tbuckley/cabot-search huggingface dataset:
Expression of cyclin-dependent kinase inhibitor 2A 16, tumour protein 53 and epidermal growth factor receptor in salivary gland carcinomas is not associated with oncogenic virus infection
Authors: Ellen Senft, Juliana Lemound, Angelika Stucki-Koch, Nils-Claudius Gellrich, Hans Kreipe, Kais Hussein
Journal: International Journal of Oral Science (2014)

It is known that human papillomavirus (HPV) infection can cause squamous cell neoplasms at several sites, such as cervix uteri carcinoma and oral squamous carcinoma. There is little information on the expression of HPV and its predictive markers in tumours of the major and minor salivary glands of the head and neck. We therefore assessed oral salivary gland neoplasms to identify associations between HPV and infection-related epidermal growth factor receptor (EGFR), cyclin-dependent kinase inhibitor 2A (CDKN2A/p16) and tumour protein p53 (TP53). Formalin-fixed, paraffin-embedded tissue samples from oral salivary gland carcinomas (n=51) and benign tumours (n=26) were analysed by polymerase chain reaction (PCR) analysis for several HPV species, including high-risk types 16 and 18. Evaluation of EGFR, CDKN2A, TP53 and cytomegalovirus (CMV) was performed by immunohistochemistry. Epstein-Barr virus (EBV) was evaluated by EBV-encoded RNA in situ hybridisation. We demonstrated that salivary gland tumours are not associated with HPV infection. The expression of EGFR, CDKN2A and TP53 may be associated with tumour pathology but is not induced by HPV. CMV and EBV were not detectable. In contrast to oral squamous cell carcinomas, HPV, CMV and EBV infections are not associated with malignant or benign neoplastic lesions of the salivary glands.
Neurological complications of coronary artery bypass graft surgery.
Authors: D P Taggart, I J Reece
Journal: BMJ (1986)

normal latency pattern reversal response has been confirmed in an independent study by Danesi et al,S and we are surprised that Dr Wright and Mr Richardson did not quote this finding.Obviously it is always easy to obtain a response to flash stimulation in patients, but it is more difficult to obtain pattern reversal responses.However, in almost all the cases we have studied we have been able to obtain such a response as it is certainly the case that using a checkerboard stimulus which subtends a visual angle of 280 (with each check subtending a visual angle of 56') we rarely find that patients are incapable of cooperating to the extent that pattern visual evoked potentials are not obtainable.The few patients who have been unable to cooperate are itemised in our various publications.Dr Wright and Mr Richardson are correct in their theoretical assumption that a delayed flash with a normal pattern reversal response could be seen in any condition which affects the visual association areas with relative sparing of the primary visual cortex.We have recently discussed and produced a theoretical model.
Expiratory Airways Collapse
Authors: L. C. Lum
Journal: BMJ (1965)

The effects of changes in norepinephrine availability on alpha-1 adrenergic receptor density and responsiveness were determined in several regions of rat brain. Receptor density was determined from specific 125I-BE 2254 binding, and responsiveness was determined by norepinephrine-stimulated increases in inositol phosphate accumulation and in cyclic AMP accumulation in the absence or presence of adenosine in slices where beta adrenergic receptors had been inactivated. Adrenergic input was reduced by destroying noradrenergic neurons with DSP-4, depleting amines with chronic reserpine treatment or blocking alpha-1 adrenergic receptors with chronic prazosin treatment. All three treatments caused similar increases in alpha-1 adrenergic receptor density in cerebral cortex but not in striatum or hippocampus. DSP-4 treatment increased the maximal cyclic AMP response to both norepinephrine and phenylephrine but did not alter the maximal inositol phosphate response or the maximal potentiation of the cyclic AMP response to adenosine. DSP-4 treatment also increased the potency of norepinephrine in activating all three responses in cerebral cortex. Adrenergic input was increased by chronic treatment with desmethylimipramine to block norepinephrine reuptake, chronic i.c.v. infusion of norepinephrine or chronic yohimbine treatment to block presynaptic autoreceptors. None of these treatments caused significant changes in alpha-1 adrenergic receptor density or functional responsiveness in any region studied. The results suggest that alpha-1 adrenergic receptor density and responsiveness in rat brain can be increased but not easily decreased. They also suggest that different brain regions are affected differently by alterations of adrenergic input and that the different responses are not coregulated.
Diabetes Mellitus and Pregnancy
Authors: C. E. Woodrow
Journal: BMJ (1942)

