Biomedical subjects
Publications and source records attributed to P E Neiman.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Infection of 18-day embryonic bursal lymphocytes with a v-myc-containing retrovirus leads directly to a polyclonal proliferation of surface immunoglobulin-positive (slg+) cells in the bursa of Fabricius detected four weeks after hatching. These v-myc-expressing bursal cells repopulate the follicles of chemically ablated bursae more efficiently than total normal 18-day embryonic bursal cells. In contrast, comparable normal bursal cells lose the ability to repopulate follicles by four weeks. Bursal lymphocytes expressing either a retroviral v-myc or a c-myc gene deregulated by adjacent retroviral integration retain the ability of embryonic bursal lymphocytes to diversify their immunoglobulin light chain genes. These results suggest that retroviral deregulation of myc expression during avian B cell development induces outgrowth of a population of cells with the cardinal phenotypic characteristics of bursal stem cells.
Previous studies have shown that the chicken lambda immunoglobulin light chain gene undergoes a single rearrangement that results in functional VJ joining of the unique variable (V lambda 1) and joining (J lambda) coding regions. The immunologic repertoire of lambda genes is created through extensive sequence diversification within the rearranged locus during B cell development in the bursa of Fabricius. This sequence diversification was detected only at the rearranged V lambda 1 segment and not within the 5' leader sequence, the J lambda segment, or the unrearranged V lambda 1 segment. The selective diversification of the rearranged V lambda 1 segment was associated with unique DNAase I-hypersensitive sites on the rearranged allele. While probes for V lambda 1 sequences detect multiple homologous V lambda segments, probes for both the 5' leader and J lambda segments fail to detect homologous sequences. Taken together, these results suggest that a highly selective process, possibly gene conversion, operates during B cell ontogeny to generate diversity within the lambda gene.
Between July 1970 and January 1985, 100 patients with malignant lymphoma were treated with high-dose chemoradiotherapy and bone marrow transplantation. Twenty-eight of the 100 are alive and the actuarial probability of disease-free survival 5 years from transplantation is 22%. The most common reason for treatment failure was disease recurrence, with an actuarial probability of 60%. A proportional hazards regression analysis showed that the likelihood of disease-free survival was less in those patients transplanted in resistant relapse and in those previously treated with chest radiotherapy. Neither disease histology (Hodgkin's disease, high-grade lymphoma or intermediate-grade lymphoma), nor source of marrow (syngeneic, allogeneic, or autologous) significantly influenced either disease-free survival or probability of relapse. The use of high-dose chemoradiotherapy and marrow transplantation appears to offer a better chance for long-term survival than any other form of therapy for young patients with disseminated malignant lymphoma whose disease has progressed after initial combination chemotherapy. The best results with marrow transplantation were obtained in patients transplanted in early relapse or second remission who had not received prior chest radiotherapy.
Explore the source record for details and available documents.
We tested the effect of anti-sense RNA on the replication of avian retroviruses in cultured cells. The replication of a recombinant retrovirus carrying a neomycin resistance gene (neor) in the anti-sense orientation was blocked when the cells expressed high steady-state levels of RNA molecules with neor in sequence in the sense was blocked when the cells expressed high steady-state levels of RNA molecules with neor sequences in the sense orientation, i.e., complementary to the viral sequence. Viral DNA bearing neor sequences was not detected specifically in host cells where this anti-sense RNA inhibition of viral replication occurred. These observations suggest that anti-sense RNA inhibition may be a useful strategy for the inhibition of retroviral infections.
Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.
A transforming gene detected by transfection of chicken B-cell lymphoma DNA has been isolated by molecular cloning. It is homologous to a conserved family of sequences present in normal chicken and human DNAs but is not related to transforming genes of acutely transforming retroviruses. The nucleotide sequence of the cloned transforming gene suggests that it encodes a protein that is partially homologous to the amino terminus of transferrin and related proteins although only about one tenth the size of transferrin.
