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6. Resistance to Several Steroids in Two Sisters*

Author

New, M I, Nimkarn, S, Brandon, D D, Cunningham-Rundles, S, Wilson, R C, Newfield, R S, Vandermeulen, J, Barron, N, Russo, C, Loriaux, D L, and O’Malley, B

Published
1999

12. LIST OF CONTRIBUTORS

Author

ABELL, C.W., primary, ALFORD, ROBERT H., additional, ALTER, B.J., additional, ANDERSON, A.O., additional, ANDERSON, DEBORAH J., additional, ANDERSON, SUSAN M., additional, ANDRON, L.A., additional, ANTON, ELIZABETH, additional, ARALA-CHAVES, M.P., additional, ARNON, R., additional, ASCHER, M.S., additional, BACH, F.H., additional, BAIRD, LYNN G., additional, BARCINSKI, MARCELLO A., additional, BARKER, BARBARA E., additional, BARTH, ROLF F., additional, BATTISTO, JACK R., additional, BELL, CLARA, additional, BEN-SASSON, SHMUEL A., additional, BERKE, GIDEON, additional, BERNHEIM, JAN L., additional, BESSLER, WOLFGANG G., additional, BETEL, IDO, additional, BETZ, SALLY J., additional, BEYER, C.F., additional, BLAESE, R. MICHAEL, additional, BLANKWATER, M.J., additional, BOCHERT, G., additional, BOCKMAN, D.E., additional, BOLDT, DAVID H., additional, BONA, CONSTANTIN, additional, BONAVIDA, BENJAMIN, additional, BONNARD, GUY D., additional, BOREL, J.F., additional, BOWERS, W.E., additional, BRAATZ, J.A., additional, BRADLEY, B., additional, BRADLEY, B.A., additional, BRAUNSTEINER, HERBERT, additional, BRODER, S., additional, BROWN, JOHN M., additional, BUNDY, BONITA M., additional, BURGER, D.R., additional, CAMBELL, D.A., additional, CARPENTER, C.B., additional, CASTAGNOLA, JAN, additional, CAVILES, ALENDRY P., additional, CHAKRAVARTY, A.K., additional, CHAPLIN, D.D., additional, CHARMOT, D., additional, CHISARI, F.V., additional, CLARK, W.R., additional, CLEMENTS, PHILIP J., additional, COHEN, I.R., additional, COOPER, HERBERT L., additional, COOPER, M.D., additional, COOPER, R.A., additional, CORLEY, RONALD B., additional, CROSIER, P., additional, CUNNINGHAM-RUNDLES, S., additional, CURTISS, LINDA K., additional, DANIELE, RONALD P., additional, DARAI, G., additional, DAUSSET, J., additional, DAVID, JOHN R., additional, DAYNES, RAYMOND A., additional, DEAN, JACK H., additional, DEBATES, MARY JO, additional, DECKER, JEAN M., additional, DE GOEDE, R.E.Y, additional, DEHEER, DAVID H., additional, DELFRAISSY, J.F., additional, DEWOLF, W.C., additional, DOOLEY, N.D., additional, DOOLEY, NANCY J., additional, DORIAN, RANDEL, additional, DORMONT, J., additional, DOUGLAS, GARY N., additional, DRAY, SHELDON, additional, DUPONT, B., additional, DURM, M., additional, DWYER, JOHN M., additional, EDGINGTON, THOMAS S., additional, ELFERINK, DIENNE, additional, ENDRES, ROBERT O., additional, ESSELMAN, WALTER J., additional, FAGAN, G., additional, FARNES, PATRICIA, additional, FAUCI, ANTHONY S., additional, FERGUSON, RONALD M., additional, FERRARINI, M., additional, FLETCHER, MARK P., additional, FRELINGER, JEFFREY A., additional, FORSDYKE, D.R., additional, FROST, A.F., additional, FUDENBERG, H. HUGH, additional, GALANAUD, P., additional, GAROVOY, M.R., additional, GARRIDO, F., additional, GEHA, RAIF S., additional, GEMSA, DIETHARD, additional, GEORGE, K., additional, GERSHWIN, M. ERIC, additional, GLICKMAN, E., additional, GOLDBLUM, R.M., additional, GOLDMAN, C., additional, GOLDSTEIN, ALLAN L., additional, GOOD, R.A., additional, GORDON, DAVID S., additional, GORDON, G., additional, GORDON, IAN L., additional, GORDON, JULIUS, additional, GORENBERG, DAVID J., additional, GORSKA, R., additional, GORSKI, A.J., additional, GOTTLIEB, M.N., additional, GRANBERG, CHRISTER, additional, GRANGER, GALE A., additional, GRAYBILL, J. RICHARD, additional, GREY, HOWARD