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Biomedical subjects

D W Hanto

Publications and source records attributed to D W Hanto.

71 records · Page 4Linked to original sources
PubMed1984

CT of abdominal lymphoma after renal transplantation.

Six patients aged 33-68 years developed posttransplant lymphoma of the abdomen an average of 105 months after successful renal transplantation. On computed tomography (CT), five lymphomas presented as bulky masses in intra- (four) or retroperitoneal (one) location. Infiltrative growth into transplanted kidney (three), colon (two), and retroperitoneum (one) resulted in poorly defined margins on CT. Central areas of lower attenuation presumably reflected tumor necrosis. Metastatic deposits in liver (two) and renal transplant (one) were of a focal nature. Prompt radiologic recognition of this serious late complication of renal transplantation is crucial.

Abdominal Neoplasms↗
PubMed1983

Epstein-Barr virus (EBV) induced polyclonal and monoclonal B-cell lymphoproliferative diseases occurring after renal transplantation. Clinical, pathologic, and virologic findings and implications for therapy.

Nineteen renal allograft recipients developed B-cell lymphoproliferative diseases. Clinically there were two groups: a) young patients (mean age, 23 years) who presented soon (mean, 9 months) after transplantation or antirejection therapy with fever, pharyngitis, and lymphadenopathy resembling infectious mononucleosis, and b) older patients (mean age, 48 years) who presented later (mean, 6 years) after transplantation with localized tumor masses. Histologically, the diseases were classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic B-cell lymphoma (PBL). Immunologic cell typing revealed either polyclonal or monoclonal B-cell proliferations. Malignant transformation of polyclonal proliferations in two patients was suggested by the finding of clonal cytogenetic abnormalities. Epstein-Barr virus (EBV) specific serology, staining of biopsy specimens for the Epstein-Barr nuclear antigen, and EBV DNA molecular hybridization studies implicated EBV as the cause of both PDBH and PBL. Acyclovir, an antiviral agent that blocks EBV replication in vitro, inhibited oropharyngeal shedding of EBV and caused complete remission in four patients with polyclonal B-cell proliferations. The monoclonal tumors were acyclovir resistant. We suggest that surgical treatment, radiotherapy, or chemotherapy may be more appropriate therapy in selected patients with acyclovir resistant tumors. Therapeutic decisions require not only documentation of the viral etiology of these tumors, but also immunologic and cytogenetic analysis to determine the stage of tumor evolution in individual patients.

Adolescent↗
PubMed1983

Lymphoma after organ transplantation: radiologic manifestations in the central nervous system, thorax, and abdomen.

The radiographic findings of post-transplantation lymphoma in 15 patients are demonstrated. Variations in patterns from those of lymphomas in nonimmunosuppressed patients, etiologic factors, histologic features, and differential diagnosis are discussed. The common finding of central lucency of masses seen on CT scans correlated with necrosis seen at histologic examination. In the post-transplant patient, single or multiple masses, particularly if centrally lucent, should suggest post-transplantation lymphoma. Histologic proof with anatomic localization is important, however, to determine appropriate therapy.

Abdominal Neoplasms↗
PubMed1983

The migration of activated murine T lymphocytes in vitro. II. Evidence for differential locomotion of T cell subsets.

