tbuckley/cabot-search huggingface dataset:
Effect of increasing degrees of ischemic injury on myocardial oxidative metabolism early after reperfusion in isolated rat hearts.
Authors: G Görge, P Chatelain, J Schaper, R Lerch
Journal: Circulation Research (1991)

The present investigation studied the effect of increasing severities of ischemic injury on recovery of oxidative metabolism after reperfusion in isolated rat hearts perfused retrogradely with erythrocyte-containing medium. Hearts subjected to 60 minutes of low-flow ischemia (5% of control perfusion) exhibited delayed but sustained recovery of left ventricular pressure development during reperfusion and preservation of ultrastructure delineated with electron microscopy. Immediately after reperfusion, myocardial oxygen consumption returned to control values, well before left ventricular pressure development recovered. Early after reperfusion release of 14CO2 from [1-14C]palmitate was reduced (-53%, p less than 0.01). Conversely, release of 14CO2 from [U-14C]glucose was increased (+131%, p less than 0.05). After 60 minutes of reperfusion 14CO2 release had completely returned to normal for both labeled substrates. Pulse-labeling experiments indicated that during transient depression of [1-14C]palmitate oxidation more tracer was incorporated into myocardial lipid esters, primarily triglycerides. In contrast to hearts subjected to low-flow ischemia, hearts subjected to 60 minutes of no-flow ischemia exhibited poor recovery of contractile function during the reperfusion period. Electron microscopic examination of reperfused hearts showed advanced myocyte damage consistent with irreversible injury. Interestingly, myocardial oxygen consumption in this group also recovered to control values. The substrate pattern during the early reperfusion period was similar to that of hearts subjected to low-flow ischemia. After 120 minutes of no-flow ischemia, recovery of oxidative metabolism was virtually absent. The results indicate a pronounced dissociation between recovery of oxidative metabolism and of contractile function in reperfused myocardium. The oxidative metabolic rate was disproportionately high compared with contractile function, not only in reversibly "stunned" hearts, but also in severely damaged hearts exhibiting signs of irreversible injury.
Coupling of the &lt;sup&gt;99m&lt;/sup&gt;Technetium-Nitrido Group to Monoclonal Antibody and Use of the Complexes for the Detection of Tumors in Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J Kanellos, G A Pietersz, I F McKenzie, J Bonnyman, J Baldas
Journal: JNCI Journal of the National Cancer Institute (1986)

The in vivo detection of tumors by immunoscintigraphy with the use of radiolabeled monoclonal antibodies (MoAb) is a new diagnostic procedure currently undergoing clinical evaluation. In the present study the use of 99mtechnetium (99mTc) for this purpose was explored. A simple method for the labeling of microgram quantities of MoAb with 99mTc based on the substitution reaction of MoAb and tetrachloronitridotechnetate ion (99mTcNCl4-) is described. The selective activity of the 99mtechnetium-nitrido-MoAb (99mTcN-MoAb) complexes was proved in vitro by a binding assay with different target cells. The 99mTcN-MoAb complexes were shown to bind reactive cells up to 20 times more avidly than nonreactive cells. The specificity of the 99mTcN-MoAb complexes was shown in vivo. (C57BL/6 X BALB/c)F1 mice bearing palpable tumors (0.3-1.5 cm in diameter) were given an iv injection of 1 of 2 MoAb (one reactive and the other nonreactive) identically labeled with 99mTcNCl4- and then scanned with a gamma camera, and/or the tissues were removed and the localization of 99mTc-nitrido group-labeled MoAb was measured. Tumor localization of the reactive MoAb (1.8-2.2% of the injected dose) was four times greater than that of the nonreactive 99mTcN-MoAb (0.3-0.4% of the injected dose). The localization of specific 99mTcN-MoAb to a murine thymoma was observed in the gamma camera image at just 2 hours after injection. At 27 hours, tumors could readily be detected by 99mTcN-MoAb without the need for background subtraction. Nonreactive 99mTcN-MoAb did not image the tumors. The use of 99mTcN-MoAb offers substantial improvement over radioiodinated (125I or 131I) MoAb for the detection of tumors. The use of 99mTcNCl4- as a labeling agent results in 99mTc-labeled MoAb with high specific activity and specificity when compared with the specific activity and specificity of the 99mTc-MoAb prepared by using the conventional SnCl2 reduction of pertechnetate.
A PUBLIC HEALTH SUCCESS: Understanding Policy Changes Related to Teen Sexual Activity and Pregnancy
Authors: Claire D. Brindis
Journal: Annual Review of Public Health (2005)

