tbuckley/cabot-search huggingface dataset:
Immune Profile of Pediatric Renal Transplant Recipients following Alemtuzumab Induction
Authors: Sacha A. De Serres, Bechara G. Mfarrej, Ciara N. Magee, Fanny Benitez, Isa Ashoor, Mohamed H. Sayegh, William E. Harmon, Nader Najafian
Journal: Journal of the American Society of Nephrology (2011)

The incidence of developing circulating anti-human leukocyte antigen antibodies and the kinetics of T cell depletion and recovery among pediatric renal transplant recipients who receive alemtuzumab induction therapy are unknown. In a collaborative endeavor to minimize maintenance immunosuppression in pediatric renal transplant recipients, we enrolled 35 participants from four centers and treated them with alemtuzumab induction therapy and a steroid-free, calcineurin-inhibitor-withdrawal maintenance regimen. At 3 months after transplant, there was greater depletion of CD4(+) than CD8(+) T cells within the total, naive, memory, and effector memory subsets, although depletion of the central memory subset was similar for CD4(+) and CD8(+) cells. Although CD8(+) T cells recovered faster than CD4(+) subsets overall, they failed to return to pretransplant levels by 24 months after transplant. There was no evidence for greater recovery of either CD4(+) or CD8(+) memory cells than naïve cells. Alemtuzumab relatively spared CD4(+)CD25(+)FoxP3(+) regulatory T cells, resulting in a rise in their numbers relative to total CD4(+) cells and a ratio that remained at least at pretransplant levels throughout the study period. Seven participants (20%) developed anti-human leukocyte antigen antibodies without adversely affecting allograft function or histology on 2-year biopsies. Long-term follow-up is underway to assess the potential benefits of this regimen in children.
PHOTODERMATITIS DUE TO TETRACHLORSALICYLANILIDE.
Authors: D. S. WILKINSON
Journal: British Journal of Dermatology (1961)

Journal Article PHOTODERMATITIS DUE TO TETRACHLORSALICYLANILIDE. Get access D. S. WILKINSON, M.D., M.R.C.P. D. S. WILKINSON, M.D., M.R.C.P. Aylesbury and High Wycombe Hospitals Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 6, 1 June 1961, Pages 213–219, https://doi.org/10.1111/j.1365-2133.1961.tb14435.x Published: 01 June 1961
Fertility in female cancer survivors: pathophysiology, preservation and the role of ovarian reserve testing
Authors: Kerryn Lutchman Singh, Melanie Davies, Ratna Chatterjee
Journal: Human Reproduction Update (2004)

The improved long-term survival of adolescents and young women treated for cancer has resulted in an increased focus on the effects of chemotherapy on ovarian function and its preservation. These women may seek advice and treatment regarding their reproductive status, including ways of preserving their fertility and preventing a premature menopause--factors that can have a profound impact on their quality of life. This article comprehensively reviews ovarian reserve testing (ORT) in general. Special emphasis is placed on patients with cancer, including the pathophysiology of gonadal damage following chemotherapy, fertility preservation and the potential role of ORT. Baseline parameters of ovarian reserve [FSH LH, estradiol, inhibin B and anti-Mullerian hormone (AMH)] have not yet performed sufficiently well in predicting poor outcome in assisted reproduction, but biochemical markers of ovarian reserve appear to be better than chronological age. Inhibin B and AMH show potential for future use. Dynamic testing appears to show much promise, especially stimulated levels of inhibin B and estradiol. The most promising tests of ovarian reserve are the biophysical markers, where total antral follicle count was found to be most discriminatory followed by ovarian volume. Combination of biochemical, biophysical and clinical markers of ovarian reserve may also improve predictive capacity. However, there is a lack of data pertinent to ORT in cancer. As yet there is no single clinically useful test to predict ovarian reserve accurately. Patients with cancer represent a distinct cohort who have particular concerns about their future fertility and the possibility of a premature menopause, they can benefit greatly from knowledge of their functional ovarian reserve. Large, prospective, randomized, adequately controlled studies specific to different geographical areas are required in a control population of comparable reproductive age to determine the potential role of ORT in clinical practice.
Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype
Authors: Sandro Rossetti, Dominique Chauveau, Vickie Kubly, Jeffrey M Slezak, Anand K Saggar-Malik, York Pei, Albert CM Ong, Fiona Stewart, Michael L Watson, Erik J Bergstralh, Christopher G Winearls, Vicente E Torres, Peter C Harris
Journal: The Lancet (2003)
The effect of in vivo IL-7 deprivation on T cell maturation.
Authors: S K Bhatia, L T Tygrett, K H Grabstein, T J Waldschmidt
Journal: The Journal of Experimental Medicine (1995)