The following case report illustrates some of the interesting changes that take place in the carbohydrate tolerance of the mother during pregnancy, and stresses the consequent necessity for careful and continuous control during this period to avoid the dangers of acidosis and to correct depletion of the glycogen stores due to any toxaemia which may arise.Since the introduction of insulin the maternal death rate in diabetics has greatly decreased.A survey of the literature shows that in pre-insulin days the immediate mortality rate was as high as 30%, and rose to something approaching 50% about two years after delivery.The average figure for immediate mortality, with control with insulin, is now 5 %, but this is still considered to be at least 6 times greater than for non-diabetic women.These somewhat favourable statistics have been obtained from series in which special care has been exercised, so it is probable that the dice are still very much loaded against the diabetic pregnant woman.The foetal mor- tality rate still remains very high, and, according to many observers, pre-partum, intra-partum, and post-partum deaths of infants born of diabetic women still continue at approximately 40%.Any method which might reduce this high death rate is worthy of trial, and for this reason early Caesarean section, followed by specialized care of the infant after delivery to prevent hypoglycaemia, as advo- cated by Prof. Wilder of the Mayo Clinic, was tried in the present case with a successful result.One case is of
Mechanisms and Management of Toxicities Associated With High-Dose Interferon Alfa-2b Therapy
Authors: John M. Kirkwood, Catherine Bender, Sanjiv Agarwala, Ahmad Tarhini, Janice Shipe-Spotloe, Barbara Smelko, Sandra Donnelly, Lori Stover
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The toxicity associated with adjuvant high-dose interferon-alfa-2b therapy (HDI) for high-risk melanoma can lead to premature discontinuation. It is important to understand the expected adverse events and their underlying mechanisms and to anticipate and aggressively manage toxicity during treatment in order to ensure that patients receive the maximum therapeutic benefit. METHODS: The toxicity profile of HDI was reviewed by examining data from the United States cooperative group trials. Available published data related to the potential mechanisms responsible for the observed adverse events are discussed, and comprehensive recommendations for managing side effects are presented. RESULTS: The HDI regimen is associated with acute constitutional symptoms, chronic fatigue, myelosuppression, elevated liver enzyme levels, and neurologic symptoms. The majority of patients tolerate 1 year of therapy with an understanding of the anticipated toxicities in conjunction with appropriate dose modifications and supportive care. Ongoing monitoring for liver dysfunction and hematologic toxicity is critical to ensure safety. Many of the toxicities associated with interferon-alfa (IFN-α) seem to be the result of endogenous cytokines and their effects on the neuroendocrine system. Recent data have also demonstrated that IFN-α suppresses the activity of specific CYP450 isoenzymes and that this correlates with discrete toxicities. Pharmacologic interventions are under study for fatigue and depression. An increased understanding of the mechanisms of IFN-α–associated toxicity will lead to more rational and effective supportive care and improved quality of life. CONCLUSION: Continued research in this area should lead to improvements in the safety and tolerability of adjuvant therapy for melanoma.
Adenosine 3', 5'-Monophosphate-Dependent Membrane Phosphorylation
Authors: PAUL J. LARAIA, EUGENE MORKIN
Journal: Circulation Research (1974)

The role of cyclic adenosine 3', 5'-monophosphate (AMP) in the control of microsomal calcium ion (Ca 2+ ) transport was studied in microsomes prepared from rabbit heart. These cardiac microsomes contained intrinsic cyclic AMP-dependent protein kinase activity that phosphorylated serine residues in a microsomal protein component with a molecular weight of about 20,000 (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Intrinsic phosphoprotein phosphatase activity of the microsomal membranes resulted in rapid dephosphorylation of these residues. Microsomes phosphorylated in the presence of 1 x 10 -6 M cyclic AMP exhibited enhanced Ca 2+ uptake. We conclude that reversible phosphorylation of microsomal membranes may be an important mechanism for regulation of microsomal Ca 2+ transport by cyclic AMP.
The future of drug development: advancing clinical trial design
Authors: John Orloff, Frank Douglas, Jose Pinheiro, Susan Levinson, Michael Branson, Pravin Chaturvedi, Ene Ette, Paul Gallo, Gigi Hirsch, Cyrus Mehta, Nitin Patel, Sameer Sabir, Stacy Springs, Donald Stanski, Matthias R. Evers, Edd Fleming, Navjot Singh, Tony Tramontin, Howard Golub
Journal: Nature Reviews Drug Discovery (2009)
Isolated Impaired Fasting Glucose and Peripheral Insulin Sensitivity
Authors: Sun H. Kim, Gerald M. Reaven
Journal: Diabetes Care (2008)

