tbuckley/cabot-search huggingface dataset:
Probucol inhibits oxidative modification of low density lipoprotein.
Authors: S Parthasarathy, S G Young, J L Witztum, R C Pittman, D Steinberg
Journal: Journal of Clinical Investigation (1986)

Previous studies have established that low density lipoprotein (LDL) incubated with endothelial cells (EC) undergoes extensive oxidative modification in structure and that the modified LDL is specifically recognized by the acetyl LDL receptor of the macrophage. Thus, in principle, EC-modified LDL could contribute to foam cell formation during atherogenesis. Oxidatively modified LDL is also potentially toxic to EC. The present studies show that addition of probucol during the incubation of LDL with EC prevents the increase in the electrophoretic mobility, the increase in peroxides, and the increase in subsequent susceptibility to macrophage degradation. It has also been shown that oxidation of LDL catalyzed by cupric ion induces many of the same changes occurring during EC modification. Addition of probucol (5 microM) also prevented this copper-catalyzed modification of LDL. Most importantly, samples of LDL isolated from plasma of hypercholesterolemic patients under treatment with conventional dosages of probucol were shown to be highly resistant to oxidative modification either by incubation with endothelial cells or by cupric ion in the absence of cells. The findings suggest the hypothetical but intriguing possibility that probucol, in addition to its recognized effects on plasma LDL levels, may inhibit atherogenesis by limiting oxidative LDL modification and thus foam cell formation and/or EC injury. Other compounds with antioxidant properties might behave similarly.
Single-Cell Storm
Authors: Susan Okie
Journal: New England Journal of Medicine (2006)

Scientists at Advanced Cell Technology, a California company, reported in August that a single cell taken from an eight-cell human embryo can sometimes be coaxed to produce embryonic stem cells, suggesting that such "biopsies" might be a way to generate new stem-cell lines while preserving embryos.The report, published online by the journal Nature, 1 stirred up considerable controversy, in part because both the journal's initial press release and a podcast interview with senior author Robert Lanza gave the impression that two new lines had been created without destroying any embryos. "What we have done, for the first time, is to . . .
Abstract 5030: Mechanistic insight of differential sensitivity to MEK inhibition
Authors: Zhenyu Ji, Ching-Ni Njauw, Hensin Tsao
Journal: Cancer Research (2010)

Abstract BRAF is mutated in melanomas and plays a role in tumorigenesis. Although depletion of oncogenic BRAF resulted in tumor regression in mouse melanoma model, clinical development of anti-BRAF signaling therapy has not been successful up to date. We performed a search of genomic alterations that are correlated to sensitivity to MEK inhibitors using human melanoma cell lines. Multiple genetic changes are identified to be of predictive value. Based on our genetic analysis, p53 is identified to be a major factor that controls sensitivity to MEK inhibitors. p53 is a major tumor suppressor and is mutated in a small set of human melanomas. Here, we show that p53 is inducible in most human melanoma cell lines in response to DNA damage. MDM2 inhibitor Nutlin-3a increases p53 protein expression as well as its activities in melanoma cells. Addition of nutlin-3a significantly increases sensitivity of melanoma cells to MEK inhibitor U0126 induced cell death or cell cycle arrest. In addition, knockdown p53 by specific shRNAs effectively rescues apoptosis induced by MEK inhibitor and/or p53 activation. This data suggests that p53 activity is required for cell death induced by MEK inhibitors and/or p53 activators. In conclusion, p53 is identified from a genetic screen for MEK inhibitor sensitivity. p53 reactivation potentiates cell death induced by BRAF/MEK signaling inhibitory agents in a group of melanomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5030.
Infant immunization surveillance: cost vs effect. A prospective, controlled evaluation of a large-scale program in Rhode Island
Authors: E. B. Byrne
Journal: JAMA (1970)

A controlled prospective study of an infant immunization surveillance program in Rhode Island demonstrated significant motivational effects of the program on parents of newborn infants. Immunizations were initiated more often at the earliest appropriate age and higher overall levels of immunization with certain vaccines were obtained in the portion of the population subjected to the program than among controls. The effect was most pronounced in the lowest social class and diminished successively with increasing social rank. Costs were estimated to be $42 per additional child immunized. Strengths and weaknesses revealed by the study suggest that costs could be further reduced by nearly one third with but minor changes in the program, and without diminishing its effectiveness.
Glycemic Control Is Related to the Morphological Severity of Diabetic Sensorimotor Polyneuropathy
Authors: Bruce A. Perkins, Douglas A. Greene, Vera Bril
Journal: Diabetes Care (2001)

