tbuckley/cabot-search huggingface dataset:
Na+/H+ exchange and regulation of intracellular Ca2+
Authors: G. GAMBASSI
Journal: Cardiovascular Research (1993)

Journal Article Na+/H+ exchange and regulation of intracellular Ca2+ Get access GIOVANNI GAMBASSI GIOVANNI GAMBASSI Istituto di Clinica Medica Generale, Università Cattolica del Sacro Cuore, Rome, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 10, October 1993, Page 1885, https://doi.org/10.1093/cvr/27.10.1885 Published: 01 October 1993
Postvaccine Era Measles Epidemiology
Authors: Charles L. Paule
Journal: JAMA (1979)

Measles incidence in the United States was calculated from estimates of the United States Immunization Survey for the years 1965 to 1975. These data were examined according to birth cohorts and cross-sectionally by age to determine the effect of live measles virus vaccine on measles epidemiology. The results showed a high rate of infection for children aged 1 year, followed by a decrease in the infection rates for preschool children, with rates increasing agin at ages 5 and 6 years. It was hypothesized that an effective vaccine-induced herb immunity exists in preschool children until they are of school age. When incidence rates were based on susceptible children, the highest rates occurred in the school-aged populations.
Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium.
Authors: A Nusrat, C A Parkos, A E Bacarra, P J Godowski, C Delp-Archer, E M Rosen, J L Madara
Journal: Journal of Clinical Investigation (1994)

Intestinal epithelial cells rest on a fibroblast sheath. Thus, factors produced by these fibroblasts may influence epithelial function in a paracrine fashion. We examined modulation of intestinal epithelial function by one such fibroblast product, scatter factor/hepatocyte growth factor (HGF/SF). This effect was studied in vitro by using model T84 intestinal epithelial cells. When applied to confluent T84 monolayers, HGF/SF attenuates transepithelial resistance to passive ion flow in a dose-dependent manner (maximum fall at 300 ng/ml, 28% control monolayer resistance, P < 0.001, ED50 of 1.2 nM), t1/2 of 20 h. This functional effect of HGF/SF and distribution of its receptor, c-met, are polarized to the basolateral membranes of T84 intestinal epithelial cells. HGF/SF effects on resistance are not attributable to altered transcellular resistance (opening of Cl- and/or basolateral K+ channels), cytotoxicity, or enhanced cell proliferation; they therefore represent specific regulation of paracellular tight junction resistance. Analysis with biochemically purified rodent HGF/SF and Madin-Darby canine kidney cells reveals that effects on paracellular tight junctions also occur in other nontransformed epithelia. Binding of HGF/SF to its receptor in T84 intestinal epithelial cells is accompanied by tyrosine phosphorylation of the receptor. Because loosening of intercellular junctions between cells could facilitate separation, spreading, and migration of epithelial cells during physiologic processes such as wound resealing, we determined the effects of HGF/SF on intestinal epithelial wound resealing using our previously published in vitro model (Nusrat, A., C. Delp, and J. L. Madara. 1992. J. Clin. Invest. 89:1501-1511). HGF/SF markedly enhanced wound closure (> 450% increase in rate, P < 0.001) by influencing the migratory and spreading response in not only cells adjoining the wound but also cells many positions removed from the wound. We thus speculate that HGF/SF may serve as an important cytokine that influences epithelial parameters such as transepithelial resistance and wound resealing. Further pharmacological approaches to manipulate HGF/SF signaling pathways may provide novel therapeutic strategies to enhance repair of intestinal epithelial erosions/ulcerations.
Psychiatric Comorbidity in Pathological Gamblers Seeking Treatment
Authors: Angela Ibáñez, Carlos Blanco, Elizabeth Donahue, Henry R. Lesieur, Ignacio Pérez de Castro, José Fernández-Piqueras, Jerónimo Sáiz-Ruiz
Journal: American Journal of Psychiatry (2001)

The authors' goal was to determine the frequency of psychiatric comorbidity among treatment-seeking pathological gamblers, compare the severity of gambling and psychological problems in gamblers with and without comorbid disorders, and investigate differences between gamblers with and without comorbid disorders in the dopamine D(2) receptor gene (DRD(2)).Sixty-nine pathological gamblers who consecutively applied to a specialized outpatient treatment program were evaluated with structured interviews, self-report questionnaires, and psychological scales and were genotyped for a DRD(2) polymorphism.A comorbid psychiatric disorder was present in 43 (62.3%) of the gamblers. The most frequent diagnoses were personality disorders (N=29 [42.0%]), alcohol abuse or dependence (N=23 [33.3%]), and adjustment disorders (N=12 [17.4%]). Gamblers with comorbid psychiatric disorders had gambling scores and psychological scale scores indicating greater severity of gambling and psychopathology. Significant differences in DRD(2) allele distribution were found in gamblers with and without comorbid disorders.Psychiatric comorbidity is common among pathological gamblers and is associated with greater severity of clinical problems. The DRD(2) gene could be a liability genetic factor for psychiatric comorbidity in pathological gambling.
ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside
Authors: Jianbiao Zhou, Boon-Cher Goh, Daniel H Albert, Chien-Shing Chen
Journal: Journal of Hematology & Oncology (2009)