▪ Abstract Teenage pregnancy prevention has long been on the American public health agenda. Over the past decade, a number of concurrent federal, state, and local policies have responded to the myriad and diverse needs of adolescents, from supporting adolescents who have not initiated sexual intercourse to strategies aimed at avoiding a repeat pregnancy among teenage parents. Key policies, including comprehensive family life education, access to contraceptive care, and youth development, have resulted in delays in sexual debut, improved contraceptive use, and have achieved reductions in pregnancies, abortions, and births. Although improvements are documented across all ethnic and racial subgroups, substantial health disparities continue to exist. Synergistic policy approaches represent a substantial change from the past when narrow, single-issue strategies were adopted and were limited in their effectiveness. Renewed efforts to implement narrow policy approaches (e.g., abstinence-until-marriage or restrictions to contraceptive access) need to be considered in light of existing research findings.
Novel Insights into the Molecular Mechanisms of Human Thyrotropin Action: Structural, Physiological, and Therapeutic Implications for the Glycoprotein Hormone Family
Authors: Mathis Grossmann, Bruce D. Weintraub, Mariusz W. Szkudlinski
Journal: Endocrine Reviews (1997)

I. Introduction A. Historical background B. TSH and the glycoprotein hormone family II. Structure-Function Relationships of TSH in Relation to Studies on Gonadotropins A. Methodological considerations B. Structure-function studies of protein domains C. Structure-function studies of carbohydrate chains III. Current Understanding of TSH/Glycoprotein Hormone Action A. Structural considerations B. Hormone-receptor interaction C. Cooperation of individual hTSH domains in receptor activation IV. Physiological and Pathophysiological Implications A. Carbohydrate heterogeneity B. Naturally occurring glycoprotein hormone mutations C. “Specificity spillover” syndromes V. Evolutionary Considerations A. Glycoprotein hormone specificity B. Evolutionary changes in TSH activity VI. Strategies in the Design of Novel TSH Analogs and Therapeutic Implications A. Clinical use of rhTSH B. Design of novel glycoprotein hormone analogs VII. Nonclassic Actions of TSH and Gonadotropins A. Extrathyroidal/extragonadal glycoprotein ho...
Secretin activation of the apical Na+-dependent bile acid transporter is associated with cholehepatic shunting in rats
Authors: Gianfranco Alpini, Shannon Glaser, Leonardo Baiocchi, Heather Francis, Xuefeng Xia, Gene LeSage
Journal: Hepatology (2005)

The role of the cholangiocyte apical Na+-dependent bile acid transporter (ASBT) in bile formation is unknown. Bile acid absorption by bile ducts results in cholehepatic shunting, a pathway that amplifies the canalicular osmotic effects of bile acids. We tested in isolated cholangiocytes if secretin enhances ASBT translocation to the apical membrane from latent preexisting intracellular stores. In vivo, in bile duct–ligated rats, we tested if increased ASBT activity (induced by secretin pretreatment) results in cholehepatic shunting of bile acids. We determined the increment in taurocholate-dependent bile flow and biliary lipid secretion and taurocholate (TC) biliary transit time during high ASBT activity. Secretin stimulated colchicine-sensitive ASBT translocation to the cholangiocyte plasma membrane and 3H-TC uptake in purified cholangiocytes. Consistent with increased ASBT promoting cholehepatic shunting, with secretin pretreatment, we found TC induced greater-than-expected biliary lipid secretion and bile flow and there was a prolongation of the TC biliary transit time. Colchicine ablated secretin pretreatment-dependent bile acid–induced choleresis, increased biliary lipid secretion, and the prolongation of the TC biliary transit. In conclusion, secretin stimulates cholehepatic shunting of conjugated bile acids and is associated with increased cholangiocyte apical membrane ASBT. Bile acid transport by cholangiocyte ASBT can contribute to hepatobiliary secretion in vivo. (HEPATOLOGY 2005.)
Interferon-γ and interleukin-4 detected in serum and saliva from patients with oral lichen planus
Authors: Wen-Zhao Liu, Ming-Jing He, Long Long, Dong-Liang Mu, Ming-Shu Xu, Xue Xing, Xin Zeng, Ga Liao, Hong-Xia Dan, Qian-Ming Chen
Journal: International Journal of Oral Science (2013)

