125 results on '"Mitsuyasu RT"'
Search Results
102. Immunologic defects in young male patients with hepatitis-associated aplastic anemia.
- Author
-
Foon KA, Mitsuyasu RT, Schroff RW, McIntyre RE, Champlin R, and Gale RP
- Subjects
- Adolescent, Adult, Anemia, Aplastic blood, Anemia, Aplastic etiology, Child, Child, Preschool, Female, Hepatitis immunology, Humans, Immunity, Cellular, Immunoglobulins analysis, Immunologic Deficiency Syndromes etiology, Infant, Leukocyte Count, Lymphocytes immunology, Male, Middle Aged, Prospective Studies, T-Lymphocytes classification, Anemia, Aplastic immunology, Hepatitis complications
- Abstract
Extensive immunologic studies were done in 97 patients with severe aplastic anemia between 1973 and 1979. Sixteen young male patients with hepatitis-associated aplastic anemia appeared to constitute a unique subset. Compared with most patients with aplastic anemia from other causes, these 16 patients had significant reductions in the mean values of circulating T lymphocytes, serum IgG and IgM, mitogen reactivity, and decreased cutaneous hypersensitivity. The ratio of peripheral blood helper to suppressor T lymphocytes identified by monoclonal antibodies was within normal limits in 3 patients studied with hepatitis-associated aplastic anemia. Interestingly, the ratio was low (less than 1) in 3 of 7 patients studied with aplastic anemia from other causes, although the mean for these 7 patients was normal. These data suggest that patients in this subset with hepatitis-associated severe aplastic anemia have a severe immunodeficiency. Whether this immunodeficiency is the cause or result of the hepatitis or aplastic anemia, or both, is unknown.
- Published
- 1984
- Full Text
- View/download PDF
103. Failure of trimethoprim-sulfamethoxazole in the therapy of recurrent Pneumocystis carinii pneumonia.
- Author
-
Mitsuyasu RT, Corwin HL, Harris AA, Trenholme GM, Levi S, and Karkusis PH
- Subjects
- Child, Drug Combinations therapeutic use, Female, Humans, Male, Pentamidine therapeutic use, Pneumonia, Pneumocystis diagnosis, Trimethoprim, Sulfamethoxazole Drug Combination, Pneumonia, Pneumocystis drug therapy, Sulfamethoxazole therapeutic use, Trimethoprim therapeutic use
- Abstract
The use of trimethoprim-sulfamethoxazole in the treatment and prophylaxis of Pneumocystis cariniii is well established. Treatment failure with this regimen has been ascribed to inadequate antibiotic serum concentrations. We describe an immunosuppressed patient with recurrent Pneumocystis carinii pneumonia who failed to respond to trimethoprim-sulfamethoxazole therapy despite high antibiotic serum concentrations. Subsequently, a response to pentamidine isethionate was obtained. The reason for failure and therapeutic implications in patients with Pneumocystis carini pneumonia who have received trimethoprim-sulfamethoxazole are discussed.
- Published
- 1982
- Full Text
- View/download PDF
104. Early effects of HIV on CD4 lymphocytes in vivo.
- Author
-
Giorgi JV, Fahey JL, Smith DC, Hultin LE, Cheng HL, Mitsuyasu RT, and Detels R
- Subjects
- Antigens immunology, Antigens, Differentiation, T-Lymphocyte, Antigens, Surface analysis, Candida albicans immunology, Flow Cytometry, Homosexuality, Humans, Lymphocyte Activation, Solubility, T-Lymphocytes classification, Tetanus Toxoid immunology, Time Factors, Acquired Immunodeficiency Syndrome immunology, HIV immunology, T-Lymphocytes immunology
- Abstract
Low circulating CD4 cell numbers and CD4 cell dysfunction are distinguishing features of HIV-mediated disease. The current study delineates the in vivo effects of HIV on distinct functional subsets of CD4 cells in homosexually active men who have been infected with HIV for different lengths of time, and examines the capacity of lymphocytes from these men to proliferate in vitro in response to soluble antigen. Although peripherial blood mononuclear cells from most acquired immune deficiency syndrome (AIDS) patients did not proliferate in response to either tetanus toxoid or Candida albicans, cells from most HIV seropositive men without AIDS, many of whom had been infected for more than 18 mo, responded normally to both. Non-responsiveness in HIV-infected men without AIDS was a late event and was associated with longer duration of infection, lower CD4 cell numbers, and subsequent development of AIDS. A defect in this response was observed in only one of 19 HIV seropositive men whose CD4 levels were greater than 300/mm3, but in eight of 10 with levels less than 300/mm3. The defect could not be attributed to a selective depletion of defined CD4 subpopulations that respond to soluble antigen. Dual-color immunofluorescent flow cytometry indicated that 4B4+, 2H4-, and HB-11- CD4 cells were not lost at a faster rate than other CD4 subsets.
- Published
- 1987
105. Reduced ecto-5'-nucleotidase activity and enhanced OKT10 and HLA-DR expression on CD8 (T suppressor/cytotoxic) lymphocytes in the acquired immune deficiency syndrome: evidence of CD8 cell immaturity.
