tbuckley/cabot-search huggingface dataset:
The calcium channel blocker nitrendipine blocks sodium channels in neonatal rat cardiac myocytes.
Authors: A Yatani, A M Brown
Journal: Circulation Research (1985)

The dihydropyridine calcium channel blocker, nitrendipine, was studied for its effects on the sodium current of single cultured ventricular cells from neonatal rats. The patch-clamp method of recording whole cell currents was used, and sodium currents were isolated by suppressing potassium and calcium currents. Potassium currents were blocked by replacing potassium with cesium in the internal and external solutions and by adding tetraethylammonium chloride and 4-aminopyridine in the external solution; calcium current was blocked by replacing calcium with cobalt in the external solution. At low frequencies (0.1 Hz), nitrendipine reduced sodium currents without any significant change in the current-voltage relation. The block was dose dependent, and assuming a single occupancy model with complete block, had a half-maximum value of 3 X 10(-6) M at a holding potential of -80 mV where half the sodium channels are activatable. This value is within the range of the Kd's that have been reported for low-affinity dihydropyridine-binding sites found in cardiac sarcolemmal vesicles. In the presence of nitrendipine, the inactivation curve was shifted to hyperpolarized potentials. The block was greater with pulse intervals shorter than 1000 msec, and repriming was prolonged in the presence of the drug. These effects are similar to those of local anesthetics of the tertiary amine class, such as lidocaine. The block was relieved by the dihydropyridine agonist Bay K8644. The results are interpreted as indicating that dihydropyridines react with sodium channels.
Progenitor Marker CD133 mRNA Is Elevated in Peripheral Blood of Cancer Patients with Bone Metastases
Authors: Niven Mehra, Maarten Penning, Jolanda Maas, Laurens V. Beerepoot, Nancy van Daal, Carla H. van Gils, Rachel H. Giles, Emile E. Voest
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We examined whether RNA expression of CD133, a surface molecule expressed on progenitors from hematopoietic and endothelial lineages, and CD146, a pan-endothelial marker, are increased in the blood of cancer patients and whether these factors correlate with patient characteristics and are predictive factors of survival. Experimental Design: We developed a real-time quantification method (nuclear acid sequence-based amplification) to determine expression of CD146 and CD133 mRNA in the peripheral blood mononuclear cells of 131 progressive cancer patients, 37 healthy volunteers, and 5 patients who received granulocyte colony-stimulating factor. Overall survival and other clinicopathologic variables were obtained. Cox proportional hazards studies were done. Results: We show that patients with metastatic disease have a significant increase in CD133 mRNA (P = 0.03), specifically patients with bone metastasis (P &amp;lt; 0.001). Cancer patients with high CD133 mRNA expression, using a defined cutoff value, show a decreased survival compared with patients with low or undetectable CD133 expression (21% versus 45% cumulative survival, respectively, after 20 months; P = 0.01). Among patients with metastasis to the bone, cumulative survival was 22%, compared with 61% for patients with high or low CD133 levels (P = 0.004). Multivariate analysis showed that CD133 expression is an independent predictor for overall survival in patients with bone metastases. CD146 mRNA was not increased in patients with cancer, nor did it correlate with clinical variables or survival. Conclusion: CD133, but not CD146, mRNA expression is increased in cancer patients with metastatic disease, specifically with bone metastasis. In addition, CD133 mRNA expression seems to be an independent prognostic factor for overall survival.
Clinical Trials of a New Drug, Ibufenac, in the Treatment of Rheumatoid Arthritis: A PRELIMINARY REPORT
Authors: T. M. Chalmers
Journal: Annals of the Rheumatic Diseases (1963)

Out-Patient TrialAfter these two in-patient trials, a further trial was designed with the object of assessing the value of Ibufenac for maintenance therapy in out-patients.358
839. Lentiviral Vectors Encoding Connexin43 Mutants Reduce Gap Junction Function: Toward Molecular Ablation of Re-Entrant Cardiac Arrhythmias
Authors: Eddy Kizana, Samantha L. Ginn, Christine Smyth, Anita Boyd, Stuart P. Thomas, David G. Allen, David L. Ross, Ian E. Alexander
Journal: Molecular Therapy (2005)

