Spatial summation and visual adaptation in the inner part of the frog retina

The spatial summation of the proximal negative response (PNR) of frog retina was analyzed during different states of adaptation induced by repetitive light stimulation with either 15 sec or 1 min interstimulus interval. The spatial summation area of the PNR was found to be wider during relatively more dark adapted conditions compared to relatively more light adapted ones. This finding indicates that lateral mechanisms in the inner network of the retina seem to be activated by adapting stimuli. Secondly, the results suggest that the activity of the amacrines, as reflected by the PNR, may initiate the series of neuronal events which underlie the oscillatory potentials (OPs) of the electroretinogram (ERG).     

Electrophysiological changes in the acute “axonal” form of Guillain–Barre syndrome

The acute “axonal” form of Guillain—Barre syndrome is characterized by rapid progression to severe widespread paralysis and respiratory dependence within 2–5 days of the onset of weakness with very poor and delayed recovery. In 3 cases studied within the first 7 days, the maximum thenar, hypothenar, tibialis anterior, and extensor digitorum bervis “M” potentials were either very reduced in size or absent in response to stimulation at the usual most distal sites of stimulation at the wrist, fibular head, and/or ankle. In the latter instances, advancing the site of stimulation closer to the motor point often evoked an M response. Furthermore, continued distal advance of the site of stimulation evoked progressively larger sized M potentials. Over succeeding days even these very distally evoked M potentials. Maximum conduction velocities in motor nerve fibers just prior to total loss of excitability were often very reduced. The pattern in these cases is most consistent with progressive loss of excitability and conduction in nerve fibers undergoing axonal degeneration, although coexisting primary demyelination in the terminal segment could not be excluded as the basis for the sometimes very slowed conduction velocities. © 1993 John Wiley & Sons, Inc.     

Ultrasound enhanced drug toxicity on Chinese hamster ovary cells in vitro

Chinese hamster ovary cells (HA1) were exposed to therapeutic ultrasound (F = 2.025 MHz) in the presence of various drugs at temperatures of 37-43 degrees C. The space averaged intensities used were 0.5-2 W/cm2. The survival of these cells was subsequently tested using the clonogenic assay. Marked enhancement by ultrasound of the cytotoxicity of Adriamycin and amphotericin B was observed. For Adriamycin, the potentiation was dependent upon the intensity of sonication (exposure duration being 30 min). At 0.5 W/cm2, there was enhancement of cytotoxicity above 41 degrees C. At 1 W/cm2, there was a 3-order increase in cytotoxicity at 37 degrees C. Thus an increase in intensity resulted in a decrease in "threshold" temperature. The effect with Adriamycin could be explained in part by an increase in net uptake of drug into the cells. Further, ultrasound was observed to increase the sensitivity of cells to Adriamycin. For amphotericin B, the enhancement was observed only at exposure durations greater than 30 min and at 43 degrees C. There was no enhancement observed for cisplatin and etoposide. From these results, it appears that ultrasound potentiates the cytotoxicity of drugs the mode of action of which (at least in part) involves the plasma membrane.     

The effect of Dextransulfate 500 on the pathogenesis of herpes simplex virus infections in weanling mice

Summary Intraperitoneal (i.p.) injection of Dextran Sulfate (D.S.) 500 during a limited period of time influences the course of herpes simplex-virus-infections. D.S.500 was found to reduce the resistance of mice for some herpes simplex-virus strains (Len, L3-2s, Haase) if given between 16 hours before and 2 hours after i.p. infection. The decrease of resistance could be correlated with an increase of the virus content of liver, spleen, brain and spinal cord. Injection of herpes simplex-virus-specific immune serum counteracted the effect of D.S.500 on the course of infections. Conversely, D.S.500 increased the resistance of mice to another group of herpes simplex-viruses (strains D-316, Thea, DD), if given 3 to 8 hours before infection.These effects are ascribed to a special interaction of D.S.500 with macrophages and probably other virus-susceptible cells of the peritoneal cavity and elsewhere with a resulting counteraction to the virus infection.With 2 FiguresIn part presented at the 76th Ordinary meeting of the Society for General Microbiology at the University of Cambridge, April 5–8, 1976.In partial fulfilment of the requirements for the MD degree.     

Infantile hypotonia as a presentation of Rett syndrome

Rett syndrome (RTT) is classically defined by meeting certain clinical diagnostic criteria. It affects mostly females, and one possible pathogenic mechanism was considered to involve mitochondrial function. This was based on the finding of ultrastructural alterations in the mitochondria and decreased respiratory chain enzyme activity. However, the principal etiology of RTT has since been found to be mutations in the MECP2 gene, which is located on the X chromosome. Molecular analysis has allowed the phenotype of MECP2 mutations to be broadened beyond RTT to include girls who have mild mental retardation, autism, and an Angelman syndrome phenotype, as well as males with severe encephalopathy. We present a girl with a previously described mutation in the MECP2 gene whose phenotype is of atypical RTT. She presented with hypotonia and developmental delay in infancy without a clear period of normal development. As part of her evaluation for hypotonia, a muscle biopsy and respiratory chain enzyme analysis showed a slight decrease in respiratory chain enzyme activity consistent with previous reports. This report supports broadening the phenotype of patients who should be considered for MECP2 mutation analysis to include cases of developmental delay and hypotonia without evidence of an initial period of normal development. Furthermore, it supports the hypothesis of an underlying secondary defect in energy metabolism contributing to the pathogenesis of RTT.     

Inefficient delivery of yeast cells as an explanation for reduced plating efficiency of Candida albicans.

The plating efficiency for fungal yeast cells is usually less than that expected from microscopic counts, and a number of explanations for this phenomenon have been proposed. The present study was undertaken to explore possible reasons for reduced plating efficiency of Candida albicans. Explanations that we evaluated and found unlikely included: ineffectiveness of different culture media and/or incubation temperatures for growing colonies, insufficient area of the plate available for expression of individual colonies, production of microcolonies, and inaccurate counting of the organisms in the inoculum. An assay for delivery of the inoculum into tissue culture plate wells indicated that reduced delivery of the organisms accounted for lower than expected plating efficiency. C. albicans yeast cells grown under low glucose conditions and expected to have reduced adhesiveness were found to have higher values for both delivery and plating efficiency in our assays. In summary, our results indicate that reduced plating efficiency for C. albicans under the conditions used for these experiments is best explained by the loss of some yeast cells during preparation of the inocula or delivery of the yeast cells onto the plates.     

PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis.

To determine functional differences between the two splice variants of PPARgamma (gamma1 and gamma2), we sought to selectively repress gamma2 expression by targeting engineered zinc finger repressor proteins (ZFPs) to the gamma2-specific promoter, P2. In 3T3-L1 cells, expression of ZFP55 resulted in >50% reduction in gamma2 expression but had no effect on gamma1, whereas adipogenesis was similarly reduced by 50%. However, ZFP54 virtually abolished both gamma2 and gamma1 expression, and completely blocked adipogenesis. Overexpression of exogenous gamma2 in the ZFP54-expressing cells completely restored adipogenesis, whereas overexpression of gamma1 had no effect. This finding clearly identifies a unique role for the PPARgamma2 isoform.