tbuckley/cabot-search huggingface dataset:
Contribution of sarcolemmal calcium current to total cellular calcium in postnatally developing rat heart
Authors: M Vornanen
Journal: Cardiovascular Research (1996)

Objective: The aim was to determine the contribution of sarcolemmal Ca influx through L-type Ca current to total cellular Ca in newborn and postnatally developing rat heart. Methods: Whole cell voltage clamp was used to study L-type Ca current in freshly isolated ventricular cells of 1, 6, 10, 15, 30-day-old and adult (120–150 days) rats. Amplitude, current density, inactivation rate and time integral of Ca current were determined at the experimental temperature of 36 °C. Width, length, surface area, volume and surface-to-volume ratio of the isolated cells were also determined. Using the time integral of Ca current and volume of the myocytes the increment in total cellular Ca was calculated for the six developmental stages. Results: The amplitude of Ca current increased strongly during the postnatal maturation from 277 ± 25 pA at day 1 to 1961 ± 98 pA in the adult rat (P < 0.001). This increase was due to an almost proportional increase in cell size; accordingly the density of Ca current remained fairly constant, being 16.9 ± 1.8, 17.0 ± 1.8, 22.8 ± 1.4, 21.2 ± 1.5, 16.2 ± 2.0 and 15.9 ± 0.7 pA/pF for 1, 6, 10, 15, 30-day-old and adult rats, respectively. Charge transfer by Cd-sensitive Ca current during 200 ms voltage pulse from −45 mV to 0 mV increased from 7.18 ± 1.00 pC at day one to 24.80 ± 1.80 pC in the adult rat heart (P < 0.001). When normalized to the capacitive surface area of the myocytes the charge transfer by L-type Ca current was more than double in newborns (0.429 ± 0.074 pC/pF) as compared to the adults (0.188 ± 0.016 pC/pF) (P < 0.01). The difference is explained by slower inactivation rate of Ca current in newborn than adult rats. Time constant of the fast component was 5.92 ± 0.62 ms and 4.5 ± 0.4 ms (P < 0.05) for 1-day-old and adult rat, respectively. Time constant of the slow component decreased from 27.7 ± 2.0 to 21.7 ± 3.0, although the difference was not statistically significant (P = 0.26). The increment in total cellular Ca due to Ca influx through Ca channels was 54 ± 9 μmol l−1 in 1-day-old rat and decreased steadily during postnatal maturation to 8 ± 1 μmol l−1 in the adult rat (P < 0.001). The change is partly due to faster inactivation of Ca current in adults but mainly as a consequence of decreasing surface-to-volume ratio of growing myocytes. Sarcolemmal surface area increases almost 9 times from 1.001 × 103 μm2 at day 1 to 8.675 × 103 μm2 for the adult rat, whereas increase in cell volume is about 28-fold from 0.991 × 103 to 27.74 × 103 μm3: accordingly surface-to-volume ratio decreases from 1.05 ± 0.02 at day 1 to 0.36 ±0.01 in the adult rat (P < 0.01). Conclusions: Contribution of sarcolemmal Ca influx through L-type Ca channels is over 6 times higher in newborn than mature rats. Therefore, the strong dependence of neonatal rat heart on extracellular Ca for contractile activation is, at least partially, explained by greater contribution of L-type Ca current to intracellular Ca.
Cold agglutinins accompanying Mycoplasma pneumoniae infection.
Authors: G N Smith, W R Weir
Journal: BMJ (1980)

full primary course of immunisation.)Normally a primary course of immunisation against pertussis would be completed by one year.In 1978, however, only 22% of children under 4 years of age in the City of Birmingham had received the full immunising course of three doses of vaccine.Only one of the 117 children under 4 years of age in our series was fully im- munised.The difference between the Birmingham and hospital 70 60 o -_ Diphtheria / tetanus 50 Immunisation acceptance rates 40 \ 30 Pertussis 20 1972 73 74 75 76 77 78 Year Immunisation acceptance rates in Birmingham children during 1972-8.figures is significant (X2=29-376; p <0-001).This strongly suggests that immunisation does protect against the more serious complications of the disease, including cyanotic and apnoeic attacks and convulsions, which may cause brain damage, and pulmonary infections, which may lead to chronic lung disease.The decline in the diphtheria and tetanus immunisation acceptance rate, which accompanied the fall in pertussis immunisation-though to a less degree-is also worrying.In 1978 only 503% of children under the age of 4 had received a full primary immunising course against diphtheria and tetanus.The unexpectedly high proportion of children in our series who
Incidental Findings With Tc-99m MIBI Imaging for Parathyroid Adenoma
Authors: Kari Vekseth Hustad, Uwe Hans Staub, Margreta í Bu, Randolf Hardersen, Steinar Jæger, Ole-Lars Brekke
Journal: Clinical Nuclear Medicine (2007)

