Justification of glioma biology beyond a cellular basis of interpretation.

Gliomas as neoplasms primarily arising from and constituted by glial cells would appear to implicate cell types that inherently reflect variation of aspects of a putative reparative process. The prominence of an astrocytic type cell of origin would further perhaps constitute a system of malignant transformation based on aberrant progression in cell proliferation and of cell pathology related to aspects on one hand of a gliosis and on the other of an autonomous process of progressiveness. In such terms, perhaps, one might consider the molecular aspects of gliomatous pathogenesis as simply a process of integral aberration of various aspects of astrocytic or glial cell responsiveness outside the normal confines of the normal reparative process and inherently beyond a strict cellular basis of interpretation in pathobiologic terms of such processes as anti-apoptosis and amplification of growth factor receptivity.

Towards a pathogenetic definition of multiple sclerosis in terms of integrative transformation of generic pathologic processes.

The multiple sclerosis disease process is presented in the light of a generic pathobiologic phenomenon on equal terms with such other phenomena as ischemia, neoplasia, infection and congenital malformation, with the added improviso that it would also constitute a true form of integrative resolution of these other generic phenomena towards a real transformation of events in terms of both cellular forms of injury and also in terms of pathogenesis and evolution. Perhaps, in the final analysis, a putative infectious agent is implicated in multiple sclerosis whose peculiar attributes are reflected in a distinctive immunologic response beyond even the conventional concepts of either hypersensitivity or of immunologic surveillance. In a sense, perhaps, a particular patient immunologic constitution in an environment conducive to exposure to a putative agent results in a form of integration of this agent leading to persistent demyelinative relapse of the affected oligodendrocyte on an essential background of a distinct plaque centered on a specific vessel of supply. The recognition of the oligodendrocyte as a specialized astrocyte might in itself strictly characterize such a generic demyelinative process of multiple sclerosis in terms of its essential remitting/relapsing course.

Is beta-amyloid fibrillogenesis a strict process of deposition inherently interactive in molecular terms?

Amyloid fibrillogenesis as a process of interactive molecular processes of deposition in Alzheimer's disease might function as a phenomenon that transforms intracellular amyloid segregation to a state of equilibration with extracellular deposition. beta-Amyloidosis might dynamically implicate loss of viability of vascular tunica media myofibers as a strict reflection of loss of viability of neurons in such an overall system of equilibration between intracellular and extracellular amyloid fibrillogenesis. In terms beyond simple concepts of strict biophysical equilibration, deposition of beta-amyloid in Alzheimer's disease might constitute a phenomenon of congophilic angiopathy as a strict pathobiologic index of activity of the Alzheimer process; such a correlate would perhaps involve a quantitative index that would qualitatively characterize the Alzheimer process as an interactive series of reactions between the intracellular and extracellular microenvironment.

A concept of essentially secondary factors central to definitive subtype characterization of Hodgkin's disease.

Conceptually, Hodgkin's disease would appear to constitute a neoplasm that integrally incorporates responsive cellular elements in terms strictly of morphologic patterns of interaction resulting especially in a predictable scale of therapeutic and prognostic implications as related particularly to pathobiologic course and response to treatment. In this sense, Hodgkin's disease might in a real sense constitute a valid point of reference in terms of processes not only in the generation of the neoplastic process but particularly in terms of how such a neoplastic process interacts with host systems in specifically characterizing the very nature of the intrinsic neoplastic process itself. In this manner, therefore, it might be valid to consider the totality of manifestations of Hodgkin's disease as a fundamental series of processes that integrally determines the genesis and nature of the neoplastic process as a function especially of various host systems in response to that neoplasm. In terms strictly related to a viral or Epstein-Barr virus-related development of Hodgkin's disease, it might perhaps be true that transcription factor NF-kappaB might induce the signaling of a CD30 receptor pathway that is intrinsically linked with anti-apoptosis of germinal center lymphocytes. In overall terms, perhaps, the Epstein-Barr viral nuclear antigens such as Latent membrane protein 1 would activate NF-kappaB as a mechanism that induces anti-apoptotic effect by multiple pathways in the added context particularly of a concerted series of cytokines that secondarily regulate T lymphocyte response. Indeed, in simple terms, Hodgkin's disease would appear to involve a basic mechanism of induced transcription as an effective anti-apoptotic mechanism as exerted on Reed-Sternberg cells. The Epstein-Barr viral nuclear antigens might be pivotal in orchestrating a full series of cytokine and T lymphocyte responses that would perhaps contribute significantly to the effective perpetuation of such anti-apoptotic effect or effects as exerted on the Reed-Sternberg cells.