tbuckley/cabot-search huggingface dataset:
T cell clones specific for hybrid I-A molecules. Discrimination with monoclonal anti-I-A (k) antibodies
Authors: BN Beck, JG Frelinger, M Shigeta, AJ Infante, D Cummings, G Hammerling, CG Fathman
Journal: The Journal of Experimental Medicine (1982)

Alloreactive and soluble antigen-reactive, I-A-restricted T cell clones were examined for their ability to recognize hybrid I-A antigens. Several clones that recognized hybrid I-A(b)/I-A(k) molecules on (C57BL/6 x A/J)F(1) [(B6A)F(1)] spleen cells were studied. We were able to distinguish clones that recognized hybrid I-A molecules of the A(b)(a)A(k)(β) type from those that recognized A(k)(a)A(b)(β) molecules. We reached this conclusion by considering data from three independent types of experiments. (a) Monoclonal antibodies were used to inhibit T cell stimulation. Antibodies 10.2.16 and H116.32 distinguished two mutually exclusive "families" of T cell clones. One group of clones was inhibited by 10-2.16 and not H116.32, the other group exhibited reciprocal inhibition. (b) T cell proliferation was assayed using antigen-presenting cells from B6.C-H-2(bml2) (bml2) and [bml2 × B10.A(4R)]F(1) mice. Because the bml2 strain has a mutation that results in an altered A(b)(β) polypeptide chain (A(bm12)(β)), we reasoned that clones that could recognize the [bm12 × B 10.A(4R)]F(1) cells were recognizing A(b)(a)A(k)(β) molecules. Alternatively, clones not recognizing [bml2 × B10.A(4R)]F(1) cells had specificity for A(k)(a)A(b)(β) molecules. (c) I-A molecules immunoprecipitated from radiolabeled (B6A)F(1) splenocyte extracts were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These experiments confirmed an earlier report that antibody 10.2.16 recognized determinants on the A(k)(β) chain (12). Antibody H116.32 immunoprecipitated products consistent with recognition of A(k)(a) determinants. Taken together, these three types of results offer conclusive evidence that T cell clones recognizing "hybrid" I-A molecules use either A(b(k)A(k)(β) or A(k)(a)A(b)(β) molecules as recognition or restriction sites. Clones whose proliferation was supported by [bm 12 x B10.A(4R)]F(1) cells and blocked by anti-I-A(k) antibody 10-2.16 recognized A(b)(a)A(k)(β) B molecules. Clones that were blocked by antibody H116.32 and did not recognize [bml2 X B10.A(4R)]F(1) cells use a recognition site(s) on A(b)(a)A(k)(β) molecules. Thus, we can demonstrate both functionally and biochemically that hybrid F(1) I-A molecules of the structure A(k)(a)A(b)(β) and A(b)(a)A(k)(β) both exist on (B6A)F(1) splenocytes and that both configurations are used in immune recognition phenomena.
Macrophage-Tropic HIV Induces and Exploits Dendritic Cell Chemotaxis
Authors: Chen-Lung Lin, Andrew K. Sewell, George F. Gao, Kathryn T. Whelan, Rodney E. Phillips, Jonathan M. Austyn
Journal: The Journal of Experimental Medicine (2000)

Immature dendritic cells (iDCs) express the CC chemokine receptor (CCR)5, which promotes chemotaxis toward the CC chemokines regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β. By contrast, mature DCs downregulate CCR5 but upregulate CXC chemokine receptor (CXCR)4, and as a result exhibit enhanced chemotaxis toward stromal cell–derived factor (SDF)-1α. CCR5 and CXCR4 also function as coreceptors for macrophage-tropic (M-tropic) and T cell–tropic (T-tropic) human immunodeficiency virus (HIV)-1, respectively. Here, we demonstrate chemotaxis of iDCs toward M-tropic (R5) but not T-tropic (X4) HIV-1. Furthermore, preexposure to M-tropic HIV-1 or its recombinant envelope protein prevents migration toward CCR5 ligands. The migration of iDCs toward M-tropic HIV-1 may enhance formation of DC–T cell syncytia, thus promoting viral production and destruction of both DC and T helper lymphocytes. Therefore, disturbance of DC chemotaxis by HIV-1 is likely to contribute to immunosuppression in primary infection and AIDS. In addition, migration of iDCs toward HIV-1 may aid the capture of R5 HIV-1 virions by the abundant DC cell surface protein DC-specific intercellular adhesion molecule (ICAM)3-grabbing nonintegrin (DC-SIGN). HIV-1 bound to DC cell–specific DC-SIGN retains the ability to infect replication-permissive T cells in trans for several days. Consequently, recruitment of DC by HIV-1 could combine with the ability of DC-SIGN to capture and transmit the virus to T cells, and so facilitate dissemination of virus within an infected individual.
Complete Sequence of the Mitochondrial DNA of the Primitive Opisthobranch Gastropod Pupa strigosa: Systematic Implication of the Genome Organization
Authors: A Kurabayashi, R Ueshima
Journal: Molecular Biology and Evolution (2000)