Tyrosine Kinase Inhibitors (TKI) have significantly changed the landscape of current cancer therapy. Understanding of mechanisms of aberrant TK signaling and strategies to inhibit TKs in cancer, further promote the development of novel agents.ABT-869, a novel ATP-competitive receptor tyrosine kinase inhibitor is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families. ABT-869 showed potent antiproliferative and apoptotic properties in vitro and in animal cancer xenograft models using tumor cell lines that were "addicted" to signaling of kinases targeted by ABT-869. When given together with chemotherapy or mTOR inhibitors, ABT-869 showed at least additive therapeutic effects. The phase I trial for ABT-869 was recently completed and it demonstrated respectable efficacy in solid tumors including lung and hepatocellular carcinoma with manageable side effects. Tumor cavitation and reduction of contrast enhancement after ABT-869 treatment supported the antiangiogenic activity. The correlative laboratory studies conducted with the trial also highlight potential biomarkers for future patient selection and treatment outcome.Parallel to the clinical development, in vitro studies on ABT-869 resistance phenotype identified novel resistance mechanism that may be applicable to other TKIs. The future therapeutic roles of ABT-869 are currently been tested in phase II trials.
A Selective Barrier to Horizontal Gene Transfer in the T4-Type Bacteriophages That Has Preserved a Core Genome with the Viral Replication and Structural Genes
Authors: Jonathan Filée, Henry Krisch, E. Bapteste, E. Susko
Journal: Molecular Biology and Evolution (2006)

Genomic analysis of bacteriophages frequently reveals a mosaic structure made up from modules that come from disparate sources. This fact has led to the general acceptance of the notion that rampant and promiscuous lateral gene transfer (LGT) plays a critical role in phage evolution. However, recent sequencing of a series of the T4-type phages has revealed that these large and complex genomes all share 2 substantial syntenous blocks of genes encoding the replication and virion structural genes. To analyze the pattern of inheritance of this core T4 genome, we compared the complete genome sequences of 16 T4-type phages. We identified a set of 24 genes present in all these T4-type genomes. Somewhat surprisingly, only one of these genes, that encodes for ribonucleotide reductase (NrdA), displayed evidence of LGT with the bacterial host. We test the congruence of the inheritance of the other 23 markers using heat map analyses and comparison of a reference topology with the 23 individual gene phylogenies. The vast majority of these core genes share a common evolutionary history. In contrast, analyses of all the noncore genes present in the same 16 genomes, located in the hyperplastic regions of the genome, show considerable evidence of frequent LGT. The similar evolution of the core replication and virion structural genes in the T4-type phage genomes suggests that, unlike the situation in many other phage groups, such portions of T4-type genome have been inherited as a block, without significant LGT, from a distant common ancestor. The preservation of the synteny of the core T4 genome could result from several factors acting in synergy, such as the constraints imposed by the sophisticated regulation of the transcription. Moreover, numerous and complex protein–protein interactions during virion morphogenesis could also impose a supplementary barrier against LGT. Finally, there may be some real evolutionary advantage to maintaining large regions of conserved sequence. Such segments could be a sort of genetic glue that maintains the genetic cohesion of the T4-type phages via recombination within the most conserved sequences. This could mediate the swapping of nonconserved sequences that they flank.
CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas
Authors: Anand Veeravagu, Bowen Jiang, Chirag G Patil, Marco Lee, Scott G Soltys, Iris C Gibbs, Steven D Chang
Journal: Journal of Hematology & Oncology (2011)

Abstract Objective Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas. Methods In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm 3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively. Results Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%. Conclusions CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.
Skeletal Muscle Metabolism Limits Exercise Capacity in Patients With Chronic Heart Failure
Authors: Koichi Okita, Kazuya Yonezawa, Hirotaka Nishijima, Akiko Hanada, Mitsunori Ohtsubo, Tetsuro Kohya, Takeshi Murakami, Akira Kitabatake
Journal: Circulation (1998)