M., additional, GRILLOT-COURVALIN, C., additional, GRIMM, ELIZABETH ANN, additional, GRINWICH, KAZIMIERA, additional, GROSSI, C.E., additional, GüNTHER, EBERHARD, additional, GUERRY, D., additional, HAMILL, BARBARA, additional, HANSEN, J.A., additional, HANTKE, KLAUS, additional, HAYWARD, A.R., additional, HEININGER, D., additional, HELDERMAN, J. HAROLD, additional, HENKART, PIERRE A., additional, HENNEY, CHRISTOPHER H., additional, HERBERMAN, R.B., additional, HESTER, RAYMOND B., additional, HIRSCHBERG, HENRY, additional, HISERODT, JOHN C., additional, HOETTE, M., additional, HOLIMAN, B.J., additional, HORSMANHEIMO, A., additional, HORSMANHEIMO, M., additional, SUNY, MICHAEL L. HOWE, additional, HUBER, CHRISTOPH, additional, HURTUBISE, P.E., additional, IKEDA, RICHARD, additional, ITZCHAKI, M., additional, JACOBS, DIANE M., additional, JANICKI, BERNARD W., additional, JARRETT-TOTH, E., additional, JENSEN, PAMELA, additional, JERRY, L. MARTIN, additional, JONES, THOMAS B., additional, JONGENEEL, C. VICTOR, additional, JUNGFER, H., additional, KACENA, AMELIA, additional, KALDANY, A., additional, KAPLAN, ALAN M., additional, KAPLAN, J.G., additional, KASHKET, EVA R., additional, KAY, H. DAVID, additional, KAZURA, J., additional, KEARNEY, J.K., additional, KERMANI-ARAB, V., additional, KIERSZENBAUM, F., additional, KEYSSNER, K., additional, KIRCHNER, H., additional, KIRKPATRICK, CHARLES H., additional, KLEIN, J., additional, KLIMPEL, GARY, additional, KOLB, W.P., additional, KORN, J., additional, KOSKI, L.J., additional, KRAKAUER, R., additional, KRUISBEEK, ADA M., additional, KRUITHOF, E.K.O., additional, KUBO, RALPH T., additional, LANOTTE, M., additional, LAUGHTER, ARLINE H., additional, LAUGHTER, BARBARA J., additional, LA VIA, D.S., additional, LA VIA, M.F., additional, LAWRENCE, E.C., additional, LAWTON, A.R., additional, LEGRAND, L., additional, LEON, MYRON A., additional, LESLIE, G.A., additional, UCLA, JOSHUA LEVY, additional, LICHTMAN, M.A., additional, LIFTON, J., additional, LIGHTBODY, JAMES J., additional, LINKER-ISRAELI, M., additional, LOPATIN, DENNIS E., additional, LORARCHER, ALOIS, additional, LORD, EDITH M., additional, LUCAS, DAVID O., additional, LUCAS, KEES, additional, LUNDIN, A.P., additional, LYDYARD, P.M., additional, MCCALMON, ROBERT T., additional, MACDERMOTT, RICHARD P., additional, MCDOUGAL, J.S., additional, MCINTIRE, K.R., additional, MACKLER, BRUCE F., additional, MADYASTHA, K.R., additional, MADYASTHA, P.R., additional, MÄHLER, BERND, additional, MAKI, TAKASHI, additional, MANNINEN, KIMMO, additional, MARTIJNSE, JOKE, additional, MAWAS, C., additional, MAYER, EUGENE P., additional, MEADE, B., additional, MENDELSOHN, JOHN, additional, MENZEL, J., additional, MERGENHAGEN, S.E., additional, METZGER, JOACHIM, additional, MILLER, GINGER W., additional, MILLER, HAROLD C., additional, MILLER, J., additional, MILLS, G., additional, MINGARI, M.C., additional, MOERMAN, C., additional, MOLDOW, C.F., additional, MONAHAN, T.M., additional, MORETTA, A., additional, MORETTA, L., additional, MORRISON, DAVID C., additional, MOTICKA, EDWARD J., additional, MUCHMORE, ANDREW V., additional, MULLER-EBERHARD, H.J., additional, MUNK, K., additional, MUUL, L., additional, NASH, GEOFFREY S., additional, NEGENDANK, W., additional, NELSON, DAVID L., additional, NELSON, J.A., additional, NETA, R., additional, NEWELL, LAURIE, additional, NG, A.K., additional, O'BRIEN, RICHARD L., additional, OEHLER, J.R., additional, O'NEILL, PEGGY A., additional, OPPENHEIM, JOOST J., additional, ORTALDO, J.R., additional, PAHWA, S., additional, PANIJEL, J., additional, PAPE, GERD R., additional, PARADYSZ, J., additional, PARKER, C.W., additional, PARKER, JOHN