Lymphocytes that were activated by various means (recovered from an in vivo allograft site, sensitized in mixed lymphocyte culture, or stimulated by Con A in vitro), were extremely motile in vitro when compared to unsensitized lymph node lymphocytes. Allosensitized lymphocytes generated in vitro and in vivo (harvested on days of peak cell-mediated cytotoxicity) were more motile than Con A-activated lymphocytes (harvested on the day of peak thymidine incorporation). Protein (bovine serum albumin, normal mouse serum, or alpha-casein) was chemokinetic for all of the lymphocyte preparations, especially those activated by alloantigen or Con A. When these bulk populations were used, no evidence was found to suggest these materials were chemotactic for activated lymphocytes; the various proteins promoted comparable chemokinetic effects. Treatment of allosensitized lymphocytes generated in vitro with Lyt-2 antisera and complement significantly reduced cell-mediated cytotoxicity, but had no effect on random motility. Conversely, treatment with anti-Lyt-1 antisera and complement impaired the motility of the residual cell population in response to chemokinetic normal mouse serum or alpha-casein. Within the bulk population of lymphocytes allosensitized in vitro, the cells that migrate most quickly are predominantly Thy-1.2, Lyt-1+2-, are not as cytotoxic, and do not incorporate thymidine as actively as the unseparated population. These experiments indicate that subpopulations of lymphocytes demonstrate locomotor heterogeneity. Studies designed to determine if a specific lymphocyte population can manifest directional motility (i.e., chemotaxis) will require the use of various antigen-sensitized lymphocyte clones at defined stages of the cell cycle.

Animals↗
PubMed1983

Cyclosporine suppression of lymphocyte recruitment, regional blood flow, and vascular permeability at sites of allogeneic cellular interactions.

Although cyclosporine (CsA) has been thought to act primarily on the afferent phase of the immune response, we can demonstrate that it also acts at the efferent phase. The effect of CsA on lymphocyte recruitment (LR), regional blood flow (RBF), and vascular permeability (VP) was studied in paired, healed, subcutaneously placed urethane sponge grafts inoculated with specifically sensitized lymphocytes (SSLs) and allogeneic target cells. Intravenous injection of 111In-labelled unsensitized lymphocytes, 86RbCl and 125I-labelled albumin were used to assess LR, RBF, and VP, respectively. Suspensions of SSL and targets in CsA at 10 and 1 microgram/ml prior to graft inoculation markedly reduce the preferential increase in LR to the site of interaction between SSLs and targets bearing the sensitizing alloantigen (P less than 0.002 for both). Similarly, CsA blocks the preferential increase in RBF (P = 0.017) and VP (P less than 0.002) to the graft site. These effects persist for at least 24 hours. If SSLs and targets are washed after incubation with CsA, LR is still reduced. These results are consistent with the idea that cell-bound CsA blocks the elaboration of lymphokines which results from the interaction between SSLs and specific alloantigen in vivo. These lymphokines increase RBF and VP and are accompanied by an increase in LR. Inhibition of these vascular effects may prevent the recruitment of additional lymphocytes to the graft site. CsA may, therefore, prevent or interrupt allograft rejection by blocking amplification of the rejection mechanism at the graft site.

Animals↗
PubMed1982

Recruitment of unsensitized circulating lymphocytes to sites of allogeneic cellular interactions.

The recruitment of indium-111-labeled unsensitized lymphocytes (ULs) from the circulation into healed subcutaneous urethane sponge implants inoculated with specifically sensitized T lymphocytes (SSLs) and allogeneic target cells was studied in mice. Intravenously injected ULs were preferentially recruited to the site of specific effector-target interaction. Preferential recruitment was demonstrable within 1 hr of i.v. injection and was maximal at 4 hr. The recruitment of ULs was proportional to the number of SSLs or targets injected into the sponge. Effector cells capable of mediating the recruitment of ULs when presented with the sensitizing alloantigenic cells are detectable early in mixed lymphocyte culture (MLC) prior to the development of strong cytotoxicity. Furthermore, effector cells can be generated in MLC between H-2 identical but Mls-disparate strains in which a proliferative response occurs, but few cytotoxic cells develop. Depletion of Lyt-2+ cells from day 5 MLC abrogates cytotoxicity, but the capacity of the remaining cells to mediate recruitment is not changed. In contrast, depletion of Lyt-1+ cells does not alter cytotoxicity, but significantly reduces recruitment mediated by the remaining sensitized cells. These results suggest that recruitment of circulating lymphocytes to the site of an allograft response is mediated by an immunologicaly specific interaction between SSLs and alloantigen. These SSLs may be proliferating noncytotoxic lymphocytes or cytotoxic T lymphocytes. The capacity of a specific immune interaction at the allograft site to recruit circulating lymphocytes may be a rapid and potentially important mechanism of immune amplification in allograft rejection.

