tbuckley/cabot-search huggingface dataset:
Osteogenesis imperfecta type IV. Biochemical confirmation of genetic linkage to the pro alpha 2(I) gene of type I collagen.
Authors: R J Wenstrup, P Tsipouras, P H Byers
Journal: Journal of Clinical Investigation (1986)

Fibroblasts from two affected members of a large pedigree in which osteogenesis imperfecta (OI) type IV is genetically linked to the pro alpha 2(I) gene of type I collagen synthesize two populations of pro alpha 2(I) chains. One population is normal; the second population appears to have a deletion of about 10 amino acid residues from the middle of the triple helical domain. The mutation in pro alpha 2(I) causes increased posttranslational modification in the amino-terminal half of some pro alpha 1(I) chains, lowers the melting temperature of type I collagen molecules that incorporate a mutant pro alpha 2(I) chain, and prevents or delays the secretion of those molecules from fibroblasts in cell culture. On the basis of this study and linkage studies in additional families, it appears that the OI type IV phenotype is often the result of heterozygosity for mutations in pro alpha 2(I) that alter the triple helical structure of type I collagen.
Randomized Controlled Trial of a Cognitive-Behavioral Therapy Plus Hypnosis Intervention to Control Fatigue in Patients Undergoing Radiotherapy for Breast Cancer
Authors: Guy H. Montgomery, Daniel David, Maria Kangas, Sheryl Green, Madalina Sucala, Dana H. Bovbjerg, Michael N. Hallquist, Julie B. Schnur
Journal: Journal of Clinical Oncology (2014)

The objective of this study was to test the efficacy of cognitive-behavioral therapy plus hypnosis (CBTH) to control fatigue in patients with breast cancer undergoing radiotherapy. We hypothesized that patients in the CBTH group receiving radiotherapy would have lower levels of fatigue than patients in an attention control group.Patients (n = 200) were randomly assigned to either the CBTH (n = 100; mean age, 55.59 years) or attention control (n = 100; mean age, 55.97 years) group. Fatigue was measured at four time points (baseline, end of radiotherapy, 4 weeks, and 6 months after radiotherapy). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue subscale and Visual Analog Scales (VASs; Fatigue and Muscle Weakness).The CBTH group had significantly lower levels of fatigue (FACIT) at the end of radiotherapy (z, 6.73; P < .001), 4-week follow-up (z, 6.98; P < .001), and 6-month follow-up (z, 7.99; P < .001) assessments. Fatigue VAS scores were significantly lower in the CBTH group at the end of treatment (z, 5.81; P < .001) and at the 6-month follow-up (z, 4.56; P < .001), but not at the 4-week follow-up (P < .07). Muscle Weakness VAS scores were significantly lower in the CBTH group at the end of treatment (z, 9.30; P < .001) and at the 6-month follow-up (z, 3.10; P < .02), but not at the 4-week follow-up (P < .13).The results support CBTH as an evidence-based intervention to control fatigue in patients undergoing radiotherapy for breast cancer. CBTH is noninvasive, has no adverse effects, and its beneficial effects persist long after the last intervention session. CBTH seems to be a candidate for future dissemination and implementation.
A Randomized Trial Examining the Effectiveness of Switching From Olanzapine, Quetiapine, or Risperidone to Aripiprazole to Reduce Metabolic Risk: Comparison of Antipsychotics for Metabolic Problems (CAMP)
Authors: T. Scott Stroup, Joseph P. McEvoy, Kimberly D. Ring, Robert H. Hamer, Lisa M. LaVange, Marvin S. Swartz, Robert A. Rosenheck, Diana O. Perkins, Abraham M. Nussbaum, Jeffrey A. Lieberman
Journal: American Journal of Psychiatry (2011)

