tbuckley/cabot-search huggingface dataset:
The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells.
Authors: A R Townsend, J J Skehel
Journal: The Journal of Experimental Medicine (1984)

Using genetically typed recombinant influenza A viruses that differ only in their genes for nucleoprotein, we have demonstrated that repeated stimulation in vitro of C57BL/6 spleen cells primed in vivo with E61-13-H17 (H3N2) virus results in the selection of a population of cytotoxic T lymphocytes (CTL) whose recognition of infected target cells maps to the gene for nucleoprotein of the 1968 virus. Influenza A viruses isolated between 1934 and 1979 fall into two groups defined by their ability to sensitize target cells for lysis by these CTL: 1934-1943 form one group (A/PR/8/34 related) and 1946-1979 form the second group (A/HK/8/68 related). These findings complement and extend our previous results with an isolated CTL clone with specificity for the 1934 nucleoprotein (27, 28). It is also shown that the same spleen cells derived from mice primed with E61-13-H17 virus in vivo, but maintained in identical conditions by stimulation with X31 virus (which differs from the former only in the origin of its gene for NP) in vitro, results in the selection of CTL that cross-react on target cells infected with A/PR/8/1934 (H1N1) or A/Aichi/1968 (H3N2). These results show that the influenza A virus gene for NP can play a role in selecting CTL with different specificities and implicate the NP molecule as a candidate for a target structure recognized by both subtype-directed and cross-reactive influenza A-specific cytotoxic T cells.
Toxic epidermal necrolysis in two patients with pustular psoriasis
Authors: SARAH C.F. ROGERS, PHILLIP H. MCKEE
Journal: British Journal of Dermatology (1977)

Two cases of toxic epidermal necrolysis are described in patients suffering from pustular psoriasis. In one of these cases there were no recognized predisposing causes. In the other, although there were alternative possibilities, we consider that the most likely cause of the toxic epidermal necrolysis was pustular psoriasis.
Vitamin D Deficiency and Coronary Artery Calcification in Subjects With Type 1 Diabetes
Authors: Kendra A. Young, Janet K. Snell-Bergeon, Ramachandra G. Naik, John E. Hokanson, David Tarullo, Peter A. Gottlieb, Satish K. Garg, Marian Rewers
Journal: Diabetes Care (2010)

OBJECTIVE The objective of this study is to examine the relationship among serum levels of 25-hydroxyvitamin D (25[OH]D), polymorphisms in vitamin D-associated genes, and the presence and progression of coronary artery calcification (CAC) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This prospective study included 374 non-Hispanic white individuals with type 1 diabetes (mean age 40 ± 9 years; 46% were male). CAC was measured at the baseline and 3- and 6-year follow-up visits were determined by electron beam computed tomography. Serum 25[OH]D levels were measured by liquid chromatography tandem mass spectrometry at the 3-year visit. RESULTS Normal (&amp;gt;30 ng/mL), insufficient (20–30 ng/mL), and deficient (&amp;lt;20 ng/mL) 25-[OH]D levels were present in 65%, 25%, and 10% of the individuals with type 1 diabetes, respectively. 25[OH]D deficiency was associated with the presence of CAC at the 3-year visit, odds ratio (OR) = 3.3 (95% CI 1.6–7.0), adjusting for age, sex, and hours of daylight. In subjects free of CAC at the 3-year visit, 25[OH]D deficiency predicted the development of CAC over the next 3 years in those with the vitamin D receptor M1T CC genotype (OR = 6.5 [1.1–40.2], P = 0.04) than in those with the CT or TT genotype (OR = 1.6 [0.3–8.6], P = 0.57). CONCLUSIONS Vitamin D deficiency independently predicts prevalence and development of CAC, a marker of coronary artery plaque burden, in individuals with type 1 diabetes.
Generation of T-helper cells in vitro. I. Cellular and antigen requirements.
Authors: J S McDougal, D S Gordon
Journal: The Journal of Experimental Medicine (1977)