- Author
-
Salazar-Gonzalez JF, Moody DJ, Giorgi JV, Martinez-Maza O, Mitsuyasu RT, and Fahey JL
- Subjects
- 5'-Nucleotidase, Acquired Immunodeficiency Syndrome enzymology, Antigens, Differentiation, T-Lymphocyte, Cell Differentiation, HLA-DR Antigens, Humans, Leukocyte Count, Lymphocyte Activation, Male, T-Lymphocytes, Cytotoxic enzymology, Acquired Immunodeficiency Syndrome immunology, Antigens, Surface immunology, Histocompatibility Antigens Class II immunology, Nucleotidases metabolism, T-Lymphocytes immunology, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Markedly reduced ecto-5'-nucleotidase activity was found in peripheral blood lymphocytes from 27 out of 30 homosexual men with the acquired immune deficiency syndrome (AIDS) in association with Kaposi's sarcoma (AIDS-KS; 2.67 +/- 1.70 U/10(6) cells; n = 13), opportunistic infections (AIDS-OI; 9.29 +/- 7.32; n = 7), or the AIDS-related complex (ARC; 9.82 +/- 6.12; n = 10). These values were significantly different from healthy controls (22.70 +/- 4.58; p less than 0.001). In AIDS-KS patients, both T cells and non-T cells exhibited significantly reduced ecto-5'-NT activity (p less than 0.001). AIDS-KS CD8 cells contained 20% of the mean ecto-5'-NT activity (7.04 +/- 3.53) displayed by control CD8 cells (34.07 +/- 4.86; p less than 0.001). No significant difference in enzyme level was observed between control and AIDS-KS CD4 cells (11.93 +/- 4.98 vs 7.98 +/- 3.28, respectively). In AIDS patients, lymphocyte ecto-5'-NT activity was inversely related (r = -0.518; p less than 0.01) to the absolute number of OKT10+ cells, but no correlation was found with the number of HLA-DR+ cells (r =-0.224). Two-color analysis of lymphocytes from AIDS-KS patients revealed that 75 +/- 12% of circulating CD8 cells expressed the OKT10 antigen, whereas only 10 +/- 6% of control CD8 cells did. HLA-DR antigens, which are not normally found on circulating resting T cells, were expressed in AIDS-KS CD8 cells, although to a lesser extent than OKT10. These data demonstrate that most AIDS CD8 cells differ from control CD8 cells. Although it has been suggested that these cells are activated cytotoxic or suppressor cells, the data presented here support the hypothesis they are immature. Reduced T cell ecto-5'-NT activity and enhanced expression of OKT10 and HLA-DR antigens on circulating CD8 cells, in conjunction with lack of transferrin receptor-(OKT9) and IL 2 receptor-(Tac) bearing lymphocytes, sustain this latter hypothesis. The correlation of the numerical reduction of CD4 cells with the reduced levels of ecto-5'-NT (r = 0.606; p less than 0.01) suggests that the abnormal maturation of CD8 cells seen in AIDS might be a consequence of the CD4 deficiency characteristic of this syndrome.
- Published
- 1985
106. Treatment of Kaposi's sarcoma with interferon alfa-2b (Intron A).
- Author
-
Volberding PA, Mitsuyasu RT, Golando JP, and Spiegel RJ
- Subjects
- Adult, Drug Evaluation, Humans, Interferon Type I adverse effects, Male, Middle Aged, Opportunistic Infections etiology, Recombinant Proteins therapeutic use, Sarcoma, Kaposi etiology, Sarcoma, Kaposi mortality, T-Lymphocytes immunology, Acquired Immunodeficiency Syndrome complications, Interferon Type I therapeutic use, Sarcoma, Kaposi therapy
- Abstract
The activity of the alpha interferons against AIDS-related Kaposi's sarcoma (KS) has been demonstrated in numerous clinical trials. Unfortunately, most reports have involved small patient cohorts and a variety of dosages and schedules of administration. We report here a series of Phase II trials with interferon alfa-2b (Intron A, Schering Corp., Kenilworth, NJ) involving 114 patients using three dose regimens. Patients received 50 X 10(6) IU/m2 intravenously (high dose), 30 X 10(6) IU/m2 subcutaneously (intermediate dose), or 1 X 10(6) IU/m2 subcutaneously (low dose). Clinical responses were seen in all regimens and, overall, 35% of the patients obtained complete or partial remissions. The response rates in the low-, intermediate-, and high-dose groups were 33%, 28%, and 45%, respectively. In addition, high-dose therapy was associated with more rapid time to response. Patients with low-stage (I or II) disease and those who lack B symptoms were more likely to respond to therapy; i.e., response rates for patients without B symptoms were 38%, 44%, and 60% in the low-, intermediate-, and high-dose groups, respectively. Seventy (61%) patients had died at the time of data collection, with a median survival of 15 months. Disease stage and the presence of B symptoms significantly affected mortality. Responders enjoyed significantly longer survival (P less than 0.10) than did nonresponders both overall and when adjusted for disease stage. Interferon alfa-2b was generally well tolerated, although almost all patients experienced flu-like symptoms. No life-threatening toxicities occurred and only six (6%) patients discontinued treatment due to adverse reactions. No significant improvement in immunologic parameters was detected during this study. These studies suggest that, in this disease setting, interferon alfa-2b may be acting through direct antiproliferative effects rather than as an immunomodulator, and higher doses appear to be more effective than very low doses.
