tbuckley/cabot-search huggingface dataset:
Circulating DNA Microsatellites: Molecular Determinants of Response to Biochemotherapy in Patients With Metastatic Melanoma
Authors: B. Taback, S. J. O'Day, P. D. Boasberg, S. Shu, P. Fournier, R. Elashoff, H.-J. Wang, D. S. B. Hoon
Journal: JNCI Journal of the National Cancer Institute (2004)

Although biochemotherapy appears to be a promising treatment for metastatic melanoma, its impact remains unpredictable. Microsatellite markers for loss of heterozygosity (LOH) appear to have prognostic significance when identified in primary tumors and serum and/or plasma from cancer patients. However, their association with response to systemic therapy has yet to be assessed. To determine whether microsatellite markers are associated with response to therapy, serum from 41 patients with metastatic melanoma, drawn before the initiation of biochemotherapy, was analyzed for LOH with nine microsatellite markers. During a median follow-up of 13 months, the overall response rate for these 41 patients was 56%, including 13 (32%) complete responses and 10 (24%) partial responses. LOH was detected in sera from 12 (29%) of the 41 patients. The response rate of these 12 patients was 17% (95% confidence interval [CI] = 5% to 45%), whereas that of the 29 patients without LOH was 72% (95% CI = 54% to 85%) (P = .001). All statistical tests were two-sided. The presence of LOH was statistically significant and independently associated with disease progression (multivariable analysis, P = .003). Circulating tumor DNA markers may be useful in assessing prognosis for advanced melanoma patients and their response to biochemotherapy.
Pharmacokinetics and Tissue Disposition of Indole-3-carbinol and Its Acid Condensation Products after Oral Administration to Mice
Authors: Mark J. Anderton, Margaret M. Manson, Richard D. Verschoyle, Andreas Gescher, John H. Lamb, Peter B. Farmer, William P. Steward, Marion L. Williams
Journal: Clinical Cancer Research (2004)

Abstract Indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM) are promising cancer chemopreventive agents in rodent models, but there is a paucity of data on their pharmacokinetics and tissue disposition. The disposition of I3C and its acid condensation products, DIM, [2-(indol-3-ylmethyl)-indol-3-yl]indol-3-ylmethane (LTr1), indolo[3,2b]carbazole (ICZ) and 1-(3-hydroxymethyl)-indolyl-3-indolylmethane (HI-IM) was studied, after oral administration of I3C (250 mg/kg) to female CD-1 mice. Blood, liver, kidney, lung, heart, and brain were collected between 0.25 and 24 h after administration and the plasma and tissue concentrations of I3C and its derivatives determined by high-performance liquid chromotography. I3C was rapidly absorbed, distributed, and eliminated from plasma and tissues, falling below the limit of detection by 1 h. Highest concentrations of I3C were detected in the liver where levels were approximately 6-fold higher than those in the plasma. Levels of DIM, LTr1, and HI-IM were much lower, although they persisted in plasma and tissues for considerably longer. DIM and HI-IM were still present in the liver 24 h after I3C administration. Tissue levels of DIM and LTr1 were found to be in equilibrium with plasma at almost every time point measured. In addition to acid condensation products of I3C, a major oxidative metabolite (indole-3-carboxylic acid) and a minor oxidative metabolite (indole-3-carboxaldehyde) were detected in plasma of mice after oral administration of I3C. ICZ was also tentatively identified in the liver of these mice. This study shows for the first time that, after oral administration to mice, I3C, in addition to its acid condensation products, is absorbed from the gut and distributed systemically into a number of well-perfused tissues, thus allowing the possibility for some pharmacological activity of the parent compound in vivo.
Sleep-disordered breathing and upper airway size in pregnancy and post-partum
Authors: B. Izci
Journal: European Respiratory Journal (2006)

