tbuckley/cabot-search huggingface dataset:
Influence of Tobacco Marketing and Exposure to Smokers on Adolescent Susceptibility to Smoking
Authors: N. Evans, A. Farkas, E. Gilpin, C. Berry, J. P. Pierce
Journal: JNCI Journal of the National Cancer Institute (1995)

Today the uptake of smoking is primarily an adolescent pursuit. Awareness of tobacco advertising and promotion is high, and evidence suggests that it plays a role in adolescent smoking uptake. We evaluated the influence of tobacco advertising and promotion and exposure to smokers on never-smoking adolescents susceptibility to smoking. We used data on 3536 adolescent never smokers (those who had never even puffed on a cigarette) from the 1993 California Tobacco Survey. That survey questioned adolescents about smoking history and inclinations. For this analysis, we defined as susceptible to smoking those never smokers who said on the survey that they could not rule out independently deciding to try a cigarette soon or smoking one offered by a friend. Also for this analysis, we devised two indices: 1) a 5-point index of an individual's receptivity to tobacco advertising as determined by the number of positive responses to five survey items (recognition of advertising messages, having a favorite advertisement, naming a brand he/she might buy, owning a tobacco-related promotional item, and willingness to use a tobacco-related promotional item) and 2) an index classifying an individual's reported exposure to family and peer smoking into one of four levels. Using logistic regression, we assessed the independent importance of our indices in predicting susceptibility to smoking after adjustment for sociodemographic variables, including age, sex, and race/ethnicity, and for perceived school performance. Tests of statistical significance were two-sided. Receptivity to tobacco advertising and exposure to smokers were independently associated with susceptibility to smoking, but the relationship appeared stronger for receptivity to advertising. Adolescents exposed to family members and peers (n = 489) who smoked were 1.89 (95%confidence interval [CI] = 1.30–2.74) times as likely to be susceptible, whereas adolescents who scored 4 or more on the index of Receptivity to Tobacco Marketing (n = 361)were 3.91 (95% CI = 2.38–6.42) times as likely to be susceptible as those who scored 0. Even adolescents who scored 2 (n = 1090) were 2.03 (95% CI = 1.31–3.15) times as likely to be susceptible. There was no interaction effect between score on the index of Receptivity to Tobacco Marketing and exposure to smokers. Our results support the hypothesis that tobacco marketing may be a stronger current influence in encouraging adolescents to initiate the smoking uptake process than exposure to peer or family smokers or sociodemographic variables including perceived school performance. [J Natl Cancer Inst 1995; 87: 1538–45]
NS-398 Upregulates Constitutive Cyclooxygenase-2 Expression in the M-1 Cortical Collecting Duct Cell Line
Authors: SHAWN FERGUSON, RICHARD L. HE[Combining Acute Accent]BERT, ODETTE LANEUVILLE
Journal: Journal of the American Society of Nephrology (1999)

