tbuckley/cabot-search huggingface dataset:
Altered renal calcium handling in hypercalcemia of malignancy.
Authors: K R Tuttle, R T Kunau, N Loveridge, G R Mundy
Journal: Journal of the American Society of Nephrology (1991)

It has been controversial whether increased renal tubular calcium reabsorption contributes to hypercalcemia in patients with malignancies. Moreover, whether this abnormality is associated with volume depletion, a parathyroid hormone-like effect, or other mechanisms has not been clarified. Eight consecutive patients with hypercalcemia due to a variety of tumor types were studied in detail. The glomerular filtration rate (iothalamate clearance) was reduced in all patients (0.98 +/- 0.10 (mean +/- SE) mL/s.1.73 m2; P less than 0.001) compared with normal controls (N = 9) (1.93 +/- 0.08 mL/s.1.73 m2), but it was similar to that in controls matched for renal insufficiency (N = 6) (1.15 +/- 0.05 mL/s.1.73 m2). During hypercalcemia produced by calcium infusion, urinary calcium excretion (millimoles of calcium per liter of glomerular filtrate) was increased in controls with renal insufficiency compared to those with normal renal function (P = 0.028). In all patients with hypercalcemia of malignancy, urinary calcium excretion was decreased compared with controls with renal insufficiency, but it was low in only five of eight patients compared with normal controls. Extracellular fluid volume (iothalamate volume of distribution) was not decreased in any patient, and urinary cAMP and/or plasma parathyroid hormone-like bioactivity were increased in six of eight patients. After treatment with an inhibitor of bone resorption, aminopropylidene 1,1 diphosphonate, abnormal renal calcium handling was not detected if the serum calcium normalized. It was concluded that increased renal tubular calcium reabsorption was consistently present in patients with hypercalcemia of malignancy compared with controls matched for renal insufficiency, but the proportion with the abnormality was underestimated if normal controls were used.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 2528: 3C23K: an anti-human Müllerian inhibiting substance type II receptor humanized monoclonal antibody for ovarian cancer targeted therapy
Authors: Alexandra Jacquet, Nathalie Kersual, Véronique Garambois, Alexandre Fontayne, Fanny Pujols, Nathalie Fournier, Martine Pugnière, Alain Chavanieu, Christophe de Romeuf, Jean-François Prost, Rémi Urbain, André Pèlegrin, Christine Gaucher, Isabelle Teulon-Navarro
Journal: Cancer Research (2012)

Abstract Asymptomatic in early stages, ovarian cancer is a “silent killer” representing the fifth leading cause of female deaths in western countries. Every year 56,967 women in Europe and USA die as a consequence of this disease. The incidence of ovarian cancer is forecast to undergo a 13 % increase in the next eight years in the seven major developed countries to reach about 72,000 annual cases in 2019. Due to the limitations of the current therapeutic approaches, there is a strong need for novel, more efficient, therapies. For this reason, we have produced a humanized monoclonal antibody 3C23K targeting the human Müllerian Inhibiting Substance type II Receptor (MISRII), expressed on most ovarian cancer subtypes, including epithelial ovarian cancer (EOC) representing more than 90% of ovarian cancers. This monoclonal antibody derives from the murine monoclonal antibody 12G4 and displays a particular glycosylation profile known to favor effector recruitment (EMABling®) as previously demonstrated in vitro. In vivo, we also showed that 3C23K exhibited a significant effect on tumor growth against several ovarian tumor xenografted models derived from patient primary EOC tumors. In this study, we first confirmed by peptide microarray that the epitope of 3C23K antibody was strictly identical to that of 12G4 antibody and a 3D-model of the full MISRII molecule was generated in order to better localize the 3C23K epitope. Furthermore, SPR studies demonstrated cross-reactivity of 3C23K with MISRII of rabbit, dog, pig, cow and primate. In vivo, antitumor activity of 3C23K against xenografted EOC tumor models was confirmed with various concentrations and treatment schedules. Moreover, interestingly, we constructed a mutant form of 3C23K harboring two mutations in the Fc region (G236R/L328R) in order to prevent binding to both murine and human FcαRs, and demonstrated that such a modification abolished antitumor activity. This data confirmed in vivo that recruitment of effectors is essential for 3C23K efficacy. Finally, in order to anticipate clinical treatment of ovarian cancers, 3C23K was tested in vivo in combination with carboplatin. Combination, when compared with treatment of each product alone, resulted in more than additive antitumor activity. Altogether these data showed that humanized monoclonal antibody 3C23K represents a promising candidate for ovarian cancer immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2528. doi:1538-7445.AM2012-2528
Multipotent Mesenchymal Stem Cells Acquire a Lymphendothelial Phenotype and Enhance Lymphatic Regeneration In Vivo
Authors: Claudius Conrad, Hanno Niess, Ralf Huss, Stephan Huber, Irene von Luettichau, Peter J. Nelson, Harald C. Ott, Karl-Walter Jauch, Christiane J. Bruns
Journal: Circulation (2009)

