Article1 May 1960A STUDY OF THE ASSOCIATION OF GROUP A STREPTOCOCCI WITH ACUTE GLOMERULONEPHRITISSTANLEY H. BERNSTEIN, M.D., F.A.C.P., MAXWELL STILLERMAN, M.D.STANLEY H. BERNSTEIN, M.D., F.A.C.P.Search for more papers by this author, MAXWELL STILLERMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-52-5-1026 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe association of group A streptococcal infections with acute glomerulonephritis in man has been demonstrated by a variety of clinical, bacteriologic, serologic and immunologic data.1-5 The incidence of antecedent streptococcal infection has been reported to be between 70% and 94%, depending upon the methods utilized to demonstrate the relationship.6-8 Our knowledge of the specificity of streptococcal strains capable of nephrotoxic action has been acquired, in the main, from the extensive studies of Rammelkamp and his co-workers,4 ,9, 10 and has subsequently been confirmed by other investigators.11, 12Some viral, rickettsial and other bacterial infections have been reported to be followed...Bibliography1. 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Christensen LR: Methods of measuring the activity of components of the streptococcal fibrinolytic system and streptococcal desoxyribonuclease, J. Clin. Investigation 28: 163-172, 1949. CrossrefMedlineGoogle Scholar27. HarrisHarris STN: The measurement of neutralizing antibodies to streptococcal hyaluronidase by turbidometric method, J. Immunol. 63: 233-247, 1949. MedlineGoogle Scholar28. HardinQuinnAvery RARWRC: A survey of hemolytic streptococci from patients with rheumatic fever, glomerulonephritis, pharyngitis and carrier state, J. Infect. Dis. 99: 84-89, 1956. CrossrefMedlineGoogle Scholar29. Updyke EL: Personal communication. Google Scholar30. CullhedWernerLaurell IJG: Type-specific antibodies in acute glomerulonephritis, Acta med. scandinav. 165: 17-24, 1959. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication October 13, 1959.From the Streptococcal Disease Unit of the Pediatric Research Laboratory, The Long Island Jewish Hospital, New Hyde Park, N. Y.†Aided in part by grants from the U. S. Public Health Service (H2613), the New York Heart Association and Eli Lilly and Company.Requests for reprints should be addressed to Stanley H. Bernstein, M.D., Streptococcal Research Unit, The Long Island Jewish Hospital, 270-05 Seventy-sixth Avenue, New Hyde Park, Long Island, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byClinical Patterns of Acute Poststreptococcal Glomerulonephritis: A Single Center's ExperienceAge at Onset, Sex Distribution and HLA Antigen Frequency in Patients with Primary Glomerulonephritis Progressing to Terminal UraemiaPoststreptococcal GlomerulonephritisRecurrent glomerulonephritisUse of radioimmunoassay for the detection of circulating antistreptococcal antibody in patients with glomerulonephritisStreptococcal immune responses in nephritis after skin infectionSecond attacks of acute glomerulonephritisDoppelseitige hämatogene NierenerkrankungenBegutachtung der NierenerkrankungenThe Pathogenesis of Poststreptococcal Carditis and GlomerulonephritisInfection as a cause and complication of renal diseaseAcute Glomerulonephritis 1 May 1960Volume 52, Issue 5Page: 1026-1034KeywordsGlomerulonephritisHeart diseasesHypertensionMedical servicesNephritisProteinuriaResearch laboratoriesRocky Mountain spotted feverSpecificityStreptococcal infections ePublished: 1 December 2008 Issue Published: 1 May 1960 PDF downloadLoading ...
Conditioning regimens used in reduced intensity transplants are designed to optimize immune suppression to allowing for prompt engraftment and robust graft versus tumor effect. The Tufts regimen (Miller KB, et al. Bone Marrow Transplant 2004;34:881) has a reduced incidence of GVHD while demonstrating disease response using extracorporeal photopheresis (ECP), pentostatin 4 mg/m2/day × 2 and a reduced dose of total body irradiation (TBI: 600 cGy given in 3 fractions). We treated 45 patients with a minimum of 6 months follow up, median age of 55 years (27-67); 33 patients were 50 years or older; 25 received sibling and 20 an unrelated donor (UD) transplant. All but one sibling transplant was a 6/6 match, whereas 8/20 UD transplants involved mismatched loci. GVHD prophylaxis consisted of tacrolimus and short course methotrexate in 43, tacrolimus/MMF in 1 and tacrolimus/sirolimus in 1. Seventeen patients had AML, 3 MDS, 2 ALL, 2 CML, 11 CLL, 8 NHL, 1 HD and 1 lymphoplasmacytic lymphoma. Eight of the 45 had prior stem cell transplantation. The median number of CD34+ cells infused was 4.54 million/kg. Nine patients were transplanted in CR or early disease phase. Five patients died before anticipated neutrophil recovery, 2 had no neutrophil nadir and median time to neutrophil engraftment was 14.5 days, and platelets recovered in 18.7 days. Donor chimerism at 30 days by VNTRs was 94% (range 34%-100%). The overall day 100 survival was 69% (31/45), with 80% (20/25) of sibling graft recipients alive and 55% (11/20) of UD recipients still living. Twelve patients developed regimen related toxicity. In five this manifested as ARDS or multiorgan failure with capillary leak syndrome, and 2 had renal failure. Ten patients had disease resistance or relapse after transplant, and all have expired. Overall survival to date is 42% (48% for sibling transplants and 35% for UD) with a range of follow-up from 283 to 1366 days (median 535 days). Acute GVHD grade III or IV was seen in only 3 patients. After day 100, 27% had extensive GVHD. The best results were seen in AML or CLL in CR or early relapse with chemosensitive disease, no AML patient in full blown relapse survived. This regimen is well tolerated and offers a suitable platform for reduced intensity allogeneic stem cell transplantation. The benefit(s) of ECP require further testing in the context of improved radiation therapy, TBI versus TLI (total lymphoid irradiation).