- Published
- 1987
- Full Text
- View/download PDF
107. Detection of non-HLA antigens: effect of lymphocyte priming and amplification signals.
- Author
-
Mitsuyasu RT and Gale RP
- Subjects
- Cytotoxicity, Immunologic, Epitopes, Humans, Kinetics, Lymphocyte Culture Test, Mixed, HLA Antigens immunology, Lymphocytes immunology
- Abstract
We studied three potential mechanisms that might account for the difficulty in detecting non-HLA antigenic disparities between HLA-identical siblings: (1) a low frequency of antigen-reactive cells; (2) the failure of antigen recognition to trigger proliferation or cytotoxicity; and (3) the development of suppressor cells or factors. In vitro sensitization was used to increase the frequency of antigen-reactive cells. Allogeneic lymphocytes or supernatants from mixed lymphocyte cultures were used to provide nonspecific proliferative signals. Neither approach was successful in facilitating the detection of proliferation or cytotoxicity between HLA-identical siblings. Furthermore, we found no evidence for the development of antigen-specific suppressor cells or factors. These data indicate that other mechanisms must underlie the difficulty in detecting non-HLA antigens in vitro.
- Published
- 1979
- Full Text
- View/download PDF
108. Clinical role of granulocyte-macrophage colony-stimulating factor.
- Author
-
Mitsuyasu RT and Golde DW
- Subjects
- Acquired Immunodeficiency Syndrome drug therapy, Animals, Bone Marrow Transplantation, Colony-Stimulating Factors adverse effects, Colony-Stimulating Factors pharmacology, Drug Evaluation, Drug Evaluation, Preclinical, Granulocyte-Macrophage Colony-Stimulating Factor, Growth Substances adverse effects, Growth Substances pharmacology, Hematopoiesis drug effects, Humans, Infections drug therapy, Neoplasms drug therapy, Radiation Injuries drug therapy, Recombinant Proteins therapeutic use, Bone Marrow Diseases drug therapy, Colony-Stimulating Factors therapeutic use, Growth Substances therapeutic use
- Abstract
The activity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for increasing leukocyte production and enhancing mature neutrophil function has been clearly demonstrated in phase I clinical trials in patients with a variety of hematologic and malignant diseases. The focus of current studies includes determination of optimal administration schedules and its use in combination with myelosuppressive chemotherapy, radiation therapy or antimicrobial agents. The utility of GM-CSF as a stimulant of host defense against infections and tumors is also under study.
- Published
- 1989
109. Immunomodulating effects in vitro of interleukin-2 and interferon-gamma on human blood and bone marrow mononuclear cells.
- Author
-
Kedar E, Rezai AR, Giorgi JV, Gale RP, Champlin RE, Mitsuyasu RT, and Fahey JL
- Subjects
- Acquired Immunodeficiency Syndrome immunology, Adult, Antibody-Producing Cells immunology, Bone Marrow immunology, Colony-Forming Units Assay, Humans, In Vitro Techniques, Killer Cells, Natural immunology, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Middle Aged, T-Lymphocytes classification, T-Lymphocytes immunology, Interferon-gamma pharmacology, Interleukin-2 pharmacology, Leukocytes, Mononuclear immunology
- Abstract
Mononuclear cells (MNC) derived from peripheral blood (PBMNC) of 23 normal donors and 4 AIDS patients, and from bone marrow (BMMNC) of 15 normal donors were incubated at 37 degrees C in culture medium alone or in the presence of either natural or recombinant human interleukin-2 (IL-2) or recombinant human interferon-gamma (IFN-gamma; 1-1,000 U/ml). The cultured cells were washed on days 1, 4 or 7 and tested for various immune functions in vitro and for cell surface phenotype. IL-2, but not IFN-gamma, was found mitogenic for both PBMNC and BMMNC. The natural killer (NK) activity of both PBMNC and BMMNC was the only function tested that was markedly augmented (over 100-fold compared to medium control) by both lymphokines. Pretreatment of PBMNC with IL-2 at greater than or equal to 10 U/ml profoundly suppressed (up to 90%) various functions, such as mitogenic responses (phytohemmagglutinin, concanavalin A, pokeweed mitogen), allogeneic mixed leukocyte reaction, antibody production and T cell colony formation in agar. In contrast, some BMMNC functions were elevated at low doses of IL-2 and IFN-gamma, and significant suppression of BMMNC was seen only with high doses of IL-2 (greater than or equal to 100 U/ml) and IFN-gamma (1,000 U/ml). IL-2 was by far more effective than IFN-gamma in both the amplification of NK activity and the suppression of most of the other functions. IL-2, but not IFN-gamma, was found to activate/induce suppressor cells and increased the proportion of Leu-2+ (CD8) cells in PBMNC; the suppressive effect was time- and dose-dependent. The IL-2-induced suppression could be diminished by inclusion of anti-IL-2 antibody during the pretreatment phase. Similar suppressive effects were noted in PBMNC from AIDS patients. These findings suggest that: (a) high-dose IL-2 may elicit immunosuppression which can be mediated by nondiscriminative highly cytotoxic cells (i.e. lymphokine-activated killer cells) and/or by noncytotoxic, nonspecific suppressor cells, and (b) that PBMNC respond differently to the lymphokines than do BMMNC.