OBJECTIVE—In a recent consensus statement, the American Diabetes Association (ADA) concluded that individuals with impaired fasting glucose (IFG) have “normal muscle insulin sensitivity.” To subject this conclusion to further validation, we evaluated the relationship between glucose tolerance categories and peripheral insulin sensitivity in a large nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was directly quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 446 nondiabetic individuals divided into four groups: normal glucose tolerance (NGT, n = 318), isolated IFG (n = 63), isolated impaired glucose tolerance (IGT, n = 33), and combined IFG and IGT (IFG/IGT, n = 32). RESULTS—Insulin sensitivity was significantly different in all three groups with pre-diabetes (IFG, IGT, IFG/IGT) as compared with NGT (P &amp;lt; 0.05). Using tertiles of SSPG concentration in the NGT group as operational definitions of insulin resistance (highest tertile) and insulin sensitivity (lowest tertile), there was considerable heterogeneity within the pre-diabetic groups. Thus, 57% of IFG individuals were insulin resistant, and 13% were insulin sensitive. The IFG/IGT group was most homogeneous, with 94% classified as insulin resistant and only 3% as insulin sensitive. CONCLUSIONS—Peripheral insulin sensitivity varies considerably in nondiabetic individuals, with IFG individuals showing the most heterogeneity within the pre-diabetes group. We believe that this heterogeneity in insulin sensitivity, and the relatively few patients in whom insulin sensitivity has been measured directly in the past, explain the discrepancy between our findings and those of the recent ADA consensus statement.
Inherited HFE-unrelated hemochromatosis in italian families
Authors: Clara Camaschella, Silvia Fargion, Maurizio Sampietro, Antonella Roetto, Sandra Bosio, Giovanni Garozzo, Cristina Arosio, Alberto Piperno
Journal: Hepatology (1999)

Hemochromatosis (HH) is usually caused by the homozygous state for C282Y mutation in the HFE gene. A minority of iron loaded patients have no mutations in this gene. An infrequent subset shows an early–onset aggressive disorder, denoted juvenile hemochromatosis (JH), which has no linkage to 6p. In this report we describe six patients from three unrelated Italian families, four men and two women, aged 21 to 44 with the typical hemochromatosis phenotype, who are homozygous for the wild type allele at the HFE gene. In two families the disorder is unlinked to 6p; in one family some features of the juvenile form are seen, but linkage to 6p is not excluded. Our results point to genetic forms of hemochromatosis not associated with HFE and raise the problem of whether non–HFE hemochromatosis in Italy is related to the “juvenile” form. They also emphasize the importance of phenotypic as well as genetic diagnosis of HH.
The Influence of the Pulmonary Arterial Pressure on the Pulmonary Capillary Venous Pressure in Man
Authors: LARS WERKÖ, E. VARNAUSKAS, H. ELIASCH, B. THOMASSON
Journal: Circulation Research (1953)

In two cases with a well-defined pulmonary capillary venous pressure pulse, the lobular pulmonary artery was occluded with a balloon while the pulmonary capillary venous pressure was registered. There was no change in the tracing obtained. In two other cases positive pressure respiration almost completely damped out the pulmonary capillary venous pressure variations, but the mean pressure remained virtually unchanged. It is concluded that the pulmonary arterial pulse wave usually does not cause artefacts in the pulmonary capillary venous tracing. Cyclic changes in pulmonary capillary venous pressure cannot be studied while the subject is on positive pressure respiration.
Understanding Cancer Clusters
Authors: M. J. Thun, T. Sinks
Journal: CA A Cancer Journal for Clinicians (2004)

