tbuckley/cabot-search huggingface dataset:
Intracellular Na in animal models of hypertrophy and heart failure: contractile function and arrhythmogenesis
Authors: S Pogwizd
Journal: Cardiovascular Research (2003)

Time for primary review 26 days. 

Myocardial hypertrophy (Hyp) and heart failure (HF) are pathologic states characterized by altered intracellular Ca handling [1,2] that can contribute to diastolic and/or systolic dysfunction and arrhythmias [1,3]. However, there is an important interplay between intracellular Na ([Na]i) and Ca handling, so that altered levels of [Na]i and Na transporters can have profound effects on both contractile function and arrhythmogenesis. Both intracellular \[Ca\] ([Ca]i) and intracellular pH (pHi) in cardiac myocytes depend strongly on [Na]i [1]. This is because Na/Ca exchange (NCX) and Na/H exchange (NHE) are powerful transport mechanisms that use the energy stored in the transmembrane [Na] electrochemical gradient to extrude Ca and protons from the cell. Thus, when [Na]i rises it can limit the ability of NCX and NHE to extrude Ca and protons from myocytes. This could slow relaxation and recovery of pHi from acid loads (e.g. during ischemia). First let us consider whether [Na]i is altered in hypertrophy and HF.

Numerous reports indicate that [Na]i is increased in hypertrophy [4–7]. The magnitude of [Na]i elevation (4–6 mM) in hypertrophied guinea pig hearts (induced by aortic banding) was consistent, whether measured by ion-sensitive electrodes (ISE) [4] or nuclear magnetic resonance [5]. Additionally, myocytes from hypertrophied rat hearts (induced by isoproterenol infusion) exhibit a ∼6 mM increase in [Na]i assessed by ISE [6]. Dogs with hypertrophy induced by chronic AV block (cAVB) demonstrate a ∼4 mM increase in subsarcolemmal [Na] compared to controls [7]. However, Baudet et al. [8] detected no change in intracellular Na activity in hypertrophied ferret heart using ISE.

Data regarding [Na]i in heart failure are more limited. In an arrhythmogenic non-ischemic HF rabbit model (induced by aortic insufficiency and … 

* Corresponding author.
microRNA-dependent modulation of histone acetylation in Waldenström macroglobulinemia
Authors: Aldo M. Roccaro, Antonio Sacco, Xiaoying Jia, Abdel Kareem Azab, Patricia Maiso, Hai T. Ngo, Feda Azab, Judith Runnels, Phong Quang, Irene M. Ghobrial
Journal: Blood (2010)
Detection of Malignant Melanoma by Tc-99m HMPAO
Authors: YOUNG HOON RYU, TAE SUB CHUNG, JONG DOO LEE, JUNG HO SUH, JONG TAE LEE, CHANG YUN PARK
Journal: Clinical Nuclear Medicine (1995)

A number of radiopharmaceutical agents have been evaluated for the detection of malignant melanoma. Because anamine is necessary for melanin synthesis, melanotic tumors may possess numerous amine receptors. Tc-99m HMPAO consists of macrocyclic amine radicals. The purpose of this study was to evaluate Tc-99m HMPAO as an effective agent for localizing malignant melanomas on the radioisotope imaging. Six patients, with malignant melanomas were studied. Tc-99m HMPAO SPECT images were obtained in all patients. SPECT was used for the localization of the primary focus, and whole body scans were used for the evaluation of unexpected metastatic lesions. The results were compared with MRI and CT. Tc-99m HMPAO SPECT revealed a high correlation with CT and MRI for the primary focus. Abnormally increased activity at the unexpected metastatic lymph nodes in two patients were also noticed. This was confirmed by CT and MRI for those sites. Tc-99m HMPAO appears to be a useful agent for the localization of both the primary focus and unexpected metastatic lesion in patients with malignant melanoma.
Antitumor Vaccination in Patients with Head and Neck Squamous Cell Carcinomas with Autologous Virus-Modified Tumor Cells
Authors: Jochen Karcher, Gerhard Dyckhoff, Philipp Beckhove, Christoph Reisser, Michael Brysch, Yvonne Ziouta, Burkhard H. Helmke, Hagen Weidauer, Volker Schirrmacher, Christel Herold-Mende
Journal: Cancer Research (2004)

