Linear prediction and single-channel recording

The measurement of individual single-channel events arising from the gating of ion channels provides a detailed data set from which the kinetic mechanism of a channel can be deduced. In many cases, the pattern of dwells in the open and closed states is very complex, and the kinetic mechanism and parameters are not easily determined. Assuming a Markov model for channel kinetics, the probability density function for open and closed time dwells should consist of a sum of decaying exponentials. One method of approaching the kinetic analysis of such a system is to determine the number of exponentials and the corresponding parameters which comprise the open and closed dwell time distributions. These can then be compared to the relaxations predicted from the kinetic model to determine, where possible, the kinetic constants. We report here the use of a linear technique, linear prediction/singular value decomposition, to determine the number of exponentials and the exponential parameters. Using simulated distributions and comparing with standard maximum-likelihood analysis, the singular value decomposition techniques provide advantages in some situations and are a useful adjunct to other single-channel analysis techniques.     

Down syndrome and male fertility: PCR-derived fingerprinting, serological and andrological investigations

Down syndrome, the most common birth defect causing mental retardation, is characterized by a specific phenotype including subfertility or sterility and hypogonadism in males. In contrast, several females with Down syndrome have borne offspring. Here, a male with trisomy 21 fathering an infant is described. This observation is verified by serological markers, DNA fingerprinting using different DNA micro-or minisatellites and andrological investigations.     

A reevaluation of the mathematical models for simulating single-channel and whole-cell ionic currents

We have developed a technique that allows for the simulation of both single-channel and whole-cell ionic currents given any arbitrary first-order kinetic scheme for the conformational states of an ion channel. The procedure is based on the solution of the master equation, which, in turn, is a general expression for a Markov process. The solution is expressed in terms of the eigenvalues and eigenvectors of the kinetic system and the system's deviation from equilibrium. Our derived expression provides a general recipe for the calculation of whole-cell currents. By further manipulation of this expression, we show how conditional probabilities are derived that can be used for the simulation of single-channel currents. We discuss computer implementation of the results so that complicated kinetic schemes can be solved numerically. Finally, we demonstrate the procedure by providing a worked example of a simple model of activation followed by inactivation.     

Dendritic reorganization in the denervated dentate gyrus of the rat following entorhinal cortical lesions: A Golgi and electron microscopic analysis

The organization of the dendritic tree and the morphology of individual dendrites of the dentate granule cell were analyzed qualitatively and quantitatively by means of the rapid Golgi technique 2, 4, 8, 10, 14, 30, 60, and 250 days after unilateral lesions of the entorhinal cortex (EC). Three dendritic field parameters were analyzed from camera lucida drawings of de-nervated granule cells at each survival time: (1) dendritic field spread, (2) dendritic length, and (3) dendritic branching. Cells in the contralateral dentate gyrus served as controls. Spines were counted at each postlesion interval from material stained with a modification of the Golgi-Kopsch method. The amount of tissue occupied by dendritic shafts at different postlesion intervals was also evaluated in samples of the ventral leaf of the dentate gyrus prepared for electron microscopy. After unilateral lesions of the EC, dendrites of the granule cells undergo modifications which appear to represent deterioration and recovery. When the dendrites reach the denervated zone, they abruptly change their orientation and tend to follow a course parallel to the granule cell layer. In contrast to normal dendrites, those in the denervated neuropil only occasionally reach the outer boundaries of the molecular layer. At the time of maximal denervation there is often a sudden reduction in dendritic diameter as the dendrite enters the denervated zone. Varicosities are also prominent. The alterations in individual dendrites are not evident 2 days after the lesion, are fully developed 10 days after deafferentation; and disappear for the most part by 30 days postlesion. The quantitative analysis of Golgi-stained granule cells reveals that there is a 40% reduction in the total length of the granule cell dendritic tree. Electron microscopic analysis confirms the Golgi observations, indicating that the amount of neuropil occupied by dendritic shafts in the denervated zone is initially reduced and later recovers to values close to those observed in control animals. While the apparent dendritic loss is mainly restricted to the denervated zone, significant modifications occur in the inner npnde-nervated molecular layer; there is an increase in the length of primary dendrites as evidenced by an increase in the distance to the first branch point. There is also a polarized redistribution of 1st, 2nd, 3rd, and 4th branch points toward the middle and outer molecular layer that persists even 30 days after the lesion. The results are discussed in terms of the capabilities of the granule cells of the dentate gyrus to reorganize and remodel their dendritic surface after partial deafferentation.     

PCNA-expression of cementoblasts and fibroblasts on the root surface after extraoral rinsing for decontamination

Abstract  – Periodontal cells capable of proliferation were studied immunohistochemically on extracted human teeth after 2-min irrigation with saline or ozonized water and marking of Proliferating Cell Nuclear Antigen (PCNA). All specimens expressed PCNA. The labelling index (LI), i.e. the number of positive cells compared to the total number of cells, was 6.6% after irrigation with saline and 7.8% after irrigation with ozone. There was no difference in number and distribution of PCNA-positive cells from the coronal to the apical thirds of the roots. Irrigation with ozonized water showed higher labelling indices in comparison with saline, but this could not be statistically substantiated ( P  = 0.24). Ozonized water, not being isotonic, had no negative effect on periodontal cells remaining on the tooth surface after irrigation for 2 min.     

A trial of chemoprophylaxis of natural influenza infection with U.K. 2371

In a five-week double-blind trial, 132 young adult volunteers received U.K. 2371, a synthetic isoquinoline derivative which had previously been shown to protect volunteers against challenge with certain influenza viruses. A comparable group of 130 volunteers received placebo. There was little difference between the groups in number or severity of acute respiratory illnesses during the trial or in the number of proven infections with influenza A2/Hong Kong/1968 virus. Tablet counts were carried out and single doses of isoniazid were used as a marker to confirm that the lack of prophylaxis was not the result of the failure of volunteers to ingest the tablets.     

Synthese und teratogene Aktivität von thalidomid-analogen 1,3-Indandionen

Synthesis and Teratogenic Activity of some Thalidomide Analogous Indane-1,3-diones Some thalidomide analogous indane-1,3-diones have been synthesized and tested on mice. They showed greater teratogenic activities than thalidomide (1) itself. Therefore, a transacylation as the possible cause of the teratogenicity of thalidomide is refuted.