tbuckley/cabot-search huggingface dataset:
Laser in situ keratomileusis for correction of myopia and astigmatism after penetrating keratoplasty
Authors: Eric D Donnenfeld, Howard S Kornstein, Abha Amin, Mark D Speaker, John A Seedor, Paul D Sforza, Lori M Landrio, Henry D Perry
Journal: Ophthalmology (1999)

Purpose To determine the safety and effectiveness of laser in situ keratomileusis (LASIK) for visual rehabilitation of residual myopia and astigmatism after penetrating keratoplasty. Design Prospective, noncomparative case series. Participants LASIK was performed on 23 eyes of 22 patients unable to wear glasses or contact lenses after penetrating keratoplasty due to anisometropia, high astigmatism, and/or contact lens-intolerance. Methods All patients underwent LASIK for visual rehabilitation after penetrating keratoplasty. Uncorrected visual acuity and best spectacle-corrected visual acuity, degree of anisometropia, and corneal transplant integrity were recorded before surgery, as well as at 1 month, 3 months, 6 months, and 12 months after LASIK surgery. Results The mean spherical equivalent before surgery was −7.58 ± 4.42 diopters (D), which was reduced to −1.09 ± 2.01 D, −0.79 ± 1.84 D, −0.77 ± 1.25 D, and −1.57 ± 1.20 D, respectively, at 1, 3, 6, and 12 months after LASIK. The mean cylinder before surgery was 3.64 ± 1.72 D, which was reduced to 1.98 ± 1.15 D, 1.64 ± 1.14 D, 1.48 ± 0.92 D, and 1.29 ± 1.04 D, respectively, at 1, 3, 6, and 12 months after LASIK. Spherical equivalent anisometropia was reduced from a mean of 6.88 ± 4.4 D to 1.42 ± 1.05 D at the final examination. Best-corrected visual acuity remained the same or improved in 21 of 23 eyes and decreased by 1 and 3 lines in 2 patients. There were no surgical flap or corneal transplant complications. Conclusions LASIK is a viable treatment alternative for myopia and astigmatism after penetrating keratoplasty in patients who are contact lens-intolerant. LASIK is more effective in treating myopia than astigmatism after penetrating keratoplasty.
Platelet and endothelial activation are requisites for the development of antiphospholipid syndrome
Authors: E del Rio Garcia
Journal: Annals of the Rheumatic Diseases (2004)

The antiphospholipid syndrome (APS) is characterised by venous and arterial thrombosis, recurrent fetal loss, and by the presence of antiphospholipid antibodies (aPL).1 aPL are also present in 2% of the healthy population,2,3 and, with the exception of those with high titres of aPL, there is no clear evidence of an increased incidence of thrombosis throughout the follow up.2–4 Thus, one of the key questions is: What causes the development of thrombosis in patients with APS? We suggest that in APS, a persistent procoagulant state,5,6 a continuous endothelial and platelet activation is present, and this may be detected by raised levels of soluble adhesion molecules.

We prospectively studied the following groups of subjects: ( a ) 20 patients …
Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study
Authors: L. H. Pedersen, T. B. Henriksen, M. Vestergaard, J. Olsen, B. H. Bech
Journal: BMJ (2009)

<b>Objective</b> To investigate any association between selective serotonin reuptake inhibitors (SSRIs) taken during pregnancy and congenital major malformations. <b>Design</b> Population based cohort study. <b>Participants</b> 493 113 children born in Denmark, 1996-2003. <b>Main outcome measure</b> Major malformations categorised according to Eurocat (European Surveillance of Congenital Anomalies) with additional diagnostic grouping of heart defects. Nationwide registers on medical redemptions (filled prescriptions), delivery, and hospital diagnosis provided information on mothers and newborns. Follow-up data available to December 2005. <b>Results</b> Redemptions for SSRIs were not associated with major malformations overall but were associated with septal heart defects (odds ratio 1.99, 95% confidence interval 1.13 to 3.53). For individual SSRIs, the odds ratio for septal heart defects was 3.25 (1.21 to 8.75) for sertraline, 2.52 (1.04 to 6.10) for citalopram, and 1.34 (0.33 to 5.41) for fluoxetine. Redemptions for more than one type of SSRI were associated with septal heart defects (4.70, 1.74 to 12.7)). The absolute increase in the prevalence of malformations was low—for example, the prevalence of septal heart defects was 0.5% (2315/493 113) among unexposed children, 0.9% (12/1370) among children whose mothers were prescribed any SSRI, and 2.1% (4/193) among children whose mothers were prescribed more than one type of SSRI. <b>Conclusion</b> There is an increased prevalence of septal heart defects among children whose mothers were prescribed an SSRI in early pregnancy, particularly sertraline and citalopram. The largest association was found for children of women who redeemed prescriptions for more than one type of SSRI.
Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs
Authors: A Bénardeau
Journal: Cardiovascular Research (2001)