The complete sequence (14,189 bp) of the mitochondrial DNA of the opisthobranch gastropod Pupa strigosa was determined. The genome contains 13 protein, 2 rRNA, and 22 tRNA genes typical of metazoan mtDNA. The Pupa mitochondrial genome is highly compact and shows the following unusual features, like pulmonate land snails: (1) extremely small genome size, (2) absence of lengthy noncoding regions (with the largest intergenic spacer being only 46 nt), (3) size reduction of encoded genes, and (4) many overlapping genes. Several tRNA genes exhibit bizarre secondary structures with reduced T or D stems, and many tRNA genes have unstable acceptor stems that might be corrected by posttranscriptional RNA editing. The Pupa mitochondrial gene arrangement is almost identical to those of pulmonate land snails but is radically divergent from those of the prosobranch gastropod Littorina saxatilis and other molluscs. Our finding that the unique gene arrangement and highly compact genome organization are shared between opisthobranch and pulmonate gastropods strongly suggests their close phylogenetic affinity.
Graft-versus-host-related immunosuppression is induced in mixed chimeras by alloresponses against either host or donor lymphohematopoietic cells.
Authors: M Sykes, M A Sheard, D H Sachs
Journal: The Journal of Experimental Medicine (1988)

Graft-vs.-host (GVH)-related immunosuppression has previously been demonstrated in F1 rodent recipients of parental lymphoid cells, and has been thought to result from an immunologic attack of the donor against the host. Since all cells of such F1 recipients could potentially bear target class I MHC alloantigens, it has not previously been possible to determine precisely the target tissues responsible for development of GVH-related effects. In the present studies we have used mixed allogeneic chimeras as recipients of host or donor-strain lymphocyte inocula, and have made the surprising observation that "GVH-induced" immune unresponsiveness does not require GVH reactivity, per se, but develops in the presence of a one-way alloresponse against lymphohematopoietic cells in either the GVH or the host-versus-graft direction.
Deletion of phosphodiesterase 4D in mice shortens α2-adrenoceptor–mediated anesthesia, a behavioral correlate of emesis
Authors: Annette Robichaud, Panagiota B. Stamatiou, S.-L.Catherine Jin, Nicholas Lachance, Dwight MacDonald, France Laliberté, Susana Liu, Zheng Huang, Marco Conti, Chi-Chung Chan
Journal: Journal of Clinical Investigation (2002)