Each year, state and local health departments respond to more than 1,000 inquiries about suspected cancer clusters. Three quarters of these reports involve situations that are clearly not clusters and can be resolved by telephone. For the remainder, follow-up is needed, first to confirm the number of persons affected, their age, type of cancer, dates of diagnosis, and other factors, and then to compare cancer incidence in the affected population with background rates in state tumor registries. In approximately 5% to 15% of the reported situations, formal statistical testing confirms that the number of observed cases exceeds the number expected in a specific area, given the age, sex, and size of the affected population. Even in these instances, however, chance remains a plausible explanation for many clusters, and further epidemiologic investigation almost never identifies the underlying cause of disease with confidence. The few exceptions have involved clusters of extremely rare cancers occurring in well-defined occupational or medical settings, generally involving intense and sustained exposure to an unusual chemical, occupation, infection, or drug. This article discusses the resources and scientific tools currently available to investigate cancer clusters. It also provides a framework for understanding cancer clusters and a realistic appraisal of what cluster investigations can and cannot provide in the context of community expectations.
Increased Second Trimester Maternal Glucose Levels Are Related to Extremely Large-for-Gestational-Age Infants in Women With Type 1 Diabetes
Authors: A. Kerssen, H. W. de Valk, G. H.A. Visser
Journal: Diabetes Care (2007)

OBJECTIVE—Large-for-gestational-age (LGA) infants (birth weight ≥90th centile) are a continuing problem in pregnancies of women with type 1 diabetes. We used the continuous glucose monitoring system (CGMS) to assess the relationship between 24-h diurnal glucose profiles in all three trimesters of pregnancy and infant birth weight.
Is There a Systemic Inflammatory Response in the Acute Charcot Foot?
Authors: Nina L. Petrova, Caje Moniz, David A. Elias, Muriel Buxton-Thomas, Maureen Bates, Michael E. Edmonds
Journal: Diabetes Care (2007)

Although patients with acute Charcot osteoarthropathy exhibit a marked local inflammatory response to trauma by the classical presentation of a red, hot swollen foot, the systemic acute phase response has not been fully investigated. The aim of this study was to measure the systemic serologic markers of inflammation in acute Charcot osteoarthropathy.

We studied 36 consecutive patients who presented to the Diabetic Foot Clinic over the last 5 years with a red, hot swollen foot and a skin temperature >2°C compared with the same site on the contralateral foot and who had no previous treatment. There was no evidence of any skin breakdown or ulceration. Foot skin temperatures were measured by Dermatemp 1001 (Exergen, Watertown, MA). The diagnosis of Charcot osteoarthropathy was confirmed in 25 cases by evidence of subluxation, dislocation, or fragmentation of bone on standard foot radiographs and in 11 cases by the presence of an increased focal uptake on the bony (third) phase of the triphasic Technetium-Diphosphonate bone scan (Tyco Healthcare) even though the radiographs at presentation were normal. In the patients with radiological abnormalities, the patterns of involvement were described using Sanders and Frykberg's classification (1). Four patients presented with pattern I …
New European Union regulation of clinical trials puts trial participants at risk
Authors: J. Hasford
Journal: BMJ (2013)

Gotzsche did not mention that the new European Union regulation of clinical trials has serious deficiencies from an ethical and trial participant’s point of view.1

The EU Commission’s proposal is fundamentally different from the current EU directive: a comprehensive and independent consideration and vote by a multidisciplinary independent ethics committee are no longer required. This violates international guidelines and ethical codes, such …
Role of the RNA-binding Protein HuR in Posttranscriptional Regulation of IL-13 in T Cells
Authors: C. Stellato, X. Fang, B. Tancowny, J. Fan, F. Wu, S.Y. Asaki, U. De Fanis, S. Huang, M. Gorospe, U. Atasoy, V. Casolaro
Journal: Journal of Allergy and Clinical Immunology (2007)
682 Ae2a,b-DEFICIENT MICE DEVELOP ANTIMITOCHONDRIAL ANTIBODIES AND OTHER FEATURES RESEMBLING PRIMARY BILIARY CIRRHOSIS
Authors: J.T. Salas, J.M. Banales, S. Sarvide, S. Recalde, A. Ferrer, I. Uriarte, R.P.J. Oude Elferink, J. Prieto, J.F. Medina
Journal: Journal of Hepatology (2009)
Lymphatic vessels clean up your arteries
Authors: Carlos Fernández-Hernando
Journal: Journal of Clinical Investigation (2013)