Background: Atrial tachycardia-induced remodeling promotes the occurrence and maintenance of atrial fibrillation (AF) and decreases L-type Ca2+ current. There is also a clinical suggestion that acute L-type Ca2 channel blockade can promote AF, consistent with an AF promoting effect of Ca2+ channel inhibition. Methods: To evaluate the potential mechanisms of AF promotion by Ca2+ channel blockers, we administered verapamil to morphine–chloralose anesthetized dogs. Diltiazem was used as a comparison drug and autonomic blockade with atropine and nadolol was applied in some experiments. Epicardial mapping with 240 epicardial electrodes was used to evaluate activation during AF. Results: Verapamil caused AF promotion in six dogs, increasing mean duration of AF induced by burst pacing, from 8±4 s (mean±S.E.) to 95±39 s (P<0.01 vs. control) at a loading dose of 0.1 mg/kg and 228±101 s (P<0.0005 vs. control) at a dose of 0.2 mg/kg. Underlying electrophysiological mechanisms were studied in detail in five additional dogs under control conditions and in the presence of the higher dose of verapamil. In these experiments, verapamil shortened mean effective refractory period (ERP) from 122±5 to 114±4 ms (P<0.02) at a cycle length of 300 ms, decreased ERP heterogeneity (from 15±1 to 10±1%, P<0.05), heterogeneously accelerated atrial conduction and decreased the cycle length of AF (94±4 to 84±3 ms, P<0.005). Diltiazem did not affect ERP, AF cycle length or AF duration, but produced conduction acceleration similar to that caused by verapamil (n = 5). In the presence of autonomic blockade, verapamil failed to promote AF and increased, rather than decreasing, refractoriness. Neither verapamil nor diltiazem affected atrial conduction in the presence of autonomic blockade. Epicardial mapping suggested that verapamil promoted AF by increasing the number of simultaneous wavefronts reflected by separate zones of reactivation in each cycle. Conclusions: Verapamil promotes AF in normal dogs by promoting multiple circuit reentry, an effect dependent on intact autonomic tone and not shared by diltiazem.
Superior mesenteric artery syndrome in a patient with HIV
Authors: T Agarwal, T A Rockall, A R Wright, S W T Gould
Journal: Journal of the Royal Society of Medicine (2003)

A man of 27 with established AIDS was referred with a diagnosis of cerebral toxoplasmosis and clinical features of high gastrointestinal obstruction. He had been vomiting profusely for six weeks and was unable to retain anything orally. He now weighed just 30 kg. Inability to retain his antiviral medication had led to worsening immunosuppression, and severe oral and oesophageal candidiasis prevented him swallowing his own saliva. The cerebral toxoplasmosis had resulted in mild left sided hemiparesis. On examination of the abdomen there was epigastric fullness with a positive succussion splash. Ultrasound showed the stomach to be massively distended, and CT demonstrated obstruction of the third part of the duodenum by extrinsic compression. A narrow aorto-mesenteric angle in the sagittal section was highly suggestive of superior mesenteric artery (SMA) syndrome (Figure 1) and hypotonic duodenography showed typical cut-off at the third part of the duodenum. An attempt was made at conservative management, initially with total parenteral nutrition and later with nasogastric feeding. However, weight loss continued and the nasogastric aspirate remained greater than 1L/day. Enteral access was necessary for administration of his antiviral and antitoxoplasmosis medication. Surgical intervention was therefore required. The options included a feeding jejunostomy alone (to improve the patient’s nutritional and immune status) or a definitive procedure for SMA syndrome. The latter was chosen. Intraoperative findings confirmed the presence of SMA syndrome. The stomach and proximal duodenum were distended and there was visible compression of the third part of the duodenum, 350 J O U R N A L O F T H E R O Y A L S O C I E T Y O F M E D I C I N E V o l u m e 9 6 J u l y 2 0 0 3
<scp>gp</scp>130 AND THE INTERLEUKIN-6 FAMILY OF CYTOKINES
Authors: Tetsuya Taga, Tadamitsu Kishimoto
Journal: Annual Review of Immunology (1997)