A number of previous studies have suggested a key role for interleukin 7 (IL-7) in the maturation of T lymphocytes. To better assess the function of IL-7 in lymphopoiesis, we have deprived mice of IL-7 in vivo by long-term administration of a neutralizing anti-IL-7 antibody. In a previous report (Grabstein, K. H., T. J. Waldschmidt, F. D. Finkelman, B. W. Hess, A. R. Alpert, N. E. Boiani, A. E. Namen, and P. J. Morrissey. 1993. J. Exp. Med. 178:257-264), we used this system to demonstrate the critical role of IL-7 in B cell maturation. After a brief period of anti-IL-7 treatment, most of the pro-B cells and all of the pre-B and immature B cells were depleted from the bone marrow. In the present report, we have injected anti-IL-7 antibody for periods of up to 12 wk to determine the effect of in vivo IL-7 deprivation on the thymus. The results demonstrate a &amp;gt; 99% reduction in thymic cellularity after extended periods of antibody administration. Examination of thymic CD4- and CD8- defined subsets revealed that, on a proportional basis, the CD4+, CD8+ subset was most depleted, the CD4 and CD8 single positive cells remained essentially unchanged, and the CD4-, CD8- compartment actually increased to approximately 50% of the thymus. Further examination of the double negative thymocytes demonstrated that IL-7 deprivation did, indeed, deplete the CD3-, CD4-, CD8- precursors, with expansion of this subset being interupted at the CD44+, CD25+ stage. The proportional increase in the CD4-, CD8- compartment was found to be due to an accumulation of CD3+, T cell receptor alpha, beta + double negative T cells. Additional analysis revealed that anti-IL-7 treatment suppressed the audition/selection process of T cells, as shown by a significant reduction of single positive cells expressing CD69 and heat stable antigen. Finally, the effects of IL-7 deprivation on the thymus were found to be reversible, with a normal pattern of thymic subsets returning 4 wk after cessation of treatment. The present results thus indicate a central role for IL-7 in the maturation of thymic-derived T cells.
Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics.
Authors: M R Klein, C A van Baalen, A M Holwerda, S R Kerkhof Garde, R J Bende, I P Keet, J K Eeftinck-Schattenkerk, A D Osterhaus, H Schuitemaker, F Miedema
Journal: The Journal of Experimental Medicine (1995)

To gain more insight into the role of HIV-1-specific cytotoxic T lymphocytes (CTL) in the pathogenesis of AIDS, we investigated temporal relations between HIV-1 Gag-specific precursor CTL (CTLp), HIV-1 viral load, CD4+ T cell counts, and T cell function. Six HIV-1-infected subjects, who were asymptomatic for more than 8 yr with CD4+ counts &amp;gt; 500 cells/mm3, were compared with six subjects who progressed to AIDS within 5 yr after HIV-1 seroconversion. In the long-term asymptomatics, persistent HIV-1 Gag-specific CTL responses and very low numbers of HIV-1-infected CD4+ T cells coincided with normal and stable CD4+ counts and preserved CD3 mAb-induced T cell reactivity for more than 8 yr. In five out of six rapid progressors Gag-specific CTLp were also detected. However, early in infection the number of circulating HIV-1-infected CD4+ T cells increased despite strong and mounting Gag-specific CTL responses. During subsequent clinical progression to AIDS, loss of Gag-specific CTLp coincided with precipitating CD4+ counts and severe deterioration of T cell function. The possible relationships of HIV-1 Gag-specific CTLp to disease progression are discussed.
Analysis of the Role of Variation of Major Histocompatibility Complex Class II Expression on Nonobese Diabetic (NOD) Peripheral T Cell Response
Authors: William M. Ridgway, Hiroaki Ito, Marcella Fassò, Chen Yu, C. Garrison Fathman
Journal: The Journal of Experimental Medicine (1998)