A sequential mouse cell culture system is described for the induction and assay of T-helper cells. Unprimed, cortisone-resistant, nylon wool-purified thymocytes cultured with adherent peritoneal exudate cells can be primed in vitro with soluble carrier protein to generate carrier-reactive helper cells. These cultured cells enhance the anti-hapten plaque-forming response of hapten-primed spleen cell cultures to hapten carrier conjugates. The culture conditions, cellular manipulations, and antigen requirements for the optimal induction of helper cells with these purified cell populations is presented. The active helper cell generated in this culture system is a thymus-derived cell which requires macrophages for its induction and must be proliferate in vitro before the manifestation of helper-cell function. Helper cells generated in vitro stimulate both carrier-specific and nonspecific enhancement of splenic anti-hapten responses. The carrier-specific and nonspecific enhancement can be distinguished by the requirement for antigen in the helper cell and spleen cell cultures, the dose of helper cells added to the spleen cell cultures, and by the requirement for additional splenic adherent accessory cell interactions.
Comparison of clinical, radionuclide, and radiographic features of osteoarthritis of the hands.
Authors: D G Macfarlane, J C Buckland-Wright, P Emery, I Fogelman, B Clark, J Lynch
Journal: Annals of the Rheumatic Diseases (1991)

Simultaneous clinical, scintigraphic, and macroradiographic assessments were carried out on 32 patients with hand osteoarthritis and the results at entry and one year reported. The presence and growth of osteophyte correlated with symptoms and a positive scan. The scan did not detect the radiographic features of juxta-articular radiolucencies, subchondral sclerosis, or cartilage thinning. Osteophytes, particularly when fast growing, produce pain, a 9hot9 scan, and may predict disintegration of joint architecture.
Improved detection of rotavirus shedding by polymerase chain reaction
Authors: J. Wilde, R. Yolken, R. Willoughby, J. Eiden
Journal: The Lancet (1991)

To improve identification of children excreting rotavirus a method for the amplification of rotavirus RNA by the polymerase chain reaction (PCR) was developed. The assay was compared with a solid-phase enzyme immunoassay in the detection of rotavirus shedding by infants in hospital during the winter peak of rotavirus infections. Forty children were studied in an intermediate care unit after transfer from intensive care units. Only two were admitted primarily because of diarrhoea; the other thirty-eight were admitted for management of various other disorders. Rotavirus shedding was detected by enzyme immunoassay in twenty of the infants, and nine of these (aged 1 week to 8 months) remained in hospital for more than 5 days after the initial detection of rotavirus and could be studied long term. Of 103 faecal samples from the nine infants, 60 (58%) contained rotavirus RNA detected by reverse-transcriptase (RT)/PCR, whereas only 37 (36%) were positive for rotavirus antigen by the immunoassay (χ2=10·3, p<0·002). The geometric mean time of rotavirus shedding was 9·5 (range 1-19) days as detected by RT/PCR and 5·7 (range 1-17) days by the immunoassay (p<0·018). In five of the nine children, RT/PCR detected rotavirus shedding for 2-7 days longer than the immunoassay and in four children RT/PCR was positive 1 or more days before rotavirus antigen was detected. Further studies should attempt to find out whether infected infants are capable of spreading wild-type virus during periods when they are not shedding antigen as detectable by enzyme immunoassay.
An Improved General Amino Acid Replacement Matrix
Authors: S. Q. Le, O. Gascuel
Journal: Molecular Biology and Evolution (2008)