The cortical collecting duct (CCD) is a major site of intrarenal prostaglandin E2 (PGE2) synthesis. This study examines the expression and regulation of the prostaglandin synthesizing enzymes cyclooxygenase-1 (COX-1) and -2 in the CCD. By indirect immunofluorescence using isoform-specific antibodies, COX-1 and -2 immunoreactivity was localized to all cell types of the murine M-1 CCD cell line. By immunohistochemistry, both COX-1 and COX-2 were localized to intercalated cells of the CCD on paraffin-embedded mouse kidney sections. When COX enzyme activity was measured in the M-1 cells, both indomethacin (COX-1 and -2 inhibitor) and the specific COX-2 inhibitor NS-398 effectively blocked PGE2 synthesis. These results demonstrate that COX-2 is the major contributor to the pool of PGE2 synthesized by the CCD. By Western blot analysis, COX-2 expression was significantly upregulated by incubation with either indomethacin or NS-398. These drugs did not affect COX-1 protein expression. Evaluation of COX-2 mRNA expression by Northern blot analysis after NS-398 treatment demonstrated that the COX-2 protein upregulation occurred independently of any change in COX-2 mRNA expression. These studies have for the first time localized COX-2 to the CCD and provided evidence that the intercalated cells of the CCD express both COX-1 and COX-2. The results also demonstrate that constitutively expressed COX-2 is the major COX isoform contributing to PGE2 synthesis by the M-1 CCD cell line. Inhibition of COX-2 activity in the M-1 cell line results in an upregulation of COX-2 protein expression.
Reproductive outcome after chromosome analysis in couples with two or more miscarriages: case-control study
Authors: Maureen T M Franssen, Johanna C Korevaar, Fulco van der Veen, Nico J Leschot, Patrick M M Bossuyt, Mariette Goddijn
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To compare reproductive outcomes in couples carrying a structural chromosome abnormality and non-carrier couples referred for chromosome analysis after two or more miscarriages. <b>Design</b> Case-control study. <b>Setting</b> Six centres for clinical genetics in the Netherlands. <b>Participants</b> 278 carrier couples and 427 non-carrier couples referred for chromosome analysis between 1992 and 2000 after two or more miscarriages before 20 weeks of gestation. Couples were followed up for at least 24 months after chromosome analysis. <b>Main outcome measures</b> The birth of at least one healthy child, at least one more miscarriage, and viable offspring with unbalanced chromosomal abnormalities after parental chromosome analysis. <b>Results</b> Mean follow-up after chromosome analysis was 5.8 years. 120 of 247 (49%) carrier couples had one or more miscarriage after chromosome analysis compared with 122 of 409 (30%) non-carrier couples (difference 19%, 95% confidence interval 11% to 26%; P &lt; 0.01). The percentage of couples with at least one healthy child was not significantly different in carrier couples (83%) and non-carrier couples (84%) (difference −1%, - 7% to 5%). Among 550 pregnancies in carrier couples, two viable unbalanced chromosome abnormalities were detected at prenatal diagnosis (0.4%) and the fetuses aborted and two children with an unbalanced karyotype were born (0.4%). <b>Conclusions</b> Couples whose carrier status was ascertained after two or more miscarriages have a low risk of viable offspring with unbalanced chromosomal abnormalities. Their chances of having a healthy child are as high as non-carrier couples, despite a higher risk of miscarriage.
Transcomplementation of HLA DQA1-DQB1 in DR3/DR4 and DR3/DR9 Heterozygotes and IDDM in Taiwanese Families
Authors: Lee Ming Chuang, Huey Peir Wu, Wen Yu Tsai, Boniface J Lin, Tong Yuan Tai
Journal: Diabetes Care (1995)

OBJECTIVE To study the human leukocyte antigen (HLA)-DQ heterodimers in the susceptible DR haplotypes for patients with insulin-dependent diabetes mellitus (IDDM) in Taiwan. RESEARCH DESIGN AND METHODS Extended class II HLA haplotypes were studied in 57 unrelated IDDM patients, 31 simplex IDDM families, and 105 unrelated control subjects recruited from the same area in Taiwan. Class II HLA genotyping was based on PCR-SSO DNA typing techniques. Extended class II HLA haplotypes were deduced unequivocally by the Taiwanese pedigree studies. RESULTS DR3/DR3, DR3/DR4, and DR3/DR9 genotypes were strongly associated with IDDM susceptibility in this population. In addition to the reported DR3/DR4 in Caucasians, the heterozygotic effect of DR3/DR9 for IDDM was remarkable in the Taiwanese population. Extended HLA haplotypes studies revealed that DRB1*0301/DQA1*0501/DQB1*0201, DRB1*0405/DQA1*0301/DQB1*0302, and DRB1*0405/DQA1*0301/DQB1*0401 were the susceptible haplotypes in this population. There were several hypothetical ways to produce susceptible HLA-DQ heterodimers to explain the susceptibility carried by DR3/DR4 and DR3/DR9 genotypes. Among all DR4 subtypes, only DRB1*0405 was associated with the increased risk of IDDM. CONCLUSIONS These data strongly suggest that the HLA-DR-associated IDDM susceptibility is most likely explained by the formation of the susceptible DQ heterodimers encoded by the DQA1/DQB1 either in cis or in trans.
Management of Transgenderism
Authors: Norman P. Spack
Journal: JAMA (2013)