Prognosis of patients with advanced head and neck squamous cell carcinomas (HNSCC) is still poor. Therefore, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe in HNSCC patients. Furthermore, we determined the influence on disease-free survival and overall survival and the vaccination-induced antitumor reactivity. In a nonrandomized pilot study, 20 patients were vaccinated postoperatively. Vaccine was prepared from the tumor cell cultures of patients by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and vaccine was applied up to five times. Antitumor immune reactivity was determined in the skin by delayed type hypersensitivity skin reaction and in the blood by enzyme-linked immunospot assay. Establishment of tumor cell cultures was successful in about 80% of the cases. After vaccination, we observed no severe side effects. Percentages of survival of vaccinated patients with stage III and stage IV tumors (n = 18) were 61% at 5 years. Immune monitoring revealed significant increases of antitumor delayed type hypersensitivity reactivity especially in disease-free patients, and in a significant proportion of vaccinated patients the presence of tumor-reactive T-cells in the peripheral blood even 5 to 7 years after the last vaccination. Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and may improve the prognosis of HNSCC patients with advanced tumors. This could be supported by antitumor immune responses that we observed especially in long-term surviving patients.
Fatal squamous cell carcinoma associated with acne conglobata in a father and daughter
Authors: M. J. WHIPP, C. I. HARRINGTON, S. DUNDAS
Journal: British Journal of Dermatology (1987)

Journal Article Fatal squamous cell carcinoma associated with acne conglobata in a father and daughter Get access M. J. WHIPP, M. J. WHIPP Weston Park Hospital, Sheffield and Departments of Dermatology and Pathology, Royal Hallamshire Hospital, Sheffield, U.K. Dr M.J.Whipp, Weston Park Hospital, Whitham Road, Sheffield SIO2SJ U.K. Search for other works by this author on: Oxford Academic Google Scholar C. I. HARRINGTON, C. I. HARRINGTON Weston Park Hospital, Sheffield and Departments of Dermatology and Pathology, Royal Hallamshire Hospital, Sheffield, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. DUNDAS S. DUNDAS Weston Park Hospital, Sheffield and Departments of Dermatology and Pathology, Royal Hallamshire Hospital, Sheffield, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 3, 1 September 1987, Pages 389–392, https://doi.org/10.1111/j.1365-2133.1987.tb04148.x Published: 01 September 1987
Six people in US die each day from alcohol poisoning, CDC reports
Authors: M. McCarthy
Journal: BMJ (2015)

More than 2200 people die from alcohol poisoning in the United States each year, an average of six a day, the US Centers for Disease Control and Prevention (CDC) has reported.

Alcohol poisoning is typically the result of binge drinking, which is defined as consuming four or more drinks on one occasion in women and five or more drinks in men. Binge drinking is common, the CDC said, as about 38 million US adults report binge drinking an average of four times a month, consuming an average of eight drinks each time. Most binge drinkers, the agency said, are not alcohol dependent.

In the new study1 researchers looked at death certificate data covering 2010-12 collected by the US National Vital Statistics System. …
Is the coupling between contraction and relaxation hyperbolic?
Authors: T Matsushita, M Takaki, T Akashi, H Suga
Journal: Circulation (1993)

indicated by echocardiography.Because of the danger of cardiac shock, the patient was transferred by helicopter to the intensive care unit of the University Hospital, Graz, Austria.Repeated echocardiogram confirmed the suspected thrombosis and revealed severely decreased left ventricular function.At this point, detailed consultation was held between a cardiac surgeon and cardiologist as to the first-line therapy to be adopted.Thrombolysis with recombinant tissue plasminogen activator (100 mg over a period of 2 hours) was given as therapy followed by heparin (1000 U/h IV).Unfortunately, the patient's condition deteriorated with pro- tracted cardiac shock, and he died 5 hours after the onset of thrombolysis.Postmortem examination showed partial lysis of aortic valve thrombosis but persistent pannus with valve dysfunc- tion in the prosthetic mitral valve (Figure).Thus, we believe that the first-line therapy for prosthetic valve thrombosis should be decided individually in each case, and it is doubtful whether thrombolytic therapy may be recommended generally.Above all, in bivalve prostheses in cardiac shock, a surgical procedure may be preferable, since the prognosis, as shown in this case, was not improved by thrombolytic therapy.
25-Hydroxycholecalciferol. A COMPARATIVE STUDY IN DEFICIENCY RICKETS AND DIFFERENT TYPES OF RESISTANT RICKETS
Authors: Sonia Balsan, Michele Garabedian
Journal: Journal of Clinical Investigation (1972)