A combination of pharmacological and genetic approaches was used to determine the role of type 4 cAMP-specific cyclic nucleotide phosphodiesterase 4 (PDE4) in reversing α2-adrenoceptor–mediated anesthesia, a behavioral correlate of emesis in non-vomiting species. Among the family-specific PDE inhibitors, PDE4 inhibitors reduced the duration of xylazine/ketamine–induced anesthesia in mice, with no effect on pentobarbital-induced anesthesia. The rank order of the PDE4 inhibitors tested was 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline (PMNPQ) > (R)-rolipram > (S)-rolipram >> (R)-N-{4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]phenyl}N′-ethylurea (CT-2450). The specific roles of PDE4B and PDE4D in this model were studied using mice deficient in either subtype. PDE4D-deficient mice, but not PDE4B-deficient mice, had a shorter sleeping time than their wild-type littermates under xylazine/ketamine–induced anesthesia, but not under that induced with pentobarbital. Concomitantly, rolipram-sensitive PDE activity in the brain stem was decreased only in PDE4D-deficient mice compared with their wild-type littermates. While PMNPQ significantly reduced the xylazine/ketamine–induced anesthesia period in wild-type mice and in PDE4B-null mice, it had no effect in PDE4D-deficient mice. These findings strongly support the hypothesis that inhibition of PDE4D is pivotal to the anesthesia-reversing effect of PMNPQ and is likely responsible for emesis induced by PDE4 inhibitors.
Toll‐like receptor‐4 deficiency attenuates doxorubicin‐induced cardiomyopathy in mice
Authors: Alexander Riad, Sandra Bien, Matthias Gratz, Felicitas Escher, Markus M. Heimesaat, Stefan Bereswill, Thomas Krieg, Stephan B. Felix, Heinz P. Schultheiss, Heyo K. Kroemer, Carsten Tschöpe
Journal: European Journal of Heart Failure (2008)
Renal vasculitis associated with renal cell carcinoma
Authors: M. Lloyd, J. de Verteuil, P. A Andrews
Journal: Journal of the Royal Society of Medicine (2002)

We present a case of renal and systemic vasculitis that was temporally associated with the clinical presentation of renal cell carcinoma. Although such associations are rare, vasculitis affecting the kidney does appear to confer an increased risk of renal cancer, particularly in the presence of Wegener's granulomatosis.
Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma
Authors: M. Kerkhof, D. S. Postma, B. Brunekreef, N. E. Reijmerink, A. H. Wijga, J. C. de Jongste, U. Gehring, G. H. Koppelman
Journal: Thorax (2010)

<h3>Background</h3> Epidemiological studies have reported adverse effects of ambient air pollution on the prevalence of asthma. Laboratory studies have suggested that innate immune responses are involved. <h3>Objective</h3> A study was undertaken to determine whether the Toll-like receptor 2 and 4 genes (<i>TLR2</i> and <i>TLR4</i>) influence the susceptibility to adverse effects of traffic-related air pollution with respect to the prevalence of childhood asthma. <h3>Methods</h3> Haplotype tagging single nucleotide polymorphisms (SNPs) in the <i>TLR2</i> (n=4) and <i>TLR4</i> genes (n=9) were genotyped in 916 children from the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Exposure to particulate matter (PM<sub>2.5</sub>), soot and nitrogen dioxide (NO<sub>2</sub>) at the birth address was estimated by land use regression models. Interactions between levels of pollutants and SNPs in relation to annual questionnaire reports of asthma diagnosis and symptoms from birth up to 8 years of age were analysed longitudinally by generalised estimating equations. <h3>Results</h3> Two <i>TLR2</i> SNPs and four <i>TLR4</i> SNPs significantly modified the effect of air pollution on the prevalence of doctor-diagnosed asthma from birth up to 8 years of age. The risk of having doctor-diagnosed asthma increased with increasing PM<sub>2.5</sub> levels in children with at least one copy of the <i>TLR2</i> rs4696480 A allele (OR 2.0 (95% CI 1.2 to 3.1) for an interquartile range increase in exposure). Similar observations were present with the following <i>TLR4</i> genotypes: rs2770150 TC (OR 2.0 (95% CI 1.1 to 3.6)), rs10759931 GG (OR 2.6 (95% CI 1.4 to 4.9)), rs6478317 GG (OR 2.2 (95% CI 1.2 to 4.3)), rs10759932 CT or CC (OR 2.9 (95% CI 1.2 to 6.9)) and rs1927911 TT (OR 4.4 (95% CI 1.7 to 11.7)). <h3>Conclusions</h3> Variant alleles of <i>TLR2</i> and <i>TLR4</i> genes influence the susceptibility to adverse effects of traffic-related air pollution on childhood asthma.
Prevalence of colonisation and genotypic characterisation of Pneumocystis jirovecii among cystic fibrosis patients in Spain
Authors: N. Respaldiza, M.A. Montes-Cano, F.J. Dapena, C. de la Horra, I. Mateos, F.J. Medrano, E. Calderon, J.M. Varela
Journal: Clinical Microbiology and Infection (2005)
Angiotensin-Converting Enzyme Inhibitors and Progression of Nondiabetic Renal Disease
Authors: Tazeen H. Jafar
Journal: Annals of Internal Medicine (2001)

