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Biomedical subjects

D L Longo

Publications and source records attributed to D L Longo.

At least 451 records · Page 25Linked to original sources
PubMed1984

Recombinant leukocyte A interferon: an active agent in advanced cutaneous T-cell lymphomas.

High-dose recombinant leukocyte A interferon (50 X 10(6) U/m2 body surface area, intramuscularly, three times weekly) was tested in a clinical trial involving patients with advanced cutaneous T-cell lymphomas to determine its effectiveness and toxicity. All 20 patients had advanced stages of disease refractory to two or more standard therapies. Objective partial remissions lasting 3 months to more than 25 months (median, 5 months) were documented in 9 patients. The major dose-limiting toxicity was a severe influenza-like syndrome with malaise, anorexia, depression, weight loss, and decreased performance status; this effect was reversible after dose reductions in all patients and did not recur with re-escalation of doses in 10 patients. This interferon preparation is highly effective in the treatment of advanced refractory cutaneous T-cell lymphomas, and new schedules to reduce toxicity and achieve complete responses, combined treatment with chemotherapy or serotherapy, and its use in earlier stages of disease should be investigated.

Adult↗
PubMed1984

Identification of distinct predominant epitopes recognized by myoglobin-specific T cells under the control of different Ir genes and characterization of representative T cell clones.

We characterized the fine specificity of antigen recognition of myoglobin-immune T cells from B10.D2, B10.GD, and B10.A(5R) mice. Polyclonal H-2d T cells show a predominant response to an epitope centering on Glu 109 and His 116. These residues localize a dominant epitope to one segment of the myoglobin surface, but probably are not the only amino acid residues involved. This response pattern maps genetically to I-Ad (or Kd) based on the B10.GD recombinant strain. A different epitope specificity was detected in B10.A(5R) T cells mapping to I-E beta b E alpha k or I-Cd, but no difference was detected between strains differing at the Igh locus. Thus, epitope specificity varied with Ia haplotype but not Igh allotype. Myoglobin-specific B10.D2 T cell lines were established, and five clones specific for the Glu 109, His 116 epitope were isolated; these were all restricted to I-Ad antigen-presenting cells. These clones represent the dominant specificity in the polyclonal T cell response to myoglobin and will be useful in characterizing the structure and function of T cell receptors for antigen and Ia. The differences in number and nature of T cell epitopes compared to B cell epitopes of myoglobin are discussed.

Animals↗
PubMed1984

T cell regulation of immunoglobulin class expression in the B cell response to TNP-Ficoll: characterization of the T cell responsible for preferential enhancement of the IgG2a response.

Syngeneic T cells injected into athymic nu/nu mice cause a preferential enhancement in the amount of IgG2a anti-TNP Ab produced by these mice to TNP-Ficoll. This enhancement appears to be caused by T cell effects on the IgG switching pathway. Through the use of F1----parent chimeras, the helper T cells were shown to affect TNP-Ficoll-responsive B cells in an H-2-unrestricted manner. The ability of T cells to mediate this IgG2a enhancement did not appear to be unique to any particular murine genetic background, because it was observed with T cells and nu/nu mice of C57BL/10, BALB/c, CBA/Ca, and B10.D2 strains. Priming of T cell donors with Ficoll or TNP-Ficoll did not increase the ability of splenic T cells, on a per cell basis, to enhance the IgG2a Ab response to TNP-Ficoll. The T cell population responsible for modulating the isotypic response was found to be sensitive to C-mediated cytotoxicity with both anti-Lyt-2 and anti-Lyt-1 hybridoma Ab. Although T cells from both the thymus and the spleen expressed enhancing activity, splenic T cells were more effective, on a per cell basis, than were thymocytes. The observations suggest that T cells that appear to enhance the switch to IgG2a in TNP-Ficoll-responsive B cells are not effectively primed by the antigen and interact with TNP-Ficoll-activated B cells through an H-2-unrestricted mechanism.