The current paradigm of major histocompatibility complex (MHC) and disease association suggests that efficient binding of autoantigens by disease-associated MHC molecules leads to a T cell–mediated immune response and resultant autoimmune sequelae. The data presented below offer a different model for this association of MHC with autoimmune diabetes. We used several mouse lines expressing different levels of I-Ag7 and I-Ak on the nonobese diabetic (NOD) background to evaluate the role of MHC class II in the previously described NOD T cell autoproliferation. The ratio of I-Ag7 to I-Ak expression correlated with the peripheral T cell autoproliferative phenotype in the mice studied. T cells from the NOD, [NOD × NOD.I-Anull]F1, and NOD I-Ak transgenic mice demonstrated autoproliferative responses (after priming with self-peptides), whereas the NOD.H2h4 (containing I-Ak) congenic and [NOD × NOD.H2h4 congenic]F1 mice did not. Analysis of CD4+ NOD I-Ak transgenic primed lymph node cells showed that autoreactive CD4+ T cells in the NOD I-Ak transgenic mice were restricted exclusively by I-Ag7. Considered in the context of the avidity theory of T cell activation and selection, the reported poor peptide binding capacity of NOD I-Ag7 suggested a new hypothesis to explain the effects of MHC class II expression on the peripheral autoimmune repertoire in NOD mice. This new explanation suggests that the association of MHC with diabetes results from “altered” thymic selection in which high affinity self-reactive (potentially autoreactive) T cells escape negative selection. This model offers an explanation for the requirement of homozygous MHC class II expression in NOD mice (and in humans) in susceptibility to insulin-dependent diabetes mellitus.
Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase in the Human Kidney
Authors: DANIEL ZEHNDER, ROSEMARY BLAND, ELIZABETH A. WALKER, ARTHUR R. BRADWELL, ALEXANDER J. HOWIE, MARTIN HEWISON, PAUL M. STEWART
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The secosteroid hormone 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) plays a vital role in calcium metabolism, tissue differentiation, and normal bone growth. Biosynthesis of 1,25(OH) 2 D 3 is catalyzed by the mitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D 3 1α-hydroxylase (1α-hydroxylase). Although activity of this enzyme has been described in several tissues, the kidneys are recognized to be the principal site of 1,25(OH) 2 D 3 production. To date, enzyme activity studies using vitamin D-deficient animals have suggested that 1α-hydroxylase is expressed exclusively in proximal convoluted tubules. With the recent cloning of 1α-hydroxylase, specific cRNA probes and in-house polyclonal antiserum have been used to determine the distribution of 1α-hydroxylase along the human nephron. Immunohistochemistry and in situ hybridization studies indicated strong expression of 1α-hydroxylase protein and mRNA in the distal convoluted tubule, the cortical and medullary part of the collecting ducts, and the papillary epithelia. Lower expression was observed along the thick ascending limb of the loop of Henle and Bowman's capsule. Weaker and more variable expression of 1α-hydroxylase protein and mRNA was seen in proximal convoluted tubules, and no expression was observed in glomeruli or vascular structures. These data show for the first time the distribution of 1α-hydroxylase expression in normal human kidney. In contrast to earlier enzyme activity studies conducted in vitamin D-deficient animals, our data indicate that the distal nephron is the predominant site of 1α-hydroxylase expression under conditions of vitamin D sufficiency.
Preclinical Activity of Nanoliposomal Irinotecan Is Governed by Tumor Deposition and Intratumor Prodrug Conversion
Authors: Ashish V. Kalra, Jaeyeon Kim, Stephan G. Klinz, Nancy Paz, Jason Cain, Daryl C. Drummond, Ulrik B. Nielsen, Jonathan B. Fitzgerald
Journal: Cancer Research (2014)