Our previous salivary study had demonstrated an apparent T helper 2 (Th2)-predominance in saliva of oral lichen planus (OLP) patients and suggested a potential of salivary interleukin-4 (IL-4) as a biomarker for monitoring disease severity. To further determine the consistency of Th1/Th2 bias of OLP, this study investigated the expression profile of interferon-γ (IFN-γ) and IL-4 in serum and the relationship of the serum levels of these cytokines with their saliva partners. Sixty ethnic Chinese patients with OLP (40 of the erythematous/ulcerative form and 20 of the reticular form) were recruited for this study, with 40 age-sex-matched healthy volunteers as control group. IFN-γ and IL-4 levels in serum and paired saliva samples were screened by enzyme-linked immunosorbent assay. OLP patient showed a low-level IFN-γ but high-level IL-4 expression profile in both serum and saliva, with a lower IFN-γ/IL-4 ratio. Serum IL-4 level in the erythematous/ulcerative group was significantly higher than that in the reticular group. Serum levels of IFN-γ and IL-4 were significantly and positively correlated with their saliva partners. These results provided more evidence for Th2 cytokine-predominant immune imbalance in OLP, as well as the potential of IL-4 as the biomarker for monitoring severity of OLP.
Changes in Triglyceride Levels Over Time and Risk of Type 2 Diabetes in Young Men
Authors: Amir Tirosh, Iris Shai, Rafael Bitzur, Ilan Kochba, Dorit Tekes-Manova, Eran Israeli, Tzippora Shochat, Assaf Rudich
Journal: Diabetes Care (2008)

The association between changes in triglyceride concentrations over time and diabetes is unknown. We assessed whether two triglyceride determinations obtained 5 years apart can predict incident type 2 diabetes.Triglyceride levels at baseline (time 1) and 5 years later (time 2), followed by subsequent follow-up of 5.5 years, were measured in 13,953 apparently healthy men (age 26-45 years) with triglycerides <300 mg/dl (<3.39 mmol/l).During 76,742 person-years, 322 cases of diabetes occurred. A multivariate model adjusted for age, BMI, total cholesterol-to-HDL cholesterol ratio, family history of diabetes, fasting glucose, blood pressure, physical activity, and smoking status revealed a continuous independent rise in incident diabetes with increasing time 1 triglyceride levels (P(trend) < 0.001). Men in the lowest tertile of time 1 triglyceride levels who progressed to the highest tertile over follow-up (low-high) exhibited a hazard ratio (HR) of 12.62 (95% CI 3.52-31.34) compared with those remaining in the lowest tertile at both time points (reference group: low-low). Whereas men who were at the top triglyceride level tertile throughout follow-up (high-high) had a HR for diabetes of 7.08 (2.52-14.45), those whose triglyceride level decreased to the lowest tertile (high-low) exhibited a HR of 1.97 (0.67-6.13). Alterations in triglyceride levels during follow-up were associated with changes in BMI, physical activity, and eating breakfast habit (P < 0.05), but remained an independent modifier of diabetes risk even after adjustment for such changes.Two measurements of fasting triglyceride levels obtained 5 years apart can assist in identifying apparently healthy young men at increased risk for diabetes, independent of traditional risk factors and of associated changes in BMI and lifestyle parameters.
DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection
Authors: Mark J Walker, Andrew Hollands, Martina L Sanderson-Smith, Jason N Cole, Joshua K Kirk, Anna Henningham, Jason D McArthur, Katrin Dinkla, Ramy K Aziz, Rita G Kansal, Amelia J Simpson, John T Buchanan, Gursharan S Chhatwal, Malak Kotb, Victor Nizet
Journal: Nature Medicine (2007)
The molecular genetics of human lung cancer
Authors: RJ Slebos, S Rodenhuis
Journal: European Respiratory Journal (1989)