The aim of the current study was to determine the independent clinical risk factors for predicting morphological severity of distal diabetic sensorimotor polynecuropathy (DSP) as determined by fiber density (FD) on sural nerve biopsy.A total of 89 patients with both type 1 and type 2 diabetes, ascertained from a large therapeutic randomized clinical trial, were included in this observational cohort study. Morphological severity of DSP was expressed as the myelinated FD in the sural nerve biopsy General linear models were used to assess the relationship between the morphological severity of DSP and various clinical risk factors.Glycated hemoglobin (GHb) was significantly related to FD in univariate and multivariate regression analyses. This relationship was present in models in which GHb was handled either as a continuous variable or as a categorical variable with the highest significance level, with a GHb cutoff level of 9%. After dividing patients into groups with optimal to moderate GHb < or = 9%) and suboptimal (GHb >9%) glycemic control, the difference in FD between the two groups ranged between 3,461 and 2,334 per mm2. FD was also significantly related to duration of diabetes and age of the patient.The severity of peripheral DSP expressed by morphological criteria was significantly related to glycemic control in type 1 and type 2 diabetic patients. Inconsistent with previously published electrophysiological data demonstrating a correlation between height and conduction velocity, increasing height is not associated with morphological severity. Based on the results of the present study, it might be hypothesized that improving glycemic control will lessen severity of DSP in terms of FD loss in subjects with diabetes.
Toll-Like Receptor 4 Is Involved in Brain Damage and Inflammation After Experimental Stroke
Authors: Javier R. Caso, Jesús M. Pradillo, Olivia Hurtado, Pedro Lorenzo, María A. Moro, Ignacio Lizasoain
Journal: Circulation (2007)

Background— Stroke is the second to third leading cause of death. Toll-like receptor 4 (TLR4) is a signaling receptor in innate immunity that is a specific immunologic response to systemic bacterial infection and cerebral injury. The role of TLR4 in brain ischemia has not been examined yet. We have therefore investigated whether cerebral ischemia and inflammation produced by permanent occlusion of the middle cerebral artery differ in mice that lack a functional TLR4 signaling pathway. Methods and Results— Permanent occlusion of the middle cerebral artery was performed on 2 strains of TLR4-deficient mice (C3H/HeJ and C57BL/10ScNJ) and respective controls (C3H/HeN and C57BL/10ScSn). Stroke outcome was evaluated by determination of infarct volume and assessment of neurological scores. Brains were collected 24 hours and 7 days after stroke. When compared with control mice, TLR4-deficient mice had lower infarct volumes and better outcomes in neurological and behavioral tests. Mice that lacked TLR4 had minor expression of stroke-induced interferon regulatory factor-1, inducible nitric oxide synthase, and cyclooxygenase-2, mediators implicated in brain damage. The levels of interferon-β and of the lipid peroxidation marker malondialdehyde were also lower in brains from TLR4-deficient mice than in those from control mice. In addition, the expression of matrix metalloproteinase-9, which is induced and mediates brain damage, was also reduced in TLR4-deficient mice after experimental stroke. Conclusions— TLR4-deficient mice have minor infarctions and less inflammatory response after an ischemic insult. These data demonstrate that TLR4 signaling and innate immunity are involved in brain damage and in inflammation triggered by ischemic injury.
Genetic analysis of C4 deficiency.
Authors: Z L Awdeh, H D Ochs, C A Alper
Journal: Journal of Clinical Investigation (1981)

The inherited structural polymorphism in the fourth component of complement was studied in the family of a child with homozygous deficiency of this protein. It was shown that a number of family members, including the child's parents, carried a C4 haplotype, C4A*QO C4B*QO, that produced no detectable protein at either the Chido (C4B) or Rodgers (C4A) locus. The family contained individuals with one, two, three, or four expressed C4 genes, and the mean serum C4 levels in such individuals roughly reflected the number of structural genes.
Treatment of hypertension with nifedipine, a calcium antagonistic agent.
Authors: M T Olivari, C Bartorelli, A Polese, C Fiorentini, P Moruzzi, M D Guazzi
Journal: Circulation (1979)