▪ Abstract Receptors for most interleukins and cytokines that regulate immune and hematopoietic systems belong to the class I cytokine receptor family. These molecules form multichain receptor complexes in order to exhibit high-affinity binding to, and mediate biological functions of, their respective cytokines. In most cases, these functional receptor complexes share common signal transducing receptor components that are also in the class I cytokine receptor family, i.e. gp130, common β, and common γ molecules. Interleukin-6 and related cytokines, interleukin-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1 are all pleiotropic and exhibit overlapping biological functions. Functional receptor complexes for this interleukin-6 family of cytokines share gp130 as a component critical for signal transduction. Unlike cytokines sharing common β and common γ chains that mainly function in hematopoietic and lymphoid cell systems, the interleukin-6 family of cytokines function extensively outside these systems as well, e.g. from the cardiovascular to the nervous system, owing to ubiquitously expressed gp130. Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. Although gp130 and its dimer partners possess no intrinsic tyrosine kinase domain, the dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. This paper reviews recent progress in the study of the interleukin-6 family of cytokines and gp130.
Targeting Oncogenes to Improve Breast Cancer Chemotherapy
Authors: Laura A. Christensen, Rick A. Finch, Adam J. Booker, Karen M. Vasquez
Journal: Cancer Research (2006)

Abstract Despite recent advances in treatment, breast cancer remains a serious health threat for women. Traditional chemotherapies are limited by a lack of specificity for tumor cells and the cell cycle dependence of many chemotherapeutic agents. Here we report a novel strategy to help overcome these limitations. Using triplex-forming oligonucleotides (TFOs) to direct DNA damage site-specifically to oncogenes overexpressed in human breast cancer cells, we show that the effectiveness of the anticancer nucleoside analogue gemcitabine can be improved significantly. TFOs targeted to the promoter region of c-myc directly inhibited gene expression by ∼40%. When used in combination, specific TFOs increased the incorporation of gemcitabine at the targeted site ∼4-fold, presumably due to induction of replication-independent DNA synthesis. Cells treated with TFOs and gemcitabine in combination showed a reduction in both cell survival and capacity for anchorage-independent growth (∼19% of untreated cells). This combination affected the tumorigenic potential of these cancer cells to a significantly greater extent than either treatment alone. This novel strategy may be used to increase the range of effectiveness of antitumor nucleosides in any tumor which overexpresses a targetable oncogene. Multifaceted chemotherapeutic approaches such as this, coupled with triplex-directed gene targeting, may lead to more than incremental improvements in nonsurgical treatment of breast tumors. (Cancer Res 2006; 66(8): 4089-94)
Failure of Frontolimbic Inhibitory Function in the Context of Negative Emotion in Borderline Personality Disorder
Authors: David Silbersweig, John F Clarkin, Martin Goldstein, Otto F. Kernberg, Oliver Tuescher, Kenneth N. Levy, Gary Brendel, Hong Pan, Manfred Beutel, Michelle T. Pavony, Jane Epstein, Mark F. Lenzenweger, Kathleen M. Thomas, Michael I. Posner, Emily Stern
Journal: American Journal of Psychiatry (2007)