Several studies have indicated that skeletal muscle is important in determining the exercise capacity of patients with chronic heart failure (CHF). However, this theory has been investigated only in experiments based on local exercise involving a small muscle mass. We investigated skeletal muscle metabolism during maximal systemic exercise to determine whether muscle metabolism limits exercise capacity in patients with CHF. We also studied the relationship between muscle metabolic abnormalities during local and systemic exercise.Skeletal muscle metabolism was measured during maximal systemic exercise on a bicycle ergometer by a combination of the metabolic freeze method and 31P magnetic resonance spectroscopy in 12 patients with CHF and 7 age- and size-matched normal subjects. We also evaluated skeletal muscle metabolism during local exercise while subjects performed unilateral plantar flexion. Muscle phosphocreatine (PCr) was nearly depleted during maximal systemic exercise in patients with CHF and normal subjects (12.5+/-0.04% and 12.3+/-0.07%, respectively, of initial level). PCr depletion occurred at a significantly lower peak oxygen uptake (peak VO2) in patients with CHF than in normal subjects (CHF, 20.2+/-3.0 versus normal, 31.8+/-3.7 mL . min-1 . kg-1, P<0. 0001). Muscle metabolic capacity, evaluated as the slope of PCr decrease in relation to increasing workload, was correlated with peak VO2 during maximal systemic exercise in patients with CHF (r=0.83, P<0.001). Muscle metabolic capacity during local exercise was impaired in patients with CHF and was correlated with capacity during systemic exercise (r=0.76, P<0.01) and with peak VO2 (r=0. 83, P<0.001).These results suggest that impaired muscle metabolism associated with early metabolic limitation determines exercise capacity during maximal systemic exercise in patients with CHF. There was a significant correlation between muscle metabolic capacity during systemic and local exercise in patients with CHF.
Short bowel, short answer?
Authors: J NIGHTINGALE
Journal: Gut (1999)

See article on page 559 

The paper by Jeppsen et al (see page559) shows that glucagon-like peptide-2 (GLP-2) concentrations are low in patients lacking an ileum and colon. This is not an unexpected finding as the L cells that produce GLP-2 are situated in the ileum and colon. GLP-2 is an enterocyte specific growth hormone that in mice causes small and large bowel villus/crypt growth and increases small and large bowel length and weight. In mice it also reduces body weight loss and restores mucosal integrity after dextran induced colitis. In pigs it reduces gastric antral motility.1 The deficiency of GLP-2 in patients with a jejunostomy may explain why these patients show no evidence of structural or functional intestinal adaptation over time.2-4 

A distal ileal/colonic peptide with glucagon-like immunoreactivity has been recognised for many years and termed enteroglucagon. However, the molecular structure of enteroglucagon was originally unknown and serum concentrations were derived by subtracting pancreatic glucagon concentrations from total …
INSULIN COMA THERAPY IN SCHIZOPHRENIA
Authors: FRANKLIN H. WEST, EARL D. BOND, JAY T. SHURLEY, C. DIXON MEYERS
Journal: American Journal of Psychiatry (1955)

1. Insulin coma therapy at the Pennsylvania Hospital produced an immediate improvement or remission in 67.7% of 780 patients treated between 1936 and 1951. 2. At least 334 patients, or 63.3% of all patients who originally improved, had a relapse; 44% of all these relapses occurred within 30 days, and 78% within 1 year of treatment. A second insulin course brought about an improvement or remission in 52% of 122 patients who had relapsed. 3. Factors associated with the most favorable prognosis include: age over 16, psychosis of less than 6 months' duration, with a clinical picture of paranoid, catatonic, or undifferentiated schizophrenia; and if during treatment the patient receives at least 30 to 60 coma hours and gains more than 30 pounds in weight. 4. We conclude that insulin coma therapy is effective in restoring the schizophrenic patient to his prepsychotic adjustment. This restoration to health is not accompanied by a permanent correction of the factors that predispose the patient to regress to schizophrenia.
Prospective Randomized Evaluation of Risk-adapted Prostate-specific Antigen Screening in Young Men: The PROBASE Trial
Authors: Christian Arsov, Nikolaus Becker, Boris A. Hadaschik, Markus Hohenfellner, Kathleen Herkommer, Jürgen E. Gschwend, Florian Imkamp, Markus A. Kuczyk, Gerald Antoch, Glen Kristiansen, Roswitha Siener, Axel Semjonow, Freddie C. Hamdy, Hans Lilja, Andrew J. Vickers, Fritz H. Schröder, Peter Albers
Journal: European Urology (2013)
Effect of Transdermal Estradiol and Oral Conjugated Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women
Authors: Andrea Decensi, Umberto Omodei, Chris Robertson, Bernardo Bonanni, Aliana Guerrieri-Gonzaga, Francesca Ramazzotto, Harriet Johansson, Serena Mora, Maria Teresa Sandri, Massimiliano Cazzaniga, Massimo Franchi, Sergio Pecorelli
Journal: Circulation (2002)