Purpose: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease. Data Sources: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease. Study Selection: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997. Data Extraction: Data on 1860 nondiabetic patients were analyzed. Data Synthesis: Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d. Conclusion: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria. *For other members of the ACE Inhibition in Progressive Renal Disease Study Group, see Appendix 1.
Carbon dioxide production during acetazolamide and medroxyprogesterone treatment
Authors: R.P. Cole
Journal: European Respiratory Journal (2003)

To the Editor: 

Wagenaar et al. 1 report improvement in gas exchange and increased minute ventilation ( V ′E) in patients with stable, moderately severe chronic obstructive pulmonary disease receiving treatment with acetazolamide and medroxyprogesterone. They estimate a baseline carbon dioxide (CO2) production rate of 400 mL·min−1 …
Heightened Peripheral Blood Lymphocyte CD69 Expression is Neither Sensitive nor Specific as a Noninvasive Diagnostic Test for Renal Allograft Rejection
Authors: Martin Karpinski, David Rush, John Jeffery, Denise Pochinco, Doug Milley, Peter Nickerson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. It has been reported that acute allograft rejection is associated with heightened expression of the peripheral blood lymphocyte (PBL) early activation marker CD69 and that this may serve as a potential biomarker of rejection. This study sought to determine whether PBL CD69 expression correlates with both acute clinical and subclinical renal allograft rejection as well as clinically inapparent cytomegalovirus (CMV) infection. Flow cytometric determination of PBL CD69 expression was performed at the time of clinical and protocol biopsies (n = 131) in 45 renal transplant recipients. Nineteen patients also underwent weekly monitoring of PBL CD69 expression for the initial 15 wk after transplantation. Simultaneous screening for CMV viremia was performed with a semiquantitative PCR assay. No differences were seen in either CD4+ or CD8+ lymphocyte CD69 expression between the biopsy diagnoses. CMV viremia however, independent of rejection, was associated with greater CD69 expression on CD8+ lymphocytes (17.8 ± 10.4% versus 9.6 ± 4.8%; P < 0.0001) but not CD4+ lymphocytes. No individuals experienced clinical CMV disease. Weekly monitoring of PBL CD69 expression did not change coincident with the diagnosis of rejection; however, CMV viremia coincided with a substantial rise in the proportion of CD8+69+ lymphocytes in a number of individuals. Thus, PBL CD69 expression is neither sensitive nor specific for the noninvasive diagnosis of renal allograft rejection. Furthermore, clinically inapparent CMV viremia is associated with heightened expression of this activation marker on CD8+ lymphocytes. This latter finding suggests that clinically inapparent CMV viremia may be a potential confounder for biomarkers of rejection that examine peripheral blood lymphocytes. E-mail: [email protected]
Remote Ischemic Preconditioning Preserves Mitochondrial Function and Influences Myocardial MicroRNA Expression in Atrial Myocardium During Coronary Bypass Surgery
Authors: Katrine Hordnes Slagsvold, Øivind Rognmo, Morten Høydal, Ulrik Wisløff, Alexander Wahba
Journal: Circulation Research (2013)

Remote ischemic preconditioning (RIPC) has been suggested to induce cardioprotection during cardiac surgery. Maintaining proper atrial function is imperative in preventing arrhythmia and thrombus formation. Mitochondria have been proposed as key targets in conveying RIPC mechanisms and effects. MicroRNA (miR) is emerging as an important regulator of mitochondrial function, arrhythmia, and protection from ischemia and reperfusion.This study aimed to evaluate the effect of RIPC on mitochondrial respiration and miR expression in human atrial tissue.Sixty patients undergoing coronary artery bypass graft surgery were randomized to RIPC (n=30) or control (n=30). RIPC was performed preoperatively by inflating a blood pressure cuff on the upper arm to 200 mm Hg for 3×5 minutes, with 5 minutes reperfusion intervals. Biopsies were obtained from the right atrial appendage before and after aortic cross-clamping. Mitochondrial respiration was measured in situ and miR assessed by commercial miR array and quantitative reverse transcription polymerase chain reaction. Postoperative atrial fibrillation occurrence was monitored by biotelemetry. Maximal mitochondrial respiration was preserved throughout surgery after RIPC but significantly reduced (-28%; P<0.05) after aortic cross-clamping in control. Incidence of postoperative atrial fibrillation was lower after RIPC versus control (14% versus 50%; P<0.01). Myocardial expression of miR-133a and miR-133b increased after aortic cross-clamping in both RIPC and control, whereas miR-1 was upregulated in control only. MiR-338-3p expression was higher in RIPC versus control after aortic cross-clamping.RIPC preserves mitochondrial respiration and prevents upregulation of miR-1 in the right atrium during coronary artery bypass graft.http://www.clinicaltrials.gov. Unique identifier: NCT01308138.
Platinum Resistance: The Role of DNA Repair Pathways
Authors: Lainie P. Martin, Thomas C. Hamilton, Russell J. Schilder
Journal: Clinical Cancer Research (2008)

