tbuckley/cabot-search huggingface dataset:
Engineering Stem Cells for Biomedical Applications
Authors: Perry T. Yin, Edward Han, Ki‐Bum Lee
Journal: Advanced Healthcare Materials (2015)

Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre‐clinical and clinical studies have utilized stem cell‐based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in‐depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer.
Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability
Authors: Lewis L. Hsu, Hunter C. Champion, Sally A. Campbell-Lee, Trinity J. Bivalacqua, Elizabeth A. Manci, Bhalchandra A. Diwan, Daniel M. Schimel, Audrey E. Cochard, Xunde Wang, Alan N. Schechter, Constance T. Noguchi, Mark T. Gladwin
Journal: Blood (2006)
Abstract 4359: Use of high resolution Doppler imaging for non-invasive, quantitative evaluation of hypoxia-driven neovascularization following surgical ligation of the femoral artery
Authors: Nick Duesbery, Elissa Boguslawski, Brittany Merrifield, Anthony Chang, Christopher Chambers
Journal: Cancer Research (2012)

Abstract A tumor's growth is inextricably linked with its vascularization. Rapidly growing tumors outstrip their blood supply, creating hypoxia. To compensate, tumor cells release angioproliferative factors that stimulate endothelial cell proliferation. Proliferating endothelial cells contribute to the formation of new blood vessels that promote tumor perfusion and stimulate further tumor growth. The close link between tumor growth and neovascularization makes it difficult to study either process in the absence of the other. To address this we have adapted a mouse model used in the study of peripheral arterial disease. Ischemia was induced by surgical ligation and excision a 3-5mm portion of the femoral artery, vein, and all nearby arterial branches in the right hindlimb of 10-12 week old athymic nude mice. Limb perfusion was measured prior to surgery and 1, 7, 14, 21, and 28 days post-surgery. A 7mm portion of hindlimb perfusion was quantified using Power Doppler mode on the VisualSonics Vevo 770 High Resolution micro Ultrasound system. Morphological changes were observed by histology and immunohistochemistry using antibodies against CD31 and F4/80. Based on quantified Doppler ultrasound data, limb perfusion was reduced as much as 80% within 24 hrs of ligation. Blood flow was restored over the course of the next 7 days. However, re-perfused limbs showed a diffuse pattern of blood flow in comparison to control limbs. Loss of perfusion was accompanied by muscle atrophy and the accumulation of intra-fasicular fat deposits. IHC revealed a marked increase of F4/80 and CD31 staining in ligated limbs. Similar changes were not observed in contralateral limbs that were not operated on or in sham-ligated hind limbs. Our data is consistent with the interpretation that femoral artery ligation causes acute loss of perfusion that is compensated for by macrophage recruitment and disseminated neovascularization. This model provides a novel opportunity to study neovascularization in the absence of tumor growth that will complement ongoing studies using tumor-based models of angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4359. doi:1538-7445.AM2012-4359
Temozolomide Preferentially Depletes Cancer Stem Cells in Glioblastoma
Authors: Dagmar Beier, Stefanie Röhrl, Deepu R. Pillai, Stefanie Schwarz, Leoni A. Kunz-Schughart, Petra Leukel, Martin Proescholdt, Alexander Brawanski, Ulrich Bogdahn, Ariane Trampe-Kieslich, Bernd Giebel, Jörg Wischhusen, Guido Reifenberger, Peter Hau, Christoph P. Beier
Journal: Cancer Research (2008)

Abstract The prognosis of patients suffering from glioblastoma (GBM) is dismal despite multimodal therapy. Although chemotherapy with temozolomide may contain tumor growth for some months, invariable tumor recurrence suggests that cancer stem cells (CSC) maintaining these tumors persist. We have therefore investigated the effect of temozolomide on CD133+ and CD133− GBM CSC lines. Although differentiated tumor cells constituting the bulk of all tumor cells were resistant to the cytotoxic effects of the substance, temozolomide induced a dose- and time-dependent decline of the stem cell subpopulation. Incubation with sublethal concentrations of temozolomide for 2 days completely depleted clonogenic tumor cells in vitro and substantially reduced tumorigenicity in vivo. In O6-methylguanine-DNA-methyltransferase (MGMT)–expressing CSC lines, this effect occurred at 10-fold higher doses compared with MGMT-negative CSC lines. Thus, temozolomide concentrations that are reached in patients were only sufficient to completely eliminate CSC in vitro from MGMT-negative but not from MGMT-positive tumors. Accordingly, our data strongly suggest that optimized temozolomide-based chemotherapeutic protocols might substantially improve the elimination of GBM stem cells and consequently prolong the survival of patients. [Cancer Res 2008;68(14):5706–15]
Putative binding sites for benzocaine on a human cardiac cloned channel (Kv1.5)
Authors: R Caballero
Journal: Cardiovascular Research (2002)