Sleep-disordered breathing and snoring are common in pregnancy. The aim of this study was to determine whether pregnancy was associated with upper airway narrowing. One-hundred females in the third trimester of pregnancy were recruited and 50 agreed to be restudied 3 months after delivery. One-hundred nonpregnant females were also recruited. Upper airway dimensions were measured using acoustic reflection. Snoring was less common in nonpregnant (17%) than pregnant females (41%; odds ratio (OR) 3.34; 95% confidence interval (CI) 1.65–6.74) and returned to nonpregnant levels after delivery (18%; OR 0.15; 95% CI 0.06–0.40). Pregnant females had significantly smaller upper airways than nonpregnant females at the oropharyngeal junction when seated (mean difference 0.12; 95% CI 0.008–0.25), and smaller mean pharyngeal areas in the seated (mean difference 0.14; 95% CI 0.001–0.28), supine (mean difference 0.11; 95% CI 0.01–0.22) and lateral postures (mean difference 0.13; 95% CI 0.02–0.24) compared with the nonpregnant females. Pregnant females had smaller mean pharyngeal areas compared with post-partum in the seated (mean difference 0.18; 95% CI 0.02–0.32), supine (mean difference 0.20; 95% CI 0.06–0.35) and lateral postures (mean difference 0.26; 95% CI 0.12–0.39). In conclusion, this study confirmed increased snoring and showed narrower upper airways during the third trimester of pregnancy.
A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma
Authors: A. Dueñas-Gonzalez, C. Lopez-Graniel, A. Gonzalez, M. Reyes, A. Mota, D. Muñoz, G. Solorza, L.M. Hinojosa, R. Guadarrama, R. Florentino, A. Mohar, J. Meléndez, V. Maldonado, J. Chanona, E. Robles, J. De la Garza
Journal: Annals of Oncology (2001)
Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study
Authors: Takashi Seto, Terufumi Kato, Makoto Nishio, Koichi Goto, Shinji Atagi, Yukio Hosomi, Noboru Yamamoto, Toyoaki Hida, Makoto Maemondo, Kazuhiko Nakagawa, Seisuke Nagase, Isamu Okamoto, Takeharu Yamanaka, Kosei Tajima, Ryosuke Harada, Masahiro Fukuoka, Nobuyuki Yamamoto
Journal: The Lancet Oncology (2014)
(42) Relapsing polychondritis
Authors: E.L. Rhodes
Journal: British Journal of Dermatology (2006)

Journal Article (42) Relapsing polychondritis Get access E.L. Rhodes E.L. Rhodes St Helier Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue s14, 1 December 1976, Page 81, https://doi.org/10.1111/j.1365-2133.1976.tb07930.x Published: 01 December 1976
TCR chain gangs
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

T cell receptors (TCRs) band together to detect minute amounts of antigen, according to Schamel and colleagues on page 493. Their new work shows that TCRs are expressed on the surface of resting T cells either individually or in groups. The grouped TCRs, but not the solitary receptors, were triggered by low dose antigen, suggesting that these receptors must cooperate when antigen is scarce.Whether TCRs exist as solitary entities or whether they group together is a long-standing matter of debate. Previous studies have failed to uncover evidence of grouped (multivalent) TCRs, but this may have resulted from dismantling of the groups as a result of overly harsh purification techniques.






Figure 

T cell receptors are expressed either individually (red arrows) or as multivalent groups (black arrows). Only grouped TCRs respond to low-dose antigen.




In the new study, Schamel et al. gently coaxed the TCRs from the cell membrane using a mild detergent, allowing the receptors to retain both their native conformation and any associations with neighboring membrane proteins. They discovered that up to 50% of TCRs expressed by naive T cells associated with other TCRs and formed linear multivalent chains on the cell surface.

Only the multivalent TCRs became phosphorylated in response to low doses of antigen, which might explain how T cells can detect and respond to rare antigenic peptide–MHC complexes amidst a sea of self peptide–MHC pairs. The authors suggest that preexisting clusters of TCRs may allow the responding TCR to facilitate phosphorylation of its neighbor, triggering a chain reaction and making the most of an otherwise weak signal. The research teams are now looking for multivalent TCRs on activated and memory T cells. They suspect that a higher proportion of multivalent TCRs on these cells might in part explain these cells' increased responsiveness to antigen.
PTEN1 is frequently mutated in primary endometrial carcinomas
Authors: Dehe Kong, Akihiko Suzuki, Tong-Tong Zou, Akira Sakurada, Lawrence W. Kemp, Shigeru Wakatsuki, Tadaaki Yokoyama, Hiromitsu Yamakawa, Toru Furukawa, Masami Sato, Noriaki Ohuchi, Shinji Sato, Jing Yin, Suna Wang, John M. Abraham, Rhonda F. Souza, Kara N. Smolinski, Stephen J. Meltzer, Akira Horii
Journal: Nature Genetics (1997)
Baroreceptor reflex control of arterial hemodynamics in the dog.
Authors: R H Cox, R J Bagshaw
Journal: Circulation Research (1975)