Patients with a BMI of 27 or higher and a non-HDL cholesterol level of 130 mg/dl or higher on stable doses of olanzapine, quetiapine, or risperidone were randomly assigned to stay on their current medication or switch to aripiprazole for 24 weeks. Patients switched to aripiprazole saw greater decreases in cholesterol levels, larger reductions in weight, and a net reduction of serum triglycerides. There was no difference in the rate of treatment failure, but nearly twice as many patients discontinued the new aripiprazole regimen before 24 weeks.
Brian Druker and Charles Sawyers receive the 2011 ASCI/Stanley J. Korsmeyer Award
Authors: Kathryn Claiborn
Journal: Journal of Clinical Investigation (2011)

Chronic myelogenous leukemia (CML) was the first cancer to be linked to a clearly defined genetic defect, a chromosomal translocation that generates a constitutively active tyrosine kinase. In the 1990s, Brian Druker and Charles Sawyers (Figure ​(Figure1)1) collaborated to develop the targeted therapies that transformed CML from a fatal disease to one that boasts a 90% cure rate. Their work has been widely recognized as revolutionizing the molecular treatment of cancer, and in April their contributions will be further celebrated as they receive the 2011 ASCI/Stanley J. Korsmeyer award. The JCI recently spoke to Druker and Sawyers about their research careers and this latest award.
The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma
Authors: D Lenze, L Leoncini, M Hummel, S Volinia, C G Liu, T Amato, G De Falco, J Githanga, H Horn, J Nyagol, G Ott, J Palatini, M Pfreundschuh, E Rogena, A Rosenwald, R Siebert, C M Croce, H Stein
Journal: Leukemia (2011)
Maintaining low HIV seroprevalence in populations of injecting drug users
Authors: Don C. Des Jarlais, Holly Hagan, Samuel R. Friedman, Patricia Friedmann, David Goldberg, Martin Frischer, Steven Green, Kerstin Tunving, Bengt Ljungberg, Alex Wodak, Michael Ross, David Purchase, Margaret E. Millson, Ted Myers
Journal: JAMA (1995)

To describe prevention activities and risk behavior in cities where human immunodeficiency virus (HIV) was introduced into the local population of injecting drug users (IDUs), but where seroprevalence has nevertheless remained low (< 5%) during at least 5 years.A literature search identified five such cities: Glasgow, Scotland; Lund, Sweden; Sydney, New South Wales, Australia; Tacoma, Wash; and Toronto, Ontario. Case histories were prepared for each city, including data on prevention activities and current levels of risk behavior among IDUs.Injecting drug users recruited from both drug treatment and non-treatment settings in each city.A variety of HIV prevention activities for IDUs had been implemented in each of the five cities.There were three common prevention components present in all five cities: (1) implementation of prevention activities when HIV seroprevalence was still low, (2) provision of sterile injection equipment, and (3) community outreach to IDUs. Moderate levels of risk behavior continued with one third or more of the IDUs reporting recent unsafe injections.In low-seroprevalence areas, it appears possible to severely limit transmission of HIV among populations of IDUs, despite continuing risk behavior among a substantial proportion of the population. Pending further studies, the common prevention components (beginning early, community outreach, and access to sterile injection equipment) should be implemented wherever populations of IDUs are at risk for rapid spread of HIV.
A Prospective Study of Positive Early-Life Psychosocial Factors and Favorable Cardiovascular Risk in Adulthood
Authors: Allison A. Appleton, Stephen L. Buka, Eric B. Loucks, Eric B. Rimm, Laurie T. Martin, Laura D. Kubzansky
Journal: Circulation (2013)

