tbuckley/cabot-search huggingface dataset:
The effects of breast cancer treatment on cognitive functions
Authors: E. Hedayati, A. Schedin, H. Nyman, M. Albertsson, B. I. Nilsson
Journal: Journal of Clinical Oncology (2008)

11531 Background: We have started a longitudinal study to investigate if a) the effects of being given a breast cancer (bc) diagnosis may affect cognitive functions in women, b) if adjuvant therapy may have detrimental effects on cognition, c) if subjects with substantial cognitive impairment after therapy may benefit from a cognitive training program. Methods: The study is dimensioned for 140 subjects. The subjects are recruited consecutively and prospectively from the mammography-screening program at Sodersjukhuset, Stockholm. According to the results of the diagnostic process the patients are divided in two main groups by “biological” randomization; healthy subjects and women with bc (n=70 in each group). All participants are examined by a web-based battery of neuropsychological tests at four times: at inclusion and before diagnosis, after diagnosis (two months), after treatment (six months), and follow-up after an additional three months. Subjects who score one standard deviation below the mean compared to baseline, in any of four cognitive domains (response speed, processing speed, memory and attention) after treatment will be offered to participate in a randomized trial of cognitive training versus control. Results: We have so far included 65 subjects. 30 have completed the third test session. Preliminary results show that patients with a recent bc diagnosis and subsequent surgery demonstrate a tendency toward a cognitive decline in attention. There is a significant cognitive decline in memory in the bc group after treatment p=0.029 (repeated measures ANOVA) and inclination of mild impairment in processing speed. Conclusions: The preliminary results may be interpreted to suggest that receiving a bc diagnosis and/or surgery may be associated to a substantial cognitive decline in a subgroup of patients. After six months of treatment a subgroups of patients have a significant decline in memory, which is not dependent on other cognitive functions, depression or anxiety. Women with bc receiving adjuvant chemotherapy often report difficulties with memory, attention and concentration difficulties. We believe that the fact that bc is the most common cancer among women and specially among women of working age in Sweden may, in itself, motivate a study of cognitive effects of its treatment. No significant financial relationships to disclose.
RNA Interference Demonstrates a Novel Role for Integrin-Linked Kinase as a Determinant of Pancreatic Adenocarcinoma Cell Gemcitabine Chemoresistance
Authors: Mark S. Duxbury, Hiromichi Ito, Eric Benoit, Talat Waseem, Stanley W. Ashley, Edward E. Whang
Journal: Clinical Cancer Research (2005)

Integrin-linked kinase (ILK) facilitates signal transduction between extracellular events and important intracellular survival pathways involving protein kinase B/Akt. We examined the role of ILK in determining pancreatic adenocarcinoma cellular chemoresistance to the nucleoside analogue gemcitabine. Cellular ILK expression was quantified by Western blot analysis. We examined the effects of overexpression of active ILK and of ILK knockdown induced by RNA interference on gemcitabine chemoresistance. We also examined the effects of modulating ILK expression on gemcitabine-induced caspase 3-mediated apoptosis, phosphorylation status of Akt (Ser473) and glycogen synthase kinase. Overexpression of ILK increased cellular gemcitabine chemoresistance, whereas ILK knockdown induced chemosensitization via increased caspase 3-mediated apoptosis. ILK knockdown attenuated Akt Ser473 and glycogen synthase kinase phosphorylation, whereas overexpression of constitutively active myristoylated Akt was sufficient to induce significant recovery in gemcitabine chemoresistance in the presence of ILK knockdown. Levels of ILK expression affect gemcitabine chemoresistance in pancreatic adenocarcinoma cells. This novel finding suggests that therapies directed against ILK and its downstream signaling targets may have the potential to enhance the efficacy of gemcitabine-based chemotherapy.
The Genetics of Atopy and Airway Hyperresponsiveness
Authors: DIRKJE S. POSTMA, GERARD H. KOPPELMAN, DEBORAH A. MEYERS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

