Brito, Albert Giralt, Lilian Enriquez-Barreto, Mar Puigdellívol, Nuria Suelves, Alfonsa Zamora-Moratalla, Jesús J. Ballesteros, Eduardo D. Martín, Nuria Dominguez-Iturza, Miguel Morales, Jordi Alberch, Sílvia Ginés
Journal: Journal of Clinical Investigation (2014)

Learning and memory deficits are early clinical manifestations of Huntington's disease (HD). These cognitive impairments have been mainly associated with frontostriatal HD pathology; however, compelling evidence provided by several HD murine models suggests that the hippocampus may contribute to synaptic deficits and memory dysfunction in HD. The neurotrophin receptor p75(NTR) negatively regulates spine density, which is associated with learning and memory; therefore, we explored whether disturbed p75(NTR) function in the hippocampus could contribute to synaptic dysfunction and memory deficits in HD. Here, we determined that levels of p75(NTR) are markedly increased in the hippocampus of 2 distinct mouse models of HD and in HD patients. Normalization of p75(NTR) levels in HD mutant mice heterozygous for p75(NTR) prevented memory and synaptic plasticity deficits and ameliorated dendritic spine abnormalities, likely through normalization of the activity of the GTPase RhoA. Moreover, viral-mediated overexpression of p75(NTR) in the hippocampus of WT mice reproduced HD learning and memory deficits, while knockdown of p75(NTR) in the hippocampus of HD mice prevented cognitive decline. Together, these findings provide evidence of hippocampus-associated memory deficits in HD and demonstrate that p75(NTR) mediates synaptic, learning, and memory dysfunction in HD.
Hypocholesterolaemia in hairy cell leukaemia
Authors: J. Hinnie, D. S. O'Reilly
Journal: BMJ (1995)

cholesterol concentration and the progress of angiographic signs of atherosclerosis; most studies have found no association between serum lipid concentrations and restenosis after angioplasty; and no trial has found a systematic association between the degree of cholesterol lowering and outcome.Oliver and colleagues claim that angiographic trials have shown a decrease in cholesterol concentration to be associated with a lessening of atheromatous obstruction.To translate a microscopic widening or delay of angiographic stenosis to a lessening of atheromatosis, however, is premature, because early stages of atheromatosis are compen- sated for by an enlargement of the lumenal area,2 indicating that a widening may be due to both an increase and a decrease in atherosclerosis.That the effect was due to cholesterol lowering is also questionable because a dose-response relation was not found in these angiographic trials.3The Scandinavian simvastatin study is seem- ingly a good argument for cholesterol lowering, but simvastatin has other effects.At least two of them may be beneficial to cardiovascular disease independent of the cholesterol concentration.4Such effects may have operated in the Scandinavian study, because the outcome was independent of baseline lipid concentrations4 and, according to the preliminary data presented at meetings arranged by Merck Sharpe and Dohme in Sweden, there was no dose-response relation with either total or low density lipoprotein cholesterol concentration.Simvastatin may be of benefit in cardiovascular
THE NEOPLASTIC POTENTIALITIES OF MOUSE EMBRYO TISSUES
Authors: William E. Smith, Peyton Rous
Journal: The Journal of Experimental Medicine (1948)