Gender identity disorder (transgenderism) is poorly understood from both mechanistic and clinical standpoints. Awareness of the condition appears to be increasing, probably because of greater societal acceptance and available hormonal treatment. Therapeutic options include hormone and surgical treatments but may be limited by insurance coverage because costs are high. For patients seeking male-to-female (MTF) change, hormone treatment includes estrogens, finasteride, spironolactone, and gonadotropin-releasing hormone (GnRH) analogs. Surgical options include feminizing genital and facial surgery, breast augmentation, and various fat transplantations. For patients seeking a female-to-male (FTM) gender change, medical therapy includes testosterone and GnRH analogs and surgical therapy includes mammoplasty and phalloplasty. Medical therapy for both FTM and MTF can be started in early puberty, although long-term effects are not known. All patients considering treatment need counseling and medical monitoring.
B-Lymphocyte Depletion With Rituximab and β-Cell Function: Two-Year Results
Authors: Mark D. Pescovitz, Carla J. Greenbaum, Brian Bundy, Dorothy J. Becker, Stephen E. Gitelman, Robin Goland, Peter A. Gottlieb, Jennifer B. Marks, Antoinette Moran, Philip Raskin, Henry Rodriguez, Desmond A. Schatz, Diane K. Wherrett, Darrell M. Wilson, Jeffrey P. Krischer, Jay S. Skyler
Journal: Diabetes Care (2013)

We previously reported that selective depletion of B-lymphocytes with rituximab, an anti-CD20 monoclonal antibody, slowed decline of β-cell function in recent-onset type 1 diabetes mellitus (T1DM) at 1 year. Subjects were followed further to determine whether there was persistence of effect.
Depression: epidemic or pseudo-epidemic?
Authors: S. Hafizi
Journal: Journal of the Royal Society of Medicine (2006)

Ezzati et al. (May 2006 JRSM 1 ) misplace their confidence by a wide margin in claiming to have reached the first 'unbiased' estimates of state and national levels and trends of obesity in the USA.To do so, they claim to have calculated rates of self-reporting biases using data from the NHANES (National Health and Nutrition Examination Survey) and Behavioral Risk Factor Surveillance System (BRFSS) surveys of the US Center for Disease Control and Prevention, which were assumed to be representative of the USA population on the basis of the original sampling design.In reality the assumption is questionable, the response rates being about 80% for NHANES and 45% for BRFSS.If nothing else, such a discrepancy sets a distance between what the two surveys may represent, also considering that the surveys represent different samples.In a crucial decision, Ezzati et al. excluded subjects who did not participate in both surveys-an exclusion that inevitably invalidates any claim that the bias estimates reached could be representative of the USA population or of individual state populations.Such elementary flaws lead to ask how scarce resources could be approved for such a wanting study design.
STUDIES ON THE ANTIPYRETIC ACTION OF CORTISONE IN PYROGEN-INDUCED FEVER
Authors: Elisha Atkins, Fred Allison, Mary Ruth Smith, W. Barry Wood
Journal: The Journal of Experimental Medicine (1955)

The mode of action of cortisone as an antipyretic has been studied in rabbits challenged with intravenous injections of bacterial pyrogens. The fever induced by pyromen or dextran was found to be markedly suppressed when cortisone was administered in liberal amounts (25 mg. twice daily) for 3 days prior to the challenge. Although the cortisone effectively blocked the febrile response to both pyrogens, it failed to influence the transient but marked leucopenia which characteristically precedes the onset of fever. The antipyretic action of the drug also was shown to bear no relation to the activity of the serum factor recently demonstrated by Farr, Grant, and others to be involved in the production of pyrogen-induced fever. In preliminary experiments with typhoid vaccine as the inciting pyrogen, the presence of serum factor activity in normal blood and its absence in the blood of pyrogen-tolerant rabbits was confirmed. Subsequently the blood of rabbits treated with antipyretically effective doses of cortisone was shown to contain just as much serum factor activity as that of normal rabbits. In addition, previous incubation of the pyrogen with serum factor failed to influence the antipyretic effect of the drug. It is concluded from these findings that in suppressing pyrogen fever, cortisone acts neither upon the leucopenic reaction nor upon the fever-accelerating factor of the serum. By exclusion it would appear that the drug must influence some later stage of the fever-producing process. The mechanisms involved in the later stages of the response to exogenous pyrogen remain undefined, and the need for determining whether they are related to the prefebrile leucopenia is emphasized.
Serum and ascitic fluid bacterial DNA: A new independent prognostic factor in noninfected patients with cirrhosis
Authors: Pedro Zapater, Rubén Francés, José M. González-Navajas, Maria A. de la Hoz, Rocío Moreu, Sonia Pascual, David Monfort, Silvia Montoliu, Carmen Vila, Amparo Escudero, Xavier Torras, Isabel Cirera, Lucía Llanos, Carlos Guarner-Argente, José M. Palazón, Fernando Carnicer, Pablo Bellot, Carlos Guarner, Ramón Planas, Ricard Solá, Miguel A. Serra, Carlos Muñoz, Miguel Pérez-Mateo, José Such
Journal: Hepatology (2008)