Hemodynamic monitoring after a single dose (10 mg) of nifedipine in 27 primary hypertensive subjects (diastolic pressure greater than 110 mm Hg) documented that this calcium antagonistic agent exerts a potent arteriolar vasodilating action, which results in prompt (-21% of control at 30 minutes) and persistent (-16% of control at 120 minutes) fall in mean arterial pressure associated with a rise in cardiac output and pulse rate. The same patients received oral treatment for 3 weeks. Hourly pressure readings showed that 1) the antihypertensive response to each dose lasts 8--12 hours; and 2) nifedipine every 6 hours significantly reduced blood pressure throughout the 24 hours, without postural hypotension. Side effect were short-lasting (headache in five patients, palpitation without arrhythmias in eight patients, burning sensation in the face and legs in five patients and sporadic extrasystoles in five patients) and tended to disappear with continued treatment. Development of drug resistance, sodium retention, plasma volume expansion, renin release or angina pectoris were not observed during the study. Although these findings seem to differentiate nifedipine from other vasodilators currently used in the treatment of hypertension, broader experience and more prolonged trials with nifedipine as an antihypertensive agent will be needed before conclusions can be drawn on these particular aspects.
Circulating Endothelin-1 Levels Increase During Euglycemic, Hyperinsulinemic Clamp in Lean NIDDM Men
Authors: Claudio Ferri, Antonio Carlomagno, Simonetta Coassin, Roberta Baldoncini, Maria R Cassone Faldetta, Oriana Laurenti, Giuliana Properzi, Anna Santucci, Giancarlo De Mattia
Journal: Diabetes Care (1995)

OBJECTIVE To evaluate whether or not insulin stimulates endothelin (ET)-l secretion in vivo. RESEARCH DESIGN AND METHODS Plasma ET-1 levels were evaluated in 16 lean normotensive men with non-insulin-dependent diabetes mellitus (NIDDM) (mean age 50.3 ±4.1 years) during either a 2-h euglycemic hyperinsulinemic clamp (40 mU insulin · m−2 · min−1) or placebo infusion (50 ml isotonic saline) according to a single-blind randomized crossover protocol. RESULTS Circulating ET-1 levels increased during the euglycemic hyperinsulinemic clamp (from 0.88 ± 0.38 pg/ml at time 0 to 1.66 ± 0.22 pg/ml and 1.89 ± 0.99 pg/ml at 60 and 120 min, respectively [P &amp;lt; 0.05 vs. time 0]) and returned to baseline levels after the discontinuation of insulin infusion (0.71 ± 0.22 pg/ml after a 30-min period of recovery [NS]). Compared with placebo, the euglycemic hyperinsulinemic clamp induced a significant increase in plasma ET-1 levels at 60 min (P &amp;lt; 0.0001) and 120 min (P &amp;lt; 0.0001). Changes in basal insulin levels and corresponding changes in circulating ET-1 levels after a 2-h euglycemic hyperinsulinemic clamp were significantly correlated (r = 0.771, P &amp;lt; 0.0001). A possible unfavorable effect of ET-1 on the tissue sensitivity to insulin-stimulated glucose uptake was suggested by the presence of a negative correlation between total glucose uptake and baseline ET-1 levels (r = –0.498, P &amp;lt; 0.05). CONCLUSIONS Our findings indicate that circulating ET-1 levels significantly increase during euglycemic hyperinsulinemic clamp in men with NIDDM. The negative correlation between total glucose uptake and circulating ET-1 levels suggests that the peptide might exert negative effects on the insulin sensitivity of target tissues. The consequent increase in insulin secretion as well as the insulin-related ET-1 release from endothelial cells could favor the development of diabetes-related vascular lesions.
Pneumoperitoneum in CAPD peritonitis
Authors: R N Saunders, P S Veitch, M L Nicholson
Journal: Journal of the Royal Society of Medicine (2003)

In continuous ambulatory peritoneal dialysis (CAPD) the CAPD tube provides a portal of entry for both microorganisms and air into the peritoneal cavity. Bacterial/fungal colonization of the fluid, with abdominal symptoms and systemic upset, will usually settle with conservative measures1 but the presence of a pneumoperitoneum may or may not signify gastrointestinal perforation.
Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome
Authors: J. Ritchie
Journal: Gut (1973)