Animals↗
PubMed1983

Therapeutic cytapheresis in chronic lymphocytic leukemia.

The role of therapeutic reductive lymphapheresis in 59 patients with chronic lymphocytic leukemia (CLL) was reviewed. Reduction in lymphocytosis, lymphadenopathy and hepatosplenomegaly was noted in 50%-60% of the patients studied. In addition to mobilization of the lymphoid tumor load, 40% of the patients showed an improvement in their hemogram. Although apheresis-induced anemia can occur, reported complications were minimal. These studies suggest that a majority of CLL patients might benefit from therapeutic lymphapheresis.

Aged↗
PubMed1983

Cerebrospinal fluid rhinorrhea as a complication of malignant lymphoma.

A 53-year-old woman with a three-year history of recurrent stage IV diffuse aggressive lymphoma involving the nasopharynx presented with fever, chills, and the sudden onset of drainage of clear, colorless fluid from the left nostril. This woman had no history of trauma or physical activity that might increase intracranial pressure. Subarachnoid instillation of 111indium resulted in the accumulation of radioactivity in a cotton stint placed in the left nares, documenting cerebrospinal fluid rhinorrhea. Computed tomography of the head revealed bony erosion of the cribriform plate by lymphoma. Defervescence occurred in the patient 48 hours after treatment with antibiotics was begun, and systemic chemotherapy directed against the lymphoma resulted in resolution of the cerebrospinal fluid rhinorrhea within a month without surgical intervention.

Cerebrospinal Fluid Rhinorrhea↗
PubMed1983

Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy.

A new treatment program was developed in an attempt to increase the complete remission rate and survival of previously untreated patients with advanced stages of diffuse aggressive lymphomas. A flexible number of cycles of ProMACE chemotherapy (prednisone, methotrexate, doxorubicin, cyclophosphamide, and epipodophyllotoxin VP-16) was alternated with a flexible number of cycles of MOPP chemotherapy (mechlorethamine, vincristine sulfate, procarbazine, and prednisone), and finally late intensification with ProMACE therapy was given. The duration of each phase of treatment was determined by the patient's rate of tumor response. Complete remissions were achieved in 55 of 74 patients (74%) with a median duration of follow-up exceeding 2 1/2 years. Only ten of the complete responders (18%) have had relapse. The dose-limiting toxicity is myelosuppression, and eight patients (10%) died from sepsis. Median survival for all patients has not been reached but is predicted to exceed 4 years with 65% of patients alive at 4 years. Previously we achieved a 46% complete remission rate with 38% of all patients alive at 4 years; relapse-free survival beyond 2 years was tantamount to cure. Therefore, ProMACE-MOPP chemotherapy represents a substantial improvement in treating patients with diffuse aggressive lymphomas.

Adolescent↗
PubMed1983

The relationship between immune interferon production and proliferation in antigen-specific, MHC-restricted T cell lines and clones.

The release of immune or gamma interferon (IFN-gamma) by major histocompatibility complex (MHC)-restricted pigeon cytochrome c-specific Lyt 1+2-, interleukin 2 (IL 2)-producing proliferative T cell clones when cultured with antigen and antigen-presenting cells (APC) is a sensitive measure of the state of activation of the cell. In general, the fine specificity of T cell activation was similar when activation was measured either by IFN-gamma production or by proliferation. In response to antigen and the correct Ia molecule, the T cell clones produced both high titered IFN-gamma and a strong proliferative response. However, IFN-gamma production and the degree of proliferation of the T cell clones differed at high antigen concentrations. As antigen concentration increased, the magnitude of proliferation became submaximal whereas the IFN-gamma response became maximal suggesting that IFN-gamma produced by the cells might act as an autoregulatory molecule inhibiting the proliferative response. Stimulating the T cell to divide via its IL 2 receptor by adding exogenous IL 2 produced high levels of proliferation but only low titers of IFN-gamma activity. In addition, irradiation of the clone eliminated the IFN-gamma release induced by IL 2 but did not affect the IFN-gamma release induced by antigen and Ia. Thus proliferation is not essential for IFN-gamma production and unlike antigen and Ia, IL 2 functions predominantly as a proliferative signal and not as a signal for factor release. Two T cell clones showed a dissociation of IFN-gamma production and proliferation. In one case, a clone that proliferated in response to both allogeneic and antigenic stimuli released IFN-gamma in response to antigen but failed to produce IFN-gamma in response to the allogeneic stimulus. A second clone that showed a strong proliferative response to pigeon cytochrome c but no proliferative response to a species variant of cytochrome c, tobacco hornworm moth (THWM) cytochrome c, produced IFN-gamma when stimulated with either of these antigens. Thus, the sensitivity of detecting activation of T cell clones as measured by the release of an individual lymphokine varies from one clone to another.