With the development of molecular biological techniques the search for genetic alterations in cancer cells has resulted in the beginning of a molecular description of cellular transformation. Most of these genetic changes occur in genes which have a role in the control of cellular growth and development, the proto oncogenes. In the last decade, it has become clear that the myc and ras oncogene families are important in the carcinogenesis of human lung cancers. The myc oncogenes are usually found to be altered in small cell lung cancer (SCLC), and these alterations appear to correlate with rapid growth and progression. Mutations in the Kras gene are specific for adenocarcinoma, a subclass of non small cell lung cancer (NSCLC). Kras gene mutations are closely associated with tobacco smoking, since all were found in adenocarcinomas from patients with a history of smoking. The erbB oncogene, which encodes the epidermal growth factor receptor, is often highly expressed in epidermoid carcinomas. The roles for other oncogenes, such as raf or myb, as well as those of "suppressor" genes remain to be investigated, but may be of paramount importance. The study of alterations in proto oncogenes may aid in the (sub)classification and diagnosis of lung cancer, and may yield useful prognostic information in the near future.
Nosocomial pneumonia in critically ill comatose patients: need for a differential therapeutic approach
Authors: J Rello, V Ausina, M Ricart, C Puzo, A Net, G Prats
Journal: European Respiratory Journal (1992)

The purpose of this prospective clinical study was to determine the incidence, bacteriology and outcome of lower respiratory tract infections developed among 208 consecutive, critically ill comatose patients, hospitalized in a university hospital, medical-surgical intensive care unit, over a three year period. Nosocomial pneumonia developed in 53 (25%) patients after a mean of 8.1 days (range 3-31 days). Furthermore, there were five superinfections, raising the mean incidence to 28%. One patient developed secondary bacteraemia, and another two had septic shock. Fifteen (28%) patients from the pneumonia group died, and six of these deaths were considered to be directly related to nosocomial pneumonia. Identification of the causative agent, using the protected specimen brush technique, was possible in 42 episodes; in 10 (24%) of these cases more than one microorganism was isolated. Gram-positive cocci represented 53% of isolates, and Staphylococcus aureus accounted for 78% of all Gram-positive cocci, being the most frequent microorganism in this population. In conclusion, nosocomial pneumonia is a common complication of critically ill comatose patients. Its characteristic aetiological spectrum in this population should affect antibiotic prescription. Consequently, we suggest including antimicrobial drugs which are active against S. aureus in the empirical regimen until aetiological diagnosis is established.
Comparability of Telephone and Face-to-Face Interviews in Assessing Axis I and II Disorders
Authors: P Rohde, P M Lewinsohn, J R Seeley
Journal: American Journal of Psychiatry (1997)

OBJECTIVE: The present study examined the comparability of data obtained by telephone and face-to-face interviews for diagnosing axis I and II disorders. METHOD: Sixty young adults from the community were interviewed face-to-face and over the telephone regarding axis I disorders; another 60 subjects were interviewed twice regarding axis II disorders. The order of interviews was counterbalanced, and subjects with a history of disorder were oversampled. Agreement between telephone and face-to-face interviews was contrasted with interrater values, which were obtained by having a second interviewer rate a recording of the original interview. RESULTS: Interrater reliability was excellent. Agreement between telephone and face-to-face assessment was excellent for anxiety disorders and very good for major depressive disorder and alcohol and substance use disorders; agreement was problematic, however, for adjustment disorder with depressed mood. Strong support was shown for the validity of the axis II telephone assessment format. Small but consistent trends were noted for lower rates of psychopathology reported in the second interview. CONCLUSIONS: This is the first study in which telephone and face-to-face assessments of axis I and II psychopathology were conducted with the same subjects assigned to conditions in a counterbalanced manner. The present findings provide qualified justification for the use of telephone interviews to collect axis I and II data. The apparent concerns do not appear sufficient to override the economic and logistic advantages of telephone interviewing. (Am J Psychiatry 1997; 154:1593–1598)
X-linked B-lymphocyte defect in CBA/N mice. III. Abnormal development of B-lymphocyte populations defined by their density of surface immunoglobulin.
Authors: I Scher, S O Sharrow, W E Paul
Journal: The Journal of Experimental Medicine (1976)

CBA/N mice have an X-linked defect in B-lymphocyte function characterized by a failure to respond to certain thymus-independent antigens. When studied by rapid flow microfluorometry, adult CBA/N splenic B lymphocytes labeled with either fluorescein-conjugated (Fl) anti-Ig or Fl anti-mu had fluorescence profiles which were considerably different from those of B lymphocytes derived from normal mice. By studying progeny of crosses of CBA/N and normal mice, it was shown that the abnormal fluorescence profiles of CBA/N B cells were determined by an X-linked gene. The fluorescence profile of adult CBA/N splenic B lymphocytes labeled with anti-mu were very similar to the patterns of neonatal normal and of neonatal CBA/N splenic B lymphocytes suggesting that the defect of CBA/N mice is due to a failure in the development of a mature B-lymphocyte population. The fluorescence profiles of adult CBA/N splenic B lymphocytes labeled with Fl anti-Ig also had immature characteristics in that the frequency of cells with large amounts of surface immunoglobulin was increased in comparison to that of normal strains and the population of cells with low-to-intermediate density of total surface immunoglobulin, which appear characteristic of normal adult splenic B lymphocytes, was markedly diminished.
The Cooked Meat Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-<i>b</i>]Pyridine Activates the Extracellular Signal–Regulated Kinase Mitogen-Activated Protein Kinase Pathway
Authors: Stuart K. Creton, Huijun Zhu, Nigel J. Gooderham
Journal: Cancer Research (2007)