We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/muL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large-volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12-month follow-up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute-on-chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow-up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end-stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission.The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute-on-chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis.
Adhesion molecule expression in the lung: a comparison between normal and diffuse interstitial lung disease
Authors: AM Southcott, I Hemingway, S Lorimer, K Sugars, PG Hellewell, CM Black, PK Jeffery, AJ Gearing, DO Haskard, RM du Bois
Journal: European Respiratory Journal (1998)

Cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues. In chronic inflammatory diseases, upregulation of the expression of these molecules may contribute to the persistent inflammatory process. The aim of this study was to determine whether there is evidence of adhesion molecule expression in chronically inflamed lung. Soluble adhesion molecules in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunoassay in 54 patients with chronic interstitial lung diseases and 16 normal controls. Adhesion molecule expression in fibrosing alveolitis (FA) lung and in control lung was assessed using immunohistology and reverse transcription-polymerase chain reaction (RT-PCR) amplification. Soluble intercellular adhesion molecule-1 (ICAM-1) was detected in all but two subjects. There was no difference in ICAM-1 concentration between disease groups and normal subjects. In contrast, soluble E-selectin was detected in 17 of the 70 subjects and was significantly associated with the presence of lung disease (p=0.0173). Furthermore, the presence of soluble E-selectin was associated with a raised lymphocyte percentage in BALF (p=0.0069). Soluble VCAM was only detected in five of the 70 subjects (two normals, three patients). There was no difference in adhesion molecule expression in lung parenchyma between FA and controls assessed by immunohistology and RT-PCR. The most striking finding of our study was the universal expression of intercellular adhesion molecule-1 in both normal and diseased lung, emphasizing the important role of the lung in immune function. Upregulation of E-selectin may contribute to inflammatory cell accumulation in chronic interstitial lung diseases.
Gastrointestinal safety of AZD3582, a cyclooxygenase inhibiting nitric oxide donator: proof of concept study in humans
Authors: C J Hawkey
Journal: Gut (2003)