Abstract Although platinum chemotherapeutic agents such as carboplatin, cisplatin, and oxaliplatin are used to treat a broad range of malignant diseases, their efficacy in most cancers is limited by the development of resistance. There are multiple factors that contribute to platinum resistance but alterations of DNA repair processes have been known for some time to be important in mediating resistance. Recently acquired knowledge has provided insight into the molecular mechanisms of DNA repair pathways and their effect on response to chemotherapy. This review will discuss the most important DNA repair pathways known to be involved in the platinum response, i.e., nucleotide excision repair (NER) and mismatch repair (MMR), and will briefly touch on the role of BRCA in DNA repair. The therapeutic implications of alterations in DNA repair which affect response to platinum in the treatment of patients with malignant disease, such as excision repair cross-complementation group 1 (ERCC1) deficiency and mismatch repair deficiency, will be reviewed.
Establishing an audio recording service for patients with prostate cancer
Authors: D. W. Good, G. D. Stewart, S. A. McNeill
Journal: BMJ (2014)

In response to Elwyn’s thought provoking article,1 we would like to share our experience at NHS Lothian.

In 2012, with the help and support of the Edinburgh and Lothian Prostate Cancer Support Group, we instituted audio recordings of consultations for all patients with prostate cancer.2 Patients are given a CD recording to keep, so that they can …
Randomized Multicenter Phase II Study of Larotaxel (XRP9881) in Combination with Cisplatin or Gemcitabine as First-Line Chemotherapy in Nonirradiable Stage IIIB or Stage IV Non-small Cell Lung Cancer
Authors: Petr Zatloukal, Radj Gervais, Johan Vansteenkiste, Léon Bosquee, Christiana Sessa, Etienne Brain, Eric Dansin, Thierry Urban, Nadine Dohollou, Michèle Besenval, Elisabeth Quoix
Journal: Journal of Thoracic Oncology (2008)
NOTES OF A CASE OF CONGENITAL ICHTHYOSIS HYSTRIX LINEARIS OR HYSTRICISMUS (<i>SYN.</i>: ICHTHYOSIS CORNEA, NAEVUS VERRUCOSUS, VEL NAEVUS PAPILLARIS, VEL PAPILLOMA NEUROTICUM, ETC.)
Authors: J. H. STOWERS
Journal: British Journal of Dermatology (1908)

AT the Meeting of the Dermatological Society of Great Britain and Ireland held on February 27th, 1907, I exhibited an unusually marked case of the above-named disease, of which a brief notice appeared in this journal (vol.xix, No. 4, p. 126).As carefully prepared coloured drawings have been made, it is desirable that a somewhat fuller account of the case should be published with illustrations.The patient, a girl, aged 8 years and 4 months, is the younger of two children born of healthy parents.She was in a somewhat enfeebled condition of health, although well grown and nourished, and the subject of talipes varus, for which deformity she was taken to the City Orthopedic Hospital to be treated by my colleague, Mr. Jackson Clarke, through whose recommendation she was referred to me.The lesions, which had slowly developed from the date of birth to the age of six years, had since undergone but little change, and there was no indication of spread or of new areas becoming involved.Unsuccessful attempts at removal, however, of some of them had been made in former years by means of the knife, escharotics, etc.So far as I could learn the disease, which in parts is characterised VOL.xx.