Background— The importance and therapeutic value of stem cells in lymphangiogenesis are poorly understood. We evaluated the potential of human and murine mesenchymal stem cells (MSCs) to acquire a lymphatic phenotype in vitro and to enhance lymphatic regeneration in vivo. Methods and Results— We assessed the lymphendothelial differentiation of human and murine MSCs after induction with supernatant derived from human dermal microvascular endothelial cells, isolated lymphatic endothelial cells, and purified vascular endothelial growth factor (VEGF)-C in vitro. We used human or murine progenitor MSC lines and then characterized the lymphatic phenotype by morphology, migratory capacity, and the expression of lymphatic markers such as Prox-1, podoplanin, Lyve-1, VEGF receptor-2, and VEGF receptor-3. Using a murine lymphatic edema model, we assessed the potential of these cells to form a functional lymphatic vasculature in vivo after injection of syngeneic MSCs. Incubation with supernatant from lymphatic endothelial cells induced an endothelium-like morphology and the expression of lymphendothelial markers in both human and murine MSCs in vitro. MSCs showed migratory activity along a VEGF-C gradient, which was enhanced by VEGF-C conditioning. In vivo, the local application of MSCs resulted in a significant decrease in edema formation (−20.1%; P &lt;0.01 versus untreated tails) after 3 weekly cell injections and restored the drainage of intradermally injected methylene blue after 7 weekly injections. Conclusions— MSCs were capable of expressing a lymphatic phenotype when exposed to lymph-inductive media and purified VEGF-C. Migratory activity toward VEGF-C in vitro suggests homing capability in vivo. Restoration of lymphatic drainage after injection of MSCs in a lymphedema model indicates that MSCs play a role in lymphatic regeneration. The potential clinical application of MSC in wound healing and reduction of lymphatic edema warrants further research.
Treg and lupus
Authors: M Bonelli, J S Smolen, C Scheinecker
Journal: Annals of the Rheumatic Diseases (2009)

Autoimmune diseases such as systemic lupus erythemathodes (SLE) display quantitative and/or qualitative deficiencies of CD4+CD25+ regulatory T cells (Treg). This might contribute to the immune dysregulation and break-down of peripheral tolerance mechanisms. In addition novel subsets of Treg might arise under specific autoimmune conditions as an effort to counteract autoimmunity. Advances in our understanding of how to characterise and manipulate Treg in patients with autoimmune diseases are required in order to develop new therapeutic strategies.
Vertebral Augmentation vs Nonsurgical Therapy
Authors: Douglas C. Bauer
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Adhesive stripping to remove epidermis in junctional epidermolysis bullosa for revertant cell therapy
Authors: A. Gostynski, F.C.L. Deviaene, A.M.G. Pasmooij, H.H. Pas, M.F. Jonkman
Journal: British Journal of Dermatology (2009)