Ninety-five patients with advanced non-Hodgkin's lymphoma were treated with four courses of cyclophosphamide, adriamycin, vincristine and prednisone, with or without procarbazine [CHOP(P)] chemotherapy; either 150 rad total body irradiation (for "extensive" disease) or 3,500 rad local radiation therapy (for "limited" disease); and a final four courses of CHOP(P) chemotherapy. Sixty-four patients had stage IV, 22 stage III, and 9 abdominal stage II disease. Histologic material was available in 80 patients for review according to the new Working Formulation: 16 had low grade, 38 intermediate grade (20 large cell, 18 diffuse small cleaved and mixed cell), and 26 high grade (12 lymphoblastic, 8 immunoblastic, 6 small noncleaved) malignancies. Complete remission was achieved in 78% of 92 evaluable patients. The remission duration curve for diffuse large cell lymphoma patients showed a plateau at 72% after 2 yr, but a pattern of continued relapse (median 3 yr) was seen in the other histologies. Multivariate analysis showed that "B" symptoms, bulky abdominal masses, and stage IV disease adversely affected survival. Overall survival by Kaplan-Meier analysis showed that 67% of diffuse small cleaved and mixed cell, 49% of large cell and immunoblastic, and 44% of lymphoblastic lymphoma patients survive 6 yr after diagnosis. When compared to reported remission duration and survival with CHOP chemotherapy alone, these data suggest a possible advantage for combined modality treatment.
Ten patients with chronic granulocytic leukaemia in the chronic phase have been treated with chemoradiotherapy followed by transplantation of bone marrow from HLA-identical siblings. Engraftment was achieved in all patients, and Philadelphia chromosome disappeared from the nine patients who had it before transplantation. Four patients have died, three with interstitial pneumonitis and one with severe graft-versus-host disease (GvHD). Six patients are alive and well in complete clinical, cytogenetic, and haematological remission, 1-3 years after transplantation, despite complications in three patients (one had interstitial pneumonitis, one had mild veno-occlusive disease of the liver, and one had severe GvHD).
A patient undergoing marrow grafting for acute lymphoblastic leukemia from his partially HLA-mismatched sister displayed a widely disseminated immunoblastic sarcoma at autopsy. The tumor was monoclonal by immunoglobulin light-chain staining. Blot hybridization analysis, using a cloned highly polymorphic locus in human DNA as a probe, showed the tumor to be of donor-cell origin. Cytogenetic analysis also demonstrated donor-cell origin. Blot hybridization analysis demonstrated Epstein-Barr virus (EBV) genomes in the tumor. By contrast, reexamination of material from a previously reported case of a donor-type relapse showed no evidence of EBV DNA. In neither case was there evidence of cytomegalovirus DNA. This study documents the association of EBV with a malignant, monoclonal B-cell lymphoma arising in a marrow graft recipient. We conclude that DNA restriction fragment length polymorphisms can be used to prove the origin (donor or host) of neoplastic relapse following allogeneic marrow grafting. Further, cell types different from those of the original leukemia may be involved.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Oncogenic avian retroviruses can be classified into three groups: sarcoma viruses, acute leukaemia viruses and lymphoid leukosis viruses (LLVs). Sarcoma and acute leukaemia viruses transform fibroblasts and/or haematopoietic cells in culture and induce tumours with short latent periods in infected birds. In contrast, LLVs do not transform cells in vitro and require long latent periods before formation of neoplasms in vivo. The most frequent neoplasm induced by LLVs is malignant lymphoma of the bursa of Fabricius, but LLVs also induce other neoplasms, including sarcomas, nephroblastomas and erythroblastosis. The genomes of both sarcoma and acute leukaemai viruses contain specific genes responsible for viral oncogenicity, whereas the genome of LLVs apparently includes only genes required for virus replication. The genetic basis for the low oncogenic potential of LLVs is therefore obscure. The present experiments indicate that LLV-induced tumours contain transforming genes that can be detected by transfection of NH 3T3 mouse cells. These transforming genes are not linked to LLV DNA sequences, suggesting that oncogenesis by LLVs may result from indirect activation of cellular transforming genes.
Explore the source record for details and available documents.
Eight recipients of marrow transplants with cytomegalovirus (CMV) pneumonia diagnosed by open lung biopsy were treated with doses of human leukocyte interferon of 2 X 10(4)--6.4 X 10(5) units/kg per day to evaluate its toxicity after marrow transplant and its effectiveness against CMV infection. All eight patients died from pneumonia, and virus was still present in lung tissue from seven patients cultured after death. Interferon doses of less than or equal to 1.6 X 10(5) units/kg per day did not affect the circulating granulocyte count. Patients treated with higher doses had a decrease in circulating granulocyte count, but study of granulocyte-macrophage colony-forming cells in culture showed no evidence of toxicity to granulocyte progenitor cells. The effect on in vitro lymphocyte function was variable. Antibody production was not impaired. Interferon was not effective against established CMV infection. However, there was less hematologic toxicity than was anticipated, and the prophylactic use of interferon after marrow transplant is feasible.
Explore the source record for details and available documents.