The observation that adenomas develop very rapidly in the pulmonary tissue of mouse embryos implanted together with methylcholanthrene, in adult animals, has led to tests of the neoplastic potentialities of this tissue in utero. C strain females in the latter half of pregnancy were injected with urethane and the lungs of their young were searched for adenomas. None could be perceived with certainty in embryos at term or in mice just born, but they were several times found 3 days after birth and they were frequent and much larger in 10-day-old animals. The controls showed none. After 60 to 70 days they were often visible in the gross. Corroboratory findings were obtained in A mice. No parallelism could be perceived in the incidence of the tumors in mothers and offspring. The adenomas arose from tissue devoid of any sign of preliminary local disturbance. Mitoses were abundant in them and they grew rapidly for a while, but within 2 months cell division had almost ceased. By this time however many of the neoplasms were as big as any adenomas in the urethanized mother animals and in some instances twice as big. While growing fast they underwent little differentiation, but this took place when proliferation slowed and in consequence the tumors came to have the morphology of the spontaneous and induced adenomas of adults. The neoplastic cells were derived from alveolar elements, yet in proportion as differentiation of them occurred they came to resemble the epithelial cells lining the small bronchioles. Occasionally the resemblance to bronchial epithelium was complete, save that the cytoplasm of the tumor cells was slightly basophilic. The following conclusions seem justified:- 1. The injection of urethane into pregnant female mice of the C strain frequently initiates the development forthwith of pulmonary adenomas in the young she is carrying. 2. Some of the pulmonary cells of mouse embryos well along toward term possess the ability to be neoplastic. 3. The adenomatous change finds swift expression in young creatures because of conditions implicit in their youth. The rapid proliferation of the tumor cells is almost entirely due to these conditions, not to the neoplastic state as such. 4. Adenomatous change prior to birth is intrinsically the same process as that occurring in the adult creature. 5. The adenomatous state does not prevent the cells of young mice from undergoing the maturation that takes place in normal elements of the same sort as the organism grows older. Though the proliferative activity natural to youth and the unnatural activity consequent on neoplastic change are summated in the young organism, they still are separable.
Second Malignant Neoplasms in Surivors of Wilms' Tumor: A Report From the National Wilms' Tumor Study
Authors: N. E. Breslow, P. A. Norkool, A. Olshan, A. Evans, G. J. D'Angio
Journal: JNCI Journal of the National Cancer Institute (1988)

Between October 1969 and December 1982, 2,438 patients were enrolled in the National Wilms' Tumor Study and contributed 14,381 person-years of observation to a follow-up study for the occurrence of second malignant neoplasms (SMNs). Fifteen SMNs were observed, whereas 1.77 would have been expected from U.S. incidence rates for 1973-1977 [relative risk = 8.5; 95% confidence interval (CI) = 4.7, 14.0]. Ten years after the Wilms' tumor diagnosis, the cumulative risk of SMN was 1%. The relative risks compared to standard rates were 12/1.11 = 10.8 (95% CI = 5.6, 18.9) for those who received radiation as part of the initial course of treatment and 3/0.60 = 5.0 (95% CI = 1.0, 14.6) for those who did not, but this difference was not statistically significant. Preliminary data suggest that substantial numbers of SMNs occur as patients are followed greater than 10 years from diagnosis.
Noninvasive Assessment of Significant Left Anterior Descending Coronary Artery Stenosis by Coronary Flow Velocity Reserve With Transthoracic Color Doppler Echocardiography
Authors: Takeshi Hozumi, Kiyoshi Yoshida, Yumiko Ogata, Takashi Akasaka, Yoshio Asami, Tsutomu Takagi, Shigefumi Morioka
Journal: Circulation (1998)

Coronary flow reserve has been considered an important diagnostic index of the functional significance of coronary artery stenosis. With Doppler technique, it has been assessed as the ratio of hyperemic to basal coronary flow velocity (coronary flow velocity reserve [CFVR]) by invasive or semiinvasive methods with a Doppler catheter, a Doppler guide wire, and a transesophageal Doppler echocardiographic probe. Recent technological advancement in transthoracic Doppler echocardiography (TTDE) provides measurement of coronary flow velocity in the distal portion of the left anterior descending coronary artery (LAD) and may be useful in the noninvasive CFVR measurement. The purpose of this study was to evaluate the value of CFVR determined by TTDE for the assessment of significant LAD stenosis.We studied 36 patients who underwent coronary angiography for the assessment of coronary artery disease. The study population consisted of 12 patients with significant LAD stenosis (group A) and 24 patients without significant LAD stenosis (group B). With TTDE, coronary flow velocities in the distal LAD were recorded at rest and during hyperemia induced by intravenous infusion of adenosine (0.14 mg x kg(-1) x min(-1)) under the guidance of color Doppler flow mapping. Adequate spectral Doppler recordings of coronary flow in the distal LAD for the assessment of CFVR were obtained in 34 of 36 study patients (94%). The peak and mean diastolic coronary flow velocities at baseline did not differ between groups A and B (23.6+/-10.3 versus 22.9+/-6.6 cm/s and 16.4+/-8.6 versus 14.5+/-4.0 cm/s, respectively). However, the peak and mean coronary flow velocities during hyperemia in group A were significantly smaller than those in group B (35.6+/-16.3 versus 54.2+/-16.3 cm/s and 24.7+/-13.1 versus 37.9+/-13.0 cm/s, respectively; P<.01). There were significant differences in CFVR obtained from peak and mean diastolic velocity between groups A and B (1.5+/-0.2 versus 2.4+/-0.4 and 1.5+/-0.2 versus 2.6+/-0.4, respectively; P<.001). A CFVR from peak diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 82% for the presence of significant LAD stenosis. A CFVR from mean diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 86% for the presence of significant LAD stenosis.CFVR determined by TTDE is useful in the noninvasive assessment of significant stenotic lesion in the LAD.
EFFECTS OF ALCOHOL ON DRIVING SKILL
Authors: Henry Newman
Journal: JAMA (1941)