Objectives: It has been demonstrated that at nanomolar concentrations benzocaine increased, whereas at micromolar concentrations, it blocked hKv1.5 channels in a voltage-dependent manner and modified the voltage-dependence of channel activation. The present study was undertaken to localize the putative binding sites involved in the 'agonists' and blocking effects of benzocaine. Methods: Experiments were carried out on wild-type and site directed mutated hKv1.5 channels stably expressed on Ltk− cells using the whole-cell patch-clamp. Results: At 35 mM [K+]i the voltage-dependent unblock produced by 500 μM benzocaine was preserved at both 4 and 140 mM [K+]o. Mutations located in the inner mouth of the pore (T477S, T505A, L508M and V512M) abolished the agonist but increased the blocking effects of benzocaine. Intracellular application of tetraethylammonium (3 mM) abolished the 'agonist' effects whereas the blocking effects of benzocaine remained unaltered. Block induced by benzocaine and intracellular tetraethylammonium was additive. In contrast, the combination of benzocaine and bupivacaine (>25 μM) produced less blockade than bupivacaine alone. However, mutation of the extracellular residue R485Y did not modify the effects of benzocaine. Extracellular application of tetraethylammonium (100 mM) did not modify the agonist effects of benzocaine, but abolished the voltage- and time-dependence of benzocaine-induced block. Conclusions: The results suggested that benzocaine binds with high affinity to an intracellular binding site to produce 'agonist' effects and to a low affinity subsite, which is also located in the inner mouth, to produce the blocking effects. Furthermore, benzocaine and extracellular K+ interact to modify the voltage-dependence of channel opening.
Variations of serum eosinophil cationic protein and tryptase, measured in serum and saliva, during the course of immediate allergic reactions to foods
Authors: L. Vila, M. L. Sanz, G. Sánchez‐López, C. García‐Avilés, I. Diéguez
Journal: Allergy (2001)

Background: Subjective complaints and reactions after placebo administration during food challenges (FC) may make their outcome difficult to interpret. We determined serum ECP and tryptase as tryptase in saliva during FC, looking for markers to support challenge outcomes. Methods: Twelve patients with systemic reactions after food intake and nine presenting oral allergy syndrome (OAS) underwent skin tests; total and specific IgE determination; double‐blind, placebo‐controlled FC (DBPCFC); and open challenges. Blood samples were collected before and 1, 2, and 5 h after challenge and saliva before and 5, 30, and 60 min after challenge. ECP and tryptase were quantified by ImmunoCAP (Pharmacia‐Upjohn, Sweden). Serum tryptase of &gt;10 µg/l was considered positive. Results: After positive DBPCFC ( n =8), ECP rose significantly ( P &lt;0.05) at 1‐h – 16.03 (12.8) μg/l (mean [standard deviation]) – and 2‐h intervals – 17.56 (10.7) μg/l – compared to basal level of 9 (6.4) μg/l. After negative DBPCFC ( n =6), ECP increased from basal 9.63 (3.9) μg/l to 24.84 (14.17) μg/l at the 2‐h time point. There were nonsignificant differences in ECP between patients with positive and negative FC. Two patients with positive challenge showed a tryptase level of &gt;10 µg/l and only one patient with OAS showed 5.6 µg/l of tryptase 5 min after FC. Conclusions: ECP and tryptase in serum and saliva were not useful markers for FC outcomes.
The Problem of Operation for Retroverted Uterus
Authors: C. Rendle-Short
Journal: BMJ (1941)