The regional differentiation of carotid sinus control of arterial pressure-flow relationships was studied in chloralose-anesthetized dogs. Simulatneous pressure-flow measurements were made in the ascending aorta, the celiac artery, the cranial mesenteric artery, the renal artery, and the femoral artery. The carotid sinuses were bilaterally isolated and perfused with pulsatile pressure. The open-loop reflex gain was not symmetrical about and was maximum at pressures below the closed loop operating point pressure. Changes in both peripheral resistance and cardiac output contributed significantly to the open-loop gain with the former predominating. Aortic impedance for frequencies above 3 Hz was at a minimum at the closed-loop operating point and increased for both higher and lower values of carotid sinus pressure. For the frequency range from 3 to 9 Hz, regional impedance in all of the beds varied inversely with carotid sinus pressure. The sensitivity of the various beds to changes in carotid sinus pressure around the operating point increased in the order celiac less than mesenteric less than renal less than femoral. Following vagotomy, operating point values of regional resistance and sensitivity were significantly increased. This fact suggests that the aortic arch receptors exert a significant influence on regional vascular impedance at operating point pressures. The fraction of cardiac output in the celiac, mesenteric, and renal beds was nearly independent of carotid sinus pressure before and after vagotomy, but that in the femoral bed increased with carotid sinus pressure. These results demonstrate the nonuniform nature of carotid sinus and aortic arch baroreceptor control of regional blood flow.
Cetacean mitochondrial DNA control region: sequences of all extant baleen whales and two sperm whale species.
Authors: U Arnason, A Gullberg, B Widegren
Journal: Molecular Biology and Evolution (1993)

The sequence of the mitochondrial control region was determined in all 10 extant species commonly assigned to the suborder Mysticeti (baleen or whalebone whales) and to two odontocete (toothed whale) species (the sperm and the pygmy sperm whale). In the mysticetes, both the length and the sequence of the control region were very similar, with differences occurring primarily in the first approximately 160 bp of the 5' end of the L-strand of the region. There were marked differences between the mysticete and sperm whale sequences and also between the two sperm whales. The control region, less its variable portion, was used in a comparison including the 10 mysticete sequences plus the same region of an Antarctic minke whale specimen and the two sperm whales. The difference between the minke whales from the North Atlantic and the Antarctic was greater than that between any acknowledged species belonging to the same genus (Balaenoptera). The difference was similar to that between the families Balaenopteridae (rorquals) and Eschrichtiidae (gray whales). The findings suggest that the Antarctic minke whale should have a full species status, B. bonaerensis. Parsimony analysis separated the bowhead and the right whale (family Balaenidae) from all remaining mysticetes, including the pygmy right whale. The pygmy right whale is usually included in family Balaenidae. The analysis revealed a close relationship between the gray whale (family Eschrichtiidae) sequence and those of the rorquals (family Balaenopteridae). The gray whale was included in a clade together with the sei, Bryde's, fin, blue, and humpback whales. This clade was separated from the two minke whale types, which branched together.
Enhanced diagnosis of HIV-1-associated tuberculosis by relating T-SPOT.TB and CD4 counts
Authors: T. Oni, J. Patel, H.P. Gideon, R. Seldon, K. Wood, Y. Hlombe, K.A. Wilkinson, M.X. Rangaka, M. Mendelson, R.J. Wilkinson
Journal: European Respiratory Journal (2010)

The sensitivity of the tuberculin skin test is impaired in HIV-1-infected persons. Enzyme-linked immunospot-based detection of immune sensitisation may be less affected. Furthermore, the quantitative response can be related to the CD4 count, potentially improving specificity for active disease. The T-SPOT. TB assay was performed on HIV-1-infected participants, 85 with active tuberculosis (TB) and 81 healthy patients (non-TB). The ratio of the sum of the 6-kDa early secretory antigenic target and culture filtrate protein 10 response to the CD4 count (spot-forming cell (SFC)/CD4) was calculated. Using the manufacturer's guidelines, active TB was diagnosed with 76% sensitivity and 53% specificity. Using an SFC/CD4 ratio of 0.12, sensitivity (80%) and specificity (62%) improved. The quantitative T-cell response increased with increasing smear-positivity in the active TB group (p = 0.0008). In the non-TB group, the proportion of persons scored positive by T-SPOT. TB assay was lower in the group with a CD4 count of &lt;200 cells·mm −3 (p = 0.029). The ratio of the summed T-cell response to CD4 count improved the diagnostic accuracy of the T-SPOT. TB assay in HIV-1-infected persons, and a ratio of SFC/CD4 of &gt;0.12 should prompt investigation for active disease. A strong association between the degree of sputum positivity and T-SPOT. TB score was found. The sensitivity of the T-SPOT. TB assay in active disease may be less impaired by advanced immunosuppression.
Hibernating Myocardium
Authors: John M. Canty, Gen Suzuki, Michael D. Banas, Fons Verheyen, Marcel Borgers, James A. Fallavollita
Journal: Circulation Research (2004)