- Published
- 1988
110. Kaposi's sarcoma in the acquired immunodeficiency syndrome.
- Author
-
Mitsuyasu RT
- Subjects
- Acquired Immunodeficiency Syndrome therapy, Humans, Sarcoma, Kaposi diagnosis, Sarcoma, Kaposi therapy, Acquired Immunodeficiency Syndrome complications, Sarcoma, Kaposi etiology
- Abstract
Kaposi's sarcoma is the most common malignancy seen in association with AIDS. Although the pathogenesis of AIDS-KS has not been clearly established, the clinical course and prognosis are closely related to the patient's immune status, prior history of opportunistic infection, and hematologic status. Treatment methods include local or regional radiation therapy, cytotoxic chemotherapy, and interferon therapy. Evaluation of the results of clinical therapeutic studies in this tumor should consider its natural history and peculiar biologic behavior and associated complications of AIDS. Effective treatment strategy would take into account the immune status of the patient, the rate of progression of tumor, the presence or risk of developing life-threatening opportunistic infections, associated hematologic or neurologic abnormalities, the toxicities of treatment, and the desire of the patient for treatment. Investigations of antiviral, antiproliferative, and immunomodulating agents singly or in combination currently are in progress. Additionally innovative approaches with biologic response modifies, adjunctive hematopoietins, and growth factor modulators may lead to newer approaches to the control of this malignancy.
- Published
- 1988
111. Ganciclovir therapy for cytomegalovirus infections in recipients of bone marrow transplants and other immunosuppressed patients.
- Author
-
Winston DJ, Ho WG, Bartoni K, Holland GN, Mitsuyasu RT, Gale RP, Busuttil RW, and Champlin RE
- Subjects
- Acquired Immunodeficiency Syndrome complications, Acyclovir adverse effects, Acyclovir pharmacokinetics, Acyclovir therapeutic use, Adult, Antiviral Agents adverse effects, Antiviral Agents pharmacokinetics, Female, Ganciclovir, Humans, Immune Tolerance, Immunosuppression Therapy, Kidney Transplantation, Liver Transplantation, Male, Middle Aged, Pneumonia, Viral drug therapy, Retinitis drug therapy, Viremia drug therapy, Acyclovir analogs & derivatives, Antiviral Agents therapeutic use, Bone Marrow Transplantation, Cytomegalovirus Infections drug therapy
- Abstract
The efficacy and safety of ganciclovir were evaluated for the treatment of 39 life-threatening or sight-threatening cytomegalovirus (CMV) infections in recipients of bone marrow transplants (15 patients), recipients of liver or renal transplants (8 patients), patients with AIDS (11 patients), and one patient each with lymphoma or systemic lupus erythematosus. Twenty-eight (72%) of 39 CMV infections improved during ganciclovir therapy, which was associated with elimination of CMV from cultures. Improvement occurred more frequently in patients with viremia, fever, and wasting (8 of 8), hepatitis (3 of 4), retinitis (5 of 5), or colitis (1 of 1), than in patients with pneumonia (11 of 21). Only two of nine marrow transplant recipients with CMV pneumonia survived, as compared with nine of 12 other immunosuppressed patients with pneumonia. However, all six marrow transplant recipients who were treated for CMV viremia, fever, and wasting without pneumonia survived. Neutropenia was the only adverse reaction associated with ganciclovir therapy and was more frequent in patients with AIDS (6 [55%] of 11) than in transplant recipients (5 [20%] of 25). These results suggest that ganciclovir is of clinical benefit for immunosuppressed patients with serious CMV infections. For bone marrow transplant recipients, ganciclovir may be more effective when used prophylactically or earlier in the course of CMV infection before the development of pneumonia.
- Published
- 1988
- Full Text
- View/download PDF
112. Potential role of granulocyte-macrophage colony stimulating factor in patients with HIV infection.
- Author
-
Mitsuyasu RT and Golde DW
- Subjects
- Animals, Colony-Stimulating Factors toxicity, Drug Evaluation, Granulocyte-Macrophage Colony-Stimulating Factor, Growth Substances toxicity, Humans, Leukocyte Count drug effects, Recombinant Proteins toxicity, Acquired Immunodeficiency Syndrome drug therapy, Colony-Stimulating Factors therapeutic use, Growth Substances therapeutic use, Recombinant Proteins therapeutic use
- Abstract
Abnormalities in leukocyte number and function contribute to the high incidence of infection in patients with HIV infection. Leukopenia is a frequent occurrence in patients with AIDS and AIDS-related diseases and is a major dose limiting factor in the treatment of HIV infected individuals with antiviral compounds and chemotherapy. Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic hormone that stimulates the growth and differentiation of myeloid progenitor cells in vitro and enhances the function of mature monocytes and neutrophils. Studies on the effects of this agent in patients with AIDS, indicate that GM-CSF causes increased production of neutrophils, monocytes, and eosinophils in a dose dependent fashion. Leukocytes produced in response to GM-CSF function normally as judged by in vitro tests. The effects of GM-CSF on HIV replication and expression in vivo are uncertain. Studies of the use of GM-CSF alone and in combination with antiretroviral, antimicrobial, antineoplastic agents or other hematopoietins and cytokines will help define its ultimate clinical utility in patients with HIV infection.