Technetium-99m-2-methoxyisobutylisonitrile (Tc-99m MIBI) is a lipophilic cation known to accumulate in certain benign and malignant cells. It is commonly used for detection of parathyroid adenomas. Previous reports have shown that increased accumulation of Tc-99m MIBI results from negative mitochondrial and plasma transmembranous potentials in cells secondary to increased metabolic requirements. We report 2 cases where Tc-99m MIBI scintigraphy revealed 2 different malignant diseases: papillary carcinoma of the thyroid gland and nonsecretory myelomatosis in the skeleton. Clinicians should keep in mind that parathyroid imaging with Tc-99m MIBI can reveal other malignant diseases as incidental findings.
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Walther F. Goebel, Rollin D. Hotchkiss
Journal: The Journal of Experimental Medicine (1937)

1. Azoprotein antigens containing glucuronic and galacturonic acids give rise in rabbits to specific antibodies. The immune sera show no serological crossing with antigens containing glucose or galactose. 2. The galacturonic acid antigen reacts in antipneumococcus horse serum Type I in high dilutions. 3. Azoprotein antigens containing galacturonic acid, benzene sulfonic and carboxylic acids precipitate in antipneumococcus horse sera of various types but not in normal horse serum. The mechanism underlying these cross reactions is discussed.
Occupation and Risk of Death From Coronary Heart Disease
Authors: Julie E. Buring
Journal: JAMA (1987)

Conflicting data have been reported regarding the association between occupation and coronary heart disease. We evaluated data on a series of 568 married men who died of coronary heart disease and an equal number of controls matched for age, sex, and neighborhood of residence. Information was collected from the wives of both cases and controls on a larger number of variables, including usual occupation, job-related and leisure-time physical activity, medical history, and life-style. Usual occupation was dichotomized into blue-collar and white-collar work according to the Edwards' classification. White-collar workers had a statistically significant 30% decreased risk of fatal coronary heart disease compared with blue-collar workers once the effects of reported coronary risk factors were considered (relative risk, 0.70; 95% confidence limits, 0.5 to 0.96). These data suggest that occupation is significantly associated with fatal coronary heart disease, and that this increased risk is not explained by a large number of known coronary risk factors. It still remains unclear, however, whether other uncontrolled variables explain the observed association.
Antismoking Efforts by Physicians-Reply
Authors: S. Edwards Dismuke
Journal: JAMA (1983)

In Reply.—  Mr Zeitlin's series of pessimistic reports emphasize a point that we made in our COMMENTARY. Physicians frequently express little enthusiasm for preventive services and are easily discouraged when overwhelming success is not immediately achieved. This expression contrasts greatly with persistent enthusiasm for therapeutic services.  We outlined evidence that would support a more optimistic viewpoint of health promotion. We hope that physicians will continue and even improve their effort to help patients give up the smoking habit. Physicians no doubt would be aided in their efforts by better advice about how to help persons stop smoking. For example, a tour of the cancer ward is unlikely to have major lasting benefit. Medical schools and continuing education programs are beginning to address this issue.  It should also be remembered that behavior change operates on a continuum. Multiple experiences over a long period can eventually result in changed behavior. Physicians, of
Report warns that cost of care by GPs out of hours could be higher than expected
Authors: Susan Mayor
Journal: BMJ (2004)

The cost of funding evening and weekend care by GPs in the United Kingdom could be much higher than the NHS had expected, according to a report published by the House of Commons Health Committee last week.

Individual GPs are currently responsible for providing out of hours care for their patients, but they will be able to opt out of providing this service from 31 December. For GPs who opt out the responsibility for out of hours services will be …
STATUS EPILEPTICUS TREATED BY MAGNESIUM SULPHATE, INJECTED INTRAVENOUSLY
Authors: Frederic Storchheim
Journal: JAMA (1933)