Amino acid replacement matrices are an essential basis of protein phylogenetics. They are used to compute substitution probabilities along phylogeny branches and thus the likelihood of the data. They are also essential in protein alignment. A number of replacement matrices and methods to estimate these matrices from protein alignments have been proposed since the seminal work of Dayhoff et al. (1972). An important advance was achieved by Whelan and Goldman (2001) and their WAG matrix, thanks to an efficient maximum likelihood estimation approach that accounts for the phylogenies of sequences within each training alignment. We further refine this method by incorporating the variability of evolutionary rates across sites in the matrix estimation and using a much larger and diverse database than BRKALN, which was used to estimate WAG. To estimate our new matrix (called LG after the authors), we use an adaptation of the XRATE software and 3,912 alignments from Pfam, comprising ∼50,000 sequences and ∼6.5 million residues overall. To evaluate the LG performance, we use an independent sample consisting of 59 alignments from TreeBase and randomly divide Pfam alignments into 3,412 training and 500 test alignments. The comparison with WAG and JTT shows a clear likelihood improvement. With TreeBase, we find that 1) the average Akaike information criterion gain per site is 0.25 and 0.42, when compared with WAG and JTT, respectively; 2) LG is significantly better than WAG for 38 alignments (among 59), and significantly worse with 2 alignments only; and 3) tree topologies inferred with LG, WAG, and JTT frequently differ, indicating that using LG impacts not only the likelihood value but also the output tree. Results with the test alignments from Pfam are analogous. LG and a PHYML implementation can be downloaded from http://atgc.lirmm.fr/LG.
Effect of atrial septostomy on the survival of patients with severe pulmonary arterial hypertension
Authors: J. Sandoval, J. Gaspar, H. Peña, L.E. Santos, J. Córdova, K. del Valle, A. Rodríguez, T. Pulido
Journal: European Respiratory Journal (2011)

Atrial septostomy (AS) is a palliative treatment for right ventricular failure from severe pulmonary arterial hypertension (PAH). We sought to investigate the effect of AS, alone or combined with PAH-specific pharmacotherapy, on the survival of patients with PAH. We performed a retrospective analysis of the functional and haemodynamic changes in patients with PAH following AS, and long-term survival characteristics for the whole group and separately for the subgroup who received post-procedural pharmacotherapy. 50 procedures performed in 34 patients (mean ± SD age 35 ± 10 yrs) resulted in haemodynamic and symptomatic improvement in most of the patients. Only one (2%) procedure-related death occurred. Due to spontaneous closure of the defect, AS was repeated in 10 patients. In 21 patients, AS was the only form of treatment, while 11 received additional pharmacotherapy after AS. During follow-up (58.5 ± 38 months), 21 patients died; median survival of the group was 60 months (95% CI 43-77 months). Median survival for patients on pharmacotherapy additional to AS was 83 months (95% CI 57-109 months), which was better than that for patients with AS alone (53 months, 95% CI 39-67 months) (log-rank 6.52; p = 0.010). In selected patients with PAH, AS is a safe and effective intervention that exerts a beneficial impact on long-term survival. Survival appears to be improved when AS is combined with PAH-specific pharmacotherapy.
Cough threshold in patients with chronic obstructive pulmonary disease
Authors: C H Wong, A H Morice
Journal: Thorax (1999)

Cough is an important symptom of patients with chronic obstructive pulmonary disease (COPD). The cough threshold to citric acid and capsaicin in patients with COPD and in normal volunteers was measured, as well as bronchial hyperresponsiveness to methacholine.Nineteen patients with COPD and 22 controls were recruited. Subjects underwent a methacholine bronchoprovocation test and a cough challenge to citric acid and capsaicin.The log citric acid cough threshold D2 (concentration causing two coughs) was significantly lower in patients with COPD (mean 2.17 versus 2.56, mean difference (95% CI) 0.39 (0.04 to 0.74), p = 0.02) but not for capsaicin cough D2 (0.66 versus 0.8, p = 0.41). Sixteen patients with COPD had bronchial hyperresponsiveness which was correlated with baseline FEV1 (r = 0.6, p = 0.01, 95% CI 0.15 to 0.84).Patients with COPD have a lower cough threshold to citric acid, possibly due to a differential effect of cigarette smoke on citric acid sensitive cough receptors.
Recognition of carbohydrate by major histocompatibility complex class I-restricted, glycopeptide-specific cytotoxic T lymphocytes.
Authors: J S Haurum, G Arsequell, A C Lellouch, S Y Wong, R A Dwek, A J McMichael, T Elliott
Journal: The Journal of Experimental Medicine (1994)

