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Biomedical subjects

G Raskin

Publications and source records attributed to G Raskin.

6 recordsLinked to original sources

Reduced intracellular ionic strength as the initial trigger for activation of endothelial volume-regulated anion channels.

Most mammalian cell types, including endothelial cells, respond to cell swelling by activating a Cl- current termed ICl,swell, but it is not known how the physical stimulus of cell swelling is transferred to the channels underlying ICl,swell. We have investigated the precise relation between cell volume and ICl,swell in endothelial cells by performing whole-cell current recordings while continuously monitoring cell thickness (Tc) as a measure for cell volume. The time course of Tc was accurately predicted by a theoretical model that describes volume changes of patch-clamped cells in response to changes in the extracellular osmolality (OSMo). This model also predicts significant changes in intracellular ionic strength (Gammai) when OSMo is altered. Under all experimental conditions ICl,swell closely followed the changes in Gammai, whereas ICl,swell and cell volume were often found to change independently. These results do not support the hypothesis that Gammai regulates the volume set point for activation of ICl,swell. Instead, they are in complete agreement with a model in which a decrease of Gammai rather than an increase in cell volume is the initial trigger for activation of ICl,swell.

Animals↗

Transepithelial capacitance decrease reveals closure of lateral interspace in A6 epithelia.

A sine wave method was used to measure transepithelial capacitance (CT) at 4.1 kHz (CHFT ). Model calculations show that CHFT reflects the equivalent capacitance of the series arrangement of apical and basolateral membrane capacitance. Cell swelling induced by reducing the basolateral osmolality from 260 to 140 mosmol/kg H2O (NaCl or sucrose removal) transiently decreased CHFT. The decrease in CHFT (DeltaCHFT ) reached its maximum 30 s after the onset of cell swelling and a complete recovery of CHFT was attained within 3-4 min. DeltaCHFT could be diminished by manoeuvres that reduced the rate or amplitude of cell swelling, i.e. lowering the temperature or treatment with low concentrations of glutaraldehyde (0.025%). DeltaCHFT increased with the magnitude of the osmotic perturbation but saturated at large volume expansions. DeltaCHFT increased with culture time. Electron micrographs showed a clear correlation between time course of CHFT changes and the closure of the lateral interspace (LIS). A striking correlation between the occurrence of CHFT recovery and the ability of the cells to develop a regulatory volume decrease (RVD) was found: Gd3+ (0.5 mM) inhibited both phenomena. The frequency dependence of CT was obtained from impedance spectra recorded over the range of 4 Hz to 22 kHz. These data agree with model calculations in which the contribution of the access resistance to the lateral membrane was included. All observations are consistent with the idea that DeltaCHFT originates from the closure of the LIS during cell swelling. The latter phenomenon increases the access resistance to the lateral membrane, which results in a marked reduction of the basolateral membrane area detected at high frequencies with capacitance measurements.

Algorithms↗

The role of childhood stressors in the intergenerational transmission of alcohol use disorders.

OBJECTIVE: This study examined relations between childhood stressors (e.g., disrupted family rituals, embarrassment, neglect, abuse), family history of paternal alcoholism, and alcohol use disorders in late adolescence and early adulthood. Of particular interest was the extent to which stressor exposure mediated the association between paternal and offspring alcohol use disorders. METHOD: A mixed-gender sample of 457 (238 female) participants, approximately half (N = 234) with a family history of paternal alcoholism, were assessed for alcohol use disorders and childhood stressors via clinical interviews. RESULTS: Family history of paternal alcoholism was associated with every childhood stressor examined, often strongly. In addition, a number of childhood stressors (e.g., verbal, emotional, physical and sexual abuse) were related to an alcohol use disorder in late adolescence/early adulthood. However, only a portion of the effect of family history on a subsequent alcohol use disorder was accounted for by the childhood stressors we examined. CONCLUSIONS: Findings indicate that self-reported childhood stressors are strongly related to a family history of alcoholism, but are only moderately and inconsistently related to the development of an alcohol use disorder. Moreover, they appear to, at best, only partially mediate the relation between family history of alcoholism and an alcohol use disorder.

Adolescent↗

An automatic monitoring system for epithelial cell height.

This paper describes an automatic method to measure cell height (h) of epithelia grown as monolayers on transparent filter supports. Tissues are mounted in an Ussing-type chamber enabling solution exchange on both sides. The apical and basal side of the epithelial cells are marked with fluorescent beads. The image of the fluospheres is captured with a video camera and processed by a computer-based video imaging system. One basal reference bead in a gelatin layer on the filter support and up to three beads attached at the apical surface are used to monitor changes in cell height of three cells simultaneously. The focusing of the microbeads is done automatically by moving the objective with a piezoelectric device mounted on the nosepiece of the microscope. The algorithm for locating the bead is based on the changes in fluorescent light intensity emitted by the fluospheres. The method has an accuracy higher than 0.1 micron and a time resolution as low as 6 s if measurements are restricted to one bead at the apical side. The method was tested on artificial model systems and used to measure volume changes in renal cultured epithelia (A6) after exposing the serosal surface to hypotonic solutions and replacing cell-impermeable sucrose by an organic compound (glycerol) with a smaller reflection coefficient. Serosal hypotonicity elicited a rapid volume increase followed by regulatory volume decrease, whereas the organic compound replacement caused a steady increase in cell volume.

Autoanalysis↗

Prevalence of DSM-III-R disorders among nonclinical compulsive checkers and noncheckers in a college student sample.

The prevalence of lifetime DSM-III-R disorders was assessed in a sample of 100 college students who were classified as compulsive checkers (n = 50) or noncheckers (n = 50) on the basis of their responses to the Checking subscale of the Maudsley Obsessional-Compulsive Inventory (MOCI). DSM-III-R disorders were assessed on the basis of responses to the Diagnostic Interview Schedule, Version III Revised (DIS-III-R), administered by trained, lay interviewers, blind to Ss' checking status. Checkers, compared to noncheckers, were significantly more likely to meet lifetime diagnostic criteria for Major Depressive Episode, Drug Abuse/Dependence, and Social Phobia. Analysis of a subsample (n = 74) selected on the basis of the consistency of responses to the MOCI across two administrations replicated the above effects, with two exceptions: (1) checkers were more likely to meet criteria for Obsessive Compulsive Disorder than were noncheckers, and (2) for males, but not females, Simple Phobia was more prevalent among checkers than among noncheckers. These findings extend our previous work by demonstrating that 'nonclinical' checking behavior is associated with a broad range of psychological syndromes and may, in fact, be more strongly associated with other disorders than it is with Obsessive Compulsive Disorder in a nonclinical sample.

Adolescent↗