<h3>To the Editor:—</h3> In view of the interest in our paper (The Journal, Nov. 9, 1940, p. 1600) dealing with the effect of alcohol, manifested by the communications of Drs. Bogen, Muehlberger, Bavis and Heise (The Journal, Dec. 21, 1940, p. 2198), it seems desirable to clarify our stand on certain points at issue. It was not our purpose in the paper, as was implied by Bavis, to investigate the impairment of driving ability at a blood alcohol concentration of 0.15 per cent but rather to demonstrate the degree of variation in the loss of skill in certain tests related to driving in different persons at the same blood alcohol concentration. Muehlberger states that this biologic variation does not exceed 10 to 15 per cent, yet our experiments showed a much greater variation. For example, a loss of 8 per cent in the tests was accompanied by blood alcohol concentrations
Vascular endothelial growth factor induces protein synthesis in renal epithelial cells: A potential role in diabetic nephropathy11See Editorial by Ziyadeh and Wolf, p. 758.
Authors: Duraisamy Senthil, Goutam Ghosh Choudhury, Colby Mclaurin, Balakuntalam S. Kasinath
Journal: Kidney International (2003)
Adaptive Responses to Dasatinib-Treated Lung Squamous Cell Cancer Cells Harboring DDR2 Mutations
Authors: Yun Bai, Jae-Young Kim, January M. Watters, Bin Fang, Fumi Kinose, Lanxi Song, John M. Koomen, Jamie K. Teer, Kate Fisher, Yian Ann Chen, Uwe Rix, Eric B. Haura
Journal: Cancer Research (2014)

DDR2 mutations occur in approximately 4% of lung squamous cell cancer (SCC) where the tyrosine kinase inhibitor dasatinib has emerged as a new therapeutic option. We found that ERK and AKT phosphorylation was weakly inhibited by dasatinib in DDR2-mutant lung SCC cells, suggesting that dasatinib inhibits survival signals distinct from other oncogenic receptor tyrosine kinases (RTK) and/or compensatory signals exist that dampen dasatinib activity. To gain better insight into dasatinib's action in these cells, we assessed altered global tyrosine phosphorylation (pY) after dasatinib exposure using a mass spectrometry-based quantitative phosphoproteomics approach. Overlaying protein-protein interaction relationships upon this dasatinib-regulated pY network revealed decreased phosphorylation of Src family kinases and their targets. Conversely, dasatinib enhanced tyrosine phosphorylation in a panel of RTK and their signaling adaptor complexes, including EGFR, MET/GAB1, and IGF1R/IRS2, implicating a RTK-driven adaptive response associated with dasatinib. To address the significance of this observation, these results were further integrated with results from a small-molecule chemical library screen. We found that dasatinib combined with MET and insulin-like growth factor receptor (IGF1R) inhibitors had a synergistic effect, and ligand stimulation of EGFR and MET rescued DDR2-mutant lung SCC cells from dasatinib-induced loss of cell viability. Importantly, we observed high levels of tyrosine-phosphorylated EGFR and MET in a panel of human lung SCC tissues harboring DDR2 mutations. Our results highlight potential RTK-driven adaptive-resistant mechanisms upon DDR2 targeting, and they suggest new, rationale cotargeting strategies for DDR2-mutant lung SCC.
Restless Genital Syndrome in Parkinson Disease
Authors: Camila C. Aquino, Tiago Mestre, Anthony E. Lang
Journal: JAMA Neurology (2014)