Cytotoxic T cells (CTL) recognize short peptide epitopes presented by class I glycoproteins encoded by the major histocompatibility complex (MHC). It is not yet known whether peptides containing posttranslationally modified amino acids can also be recognized by CTL. To address this issue, we have studied the immunogenicity and recognition of a glycopeptide carrying an O-linked N-acetylglucosamine (GlcNAc) monosaccharide-substituted serine residue. This posttranslational modification is catalyzed by a recently described cytosolic glycosyltransferase. We show that glycosylation does not affect peptide binding to MHC class I and that glycopeptides can elicit a strong CTL response that is glycopeptide specific. Furthermore, glycopeptide recognition by cytotoxic T cells is dependent on the chemical structure of the glycan as well as its position within the peptide.
Impact of Nedd4 Proteins and Serum and Glucocorticoid-Induced Kinases on Epithelial Na+ Transport in the Distal Nephron
Authors: Olivier Staub, Franc[COMBINING CEDILLA]ois Verrey
Journal: Journal of the American Society of Nephrology (2005)

The precise control of BP occurs via Na(+) homeostasis and involves the precise regulation of the epithelial Na(+) channel (ENaC) in the aldosterone-sensitive distal nephron. This has been corroborated by the linkage of mutations in the genes encoding ENaC subunits and Liddle's syndrome, a heritable form of human hypertension. Mapping of these mutations on ENaC indicated that inactivation of PY motifs is responsible and leads to the proposition that the channel interacts via its PY motifs with the WW domains of the Nedd4/Nedd4-like ubiquitin-protein ligase family. It is now well established that the cell surface expression of ENaC is controlled via ubiquitylation by this protein family and that this ubiquitylation is regulated by the aldosterone-induced protein serum and glucocorticoid induced kinase 1.
Clinical Features and Short-term Outcomes of 144 Patients With SARS in the Greater Toronto Area
Authors: Christopher M. Booth
Journal: JAMA (2003)

Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in China in November 2002 and has subsequently spread worldwide.To describe the clinical characteristics and short-term outcomes of SARS in the first large group of patients in North America; to describe how these patients were treated and the variables associated with poor outcome.Retrospective case series involving 144 adult patients admitted to 10 academic and community hospitals in the greater Toronto, Ontario, area between March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS. Patients were included if they had fever, a known exposure to SARS, and respiratory symptoms or infiltrates observed on chest radiograph. Patients were excluded if an alternative diagnosis was determined.Location of exposure to SARS; features of the history, physical examination, and laboratory tests at admission to the hospital; and 21-day outcomes such as death or intensive care unit (ICU) admission with or without mechanical ventilation.Of the 144 patients, 111 (77%) were exposed to SARS in the hospital setting. Features of the clinical examination most commonly found in these patients at admission were self-reported fever (99%), documented elevated temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%). Common laboratory features included elevated lactate dehydrogenase (87%), hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea. A total of 126 patients (88%) were treated with ribavirin, although its use was associated with significant toxicity, including hemolysis (in 76%) and decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were admitted to the ICU with or without mechanical ventilation, and 8 patients died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95% CI, 1.4-7.2; P =.01) or other comorbid conditions (RR, 2.5; 95% CI, 1.1-5.8; P =.03) were independently associated with poor outcome (death, ICU admission, or mechanical ventilation).The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived.
Infection of Human Fetal Cardiac Myocytes by a Human Immunodeficiency Virus-1–Derived Vector
Authors: Michael A. Rebolledo, Paul Krogstad, Fuhua Chen, Kevin M. Shannon, Thomas S. Klitzner
Journal: Circulation Research (1998)