The effects of 25-hydroxycholecalciferol were studied in 4 children with deficiency rickets and 22 children with D-resistant rickets, including patients with hereditary hypophosphatemic D-resistant rickets, “pseudo-deficiency” rickets, and rickets secondary to cystinosis or to tyrosinosis. Three protocols were used. (a) 8 days after a single oral dose of 16,000 IU of 25-hydroxycholecalciferol, normalization of all biological parameters was observed in all cases of deficiency rickets. A complete lack of response was observed in the different types of resistant rickets. (b) Under prolonged administration of 2,640 IU/day for 2 months, clinical-biological symptoms and X-ray lesions disappeared, and a catch-up growth pattern was observed in deficiency rickets; no relapse of rickets occurred up to 5 months after therapy was stopped. The same dose had no significant effect in 10 patients with hereditary hypophosphatemic D-resistant rickets. A bone biopsy performed in one case showed the persistence of characteristic lesions. (c) With increasing doses of 25-hydroxycholecalciferol varying from 6,000 to 30,000 IU/day and a follow-up of 6 months up to 2 yr duration, clinical-biological-radiologic recovery and catch-up growht was obtained in all cases of “pseudo-deficiency” rickets. In hypophosphatemic hereditary D-resistant rickets, 5 out of 13 patients' serum concentration of phosphorus reached at least 30 mg/liter, but a catch-up growth pattern was not observed. These results indicate that (a) 25-hydroxycholecalciferol is highly active in deficiency rickets; (b) a defect in the conversion of vitamin D3 to its active 25-hydroxy metabolite is probably not the metabolic defect in any of the different types of vitamin D-resistant rickets studied.
Associations between Long-Term Exposure to Chemical Constituents of Fine Particulate Matter (PM <sub>2.5</sub> ) and Mortality in Medicare Enrollees in the Eastern United States
Authors: Yeonseung Chung, Francesca Dominici, Yun Wang, Brent A. Coull, Michelle L. Bell
Journal: Environmental Health Perspectives (2015)

Several epidemiological studies have reported that long-term exposure to fine particulate matter (PM2.5) is associated with higher mortality. Evidence regarding contributions of PM2.5 constituents is inconclusive.We assembled a data set of 12.5 million Medicare enrollees (≥ 65 years of age) to determine which PM2.5 constituents are a) associated with mortality controlling for previous-year PM2.5 total mass (main effect); and b) elevated in locations exhibiting stronger associations between previous-year PM2.5 and mortality (effect modification).For 518 PM2.5 monitoring locations (eastern United States, 2000-2006), we calculated monthly mortality rates, monthly long-term (previous 1-year average) PM2.5, and 7-year averages (2000-2006) of major PM2.5 constituents [elemental carbon (EC), organic carbon matter (OCM), sulfate (SO42-), silicon (Si), nitrate (NO3-), and sodium (Na)] and community-level variables. We applied a Bayesian hierarchical model to estimate location-specific mortality rates associated with previous-year PM2.5 (model level 1) and identify constituents that contributed to the spatial variability of mortality, and constituents that modified associations between previous-year PM2.5 and mortality (model level 2), controlling for community-level confounders.One-standard deviation (SD) increases in 7-year average EC, Si, and NO3- concentrations were associated with 1.3% [95% posterior interval (PI): 0.3, 2.2], 1.4% (95% PI: 0.6, 2.4), and 1.2% (95% PI: 0.4, 2.1) increases in monthly mortality, controlling for previous-year PM2.5. Associations between previous-year PM2.5 and mortality were stronger in combination with 1-SD increases in SO42- and Na.Long-term exposures to PM2.5 and several constituents were associated with mortality in the elderly population of the eastern United States. Moreover, some constituents increased the association between long-term exposure to PM2.5 and mortality. These results provide new evidence that chemical composition can partly explain the differential toxicity of PM2.5.
Cardiac angiotensin converting enzyme and myocardial fibrosis in the rat
Authors: Y. Sun, J. P M Cleutjens, A. A Diaz-Arias, K. T Weber
Journal: Cardiovascular Research (1994)