Animals↗
PubMed1982

Lymphocyte recruitment, regional blood flow, and vascular permeability at sites of allogeneic cellular interactions.

The mechanisms responsible for the accumulation of lymphocytes in rejecting allografts may involve lymphokine-mediated changes in blood flow and vascular permeability. Changes in lymphocyte recruitment (LR), regional blood flow (RBF), and vascular permeability (VP) were studied in paired healed subcutaneous urethane sponge grafts inoculated with specifically sensitized lymphocytes (SSL) and allogeneic target cells. Intravenous injection of Indium-111-labeled unsensitized lymphocytes (UL), rubidium-86-chloride, and Iodine-125-labeled albumin was used to assess LR, RBF, and VP, respectively. An increase in LR (p less than 0.001), RBF (p less than 0.001), and VP (p less than 0.001) could be demonstrated at the site of interaction between specifically sensitized lymphocytes and targets bearing the sensitizing alloantigen. Lymphocyte recruitment, blood flow, and vascular permeability indexes were all elevated within 4 hr after graft inoculation, peaked at 8 hr, and declined at approximately the same rate over the subsequent 24 hr. RBF returned to baseline levels by 24 hr, whereas LR and VP remained elevated. Suspension of SSL and targets in dexamethasone acetate (1 x 10(-5) M) before graft inoculation completely inhibited the early increase in RBF, but only incompletely blocked LR and VP. At 24 hr, however, VP was almost totally inhibited and LR remained elevated. These results are consistent with the idea that the interaction between SSL and specific alloantigen in vivo leads to the rapid elaboration of lymphokines, which increases RBF and VP, in addition to the accumulation of circulating unsensitized cells. These vascular effects could partly be responsible for the heterogeneity and nonspecificity of the cellular infiltrate in rejecting allografts. Specific enrichment of the graft infiltrate with sensitized cells would require that other mechanisms be operative.

Animals↗
PubMed1981

The Epstein-Barr virus in the pathogenesis of posttransplant lymphoproliferative disorders. Clinical, pathologic, and virologic correlation.

Twelve renal transplant patients with lymphoproliferative disorders (LPDs) were studied. Two clinical patterns were identified: (1) Young patients present with an infectious mononucleosis-like illness with fever, sore throat, and lymphadenopathy soon after transplantation or antirejection therapy. Many organs are ultimately involved, and the clinical course is one of a rapidly fatal LPD. (2) Older patients present a longer time after transplantation with symptoms of solid tumors involving the central nervous system, oropharynx, liver, or small bowel. The clinical course is slower, but it is progressive and fatal. Morphologically these LPDs can all be classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic diffuse B-cell lymphoma (PBL). Cell marker studies in four patients demonstrated a polyclonal B-cell proliferation. Transition from a polyclonal B-cell proliferation to a monoclonal tumor may occur. Epstein-Barr virus (EBV) specific antibody titers, anticomplement immunofluorescence staining of tumors for the presence of the Epstein-Barr nuclear antigen (EBNA), and EBV complementary ribonucleic acid (cRNA)/deoxyribonucleic acid (DNA) hybridization and vDNA/DNA reassociation analysis implicate EBV as the probable etiologic agent in these disorders. Successful management of these lethal LPDs may depend on discontinuation of immunosuppression and removal of the allograft. Antiviral therapy, however, may prove to be useful.

Adolescent↗
PubMed1981

Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus.