Animals↗
PubMed1983

The human T-cell leukemia/lymphoma virus associated with American adult T-cell leukemia/lymphoma.

The human T-cell leukemia/lymphoma virus (HTLV) is a novel type-C retrovirus isolated from patients with T-lymphoproliferative malignancies. Thirteen cases of HTLV-associated malignancy from US centers were studied in detail. Ten of these cases share common clinical features and define a typical virus-associated adult T-cell leukemia/lymphoma (ATL). All ten patients presented with Ann Arbor stage IV lymphoma because of skin involvement, bone marrow involvement, or lymphomatous leptomeningitis. Lymphadenopathy occurred in 7 of 10 patients at presentation, and the malignant cells were cytologically pleomorphic. Leukemia occurred in 60% of the patients at presentation. Hypercalcemia was found initially in two-thirds of the patients, with lytic bone lesions or positive bone scans in 7 of 10. Complete remission occurred in 40%, but all have relapsed. These cases closely resemble those virus-positive cases of adult T-cell leukemia/lymphoma (ATL) reported from Japan and the Caribbean. Three additional virus-positive patients had atypical presentations and diagnoses (acute lymphocytic leukemia, Sézary's syndrome, leukemic reticuloendotheliosis), usually with less aggressive clinical courses and atypical demographic and laboratory features. Presence of HTLV serum antibodies in cases of ATL (with hypercalcemia and circulating malignant cells) appears to define a distinct clinicopathologic entity that may occur in geographic clusters.

Adult↗
PubMed1983

Early appearance of donor-type antigen-presenting cells in the thymuses of 1200 R radiation-induced bone marrow chimeras correlates with self-recognition of donor I region gene products.

The thymus exerts a potent influence on the development of I region self-recognition and antigen recognition by T cells. The mechanism by which the thymus acts on nascent T cells is unknown. It is assumed, however, that a cell interaction between the developing T cell and an la antigen-bearing cell in the thymus is involved. There are several candidates for the critical thymic cell; thymic epithelial, nurse, and antigen-presenting cells (APC) or dendritic cells. Because thymic epithelial cells derive from the third pharyngeal pouch and thymic APC derive from bone marrow, radiation-induced bone marrow chimeras allow the artificial creation of a chimeric thymus gland in which thymic epithelial cells and APC can be genetically different. We made radiation-induced bone marrow chimeras (F1 leads to P) using supralethal radiation doses (1200 R) and found bone marrow donor- (F1) type APC in the thymuses 3 wk after radiation. When such mice fully reconstitute their immune systems, their T cells behave as donor F1 phenotype T cells. Thus, the I region self-restriction and antigen-recognition repertoire of the T cells correlates with the genotype of the bone marrow-derived thymic APC, not the thymic epithelial cell.

Animals↗
PubMed1983

Ovarian cancer: epidemiology, diagnosis, and management.

Ovarian cancer is a common malignancy for which no widely effective prevention or early detection strategies are known. It is one of the most responsive of adult solid tumors, however, and patients can be cured by appropriately applied regimens of surgery, radiation, and chemotherapy. Expertise is required to select and coordinate the appropriate combinations. Therapeutic trials are underway at various centers, including the Medicine Branch of the NCI, to develop new treatment strategies and refine existing modalities.