Objective: The authors sought to test the hypothesis that in patients with borderline personality disorder, the ventromedial prefrontal cortex and associated regions would not be activated during a task requiring motor inhibition in the setting of negative emotion. Such a finding would provide a plausible neural basis for the difficulty borderline patients have in modulating their behavior during negative emotional states and a potential marker for treatment interventions. Method: A specifically designed functional magnetic resonance imaging (fMRI) activation probe was used, with statistical parametric mapping analyses, to test hypotheses concerning decreased prefrontal inhibitory function in the context of negative emotion in patients with borderline personality disorder (N=16) and healthy comparison subjects (N=14). 3-T fMRI scanning was used to study brain activity while participants performed an emotional linguistic go/no-go task. Results: Analyses confirmed that under conditions associated with the interaction of behavioral inhibition and negative emotion, borderline patients showed relatively decreased ventromedial prefrontal activity (including medial orbitofrontal and subgenual anterior cingulate) compared with healthy subjects. In borderline patients, under conditions of behavioral inhibition in the context of negative emotion, decreasing ventromedial prefrontal and increasing extended amygdalar-ventral striatal activity correlated highly with measures of decreased constraint and increased negative emotion, respectively. Conclusions: These findings suggest specific frontolimbic neural substrates associated with core clinical features of emotional and behavioral dyscontrol in borderline personality disorder.
Dietary flavonoids in cancer therapy and prevention: Substrates and inhibitors of cytochrome P450 CYP1 enzymes
Authors: Vasilis P. Androutsopoulos, Athanasios Papakyriakou, Dionisios Vourloumis, Aristidis M. Tsatsakis, Demetrios A. Spandidos
Journal: Pharmacology & Therapeutics (2010)
The Tetratricopeptide Repeats of Receptors Involved in Protein Translocation across Membranes
Authors: T. Schlegel, O. Mirus, A. von Haeseler, E. Schleiff
Journal: Molecular Biology and Evolution (2007)

Transport of polypeptides across membranes is a general and essential process in every cell. This process is utilized by molecular machines composed of soluble and membrane-inserted proteins. At least one component of the molecular transport machines present in different membranes contains a subunit with a domain composed of 3 tetratricopeptide repeat (TPR) motifs. These domains are important for protein–protein interaction, for example, recognition of chaperones. To understand the evolution of these TPR domain–containing receptors involved in protein translocation, we inferred their phylogenetic relationships. We show that the evolutionary rate of these TPR domains is reduced when compared with the remaining sequence. The reduction is explained by the interaction of the TPR domains with their substrates. Based on the TPR tree, we propose that Sec72 recognizes Hsp70 and that Tom34 recognizes Hsp90. The phylogeny can further be used to assign the localization of the Toc64 isoforms to mitochondria or chloroplasts. Our findings are discussed in the context of the evolutionary development of translocation systems with focus on the occurrence of Hsp70/Hsp90-recognizing TPR domains in these machineries.
Loss of Tumorigenicity and Metastatic Potential in Carcinoma Cells Expressing the Extracellular Domain of the Type 1 Insulin-Like Growth Factor Receptor
Authors: Amir Abbas Samani, Eric Chevet, Lucia Fallavollita, Jacques Galipeau, Pnina Brodt
Journal: Cancer Research (2004)

Abstract The receptor for the type 1 insulin-like growth factor (IGF-IR) was identified as a major regulator of the malignant phenotype and a target for cancer therapy. In the present study, a novel IGF-IR mutant consisting of the entire extracellular domain of the receptor (IGFIR933) was genetically engineered and expressed in highly metastatic H-59 murine lung carcinoma cells. We show here that the cells expressed a truncated heterotetramer (βm-α-α-βm) that was secreted into the medium and could neutralize the effects of exogenous IGF-I, thus diminishing IGF-I-induced signaling and blocking IGF-I-mediated cellular functions such as cell proliferation, invasion, and survival. In vivo, tumor incidence and growth rate were markedly reduced in mice inoculated s.c. with H-59/IGFIR933 cells. Moreover, after the intrasplenic/portal inoculation of these cells, there was a 90% reduction in the incidence of hepatic metastases and a significant increase in the long-term, disease-free survival of the mice compared with controls. Our results identify the IGFIR933 as a potent antitumorigenic and antimetastatic agent with potential applications for cancer gene therapy.
Electrophysiological response of vascularized hamster cardiac transplants to ischemia.
Authors: R F Gilmour, D P Zipes
Journal: Circulation Research (1982)