Background— The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2×2 retinoid-placebo trial. Methods and Results— A total of 189 postmenopausal women were randomized to 50 μg/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 μg/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI −9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI −14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was −48% (95% CI −85% to −7%, P =0.012), whereas fenretinide was associated with a mean change of −1% (95% CI −34% to 40%, P =0.79) compared with placebo. Conclusions— In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.
Déjà Vu: EGF Receptors Drive Resistance to BRAF Inhibitors
Authors: Maria Romina Girotti, Richard Marais
Journal: Cancer Discovery (2013)

Abstract Summary: The promise of personalized medicine is upon us, and in some cancers, targeted therapies are rapidly becoming the mainstay of treatment for selected patients based on their molecular profile. The protein kinase BRAF is a driver oncogene in both thyroid cancer and melanoma, but while drugs that target BRAF and its downstream signaling pathway are effective in melanoma, they are ineffective in thyroid cancer. In this issue of Cancer Discovery, Montero-Conde and colleagues investigate why thyroid cancer is resistant to BRAF inhibitors despite the presence of BRAF mutation. Cancer Discov; 3(5); 487–90. ©2013 AACR. See related article by Montero-Conde et al., p. 520
IMPORTANCE OF BLOOD GROUPS IN COMPLEMENT FIXATION REACTIONS
Authors: William C. Williams
Journal: The Journal of Experimental Medicine (1920)

1. The presence of a natural anti-human hemolysin, only active against Group I and Group II cells, was demonstrated in over 50 guinea pigs, obtained from different sections of the surrounding country. It was shown that, in a majority of the sera tested, this hemolysin would be a contributing factor to an excess of amboceptor in the reaction, in the quantities of complement used in an antihuman complement fixation reaction. The hemolysin is specific, in as far as it can be absorbed with either Group I or Group Il cells, but cannot be absorbed with Group III or Group IV cells. 2. To determine the effect of the isohemolysins in human serum, twenty sera were tested against cell suspensions of the four human groups. Tests were also run with twenty-six human sera against all four group cell suspensions, with complement that had the natural anti-human hemolysin absorbed from it. In both experiments various degrees of hemolysis were obtained with all but two sera against cell suspensions from Groups I, II, and III, but no hemolysis was obtained with any serum against a Group IV cell suspension. 3. The importance of the human isohemolysins and the natural anti-human hemolysm in complement was demonstrated by performing complement fixation tests upon twenty-six human sera, cell suspensions of all four human groups for each serum tested being used. A marked variation in the reaction occurred with a large percentage of the sera tested. This variation in a single serum might be as great as a negative reading with Group I cells to a double plus reading with Group IV cells. 4. That the isohemolysins, alone, in human serum are of importance in the reaction was shown by running complement fixation tests upon seventeen human sera with the four group cell suspensions and complement from which the natural anti-human hemolysin had been absorbed. Results showed a much weaker reaction, in a large number of the sera, with Group I, Group II, and Group III cells than with Group IV cells. 5. Experiments to determine a relation between the human blood groups and natural anti-sheep hemolysin present in human serum gave negative results. It was shown, however, with twenty-six human sera tested against twenty-three different sheep cell suspensions that there is a wide variation in the activity of the natural anti-sheep amboceptor present in any human serum when it is tested against different sheep cell suspensions. A human serum capable of completely hemolyzing the cells of one sheep may fail to give any hemolysis whatever when tested against another sheep cell suspension. 6. Tests were made for natural anti-sheep hemolysin in guinea pig serum. The serum from sixteen different guinea pigs was tested against a total of twenty-one sheep cell suspensions. A natural anti-sheep hemolysin was present in all the guinea pigs tested against one of the sheep cell suspensions. The same guinea pigs tested against the other sheep cell suspensions failed to show any hemolysis.
How patients use access to their full health records: a qualitative study of patients in general practice
Authors: Brian Fisher, Vanita Bhavnani, Marlene Winfield
Journal: Journal of the Royal Society of Medicine (2009)

To explore how patients use record access, its impact and the benefits and drawbacks of using it.Qualitative study using focus group interviews, individual interviews and telephone interviews.General practice offering electronic access to full medical records using PAERS system.Forty-three patients aged between 20 and 71 years participated. Of these, nine were in the healthy group, eight had long-term health conditions, 10 were in the mental health group and 16 were pregnant.Three themes emerged as to how patients used record access - participation in care, quality of care and self-care strategies. Record access was used to help prepare patients for consultations, compensate for poor or complex communication during consultations and to reduce the fragmentation of care. Record access had a small impact on health behavior intentions. Overall patients felt that record access reinforced trust and confidence in doctors and helped them feel like partners in healthcare.This study suggests that record access improves shared management, with patients using their records to improve interactions with healthcare providers, make decisions about their health and improve the quality of the care they receive. These findings also suggest a possible long-term potential for record access to improve health outcomes.