Symptoms in the genital region, such as pain, discomfort, tingling, and burning sensations, have rarely been reported in Parkinson disease (PD), and the previous cases were attributed to nonmotor off symptoms. We report a patient with PD and severe genital discomfort unrelated to motor fluctuations but compatible with restless genital syndrome.A 65-year-old woman with PD experienced a disabling discomfort in her pelvis and genital region for 3 years. The episodes occurred in the evening and were triggered by sitting or lying down for a period. Gynecological investigation was unrevealing. She experienced improvement with a low dose of a dopamine agonist.Restless genital syndrome is a rare disorder that can be a source of distress and disability. In patients with PD, restless genital syndrome should be included in the differential diagnosis of genital symptoms and restlessness, along with nonmotor wearing off and akathisia. A detailed clinical history is essential for this diagnosis and treatment with dopamine agonists can provide benefit.
A receptor for the third component of complement in the human renal glomerulus
Authors: MC Gelfand, MM Frank, I Green
Journal: The Journal of Experimental Medicine (1975)

In the course of studying the nature of mononuclear cellular infiltrates in tissue sections of human kidney it was noted that indicator sheep erythrocytes densely coated with the third component of complement (C3) specifically adhered to all of the glomeruli in the tissue sections. The deposition of complement (C) within the glomerulus is a feature of many immunologically related renal diseases (1,2), yet the precise mechanism by which C is deposited remains unexplained. We feel that this observation, suggesting the presence of a receptor for C, is, therefore, of particular interest.
Outcome of assisted ventilation for acute respiratory failure in cystic fibrosis
Authors: Martijn G. Slieker, Josephus P. J. van Gestel, Harry G. M. Heijerman, Gerdien A. Tramper-Stranders, Ferdinand Teding van Berkhout, Cornelis K. van der Ent, Nicolaas J. G. Jansen
Journal: Intensive Care Medicine (2006)
Drug company accused of breaking advertising regulations
Authors: F. Waechter
Journal: BMJ (2003)

The Drug and Therapeutics Bulletin has accused the drug company Novartis of breaching advertising regulations in its advertisement for pimecrolimus, a new cream for treating dermatitis (2003;41(5):33-6).

A recent review by the bulletin resulted in three criticisms. The main concern was that while the licence limits the use to patients aged 2 years and older, the recent advertisement, published in many medical journals, shows a baby who looks younger than 2 years, implying that the cream could be used on babies below that age. The bulletin is consequently demanding that the drug's licence be withdrawn.

But a spokesman …
Interaction of histidine-rich glycoprotein with fibrinogen and fibrin.
Authors: L L Leung
Journal: Journal of Clinical Investigation (1986)