Reverse cholesterol transport (RCT) is the pathway by which cholesterol accumulated in peripheral tissues, including the artery wall, is transported to the liver for excretion. There is strong evidence suggesting that interventions that increase macrophage cholesterol efflux and RCT would be antiatherogenic. In this issue of the JCI, Martel et al. investigate the contribution of lymphatic vasculature to RCT. Their results support the concept that the lymphatic vessel route is critical for RCT from atherosclerotic plaques. Therefore, strategies to improve lymphatic transport might be useful for treating atherosclerotic vascular disease.
Role of Blood Pressure in the Development of Congestive Heart Failure
Authors: William B. Kannel, William P. Castelli, Patricia M. McNamara, Patrick A. McKee, Manning Feinleib
Journal: New England Journal of Medicine (1972)

A representative population sample of 5192 men and women was followed for 16 years, during which overt congestive heart failure (CHF) developed in 142. In the age range from 30 to 62 years the dominant etiologic precursor was hypertension, which preceded CHF in 75 per cent of the cases. Six times more CHF developed in hypertensive than in normotensive persons. Examination of the association of myocardial hypertrophy on x-ray or electrocardiographic study with systolic versus diastolic pressure revealed little to suggest a greater role for diastolic pressure. Systolic and diastolic pressure together, mean arterial pressure, pulse pressure, and tension-time index discriminated potential hypertrophy and CHF no better than systolic pressure alone. Examination of the correlation of heart weight and left ventricular thickness at autopsy with premorbid systolic versus diastolic pressure revealed a better correlation with systolic than with diastolic pressure. CHF was a lethal phenomenon, with only 50 per cent surviving for five years. Early, vigorous and sustained control of elevated blood pressure — systolic as well as diastolic — appears the chief means for preventing CHF in the general population.
X Rays in the Treatment of Graves's Disease
Authors: G. Cooper
Journal: BMJ (1933)

<h3>Abstract</h3> Super-resolution chromatin imaging techniques are emerging as powerful tools for spatial genomics. However, it remains challenging to visualize the genome on the order of tens of nanometers, a scale that can reveal rich structural detail about the nuclear organization. Here we introduce Decode-PAINT, a multiplexed in situ method, which leverages rapid diffraction-limited pre-decoding and DNA-PAINT (DNA points accumulation for imaging nanoscale topography). Decode-PAINT visualizes multiple discrete genomic regions at a resolution close to the nucleosome scale with a simple and easy-to-implement optical setup, reduces total imaging time by omitting multiple rounds of single-molecule recording, and enables the interrogation of the ultrastructure of the targets with &lt;12 nm lateral and &lt;20 nm axial resolution. We showcase the ability of our approach to perform multiplexed, high-resolution profiling of chromatin structure by performing targeted imaging of nine regions of active and inactive X chromosomes in individual cells. In short, Decode-PAINT accelerates in situ structural genomics.
Do sex and site matter? Different age distribution in melanoma of the trunk among Swedish men and women
Authors: B. Pérez-Gómez, N. Aragonés, P. Gustavsson, V. Lope, G. López-Abente, M. Pollán
Journal: British Journal of Dermatology (2008)

Recent research on cutaneous malignant melanoma (CMM) points to the coexistence of several biological pathways linked to the anatomical site of the lesion, which could lead to this neoplasm. Although the different anatomical distribution of CMM by sex is usually attributed to gender-specific patterns of sun exposure, it has been suggested that an alternative explanation might lie in gender-specific site susceptibility.This paper aimed at analysing the age distribution of CMM by site and sex to gain in-depth knowledge of differences between the sexes.Using a large Swedish cohort comprising 2 992 166 workers, Poisson models were fitted to estimate age-specific incidence rates by site and sex, duly adjusted for several factors that might account for changes in environmental exposures (period, birth cohort, socioeconomic level, latitude and rurality).Incidence rates were 17.4 cases per 100 000 person-years in men and 16.5 in women. Sex differences were particularly striking for CMM of the trunk, where both crude and adjusted incidence rates displayed a steady increase with age in men, but reached a plateau in women at around four cases per 100 000 person-years from the 40-45-year age group (perimenopausal period) upwards. There was an almost fivefold increase in the sex ratio for this body site between the younger and older age groups, a difference which could not be attributed to period or cohort effects.If different aetiological pathways can be assumed to lead to melanoma, then disparities between men and women, particularly in CMM of the trunk, suggest that a possible interaction between site and sex should be borne in mind.