Status epilepticus, while not very commonly seen, is one of the gravest symptom pictures encountered by physicians. According to Wechsler,<sup>1</sup>it "generally ends fatally." The great majority of true status attacks, when the patient is unconscious and has epileptiform attacks, between which he does not regain consciousness, with the convulsions coming on with a half hour down to a few minutes or even several seconds between, terminate in death. When the physician reaches the stricken patient the latter is usually flat on his back, in deep coma, breathing stertorously, with copious white froth escaping from his mouth and often from his nostrils. The face may be pale or deeply cyanotic and the entire body wringing wet from perspiration. The pulse is often extremely rapid, especially in the later stage, and of varying quality, and the respiratory rate is usually somewhat increased. The breathing is handicapped by the large quantity
Do changes in cardiovascular risk factors explain changes in mortality from stroke in Finland?
Authors: E. Vartiainen, C. Sarti, J. Tuomilehto, K. Kuulasmaa
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objectives</b>: To estimate the extent to which the changes in the main cardiovascular risk factors (blood pressure, smoking, and serum cholesterol concentration) can explain the observed changes in mortality from stroke in Finland during the past 20 years. <b>Design</b>: Predicted changes in mortality from cerebrovascular disease mortality were calculated by a proportional hazards model from data obtained in cross sectional population surveys in 1972, 1977, 1982, 1987, and 1992. Predicted changes were compared with the observed changes in mortality statistics. <b>Setting</b>: North Karelia and Kuopio provinces, Finland. <b>Subjects</b>: 16741 men and 16389 women aged 30-59 randomly selected from the national population register, of whom 14054 men and 14546 women participated. <b>Main outcome measures</b>: Levels of risk factors and predicted and observed changes in mortality from cerebrovascular disease. <b>Results</b>: The observed changes in diastolic blood pressure, total serum cholesterol concentration, and smoking in the population from 1972 to 1992 predicted a 44% fall in mortality from stroke in men and changes in diastolic blood pressure and smoking predicted a 34% fall in women. The observed fall in mortality from stroke was 66% in men and 60% in women. <b>Conclusions</b>: Two thirds of the fall in mortality from stroke in men and half in women can be explained by changes in the three main cardiovascular risk factors. <h3>Key messages</h3> Key messages In this study blood pressure and smoking were independent risk factors for stroke in both sexes and serum cholesterol concentration was also a risk factor in men Mortality fell by 62% in men and 63% in women over 20 years Changes in risk factors explained 71% of the fall in men and 54% in women Continued emphasis on promoting healthier lifestyles and effective treatment for hypertension are essential to maintain the fall in deaths
Activity of MM-398, Nanoliposomal Irinotecan (nal-IRI), in Ewing's Family Tumor Xenografts Is Associated with High Exposure of Tumor to Drug and High <i>SLFN11</i> Expression
Authors: Min H. Kang, Jing Wang, Monish R. Makena, Joo-Sang Lee, Nancy Paz, Connor P. Hall, Michael M. Song, Ruben I. Calderon, Riza E. Cruz, Ashly Hindle, Winford Ko, Jonathan B. Fitzgerald, Daryl C. Drummond, Timothy J. Triche, C. Patrick Reynolds
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To determine the pharmacokinetics and the antitumor activity in pediatric cancer models of MM-398, a nanoliposomal irinotecan (nal-IRI). Experimental Design: Mouse plasma and tissue pharmacokinetics of nal-IRI and the current clinical formulation of irinotecan were characterized. In vivo activity of irinotecan and nal-IRI was compared in xenograft models (3 each in nu/nu mice) of Ewing's sarcoma family of tumors (EFT), neuroblastoma (NB), and rhabdomyosarcoma (RMS). SLFN11 expression was assessed by Affymetrix HuEx arrays, Taqman RT-PCR, and immunoblotting. Results: Plasma and tumor concentrations of irinotecan and SN-38 (active metabolite) were approximately 10-fold higher for nal-IRI than for irinotecan. Two doses of NAL-IRI (10 mg/kg/dose) achieved complete responses maintained for &amp;gt;100 days in 24 of 27 EFT-xenografted mice. Event-free survival for mice with RMS and NB was significantly shorter than for EFT. High SLFN11 expression has been reported to correlate with sensitivity to DNA damaging agents; median SLFN11 mRNA expression was &amp;gt;100-fold greater in both EFT cell lines and primary tumors compared with NB or RMS cell lines or primary tumors. Cytotoxicity of SN-38 inversely correlated with SLFN11 mRNA expression in 20 EFT cell lines. Conclusions: In pediatric solid tumor xenografts, nal-IRI demonstrated higher systemic and tumor exposures to SN-38 and improved antitumor activity compared with the current clinical formulation of irinotecan. Clinical studies of nal-IRI in pediatric solid tumors (especially EFT) and correlative studies to determine if SLFN11 expression can serve as a biomarker to predict nal-IRI clinical activity are warranted. Clin Cancer Res; 21(5); 1139–50. ©2015 AACR.
The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung
Authors: Francis X. McCormack, Jeffrey A. Whitsett
Journal: Journal of Clinical Investigation (2002)

