Topical magnetic resonance for the study of muscle metabolism in human myopathy

The role of changes in energy metabolism are obvious in the myopathies with described enzyme defects, but the ability afforded by topical magnetic resonance spectroscopy to study these changes repeatedly and non-invasively helps provide an understanding of the alterations in energy metabolism seen in muscle complaints of which the aetiologies are still unclear. Attention is focused on interpreting the findings with particular regard to Duchenne muscular dystrophy.     

Long-range temporal correlations in the spontaneous spiking of neurons in the hippocampal-amygdala complex of humans

The spontaneous or background discharge patterns of in vivo single neuron is mostly considered as neuronal noise, which is assumed to be devoid of any correlation between successive inter-spike-intervals (ISI). Such random fluctuations are modeled only statistically by stochastic point process, lacking any temporal correlation. In this study, we have investigated the nature of spontaneous irregular fluctuations of single neurons from human hippocampus-amygdala complex by three different methods: (i) detrended fluctuation analysis (DFA), (ii) multiscale entropy (MSE), (iii) rate estimate convergence. Both the DFA and MSE analysis showed the presence of long-range power-law correlation over time in the ISI sequences. Moreover, we observed that the individual spike trains presented non-random structure on longer time-scales and showed slow convergence of rate estimates with increasing counting time. This power-law correlation and the slow convergence of statistical moments were eliminated by randomly shuffling the ISIs even though the distributions of ISIs were preserved. Thus the power-law relationship arose from long-term correlations among ISIs that were destroyed by shuffling the data. Further, we found that neurons which showed long-range correlations also showed statistically significant correlated firing as measured by correlation coefficient or mutual information function. The presence of long-range correlations indicates the history-effect or memory in the firing pattern by the associative formation of a neuronal assembly.     

Organization of radial glia and related cells in the developing murine CNS. An analysis based upon a new monoclonal antibody marker

A monoclonal antibody, RC1, has been generated which provides a selective and sensitive immunohistochemical marker of radial glial cells and related cell forms during development of the mouse CNS. Beginning on embryonic day E10, immunocytochemistry performed on cryostat sections stains throughout the CNS a subpopulation of cells in the ventricular zone with radial processes that terminate with endfeet at the pial surface. These processes become fasciculated and attain maximal densities by E12-14 in the spinal cord and lower brainstem and by E14-16 in the midbrain, cerebellum and forebrain. Fasciculation is especially prominent for a subclass of these cells at the midline of the brainstem and spinal cord. As nuclear and cortical structures develop, the trajectories of the radial fiber fascicles undergo systematic and region-specific distortions in their initially simple linear configuration, in the process maintaining a consistent spatial registration of germinal ventricular zones with distal sites of assembly of post-migratory neurons. In the late fetal period, radial glial progressively disappear and scattered immature astrocytes bearing multiple fine processes appear in most regions of the CNS. In the spinal cord, a transitional unipolar radial form is identified in the emerging ventral and lateral funiculi between E13 and E17. In the cerebellum, precursors to the unipolar Bergmann glial cell are identified by E15, and in the retina, precursors of the bipolar Müller cell are identified by E16. Postnatally, RC1-stained radial glia become sparse, and after one week, immunoreactive cells include only ependymal cells, hypothalamic tanycytes, Bergmann glia, Müller cells, a unipolar radial form in the dentate gyrus, and a subpopulation of white matter astrocytes. These results suggest that radial cells of astroglial lineage comprise a diverse set of cell classes which subserve multiple functions in the developing and adult brain.     

Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels

Interlobular arteries and superficial afferent and efferent arterioles were isolated from rabbit kidney, and the effects of intraluminal pressure, norepinephrine (NE), and angiotensin II (ANG II) on lumen diameter were examined. A single microvessel was dissected and one end was cannulated. The other end of the vessel was occluded and lumen diameter was measured at fixed intraluminal pressures. With step increases in intraluminal pressure over the range of 70-180 mmHg, lumen diameters of the interlobular arteries and afferent arterioles remained constant or decreased by up to 11%. In contrast, lumen diameters of efferent arterioles continued to increase as intraluminal pressure was elevated. In all three vessels NE (10(-9) to 10(-5) M) caused a dose-dependent decrease in lumen diameter. However, only the efferent arteriole responded to ANG II (10(-12) to 10(-8) M). The contractile response of the efferent arteriole to NE or ANG II was localized to the first 50-75 micrometers of the vessel as it emerged from the glomerulus. This finding suggests that smooth muscle cells are located only in this portion of the efferent arteriole. It is concluded that at least part of the autoregulation of renal blood flow can be explained by a myogenic mechanism in preglomerular vessels and that ANG II acts primarily on postglomerular segments of the rabbit renal microcirculation.     

Sindbis virus infection of a Chinese hamster ovary cell mutant defective in the acidification of endosomes

Sindbis virus infection of a Chinese hamster ovary temperature-sensitive mutant cell line defective in its ability to acidify endosomes was examined to evaluate the importance of this step in the process of alphavirus penetration of host cells by measuring the time at which viral RNA synthesis was initiated. We found that RNA synthesis was initiated in these mutant cells at the same time after addition of virus at either permissive or nonpermissive temperature. We conclude that exposure to the acidic environment of an endosome is not a prerequisite for alphavirus infection.     

Assignment of human 3-hydroxy-3-methylglutaryl coenzyme A reductase gene to q13 → q23 region of chromosome 5

We have used hamster cDNA probes for 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (HMGCR) to determine the chromosomal location of the human gene for HMG CoA reductase. Southern blot analysis of genomic DNA from 16 independent mouse-human somatic cell hybrids showed that the human gene for HMG CoA reductase resides on chromosome 5. Analysis of Chinese hamster-human somatic cell hybrids selectively retaining human 5 or a portion of it showed that the gene locus for HMG CoA reductase can be assigned to the q13 q23 region of chromosome 5.