Six renal transplant recipients with abnormal lymphoproliferative disorders were studied in an attempt to define their clinical features and the role of Epstein-Barr virus (EBV) in their pathogenesis. Patients were either teenage (three) or in the sixth decade (three). The younger patients presented an average of 3 months after transplantation with fever, sore throat, and lymphadenopathy; had been markedly immunosuppressed; frequently had preceding or concomitant cytomegalovirus infections; and two of three had a rapidly fatal course. The older patients presented an average of 5 years after transplantation while on maintenance immunosuppressive drugs; in two of three cases with an oropharyngeal tumor; and had a more indolent, but frequently fatal, clinical course. The most frequent sites of biopsy-proven involvement in these patients were lymph nodes (three), the oropharynx (three), liver (three), bone marrow (three), transplanted kidney (three), colon (two), and central nervous system (two). EBV-specific antibody titers including anti-viral capsid antigen IgG, anti-viral capsid antigen IgM, anti-early antigen, and anti-Epstein-Barr nuclear antigen were serially measured in all patients. Four patients demonstrated serological evidence of a primary (one) or reactivation (three) EBV infection. No patient had significant changes in anti-early antigen or anti-Epstein-Barr nuclear antigen titers. All three patients tested for oropharyngeal shedding of EBV were positive. A touch imprint of one tumor was stained for the presence of Epstein-Barr nuclear antigen, and a majority of cells were positive. EBV complementary RNA/DNA filter hybridization and/or viral DNA/DNA reassociation analysis performed on tumor biopsy specimens in five patients demonstrated multiple EBV genome equivalents per cell in all eight specimens tested. Clinical, pathological, serological, and molecular hybridization studies provide substantial evidence that EBV was the cause of these lymphoproliferative disorders occurring after renal transplantation. Impaired host defenses allow the EBV-transformed B-lymphocytes to escape normal control mechanisms. This impairment is invariable and influenced by many factors resulting in the observed spectrum of disease. Cytogenetic changes, however, may also be important.

Adolescent↗
PubMed1981

Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients.

The lymphoproliferative processes that developed in five renal transplant recipients were studied in an attempt to characterize and classify them morphologically. Nine surgical specimens, hematological material on all patients, and autopsy specimens from three patients were available. Studies performed included: conventional histopathology; evaluation of cell markers (immunoglobulins and sheep erythrocyte, complement, and Fc receptors) and cytoplasmic immunoglobulins (peroxidase-antiperoxidase technique); ultrastructural examination; and karyotype analysis. The lymphoid lesions in our patients shared marked cytological polymorphism (small and large cells, of both follicular center and "medullary" type) and polyclonal B-cell features, which indicated a common reactive nonneoplastic origin. However, other features, such as morphological atypia of the immunoblasts, extensive necrosis, chromosomal aberrations, and an incipient monoclonal component suggested the development of lymphoma in some of these lesions. In contradistinction, the abundance of typical immunoblasts was a feature that seemed to correlate with the clinical activity of the disease rather than with the biological malignancy. The multiplicity of B-cell types and the presence of a follicular center cell component with diffuse distribution, as well as the extensive necrosis in the malignant forms, seem to differentiate morphologically the lymphoproliferative processes arising in transplant recipients from both the hyperplasias and the lymphomas developing in immunologically normal hosts. For the former, we propose the terms of "polymorphic diffuse B-cell hyperplasias" and "polymorphic B-cell lymphomas."

Adolescent↗
PubMedDate not supplied

Blood component use in orthotopic liver transplantation.

Blood component use during orthotopic liver transplantation (OLT) was evaluated after an initial 23-month experience with 37 consecutive transplant procedures. Blood component support of OLTs in 24 adult and 13 pediatric patients was reviewed. Adult procedures required intraoperatively a mean of 24.5 units of red cells (RBCs), 38.7 units of fresh-frozen plasma (FFP), 26.1 random-donor platelets (RDP), and 12.2 units of cryoprecipitate (Cryo); pediatric procedures required 4.8 units of RBCs, 5.8 of FFP, 3.9 of RDP, and 1.2 of Cryo. RBC salvage constituted 17 percent of the RBCs transfused intraoperatively. Intraoperative support in adult and pediatric OLT patients accounted for the majority of the total components required for the entire hospital stay. OLT blood component use constituted 1.3, 7.0, 3.6, and 8.1 percent of hospital-wide use of RBC, FFP, RDP, and Cryo, respectively, during the period of the study.

Adolescent↗