Innate defenses in the lungEach day respiration moves 15,000 liters of air containing hundreds of microorganisms over the 150-m 2 respiratory epithelial surface.Most inhaled microbes are trapped on the mucus layer coating the nasal epithelium and upper respiratory tract and are transported by ciliary motion to the pharynx, where they are swallowed.Organisms that reach the alveolar compartment are deposited on the alveolar lining layer (ALL), a thin aqueous film containing pulmonary surfactant that lines the gas-exchanging surface of the pulmonary epithelium.After "touchdown," complex offensive and defensive strategies are initiated by both the invader and the host.Sensing of the physiologic body temperature and the pH and ionic strength of the ALL by the organism triggers a program of gene expression designed to optimize survival under adverse conditions.These include upregulation of microbial genes required for proliferation and host evasion and downregulation of genes that regulate less necessary functions.The lung response to this threat is coordinated by the pulmonary epithelium and alveolar macrophages, which release cytokines and chemokines to recruit additional inflammatory cells to the airspace.However, a single organism capable of dividing every 20 minutes will give rise to a population of millions within hours, so control of proliferation must begin well before reinforcements arrive.For the naive host, the primary antimicrobial defenses in the ALL are the resident alveolar macrophages and protein components of the innate immune system, including the cell wall-degrading enzyme lysozyme, the iron-chelating protein lactoferrin, and specific membrane-permeabilizing members of the defensin, cathelicidin, and pentraxin families.Macrophages are activated by innate immune receptors such as CD14, which detect LPS, peptidoglycan, and other molecules displayed on the surface of microorganisms.Phagocytosis is triggered by pattern recognition receptors on the surface of the phagocyte, including the mannose receptor and the macrophage scavenger receptor, which identify signature carbohydrate structures on microbial surfaces.If the microbe has been previously encountered, recognition may also proceed through opsonization by specific antibody and Fc receptor-dependent uptake.These events result in extracellular microbial incapacitation and internalization into activated phagolysosomes, which kill the organism through exposure to lethal reactive oxygen species and lytic enzymes.
Impact of Systolic and Diastolic Deformation Indexes Assessed by Strain-Encoded Imaging to Predict Persistent Severe Myocardial Dysfunction in Patients After Acute Myocardial Infarction at Follow-Up
Authors: Mirja Neizel, Grigorios Korosoglou, Dirk Lossnitzer, Harald Kühl, Rainer Hoffmann, Christina Ocklenburg, Evangelos Giannitsis, Nael F. Osman, Hugo A. Katus, Henning Steen
Journal: Journal of the American College of Cardiology (2010)
Two Distinct Quinidine-Induced Rheumatic Syndromes
Authors: MICHAEL G. COHEN
Journal: Annals of Internal Medicine (1988)

Of seven patients with quinidine-induced polyarthropathy, four had positive antinuclear antibodies and could be considered to have had quinidine-induced lupus erythematosus. The remaining three patients had milder symptoms, which occurred soon after the start of quinidine therapy, and did not have antinuclear antibodies. To confirm the association, the latter three patients were rechallenged with quinidine therapy, which caused recurrence of symptoms within 1 week. Antihistone antibodies, which are characteristic of drug-induced lupus erythematosus associated with procainamide and hydralazine therapy, were detected in all patients with quinidine-induced lupus erythematosus. An unusual characteristic of antihistone antibodies seen in two patients was the presence of high levels of IgG antibodies to histone H1 as well as H2A-H2B and H3-H4 complexes, without antibodies to the individual core histones.
Lectures on Preventive Cardiology
Authors: David H. Spodick
Journal: JAMA (1967)

Cholesterol, lipids, lipoproteins are the three rings of the atheroma circus which have entertained and bewildered us in the past 20 years. In focusing on the current pandemic of premature (as well as appropriately mature) atherosclerosis, Dr. Stamler has produced a well-documented and smoothly readable guide for the perplexed in this proliferating field. Yet the book's contents are faithful to its title. One third of the book is given to hypertensive, cerebrovascular, pulmonary, rheumatic, and congenital diseases, completed by an incisive deterrent to iatrogenic heart disease in children.  For each disease category, Dr. Stamler analyzes epidemiologic, clinical, and laboratory information followed by a concise synthesis of its present (1966) status. Lucid discussion of complexities is followed by concrete proposals for prevention and control based on current knowledge. The pervasive theme is mobilization of individual and collective effort to attack the roots of the disorders as well as any known steps
Nitric oxide and angiogenic activity of endothelial cells: direct or VEGF-dependent effect?
Authors: J Dulak
Journal: Cardiovascular Research (2002)