Replacing mutant skin in epidermolysis bullosa (EB) by epithelial sheets of transduced autologous keratinocytes is the essential surgical step of ex vivo gene therapy. The same applies for revertant cell therapy in which epithelial sheets of revertant autologous keratinocytes are used. Revertant cells can be found in patches of normal skin in patients with junctional EB (JEB) due to revertant mosaicism caused by in vivo reversions.To develop a technique of adhesive tape stripping as a method for epidermis removal to prepare the acceptor site for revertant cell therapy in a patient with revertant mosaic JEB.We performed revertant cell therapy on a patient with mosaic type XVII collagen-deficient non-Herlitz JEB. Skin biopsies were taken from revertant skin on the wrist. Graft production took place on a 3T3-J2 feeder layer resulting in two 6 x 7 cm grafts. An innovative method that uses the pathological plane of least resistance of JEB skin was developed to prepare the acceptor site. A polyacrylate adhesive plaster was placed on the skin and then pulled off with the epidermis.The epidermis was easily removed with the plaster. The skin separated at the level of the lamina lucida, leaving a bloodless wound bed of naked lamina densa. Transplantation was successful; the acceptor site healed without scarring. However, blistering could be provoked. The functional repair was not achieved due to the low percentage of revertant cells in the graft.We conclude that adhesive stripping is a simple, effective and almost painless procedure for removing epidermis for ex vivo cell therapy in EB.
A Novel Aldehyde Dehydrogenase-3 Activator (Alda-89) Protects Submandibular Gland Function from Irradiation without Accelerating Tumor Growth
Authors: Nan Xiao, Hongbin Cao, Che-Hong Chen, Christina S. Kong, Rehan Ali, Cato Chan, Davud Sirjani, Edward Graves, Albert Koong, Amato Giaccia, Daria Mochly-Rosen, Quynh-Thu Le
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To determine the effect of Alda-89 (an ALDH3 activitor) on (i) the function of irradiated (radiotherapy) submandibular gland (SMG) in mice, (ii) its toxicity profile, and (iii) its effect on the growth of head and neck cancer (HNC) in vitro and in vivo. Experimental Design: Adult mice were infused with Alda-89 or vehicle before, during, and after radiotherapy. Saliva secretion was monitored weekly. Hematology, metabolic profile, and postmortem evaluation for toxicity were examined at the time of sacrifice. Alda-89 or vehicle was applied to HNC cell lines in vitro, and severe combined immunodeficient (SCID) mice transplanted with HNC in vivo with or without radiation; HNC growth was monitored. The ALDH3A1 and ALDH3A2 protein expression was evaluated in 89 patients with HNC and correlated to freedom from relapse (FFR) and overall survival (OS). Results: Alda-89 infusion significantly resulted in more whole saliva production and a higher percentage of preserved acini after radiotherapy compared with vehicle control. There was no difference in the complete blood count, metabolic profile, and major organ morphology between the Alda-89 and vehicle groups. Compared with vehicle control, Alda-89 treatment neither accelerated HNC cell proliferation in vitro, nor did it affect tumor growth in vivo with or without radiotherapy. Higher expression of ALDH3A1 or ALDH3A2 was not significantly associated with worse FFR or OS in either human papillomavirus (HPV)-positive or HPV-negative group. Conclusion: Alda-89 preserves salivary function after radiotherapy without affecting HNC growth or causing measurable toxicity in mice. It is a promising candidate to mitigate radiotherapy-related xerostomia. Clin Cancer Res; 19(16); 4455–64. ©2013 AACR.
T cell receptor beta gene has two downstream DNase I hypersensitive regions. Possible mechanisms of tissue- and stage-specific gene regulation.
Authors: Y Hashimoto
Journal: The Journal of Experimental Medicine (1989)

Two DNase I-hypersensitive regions were identified downstream of the TCR gene constant region. One of these regions is located at the site of a putative enhancer element and was observed only in T cell lines and not in cell lines derived from other tissues. The other DNase-hypersensitive region was also detected only in T cell lines but only in those expressing TCR-beta RNA. Thus, the first region is probably tissue specific, while the second region is probably tissue and stage specific. The DNA sequence of the second DNase I-hypersensitive region revealed several stretches of nucleotides that are characteristic of consensus sequences for regulatory elements. These results, together with the observations in transgenic mice that indicate a requirement for two distinct regions for optimal TCR gene expression, suggest the presence of at least two regulatory regions downstream of the C-beta-2 region; one is an enhancer region and the other is a transcriptionally related regulatory region. The tissue/stage specificity of these DNase I-hypersensitive regions supports the notion that changes in chromatin structure control tissue-specific gene expression.
Sister Group Relationship of Turtles to the Bird-Crocodilian Clade Revealed by Nuclear DNA–Coded Proteins
Authors: Naoyuki Iwabe, Yuichiro Hara, Yoshinori Kumazawa, Kaori Shibamoto, Yumi Saito, Takashi Miyata, Kazutaka Katoh
Journal: Molecular Biology and Evolution (2004)