W., additional, PARRILLO, JOSEPH E., additional, PAWELEC, G.P., additional, PEARSON, CARL M., additional, PERLMANN, PETER, additional, PILARSKI, LINDA M., additional, PLATA, FERNANDO, additional, PLESCIA, ANNE M., additional, PLESCIA, OTTO J., additional, PONZIO, N.M., additional, POPLACK, D.G., additional, PRATT, KAREN R., additional, PUNTIS, M.C.A, additional, RANNEY, DAVID F., additional, RASMUSSEN, HOWARD, additional, REDELMAN, DOUG, additional, RESCH, KLAUS, additional, RICH, ROBERT R., additional, RICH, SUSAN SOLLIDAY, additional, ROBERTS, R.L., additional, RODE, HAROLD N., additional, ROSENSTREICH, DAVID L., additional, ROSENTHAL, ALAN S., additional, ROSSIO, JEFFREY L., additional, ROWDEN, GEOFFREY, additional, ROWLAND, GEORGE, additional, RUBIN, ARNOLD S., additional, RüDE, ERWIN, additional, RüHL, H., additional, RüHL, U., additional, RYAN, JOHN L., additional, SALVIN, S.B., additional, SASPORTES, M., additional, SCHIRRMACHER, V., additional, SCHMALSTIEG, F.C., additional, SCHMIDTKE, JON R., additional, SCHOLLE, H., additional, SCHRIEBER, A.D., additional, SCHUBERT, RICHARD D., additional, SEGEL, G.B., additional, SELL, STEWART, additional, SHALLER, C., additional, SHARON, N., additional, SHEA, MARY, additional, SHEEHAN, JAMES M., additional, SHEPPARD, HAYNES W., additional, SHEPPARD, J.R., additional, SHERIDAN, JOHN, additional, SHEVACH, ETHAN M., additional, SHIFRINE, M., additional, SHIFTAN, THOMAS A., additional, SHORE, STEVEN L., additional, SIMMONS, RICHARD L., additional, SMITH, ALAN, additional, SMITH, TERRILL K., additional, SOULILLOU, J.P., additional, SPECKART, STEPHEN F., additional, SPELLMAN, CRAIG W., additional, STEGGEMANN, LUDWIG, additional, STEINMAN, L., additional, STEJSKAL, VERA, additional, STEWART, CARLETON C., additional, STITES, DANIEL P., additional, ST. LOUIS, G., additional, STOBO, J.D., additional, STOECK, MICHAEL, additional, STRAUSS, PHYLLIS R., additional, STROBER, W., additional, STROM, TERRY B., additional, SULLIVAN, ARTHUR K., additional, SUNDSMO, J.S., additional, SUTCLIFFE, MARILYN C., additional, SUTHANTHIRAN, M., additional, SWART, A.C.W., additional, TAYLOR, CLIVE R., additional, TEITELBAUM, D., additional, TEODORESCU, MARIUS, additional, TERMIJTELEN, A., additional, THESTRUP-PEDERSEN, KRISTIAN, additional, LE THI, HIEN, additional, THOMAS, DAVID W., additional, THORBECKE, G.J., additional, THORSBY, ERIK, additional, THURMAN, GARY B., additional, TILL, GERD, additional, TILNEY, N.L., additional, TOIVANEN, PAAVO, additional, TOMASI, THOMAS B., additional, TOUTON, M., additional, TRAININ, N., additional, TREFTS, PARK E., additional, TROWBRIDGE, SIDNEYE, additional, TRUFFA-BACHI, PAULO, additional, UBELS-POSTMA, JOSÉ, additional, UMIEL, T., additional, VAN BEKKUM, D.W., additional, VAN DE BERG, TINEKE, additional, VAN DEN TWEEL, JAN G., additional, VAN DEN WESTEN, GERARD, additional, VAN HEES, MARITA, additional, VAN OERS, M.H.J., additional, VAN ROOD, J.J., additional, VOGT, W., additional, WAKSMAN, B.H., additional, WALDMANN, T.A., additional, WALKER, WILLIAM S., additional, WALLON, CH., additional, WARE, CARL F., additional, WEBB, S.R., additional, WEBER, W.T., additional, WEDNER, H.J., additional, WERNET, P., additional, WEST, WILLIAM H., additional, WHISLER, R.L., additional, WIESINGER, DOROTHEE, additional, WIGZELL, HANS, additional, WILCOX, C., additional, WILSON, F.D., additional, WINKELSTEIN, A., additional, WOOD, DAVID D., additional, WOODWARD, JEROLD G., additional, WRIGHT, S.C., additional, YEN, BELINDA, additional, YOSHIDA, TAKESHI, additional, YU, DAVID TAK YAN, additional, ZEIJLEMAKER, W.P., additional, ZICCA, A., additional, ZIER, KAREN, additional, and ZIMMERMANN, RITA, additional