Background and Aims: Sudden cardiac death (SCD) is a devastating complication of myocardial infarction and is most commonly attributable to the arrhythmia of ventricular tachycardia (VT). The pathophysiology of VT consists of re-entrant electrical conduction at the border-zone of infarcted and viable myocardium for which the electrophysiological substrate is provided by structural and functional abnormalities at this region. Contemporary therapies for VT/SCD are unsatisfactory due to moderate efficacy (drugs and radiofrequency ablation) or due to their palliative nature (automated implantable cardioverter defibrillator). In the current study we sought to design a therapy which directly targets the pathophysiology of focal abnormal electrical conduction by reducing gap junctional intercellular communication (GJIC) and hence the electrical connections between cells subserving the re-entry circuit.
Extranodal T‐cell lymphoma mimicking malignant histiocytosis
Authors: Tsieh Sun, Judith Brody, Myron Susin, Eleonore Boss, Lisa Moskowitz, Stuart Lichtman
Journal: American Journal of Hematology (1990)

Abstract We report a case of extranodal T‐cell lymphoma with fever, hepatosplenomegaly, pancytopenia, and diffuse sinusoidal infiltration of the spleen, liver, and bone marrow by the tumor cells, mimicking malignant histiocytosis. This is the second case of T‐γ (T‐cell suppressor) lymphoma resembling the case reported by Kadin et al. [N Engl J Med 304:648, 1981]. The lack of lymph node involvement in this case supports the theory that this type of lymphoma arises in the spleen. This paper draws attention to the extranodal T‐cell lymphoma groups that mimic malignant histiocytosis and to the need of immunophenotyping for a correct diagnosis. The causes for the absence of T‐cell receptor gene rearrangement in T‐cell tumors are discussed.
Dietary variables and glucose tolerance in pregnancy.
Authors: Y Wang, L H Storlien, A B Jenkins, L C Tapsell, Y Jin, J F Pan, Y F Shao, G D Calvert, R G Moses, H L Shi, X X Zhu
Journal: Diabetes Care (2000)

OBJECTIVE: To investigate relationships between dietary macronutrient intakes and glucose tolerance in pregnancy RESEARCH DESIGN AND METHODS: Nulliparous pregnant Chinese women diagnosed with gestational diabetes mellitus (GDM) (n = 56) were compared to age-, gestational age-, height-, and parity-matched groups with normal glucose tolerance (n = 77) and glucose intolerance (IGT) (n = 38) based on the results of an oral glucose tolerance test (National Diabetes Data Group criteria), performed between 24 and 28 weeks of pregnancy. A 24-h recall dietary assessment was also obtained at the time of screening. RESULTS: Subjects with IGT and GDM were significantly heavier (66.1 +/- 1.4 and 68.6 +/- 1.2 kg, respectively, mean +/- SEM) (P &amp;lt; 0.0001) than the normal group (61.2 +/- 1.8 kg) and had a higher BMI. Overall energy intake was similar between groups, as were the intakes of each macronutrient (%kcal). However, there was a highly significant reduction in polyunsaturated fat intake in the IGT and GDM groups whether expressed as %kcal, % of total fat, or fat kcal. This effect was independent of body weight or BMI whether assessed by ordinal logistic regression or by analysis of a weight- and BMI-matched subgroup of the subjects (P = 0.002 for %kcal; n = 47 normal, 26 IGT, and 43 GDM subjects). In logistic regression analysis of the complete data set, increased body weight (P &amp;lt; 0.0001) and decreased polyunsaturated fat intake (P = 0.0014) were both independent predictors of glucose intolerance (IGT and GDM), as were increased body weight and a low dietary polyunsaturated to saturated fat ratio. CONCLUSIONS: Increased polyunsaturated fat intake is associated with a reduced incidence of glucose intolerance during pregnancy. This finding may have major implications for dietary management of women with or at risk of developing GDM.
Five hospitals under threat as Hungary's largest healthcare privatisation company nears collapse
Authors: M. Hotopf
Journal: BMJ (2009)

Hungary’s underfunded public healthcare system has hit a crisis as Hospinvest, the company that dominates hospital privatisation in the country, is on the verge of collapse. The company looks set to hand back five hospitals to the public sector and is talking to external investors to raise more capital.