According to the available literature, there is a clear suggestion that atopy and airway hyperresponsiveness are genetically determined. Current knowledge suggests that many genes are involved in the clinical expression of these clinical entities. However, it must be established whether the genes for these two traits are acting completely independently of each other. Atopy by itself can be defined in several ways ( see below ) and atopy can express itself in different organs (e.g., skin, nose, and airways). Hence, it is questionable whether there exists one gene for atopy or whether there exist many genes that may interact, resulting in different disease expressions. Twin studies have suggested that part of the genetic background for hay fever and asthma is similar (1, 2). Asthma and rhinitis coexist frequently, suggesting a common heritable origin. There are, however, also some arguments to suggest that some genes may be responsible for asthma, and others for atopy. A study in a London population showed that only 23% of patients with seasonal allergic rhinitis also experienced wheezing (3). Furthermore, Dold and coworkers (4) showed that having a relative with atopic dermatitis or rhinitis alone does not constitute a risk factor for children to develop asthma. But having a parent with asthma significantly increased the risk for development of asthma in the child. The study separately analyzed families with single allergic diseases of one parent and showed that only asthma, and not allergic rhinitis, is a predisposing factor for asthma in the offspring. Finally, children with two family members with an identical type of allergy had the highest risk of developing that specific type of allergy. This might suggest that there are more genes necessary for the expression of different allergies.
Water and protein permeability is regulated by the glomerular epithelial slit diaphragm.
Authors: R C Blantz, F B Gabbai, O Peterson, C B Wilson, I Kihara, H Kawachi, F Shimizu, T Yamamoto
Journal: Journal of the American Society of Nephrology (1994)

The glomerular barriers to water and macromolecular movement were examined 2 and 24 h after the administration of a monoclonal antibody (mAb) specific to an antigen located on the epithelial slit diaphragm and the external aspect of the glomerular basement membrane. By micropuncture techniques 2 h after mAb administration, single-nephron GFR (SNGFR) and plasma flow were unchanged but the glomerular capillary hydrostatic pressure gradient and glomerular capillary hydrostatic pressure were increased and the glomerular ultrafiltration coefficient (LpA) decreased to values that were 50% of the normal control. There was no increase in urinary protein excretion at 2 h. However, at 24 h after mAb, nephron plasma flow (SNPF) and SNGFR increased and the glomerular ultrafiltration coefficient returned to values indistinguishable from the normal control. At 24 h, there was a marked increase in protein excretion. The administration of meclofenamate decreased values for SNGFR and SNPF to normal. Immunoglobulin G was exclusively bound to glomerular capillary walls in a linear or continuous fashion at 2 h, but in a discontinuous, granular pattern at 24 h. These studies suggest that after mAb, important limiting glomerular barriers for hydraulic conductivity and protein excretion reside on the epithelial aspect of the glomerular capillary basement membrane, specifically at the level of the slit diaphragm. Studies also suggest that alterations in glomerular capillary hydraulic conductivity can be effectively separated from increases in macromolecular permeability.
The Coupling of the Neuronal Muscarinic Receptor to Responses
Authors: M McKinney, E Richelson
Journal: The Annual Review of Pharmacology and Toxicology (1984)