Published
1977
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13. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura

Author

Cooper, N, Stasi, R, Cunningham Rundles, S, Feuerstein, Ma, Leonard, Jp, Amadori, S, and Bussel, Jb

Subjects
Adult, Male, Neutropenia, Neutrophils, Immunoglobulins, Autoimmunity, Antineoplastic Agents, Lymphocyte Depletion, Antibodies, Monoclonal, Murine-Derived, Leukocyte Count, Humans, Aged, B-Lymphocytes, Purpura, Thrombocytopenic, Idiopathic, Platelet Count, Antibodies, Monoclonal, Gammaglobulins, Middle Aged, Antigens, CD20, Immune thrombocytopenic purpura, Rituximab, Treatment Outcome, Splenectomy, Female, Settore MED/15 - Malattie del Sangue
Abstract

Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts30 x 10(9)/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m(2) weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count50 x 10(9)/l: 18 achieved a complete response (CR: platelet count150 x 10(9)/l) and 13 a partial response (PR: platelet count 50-150 x 10(9)/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72.5 weeks; 15 of 16 are1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1-2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to0.03 x 10(9)/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP.

Published
2004

14. Probiotics and prebiotics to combat enteric infections and HIV in the developing world: A consensus report

Author

Monachese, M., Cunningham-Rundles, S. (Susanna), Diaz, M.A. (Maria Alejandra), Guerrant, R. (Richard), Hummelen, R.B.S. (Ruben), Kemperman, R. (Rober), Kerac, M. (Marko), Kort, R. (Remco), Merenstein, D. (Dan), Panigrahi, P. (Pinaki), Ramakrishna, B. (Balakrishnan), Safdar, N. (Nasia), Shane, A. (Andi), Trois, L. (Livia), Reid, G. (Gregor), Monachese, M., Cunningham-Rundles, S. (Susanna), Diaz, M.A. (Maria Alejandra), Guerrant, R. (Richard), Hummelen, R.B.S. (Ruben), Kemperman, R. (Rober), Kerac, M. (Marko), Kort, R. (Remco), Merenstein, D. (Dan), Panigrahi, P. (Pinaki), Ramakrishna, B. (Balakrishnan), Safdar, N. (Nasia), Shane, A. (Andi), Trois, L. (Livia), and Reid, G. (Gregor)

Abstract

Infectious disease in the developing world continues to represent one of the greatest challenges facing humanity. Every year over a million children suffer and die from the sequela of enteric infections, and in 2008 was estimated almost 2.7 million (UNAIDS 2009 update) adults and children became infected with human immunodeficiency virus (HIV). While oral rehydration therapy for diarrhea and antiretrovirals (ARV) for HIV are critical, there is a place for adjunctive therapies to improve quality of life. The importance of the human microbiota in retaining health is now recognized, as is the concept of replenishing beneficial microbes through probiotic treatments. Studies have shown that probiotics can reduce the duration of diarrhea, improve gut barrier function, help prevent bacterial vaginosis (BV) and enhance immunity even in HIV-infected subjects. However, many issues remain before the extent of probiotic benefits can be verified, and their application to the developing world realized. This consensus report outlines the potential probiotic, and to a lesser extent prebiotic, applications in resource disadvantaged settings, and recommends steps that could bring tangible relief to millions of people. The challenges to both efficacy and effectiveness studies in these settings include a lack of infrastructure and funding for scientists, students and research projects in developing countries; making available clinically proven probiotic and prebiotic products at affordable prices; and undertaking approp

Published
2011
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15. J Nutr: Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults

Author

Neff, L.M., Culiner, J., and Cunningham-Rundles, S.

Subjects
Obesity -- Diagnosis -- Care and treatment -- Research, Adults -- Health aspects -- Research, Cardiovascular diseases -- Risk factors -- Research, Omega-3 fatty acids -- Health aspects -- Research, Health
Abstract

Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects, but less is known about the independent effects of DHA. This study was designed to [...]

Published
2011

20. A human milk protein specifically activates peripheral blood lymphocytes

Author

Sabharwal, H., Rivlin, R., Simms, Maciej, and Cunningham-Rundles, S.