The inability to reproduce spontaneous ventricular fibrillation in an animal model of chronic coronary artery disease has limited advances in understanding mechanisms of sudden cardiac death (SCD). Swine with hibernating myocardium arising from a chronic left anterior descending coronary artery (LAD) occlusion have a high rate of SCD that parallels the poor clinical survival of medically treated patients with hibernating myocardium. Kaplan-Meier analysis (n=426) demonstrated a cumulative mortality of 49% after 5 months that was almost entirely attributable to spontaneous SCD. Using implantable loop recorders, ventricular fibrillation was documented as the arrhythmic mechanism of death in all animals (n=10) and was usually preceded by ventricular tachycardia (n=8). Physiological studies before SCD (n=7) demonstrated total LAD occlusion and collateral-dependent myocardium (n=5), excluding acute occlusion as a major trigger of arrhythmia. The physiological substrate of hibernating myocardium was present before SCD, with reductions in LAD perfusion (SCD 0.79+/-0.13 versus 0.80+/-0.08 mL/min per g) and wall thickening (SCD 28+/-3% versus 22+/-3%) that were similar to survivors (n=14). Triphenyltetrazolium chloride infarcts among animals with SCD were infrequent (4 of 32) and small, averaging 4.6% of LV mass. Histology (n=4) showed postmortem changes but no acute inflammation nor contraction band necrosis. These data support the notion that hibernating myocardium is a pathophysiological substrate at high risk of SCD. This is independent of changes in functional stenosis severity, acute myocardial necrosis, or fibrotic scar. Thus, regional adaptations that promote myocyte survival in the setting of chronic repetitive ischemia result in a substrate with enhanced vulnerability to lethal arrhythmias and SCD.
Mechanisms of Placebo and Placebo-Related Effects Across Diseases and Treatments
Authors: Fabrizio Benedetti
Journal: The Annual Review of Pharmacology and Toxicology (2007)

The placebo effect has evolved from being thought of as a nuisance in clinical and pharmacological research to a biological phenomenon worthy of scientific investigation in its own right. It is now clear that the term placebo effect is too restrictive and, in fact, many placebo-related effects have recently been investigated. A placebo effect differs from a placebo-like effect in that the former follows the administration of a placebo, whereas in the latter no placebo is administered. However, in both cases, the psychosocial context around the treatment plays a key role. In recent years, placebo and placebo-related effects have been analyzed with sophisticated biological tools that have uncovered specific mechanisms at both the biochemical and cellular level. This recent research has revealed that these psychosocial-induced biochemical changes in a patient's brain and body in turn may affect the course of a disease and the response to a therapy.
A preliminary randomized controlled study to determine the application frequency of a new lymphoedema bandaging system
Authors: C.J. Moffatt, P.J. Franks, D. Hardy, M. Lewis, V. Parker, J.L. Feldman
Journal: British Journal of Dermatology (2011)