Background— The American Heart Association’s national goals for cardiovascular health promotion emphasize that cardiovascular risk originates early in life, but little is known about childhood factors that may increase the likelihood of having a favorable cardiovascular risk (FCR) in adulthood. We examined the prospective association between positive childhood factors and the likelihood of midlife FCR. We also considered pathways through which childhood factors may influence FCR. Methods and Results— We studied 415 adults (mean age=42.2 years) of the Collaborative Perinatal Project, a national cohort initiated in 1959 to 1966. We examined 3 positive childhood factors assessed at age 7 years: attention regulation (ability to stay focused), cognitive ability, and positive home environment. Of these adults, 10.6% had FCR in midlife. Adjusting for demographics and childhood cardiovascular health, a 1-unit increase in childhood attention regulation, cognitive ability, and positive home environment was associated with 2.4 (95% confidence interval, 1.1–4.7), 1.8 (95% confidence interval, 1.1–2.9), and 1.3 (95% confidence interval, 1.1–1.6) higher respective odds of having midlife FCR. The association with childhood attention regulation was maintained when accounting for adulthood factors; education and diet in part explained the associations with childhood cognitive ability and home environment. The effect of each attribute was additive as those with high levels of each childhood factor had 4.3 higher odds (95% confidence interval, 1.01–18.2) of midlife FCR in comparison with those low in all factors. Conclusions— Positive childhood psychosocial factors may promote healthy adult cardiovascular functioning. Primordial prevention efforts aimed at preventing the development of cardiovascular risk should consider building on childhood psychosocial resources.
Lysine kinetics in preterm infants: the importance of enteral feeding
Authors: S R D van der Schoor
Journal: Gut (2003)

Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake.Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) micromol/(kg x h); and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) micromol/(kg x h). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics.Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) micromol/(kg x h); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) micromol/(kg x h); p<0.05).Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.
Long-Term Phenotypic Study after Allogeneic Cultivated Corneal Limbal Epithelial Transplantation for Severe Ocular Surface Diseases
Authors: Takahiro Nakamura, Chie Sotozono, Adams J. Bentley, Sachiko Mano, Tsutomu Inatomi, Noriko Koizumi, Nigel J. Fullwood, Shigeru Kinoshita
Journal: Ophthalmology (2010)
THE PATHOGENESIS OF CHRONIC INFLAMMATION IN EXPERIMENTAL ANTIGEN-INDUCED ARTHRITIS
Authors: T. Derek Cooke, Eric R. Hurd, Morris Ziff, Hugo E. Jasin
Journal: The Journal of Experimental Medicine (1972)

In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera. The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of (125)I-labeled-inducing antigen to menisci from arthritic joints of immunized animals. The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.
Increased Expression of Urokinase-Type Plasminogen Activator mRNA Determines Adverse Prognosis in ErbB2-Positive Primary Breast Cancer
Authors: Patrick Urban, Vincent Vuaroqueaux, Martin Labuhn, Mauro Delorenzi, Pratyaksha Wirapati, Edward Wight, Hans-Jörg Senn, Christopher Benz, Urs Eppenberger, Serenella Eppenberger-Castori
Journal: Journal of Clinical Oncology (2006)

To evaluate and validate mRNA expression markers capable of identifying patients with ErbB2-positive breast cancer associated with distant metastasis and reduced survival.Expression of 60 genes involved in breast cancer biology was assessed by quantitative real-time PCR (qrt-PCR) in 317 primary breast cancer patients and correlated with clinical outcome data. Results were validated subsequently using two previously published and publicly available microarray data sets with different patient populations comprising 295 and 286 breast cancer samples, respectively.Of the 60 genes measured by qrt-PCR, urokinase-type plasminogen activator (uPA or PLAU) mRNA expression was the most significant marker associated with distant metastasis-free survival (MFS) by univariate Cox analysis in patients with ErbB2-positive tumors and an independent factor in multivariate analysis. Subsequent validation in two microarray data sets confirmed the prognostic value of uPA in ErbB2-positive tumors by both univariate and multivariate analysis. uPA mRNA expression was not significantly associated with MFS in ErbB2-negative tumors. Kaplan-Meier analysis showed in all three study populations that patients with ErbB2-positive/uPA-positive tumors exhibited significantly reduced MFS (hazard ratios [HR], 4.3; 95% CI, 1.6 to 11.8; HR, 2.7; 95% CI, 1.2 to 6.2; and, HR, 2.8; 95% CI, 1.1 to 7.1; all P < .02) as compared with the group with ErbB2-positive/uPA-negative tumors who exhibited similar outcome to those with ErbB2-negative tumors, irrespective of uPA status.After evaluation of 898 breast cancer patients, uPA mRNA expression emerged as a powerful prognostic indicator in ErbB2-positive tumors. These results were consistent among three independent study populations assayed by different techniques, including qrt-PCR and two microarray platforms.
Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer
Authors: Rebeca Sanz-Pamplona, Antoni Berenguer, David Cordero, David G Molleví, Marta Crous-Bou, Xavier Sole, Laia Paré-Brunet, Elisabet Guino, Ramón Salazar, Cristina Santos, Javier de Oca, Xavier Sanjuan, Francisco Rodriguez-Moranta, Victor Moreno
Journal: Molecular Cancer (2014)