The phylogenetic position of turtles is a currently controversial issue. Recent molecular studies rejected a traditional view that turtles are basal living reptiles (Hedges, S. B., and L. L. Poling. 1999. A molecular phylogeny. Science83:998–1001; Kumazawa, Y., and M. Nishida. 1999. Complete mitochondrial DNA sequences of the green turtle and blue-tailed mole skink, statistical evidence for archosaurian affinity of turtles. Mol. Biol. Evol.16:784–792). Instead, these studies grouped turtles with birds and crocodiles. The relationship among turtles, birds, and crocodiles remained unclear to date. To resolve this issue, we have cloned and sequenced two nuclear genes encoding the catalytic subunit of DNA polymerase α and glycinamide ribonucleotide synthetase–aminoimidazole ribonucleotide synthetase–glycinamide ribonucleotide formyltransferase from amniotes and an amphibian. The amino acid sequences of these proteins were subjected to a phylogenetic analysis based on the maximum likelihood method. The resulting tree showed that turtles are the sister group to a monophyletic cluster of archosaurs (birds and crocodiles). All other possible tree topologies were significantly rejected.
Dipstick Proteinuria as a Screening Strategy to Identify Rapid Renal Decline
Authors: William F. Clark, Jennifer J. Macnab, Jessica M. Sontrop, Arsh K. Jain, Louise Moist, Marina Salvadori, Rita Suri, Amit X. Garg
Journal: Journal of the American Society of Nephrology (2011)

Rapid kidney function decline (RKFD) predicts cardiovascular morbidity and mortality, but serial assessment of estimated GFR (eGFR) is not cost-effective for the general population. Here, we evaluated the predictive value of albuminuria and three thresholds of dipstick proteinuria to identify RKFD in 2,574 participants in a community-based prospective cohort study with a median of 7 years follow-up. Median change in eGFR was -0.78 ml/min per 1.73 m(2) per year; with 8.5% experiencing RKFD, defined as a >5% annual eGFR decline from baseline. Of those with RKFD, 65% advanced to a new CKD stage compared with 19% of those without RKFD. Dipstick protein ≥ 1 g/L was a stronger predictor of RKFD than albuminuria. Overall, 2.5% screened positive for dipstick protein ≥ 1 g/L at baseline; one of every 2.6 patients would have RKFD if all were followed with serial eGFR measurement. Overall, the screening strategy correctly identified progression status for 90.8% of patients, mislabeled 1.5% as RKFD, and missed 7.7% with eventual RKFD. Among those with risk factors (cardiovascular disease, age >60, diabetes, or hypertension), the probability of identifying RKFD from serial eGFR measurements increased from 13 to 44% after incorporating dipstick protein (≥ 1 g/L threshold). In summary, inexpensive screening with urine dipstick should allow primary care physicians to follow fewer patients with serial eGFR assessment but still identify those with rapid decline of kidney function.
Notch Suppresses Angiogenesis and Progression of Hepatic Metastases
Authors: Debarshi Banerjee, Sonia L. Hernandez, Alejandro Garcia, Thaned Kangsamaksin, Emily Sbiroli, John Andrews, Lynn Ann Forrester, Na Wei, Angela Kadenhe-Chiweshe, Carrie J. Shawber, Jan K. Kitajewski, Jessica J. Kandel, Darrell J. Yamashiro
Journal: Cancer Research (2015)

Abstract The Notch pathway plays multiple key roles in tumorigenesis, and its signaling components have therefore aroused great interest as targets for emerging therapies. Here, we show that inhibition of Notch, using a soluble receptor Notch1 decoy, unexpectedly caused a remarkable increase in liver metastases from neuroblastoma and breast cancer cells. Increased liver metastases were also seen after treatment with the γ-secretase inhibitor PF-03084014. Transgenic mice with heterozygous loss of Notch1 demonstrated a marked increase in hepatic metastases, indicating that Notch1 signaling acts as metastatic suppressor in the liver microenvironment. Inhibition of DLL1/4 with ligand-specific Notch1 decoys increased sprouting of sinusoidal endothelial cells into micrometastases, thereby supporting early metastatic angiogenic growth. Inhibition of tumor-derived JAG1 signaling activated hepatic stellate cells, increasing their recruitment to vasculature of micrometastases, thereby supporting progression to macrometastases. These results demonstrate that inhibition of Notch causes pathologic activation of liver stromal cells, promoting angiogenesis and growth of hepatic metastases. Our findings have potentially serious implications for Notch inhibition therapy. Cancer Res; 75(8); 1592–602. ©2015 AACR.
Three-dimensional, task-specific robot therapy of the arm after stroke: a multicentre, parallel-group randomised trial
Authors: Verena Klamroth-Marganska, Javier Blanco, Katrin Campen, Armin Curt, Volker Dietz, Thierry Ettlin, Morena Felder, Bernd Fellinghauer, Marco Guidali, Anja Kollmar, Andreas Luft, Tobias Nef, Corina Schuster-Amft, Werner Stahel, Robert Riener
Journal: The Lancet Neurology (2014)
Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo
Authors: Henry W. Lim, Pearl E. Grimes, Oma Agbai, Iltefat Hamzavi, Marsha Henderson, Madelaine Haddican, Rita V. Linkner, Mark Lebwohl
Journal: JAMA Dermatology (2014)