Subjects
Lymphocyte transformation -- Research, Breast milk -- Physiological aspects, Milk proteins -- Physiological aspects, Food/cooking/nutrition
Abstract

This study describes the effect of a human milk protein on the activation of peripheral blood lymphocytes. A folding variant of [alpha]-lactalbumin from human milk has been isolated and characterized. The active complex precipitated with the casein fraction at pH 4.6 and was purified from casein by a combination of anion exchange and gel chromatography. The fraction showed N-terminal and mass spectrometric identity with human milk [alpha]-lactalbumin, but monomeric, native [alpha]-lactalbumin had no effect on blood lymphocytes. The active fraction was previously shown to induce apoptotic cell death in immature undifferentiated cells but spared normal cells. This human milk fraction was identified as multimeric [alpha]-lactalbumin (MAL). Our continued studies with MAL have focused on the hypothesis that milk components may have a modulating effect on the development of the immune system in breast-fed infants very early in life. We compared the effect of short-term exposure to MAL, monomeric [alpha]-lactalbumin and human milk casein on mononuclear cell activation by flow cytometry using CD69 expression as the measure of early activation. In contrast to monomeric [alpha]-lactalbumin and casein, MAL proved to have a strong activating effect on lymphocytes leading to a fivefold increase in expression. Analysis of the lymphocyte activation response brings us one step closer to proving our hypothesis.

Published
2002

21. Resistance to multiple steroids in two sisters

Author

New, Maria I., primary, Nimkarn, S., additional, Brandon, D.D., additional, Cunningham-Rundles, S., additional, Wilson, R.C., additional, Newfield, R.S., additional, Vandermeulen, J., additional, Barron, N., additional, Russo, C., additional, Loriaux, D.L., additional, and O'Malley, B., additional

Published
2001
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29. CD56+dim and CD56+bright cell activation and apoptosis in hepatitis C virus infection.

Author

Lin, A. W., Gonzalez, S. A., Cunningham-Rundles, S., Dorante, G., Marshall, S., Tignor, A., Ha, C., Jacobson, I. M., and Talal, A. H.

Subjects
KILLER cells, HEPATITIS C virus, HEPATITIS, INTERFERONS, CELLS, DIAGNOSTIC use of flow cytometry
Abstract

CD3–CD56+dim natural killer (NK) cells, which are cytotoxic against virally infected cells, may be important in hepatitis C virus (HCV)-infected patients who are successfully treated with pegylated interferon (PEG-IFN)- α. We used flow cytometry to enumerate activated (CD69+) and apoptotic (annexin-V+) dim (CD3–CD56+dim) and bright (CD3–CD56+bright) NK cells obtained from HCV-infected patients before treatment ( n = 16) and healthy controls ( n = 15) in the absence and presence of pegylated interferon (PEG-IFN)- α-2b. A subset of HCV-infected patients, subsequently treated with PEG-IFN- α-2b in vivo, was determined to have a sustained virological response (SVR, n = 6) or to not respond (NR) to treatment ( n = 5). In the absence of IFN, activated dim (CD3–CD56+dim CD69+) NK cells were significantly decreased ( P = 0·04) while activated apoptotic dim (CD3–CD56+dimCD69+annexin-V+) NK cells tended to be increased ( P = 0·07) in SVR patients compared with NR patients. Activated bright (CD3–CD56+brightCD69+) and activated apoptotic bright (CD3–CD56+brightCD69+annexin-V+) NK cells were significantly correlated ( P = 0·02 and P = 0·01, respectively) with increasing hepatic inflammation. These findings suggest that in the absence of PEG-IFN, activated dim (CD3–CD56+dimCD69+) NK cell turnover may be enhanced in SVR compared with NR patients and that activated bright (CD3–CD56+brightCD69+) NK cells may play a role in liver inflammation. [ABSTRACT FROM AUTHOR]

Published
2004
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32. Multivariate analysis of T-cell functional defects and circulating serum factors in Hodgkin's disease.

Author

Schulof, Richard S., Bockman, Richard S., Garofalo, John A., Cirrincione, Constance, Cunningham-Rundles, Susanna, Fernandes, Gabriel, Day, Noorbibi K., Pinsky, Carl M., Incefy, Genevieve S., Thaler, Howard T., Good, Robert A., Gupta, Sudhir, Schulof, R S, Bockman, R S, Garofalo, J A, Cirrincione, C, Cunningham-Rundles, S, Fernandes, G, Day, N K, and Pinsky, C M

Published
1981
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35. The use of cryopreserved lymphocytes for longitudinal studies of immune function and enumeration of subpopulations.

Author

Jewett, M. A. S., Gupta, S., Hansen, J. A., Cunningham-Rundles, S., Siegal, F. P., Good, R. A., and Dupont, B.

