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Biomedical subjects

R T Mitsuyasu

Publications and source records attributed to R T Mitsuyasu.

At least 73 records · Page 4Linked to original sources
PubMed1987

Treatment of Kaposi's sarcoma with interferon alfa-2b (Intron A).

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.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Trisomy 12 in Burkitt-like lymphoma associated with acquired immunodeficiency syndrome.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Clinical variants and staging of Kaposi's sarcoma.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Heterogeneity of epidemic Kaposi's sarcoma. Implications for therapy.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1986

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.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Simultaneous occurrence of Hodgkin's disease and Kaposi's sarcoma in a patient with the acquired immune deficiency syndrome.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Illness concerns, attitudes towards homosexuality, and social support in gay men with AIDS.

High levels of illness-related psychologic distress, marked social stigmatization and loss of social support, and negative internalized feelings towards homosexuality have previously been reported in homosexual men with the diagnosis of acquired immune deficiency syndrome (AIDS). We assessed 50 homosexual or bisexual men who were within 3 months of their AIDS diagnosis with respect to medical status, illness concerns, attitudes towards homosexuality, and social support. Subjects reported levels of illness-related concerns comparable to previously studied cancer patients. Their attitudes towards homosexuality were similar to previously studied healthy homosexual males. Their social support needs were variable, as was their satisfaction with specific types of social support. Their social networks were moderately small. In this AIDS subject group, illness concerns, attitudes toward homosexuality, and social support satisfaction were significantly correlated with each other, and with previously reported levels of psychologic distress and subjective (but not objective) measures of health status.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. A prospective, randomized, double-blind trial.

The effects of ex-vivo depletion of T lymphocytes from donor bone marrow using a monoclonal anti-T-cell antibody (CT-2) and complement on the outcome of allogeneic bone marrow transplantation was evaluated in a prospective, randomized, double-blind study of 40 patients with leukemia. Patients receiving T-cell-depleted bone marrow had a lower incidence of acute graft-versus-host disease than control patients (3 of 20 compared with 13 of 20; p = 0.004), and mortality due to acute graft-versus-host disease was reduced. Five patients in the T-cell-depletion group developed graft failure; all control patients had sustained engraftment (p less than 0.05). Clinically apparent relapse of leukemia occurred in 7 patients from the T-cell-depletion group and in 2 controls (p, not significant). Cytogenetic evidence of residual leukemia was also detected in the 5 patients with graft failure without overt relapse. Infections and overall survival were similar in the two groups. The effects of T-cell depletion on engraftment and recurrence of leukemia require further evaluation.

Actuarial Analysis↗
PubMed1986

Abnormal T-lymphocyte colonies (CFU-TL) following bone marrow transplantation.

We studied the presence of peripheral-blood- and bone-marrow-derived T-lymphocyte colony formation (CFU-TL) in 28 bone marrow transplant recipients from 1 month to six years after transplantation. Peripheral blood leukocyte and lymphocyte counts were generally normal, and all had morphologic evidence of engraftment without leukemia at the time of study. Both peripheral-blood- and bone-marrow-derived CFU-TL were markedly reduced after transplantation as compared to normal controls, which included bone marrow donors (14.2 +/- 5/4 X 10(4) vs 313 +/- 100/4 X 10(4) [p less than 0.001] and 26 +/- 4/2 X 10(5) vs 1004 +/- 60/2 X 10(5) [p less than 0.001]). Among the patients, four had no detectable bone-marrow-derived CFU-TL when tested less than six months after transplantation. Peripheral blood CFU-TL, while present in all patients, was markedly decreased for more than 12 months after transplantation. After two years, the number of CFU-TL returned to normal in several patients. The abnormalities in CFU-TL were unrelated to diagnosis, age, sex, graft-versus-host disease (GVHD), pretransplant conditioning, or posttransplant immunosuppressive treatment. Patients receiving autologous bone marrow transplants also had decreased CFU-TL. Cocultures of normal peripheral-blood- or bone-marrow-derived mononuclear cells with recipients' mononuclear cells or sera did not inhibit normal CFU-TL growth. Furthermore, the addition of mononuclear cells or sera from normal individuals, or of exogenous interleukin 1 or interleukin 2, did not correct the deficiency of CFU-TL growth by recipient cells. Depletion of T-lymphocytes from bone marrow or peripheral blood in transplant recipients by physical techniques or with a monoclonal antibody (CT-2) and complement had no effect on CFU-TL recovery. Similarly, addition of recipients' T cells to normal peripheral blood or bone marrow mononuclear cells did not suppress CFU-TL. These data indicate that most transplant recipients have a marked reduction in CFU-TL which persists for up to two years after transplantation. This reduction in the growth of T-cell colonies appears to be due to deficient numbers of these cells or an intrinsic defect in their responsiveness to T-cell lymphokines, rather than a result of growth suppression by inhibitory cells or serum factors. This observed defect in CFU-TL may have implications for therapeutic attempts to facilitate immune reconstitution after bone marrow transplantation.