<h3>Importance</h3> Narrowband UV-B (NB–UV-B) phototherapy is used extensively to treat vitiligo. Afamelanotide, an analogue of α–melanocyte-stimulating hormone, is known to induce tanning of the skin. <h3>Objective</h3> To evaluate the efficacy and safety of combination therapy for generalized vitiligo consisting of afamelanotide implant and NB–UV-B phototherapy. <h3>Design, Setting, and Participants</h3> This study was performed in 2 academic outpatient dermatology centers and 1 private dermatology practice. We enrolled men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% of total body surface area. Vitiligo was stable or slowly progressive for 3 months. Patients were randomized to combination therapy (n = 28) vs NB–UV-B monotherapy (n = 27). After 1 month of NB–UV-B phototherapy, 16 mg of afamelanotide was administered subcutaneously to the combination therapy group monthly for 4 months while NB–UV-B phototherapy continued; the other group continued to receive NB–UV-B monotherapy. <h3>Interventions</h3> Narrowband UV-B monotherapy vs combined NB–UV-B phototherapy and afamelanotide. <h3>Main Outcomes and Measures</h3> Response on the Vitiligo Area Scoring Index and Vitiligo European Task Force scoring system. <h3>Results</h3> Response in the combination therapy group was superior to that in the NB–UV-B monotherapy group (<i>P</i> &lt; .05) at day 56. For the face and upper extremities, a significantly higher percentage of patients in the combination therapy group achieved repigmentation, and at earlier times (face, 41.0 vs 61.0 days [<i>P</i> = .001]; upper extremities, 46.0 vs 69.0 days [<i>P</i> = .003]). In the combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB–UV-B monotherapy group. Notable adverse events included erythema in both groups and minor infections and nausea in the combination therapy group. Comparison between Fitzpatrick SPTs showed patients with SPTs IV to VI in the combination therapy group had improvement in the Vitiligo Area Scoring Index at days 56 and 84 (<i>P</i> &lt; .05); no significant difference was noted in patients with SPT III. <h3>Conclusions and Relevance</h3> A combination of afamelanotide implant and NB–UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB–UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01430195
Prospective Temporal Analysis of the Onset of Preinfarction Angina Versus Outcome
Authors: Robert A. Kloner, Thomas Shook, Elliott M. Antman, Christopher P. Cannon, Karin Przyklenk, Kissok Yoo, Carolyn H. McCabe, Eugene Braunwald
Journal: Circulation (1998)

The timing of onset of angina before myocardial infarction in relation to outcome is unknown.We prospectively determined the importance of the time of onset of preinfarction angina in relation to 30-day outcomes in the TIMI-9B study from standardized forms. Of the 3002 patients entered into the study, 425 reported angina before their myocardial infarction. Patients with angina onset within 24 hours of infarction had a lower 30-day cardiac event rate (mortality, recurrent myocardial infarction, heart failure, or shock) at 4% than those with onset of angina >24 hours (17%; P=.030). A history of any angina alone was not associated with reduced event rate. Peak creatine kinase levels tended to be lower in the group with angina within 24 hours. These benefits were not due to higher rates of use of antianginal medicines or aspirin and were not a consequence of differences in baseline characteristics or disease states (hypertension, hypercholesterolemia) among subgroups.These temporal observations are consistent with the concept of preconditioning by preinfarction angina but do not rule out other mechanisms.