Cystadenocarcinoma↗
PubMed1982

B lymphocyte immune response gene phenotype is genetically determined.

We examined the effects of the developmental milieu on the capacity of B cells to undergo immune response gene-controlled, T cell-dependent polyclonal proliferation. Although I-Aq poly(Glu60 Ala30 Tyr10)n (GAT)-nonresponder T cells developing in a responder environment become phenotypic GAT-responders, I-Aq B cells remain unresponsive to GAT, even after maturation in a GAT-responder animal. Conversely, (B10.A x B10.Q)F1 ([GAT responder x GAT nonresponder]F1) T cells developing in a B10.Q GAT nonresponder host fail to respond to GAT, but F1 B cells from the same F1 leads to parent chimeras make excellent proliferative responses in the presence of GAT and responder T cells. Thus, by this assay, B cell immune response gene function is genetically determined and is not affected by the developmental milieu.

Animals↗
PubMed1982

The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c.

The activation of proliferative T lymphocytes normally involves the simultaneous recognition of a particular foreign antigen and a particular Ia molecule on the surface of antigen-presenting cells, the phenomenon of major histocompatibility complex (MHC) restriction. An analysis of T cell clones specific for pigeon cytochrome c, from B10.A and B10.S(9R) strains of mice, revealed the unusual finding that several of the clones could respond to antigen in association with Ia molecules from either strain. Using these cross-reactive clones, we performed experiments which demonstrated that both the Ia molecule and the T cell receptor contribute to the specificity of antigen recognition; however, MHC-linked low responsiveness to tuna cytochrome c (an immune response gene defect) could not be attributed solely to the efficacy with which the Ia molecules associated with the antigen. These results imply that antigen and Ia molecules are not recognized independently, but must interact at least during the process of T cell activation.

Animals↗
PubMed1982

EOE-13 in the detection of hepatosplenic lymphoma.

Thirty-nine patients with lymphoma were evaluated prospectively to determine the usefulness of Ethiodol-Oil-Emulsion-13 (EOE-13) in the detection of hepatosplenic lymphoma by computed tomography. The detection rate in the spleen increased from 8% (before EOE-13 infusion) to 92% (after EOE-13 infusion). In ten of 39 patients (25%) in this series, lymphomatous disease was recognized only on the postinfusion computed tomographic scan. The postinfusion EOE-13 study demonstrated additional visceral abnormalities in 38% of the patients. The potential usefulness, limitations, and toxicity of this hepatosplenic-specific imaging agent are discussed.

Ethiodized Oil↗
PubMed1982

The specificity of the syngeneic mixed leukocyte response, a primary anti-I region T cell proliferative response, is determined intrathymically.

In previous studies, the syngeneic MLR of peripheral T cells was shown to be predominantly an I region-restricted function. In this report we show that adult thymocytes are also capable of responding to syngeneic irradiated stimulator cells in a syngeneic MLR, provided that TCGF is added to the culture system. Using this assay, it was possible for the first time to examine the pattern of I region restriction within the thymus itself. Analysis of the thymocyte syngeneic MLR in thymuses from radiation-induced bone marrow chimeras demonstrated that the MHC preference seen in the peripheral T cell population also existed in cells resident within the thymus. Experiments utilizing congenitally athymic mice transplanted with allogeneic thymic grafts demonstrated that both peripheral T cells and thymocytes from such animals displayed a strong preferential proliferation toward stimulator cells bearing thymic-type MHC determinants. The results in the nude model thus demonstrate that the thymus by itself is sufficient to impart such restriction specificity on a developing T cell repertoire. These results are consistent with the notion that the thymus exerts selective pressure on maturing T cell populations that results in a skewing of the T cell repertoire toward the recognition of thymic-type I region products, and that this MHC preference exists before expansion of T cells in the periphery.

Animals↗