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Biomedical subjects

H Rosenbaum

Publications and source records attributed to H Rosenbaum.

At least 37 records · Page 2Linked to original sources
PubMed1990

In vitro studies of erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes.

Erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring the in vitro response of primitive (BFU-E) and relatively mature (CFU-E) erythroid progenitors from 12 patients and from eight healthy donors to recombinant human erythropoietin (rhEPO), and by quantifying relationships between circulating EPO levels and progenitor cell frequencies in MDS marrow. Half-maximal growth of MDS CFU-E and BFU-E was detected at a 4-fold higher rhEPO concentration than required by control erythroid progenitors. Nine of the patients evaluated exhibited maximal growth of erythroid colonies at 5- to 20-fold higher than control saturating rhEPO concentrations. Circulating EPO levels in MDS patients were elevated, with a mean value approximately 35-fold higher than that of controls. The frequency of MDS marrow CFU-E and BFU-E was 57 +/- 42% and 18 +/- 9% of the mean control values, respectively. Correlation analysis of the relationships between MDS EPO levels and erythroid progenitors indicated that the anemia in MDS is not attributable to an abnormality in the capacity of EPO to induce the generation of CFU-E, but may be influenced by the BFU-E population, whose severe deficiency results in insufficient influx of EPO-responsive cells. Our findings therefore suggest that treatment of MDS patients with rhEPO may be of limited benefit, since the generation of BFU-E from more primitive ancestors and the initial growth requirements of these cells are not under the regulatory influence of this hormone.

Adolescent↗
PubMed1989

Lymphoid neoplasia and the control of haemopoietic differentiation.

Our broad aims are to delineate oncogenic events in lymphoid neoplasia and to search for genes that control haemopoietic differentiation. To explore lymphoid neoplasia, we have constructed transgenic mice bearing different oncogenes coupled to the immunoglobulin heavy chain enhancer (E mu), to force expression within lymphocytes. The prototype E mu-myc mice are highly prone to lymphomagenesis, generating pre-B and B cell lymphomas. In their pre-neoplastic phase, E mu-myc expression perturbs B cell development, accelerating the accumulation of pre-B cells. Lymphomagenesis requires additional oncogenic events, such as ras activation, and can be reconstructed in vitro. Transgenic mice bearing the N-myc, N-ras, v-abl and bcr-v-abl oncogenes are also prone to tumours. A striking demonstration that oncogenes can perturb lineage commitment has emerged. Introduction of the v-raf gene into cloned E mu-myc transgenic B cells frequently led to a switch in haemopoietic lineage: the cells became macrophages. Two clues to this remarkable metamorphosis are that the macrophage lines produce a myeloid growth factor and most bear marked karyotypic alterations, perhaps indicating that the balance between a few critical lineage control genes has been disturbed. To explore the hypothesis that genes encoding the DNA-binding homeo box domain participate in haemopoiesis, cDNA libraries from haemopoietic sources were screened, and several distinct homeo box cDNAs were isolated. They revealed a complex pattern of expression among haemopoietic cell lines. These genes are attractive candidates for regulators of haemopoietic differentiation.

Animals↗
PubMed1989

N-myc transgene promotes B lymphoid proliferation, elicits lymphomas and reveals cross-regulation with c-myc.

To assess the impact of constitutive N-myc expression on lymphocytes, we generated lines of transgenic mice bearing the murine N-myc oncogene coupled to the immunoglobulin heavy chain enhancer (E mu). As in mice carrying an analogous c-myc construct, E mu-N-myc mice exhibit a limited overgrowth of cycling pre-B cells and eventually succumb to clonal B lymphoid tumours. The endogenous N-myc and c-myc alleles are silent in both E mu-N-myc and E mu-myc lymphomas, suggesting that these genes are subject to auto- and cross-regulation. The regulatory interaction and the similar biological effects of N-myc and c-myc imply that the two genes perform interchangeable functions in the promotion of cell proliferation.

Animals↗
PubMed1989

The transgenic window on lymphoid malignancy.

Transgenic mice bearing an oncogene targetted for expression in a specific tissue can reveal how that oncogene influences differentiation and help to delineate the pathways to malignancy. To explore lymphoid neoplasia, we have made strains of transgenic mice bearing different oncogenes driven by the immunoglobulin heavy chain enhancer (E mu), which promotes expression within lymphocytes and certain myeloid cells. The prototype E mu-myc mice succumb to pre-B and B cell lymphomas, following a preneoplastic phase in which cycling pre-B cells are overproduced. The similar fate of E mu-N-myc mice suggests that N-myc and myc have overlapping functions. Surprisingly, E mu-N-ras mice develop T lymphomas and macrophage tumours but no B lineage tumours; thus the ability of ras to initiate tumorigenesis may be lineage specific. Similarly, the high predisposition of E mu-v-abl mice to develop plasmacytomas may indicate that v-abl is oncogenic only at certain stages of B cell maturation. The bcl-2 gene promotes cell survival rather than proliferation, and E mu-bcl-2 mice produce copious resting B lymphocytes. The random onset and monoclonality of tumours in the transgenic strains argues for spontaneous genetic alterations that cooperate with the trans-oncogene. Indeed, most plasmacytomas of E mu-v-abl mice bear spontaneous myc rearrangements. Moreover, a minority of E mu-myc B lymphomas exhibit ras mutation, and the tumorigenesis can be reconstructed by crossing E mu-myc and E mu-ras mice, or by retroviral delivery of v-ras or v-raf, either in vitro or in vivo. To access novel cooperating oncogenes, we are using a retrovirus lacking an oncogene as an insertional mutagen. This approach should be applicable to any trans-oncogenic strain and help to delineate the genetic events that trigger malignant clones.