Subjects
CRYOBIOLOGY, LYMPHOCYTES, MITOGENS, ANTIGENS, T cells, LEUCOCYTES
Abstract

The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared using samples collected on five separate occasions from one normal donor. The day-to-day variation seen with the fresh cells was eliminated by the use of frozen cells. Thawed cells from one donor collected on one occasion hut studied on five separate occasions and compared to fresh cells on the same days showed fluctuations from day to day as well, confirming that the day-today variation seen is due to technical and not biological phenomena. Cryopreserved cells showed a decrease in responses to specific microbial antigens, a slight shift in the PHA dose-response curve, but no significant difference in responses to Con A or PWM. The relative proportion of lymphocyte subpopulations changed with freezing and thawing. The proportion of T cells increased slightly and the proportion of H cells decreased. [ABSTRACT FROM AUTHOR]

Published
1976

36. Generalized lymphadenopathy in homosexual men.

Author

Metroka, Craig E., Cunningham-Rundles, Susanna, Pollack, Marilyn S., Sonnabend, Joseph A., Davis, John M., Gordon, Bruce, Fernandez, Richard D., Mouradian, Janet, Metroka, C E, Cunningham-Rundles, S, Pollack, M S, Sonnabend, J A, Davis, J M, Gordon, B, Fernandez, R D, and Mouradian, J

Subjects
GAY people, HIV, DISEASES
Abstract

The cases of 90 homosexual or bisexual men with generalized lymphadenopathy were studied by epidemiologic, clinical, pathologic, immunologic, and genetic methods. The patients ranged in age from 20 to 52 years and had histories of multiple sexually transmitted diseases and both recreational and prescription drug use. Histologically, their lymph nodes showed three patterns: explosive follicular hyperplasia; follicular involution with expansion of the paracortical area; and a mixed pattern of follicular hyperplasia and follicular involution in the same lymph node. The frequency of HLA-DR5 was significantly increased in these patients (p less than 0.005) compared with that in controls. All patients had impaired cell-mediated immunity. Opportunistic infections, lymphomas, or Kaposi's sarcoma subsequently developed in 15 patients who had had severe immune dysfunction for the previous 3 to 13 months. We suggest that generalized lymphadenopathy is part of the spectrum of a disorder manifested by acquired immunodeficiency, opportunistic infections, Kaposi's sarcoma, and malignant lymphomas. [ABSTRACT FROM AUTHOR]

Published
1983
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37. Acquired immunodeficiency syndrome in male prisoners. New insights into an emerging syndrome.

Author

Wormser, Gary P., Krupp, Lauren B., Hanrahan, John P., Gavis, Gustave, Spira, Thomas J., Cunningham-Rundles, Sussana, Wormser, G P, Krupp, L B, Hanrahan, J P, Gavis, G, Spira, T J, and Cunningham-Rundles, S

Subjects
AIDS, PRISONERS, PNEUMOCYSTIS pneumonia, DISEASES
Abstract

Between September 1981 and June 1982, the acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia were diagnosed in seven previously healthy young men incarcerated for 5 to 38 months in New York State correctional facilities. All seven patients were anergic, six were lymphopenic, and all developed oral candidiasis. Immunologic evaluation in vitro showed profound defects in cellular immune function in patients tested, with inversion of the normal ratio of helper to suppressor T-cell populations in four of five patients studied. No underlying immunosuppressive disorder was found in any patient, including three patients who had postmortem examinations. Based on these cases, the incidence of this syndrome among inmates of New York State correctional facilities is estimated to be at least 20 out of 100 000 per year. None of the inmates was homosexual but all had used intravenous drugs extensively before incarceration. If intravenous drug use is a cause of the syndrome, then the epidemiologic findings of this study suggest a prolonged incubation period (mean, 14.6 months) before development of serious opportunistic infection. Recognition that certain prisoners are at high risk for the acquired immunodeficiency syndrome has important implications for the prison health-care system. [ABSTRACT FROM AUTHOR]

Published
1983
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38. Impaired Proliferative Response to B-Lymphocyte Activators in Common Variable Immunodeficiency.

Author

Cunningham-Rundles, S., Cunningham-Rundles, C., Ma, D. I., Siegal, F. P., Gupta, S., E. M. Smithwick, Kosloff, C., and Good, R. A.

Subjects
CELLULAR immunity, IMMUNODEFICIENCY, STAPHYLOCOCCUS aureus, ESCHERICHIA coli, CANDIDA albicans, LYMPHOCYTES, IMMUNOGLOBULIN G
Abstract

The cell-mediated immune responses of 39 patients with common variable immunodeficiency (CVI) were studied in vitro, using Staphylococcus aureus and Escherichia coli prepared as whole cells and Candida albicans extract. These microbial activators were found to require intact B-lymphocyte function for normal proliferative response. The patient group was observed to have significantly depressed lymphocyte responses compared with those of controls studied in parallel (P<0.01). Negative lymphocyte response to one activator and strongly positive response to another were found in individual patients. Examination of patients' lymphocyte response to S. aureus and E. coli in association with serum IgG levels demonstrated that a rough correlation could be drawn, showing that patients with serum IgG < 125 mg/dl had markedly lower (P<0.01) lymphocyte responses than those with serum IgG > 300 mg/dl. No similar correlation with phytohaemagglutinin activation was observed. Since depressed lymphocyte responses did not correlate with reduced B-cell number in these patients, intrinsic B-lymphocyte deficiency was indicated. These preparations of microbial activators are potentially useful tools in exploring lymphocyte subpopulation functions in primary immunodeficiency diseases. [ABSTRACT FROM AUTHOR]

Published
1982
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40. Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells

Author

Reisner, Y, Kapoor, N, Kirkpatrick, D, Pollack, MS, Cunningham-Rundles, S, Dupont, B, Hodes, MZ, Good, RA, and O'Reilly, RJ

Abstract

Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA- mismatched marrow cells.

