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Biomedical subjects

Z Grossman

Publications and source records attributed to Z Grossman.

66 records · Page 4Linked to original sources

A non-programmatic approach to hemopoiesis.

The currently prevailing concept of hemopoietic differentiation is that the pathway starts at the multipotential stem cell and proceeds in a programmatic, relatively fixed fashion to the development of circulating blood cells. We have presented considerations supporting a more dynamic regulation. Self-renewal capacity within a compartment is seen as a measure of the cell's resistance to differentiation pressures. Mutable environmental factors, including feedback interactions, are proposed to regulate in each compartment the relative probabilities of renewal and maturation. We question the rigid distinction between multipotential and committed cells, generally believed to be separated by a discrete "determination" event. We prefer to see commitment as a manifestation of a gradually increasing bias for a given developmental fate. Such commitment might be modulated under different environmental conditions. Multipotency and stemness are two aspects of cellular resistance to maturation pressures.

Adaptation, Physiological↗

Structure of simian virus 40-adeno-associated virus recombinant genomes.

The structures of recombinant genomes formed by recombination between simian virus 40 (SV40) and adeno-associated virus 2 (AAV) DNAs after either DNA cotransfection or coinfection by virions were characterized. Two types of structures were found. Group A structures, found after cotransfection and in one of seven recombinants arising from coinfection, represented a simple deletion of SV40 sequences replaced by a slightly shorter AAV sequence. Group B structures were found in six of seven recombinants arising after virion coinfection. All contained either the left or right terminal sequences (approximately 250 to 450 bases) of the AAV genome adjacent to the SV40 origin of DNA replication. Only 350 to 650 bases (including the origin) remained of the SV40 sequence. The joined SV40-AAV sequences were present in the recombinant genome as a tandem repeat of a size that can be packaged into SV40 capsids.

Base Sequence↗

Recombination between simian virus 40 and adeno-associated virus: virion coinfection compared to DNA cotransfection.

Recombination between simian virus 40 (SV40) and adeno-associated virus (AAV) has been detected, by infectious center in situ plaque hybridization procedures, after both DNA contransfection and virion coinfection of monkey BSC-1 cells. The number of cells producing recombinants (1 in a 1000) was the same irrespective of the way in which the SV40 and AAV genomes were delivered to the cell, despite the fact that 5-10 times more cells were infected after virion coinfection. Several other dosage-response parameters of the recombination process consequent to virion coinfection were comparable to those after DNA cotransfection. The sole difference observed between the two infection systems was that the SV40/AAV recombinants formed after virion coinfection contained an inordinately high proportion of AAV terminal DNA sequences. By separating the SV40 and AAV infections in time, such that the AAV infection was delayed until after certain events in the SV40 cycle had taken place, an optimum phase for recombination in the SV40 cycle was identified. This phase occurs a few hours after infection, well before the onset of SV40 DNA replication and the synthesis of SV40-specific early proteins.

Animals↗

Recognition of self and regulation of specificity at the level of cell populations.

It is suggested that immunologic specificity and selective responsiveness, assayed by effector and memory cells, are, in part, determined by the existing repertoire of lymphocytes and, in part, by the dynamic nature of cellular growth. Clones within horizontal networks resemble competing species in a Darwinian world. Upon stimulation, the development of a clone is greatly affected, in a dynamic way, by factors that determine the balance between self-renewal and differentiation. Antigen is a major factor. The amount of antigen and the nature of encounter with the immune system (sudden, graded or continuous), through the selection of a particular subset of clones, can be correlated with a weak or a strong expression of effector function and with the generation of effective memory or of tolerance. The encounter with self antigens obeys the same rules. Thus, the distinction between self and non-self is a quantitative one, both at the single-cell level and at the systemic level. The encounter of developing lymphocytes with self antigens, and in particular with idiotypes and MHC-antigens, restricts the repertoire and imposes major constraints both on the mode of interaction with foreign antigens and on potential self-recognition networks. The proposed "dynamic scheme", differing from "structural schemes" in a number of fundamental aspects, calls for reevaluation of present concepts of immunoregulation and for reinterpretation of data.

Animals↗

Diagnosis of angiotensinogenic hypertension: the complementary roles of renal scintigraphy and the saralasin infusion test.

A recently developed 1-day screening procedure for angiotensinogenic ("high-renin") hypertension is based on (A) a fall in blood pressure in response to intravenous infusion of the angiotensin antagonist, saralasin (P-113), and (B) peripheral venous renin assays by radioimmunoassay, in a sodium-depleted state. Out of 700 hypertensive patients screened by these tests, 160 had renal imaging performed with technetium-99m glucoheptonate and iodine-131 Hippuran. The P-113 infusion test proved superior to peripheral venous renin assays for the detection of angiotensinogenic hypertension. Positive infusion tests correlated well with renal vein renin assays. Frequently, however, both these tests were positive with bilateral renal disease and/or malignant hypertension. While renal imaging proved valuable in indicating which patients had a unilateral abnormality, it frequently could not distinguish unilateral renovascular disease from unilateral parenchymal disease unrelated to angiotensinogenic hypertension. Twenty-five patients in this series had arteriographic renal artery stenosis, of whom 3 had false negative P-113 infusion tests, 9 had negative peripheral renin assays, and 3 had no imaging abnormalities. This study indicates that scintigraphy is a useful procedure for the investigation of hypertensive patients when the initial P-113 infusion test is positive, or discordant with other findings. By imaging, angiotensinogenic hypertension due to bilateral renal disease can be distinguished from unilateral renovascular disease, and the site of the ischemic renal tissue can usually be identified.

Adult↗

Neural modulation of immunity: conditioning phenomena and the adaptability of lymphoid cells.

The behavioral conditioning of alterations in the immune response is one pillar supporting the growing edifice of central nervous system (CNS) modulation of immunity. The mechanisms underlying such conditioning phenomena are not understood. In this communication, we attempt to develop a theoretical position based on the concept of phenotypic and functional adaptability of lymphoid cells. We propose that these cells can learn to associate responsiveness to antigens and to other "immunoactive" agents, with responsiveness to signals originating in the CNS delivered via neuroendocrine or autonomic nervous channels. Neural/endocrine signals act on the immune system in conjunction with immunological stimuli, in a way that leads to "storage" of the association (memory) of these two kinds of stimuli in the immune system rather than in the brain.

Animals↗