Objective: The aim was to test the hypothesis that cardiac angiotensin converting enzyme (ACE) is related to the accumulation of fibrous tissue in the heart. Methods: A model of tissue repair (pericardiotomy with left coronary artery ligation) was used, together with the following: quantitative in vitro autoradiography (125I-351A) to determine ACE binding density; immunohistochemistry (monoclonal ACE antibody, 9B9) to identify cells expressing ACE; and in situ hybridisation to localise cells expressing type I collagen mRNA. Age and sex matched rats receiving this operative procedure without subsequent infarction (sham operated) served as controls to those with left ventricular myocardial infarction. Serial heart sections obtained from each group at 3 days and at 1, 2, 4, and 8 weeks following operation were examined for morphological evidence of injury and inflammatory cells (haematoxylin/eosin) and fibrillar collagen (picrosirius red). Results: Following myocardial infarction: (a) on day 3, neutrophils and macrophages were present at the site of infarction, while fibrillar collagen and ACE binding were not increased compared with control; (b) at week 1, fibrillar collagen and ACE binding were present at the site of infarction and became progressively more advanced at 2, 4, and 8 weeks; (c) at week 2, there was increased ACE binding in the right ventricle and interventricular septum, when perivascular fibrosis of intramural coronary arteries and microscopic scars appeared, together with endomyocardial fibrosis of the septum; (d) there was marked ACE binding in the fibrosed visceral pericardium two weeks after operation in both myocardial infarction and sham operated groups; (e) there was type I collagen mRNA expression on postoperative week 1, localised within fibroblasts or fibroblast-like cells found at infarct and fibrous tissue sites in the right ventricle, septum, and pericardium; and (f) ACE-labelled cells included fibroblast-like cells, as well as macrophages and endothelial cells. Conclusions: Thus in this model of tissue repair, marked ACE binding density is associated with fibrillar collagen formation that appears within and remote to the site of myocardial infarction, including the pericardium. Cardiac ACE, originating from type I collagen producing cells, therefore represents an integral component of fibrous tissue formation in this rat model of tissue injury. Cardiovascular Research 1994;28:1423-1432
Determinants of elevated blood lead during pregnancy in a population surrounding a lead smelter in Kosovo, Yugoslavia
Authors: Joseph H. Graziano, Dusan Popovac, Pam Factor-Litvak, Patrick Shrout, Jennie Kline, Mary J. Murphy, Yu-hua Zhao, Ali Mehmeti, Xhemal Ahmedi, Biljana Rajovic, Zorica Zvicer, Dragoslav U. Nenezic, Nancy J. Lolacono, Zena Stein
Journal: Environmental Health Perspectives (1990)

We are prospectively examining the relation between environmental lead exposure and pregnancy outcome in cohorts of women exposed to a wide range of air lead concentrations. Titova Mitrovica, Yugoslavia, is the site of a large lead smelter, refinery, and battery factory. At midpregnancy, 602 women in T. Mitrovica and 900 women in Pristina, a non-lead-exposed control town, were interviewed. Blood was obtained for blood lead (PbB), hemoglobin, erythrocyte protoporphyrin, and serum ferritin measurements. Women were seen again at delivery, at which time maternal and umbilical cord blood samples were obtained. While many demographic and social characteristics were similar across the two towns, women in Pristina were more likely to report employment outside the home, cigarette smoking, and alcohol use during pregnancy. As expected, PbB levels were substantially higher in the smelter town. At midpregnancy, PbB geometric means were 17.1 micrograms/dL in T. Mitrovica and 5.1 micrograms/dL in Pristina; 86% of the pregnant women in T. Mitrovica, compared to 3.4% of those in Pristina, had PbB levels greater than 10 micrograms/dL. Within T. Mitrovica, distance between the home and the smelter was the most important predictor of PbB at mid-pregnancy and delivery. Husband's employment in the lead industry was associated with a significant increase in maternal PbB levels independent of place of residence. Higher maternal serum ferritin concentrations were associated with lower PbB levels, suggesting that dietary iron inhibits lead absorption. Overall, the placenta was a poor barrier to lead; the relationship between maternal PbB and umbilical cord PbB was linear across a wide range of PbB levels.
Positive selection and sequence rearrangements generate extensive polymorphism in the gamete recognition protein bindin
Authors: E. C. Metz, S. R. Palumbi
Journal: Molecular Biology and Evolution (1996)

