Cell proliferation kinetics of normal and tumour tissue in vitro: quiescent reproductive cells and the cycling reproductive fraction

Current methods for measuring the cell kinetics of human tumours are made and interpreted within the context of a simplistic two compartment model for cell proliferation, consisting of cells that are cycling and those that are not. It is now recognized that the non-cycling compartment of many tumours is heterogeneous, composed of non-reproductive end-stage cells and reproductive cells that are dormant/quiescent. We have developed an in vitro analysis that distinguishes for the first time quiescent reproductive cells from non-reproductive end-stage cells and have integrated this analysis with monolayer clonogenic and suicide assays to simultaneously quantitate the duration of the cell cycle and reproductive cells that are: cycling, quiescent, clonogenic, and non-reproductive end-stage cells. We have defined a new parameter, the Cycling Reproductive Fraction (CRF), which is the cycling cell population referenced specifically to the reproductive cell population. Measurements of CRF from 72 tumour biopsies and from 5 normal foreskins showed that CRF approached 100% in some tumours; however, CRF showed near normal values (< 1%) in others suggesting that cell cycle control may be maintained in some tumours. Because of CRF's improved specificity, we believe that CRF may enhance classification, prognostication, and the optimization and prediction of response to chemotherapy.     

GABA and the behavioral effects of anxiolytic drugs

Much recent research has shown that benzodiazepine binding sites in the central nervous system are associated with GABA receptors. It is therefore possible that the pharmacological and therapeutic effects of benzodiazepines and drugs with similar profiles are mediated through GABAergic mechanisms. In this paper the evidence is considered for a possible involvement of GABA in the behavioral effects of anxiolytic drugs. There are a number of reports that the behavioral actions of anxiolytics can be antagonised by GABA antagonists such as bicuculline or picrotoxin but there are many contradictory findings and these drugs are difficult to use effectively in behavioral studies. In general, GABA agonists do not exert anxiolytic-like behavioral effects after systemic injection but intracerebral administration of muscimol has been shown to produce benzodiazepine-like actions. Although a number of questions remain unanswered, current evidence does not provide strong support for a role for GABA in the behavioral effects of anxiolytic drugs.     

Analysis of the two-dimensional receptive fields learned by the Generalized Hebbian Algorithm in response to random input

The Generalized Hebbian Algorithm has been proposed for training linear feedforward neural networks and has been proven to cause the weights to converge to the eigenvectors of the input distribution (Sanger 1989a, b). For an input distribution given by 2D Gaussian smoothed white noise inside a Gaussian window, some of the masks learned by the Generalized Hebbian Algorithm resemble edge and bar detectors. Since these do not match the form of the actual eigenvectors of this distribution (Linsker 1987, 1990), we seek an explanation of the development of the masks prior to complete convergence to the correct solution. Analysis in the spatial and spatial frequency domains sheds light on this development, and shows that the masks which occur tend to be localized in the spatial frequency domain, reminiscent of one of the properties of 2D Gabor filters proposed by Daugman ( 1980, 1985) as a model for the receptive fields of cells in primate visual cortex.     

Linkage studies in X-linked retinitis pigmentosa

Summary In a pedigree with X-linked retinitis pigmentosa, one recombination was observed between the pigmentosa locus and the locus for the Xg blood groups. Two examples of recombination were found between the loci for pigmentosa and deuteranomaly. An investigated carrier for retinitis pigmentosa had no fundus abnormalities similar to those reported in such heterozygotes. Together with the information from other families described in the literature, it seems likely that the 3 loci, that for retinitis pigmentosa, for color vision and for Xg blood groups, are well spread out on the X chromosome.

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Zusammenfassung In einer Sippe mit X-chromosal vererbter Retinopathia pigmentosa wurde eine Rekombination beobachtet zwischen den Genorten, die für die Netzhautdegeneration und für die Xg-Blutgruppen verantwortlich sind. Zwei Rekombinationen wurden gefunden für die Genorte, die Netzhautdegeneration und Deuteranomalie bestimmen. In Zusammenhang mit anderen, in der Literatur mitgeteilten Sippen scheinen die Genorte für Retinopathia pigmentosa, Farbensehen und Xg-Blutgruppen auf dem X-Chromosom weit verstreut zu liegen. Eine für das Netzhautleiden heterozygote Konduktorin zeigte keine Fundusauffälligkeiten, wie sie bisher bei solchen Personen beschrieben worden sind.

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From the University Hospital, Department of Ophthalmology, University of Iowa College of Medicine. Presented at the Third International Congress of Neuro-Genetics and Neuro-Ophthalmology, Brussels 1970. Supported in part by USPHS Grant No. 9 P15 EY 00117-03 from the National Eye Institute.