A major challenge in the clinical use of cytotoxic chemotherapeutics is maximizing efficacy in tumors while sparing normal tissue. Irinotecan is used for colorectal cancer treatment but the extent of its use is limited by toxic side effects. Liposomal delivery systems offer tools to modify pharmacokinetic and safety profiles of cytotoxic drugs. In this study, we defined parameters that maximize the antitumor activity of a nanoliposomal formulation of irinotecan (nal-IRI). In a mouse xenograft model of human colon carcinoma, nal-IRI dosing could achieve higher intratumoral levels of the prodrug irinotecan and its active metabolite SN-38 compared with free irinotecan. For example, nal-IRI administered at doses 5-fold lower than free irinotecan achieved similar intratumoral exposure of SN-38 but with superior antitumor activity. Tumor response and pharmacokinetic modeling identified the duration for which concentrations of SN-38 persisted above a critical intratumoral threshold of 120 nmol/L as determinant for antitumor activity. We identified tumor permeability and carboxylesterase activity needed for prodrug activation as critical factors in achieving longer duration of SN-38 in tumors. Simulations varying tumor permeability and carboxylesterase activity predicted a concave increase in tumor SN-38 duration, which was confirmed experimentally in 13 tumor xenograft models. Tumors in which higher SN-38 duration was achieved displayed more robust growth inhibition compared with tumors with lower SN-38 duration, confirming the importance of this factor in drug response. Overall, our work shows how liposomal encapsulation of irinotecan can safely improve its antitumor activity in preclinical models by enhancing accumulation of its active metabolite within the tumor microenvironment.
Glomerular Activation of the Lectin Pathway of Complement in IgA Nephropathy Is Associated with More Severe Renal Disease
Authors: Anja Roos, Maria Pia Rastaldi, Novella Calvaresi, Beatrijs D. Oortwijn, Nicole Schlagwein, Danielle J. van Gijlswijk-Janssen, Gregory L. Stahl, Misao Matsushita, Teizo Fujita, Cees van Kooten, Mohamed R. Daha
Journal: Journal of the American Society of Nephrology (2006)

IgA nephropathy (IgAN) is characterized by glomerular co-deposition of IgA and complement components. Earlier studies showed that IgA activates the alternative pathway of complement, whereas more recent data also indicate activation of the lectin pathway. The lectin pathway can be activated by binding of mannose-binding lectin (MBL) and ficolins to carbohydrate ligands, followed by activation of MBL-associated serine proteases and C4. This study examined the potential role of the lectin pathway in IgAN. Renal biopsies of patients with IgAN (n=60) showed mesangial deposition of IgA1 but not IgA2. Glomerular deposition of MBL was observed in 15 (25%) of 60 cases with IgAN and showed a mesangial pattern. All MBL-positive case, but none of the MBL-negative cases showed glomerular co-deposition of L-ficolin, MBL-associated serine proteases, and C4d. Glomerular deposition of MBL and L-ficolin was associated with more pronounced histologic damage, as evidenced by increased mesangial proliferation, extracapillary proliferation, glomerular sclerosis, and interstitial infiltration, as well as with significantly more proteinuria. Patients who had IgAN with or without glomerular MBL deposition did not show significant differences in serum levels of MBL, L-ficolin, or IgA or in the size distribution of circulating IgA. Furthermore, in vitro experiments showed clear binding of MBL to polymeric but not monomeric patient IgA, without a significant difference between both groups. Together, these findings strongly point to a role for the lectin pathway of complement in glomerular complement activation in IgAN and suggest a contribution for both MBL and L-ficolin in the progression of the disease.
Fractional carbon dioxide laser resurfacing of rhytides and photoageing: a prospective study using profilometric analysis
Authors: E. Kohl, J. Meierhöfer, M. Koller, F. Zeman, A. Klein, U. Hohenleutner, M. Landthaler, S. Hohenleutner
Journal: British Journal of Dermatology (2013)