Hospinvest has debts of two to three billion Hungarian forints (£6m-9m; €7m-11m; $10m-15m) and has said it cannot meet its commitments to install new equipment by specific dates in each hospital. This will mean that the company is in …
Maximum oxygen uptake utilising different treadmill protocols.
Authors: B. Davies, A. Daggett, P. Jakeman, J. Mulhall
Journal: British Journal of Sports Medicine (1984)

The study compared five treadmill protocols (four utilising a motorised, and one a non-motorised, treadmill) on maximum oxygen uptake. The five male and five female subjects, all actively engaged in training, were assigned the tests in random order. Statistical analysis revealed no significant differences between the five protocols for maximal oxygen uptake, maximum ventilation, maximum heart rate and blood lactate inflection point, relative to maximal oxygen uptake. Significant differences were observed between the 3' protocol with incline increments of 1.5% and all other protocols on time to exhaustion (p = less than 0.01) and maximum blood lactate levels (HLA, p = less than 0.05). The results indicate that the protocols used in this study did not significantly influence the maximum oxygen uptake attained.
Strange Bedfellows? Reflections on Bioethics' Role in Disaster Response Planning
Authors: Jessica Berg, Nicholas King
Journal: The American Journal of Bioethics (2006)

This essay considers the potential role of bioethics in disaster response planning and preparedness. Bioethicists can make substantial contributions, by ensuring that decision-making and distribution of resources during crises is carried out in a fair and just manner, as well as by examining the assumptions upon which disaster planning are based. Bioethicists should also be aware of potential pitfalls of overly-hasty engagement with this new field.
Subcellular calcium pools of ischaemic and reperfused myocardium characterised by electron probe
Authors: T. W Miller, J. M. Tormey
Journal: Cardiovascular Research (1995)

Objective: The subcellular redistribution of calcium and other electrolytes was analysed in myocardium subjected to global ischaemia and reperfusion in order to establish possible causes of reperfusion injury. Methods: Isolated ferret papillary muscles (maintained at 37 °C, 1.2 Hz stimulation) were exposed to ischaemic conditions for 1 h by isolating from room air, removing buffer, and exposing to a constant flow of water-saturated 98% N2/5% CO2 gas. Some muscles were “reperfused” for 5 min by exposing to control buffer. Electron probe microanalysis was used to measure subcellular electrolyte content. Results: Ischaemia caused severe swelling and doubling of cell sodium [84(SEM 5) to 156(9) mmol·kg−1 dry weight (dw), P < 0.05]. Mitochondrial electrolyte concentrations were generally increased, most notably calcium [0.40(0.15) to 1.99(0.32) mmol·kg−1 dw, P < 0.05]. Electrolytes in other structures were more moderately affected. Reperfusion resulted in two general myocyte populations. Irreversibly injured cells exhibited contracture knots and an influx of extracellular fluid. Analysis was restricted to moderately injured cells, which had reduced swelling and varying numbers of vacuolated mitochondria. In the moderately injured cells, sodium remained high [167(11) mmol·kg−1 dw] and magnesium had increased from 39(2) to 52(2) mmol·kg−1 dw (P < 0.05). Mitochondrial calcium was near control levels [0.64(0.42) mmol·kg−1 dw]. Junctional sarcoplasmic reticular calcium significantly increased [6.56(0.59) to 18.53(1.64) mmol·kg−1 dw in control and reperfused cells, respectively, P < 0.05], while calcium had not changed significantly in T tubule lumen or “3rd compartment”, composed of sarcoplasmic reticulum, T tubules, and free sarcoplasm. “3rd compartment” and junctional sarcoplasmic reticulum results suggest that sarcolemma bound calcium had decreased. Conclusions: Surviving myocytes had no change in total calcium, but showed a large degree of calcium redistribution. Mitochondria accumulated calcium during ischaemia, but released it upon reperfusion. Sarcoplasmic reticulum in reperfused cells appeared functional and may have helped maintain physiological [Ca2+]; by storing calcium released from mitochondria and the sarcolemma. Mitochondrial and sarcolemmal damage are proposed as critical factors in reperfusion injury.
EFFECT OF ANAEROBICALLY PREPARED PNEUMOCOCCUS AUTOLYSATE TOXIN ON MICE AND EVALUATION OF PNEUMOCOCCUS AUTOLYSATE ANTITOXIN IN MICE
Authors: Julia T. Weld, Anne Gunther
Journal: The Journal of Experimental Medicine (1935)