collapsed and developed on the face, neck, and hands a " deep blue-black colour."The replies diagnosed the occurrence as a case of aniline poisoning with formation of methaemoglobin- aemia.Commenting on the case, I drew attention (Journal, 1930, 2, 980) to the fact that there was not enough benzene chemical (nitro or amido) in a few drops of dye to cause methaemoglobinaemia, and suggested that the dye soaked into the fibre stopping and dissolved in the lipoids in the inc.sive nerve and thus reachMd the brain.The blueness and the dis- tribution could not have been a blood change, but'could arise from action of the sympathetic or central nervous system, or of both.
Validation of local venous sampling within the at risk left anterior descending artery vascular bed in the canine left ventricle
Authors: J VINTEN-JOHANSEN, W. E JOHNSTON, G. J CRYSTAL, S. A MILLS, W. P SANTAMORE, A R. CORDELL
Journal: Cardiovascular Research (1987)

The validity of using blood sampled from the anterior interventricular vein (AIV), anatomically located within the myocardium perfused by the left anterior descending (LAD) coronary artery, to represent venous drainage originating from the LAD vascular territory was studied in eight anaesthetised, open chest dogs. The LAD was cannulated and perfused from a blood reservoir isolated from the systemic circulation. To determine the presence of blood from non-LAD sources that appears in the AIV sample, 51Cr-labelled red blood cells were injected into the left atrium and distributed in the systemic circulation while the LAD was perfused by non-radioactive blood. The percentage spillover of red blood cells from non-LAD sources into the AIV drainage was determined under control, reduced LAD flow, ischaemia, and reperfusion conditions as 100 × (AIV chromium content/arterial chromium content). Spillover of red blood cells into AIV blood samples averaged only 1.5(1.3)% under control conditions and increased insignificantly to 8.6(3.5)% during reduced LAD flow. During ischaemia red blood cells in AIV blood increased significantly to 98.3(5.0)% but decreased to 1.9(1.3)% after reperfusion. Studies in five dogs with microspheres showed that a portion of this admixture from non-LAD sources originated from precapillary nutritional collateral or overlapping blood flow. It is concluded that (a) blood sampled from the anterior interventricular vein accurately reflects venous drainage originating almost exclusively from myocardium perfused by the LAD under normal and low flow conditions and (b) reperfusion after transient ischaemia does not change the unique origin of AIV blood. This technique may therefore be used reliably to assess oxygen utilisation and metabolic variables in the myocardium perfused by the LAD.
Increased cholecystectomy rate after the introduction of laparoscopic cholecystectomy in Scotland.
Authors: C M Lam, F E Murray, A Cuschieri
Journal: Gut (1996)

This survey determined the effect of the introduction of laparoscopic cholecystectomy on the rates of cholecystectomy (total and laparoscopic) in Scotland. From 1977 to 1990, the Scottish cholecystectomy rate fell by an average of almost 1% per annum. With the advent of laparoscopic cholecystectomy, the total cholecystectomy rate (open and laparoscopic) rose considerably--by 18.7% from 1989-93 (p &lt; 0.05). The largest increase (25%) was observed in the 45-64 years age group but it was also particularly evident (19%) in elderly patients (65-74 years). Subjects were more likely to undergo laparoscopic cholecystectomy than open cholecystectomy if they were young and female. The increased cholecystectomy rate observed merits careful scrutiny and health economic evaluation.
BILATERAL ABDUCTOR PARALYSIS OF THE LARYNX CAUSED BY "MOONSHINE" WHISKY
Authors: SAMUEL SALINGER
Journal: JAMA (1922)

Bile was collected in fifteen minute fractions for one hour in order to determine the normal flow.The solu¬ tion of magnesium sulphate was then injected into the duodenum, and observations on the flow of the bile were made for one hour in fifteen minute fractions (Table 2 andChart 2).Similar observations were made before and after intravenous injection of mag¬ nesium sulphate (Table 3 andChart 3).In order to test the validity of the procedure of the intraduodenal injection of magnesium sulphate, experi¬ ments were carried out in which fresh bile was injected into the duodenum in the same manner (Table 4 and Chart 4).The experiment was controlled by another in which physiologic sodium chlorid solution was used instead of bile. COMMENTThe experiments outlined were undertaken in order to determine whether magnesium sulphate introduced directly into the duodenum or into the circulation would cause any change in the volume or in the character of the bile.The data tabulated are representative of
Molecular dosimetry of genotoxic damage: biochemical and immunochemical methods to detect DNA damage
Authors: Paul H.M. Lohman, Rob A. Baan, Anne Marie J. Fichtinger-Schepman, Marianne A. Muysken-Schoen, Ria J. Lansbergen, Frits Berends
Journal: Trends in Pharmacological Sciences (1985)
Six GPs who signed cremation forms for Shipman face GMC
Authors: Owen Dyer
Journal: BMJ (2004)