Results of profilometric skin analyses after fractional ablative skin resurfacing are not only important for evaluating the efficacy of this therapy but are also relevant for physicians practising laser and aesthetic skin therapy. Currently, objective measurements of wrinkle reduction after fractional CO2 laser resurfacing are scarce, and it remains unclear whether the various facial areas respond differently to this therapy.To measure wrinkle parameters, the homogeneity of melanin distribution and skin roughness in four facial areas (periorbital, perioral, forehead, cheeks) before and after three fractional CO2 laser treatments.Twenty-five women were analysed with regard to wrinkle parameters and mottled pigmentation on the face. We measured wrinkle size, depth and width and the homogeneity of melanin distribution and skin roughness in four facial areas before and after three fractional CO2 laser treatments. Additionally, the investigators rated clinical improvement using five-point grading scales.Wrinkles were significantly reduced in all facial areas, and the best results for wrinkle size and depth were found for the cheeks (-58·3%, P = 0·018 and -51·3%, P = 0·018) and the periorbital area (-35·1%, P < 0·001 and -31·1%, P = 0·001, respectively). The percentage improvements of rhytides evaluated by the investigators were mostly similar to those found from in vivo measurements. The homogeneity of melanin distribution in the skin was improved by 21·4% on the cheeks (P = 0·012) and by 24·0% in the periorbital area (P < 0·001). Clinical investigators rated the improvement of mottled pigmentation considerably higher (51-75%).After a serial treatment with the fractional CO2 laser, we measured considerably varying wrinkle reduction depending on the area of the face, and the best results were found for the cheeks.
Amiodarone versus Sotalol for Atrial Fibrillation
Authors: Bramah N. Singh, Steven N. Singh, Domenic J. Reda, X. Charlene Tang, Becky Lopez, Crystal L. Harris, Ross D. Fletcher, Satish C. Sharma, J. Edwin Atwood, Alan K. Jacobson, H. Daniel Lewis, Dennis W. Raisch, Michael D. Ezekowitz
Journal: New England Journal of Medicine (2005)

The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial.In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring.Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups.Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.
Target Cell of the Polycythemia-Inducing Friend Virus: Studies With Myleran&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: T Fredrickson, P Tambourin, F Wendling, C Jasmin, F Smajda
Journal: JNCI Journal of the National Cancer Institute (1975)

A single injection of Myleran reduced the pluripotent hematopoietic stem cell, i.e., colony forming unit(s) (CFU), and the erythropoietin-responsive cell (ERC) in polycythemic mice to around 0.5% that of the controls. Repeated injections of erythropoietin (EP) restored ERC populations, whereas the CFU remained at very low levels. This selective action of Myleran and EP in polycythemic mice seemed to be a good approach for the study of oncogenic action of Friend virus on target cells. When the CFU and ERC compartments were decreased, practically no response to the virus was obtained. When there was an appreciable ERC population present with decreased CFU, leukemogenesis still occurred (as judged by the increased spleen weight). This result was in proportion to the dose of EP, i.e., stimulation of the ERC or closely related cells.
FOLLOW-UP REPORT ON A SERIES OF POSTTRAUMATIC EPILEPTICS
Authors: A. EARL WALKER, FRED A. QUADFASEL
Journal: American Journal of Psychiatry (1948)

In spite of the irregular anticonvulsant therapy 55.5% of the patients originally discharged as controlled for at least 4 months have been free from seizures for from 12 to 18 months (Table 1). Approximately 20% have had only one attack. This response to anticonvulsant medication is quite encouraging, indicating that about three-fourths of the patients considered controlled medically maintained their healthy state.[SEE TABLE 1 IN SOURCE PDF] In the group of medical failures some 40 cases were subjected to surgical removal of an epileptogenic focus. The remaining 26 cases serve as a control group for the surgical treatment. Approximately one year after operation one-third of the cases treated by cortical excision have had no further attacks and another fifth have had only one attack or the aura of their attacks. In the control group only 3 patients of 20 have had one or no attacks, and there is doubt of the reliability of the report on one of the cases. The ultimate value of the surgical treatment of posttraumatic epilepsy can only be determined after a 5-or 10-year follow-up. There seems some reason to believe, however, that cortical excisions may offer help to a certain group of patients not benefited by medical management. With greater experience [see Table 2 in the Source PDF] and more precise knowledge of cortical physiology in focal epileptic states, surgical therapy may be of even greater value. However, the posttraumatic epileptic has more social than medical difficulties. Economic and social rehabilitation is a primary need of these patients. Only when the posttraumatic epileptic is a useful member of society can the problem of posttraumatic epilepsy be considered solved.