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Biomedical subjects

R Ambinder

Publications and source records attributed to R Ambinder.

7 recordsLinked to original sources

Epstein-Barr virus and bone marrow transplantation.

The development of Epstein-Barr virus-associated posttransplantation lymphoproliferative disease correlates with increased viral burden in lymphocytes. Patterns of viral gene expression in tumors are complex and heterogenous. Conventional chemotherapy for postransplantation lymphoproliferative disease is sometimes associated with long-term disease-free survival. A promising new approach involves adoptive cellular immunotherapy with donor lymphocytes or T-cell lines. Allogeneic bone marrow transplantation has been successful in patients with an inherited lack of immune response to Epstein-Barr virus.

Antineoplastic Combined Chemotherapy Protocols

BMT for severe aplastic anemia using cyclosporine.

Between 1984 and 1991 24 patients with severe aplastic anemia (SAA) were transplanted with HLA identical sibling donor BM. The overall long-term survival was 79 +/- 8%. The average age was 21 years (range 4-53 years) and the median pre-transplant disease duration was 35 days (range 12-2998 days). Over one-half (15 of 24) of the patients had received > 10 units of blood product transfusions prior to BMT. The pre-transplant conditioning regimen consisted of 200 mg/kg cyclophosphamide (CY). Cyclosporine (CYA) was administered from 2 days prior to BMT and continued for 6-12 months. Two of the 24 patients failed to achieve primary engraftment (FTE). One of these patients had autologous recovery of BM function and is alive and well. Five of the 22 patients who engrafted failed to sustain engraftment (FTSE). Of these, three are alive and well following a second BMT or marrow boost. Only 1 of the 22 patients who engrafted had clinically significant (i.e. Stage II-IV) acute GVHD. No patient developed chronic GVHD. Our results indicate that BMT following a regimen consisting of CY with the continuous use of CYA in the post-transplant period is well tolerated and associated with excellent long-term survival. The high incidence of secondary graft instability (i.e. FTSE), however, suggests that future studies should focus on post-transplantation immunomodulation.

Adolescent

t(11;18)(q21;q21) is a recurrent chromosome abnormality in small lymphocytic lymphoma.

We have identified two cases of previously untreated, small lymphocytic lymphoma with extranodal involvement, which had a reciprocal translocation, t(11;18)(q21;q21), as the sole cytogenetic abnormality. These two cases are remarkably similar to two previously reported cases carrying this translocation with regard to clinical features, cytogenetic abnormality, histologic subtype, and immunophenotype. Molecular genetic analysis of these two cases revealed clonal gene rearrangement of the IGH locus but only germline configuration of the BCL2 oncogene at 18q21 when probes and conditions that usually identify BCL2 rearrangement in lymphomas were used. Lymphomas bearing an (11;18) rearrangement appear to make up a phenotypically identifiable subgroup. Identification of the genes at the translocation breakpoints will be important.

Aged

A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease.

A total of 151 unselected malignant and nonmalignant lymphoid tissue samples were surveyed by Southern blotting for the presence of Epstein-Barr virus (EBV) DNA. Eight of 28 Hodgkin's disease (HD) samples (29%) had detectable EBV DNA. Both nodular sclerosis and mixed cellularity histologic results were positive. The tumor type with the next highest frequency, 8%, was diffuse large cell lymphoma. The presence of EBV DNA in some HD biopsies suggests that EBV may be a factor in the pathogenesis of this disease. Alternatively, its presence may be secondary to the immune deficiency characteristic of HD. The clonal B-lymphocyte expansions reported in some cases of HD may result from EBV infection.

Blotting, Southern

Structural organization of human herpesvirus DNA molecules.

The herpesviruses are among the largest and most complex of all DNA viruses, and their genomes display an astonishing diversity in size, structure, and organization. In 1974, the features of large inverted repeats and structural isomerization were first discovered, and these proved to be characteristic properties of many herpesvirus genomes. Since then, research using the powerful techniques of modern molecular biology has revealed a great deal of comparative structural information about the arrangement of repetitive sequences and the location, structure, and primary nucleotide sequences of the genes for several easily assayed or abundantly expressed gene products. Extensive restriction enzyme cleavage maps and complete sets of cloned DNA fragments have been constructed for each of the five human herpesviruses, HSV-1, HSV-2, CMV, EBV, and VZV, and the entire 175,000-bp nucleotide sequence of EBV DNA has been determined. Based on these maps and reagents, the procedures of "DNA fingerprinting" and "dot hybridization" are proving useful at a clinical level for characterization of isolates and studying herpesvirus epidemiology. Strain differences, localized heterogeneity, tandem-repeat-defective genomes, and sites of cell-virus DNA homology have been described in some detail. The attention of basic researchers is now turning to equating structure with function, and rapid progress is expected in studies aimed at a better understanding of the mechanisms of viral DNA replication, maintenance of the latent state, reactivation, transformation, packaging, and regulation of the lytic cycle, etc using cloned functionally active DNA fragments, isolated intact genes and promoters, and DNA transfection and in vitro expression systems.

Base Sequence

Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections. A randomized, double-blind trial.

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Adult