- Published
- 1988
113. Transplantation of T lymphocyte depleted bone marrow to prevent graft-versus-host disease: its implications for fetal liver transplantation.
- Author
-
Champlin RE, Mitsuyasu RT, and Gale RP
- Subjects
- Adolescent, Adult, Bone Marrow Cells, Child, Female, Fetus, HLA Antigens analysis, Humans, Liver embryology, Male, Middle Aged, Pregnancy, Bone Marrow Transplantation, Graft vs Host Disease prevention & control, Leukemia, Lymphoid therapy, Leukemia, Myeloid therapy, Leukemia, Myeloid, Acute therapy, Liver Transplantation, T-Lymphocytes cytology
- Published
- 1985
114. Simultaneous occurrence of Hodgkin's disease and Kaposi's sarcoma in a patient with the acquired immune deficiency syndrome.
- Author
-
Mitsuyasu RT, Colman MF, and Sun NC
- Subjects
- Acquired Immunodeficiency Syndrome pathology, Adult, Biopsy, Humans, Lymph Nodes pathology, Male, Acquired Immunodeficiency Syndrome complications, Hodgkin Disease pathology, Neoplasms, Multiple Primary pathology, Sarcoma, Kaposi pathology, Skin Neoplasms pathology
- Abstract
Kaposi's sarcoma and Hodgkin's disease have each been associated with abnormalities in T lymphocyte function and occur with increased frequency in the immunosuppressed host. Although the association of Kaposi's sarcoma with lymphoreticular disorders has long been recognized, only sporadic cases of Hodgkin's disease have been described in patients with the acquired immune deficiency syndrome (AIDS) in contrast to the frequent occurrence of non-Hodgkin's lymphoma in these patients. The simultaneous occurrence of Kaposi's sarcoma and Hodgkin's disease in the same lymph node is described in a patient with AIDS. This case suggests an association of AIDS with both Kaposi's sarcoma and malignant lymphomas and raises the question of a common pathogenetic mechanism.
- Published
- 1986
- Full Text
- View/download PDF
115. Medical aspects of HIV spectrum disease.
- Author
-
Mitsuyasu RT
- Subjects
- Acquired Immunodeficiency Syndrome therapy, Acquired Immunodeficiency Syndrome transmission, Antiviral Agents administration & dosage, Humans, Immunity, Cellular drug effects, Vaccines, Synthetic administration & dosage, Virus Replication drug effects, Acquired Immunodeficiency Syndrome immunology, HIV immunology
- Published
- 1989
116. The enhanced potential use of recombinant alpha interferon in the treatment of AIDS-related Kaposi's sarcoma.
- Author
-
Mitsuyasu RT
- Subjects
- Humans, Interferon Type I administration & dosage, Interferon Type I pharmacology, Male, Recombinant Proteins, Sarcoma, Kaposi etiology, Acquired Immunodeficiency Syndrome complications, Interferon Type I therapeutic use, Sarcoma, Kaposi therapy
- Abstract
Alpha interferon has been extensively studied in the treatment of the epidemic form of Kaposi's sarcoma (KS) common in the acquired immunodeficiency syndrome (AIDS). Its safety and efficacy against KS have been well documented, with objective tumor responses seen in 25%-50% of cases. In a number of large uncontrolled studies, patients had a low incidence of opportunistic infections (OIs) during recombinant alpha interferon therapy. Although several factors may be involved, individuals responding to interferon have a distinct survival advantage over those not responding. Patients with better prognostic features, such as CD4 (T-4/T-helper cell)* counts greater than 200/mm3, no history of OIs, and no lymphoma-like "B" symptoms, are most likely to respond to interferon. Recent studies have identified a soluble growth factor produced by human immunodeficiency virus (HIV)-infected T-lymphocytes, which may be important in the propagation of KS cells in vitro. Studies demonstrating in vivo and in vitro HIV inhibitory effects of alpha interferon and the correlation of antiviral and antitumor responses now suggest that the antiretroviral action of this agent may be critical in the control of KS. Phase I trials of interferon alpha plus the antiretroviral drug zidovudine (azidothymidine, AZT) have shown the combination to be well-tolerated and to produce anti-KS responses at lower doses of each agent than is generally administered. Synergistic antiretroviral activity has been demonstrated with zidovudine and interferon alpha in vitro. Phase II trials of this combination currently are in progress.