The effects of inflating a balloon introduced through a sigmoidoscope to 35 cm in the pelvic colon have been observed and compared in 67 patients with the irritable colon syndrome and in 16 normal and constipated subjects acting as controls. Inflation to 60 ml caused pain in 6% of the controls at a mean diameter of 3.8 cm and in 55% of patients with the irritable colon syndrome (diameter 3.4 cm). An estimate of gut wall tension at this volume of inflation showed it to be normal in patients with the irritable colon syndrome; the incidence of pain in relation to wall tension was increased nearly tenfold in the irritable colon group. Inflation of the balloon to different volumes was normally painless to a maximum acceptable diameter which remained constant for each study under constant conditions; continued inflation eventually gave rise to pain without increasing the diameter. The pain was felt in the hypogastrium in 40%, in one or both iliac fossae in 31%, and in the rectum in 21%; the other 8% felt pain in the back or elsewhere and there were no significant differences between clinical groups. Exceptionally, in 6% of the controls, and in 52% of patients with the irritable colon syndrome, pain occurred at balloon diameters that could still be increased by 10% or more with further inflation. This was probably the outcome of a low threshold for visceral pain in the section of bowel in contact with the balloon. Colonic hyperalgesia of this kind, possibly a random occurrence, may be an important contributory factor in the aetiology of the irritable colon syndrome.
Osteoporosis and cystic fibrosis.
Authors: T C Stamp, D M Geddes
Journal: Thorax (1993)

Editorials Osteoporosis and cystic fibrosisIn the past, cystic fibrosis was a disease of children with a high early mortality resulting predominantly from lung infection.The pulmonary disease therefore took the cen- tre of the stage in terms of treatment and investigations.Now that people with cystic fibrosis are living so much longer, more attention needs to be given to the other organs which may be directly or secondarily affected by the disease.Diabetes occurs in 10% or more, and while it used to be thought that this was relatively mild without vascular complications, evidence to the contrary is begin- ning to accumulate.Similarly, liver disease has been clin- ically important in only a small minority, but hepatic complications may progress and become increasingly important in the third and fourth decades.Dietary prob- lems were commonplace in the early days of cystic fibrosis, but have improved for two reasons.In the first place dietary advice has radically altered from low to high fat with high caloric energy-as much as 150% of usual requirements-and this approach has been helped by the development of much more effective pancreatic replacement therapy.Secondly, vitamin supplements have become a routine part of the management of cystic fibro- sis and so specific vitamin deficiencies are no longer seen.The report of osteoporosis in this issue of Thorax is therefore particularly important as it draws attention to a pre- viously unrecognised problem that may be quite common and may increase as patients survive longer.In the pathogenesis of osteoporosis, the peak bone density reached at maturity is as important as the ulti- mate bone loss, and it has recently been restated that "senile osteoporosis is a paediatric disease."'The age at which peak bone density occurs is undefined, but it is probably reached by the end of the second decade.In cystic fibrosis Grey and colleagues (p 589) have shown clearly that the skeletons of young adults with an average age of 23 years are significantly compromised in this respect.Patients had a mean bone mineral deficit of 7-13% depending on the bones measured.How compar- atively severe is this?Many studies indicate that, at the menopause when bone mineral density (BMD) closely approximates peak values, two standard deviations (SD) span 20% of BMD above and below the mean.2In nor- mal subjects each SD below average more than doubles
The Renaissance; six essays
Authors: Lester S. King
Journal: JAMA (1963)

The physician who wants to know about his heritage will naturally turn to that steadily growing literature which is labeled "medical history." He may, however, quite properly raise the question, what are the limits of this subject matter? What may properly be included in the area of medical history? The textbooks usually intertwine bare chronicles of major events with biographical and doctrinal data of the great physicians. Such books indicate the major medical figures and major medical doctrines, but the background information may be extraordinarily slight. The reader may be left rather frustrated, with a large number of facts but no adequate framework in which to place them, no adequate concepts with which to interpret and evaluate the medical information. But we also have that vague category which is often called "collateral reading"—the delight of college professors assigning term papers—which will furnish the background. While in a sense almost everything
929. CD9 Gene Therapy Inhibits Cardiac Hypertrophy and Tachycardia, and Attenuates the Remodeling after Myocardial Infarction in Mice
Authors: Hiroaki Ushikoshi, Tomoyuki Takahashi, Genzou Takemura, Yuwen Li, Masayasu Esaki, Ngin Cin Khai, Takao Kawai, Shinya Minatoguchi, Takako Fujiwara, Hisayoshi Fujiwara, Ken-ichiro Kosai
Journal: Molecular Therapy (2005)