Published
1983
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41. Kaposi's sarcoma

Author

Saltz, R. K., Kurtz, R. C., Lightdale, C. J., Myskowski, P., Cunningham-Rundles, S., Urmacher, C., and Safai, B.

Abstract

We have evaluated 19 homosexual/bisexual male patients with biopsy-proven Kaposi's sarcoma (KS) of the skin in order to define the extent of gastrointestinal involvement and determine its correlation with oral mucosal disease, skin findings, and immunologic function. Nearly half the patients had oral mucosal lesions. In patients with oral mucosal lesions, 75% had gastrointestinal lesions. Some gastrointestinal involvement during the period of observation was present in 10 of the 19 patients. Involvement of the upper gastrointestinal tract was more common than colonic involvement: esophagus 1, stomach 8, duodenum 3, and colon 6. Significant immunosuppression was observed in these patients, measuredin vitro by natural killer (NK) assay, and lymphocyte proliferation response to mitogens.

Published
1984
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43. Ribosomal distribution in a polyamine auxotroph of Escherichia coli

Author

Algranati, I D, Echandi, G, Goldemberg, S H, Cunningham-Rundles, S, and Maas, W K

Abstract

The distribution of ribosomal particles has been studied in a polyamine-deficient mutant of Escherichia coli by sucrose gradient centrifugation analysis. Lysates from starved cells contained less 70S monomers and 30S subunits but more 50S particles than those prepared from bacteria supplemented with putrescine. The addition of the polyamine to putrescine-depleted cells induced a rapid change of the ribosomal profile. A similar effect could be obtained in vitro by equilibrium dialysis against a polyamine-containing solution. The ribosomal pattern obtained from starved bacteria was specific for polyamine deficiency. We conclude that the changes in ribosomal profiles upon restoration of putrescine levels in previously starved cells denote a shift of the equilibrium between 30S-50S couples and ribosomal subunits.

Published
1975
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44. Isolation, characterization, and mapping of Escherichia coli mutants blocked in the synthesis of ornithine decarboxylase

Author

Cunningham-Rundles, S and Maas, W K

Abstract

Several Escherichia coli K-12 mutants blocked in the synthesis of ornithine decarboxylase (OD) were isolated after transduction for serA+ in a strain (MA197) blocked in agmatine ureohydrolase (AUH) with a mutagenized phage lysate of P1. The new double-polyamine mutants were characterized by an unconditional polyamine dependence; either putrescine or spermidine was required for normal growth. The mutational block was varified by the demonstration of a virtual absence of OD activity in cellular extracts. The mutation, designated speC, was mapped by P1 transduction in several strains and was shown to have a cotransduction frequency of 17.2% with serA. Map order was established as serA speB speC metK. A derivative of one of the OD mutants having wild-type levels of AUH and blocked in OD was utilized along with an OD AUH mutant and an OD+ AUH strain to explore the phenomenon of "pathway selection" using growth rate as a parameter. Polyamine pool studies were carried out simultaneously. The results presented here support the hypothesis of pathway selection, implying a preferential utilization of exogenous arginine rather than endogenously produced arginine in polyamine biosynthesis.

Published
1975
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45. Immunological variables as predictors of prognosis in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome

Author

Vadhan-Raj S, Wong G, Gnecco C, Cunningham-Rundles S, Krim M, Francisco X Real, Hf, Oettgen, and Se, Krown

Subjects
Antigens, Differentiation, T-Lymphocyte, Acquired Immunodeficiency Syndrome, Time Factors, T-Lymphocytes, Immunoglobulins, Lymphocyte Activation, Prognosis, Recombinant Proteins, Killer Cells, Natural, Antigens, Surface, Interferon Type I, Humans, Hypersensitivity, Delayed, Interferons, beta 2-Microglobulin, Sarcoma, Kaposi, Skin Tests
Abstract

Multivariate analysis was used to identify which of a large number of pretreatment immunological parameters correlated with therapeutic response, subsequent development of opportunistic infection, and survival from the time of diagnosis in a group of 70 patients with Kaposi's sarcoma and acquired immunodeficiency syndrome treated with recombinant leukocyte A interferon. In a logistic regression model, delayed type hypersensitivity response to one or more recall antigens and high proliferative response to Escherichia coli were significant predictors for response to recombinant leukocyte A interferon (for the model, P = 0.01). For prediction of the development of opportunistic infection, the model selected low proliferative responses to phytohemagglutinin and E. coli (P less than 0.001). Favorable factors predicting survival in the Cox regression model were the absence of endogenous serum interferon activity and a high proliferative response to E. coli (P less than 0.001). The estimated median survival for the group with endogenous serum interferon activity and low E. coli response was 12 months; the median has not yet been reached for the group with no serum interferon and a high E. coli response. We conclude that immunological parameters may be useful in predicting prognosis in patients with Kaposi's sarcoma and acquired immunodeficiency syndrome.