In a recent interesting paper Babaei and Stewart [1] demonstrated that coculture of endothelial cells (ECs) with smooth muscle cells (SMCs) may result in the formation of extensive capillary-like structure. However, the effect was observed only when SMCs were previously transfected with vector containing the endothelial nitric oxide synthase (eNOS) cDNA. Such an in vitro angiogenic-like events were abrogated by l-NAME, a NOS inhibitor. A similar angiogenic response has been observed when SMCs were transfected with plasmids containing VEGF121 cDNA, the effect again being inhibited by l-NAME. Similarly, in a Boyden chamber model the EC migration was potently enhanced in the presence of SMC transfected with eNOS or VEGF121, and was significantly attenuated by l-NAME.

Much evidence indicates that NO plays an integral role in VEGF signaling (see Ref. [1]). It has …
Advanced fibrosis is not a negative pretreatment predictive factor for genotype 2 or 3 chronic hepatitis C patients
Authors: Hyun Seok Lee, Young Oh Kweon, Won Young Tak, Soo Young Park, Eun Jung Kang, Yu Lim Lee, Hae Min Yang, Hyun Woo Park
Journal: Clinical and Molecular Hepatology (2013)

Chronic hepatitis C patients with advanced fibrosis have unsatisfactory sustained virological response (SVR) rates. Few data demonstrating the efficacy of combination therapy in chronic hepatitis C patients with advanced fibrosis in South Korea are available. The purpose of this study was to assess whether the stage of fibrosis impacts the efficacy of combination therapy for chronic hepatitis C.We retrospectively reviewed data for a total of 109 patients with chronic hepatitis C, treated with peginterferon alfa and ribavirin. SVR according to the stage of liver fibrosis assessed by pretreatment liver biopsy and genotype results were analyzed.Data from 66 genotype 1 patients (60.6%) and 43 genotype 2 or 3 patients (39.4%) among the 109 patients were analyzed. SVR rates for the genotype 1 patients were significantly lower for the stage 3-4 group (32.1%) than the stage 0-2 group (78.9%; P<0.001). SVR rates (92.0% for stage 0-2, 77.8% for stage 3-4, P=0.184) of genotype 2 or 3 patients were not significantly different according to fibrosis stage. Likewise, the frequency of adverse events was not significantly different according to fibrosis stage.Compared to patients without advanced fibrosis, we can anticipate good SVR rates for genotype 2 or 3 patients with advanced fibrosis and they did not show an inferior tolerability for peginterferon and ribavirin combination therpy. Our results suggest that active treatment is needed for genotype 2 or 3 patients with advanced fibrosis.
Resectable rectal cancers. Treatment by curative endocavitary irradiation
Authors: J. Papillon
Journal: JAMA (1975)

IT IS GENERALLY considered that rectal carcinoma is only slightly radiosensitive, and that radiation therapy has no place in its curative treatment. This opinion is not true in the case of early rectal cancers that can be treated by<i>endocavitary irradiation</i>. Rectal adenocarcinoma proves to be very radiosensitive with this method. The response of the tumor is favorable, even surprising; the chances of local control are good, as long as the indications are strictly respected. Endocavitary irradiation of rectal cancers consists of two techniques, contact x-ray therapy and interstitial curietherapy. <h3>Contact X-ray Therapy</h3> The characteristics of the machine used for contact x-ray therapy are a low voltage (50 kv), short focal distance (4 cm), high output (1,500 roentgen/min in air), a narrow tube (able to be introduced in a special rectoscope 3 cm in diameter) and substantial absorption of the radiation in the first 2 cm. The tube is very
Gene therapy for rat hepatocarcinoma (HCC) using intratumorous injection of recombinant adenoviruses carrying herpes simplex virus thymidine kinase gene (HSVTK)
Authors: R. Gérolami, M. Lewin, MP. Bralet, O. Clément, F. Frija, PL. Tran, C. Bréchot
Journal: Journal of Hepatology (1998)
Reply to Rafael Boscolo-Berto, Antonio Galfano and Massimo Iafrate's Letter to the Editor re: Noburu Numao, Satoru Kawakami, Minato Yokoyama et al. Improved Accuracy in Predicting the Presence of Gleason Pattern 4/5 Prostate Cancer by Three-Dimensional 26-Core Systematic Biopsy. Eur Urol 2007;52:1663–9
Authors: Noboru Numao, Satoru Kawakami
Journal: European Urology (2008)