Muscarinic acetylcholine receptors are plasma membrane proteins that bind the neurotransmitter acetylcholine and by their conformational changes elicit spe­ cific biological events within cells. They are pharmacologically defined by their binding selectivity for a specific class of drugs, among which are the agonists muscarine and oxotremorine and the various atropine-like antagonists. Muscarinic receptors mediate various types of responses in cardiac muscle, in numerous smooth muscles, in exocrine glands, throughout the peripheral and central nervous system, and in some kinds of cultured nerve cells. Usually two or three subtypes of muscarinic receptors exist, distinguished by their relative binding affinity for agonists (I). Though the types of biological responses among these tissues are varied. the respective proteins that bind the agonist appear to be similar or identical in binding properties and molecular size. It is probably their coupling to unique tissue-specific effectors that gives rise to varied responses. Responses mediated by muscarinic receptors are slow in onset and develop­ ment and thus are distinctly different from nicotinic responses, but like nicotin­ ic responses they can desensitize. In the brain, where the muscarinic receptor is the predominant cholinergic receptor, its activation can lead to either excitation or inhibition of neurons (2). In the cerebral cortex, for example, pyramidal cells become depolarized from decreases in potassium (K+) conductance (3),
Defining HNPCC and Lynch syndrome: what's in a name?: Table 1
Authors: S E Kravochuck, M F Kalady, C A Burke, B Heald, J M Church
Journal: Gut (2014)

Dear Sir,

In June 2013, the Mallorca Group published revised guidelines for the clinical management of Lynch syndrome.1 In the title, HNPCC (Hereditary NonPolyposis Colorectal Cancer) is equated with Lynch syndrome, continuing a misuse of terms that has fuelled confusion for many years. The two terms describe different, although overlapping, diseases: the distinction is critical to an accurate understanding of hereditary colorectal cancer.

HNPCC is defined clinically, usually as families satisfying Amsterdam I or II criteria.2 Lynch syndrome is defined genetically, by the presence of a germline mutation in DNA mismatch repair (MMR) or EPCAM genes.3 Not all HNPCC families have Lynch syndrome and not all Lynch syndrome families have HNPCC. To determine the extent of the misuse of terms, we searched PubMed and Medline databases in …
Loss of surface immunoglobulin expression precedes B cell death by apoptosis in the bursa of Fabricius.
Authors: E Paramithiotis, K A Jacobsen, M J Ratcliffe
Journal: The Journal of Experimental Medicine (1995)

The vast majority of lymphocytes generated daily in the chicken bursa of Fabricius do not emigrate to the periphery but die in situ. Apoptotic cells in the bursa can be readily detected by the presence of fragmented DNA and by the large numbers of condensed cellular nuclei observed by electron microscopy. Consequently, most newly generated lymphocytes die by programmed cell death. We show that bursal cells divide rapidly and apoptotic cells are derived from rapidly dividing precursors. Analysis of the phenotype of bursal cells undergoing apoptosis demonstrated that cell death does not occur in the most mature bursal cell population and is therefore not random. High levels of surface Ig are expressed on bursal cells entering S phase of the cell cycle. In contrast, bursal cells in the early stages of apoptosis in vivo express very low to undetectable levels of surface Ig but were unequivocally confirmed as being of the B lineage by polymerase chain reaction (PCR) detection of rearranged Ig genes. Bursal cells induced to undergo apoptosis in vitro express high levels of surface Ig demonstrating that induction of apoptosis does not in itself induce a loss of surface Ig expression. Consequently, loss of surface Ig expression precedes bursal cell death by apoptosis in vivo, suggesting that maintenance of a threshold level of surface Ig may be a requirement for the continued progression of chicken B lymphocyte development in the bursa.
Biochemistry of Vertebrate Olfaction and Taste
Authors: C R Bruch, D L Kalinoski, M R Kare
Journal: Annual Review of Nutrition (1988)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Association of a Triallelic Serotonin Transporter Gene Promoter Region (5-HTTLPR) Polymorphism With Stressful Life Events and Severity of Depression
Authors: Gil Zalsman, Yung-yu Huang, Maria A. Oquendo, Ainsley K. Burke, Xian-zhang Hu, David A. Brent, Steven P. Ellis, David Goldman, J. John Mann
Journal: American Journal of Psychiatry (2006)