- Published
- 1989
117. Heterogeneity of epidemic Kaposi's sarcoma. Implications for therapy.
- Author
-
Mitsuyasu RT, Taylor JM, Glaspy J, and Fahey JL
- Subjects
- Antigen-Antibody Complex analysis, Antigens, Differentiation, T-Lymphocyte, Antigens, Surface analysis, Humans, Immunoglobulin A analysis, Interferon Type I therapeutic use, Leukocyte Count, Lymphocyte Activation, Prognosis, Recombinant Proteins therapeutic use, Sarcoma, Kaposi etiology, Sarcoma, Kaposi therapy, T-Lymphocytes immunology, Acquired Immunodeficiency Syndrome complications, Sarcoma, Kaposi immunology
- Abstract
Kaposi's sarcoma (KS) in acquired immune deficiency syndrome (AIDS) is a new manifestation of a previously rare disease, and generally has a fatal course. Variations in the clinical course and in response to treatment by patients with this disease suggest that specific immunologic or clinical parameters may be important in the prognosis. Retrospective analyses of clinical parameters with respect to survival in 96 patients with epidemic Kaposi's sarcoma indicated that earlier tumor stage, the lack of prior opportunistic infections, and the absence of systemic symptoms correlated most closely with survival. Sixteen immune parameters were also assessed for their prognostic value. Total T4 (CD-4) cell number levels and the T4: T8 ratio correlated most closely with survival. Response to treatment with recombinant alpha interferons, while not well correlated with tumor stage, was more frequent in patients without systemic symptoms or a history or prior opportunistic infections. Treatment response was associated with a greater degree of intact T-cell function. These findings emphasize the importance of cellular immunity in the pathogenesis and subsequent course of patients with epidemic Kaposi's sarcoma, suggesting that different therapeutic strategies may be necessary to address specific prognostic subgroups.
- Published
- 1986
- Full Text
- View/download PDF
118. Infection with the human immunodeficiency virus (HIV) is associated with an in vivo increase in B lymphocyte activation and immaturity.
- Author
-
Martínez-Maza O, Crabb E, Mitsuyasu RT, Fahey JL, and Giorgi JV
- Subjects
- Antigens, Neoplasm immunology, Antigens, Surface analysis, B-Lymphocytes classification, Cell Differentiation, Humans, Immunoglobulin G biosynthesis, Immunoglobulin M biosynthesis, Lymphocyte Activation, Neprilysin, T-Lymphocytes classification, Acquired Immunodeficiency Syndrome immunology, B-Lymphocytes immunology, HIV immunology
- Abstract
The expression of phenotypic markers on B lymphocytes in patients with the acquired immune deficiency syndrome (AIDS), in human immunodeficiency virus (HIV) seropositive individuals, and in healthy seronegative donors was examined by two-color flow cytometry. Patients with AIDS and HIV-seropositive individuals showed an elevated percentage of B cells bearing an activation marker, the transferrin receptor, when compared with donors not infected with HIV. A decrease in the percentage of resting (Leu-8 positive) B cells was also seen in AIDS patients and HIV-seropositive individuals. An increased percentage of circulating, immature (CALLA-positive, CD10) B cells was seen in AIDS patients. These phenotypic changes were accompanied by an increased level of spontaneous IgG and IgM secretion, and increased cell size within the total B cell population and in some B cell subpopulations, in patients with AIDS and in HIV-seropositive people. These results demonstrate that phenotypic changes indicative of in vivo B cell activation and immaturity accompany the polyclonal production of Ig seen in HIV-infected individuals.
- Published
- 1987
119. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome.
- Author
-
Groopman JE, Mitsuyasu RT, DeLeo MJ, Oette DH, and Golde DW
- Subjects
- Acquired Immunodeficiency Syndrome therapy, Adolescent, Adult, Bone Marrow drug effects, Drug Evaluation, Humans, Interleukin-3 administration & dosage, Interleukin-3 adverse effects, Leukocyte Count, Male, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Acquired Immunodeficiency Syndrome physiopathology, Hematopoiesis drug effects, Interleukin-3 therapeutic use
- Abstract
We administered recombinant (biosynthetic) human granulocyte-macrophage colony-stimulating factor (GM-CSF) to 16 patients with the acquired immunodeficiency syndrome (AIDS) and leukopenia (2225 +/- 614 cells per microliter [mean +/- SD]). Each patient first received a single intravenous dose; 48 hours later a 14-day continuous intravenous infusion of the agent was begun. The doses used were 1.3 X 10(3) (n = 4), 2.6 X 10(3) (n = 4), 5.2 X 10(3) (n = 4), 1.0 X 10(4) (n = 3), or 2.0 X 10(4) (n = 1) U per kilogram of body weight per day. Administration of recombinant GM-CSF resulted in dose-dependent increases in circulating leukocytes and in increases in circulating neutrophils, eosinophils, and monocytes. The peak leukocyte count ranged from 4575 +/- 2397 cells per microliter at the lowest dose, to 48,700 in the patient receiving the highest dose. Mild side effects--low-grade fever, myalgia, phlebitis, and flushing--were observed in some patients; there were no life-threatening toxic reactions. Our data demonstrate that recombinant human GM-CSF is well tolerated and biologically active in leukopenic patients with AIDS. Strategies to increase the number and function of circulating leukocytes may reduce the morbidity and mortality of infections in these and other patients with leukopenia.