Abstract —Cardiomyopathy associated with HIV-1 infection is a well-recognized complication. However, it is unknown whether direct cardiomyocyte infection is involved in the pathogenesis of the cardiomyopathy. An HIV-1–based lentiviral vector and wild-type HIV-1 were used to infect human fetal cardiac myocytes in a primary culture. Quantitative polymerase chain reaction, viral p24 antigen determination, and immunofluorescence were used to detect the synthesis of HIV-1 DNA and proteins after the infection. High-efficiency infection occurred using the HIV-1–based lentiviral vector, although no infection occurred with the wild-type HIV-1 strain. Dual-labeling immunofluorescence for HIV-1 proteins and myosin confirmed that cardiomyocytes were infected. This in vitro analysis suggests that direct myocyte infection with wild-type HIV-1 may not be involved in the pathogenesis of HIV-1 cardiomyopathy. However, HIV-1–based vectors may prove useful for ex vivo cardiovascular gene therapy.
Re: Reason for Late-Stage Breast Cancer: Absence of Screening or Detection, or Breakdown in Follow-Up?
Authors: A. S. Whittemore
Journal: JNCI Journal of the National Cancer Institute (2005)

BACKGROUND Mammography screening increases the detection of early-stage breast cancers. Therefore, implementing screening should reduce the percentage of women who are diagnosed with late-stage disease. However, despite high national mammography screening rates, late-stage breast cancers still occur, possibly because of failures in screening implementation. METHODS Using data from seven health care plans that included 1.5 million women aged 50 years or older, we conducted retrospective reviews of chart and automated data for 3 years before 1995-1999 diagnoses of late-stage (metastatic and/or tumor size > or =3 cm; case subjects, n = 1347) and early-stage breast cancers (control subjects, n = 1347). We categorized the earliest screening mammogram during the period 13-36 months before diagnosis as none (absence of screening), negative (absence of detection), or positive (potential breakdown in follow-up). We compared the proportion of case and control subjects in each category of screening implementation and estimated the likelihood (odds ratio [OR] with 95% confidence intervals [CIs]) of late-stage breast cancer. We also evaluated demographic characteristics associated with absence of screening in women with late-stage disease. All statistical tests were two-sided. RESULTS Absence of screening, absence of detection, and potential breakdown in follow-up were distributed differently among case (52.1%, 39.5%, and 8.4%, respectively) and control subjects (34.4%, 56.9%, and 8.8%, respectively) (P = .03). Among all women, the odds of having late-stage cancer were higher among women with an absence of screening (OR = 2.17, 95% CI = 1.84 to 2.56; P<.001). Among case patients, women were more likely to be in the absence-of-screening group if they were aged 75 years or older (OR = 2.77, 95% CI = 2.10 to 3.65), unmarried (OR = 1.78, 95% CI = 1.41 to 2.24), or without a family history of breast cancer (OR = 1.84, 95% CI = 1.45 to 2.34). A higher proportion of women from census blocks with less education (58.5% versus 49.4%; P = .003) or lower median annual income (54.4% versus 42.9%; P = .004) were in the absence-of-screening category compared with the proportion for the other two categories combined. CONCLUSIONS To reduce late-stage breast cancer occurrence, reaching unscreened women, including elderly, unmarried, low-income, and less educated women, should be made a top priority for screening implementation.
The Vicissitudes of the Adoption Process
Authors: ENID W. ROTHENBERG, HARVEY GOLDEY, ROSALIND M. SANDS
Journal: American Journal of Psychiatry (1971)

A child guidance center that does not itself handle adoptions has had discussion groups for adoptive parents for several years. The authors describe the program and their increasing awareness of the discrepancies between their observations from the groups and the practices of many adoption agencies. They believe it is necessary to study in greater depth the dynamics of adoption and carry on further clinical investigation of conscious and unconscious forces in the process; collaboration between mental health facilities and adoption agencies is necessary if primary prevention in this important area is to succeed.
Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations.
Authors: W D Neithercut, A Milne, R S Chittajallu, A M el Nujumi, K E McColl
Journal: Gut (1991)

Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their H pylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0.8 mmol/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0-13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated--the ratios ranged from 0.04-0.7 (median 0.26) and from 1.1-113 (median 3.4) in infected and uninfected subjects respectively (p less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication.