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G T Matioli

Publications and source records attributed to G T Matioli.

16 recordsLinked to original sources
PubMed1992

Precipitous stem cell (SC) differentiation and 1/f noise.

After a brief digression on certain types of noise of generic interest, it is concluded that 1/f noise offers interesting interpretations for unusual modes of SC differentiation such as the precipitous maturation of a subset of the macrophage lineage. Functionally equivalent to weak, spurious sources these specialized cells support the proliferation and maturation of erythroid cells extending thus the stimulatory influence of true, strong sources although in a rather indirect fashion.

Animals↗
PubMed1991

On monosegmental sister chromatid exchanges (SCE).

Considerations are given to special features of the nuclear envelope that might occasion segmental exchange between sister chromatids. The underlying dynamics may lead to illegal apposition of originally distant sequences and/or to modulations in the topologic orientation of genes on chromatid segments involved in such exchanges.

Animals↗
PubMed1991

Midsegmental exchanges between sister chromatids.

The model for SCE, proposed by (1), is adapted to the exchange of one or more segments located midway along the chromatid axis. In spite of conflicts in the handedness of these midsegments, the model accounts for the undistorted stacking of both sister chromatids.

Animals↗
PubMed1991

Scaling concepts in cellular and subcellular dynamics.

After developing a map for certain states typical of hemopoietic stem cells (SCs), we identify a number of parameters (e.g. fractal dimensions, oscillatory behavior in a multistable landscape, etc.) that scale down to subcellular structures such as interphase genome, chromatids, chromatin entanglements and DNA segmental motions. A curious aspect is the continuous reappearance of recursive processes even at very small biologic scales. These iterations are relevant not only for the normal behavior of (hemopoietic) cells but also for amplifying hidden genomic singularities above some critical threshold. When that happens, there are sudden quali-quantitative and often clonal changes in the cell behavior. As illustrated by specific leukemic cases, many paradoxes of malignant growth seem best explained by the peculiar sensitivity to initial condition of (hemopoietic) cells. Interpreted as chaotic oscillators, these cells display a spectrum of disorders that, in spite of appearing as random, are in fact triggered by amplification of subtle preconditions with statistico-deterministic outcomes, that are predictable within certain time limits.

Animals↗
PubMed1991

On the handedness of the scaffolds of sister chromatids.

We discuss a mechanical model for the mirror-symmetric inversion of the scaffold's helicity of replicated chromatids vis-a-vis that of their templates. The paper ends with comments on the orientability of certain genes and on the effects of such topologies upon (a)symmetric gene expression, in general. Our model and its generalizations apply only to the special subclass of 'coiled' chromatids whose statistical distribution in the genome of normal and of malignant cells is not known precisely.

Biomechanical Phenomena↗
PubMed1991

On the myeloblast as initiator of certain human leukemias.

We reconsider the proposal that a stem cell (SC) is the initiator of clonal (human) leukemias. Using chronic myeloid leukemia (CML) as an example, we discuss some conceptual and experimental inconsistencies of the above conjecture. As an alternative, it is proposed that CML is initiated by an immature myeloblast. The main idea is that CML results from certain growth-related accidents encountered along the myeloid differentiation path. Retrodifferentiation of (semi) autonomous myeloblasts back to the SC state seems the principle cause for the distribution of clonal markers across all hemopoietic lineages, including those that are not involved in the leukemic process.

Bone Marrow↗
PubMed1990

Differentiation trajectories in normal and malignant cells.

We discuss a model for the organization of differentiation paths within the vector spaces of the cell genome. It is conjectured that the nuclear vesicle apparatus participates in the coordination of genes along nuclear trajectories directing cell commitment to terminal maturation. In this scenario, nuclear (onco)genes are interpreted as regulators of transcriptional exchanges among spatially correlated genes. The paper digresses on events leading to anachronistic acquisition of immortal growth by normally dependent cells as well as on the time and path dependent incidence of cancer, in vivo. Albeit the mathematico-physical foundations have been largely ignored, the basic ideas were derived from order-disorder transitions in chaotic systems whose dynamics are not pervasively random. The paper ends with a brief note on tumor heterogeneity, seen as a logistic phenomenon complementing the interpretation offered by (1).

Animals↗
PubMed1990

On the topology of normal chromatids and on their translocations in myelogenous leukemia.

After some comments on the topology of chromatids, restructuring of the interphase nucleus is conjectured to depend upon the nuclear vesicle apparatus. These vesicles change the intrinsic shape of chromatids to fit the different topology of the interphase nuclear spheroid. Reciprocal translocations between selected chromatids result whenever the nucleus of malignant cells organizes de novo certain exceptional or emergency differentiation paths. However, the almost unavoidable chimeric genes resulting from these translocations may be less ominous than hitherto suspected. This seems to be the case for chronic myelogenous leukemia, where the bcr-abl chimeric gene lessens the aggressiveness of the primary clone when functioning in the context of myelomonocitic differentiation. Finally, our model estimates the statistical incidences of the bcr-abl chimera. These estimates are found to agree with clinical data better than evaluations from the random mutation theory.

Chromatids↗
PubMed1990

Relative stimulatory efficiency of various points on the surface of hemopoietic source cells.

We make quantitative estimates for the relative stimulatory efficiency at various points on the membrane of a hemopoietic source. This cell produces a stimulus, P, which supports renewal of parasitic stem cells (SCs) in physical contact with the source's surface. We find that the tips of long pseudopods extending from the source's main body should have the highest stimulatory efficiency.

Animals↗
PubMed1989

A proposal for the development of clonal hemopoietic leukemias.

We elaborate on the pathogenesis of (human) hemopoietic leukemias according to a model whereby malignant growth follows the anachronistic expression of gene P in a rare cell at a certain stage of differentiation (1,2). P is a stimulus needed for renewal of hemopoietic cells. When illegally autocatalytic for P any mitotically competent cell (not necessarily pluripotent, at least originally) acquires the marginal (seldom complete) autonomous growth of malignant cells. Rather than confrontational, these views complement advantageously the mutation model and account for certain peculiarities of (human) leukemic cells, such as the propensity to differentiate terminally when isolated from their in vivo microenvironments. In addition, we discuss the rare occurrence of certain human leukemias (e.g., erythroleukemias and polycythemia veras) comparatively to the surprisingly more frequent chronic and acute myelogenous leukemias. This occurs in spite of the similarity between erythroid and myeloid populations in terms of size (mass of cells) and number of targets at mutational risk. Thus the classic mutation model predicts that random hits, after radiation exposure for example, should induce erythroid and myeloid leukemias with similar frequencies in contrast to clinical findings (3) and the predictions from our model.

Cell Division↗
PubMed1988

Cancer clonality and field theory.

We discuss a "genomic" mechanism capable of yielding clonal malignancies (e.g. hemopoietic leukemias) without the prerequisite of multiple or single mutations. This hypothetical mechanism is based upon the anachronistic (illegal) expression of a special gene P, where P stands for "potential". P. is a stimulus promoting renewal of stem and most immature cells of hemopoietic tissues. In normal conditions, these cells renew themselves only after receiving P from special microenvironmental cells or field "sources". When illegally expressed by a previously dependent cell, the autocatalyzed potential competes with differentiating factors and slows down terminal differentiation. This sets the cell on a temporary (or extended) "limit cycle" between competing attractors viz: renewal and extinction, whereby both progenitor and clonal progeny are locked between continuous proliferation and terminal differentiation for a time longer than their normal, absolutely source dependent counterparts.

Cell Differentiation↗
PubMed1965

Electrophoresis of hemoglobin in single erythrocytes.

A technique for electrophoretic analysis of the hemoglobin mixtures from single erythrocytes has been developed. Hemoglobin mixtures were separated into their constituents, A(2), A, C, S, and J, at least qualitatively.

Electrophoresis↗