Abstract During the cooking of meat, mutagenic and carcinogenic heterocyclic amines are formed, the most abundant of which, 2-amino-1-methyl-6-phenylimidazo[4-5-b]pyridine (PhIP), induces tumors of the prostate, colon, and mammary gland in rats. Humans consuming cooked meat are exposed to PhIP on a daily basis, yet few studies have assessed the effects of PhIP at dietary relevant concentrations. In addition to its genotoxic properties, recent studies have shown that PhIP can activate estrogen receptor–mediated signaling pathways at doses that are similar to those that may be present in the body following consumption of a cooked meat meal. In the present study, we examined whether such doses of PhIP can affect estrogen receptor–independent signal transduction via the mitogen-activated protein kinase (MAPK) extracellular signal–related kinase (ERK) pathway to influence proliferation and migration in the human mammary epithelial cell line MCF10A and the prostate cancer cell line PC-3. At doses shown to have a proliferative effect on MCF10A cells (10−11–10−7 mol/L), PhIP induced a rapid, transient increase in phosphorylation of both MAPK/ERK kinase 1/2 and ERKs. Inhibition of this pathway significantly reduced the PhIP-induced proliferation of MCF10A cells and the migration of PC-3 cells. The data presented here show that levels of PhIP that approximate to human dietary exposure stimulate cellular signaling pathways and result in increased growth and migration, processes linked to the promotion and progression of neoplastic disease. These findings provide strong evidence that PhIP acts as a tumor initiator and promoter and that dietary exposure to this compound could contribute to carcinogenesis in humans. [Cancer Res 2007;67(23):11455–61]
On treating effort as a dynamically varying cost input
Authors: Wilhelm Hofmann, Hiroki Kotabe
Journal: Behavioral and Brain Sciences (2013)

Abstract Kurzban et al.'s framework may be extended in fruitful ways by treating effort also as a cost input that affects the utility computation of a given option (rather than only as the output of a utility comparison between options). The weight people assign to effort as a cost may vary dynamically as a function of situational and dispositional factors.
Urinary Ultrastructural Findings in Fabry Disease
Authors: Sheila Moriber Katz
Journal: JAMA (1977)

FABRY disease (angiokeratoma corporis diffusum universale) is a rare, sex-linked, familial disease associated with deficiency of the enzyme ceramide trihexosidase.<sup>1</sup>The lipid trihexosylceramide accumulates in the blood and several tissues. Lesions occur in the skin and visceral organs, particularly the heart, blood vessels, central nervous system, and kidneys. In the involved skin, dark red macules and papules contain dilated superficial capillaries. Lipid-laden vacuolated cells are a characteristic component of the visceral lesions. Typical ultrastructural "myelin" figures occur within the vacuoles of affected cells. These structures are composed of dense laminations of lipid material, resembling myelin sheaths. Using electron microscopy, we attempted to detect myelin figures in a urine sample from a patient with renal involvement by Fabry disease. <h3>Report of a Case</h3> A 48-year-old man was admitted to Hahnemann Medical College Hospital for evaluation of proteinuria and intermittent febrile episodes. Proteinuria was first noted at the age of 24
Computational challenges in the analysis of ancient DNA
Authors: Kay Prüfer, Udo Stenzel, Michael Hofreiter, Svante Pääbo, Janet Kelso, Richard E Green
Journal: Genome biology (2010)

Abstract High-throughput sequencing technologies have opened up a new avenue for studying extinct organisms. Here we identify and quantify biases introduced by particular characteristics of ancient DNA samples. These analyses demonstrate the importance of closely related genomic sequence for correctly identifying and classifying bona fide endogenous DNA fragments. We show that more accurate genome divergence estimates from ancient DNA sequence can be attained using at least two outgroup genomes and appropriate filtering.