Bindin is a gamete recognition protein of sea urchins that mediates species-specific attachment of sperm to an egg-surface receptor during fertilization. Sequences of bindin from closely related urchins show fixed species-specific differences. Within species, highly polymorphic bindin alleles result from point substitution, insertion/deletion, and recombination. Since speciation, positive selection favoring allelic variants has generated diversity in bindin polypeptides. Intraspecific bindin variation can be tolerated by the egg receptor, which suggests functional parallels between this system and other flexible recognition systems, including immune recognition. These results show that polymorphism in mate recognition loci required for rapid evolution of sexual isolation can arise within natural populations.
EXPERIMENTAL SYPHILIS IN THE RABBIT
Authors: Wade H. Brown, Louise Pearce, William D. Witherbee
Journal: The Journal of Experimental Medicine (1921)

A systematic study was made of the affections of bone, cartilage, tendons, and synovial membranes which occurred in a series of rabbits with generalized syphilis. Localized infection of this group of structures was found to be of very frequent occurrence. The parts involved were, in the order of their frequency, the facial and cranial bones and cartilages, the bones, tendons, and joints of the feet and legs, the cervical and caudal vertebræ, the ribs, and the sternum. These infections often gave rise to characteristic manifestations of disease which could be detected without difficulty by inspection or palpation of the part. In many instances, however, clinical manifestations were so slight that the presence of lesions could be detected only by radiographic or pathological examination. Detailed descriptions of various clinical types of disease were given and the clinical manifestations correlated with the pathological process. It was pointed out that bone lesions exhibited a decided predilection for certain exposed bony prominences, for lines of bony union, and for epiphyseal lines in particular. A study of the clinical history of bone lesions brought out the fact that they were among the earliest of the generalized forms of disease; they tended to pursue a comparatively rapid course, and relapse was never observed. Especial emphasis was laid upon three aspects of the experimental infection: the analogy existing between certain forms of the animal and human affections, the relation of syphilis of the osseous system to other evidences of disease, and the occurrence of obscure bone lesions. In this connection, it was pointed out that the nasal and epiphyseal lesions of the rabbit presented a striking analogy to those of congenital syphilis in man. It was also pointed out that syphilis of the osseous system occupied a definite position in the scheme of defensive reactions such that lesions of these tissues might be favored or inhibited according to the experimental conditions employed. Finally, the frequency with which infections occurred which were not accompanied by sufficiently distinctive signs even to suggest the possibility of their existence was interpreted as evidence that some cases of latent or obscure infection in man might find their explanation in the presence of a similar group of affections.
HIGH-RISK PLAQUE CHARACTERISTICS IN TYPE II DIABETIC PATIENTS: EVALUATION BY CORONARY CT ANGIOGRAPHY
Authors: Takeshi Hatani, Shuichiro Kaji, Kitae Kim, Takeshi Kitai, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Tomoko Tani, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2013)
A case of recurrent ventricular tachycardia
Authors: C. Inglis, F. Chedgy, D. C. Howlett
Journal: BMJ (2011)

A 76 year old woman collapsed at home after feeling ill and faint, with central chest pain radiating to both arms. She was found to be in pulsatile ventricular tachycardia by paramedics and her arrhythmia was converted to sinus rhythm with 100 mg of intravenous lidocaine. Her medical history included an anteroapical myocardial infarction eight years previously and subsequent New York Heart Association class III heart failure with moderate to severe systolic dysfunction. Before this admission she had been maintained on lisinopril 20 mg once daily, isosorbide mononitrate 40 mg once daily, frusemide 40 mg twice daily, warfarin, atorvastatin 20 mg once daily, digoxin 250 µg once daily, carvedilol 6.25 mg once daily, and glyceryl trinitrate as needed. In the months before this episode she had experienced recurrent attacks of dizziness and palpitations and occasional episodes of anginal chest pain. Serial electrocardiographs showed sinus rhythm, QRS duration of 125 ms, septal Q waves, and non-dynamic 1 mm ST elevation unchanged from previous electrocardiographs. Cardiac enzymes were not raised. She had more episodes of ventricular tachycardia on the coronary care unit, however, and she underwent further treatment. Chest radiography (fig 1⇓) was performed before she was discharged.





### 1 What abnormalities are seen on the chest radiograph and what are the most likely causes?

#### Short answer

The heart is enlarged with dilation of the left ventricle and left atrium (fig 2⇓). Extensive curvilinear calcification is seen overlying the cardiac apex consistent with myocardial calcification within a longstanding left ventricular aneurysm. A left sided pacemaker and an implantable cardioverter defibrillator were fitted after further episodes of ventricular tachycardia occurred on the coronary care unit. These are also seen in the chest radiograph, with leads placed in …