Histidine-rich glycoprotein (HRGP) is a human plasma and platelet protein of apparently diverse biological functions. In this study a new interaction for HRGP is described. HRGP specifically interacts with fibrinogen as demonstrated by two independent systems. Using an enzyme-linked immunosorbent assay it was demonstrated that HRGP bound to adsorbed fibrinogen in a concentration-dependent and saturable manner, with an apparent dissociation constant (Kd) of 6.7 nM. The binding was specific, reversible, and not mediated by a conformationally altered adsorbed fibrinogen molecule. The interaction was divalent cation-dependent and ionic in nature. The HRGP-fibrinogen interaction was also demonstrated using rocket immunoelectrophoresis. The HRGP-fibrinogen interaction had an effect on the kinetics of conversion of fibrinogen to fibrin as demonstrated by a prolongation of the thrombin time. HRGP also became incorporated into fibrin clots in a concentration-dependent and saturable manner, with an apparent Kd of 0.25 microM. The incorporation of HRGP into fibrin clots occurred in a plasma milieu as demonstrated by the direct incorporation of radiolabeled HRGP into plasma clots and by a significant decrease in serum HRGP levels as compared with plasma levels. HRGP prolonged the lag time phase of fibrin gel formation, and decreased the rate of turbidity rise, as well as the final absorbance of fibrin gels. Since the extent of fibrin polymerization was not influenced by the presence of HRGP, these data suggest that fibrin is distributed over more, but thinner, fibrils in the presence of HRGP. In addition to its potential effect on fibrin polymerization, the HRGP-fibrin interaction may play a role in the cell-cell interactions of platelets and macrophages.
White Coat Hypertension and Poor Sleep Quality
Authors: Zeynettin Kaya, Mehmet Kayrak, Kenan Demir, Mehmet Gündüz, Hayruddin Alibasiç, Mustafa Karanfil, Hakan Akıllı, Alpay Arıbaş, Abdullah İçli
Journal: Journal of the American College of Cardiology (2013)
The Effect of Ileostomy and Colectomy on the Personality Adjustment of Patients with Ulcerative Colitis
Authors: Benjamin V. White
Journal: New England Journal of Medicine (1951)

THE importance of psychiatric factors in ulcerative colitis is well recognized. Major contributions to our understanding have been made by Murray,1 , 2 Sullivan,3 4 5 Lindemann,6 Daniels7 , 8 and Kaufman.† Daniels has pointed out that the psychiatric aspect of the disease can most easily be comprehended through an understanding of three components: the personality make-up of the patient, environmental situations that appear to be related to exacerbations and the clinical picture, or mental status, observed during periods of severe illness. There is a remarkable unanimity of opinion on the part of psychiatrists that the personality make-up most often observed in ulcerative colitis is characterized . . .
microRNA-29 negatively regulates EMT regulator N-myc interactor in breast cancer
Authors: Jack W Rostas, Hawley C Pruitt, Brandon J Metge, Aparna Mitra, Sarah K Bailey, Sejong Bae, Karan P Singh, Daniel J Devine, Donna L Dyess, William O Richards, J Allan Tucker, Lalita A Shevde, Rajeev S Samant
Journal: Molecular Cancer (2014)

N-Myc Interactor is an inducible protein whose expression is compromised in advanced stage breast cancer. Downregulation of NMI, a gatekeeper of epithelial phenotype, in breast tumors promotes mesenchymal, invasive and metastatic phenotype of the cancer cells. Thus the mechanisms that regulate expression of NMI are of potential interest for understanding the etiology of breast tumor progression and metastasis. Web based prediction algorithms were used to identify miRNAs that potentially target the NMI transcript. Luciferase reporter assays and western blot analysis were used to confirm the ability of miR-29 to target NMI. Quantitive-RT-PCRs were used to examine levels of miR29 and NMI from cell line and patient specimen derived RNA. The functional impact of miR-29 on EMT phenotype was evaluated using transwell migration as well as monitoring 3D matrigel growth morphology. Anti-miRs were used to examine effects of reducing miR-29 levels from cells. Western blots were used to examine changes in GSK3β phosphorylation status. The impact on molecular attributes of EMT was evaluated using immunocytochemistry, qRT-PCRs as well as Western blot analyses. Invasive, mesenchymal-like breast cancer cell lines showed increased levels of miR-29. Introduction of miR-29 into breast cancer cells (with robust level of NMI) resulted in decreased NMI expression and increased invasion, whereas treatment of cells with high miR-29 and low NMI levels with miR-29 antagonists increased NMI expression and decreased invasion. Assessment of 2D and 3D growth morphologies revealed an EMT promoting effect of miR-29. Analysis of mRNA of NMI and miR-29 from patient derived breast cancer tumors showed a strong, inverse relationship between the expression of NMI and the miR-29. Our studies also revealed that in the absence of NMI, miR-29 expression is upregulated due to unrestricted Wnt/β-catenin signaling resulting from inactivation of GSK3β. Aberrant miR-29 expression may account for reduced NMI expression in breast tumors and mesenchymal phenotype of cancer cells that promotes invasive growth. Reduction in NMI levels has a feed-forward impact on miR-29 levels.