<b>Background:</b> Cyclooxygenase inhibiting nitric oxide donators (CINODs) are a new class of anti-inflammatory and analgesic drugs that may minimise gastrointestinal toxicity compared with standard non-steroidal anti-inflammatory drugs (NSAIDs) by virtue of nitric oxide donation. <b>Methods:</b> A proof of concept study of the gastrointestinal safety of AZD3582, the first CINOD available for human testing, was conducted. Thirty one subjects were randomised to receive placebo, naproxen 500 mg twice daily, or its nitroxybutyl derivative AZD3582 in an equimolar dose (750 mg twice daily) for 12 days in a double blind three period crossover volunteer study. At the start and end of each dosing period, gastroduodenal injury was assessed by endoscopy and small bowel permeability by differential urinary excretion of lactulose and l-rhamnose. Pharmacokinetic profiles were assessed at steady state. <b>Results:</b> On naproxen, the mean total number of gastroduodenal erosions was 11.5 (and one subject developed an acute ulcer) versus 4.1 on AZD3582 (p&lt;0.0001). More than half of the subjects had no erosions on AZD3582. Differences were seen for both the stomach and duodenum. Naproxen increased intestinal permeability (lactulose:l-rhamnose ratio 0.030 before <i>v</i> 0.040 after treatment) whereas AZD3582 (0.029 before, 0.029 after; p=0.006 <i>v</i> naproxen) and placebo (0.030 before, 0.028 after; p&lt;0.001 <i>v</i> naproxen) did not. The steady state bioavailability of naproxen metabolised from AZD3582 was 95% (95% confidence interval 87–101%) of that after naproxen administration. <b>Conclusions:</b> This human study supports animal data showing reduced gastrointestinal toxicity with the CINOD AZD3582. The potential combination of effective pain relief and gastrointestinal protection offered by AZD3582 warrants further evaluation in human clinical studies.
Macrophage Infection via Selective Capture of HIV-1-Infected CD4+ T Cells
Authors: Amy E. Baxter, Rebecca A. Russell, Christopher J.A. Duncan, Michael D. Moore, Christian B. Willberg, Jose L. Pablos, Andrés Finzi, Daniel E. Kaufmann, Christina Ochsenbauer, John C. Kappes, Fedde Groot, Quentin J. Sattentau
Journal: Cell Host & Microbe (2014)

Highlights•Macrophages selectively capture and engulf HIV-1-infected T cells•Uptake of HIV-1-infected T cells drives efficient macrophage infection•T cell capture is viral Env independent; macrophage infection is Env-receptor dependent•This represents a route for macrophage infection by transmitted/founder virusesSummaryMacrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection. Infected T cells, both healthy and dead or dying, were taken up through viral envelope glycoprotein-receptor-independent interactions, implying a mechanism distinct from conventional virological synapse formation. Macrophages infected by this cell-to-cell route were highly permissive for both CCR5-using macrophage-tropic and otherwise weakly macrophage-tropic transmitted/founder viruses but restrictive for nonmacrophage-tropic CXCR4-using virus. These results have implications for establishment of the macrophage reservoir and HIV-1 dissemination in vivo.Graphical abstract
Increased Release of Dopamine in the Striata of Young Adults With Hearing Impairment and Its Relevance for the Social Defeat Hypothesis of Schizophrenia
Authors: Martin Gevonden, Jan Booij, Wim van den Brink, Dennis Heijtel, Jim van Os, Jean-Paul Selten
Journal: JAMA Psychiatry (2014)

An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis.To investigate whether young adults with severe hearing impairment (SHI) experience more feelings of social defeat, show greater dopamine release in response to dexamphetamine, and report a stronger subjective reaction to this substance than normal-hearing young adults and to examine whether dopamine release is associated with both self-reported social exclusion and dexamphetamine-induced psychotic experiences.A sample of 19 participants with SHI and 19 smoking-, age-, and sex-matched healthy controls underwent single-photon emission computed tomography with iodine 123-labeled iodobenzamide as a radiotracer before and after an amphetamine challenge at an academic hospital.Dexamphetamine sulfate (0.3 mg/kg) administered intravenously.Baseline D2/3 receptor binding and endogenous dopamine release.The participants with SHI reported experiencing more feelings of social defeat (U=109, z=-2.09, P=.04) and loneliness (U=87.5, z=-2.72, P=<.001) than did healthy controls, but they did not differ from healthy controls with regard to baseline psychotic symptoms (U=156.5, z=-0.70, P=.48). There were no significant group differences in baseline D2/3 receptor binding. However, repeated-measures multivariate analysis of covariance with age (in months) and tobacco smoking (in pack-years) as covariates showed that there was a greater amphetamine-induced striatal dopamine release among the participants with SHI than among the healthy controls (F1,34=4.55, P=.04). After amphetamine administration, the participants with SHI reported more changes in affect than the healthy controls, but not a greater increase in psychotic symptoms. Likewise, reports of social exclusion and an increase in psychotic symptoms were not associated with dopamine release.Our study presents preliminary evidence of dopamine sensitization in a socially excluded group of people with hearing impairment. If replicated by future studies in other excluded groups, this finding may have major implications for our understanding of the underlying mechanism and for prevention of psychotic disorders.