- Published
- 1987
- Full Text
- View/download PDF
120. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms.
- Author
-
Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV, and Chen IS
- Subjects
- Acquired Immunodeficiency Syndrome pathology, Brain pathology, Cells, Cultured, HIV isolation & purification, Humans, Lymphocyte Activation, Lymphocytes immunology, Lymphocytes microbiology, Macrophages microbiology, Monocytes microbiology, Species Specificity, Virus Replication, Acquired Immunodeficiency Syndrome microbiology, Brain microbiology
- Abstract
Human immunodeficiency virus (HIV) is the causative agent of the acquired immune deficiency syndrome (AIDS). A large number of AIDS patients show evidence of neurologic involvement, known as AIDS-related subacute encephalopathy, which has been correlated with the presence of HIV in the brain. In this study, two genetically distinct but related viruses were isolated from one patient from two different sources in the central nervous system: brain tissue and cerebrospinal fluid. Both viruses were found to replicate in peripheral blood lymphocytes, but only virus from brain tissue will efficiently infect macrophage/monocytes. The viruses also differ in their ability to infect a brain glioma explant culture. This infection of the brain-derived cells in vitro is generally nonproductive, and appears to be some form of persistent or latent infection. These results indicate that genetic variation of HIV in vivo may result in altered cell tropisms and possibly implicate strains of HIV with glial cell tropism in the pathogenesis of some neurologic disorders of AIDS.
- Published
- 1987
- Full Text
- View/download PDF
121. Trisomy 12 in Burkitt-like lymphoma associated with acquired immunodeficiency syndrome.
- Author
-
Kosmo MA, Mitsuyasu RT, Sparkes RS, and Gale RP
- Subjects
- Adult, Bone Marrow pathology, Burkitt Lymphoma complications, Burkitt Lymphoma pathology, Humans, Karyotyping, Male, Acquired Immunodeficiency Syndrome complications, Burkitt Lymphoma genetics, Chromosomes, Human, Pair 12, Trisomy
- Abstract
Cytogenetic abnormalities have been reported in lymphoproliferative disorders, the most common of which is the t(8;14) translocation in Burkitt and Burkitt-like lymphomas. We report a 30-year-old homosexual male with Burkitt-like lymphoma and trisomy 12. This patient presented with persistent generalized lymphadenopathy and subsequently developed advanced lymphoma. Cell surface markers revealed a monoclonal pattern containing mu heavy chain and kappa light chain immunoglobulins. Cytogenetic analysis of bone marrow involved with lymphoma revealed an additional chromosome #12. Mitogen-stimulated cultures of peripheral blood showed a normal 46,XY karyotype. Trisomy 12 has been found in chronic lymphocytic leukemia and in other low-grade B-cell lymphoproliferative disorders, but not in Burkitt-like lymphoma.
- Published
- 1987
- Full Text
- View/download PDF
122. Granulocyte-macrophage colony-stimulating factor enhances neutrophil function in acquired immunodeficiency syndrome patients.
- Author
-
Baldwin GC, Gasson JC, Quan SG, Fleischmann J, Weisbart R, Oette D, Mitsuyasu RT, and Golde DW
- Subjects
- Antibody-Dependent Cell Cytotoxicity drug effects, Blood, Blood Bactericidal Activity drug effects, Colony-Stimulating Factors pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor, Growth Substances pharmacology, Humans, Immunity, Cellular drug effects, Immunotherapy, In Vitro Techniques, Oxygen Consumption, Phagocytosis drug effects, Recombinant Proteins pharmacology, Staphylococcus aureus immunology, Acquired Immunodeficiency Syndrome therapy, Colony-Stimulating Factors therapeutic use, Growth Substances therapeutic use, Neutrophils immunology
- Abstract
We conducted a clinical trial of human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in leukopenic patients with acquired immunodeficiency syndrome (AIDS) and analyzed neutrophil function before, during, and after in vivo administration of rGM-CSF. Prior to GM-CSF infusion, AIDS patients' neutrophil superoxide generation and neutrophil antibody-dependent cell-mediated cytotoxicity were enhanced normally by in vitro exposure to GM-CSF. Neutrophil phagocytosis and intracellular killing of Staphylococcus aureus were also normal in the majority of these patients. Two patients, however, had discrete neutrophil functional defects: one in phagocytosis and one in intracellular killing. During the period of GM-CSF infusion, these abnormalities were corrected. The number of circulating neutrophils increased in all patients treated with GM-CSF in a dose-dependent manner. Neutrophils produced in vivo in response to GM-CSF administration functioned normally and there was evidence for neutrophil priming and activation in vivo. We conclude that GM-CSF treatment of AIDS patients leads to the production of functionally active neutrophils, suggesting therapeutic potential for GM-CSF in the treatment of patients with impaired host defense.