1. Certain anaerobically produced autolysates of pneumococcus injected intravenously kill mice in 0.1 to 0.2 cc. quantities in a few hours to 8 days. 2. The symptoms of mice inoculated with these autolysates are weakness and increasing prostration until death. Massive albuminuria is found, appearing 18 hours after injection. During the course of a prolonged intoxication ascites and edema of the subcutaneous tissues may develop. Large pale yellow or white kidneys are found in mice that survive 5 days. In these latter animals, emaciation is usually marked at death. 3. The antitoxin prepared in horses by immunization with the anaerobically prepared toxic autolysates of pneumococcus neutralizes the poisonous autolysates whether mixed in vitro before injection or injected separately after the autolysate. 4. The injection of pneumococcus autolysate toxin incompletely neutralized with autolysate antitoxin causes a protracted intoxication with symptoms and pathologic findings similar to those found in mice dying slowly after injections of the toxic autolysate alone.
Familial cutaneous collagenoma: genetic studies on a family*
Authors: JOUNI UITTO, DANIEL J. SANTA-CRUZ, ARTHUR Z. EISEN
Journal: British Journal of Dermatology (1979)

Familial cutaneous collagenoma is an inherited condition characterized by the presence of multiple dermal nodules symmetrically distributed on the trunk and upper arms. In this study, six patients, the proband, his four siblings and a niece, representing a kindred of fifty-two subjects, were examined for aymptomatic cutaneous nodules mainly on the back and chest. The individual lesions varying from a few millimetres to several centimetres in size, were indurated, and showed minimal epidermal changes. Histologically, the nodules were characterized by an excessive accumulation of dense, coarse collagen fibres in the dermis. The elastic fibres appeared diminished in number, and in some areas they were abnormally thin and fragmented. The lesions, therefore, were connective tissue naevi of the collagen type. On the basis of the family history and histological observations the patients were diagnosed as having familial cutaneous collagenoma. Examination of the family pedigree indicated that the dermal nodules in familial cutaneous collagenoma were inherited in an autosomal dominant pattern. It was also observed that the lesions had an onset at the age of 15 to 19 years, and their number increased significantly during pregnancy. It is conceivable that familial cutaneous collagenoma is an inherited condition whose expression may be under a hormonal control.
Sonic hedgehog negatively regulates pre-TCR–induced differentiation by a Gli2-dependent mechanism
Authors: Nicola J. Rowbotham, Ariadne L. Hager-Theodorides, Anna L. Furmanski, Susan E. Ross, Susan V. Outram, Johannes T. Dessens, Tessa Crompton
Journal: Blood (2009)

Abstract Hedgehog signaling regulates differentiation, survival, and proliferation of the earliest double-negative (DN) thymocytes, but its importance at later stages of T-cell development is controversial. Here we use loss- and gain-of-function mouse models to show that Shh, by signaling directly to the developing thymocyte, is a negative regulator of pre-TCR–induced differentiation from DN to double-positive (DP) cell. When hedgehog signaling was reduced, in the Shh−/− and Gli2−/− thymus, or by T lineage–specific transgenic expression of a transcriptional-repressor form of Gli2 (Gli2ΔC2), differentiation to DP cell after pre-TCR signal transduction was increased. In contrast, when Hh signaling was constitutively activated in thymocytes, by transgenic expression of a constitutive transcriptional-activator form of Gli2 (Gli2ΔN2), the production of DP cells was decreased. Gene expression profiling showed that physiologic Hh signaling in thymocytes maintains expression of the transcription factor FoxA2 on pre-TCR signal transduction.
Im/partial Science: Gender Ideology in Molecular Biology
Authors: Elaine R. Radwanski
Journal: JAMA (1996)

Bonnie B. Spanier's<i>Im/partial Science</i>is an eye-opening introduction to the way philosophical views influence biology. This topic is both intrinsically interesting and significant for the practice of medicine. Spanier's thesis is that assumptions about proper social relationships can color all our enterprises, even apparently neutral ones like molecular biology. Thus, if we see sex differences as fundamental, our theory construction— even our perception of data—will tend to be compatible with that assumption. And if we embrace social hierarchy rather than egalitarianism, our theories will also reflect that view. Spanier believes these patterns of thought have led to the adoption of paradigms without sufficient consideration of possible alternatives, and to the failure to notice data inconsistent with those paradigms. Consequently, potentially fruitful paths of inquiry are ignored. So allegedly "objective" knowledge is incomplete or even erroneous, and this "knowledge" reinforces the questionable assumptions that informed it initially. Thus, for example,
Closure of Skin Wounds with Adhesive Tape
Authors: P. J. B. Murray
Journal: BMJ (1963)