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterized by overexpression of cyclin D1 and the t(11;14)(q13;q32) chromosomal translocation. MCL is biologically and clinically heterogeneous and frequently disseminates to extranodal areas. While a subset of patients have an indolent clinical course, the overall outcome for patients with MCL remains poor. There is no proven curative therapy, and no standard of care has been established for initial or subsequent lines of therapy. Several regimens are highly active in previously untreated patients, and recent research has led to improvements in currently available therapy. Moreover, investigational agents have recently demonstrated promising activity in clinical trials. A workshop was held to review recent data on MCL pathogenesis, novel molecular targets and alternative approaches to immunotherapy, and to discuss recent and ongoing clinical trials in MCL. The presentations are summarized in this article, which is intended to highlight areas of active investigation and identify important avenues for future research.
Abstract CD23 is a trans-membrane protein belonging to the C-type lectin family, widely expressed in the immune system. Originally identified as the low-affinity receptor for IgE, CD23 was later shown to also bind CD21, MHCII and various integrins, and to have pleiotropic roles, including modulation of cell proliferation, differentiation, Ig and cytokine secretion. Expression of membrane CD23 (mCD23) is regulated at least in part by its shedding from the cell surface via activity of metalloproteinases, the most important of which is ADAM10. Interestingly, secreted CD23 (sCD23) isoforms can exert immunomodulatory functions as soluble factors. B cells upregulate mCD23 and serum sCD23 levels have been found to be elevated in inflammatory and autoimmune conditions, including rheumatoid arthritis, and in B cell chronic lymphocytic leukemia. However, the mechanisms responsible for CD23 modulation on B cells are still unclear. Here we show that mCD23 is upregulated on mouse and human B cells found in inflamed lymphoid tissues. Furthermore, in vitro experiments demonstrate that B cell mCD23 upregulation is strictly dependent on soluble signals provided by stromal cells from inflamed, but not non-inflamed lymph nodes, and can be reversed by ADAM10-specific inhibitors. We propose therefore that the balance between B cell mCD23 and sCD23 expression in inflammatory conditions is modulated by microenvironmental signals provided by stromal cells within lymphoid tissues.
Abstract Regulatory T cells (TR) play a critical role in the inhibition of self-reactive immune responses and as such have been implicated in the suppression of tumor-reactive effector T cells. In this study, we demonstrate that follicular lymphoma (FL)-infiltrating CD8+ and CD4+ T cells are hyporesponsive to CD3/CD28 costimulation. We further identify a population of FL-infiltrating CD4+CD25+GITR+ TR that are significantly overrepresented within FL nodes (FLN) compared with that seen in normal (nonmalignant, nonlymphoid hyperplastic) or reactive (nonmalignant, lymphoid hyperplastic) nodes. These TR actively suppress both the proliferation of autologous nodal CD8+CD25− and CD4+CD25− T cells, as well as cytokine production (IFN-γ, TNF-α and IL-2), after CD3/CD28 costimulation. Removal of these cells in vitro by CD25+ magnetic bead depletion restores both the proliferation and cytokine production of the remaining T cells, demonstrating that FLN T cell hyporesponsiveness is reversible. In addition to suppressing autologous nodal T cells, these TR are also capable of suppressing the proliferation of allogeneic CD8+CD25− and CD4+CD25− T cells from normal lymph nodes as well as normal donor PBL, regardless of very robust stimulation of the target cells with plate-bound anti-CD3 and anti-CD28 Abs. The allogeneic suppression is not reciprocal, as equivalent numbers of CD25+FOXP3+ cells derived from either normal lymph nodes or PBL are not capable of suppressing allogeneic CD8+CD25− and CD4+CD25− T cells, suggesting that FLN TR are more suppressive than those derived from nonmalignant sources. Lastly, we demonstrate that inhibition of TGF-β signaling partially restores FLN T cell proliferation suggesting a mechanistic role for TGF-β in FLN TR-mediated suppression.
Treatment of human myeloid leukemic cells with phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with activation and then partial down-regulation of protein kinase C activity. Previous work has suggested that the activation of protein kinase C by TPA contributes to the decrease in c-myc expression during differentiation of these cells. The present studies demonstrate that the decline in c-myc mRNA levels following exposure of HL-60 cells to TPA is preceded by an increase in expression of this gene. In contrast, exposure of HL-60 cells to inhibitors of protein kinase C activity is associated with down-modulation of c-myc expression. Similar findings have been obtained in U-937 myeloid leukemia cells. Taken together, these findings suggest that phorbol esters have a biphasic effect on c-myc expression. Whereas the activation of protein kinase C by phorbol esters may be associated with an increase in c-myc gene expression, the subsequent partial down-regulation of kinase activity may initiate a cascade of events resulting in the down-modulation of c-myc expression.