- Published
- 1988
- Full Text
- View/download PDF
123. AIDS-related Kaposi's sarcoma: a review of its pathogenesis and treatment.
- Author
-
Mitsuyasu RT
- Subjects
- Humans, Sarcoma, Kaposi drug therapy, Sarcoma, Kaposi radiotherapy, Acquired Immunodeficiency Syndrome complications, Sarcoma, Kaposi etiology
- Abstract
One of the most unusual manifestations of the acquired immunodeficiency syndrome is the cutaneous tumor, Kaposi's sarcoma. This rare and indolent tumor was once thought of as an interesting curiosity in Europe and Africa prior to the recognition of AIDS. Currently, however, this tumor accounts for approximately one quarter of all cases of AIDS recognized in the United States, and while not the proximate cause of death in most cases, Kaposi's sarcoma may cause severe physical and psychological morbidity in many patients. Treatment approaches must incorporate an understanding of the severe immunologic impairment in these individuals as well as their relatively poor tolerance to the myelosuppressive effects of many therapeutic agents. Treatment for Kaposi's sarcoma includes chemotherapy and radiation therapy, and more recently antiretroviral agents and immunomodulators in patients with indolent disease. Prophylactic treatment for Pneumocystis carinii pneumonia as well as nutritional and psychological support, and pain control are also important aspects of the care of these patients. This review will focus on the pathogenesis and natural history of Kaposi's sarcoma and review the treatment approaches and limitations of therapy for this tumor.
- Published
- 1988
- Full Text
- View/download PDF
124. Characterization of a distinct subgroup of high-risk persons with Kaposi's sarcoma and good prognosis who present with normal T4 cell number and T4:T8 ratio and negative HTLV-III/LAV serologic test results.
- Author
-
Afrasiabi R, Mitsuyasu RT, Nishanian P, Schwartz K, and Fahey JL
- Subjects
- Acquired Immunodeficiency Syndrome complications, Adult, Enzyme-Linked Immunosorbent Assay, Humans, Hypersensitivity, Delayed immunology, Immunoglobulins analysis, Leukocyte Count, Lymphocyte Activation, Male, Middle Aged, Prognosis, Sarcoma, Kaposi complications, T-Lymphocytes, Helper-Inducer immunology, Acquired Immunodeficiency Syndrome immunology, Antibodies, Viral analysis, HIV immunology, Sarcoma, Kaposi immunology
- Abstract
Three homosexual male patients with biopsy-proved Kaposi's sarcoma were classified as having the acquired immune deficiency syndrome (AIDS) by Centers for Disease Control criteria when first seen in 1983 and 1984. These patients, however, differed from most patients with AIDS and Kaposi's sarcoma in having normal CD4 cell numbers and normal CD4:CD8 ratio. Furthermore, these immunologic parameters remained normal for eight to 24 months of follow-up, and the disease did not progress. Results of recent testing of serum from these patients were negative for HTLV-III/LAV antibodies. The Kaposi's sarcoma was limited to skin (stage I tumors) and the patients did not have persistent lymphadenopathy, fever, night sweats, or weight loss. In contrast to AIDS, the serum immunoglobulin levels (IgG, IgA, IgM) and number of B cells that were spontaneously forming immunoglobulin were within normal range with no evidence of polyclonal activation. The lymphocyte proliferative responses to phytohemagglutinin and Candida were reduced in two of the three patients, and skin test anergy was observed in the two patients tested. These findings are not frequently encountered in other healthy, homosexually active men or in classic Kaposi's sarcoma. They may be indicative of functional T cell changes (without numerical changes) induced by factors other than HTLV-III/LAV virus, which made these homosexually active men susceptible to development of low-grade Kaposi's sarcoma lesions.
- Published
- 1986
- Full Text
- View/download PDF
125. Clinical variants and staging of Kaposi's sarcoma.
- Author
-
Mitsuyasu RT
- Subjects
- Adult, Humans, Interferon Type I therapeutic use, Male, Middle Aged, Neoplasm Staging, Sarcoma, Kaposi etiology, Sarcoma, Kaposi pathology, Sarcoma, Kaposi therapy, Skin Neoplasms pathology, Acquired Immunodeficiency Syndrome complications, Sarcoma, Kaposi classification
- Abstract
Kaposi's sarcoma (KS) in the acquired immunodeficiency syndrome (AIDS) is a new and aggressive presentation of a previously rare malignancy. Variation in the clinical course of this disease and its response to treatment suggest that clinical or immunologic parameters may be important in its prognosis. A review of the clinical staging systems for epidemic (AIDS-related) KS (EKS) suggests an improved survival with lower tumor stages, the lack of prior opportunistic infections, and the absence of systemic symptoms. In addition, retrospective analysis of 16 immune parameters for their prognostic value showed that total CD4 (T4) cell numbers and the CD4:CD8 ratio correlated most closely with survival. Response to treatment with recombinant alpha-interferon did not correlate with tumor stage, but was more frequent in patients without systemic symptoms or prior opportunistic infections. Several studies suggest that treatment response is associated with a greater degree of intact T cell function. These findings point out the importance of cellular immunity in the prognosis of patients with EKS.
- Published
- 1987
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.