Objective: The lower expressing allele of the serotonin transporter gene 5′ promoter region (5-HTTLPR) polymorphism is reported to be associated with susceptibility to depression and suicidality in response to stressful life events. The authors examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events, severity of major depression, and suicidality. Method: Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasian subjects of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism (higher expressing allele: L A ; lower expressing alleles: L G , S). All subjects underwent structured clinical interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed in a subgroup of subjects. Results: Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate to severe life events compared with the higher expressing L A allele. No associations with suicidal behavior and CSF 5-HIAA were found. Conclusions: Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated.
Diagnostic labels applied to model case histories of chronic airflow obstruction. Responses to a questionnaire in 11 North American and Western European countries
Authors: NB Pride, P Vermeire, L Allegra
Journal: European Respiratory Journal (1989)

In Canada, USA and 9 Western European Countries, 121 respiratory physicians responded to an English language questionnaire asking them to state how they would investigate, treat and label four model patients, chosen to represent well-recognized patterns of clinical features of chronic airflow obstruction. Selection of further investigations appeared to be determined more by the probable diagnostic label than by the need to define selected characteristics in the whole range of such patients. Differences in recommended treatment between countries were less than others have reported for the treatment of asthma. Analysis of the diagnostic labels showed: the classic terms asthma, chronic bronchitis, emphysema still predominated in clinical practice and were considered to be better defined entities than any of the many terms introduced to describe chronic airflow obstruction in the last 30 yrs; the term chronic bronchitis was a source of confusion unless qualified to indicate presence or absence of obstruction; the use of combination terms such as chronic asthmatic bronchitis and chronic obstructive bronchitis showed large differences between countries; there were few differences related to national language. The implications of these findings are discussed.
Opposing Effects of Angiotensin II on Muscle and Renal Blood Flow under Euglycemic Conditions
Authors: DANILO FLISER, RALF DIKOW, SADRI DEMUKAJ, EBERHARD RITZ
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Angiotensin II (Ang II) enhances insulin sensitivity in humans, and this is associated with a paradoxical increase in skeletal muscle blood flow. It is unclear whether these effects are mediated via subtype 1 receptors of Ang II, because these receptors are thought to mediate vasoconstriction. Insulin-stimulated glucose uptake (euglycemic clamp technique) and leg muscle blood flow (plethysmography) were measured in nine healthy male volunteers (mean age, 24 ± 2 yr) on three occasions using a double-blind, placebo-controlled study design. The subjects were allocated in random order to ( 1 ) placebo premedication per os plus placebo infusion, ( 2 ) placebo premedication per os plus infusion of 5 ng Ang II/kg per min, and ( 3 ) premedication with 300 mg of the angiotensin II-1-receptor antagonist irbesartan per os plus infusion of 5 ng Ang II/kg per min. In addition, GFR and effective renal plasma flow were assessed using the steady-state inulin- and paraaminohippurate clearance. Insulin sensitivity ( i.e. , M value) and muscle blood flow after infusion of Ang II (9.3 ± 1.8 mg/kg per min; 17.7 ± 2.1 ml/100 g per min) were significantly higher than after placebo infusion (7.2 ± 1.6 mg/kg per min, P &lt; 0.02; 13.5 ± 1.8 ml/100 g per min, P &lt; 0.01). In contrast, after premedication with irbesartan, they were not significantly different (7.5 ± 1.7 mg/kg per min; 14.3 ± 1.9 ml/100 g per min) as compared with placebo infusion. Mean GFR and effective renal plasma flow were significantly lower ( P &lt; 0.01), and renal vascular resistance was significantly higher ( P &lt; 0.01) with Ang II infusion as compared with the placebo infusion study. Premedication with irbesartan almost completely blocked the vasoconstrictive effect of Ang II on renal vasculature. Under hyperinsulinemic euglycemic conditions, infusion of Ang II has opposing effects on regional arterial blood flow, i.e. , an increase in skeletal muscle blood flow, but vasoconstriction of renal vasculature. Both effects are antagonized by blockade of subtype 1 Ang II receptors.