We previously reported that endothelin (ET) may function as an inhibitory modulator of renal noradrenergic neurotransmission (Suzuki<i>et al., J. Cardiovasc. Pharmacol. </i><b>19:</b> 905–910, 1992). In our study, we examined the effect of sarafotoxin S6c (S6c), a selective ET<sub>B</sub> receptor agonist, on changes in renal function and norepinephrine overflow induced by renal nerve stimulation (RNS) in anesthetized dogs. RNS at a low frequency (0.5–2.0 Hz) caused significant decreases in urine flow, urinary excretion of sodium and fractional excretion of sodium and increased norepinephrine secretion rate, without affecting systemic and renal hemodynamics. RNS at a high frequency (2.5–5.0 Hz), which diminishes renal hemodynamics, produced more potent decreases in urine formation and increase in norepinephrine secretion rate than seen with low frequency RNS. When S6c (1 ng/kg/min) was infused intrarenally, there was a slight and transient increase in renal blood flow, and then this response was followed by a gradual reduction. S6c administration produced increase in the basal level of urine flow with no apparent effects on urinary excretion of sodium and fractional excretion of sodium. During S6c infusion, low frequency RNS-induced antidiuretic action and increase in norepinephrine secretion rate were markedly attenuated. Qualitatively, similar results were observed in the case of high frequency RNS. In addition, high frequency RNS-induced decreases in glomerular filtration rate and filtration fraction were significantly suppressed by S6c infusion. Taken together with our previous findings, it seems likely that ET plays an important role as an inhibitory modulator of renal noradrenergic neurotransmission, through ET<sub>B</sub> receptor mechanisms.
Disease Control Programs in the United States
Authors: Joseph B. McCormick, David W. Fraser
Journal: JAMA (1978)

Programs administered by health departments and heart associations for control of streptococcal and poststreptococcal disease differ greatly from state to state. The year 1974 was used as a representative year when studying the variety of state policies and programs regarding surveillance of streptococcal disease, primary and secondary prevention of rheumatic fever, and prevention of poststreptococcal glomerulonephritis. A uniform national policy for streptococcal control is desirable but should be based on evidence not now available concerning the impact of various elements of control programs on morbidity and mortality.
Abstract 2155: Achieving complete response to locoregional disease without toxicity using temperature-sensitive liposomes and ultrasound-mediated hyperthermia.
Authors: Azadeh Kheirolomoom, Chun-Yen Lai, Sarah M. TAM, Lisa M. Even, Elizabeth S. Ingham, Brett Z. Fite, Katherine D. Watson, Katherine W. Ferrara
Journal: Cancer Research (2013)

