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Biomedical subjects

P E Neiman

Publications and source records attributed to P E Neiman.

At least 19 recordsLinked to original sources
PubMed1991

Induction of apoptosis during normal and neoplastic B-cell development in the bursa of Fabricius.

The lymphoid cells of embryonic bursal follicles are engaged in rapid growth and preimmune diversification of immunoglobulin genes. Disruption of follicular architecture by mechanical dispersion of these cells in short-term tissue culture was accompanied by continued cell division and extensive cell death by apoptosis. Apoptosis was suppressed in parallel cultures of intact follicles. gamma Radiation also triggered extensive apoptosis in embryonic bursal follicles within a few hours. Preneoplastic bursal stem cell populations induced by a v-myc oncogene were hypersensitive to induction of apoptosis by follicular dispersion and radiation. In contrast, tumor progression in v-myc- and v-rel-initiated bursal neoplasms was accompanied by development of resistance to induction of apoptosis. A programmed cell death pathway can be activated during normal B-cell development in the bursa, and alterations in the expression of this pathway accompany neoplastic change in this system.

Animals↗
PubMed1986

Inhibition of retroviral replication by anti-sense RNA.

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.

Animals↗
PubMed1985

Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease.

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.

Adult↗
PubMed1979

Lymphoid neoplasms in chicken flocks free of infection with exogenous avian tumor viruses.

More than 4,500 breeding female chickens of nine inbred lines maintained under specific-pathogen-free conditions to approximately 500 days of age were studied. Routine monitoring and special assays indicated that they were free of infection by exogenous viruses of the leukosis-sarcoma and the reticuloendotheliosis groups. Some birds were maintained free of Marek's disease (MD) virus infection in plastic isolators, and others were maintained in conventional chicken houses and vaccinated with the herpesvirus of turkeys to prevent the lesions of MD. Ten birds bearing lymphoid tumors were observed in two sublines of one line of chickens known to produce embryos that spontaneously produce Rous-associated virus, type 0 (RAV-O), an endogenous virus of the chicken. Four tumors were found in chickens of one subline maintained free of MD virus infection in isolators. These tumors did not involve the bursa and had some histologic features different from those typical of lymphoid leukosis. Six tumors were found in chickens of the other subline that were vaccinated to prevent MD; these tumors involved the bursa and were typical of lymphoid leukosis but not MD. These results suggest that two types of tumors may have been observed. The fact that DNA extracted from both types of tumors did not contain exogenous lymphoid leukosis virus sequences confirms the virologic evidence that exogenous viruses were not involved. The fact that endogenous viral sequences were not increased in copy number suggests that the endogenous virus RAV-O did not directly induce the tumors. Two birds with tumors not involving the bursa were found alive, and transplantable lymphoid tumors were developed. These tumors were of T-cell origin rather than of bursa cell origin as would be expected of lymphoid leukosis. These are the first reported lymphoid tumors that have been observed in the absence of known exogenous tumor virus infection in chickens. Our evidence suggests that the endogenous virus RAV-O did not play a primary role in the induction of these tumors.

Animals↗
PubMed1978

Combined modality therapy for advanced, diffuse lymphocytic and histiocytic lymphomas.

Forty-six previously untreated patients with advanced aggressive non-Hodgkin's (34 poorly differentiated and mixed diffuse, 8 histiocytic and 4 undifferentiated) were treated with a 3 phase combined modality program employing cyclophosphamide (C), hydroxyl-daunomycin (H), vincristine (O), prednisone (P), procarbazine (P) [CHOP(P)] combination chemotherapy in an initial induction phase, radiotherapy and nonmarrow toxic chemotherapy as a second consolidation phase, followed by a third phase of CHOP(P) chemotherapy for four more cycles. Long-term maintenance therapy was not given. High dose involved field radiation in phase II was limited to volumes encompasing less than 50% of the marrow bearing skeleton. The large majority of patients (82%) had such widespread involvement that this limitation precluded the use of local radiation and were treated instead with a mean of 132 rad of fractionated total body irradiation (TBI). Thirty-eight patients (83%) achieved complete remission. Twenty-nine (66%) of the 44 patients evaluable for follow-up, and 22 (61%) of the 36 patients receiving TBI, remain alive in complete remission for observation periods of up to 26 months.

Adolescent↗
PubMed1978

Prophylactic adenine arabinoside following marrow transplantation.

Interstitial pneumonia is a major cause of morbidity and mortality following allogeneic marrow transplantation for hematologic malignancy. In this prospective randomized study, 22 of 40 patients received prophylactic adenine arabinoside (Ara-A) at a dose of 5 mg/kg/day administered intravenously on an intermittent schedule. Thirteen episodes of interstitial pneumonia occurred among treated patients, including three cases associated with cytomegalovirus (CMV) in the lung. Ten episodes of interstitial pneumonia were seen in the untreated group, with CMV cultured from five. Surveillance viral cultures were positive from 18 different sites in 12 treated patients compared to 10 sites from 7 patients in the untreated group. No significant toxicity from Ara-A was encountered, and no difference in overall survival between the two groups was detected. Ara-A did not reduce the frequency of interstitial pneumonia or viral isolation from routine cultures.

Bone Marrow Transplantation↗
PubMed1977

A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts.

A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant.

Acute Disease↗
PubMed1977

One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation.

One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3-17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1-4 1/2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). Four patients are alive 1 1/2 - 3 1/2 yr after grafting but have had a relapse of their leukemia. Of 93 evaluable patients, 19 did not develop GVHD and 24 developed very mild GVHD. Fifty patients developed moderate to severe GVHD, and 40 of these were treated with antithymocyte globulin. Interstitial pneumonia occurred in 54 patients and was the primary cause of death in 34. Interstitial pneumonia often occurred in association with GVHD and the most common etiologic agent was cytomegalovirus. A total of 31 patients have had a relapse of leukemia. There was no definite correlation between relapse of leukemia and the presence or absence of GVHD. The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor.

Antilymphocyte Serum↗