Backgrounds: Cardiac hypertrophy is an adaptive response of the injured heart, but usually results in heart failure and sudden death. Tachycardia is accompanied with various cardiovascular diseases and is a cause of sudden death. Although many studies of cardiac gene therapy were previously reported, none of them directly targeted cardiac hypertrophy nor tachycardia, and therapeutic genes used in them mainly targeted to enhance the angiogenesis rather than to directly modulate pathologic conditions of cardiomyocytes. On the other hand, a definitive biological function of CD9, a member of transmembrane 4 superfamily, remains elusive although its multifunctional characteristics have been reported; knockout mouse studies by us and others solely revealed the crucial role of CD9 in gamete membrane fusion (Science 287, 321-324; 2000). Here we present a novel biological function of CD9, by which we develop an innovative cardiac gene therapy.
METHODS, VALUE AND LIMITATIONS OF THE KNOWLEDGE OF THE GASTRIC CONTENTS.
Authors: GEORGE DOCK
Journal: JAMA (1905)

I think it will be admitted that instrumental and laboratory examinations with reference to the stomach are unduly neglected in practice. The reasons for this are similar to those that cause the neglect of other diagnostic manipulations—technical difficulties, real and imaginary, and erroneous views as to clinical value. Many fail to make examinations of stomach contents solely because they think the passage of the stomach tube is difficult and often objected to by the patieut. Contrary to this view, I find very few people who require any persuasion and still fewer who offer serious verbal or physical difficulty. Out of many thousands examined, I have encountered only two people in whom I could not successfully use the stomach tube at the first trial. I am not considering, of course, the very important contraindications to the use of the tube (necessary to remember in every case), or real obstructions to the
Hyperkalemia in patients infected with the human immunodeficiency virus: Involvement of a systemic mechanism
Authors: Carlos Caramelo, Elena Bello, Elisa Ruiz, Adela Rovira, Rosa M. Gazapo, Jose M. Alcazar, Nieves Martell, Luis M. Ruilope, Santos Casado, Manuel Fernández Guerrero
Journal: Kidney International (1999)
Diseases of the Breast
Authors: Benjamin F. Rush
Journal: JAMA (1971)

Fifteen years have elapsed since first publication of this volume. The first edition, rich in detail and scholarship, was judged the classic in its field; this work has maintained the same standard. Extensively rewritten, expanded, and updated, the new edition has a larger page size and 78 pages have been added. Organization of the subject includes an initial 3 chapters on normal and abnormal anatomy and physiology, followed by 3 chapters on diagnosis, 14 on various aspects of benign and malignant lesions other than adenocarcinoma, 14 on the various lesions of adenocarcinoma, and 5 on treatment. Everything one could possibly wish to know concerning the breast seems to be covered. Much of the work bears the authority of Haagensen's 40 years of experience at Columbia-Presbyterian Medical Center where he specialized in disease of the breast. The chapter on selection of patients for operation describes many criteria which he introduced and
Abnormal Distribution and Hyperplasia of Thyroid C-Cells in PTEN-Associated Tumor Syndromes
Authors: Eduardo Zambrano, Ingrid Holm, Jonathan Glickman, Stephen Huang, Antonio Perez-Atayde, Harry P. W. Kozakewich, Robert C. Shamberger, Vânia Nosé
Journal: Endocrine Pathology (2004)
Secret remedies: 100 years on
Authors: D. Colquhoun
Journal: BMJ (2009)

In a society of diverse views, faiths and beliefs, what can paediatric palliative care contribute to our understanding of children's spirituality? By failing to recognise and respond to their spirituality in this work, we risk missing something of profound importance to children and their families. We overlook their search for wholeness in the absence of cure and fall short of offering truly holistic care. This paper explores how developments in advance care planning and related documentation are addressing these issues. Since children's spirituality is elusive and rarely explored in practice, it aims to clarify our understanding of it with a variety of examples and contains suggestions for hearing the voice of the child amid the needs of parents and professionals.