Adolescent↗
PubMed1985

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.

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.

5'-Nucleotidase↗
PubMed1984

Immunologic defects in young male patients with hepatitis-associated aplastic anemia.

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.

Adolescent↗
PubMed1984

Recombinant alpha-2 interferon therapy for Kaposi's sarcoma associated with the acquired immunodeficiency syndrome.

In a randomized prospective study we tested the toxicity and efficacy of recombinant alpha-2 interferon in the treatment of Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. High doses (50 X 10(6) U/m2 body surface area, intravenously) or low doses (1 X 10(6) U/m2, subcutaneously) of recombinant alpha-2 interferon were administered to 20 patients for 5 days/wk, every other week, for four treatment cycles. Therapy was well tolerated subjectively and caused only mild hematologic and hepatic toxicity at both dose levels. No consistent or sustained changes were seen in immunologic variables during or after treatment. Six patients with Kaposi's sarcoma, four at high dose and two at low dose, had objective responses (complete or partial) to treatment. However, therapy did not appear to eradicate cytomegalovirus carriage or prevent opportunistic infections related to cytomegalovirus.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Failure of trimethoprim-sulfamethoxazole in the therapy of recurrent Pneumocystis carinii pneumonia.

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.

Child↗
PubMed1979

Detection of non-HLA antigens: effect of lymphocyte priming and amplification signals.

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.

Cytotoxicity, Immunologic↗
PubMedDate not supplied

Ganciclovir therapy for cytomegalovirus infections in recipients of bone marrow transplants and other immunosuppressed patients.

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.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Use of recombinant interferons and hematopoietic growth factors in patients infected with human immunodeficiency virus.

The recombinant cytokines are increasingly important therapeutic agents for patients with AIDS. Recombinant interferon-alpha has demonstrated antitumor and antiretroviral activities in patients with Kaposi's sarcoma. Limited studies with interferon-beta suggest that it also has antitumor effects in patients with Kaposi's sarcoma, but interferon-gamma appears to be ineffective in controlling this tumor. The hematopoietic growth factors, including erythropoietin, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been evaluated in several populations of human immunodeficiency virus (HIV)-infected individuals. The combination of G-CSF and recombinant human erythropoietin completely reversed the zidovudine-induced neutropenia of AIDS patients but was only partially effective in reversing anemia. In several clinical trials, GM-CSF induced marked increases in leukocyte counts and improved neutrophil function in some AIDS patients. In severely immunocompromised patients with disease caused by HIV who were receiving therapy with either G-CSF or GM-CSF, opportunistic infections continued to occur despite increases in circulating white blood cell counts. Recombinant cytokines may be used in the future in AIDS patients as adjunctive treatment with myelosuppressive antibiotics and chemotherapeutic drugs, as a possible means of enhancing host defense, or as agents of immune reconstitution.

Granulocyte Colony-Stimulating Factor↗