MMDICAL -JOURNLIn the out-patient series it was found practicable to manage most minor wounds and lacerations by sutureless closure without the use of local anaesthesia.Gentle cleaning of the wound and excision of small areas of devitalized tissue were usually possible without causing discomfort to the patient.Because of the ease of application of the strips and lack of necessity for local anaesthesia, this method has many advantages for small wounds of the kind usually treated in general practice or in an out-patient department.Indeed, the very simplicity of the technique engenders a risk that wounds in which full exploration is required may be closed ab initio.Careful assessment of traumatic lesions is therefore necessary before proceeding to sutureless closure without anaesthesia.The combined results of this clinical trial have demonstrated that steri-strip tape is a reliable and practical means of skin closure for the majority of wounds and incisions.We would particularly advocate the use of tape closure in the following circumstances: (1) where incisions transgress skin devitalized by ischaemic or venous disease, or when- ever there is a special risk of infection; (2) incisions and wounds in children; (3) suitable traumatic wounds; and (4) fixation of small skin grafts.Summary A clinical trial of a new form of adhesive tape was carried out to assess its use in skin closure.The results obtained in 157 wounds and lacerations in out-patients and 124 operation incisions in in-patients are given.Satisfactory primary healing was obtained in most of the patients, and the reasons for any delay in healing are analysed.The advantages of the tape are discussed and certain indications are given for its use.We wish to thank Sister P. E. M. Cocking for her help in the out-patient trial and the photographic department of St. Bartholomew's Hospital for the illustrations.The steri- strips were supplied by the Minnesota Mining & Manufacturing
Regulation of Anti-DNA B Cells in Recombination-activating Gene–deficient Mice
Authors: Hui Xu, Hui Li, Elisabeth Suri-Payer, Richard R. Hardy, Martin Weigert
Journal: The Journal of Experimental Medicine (1998)

Anti-DNA antibodies are regulated in normal individuals but are found in high concentration in the serum of systemic lupus erythematosus (SLE) patients and the MRL lpr/lpr mouse model of SLE. We previously studied the regulation of anti–double-stranded (ds)DNA and anti–single-stranded (ss)DNA B cells in a nonautoimmune background by generating mice carrying immunoglobulin transgenes coding for anti-DNAs derived from MRL lpr/lpr. Anti-dsDNA B cells undergo receptor editing, but anti-ssDNA B cells seem to be functionally silenced. Here we have investigated how anti-DNA B cells are regulated in recombination- activating gene (RAG)-2−/− mice. In this setting, anti-dsDNA B cells are eliminated by apoptosis in the bone marrow and anti-ssDNA B cells are partially activated.
Fatal Case of Deer Tick Virus Encephalitis
Authors: Norma P. Tavakoli, Heng Wang, Michelle Dupuis, Rene Hull, Gregory D. Ebel, Emily J. Gilmore, Phyllis L. Faust
Journal: New England Journal of Medicine (2009)

Summ a r yDeer tick virus is related to Powassan virus, a tickborne encephalitis virus.A 62-yearold man presented with a meningoencephalitis syndrome and eventually died.Analyses of tissue samples obtained during surgery and at autopsy revealed a widespread necrotizing meningoencephalitis.Nucleic acid was extracted from formalin-fixed tissue, and the presence of deer tick virus was verified on a flavivirus-specific polymerase-chain-reaction (PCR) assay, followed by sequence confirmation.Immunohistochemical analysis with antisera specific for deer tick virus identified numerous immunoreactive neurons, with prominent involvement of large neurons in the brain stem, cerebellum, basal ganglia, thalamus, and spinal cord.This case demonstrates that deer tick virus can be a cause of fatal encephalitis.
Comparative Atherosclerosis: The Morphology of Spontaneous and Induced Atherosclerotic Lesions in Animals and Its Relation to Human Disease
Authors: Sigmund L. Wilens
Journal: JAMA (1965)

This new but excellent manifestation of symposiarrhea will be cherished by the compact group of investigators interested in comparative arteriosclerosis and should be invaluable as a reference book to all others in the field. Book-selection committees of medical libraries ought to give it a high priority in spite of its specialized character. Vascular disease found in over 400 species is discussed by 56 authors, also of many diverse kinds. While the book is highly informative, the seasoned reader may miss the literate style and authoritative manner found in the pioneer and classic monographs on the subject by Herbert Fox. The 416 colored prints reproduced in atlas form, despite their high quality and obvious opulence, prove clearly the superiority of black-and-white photography for the demonstration of fine detail. Reduction of colored photographs of gross specimens to postage-stamp size leads to a further loss of clarity. The atlas portion of the book