Use of Exclusion Criteria in Selecting Research Subjects and Its Effect on the Generalizability of Alcohol Treatment Outcome Studies
Authors: Keith Humphreys, Constance Weisner
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Researchers have not systematically examined how exclusion criteria used in selection of research subjects affect the generalizability of treatment outcome research. This study evaluated the use of exclusion criteria in alcohol treatment outcome research and its effects on the comparability of research subjects with real-world individuals seeking alcohol treatment. METHOD: Eight of the most common exclusion criteria described in the alcohol treatment research literature were operationalized and applied to large, representative clinical patient samples from the public and private sectors to determine whether the hypothetical research samples differed substantially from real-world samples. Five hundred ninety-three consecutive individuals seeking alcohol treatment at one of eight treatment programs participated. A trained research technician gathered information from participants on demographic variables and on alcohol, drug, and psychiatric problems as measured by the Addiction Severity Index. RESULTS: Large proportions of potential research subjects were excluded under most of the criteria tested. The overall pattern of results showed that African Americans, low-income individuals, and individuals who had more severe alcohol, drug, and psychiatric problems were disproportionately excluded under most criteria. CONCLUSIONS: Exclusion criteria can result in alcohol treatment outcome research samples that are more heavily composed of white, economically stable, and higher-functioning individuals than are real-world samples of substance abuse patients seen in clinical practice, potentially compromising the generalizability of results. For both scientific and ethical reasons, in addition to studies that use exclusion criteria, outcome research that uses no or minimal exclusion criteria should be conducted so that alcohol treatment outcome research can be better generalized to vulnerable populations.
Acute phase protein synthesis: Regulation by the action of the cytokines interleukin-6, interleukin-1 and tumor necrosis factor α
Authors: T. Andus, J.V. Castell, T. Geiger, M.J. Gomez-Lechon, M. David, V. Gross, W. Gerok, P.C. Heinrich
Journal: Journal of Hepatology (1989)
Incidence of Serious Side Effects from First-Line Antituberculosis Drugs among Patients Treated for Active Tuberculosis
Authors: Daphne Yee, Chantal Valiquette, Marthe Pelletier, Isabelle Parisien, Isabelle Rocher, Dick Menzies
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Major adverse reactions to antituberculosis drugs can cause significant morbidity, and compromise treatment regimens for tuberculosis (TB). Among patients treated for active TB we estimated the incidence, and risk factors, of major side effects from first-line anti-TB drugs. Side effects, resulting in modification or discontinuation of therapy, or hospitalization, were attributed on the basis of resolution after withdrawal, and/or recurrence with rechallenge. Among 430 patients treated between 1990 and 1999, the incidence of all major adverse effects was 1.48 per 100 person-months of exposure (95% confidence interval [95% CI], 1.31 to 1.61) for pyrazinamide, compared with 0.49 (95% CI, 0.42 to 0.55) for isoniazid, 0.43 (95% CI, 0.37 to 0.49) for rifampin, and 0.07 (95% CI, 0.04 to 0.10) for ethambutol. Occurrence of any major side effect was associated with female sex (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 4.7), age over 60 years (adjusted hazard ratio, 2.9; 95% CI, 1.3 to 6.3), birthplace in Asia (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 5.0), and human immunodeficiency virus-positive status (adjusted hazard ratio, 3.8; 95% CI, 1.05 to 13.4). Pyrazinamide-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 2.6; 95% CI, 1.01 to 6.6) and birthplace in Asia (adjusted hazard ratio, 3.4; 95% CI, 1.4 to 8.3), whereas rifampin-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 3.9; 95% CI, 1.02 to 14.9) and human immunodeficiency virus-positive status (adjusted hazard ratio, 8.0; 95% CI, 1.5 to 43). The incidence of pyrazinamide-induced hepatotoxicity and rash during treatment for active TB was substantially higher than with the other first-line anti-TB drugs, and higher than previously recognized.