A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient's gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients.
Raising Questions about Antidepressants
Authors: David O. Antonuccio, William G. Danton, Garland Y. DeNelsky, RogerP. Greenberg, James S. Gordon
Journal: Psychotherapy and Psychosomatics (1999)

Antidepressant medication has apparently become the most popular treatment for depression in the USA. Several beliefs about the efficacy of antidepressant medications prevail among mental health professionals and the public. This paper explores relevant research data and raises questions about these beliefs. Many of the common beliefs about these medications are not adequately supported by scientific data. The following issues are raised: (1) industry-funded research studies which result in negative findings sometimes do not get published; (2) placebo washout procedures may bias results in some studies; (3) there are serious questions about the integrity of the double-blind procedure; (4) the ‘true’ antidepressant drug effect in adults appears to be relatively small; (5) there is minimal evidence of antidepressant efficacy in children; (6) side effects are fairly common even with the newer antidepressants; (7) combining medications raises the risk for more serious complications; (8) all antidepressants can cause withdrawal symptoms; (9) genetic influences on unipolar depression appear to be weaker than environmental influences; (10) biochemical theories of depression are as yet unproven; (11) biological markers specific for depression have been elusive; (12) dosage and plasma levels of antidepressants have been minimally related to treatment outcome; (13) preliminary evidence suggests that patients who improve with cognitive-behavioral psychotherapy show similar biological changes as those who respond to medication, and (14) the evidence suggests that psychological interventions are at least as effective as pharmacotherapy in treating depression, even if severe, especially when patient-rated measures are used and long-term follow-up is considered.
Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance
Authors: J.J. Hoefnagel, M.H. Vermeer, P.M. Jansen, G.J. Fleuren, C.J.L.M. Meijer, R. Willemze
Journal: British Journal of Dermatology (2003)

Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas.To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders.Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10.The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases.The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.
Curing HIV: Pharmacologic Approaches to Target HIV-1 Latency
Authors: Shailesh K. Choudhary, David M. Margolis
Journal: The Annual Review of Pharmacology and Toxicology (2011)

HIV-1 infection persists even after years of antiretroviral therapy (ART). Although ART can halt viral replication and thereby reduce viremia to clinically undetectable levels, proviral latency established within the host genome remains largely unaffected by ART and can replenish systemic infection following interruption of therapy. Pharmacologic strategies, which not only target viral replication but also deplete proviral infection, are required for successful clearance of HIV-1 infection. This review highlights the current understanding of molecular mechanisms that establish and maintain HIV-1 latency in its major reservoir, the resting memory CD4 + T cell. We also identify the molecular targets that might be exploited to induce HIV-1 expression, remove epigenetic restrictions, or enhance effective transcription. Finally, we discuss the potential pharmacologic approaches toward targeting viral persistence in different cellular and anatomical reservoirs to achieve a cure of HIV-1 infection.
Relational complexity, the central executive, and prefrontal cortex
Authors: James A. Waltz, Barbara J. Knowlton, Keith J. Holyoak
Journal: Behavioral and Brain Sciences (1998)

Halford et al.'s analysis of relational complexity provides a possible framework for characterizing the symbolic functions of the prefrontal cortex. Studies of prefrontal patients have revealed that their performance is selectively impaired on tasks that require integration of two binary relations (i.e., tasks that Halford et al.'s analysis would identify as three-dimensional). Analyses of relational complexity show promise of helping to understand the neural substrate of thinking.