46. American cancer society Phase I trial of naturally produced beta-interferon

Author

Mj, Hawkins, Se, Krown, Ec, Borden, Krim M, Francisco X Real, Bs, Edwards, Sa, Anderson, Cunningham-Rundles S, and Hf, Oettgen

Subjects
American Cancer Society, Male, Lymphoma, Breast Neoplasms, Kidney Neoplasms, United States, Kinetics, Poly I-C, Neoplasms, Colonic Neoplasms, Interferon Type I, Drug Evaluation, Humans, Carcinoma, Renal Cell, Skin
Abstract

Naturally produced beta-interferon was evaluated following i.m. and i.v. administration to 18 patients with advanced cancer. Fever (mean +/- S.E. = 38.1 degrees +/- 1.7 degrees), enhancement of natural killer cell cytotoxicity, and depression of the white blood cell count occurred following a single i.m. injection in the absence of detectable serum antiviral activity. Fever, rigors, and fatigue were dose-limiting toxicities following daily i.v. administration of 10 million units. Tachyphylaxis, as reported following repetitive administration of alpha-interferons, did not occur. Side effects, depression of the white blood cell count, and enhancement of natural killer cell cytotoxicity were similar when beta-interferon was administered daily as a 10-min bolus or as a 6-hr infusion. However, while natural killer cell cytotoxicity increased progressively over 10 days of bolus injections, it was maximal after the initial 6-hr infusion of beta-interferon. Administration of 10 million units of beta-interferon divided equally between a 10-min bolus injection and a 3-hr infusion was well tolerated and resulted in high initial peak and lower sustained serum interferon levels. Based on pharmacokinetic criteria, this schedule of administration can be recommended for further study in Phase II trials. However, in light of the biological activity of beta-interferon following i.m. administration, the level of beta-interferon in the serum may have limited value as a predictor of antitumor response, toxicity, or biological response modification.

47. Immunomodulation in choroidal melanoma: reversal of inverted CD4/CD8 ratios following treatment with ultrasonic hyperthermia

Author

Df, Rosberger, Dj, Coleman, Silverman R, Woods S, Mark Rondeau, and Cunningham-Rundles S

Subjects
Male, T-Lymphocyte Subsets, Choroid Neoplasms, Ultrasonic Therapy, CD4-CD8 Ratio, Humans, Female, Hyperthermia, Induced, Middle Aged, Melanoma, Aged
Abstract

It has long been suggested that malignant melanomas, cutaneous as well as uveal, are responsive to human immune-mediated host defenses. We report here 5 consecutive cases of posterior choroidal melanomas which were treated with hyperthermia generated by high-intensity focused ultrasound. Patient immune function was monitored by determination of T-cell helper/suppressor (CD4/CD8) ratios immediately before and approximately 1 week following hyperthermia treatment. All 5 patients had normal total T-cell counts as measured by the pan-T-cell marker CD3. Two patients were noted to have inverted CD4/CD8 ratios (1:1) before hyperthermia. In both these cases, the ratio reverted to normal (1:1) 1 week following treatment. One patient whose CD4/CD8 ratio was not inverted was noted to have a further increase in his CD4 T cells relative to his CD8 (37% increase). Two patients with initially normal CD4/CD8 demonstrated no significant change following hyperthermia. It appears that ultrasonic hyperthermia may induce a systemic immunomodulatory effect in patients with posterior choroidal melanoma and inverted T-cell helper/suppressor resulting in a normalization of T-cell subset ratios.

49. Severe Acquired Immunodeficiency in Male Homosexuals, Manifested by Chronic Perianal Ulcerative Herpes Simplex Lesions

Author

Siegal, F.P., primary, Lopez, C., additional, Hammer, G.S., additional, Brown, A.E., additional, Kornfeld, S.J., additional, Gold, J., additional, Hassett, J., additional, Hirschman, S.Z., additional, Cunningham-Rundles, C., additional, Adelsberg, B.R., additional, Parham, D.M., additional, Siegal, M., additional, Cunningham-Rundles, S., additional, and Armstrong, D., additional

Published
1982
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