Animals↗
PubMed1988

Organ doses from radionuclides on the ground. Part I. Simple time dependences.

Organ dose equivalents of mathematical, anthropomorphical phantoms ADAM and EVA for photon exposures from plane sources on the ground have been calculated by Monte Carlo photon transport codes and tabulated in this article. The calculation takes into account the air-ground interface and a typical surface roughness, the energy and angular dependence of the photon fluence impinging on the phantom and the time dependence of the contributions from daughter nuclides. Results are up to 35% higher than data reported in the literature for important radionuclides. This manuscript deals with radionuclides, for which the time dependence of dose equivalent rates and dose equivalents may be approximated by a simple exponential. A companion manuscript treats radionuclides with non-trivial time dependences.

Female↗
PubMed1988

Organ doses from radionuclides on the ground. Part II. Non-trivial time dependences.

Organ dose equivalent rates and cumulative organ dose equivalents for photon exposures from plane sources on the ground have been calculated for 159 radionuclides, which can be expected to be released in relevant quantities during accidents in nuclear reactors or reprocessing plants. For 45 of these radionuclides, the contributions of daughter nuclides induce a dependence of the dose equivalents on time, which is not approximated accurately enough by the method proposed for the other radionuclides in a companion article. Results are presented in tables which allow easy reference for radiological calculations.

Accidents↗
PubMed1986

Autoimmune hemolytic anemia due to monoclonal IgM lambda anti-Tja (Anti-P+1+Pk).

A patient with autoimmune hemolytic anemia of the cold antibody type is described. The monoclonal autoantibody had mu heavy and lambda light chains and Tja blood group specificity. The antibody resulted in acute hemolysis responsive to steroid treatment and appeared simultaneously with an increase in CMV titer.

Journal Article↗
PubMed1985

A possible mechanism in arterial wall for mediation of sex difference in atherosclerosis.

Female rabbits on an atherogenic diet were treated with cottonseed oil (control), tamoxifen, testosterone, or progesterone. After 10 weeks the rabbits were killed, the aortas quickly removed, graded for atherosclerosis, and incubated with [14C]proline to determine collagen and elastin synthesis. Rabbits treated with testosterone and progesterone had the greatest degree of atherosclerosis, the highest DPM in hydroxyproline of collagen and elastin, and the greatest accumulation of collagen and elastin in the aorta. Tamoxifen-treated rabbits had less incorporation of radioactivity. In separate experiments aortas of similarly treated rabbits were analyzed for estradiol and progesterone receptor density. These receptors were found to be present, and progesterone and testosterone administration caused a translocation of progesterone receptors from cytosol to nucleus. Results are consistent with the hypothesis that sex hormones can affect the development of atherosclerosis through a direct effect of the hormones on arterial wall to alter collagen and elastin synthesis, the effect being mediated through hormone receptors in the wall.

Animals↗
PubMed1985

Severe pancytopenia due to marked marrow fibrosis associated with angioimmunoblastic lymphadenopathy.

A patient with angioimmunoblastic lymphadenopathy (AILD) is presented. Manifestations of the disease appeared after short-term treatment with oxprenolol hydrochloride. Following treatment with prednisone, the patient remained in remission for 25 months. The disease relapsed following reuse of oxprenolol hydrochloride. Severe pancytopenia due to bone marrow involvement by AILD and myelofibrosis led to a fatal outcome. The association of AILD and myelofibrosis has been rarely encountered and is hereby discussed. In addition, the possible relationship between AILD and oxprenolol hydrochloride is considered.

Angina Pectoris↗
PubMed1982

L-dopa treatment of Parkinson's disease: a ten-year follow up study.

A ten-year follow-up study of parkinsonian patients treated with L-dopa is presented. Originally 130 patients entered the study, and previous reports were presented in 1971 and 1973. This report concerns the 47 remaining patients now available for examination. The effectiveness of L-dopa diminished over the ten-year period, so that the disability states of these patients are now similar to those prevailing just before the study began ten years ago. Despite the decline, the interim improvement and the patients' relatively asymptomatic existence for part of the time confirm the effectiveness of L-dopa therapy in the treatment of Parkinson's disease.

Aged↗
PubMed1979

Necrolytic migratory erythema without glucagonoma.

Two patients with clinical and histologic findings consistent with necrolytic migratory erythema are presented. Unlike previously described patients with this disorder, neither patient had substantially elevated glucagon levels nor an associated pancreatic islet cell tumor. The cause of the skin disease in these patients remains unknown but may be related to the underlying small-bowel disorder present in both.

Adult↗
PubMed1978

Human neurolymphomatosis.

A patient with a chronically progressive fatal sensorimotor neuropathy showed, at autopsy, extensive and selective lymphocytic infiltration of peripheral and cranial nerves and a segmental demyelinative process. A clinically occult retroperitoneal lymphoma without spread to other systemic organs was also present. The possibility of a selective infiltration of the peripheral nervous system by the retroperitoneal malignancy is rejected as unlikely. Our case bears a strong similarity to 3 other cases previously reported which may be grouped together under the heading "human neurolymphomatosis". The clinical and pathological features of this rare entity are discussed. It bears a resemblance to Marek's disease of chickens and seems to represent an unusual inflammatory neuropathy or form of malignancy.

Brain↗