Bandaging plays an important role in the treatment of lymphoedema.To investigate efficacy and safety of the 3M™ Coban™ 2 compression system (Coban 2 system) with different application frequencies in comparison to short-stretch bandaging.A multicentre, randomized, prospective study was performed with 82 patients suffering from arm or leg lymphoedema stage II or late stage II. Patients were allocated to traditional short-stretch bandaging five times per week or to the Coban 2 system applied two, three or five times per week for 19 days. Limb volume and adverse events were recorded at each study visit. The primary endpoint was percentage volume reduction.The highest lymphoedema volume reduction was achieved with the Coban 2 system applied two times per week. A mean reduction of 18·7% (SD 14·5) in legs and 10·5% (SD 8·3) in arms was achieved. More frequent bandage changes of three and five times per week did not demonstrate additional benefits. Short-stretch bandaging five times per week showed a mean volume reduction of 10·9% (SD 5·2) and 8·2% (SD 3·1) for legs and arms, respectively. Bandage slippage was low for all treatment groups. A relevant change in overall mobility was achieved during the use of the Coban 2 system. The adverse reactions were in agreement with already known side-effects and did not differ remarkably between the treatment groups.The 3M™ Coban™ 2 compression system applied twice weekly demonstrated a high rate of volume reduction and a good safety profile. Oedema reduction was still effective with 4 days between bandage change, which allows a constant therapeutic effect in routine practice. This should give the patient a high degree of independence and mobility.
Glycolytic Phenotype and AMP Kinase Modify the Pathologic Response of Tumor Xenografts to VEGF Neutralization
Authors: Giorgia Nardo, Elena Favaro, Matteo Curtarello, Lidia Moserle, Elisabetta Zulato, Luca Persano, Elisabetta Rossi, Giovanni Esposito, Marika Crescenzi, Oriol Casanovas, Ulrike Sattler, Wolfgang Mueller-Klieser, Barbara Biesalski, Oliver Thews, Rossella Canese, Egidio Iorio, Paola Zanovello, Alberto Amadori, Stefano Indraccolo
Journal: Cancer Research (2011)

Abstract VEGF antagonists are now widely used cancer therapeutics, but predictive biomarkers of response or toxicity remain unavailable. In this study, we analyzed the effects of anti-VEGF therapy on tumor metabolism and therapeutic response by using an integrated set of imaging techniques, including bioluminescence metabolic imaging, 18-fluorodeoxyglucose positron emission tomography, and MRI imaging and spectroscopy. Our results revealed that anti-VEGF therapy caused a dramatic depletion of glucose and an exhaustion of ATP levels in tumors, although glucose uptake was maintained. These metabolic changes selectively accompanied the presence of large necrotic areas and partial tumor regression in highly glycolytic tumors. In addition, we found that the central metabolic protein kinase AMP-activated protein kinase (AMPK)—a cellular sensor of ATP levels that supports cell viability in response to energy stress—was activated by anti-VEGF therapy in experimental tumors. AMPK-α2 attenuation increased glucose consumption, tumor cell sensitivity to glucose starvation, and tumor necrosis following anti-VEGF therapy. Taken together, our findings reveal functional links between the Warburg effect and the AMPK pathway with therapeutic responses to VEGF neutralization in tumor xenograft models. Cancer Res; 71(12); 4214–25. ©2011 AACR.
Peripheral T cell activation in long-term renal transplant patients
Authors: F Kern, S Ode-Hakim, H Nugel, K Vogt, H D Volk, P Reinke
Journal: Journal of the American Society of Nephrology (1996)

In renal transplant, patients, the number of T cells expressing high levels of LFA-1 (LFA-1-bright) and of T cells expressing CD57 increases in response to viral infection, even if the latter is asymptomatic. Their role in long-term renal transplant patients with cytomegalovirus (CMV) antigenemia and concomitant transplant dysfunction was investigated. For this purpose, this study used triple-color flow cytometry, fluorescence-activated cell sorting of peripheral blood T cells (CD3+/LFA-1-dim or -bright and CD8+/CD57+ or CD57- subsets), and subsequent semiquantitative reverse transcription-polymerase chain reaction. Cytokine mRNA levels for interleukin (IL)-1 beta, IL-2, IL-4, IL-8, IL-10, tumor necrosis factor alpha, and interferon-gamma, as well as Granzyme A and IL-2R p55 and p75 transcripts were determined and compared in peripheral blood mononuclear cells and in separated T cell subsets. Although in patients with CMV infection and/or rejection, cytokine transcripts were readily detected and the levels in the CD3+/LFA-1-bright subsets were, by orders of magnitudes, higher than in the LFA-1-dim subset, hardly any cytokine message was found in patients without CMV infection or rejection episodes or in control subjects. The expression of Granzyme A, which is involved in cytotoxic T lymphocyte-mediated cytotoxicity, was not upregulated in LFA-1-bright T cells, which is in discordance with cytokine levels. Differences between CD57+ and CD57- T cells were limited to the IL-2R p55 mRNA, of which the former expressed significantly less than the latter. It is concluded that upon virus-induced activation of peripheral blood T cells, an effector type that is marked by high inflammatory but small cytotoxic potential is produced. The results of this study propose that these cells represent a correlate of persistent immune activation and are liable to produce graft dysfunction, although they are unable to clear the organism from virus infection because of their lack of cytotoxic potential.