Abstract By stabilizing doxorubicin within temperature-sensitive liposomes and repeating delivery twice per week for four weeks, extended survival and complete response were obtained in syngeneic murine breast tumors. Further, with the stabilized formulation, cardiac toxicity and leukopenia were not detected. Liposomes composed of DPPC:MPPC:DSPE-PEG2k, 86:10:4 were prepared in the presence of copper(II) gluconate and triethanolamine and extruded with 100 nm membrane filters. Cu-liposomes were loaded with Dox at 0.2 mg-drug/mg-lipid with 100% loading. We studied the efficacy of CuDox liposomes (CuDox-LTSLs) using the highly invasive neu deletion (NDL) tumor. Treatment began when the tumor diameter reached 4 mm. The fluorescence of circulating doxorubicin in blood was quenched after the digestion of liposomes with Triton X-100, indicating that the circulating drug remained associated with copper. Dox fluorescence was restored upon reducing the pH using a citrate-saline buffer. Over the 28 days of the study, CuDox-LTSLs were administrated intravenously two times per week at a therapeutic level of 6 mg-drug/kg-body weight. The entire tumor was insonified with a peak ultrasound pressure of 1.1 MPa at a frequency of 1.5 MHz at 42°C for 5 min prior to and 20 min post drug injection. A total of 30 mice were studied, including groups spanning drug treatment with ultrasound, ultrasound, drug treatment and no treatment. Although a single dose administration of CuDox-LTSLs combined with insonation of the entire tumor suppressed the tumor growth, complete response was achieved only upon repeated treatment over a period of 28 days. At 30 days after the last administered dose, none of the mice from the other groups survive; however, 100% of mice treated with ultrasound combined with CuDox-LTSLs survive and the remaining tumor is undetectable. In conclusion, repeated treatment of stabilized temperature sensitive doxorubicin liposomes is highly effective in the treatment of aggressive murine tumors. Acknowledgement: NIHR01CA134659 and NIHR01CA103828 Citation Format: Azadeh Kheirolomoom, Chun-Yen Lai, Sarah M. TAM, Lisa M. Even, Elizabeth S. Ingham, Brett Z. Fite, Katherine D. Watson, Katherine W. Ferrara. Achieving complete response to locoregional disease without toxicity using temperature-sensitive liposomes and ultrasound-mediated hyperthermia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2155. doi:10.1158/1538-7445.AM2013-2155
MODERN HOSPITAL CONSTRUCTION.
Authors: W. GILMAN THOMPSON
Journal: JAMA (1907)

The modern idea of the construction of the general hospital building is that the building itself should bear a definite relationship to treatment, that it is more than a mere convenient form of lodging house for the sick, and that environment is a potent factor in the control of disease, often more powerful than the giving of pills and potions. One reason among many for this position is the lesson taught by tuberculosis, namely, that fresh air is not a specific for that disease alone, but acts through increasing the resisting power of the organism. If this be true of tuberculosis, why is it not also true of many other diseases? Hence hospitals are built with almost as much ward space outside as inside the retaining walls, with wide verandas opening off every ward, and broad flat roofs for exercise, fresh air and sunlight. Another reason is a demand for
Living histamine-containing cells from the bronchial lumens of humans. Description and comparison of histamine content with cells of rhesus monkeys.
Authors: R Patterson, J M McKenna, I M Suszko, N H Solliday, J J Pruzansky, M Roberts, T J Kehoe
Journal: Journal of Clinical Investigation (1977)

Cell populations obtained by bronchial lavage from human subjects were examined for the presence of cells related to the mast cell-basophil series. Such bronchial lumen histamine-containing cells (BLHCC) were identified. The BLHCC stained with toluidine blue may be identified by bright field or dark field microscopy. The BLHCC are alive as evidenced by ability to release histamine (H) after exposure to anti-IgE or calcium ionophore. Although H release from peripheral blood leukocytes by these two agents is potentiated by the presence of D2O, H release from BLHCC of the same subjects by anti-IgE or calcium ionophore was not potentiated by D2O. In studies comparing bronchial cell populations of humans and rhesus monkeys with peripheral blood leukocyte populations of the same subjects, the histamine content of the bronchial cell population was much higher in rhesus monkeys. IgE/Alb ratios of respiratory secretions and serum of the same human subjects were of the same order of magnitude in contrast to previous comparisons done on these fluids in rhesus monkeys.
Effect of Ventricular Extrasystoles on Closure of Mitral Valve
Authors: RUSSELL A. VANDENBERG, JOHN C.P. WILLIAMS, RALPH E. STURM, EARL H. WOOD
Journal: Circulation (1969)

Mitral valve function was assessed by roentgen videodensitometry. Mitral reflux was rare when single ventricular ectopic systoles were produced by electronic stimulation of the right or left ventricle at various times in the cardiac cycle. It was also rare during the compensatory pause after the ectopic systole or with the following postectopic systole. Recurrent ventricular ectopic systoles interposed once per cycle were associated with minor reflux when introduced in mid-cycle. Such extrasystoles occurred late enough in the cardiac cycle for the ventricle to relax after the primary systole and for the mitral valve to open before the extrasystole. The extrasystolic contractions were, however, weak and incapable of opening the aortic valve. When interposed early in the cardiac cycle, extrasystolic potentiation of the primary ventricular contraction occurred, and no or minimal mitral reflux was observed.