To study transmembrane electrophysiological properties of blood-perfused mammalian heart cells during normal perfusion and during acute ischemia, 1- to 2-mm cubes of neonatal hamster atrial and ventricular myocardium were transplanted to the adult hamster cheek pouch and studied with microelectrodes 4--7 days later, when vascularization and spontaneous contractions occurred. Action potentials recorded from the transplants were similar to those recorded from neonatal and adult hamster myocardium studied in vitro. Interrupting blood flow to spontaneously beating transplants reduced diastolic depolarization and suppressed automaticity. After automaticity ceased, the transplants were paced with a bipolar electrode or intracellular microelectrode. Action potential amplitude, resting potential, and dV/dtmax decreased during ischemia. Action potential duration and the intracellular current threshold for excitation increased initially, subsequently decreased to values less than control, and increased again prior to the onset of inexcitability. Conduction delay and block occurred during the late stages of ischemia. Depressed action potentials recorded during ischemia were suppressed by tetrodotoxin (10(-5) M) but not by verapamil (2 x 10(-6) M). These data indicate that: (1) the electrophysiological properties of cheek pouch cardiac transplants are normal, (2) ischemia suppresses transplant automaticity, (3) cellular excitability increases during the early stages of ischemia and decreases at a time when conduction delay and block occur, and (4) action potentials generated during the later stages of ischemia appear to be depressed fast responses, rather than slow responses.
RTOG 94-10: Keenly Awaited Results Validating the Best Therapeutic Strategy for Locally Advanced Non-Small Cell Lung Cancer
Authors: P. Fournel
Journal: JNCI Journal of the National Cancer Institute (2011)

About 30% of patients diagnosed with non–small cell lung cancer (NSCLC) have inoperable locally advanced disease. Despite therapeutic advances over the past two decades, these patients’ prognosis remains poor, with a 5-year survival rate of only 10%–15%. Until the late 1980s, radiotherapy was the only treatment option. The Radiation Therapy Oncology Group (RTOG) had shown that local disease control was improved by increasing the total dose to 60 Gy delivered in 30 fractions over 6 weeks (1). The 1990s saw the emergence of both sequential and concurrent combinations of chemotherapy and radiotherapy. A number of randomized phase III trials, and several meta-analyses, showed that chemoradiotherapy was superior to radiotherapy alone in terms of overall survival (2,3). Concurrent therapy seemed to give better results than sequential therapy, but this needed to be demonstrated. The Japanese trial published by Furuse et al. (4) was the first randomized phase III trial to show a statistically significant improvement in overall survival after concurrent chemoradiotherapy, with no increase in esophageal toxicity. In this issue of the Journal, Curran et al. (5) report the results of the RTOG 94-10 study, which compared three schedules: sequential treatment with cisplatin–vinblastine induction chemotherapy followed by radiotherapy at a total dose of 63 Gy (arm 1); a concurrent schedule in which two cycles of cisplatin–vinblastine were administered during the same radiotherapy schedule as in arm 1 (arm 2); and another concurrent schedule combining cisplatin–etoposide chemotherapy with bifractionated radiotherapy at a total dose of 69.6 Gy (arm 3), as used in the RTOG 91-06 study. Arm 2 was first compared with the sequential schedule, which served as the reference treatment, and then arm 3 was compared with the better of the other two arms. The results showed that concurrent cisplatin–vinblastine and radiotherapy statistically significantly increased overall survival compared with the sequential treatment, whereas there was no statistically significant difference between the two concurrent schedules. The benefit persisted at 5 years, as in the French GLOT-GFPC NPC 95-01 study in which the improvement in overall survival observed with the concurrent schedule was stable at 5 years (18.5% vs 8.5%) and at 7 years (15% vs 5.8%) (6, 7). The RTOG 94-10 study, already presented partially on two occasions, has been awaited for several years. Individual data from this study were included in the NSCLC Collaborative Group meta-analysis of six randomized trials that confirmed the superiority of concurrent treatment (8). The gain in overall survival was associated with better local control. As expected, acute esophageal toxicity was more