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Biomedical subjects

L Rueckert

Publications and source records attributed to L Rueckert.

11 recordsLinked to original sources

Secretin induces the apical insertion of aquaporin-1 water channels in rat cholangiocytes.

Aquaporin-1 (AQP1) water channels are present in the apical and basolateral plasma membrane domains of bile duct epithelial cells, or cholangiocytes, and mediate the transport of water in these cells. We previously reported that secretin, a hormone known to stimulate ductal bile secretion, increases cholangiocyte osmotic water permeability and stimulates the redistribution of AQP1 from an intracellular vesicular pool to the cholangiocyte plasma membrane. Nevertheless, the target plasma membrane domain (i.e., basolateral or apical) for secretin-regulated trafficking of AQP1 in cholangiocytes is unknown, as is the functional significance of this process for the secretion of ductal bile. In this study, we used primarily an in vivo model (i.e., rats with cholangiocyte hyperplasia induced by bile duct ligation) to address these issues. AQP1 was quantitated by immunoblotting in apical and basolateral plasma membranes prepared from cholangiocytes isolated from rats 20 min after intravenous infusion of secretin. Secretin increased bile flow (78%, P < 0.01) as well as the amount of AQP1 in the apical cholangiocyte plasma membrane (127%, P < 0.05). In contrast, the amount of AQP1 in the basolateral cholangiocyte membrane and the specific activity of an apical cholangiocyte marker enzyme (i.e., gamma-glutamyltranspeptidase) were unaffected by secretin. Similar observations were made when freshly isolated cholangiocytes were directly exposed to secretin. Immunohistochemistry for AQP1 in liver sections from secretin-treated rats showed intensified staining at the apical region of cholangiocytes. Pretreatment of rats with colchicine (but not with its inactive analog beta-lumicolchicine) inhibited both the increases of AQP1 in the cholangiocyte plasma membrane (94%, P < 0.05) and the bile flow induced by secretin (54%, P < 0.05). Our results in vivo indicate that secretin induces the microtubule-dependent insertion of AQP1 exclusively into the secretory pole (i.e., apical membrane domain) of rat cholangiocytes, a process that likely accounts for the ability of secretin to stimulate ductal bile secretion.

Animals

Sustained attention deficits in patients with lesions of posterior cortex.

Patients with lesions to posterior cortex were compared to controls, matched for age and education, on tests on sustained attention. One test was a simple reaction time task requiring subjects to respond whenever they saw an 'X'. The other was a Continuous Performance Test that required subjects to respond to an 'X' but refrain from responding to other letters. The patients missed more targets than control subjects on both tests. On the Continuous Performance Test the difference between patients and controls increased with time on task, suggesting a sustained attention deficit similar to that previously observed in patients with right frontal lesions. However, whereas frontal patients showed a tendency toward greater impairment when the rate of stimulus presentation was relatively slow, the posterior patients performed significantly worse when the stimuli were presented at a faster rate.

Analysis of Variance

Visualizing cortical activation during mental calculation with functional MRI.

Cortical activation during arithmetic calculation (silent subtraction by sevens) was compared to that observed during a control condition for which subjects were required to count forward by ones. Nine normal subjects underwent 1.5-T functional magnetic resonance imaging while performing these tasks. All subjects showed bilateral premotor, posterior parietal, and prefrontal cortex activation during serial calculation. There was a large degree of individual variation in activation outside of these areas. These results confirm the role of posterior parietal cortex in arithmetic calculation and implicate other regions, including prefrontal cortex.

Adult

Further evidence that the callosum is involved in sustaining attention.

This study is a follow-up to a previous study that found a correlation between callosal efficiency and sustained attention. Normal children were tested on a vigilance task in which the amount of time between target presentations (interstimulus interval; ISI) was varied. Efficiency of the anterior callosum was assessed by a task that required subjects to perform incongruent movements with the left and right hands simultaneously. Subjects who showed less interference between the two hands missed fewer signals on the vigilance task after the longer ISIs, suggesting callosal involvement in the ability to sustain attention over a long period of time in the absence of sensory input. Age differences in the sustained attention were also observed.

Age Factors

Sustained attention deficits in patients with right frontal lesions.

Patients with frontal lobe lesions were compared to controls matched for age and education on several tests of sustained attention. One was a simple reaction time task requiring subjects to respond whenever they saw an "X', one was a Continuous Performance Test that required subjects to respond to an "X' but refrain from responding to other letters, and one involved reading a story and responding to a specified target. Patients with right frontal lesions showed longer RTs and missed more targets than control subjects for all three tests. In addition, right frontal patients got worse with time on the CPT. These results suggest a special role for the right frontal lobe in sustaining attention over time.

Arousal

Functional magnetic resonance imaging of the brain.

This conference reviewed the potential scope of application of recently developed techniques for functional magnetic resonance imaging (fMRI) of the brain. The most successful technique is based on the sensitivity of magnetic resonance imaging (MRI) to magnetic effects caused by the modulation of the oxygenation state of hemoglobin, which is induced by local variations in blood flow during task activation. Typically, the MRI signal increases by a few percentage points during brain activation because blood flow and oxygen supply sharply increase. Brain activation images with excellent combined spatial and temporal resolution have been obtained noninvasively using visual, sensorimotor, or auditory stimuli, or during higher-order cognitive processes such as language or mental imagery. Although sensitive to misregistration artifacts and macroscopic vessels, MRI permits both the direct correlation of function with underlying anatomy and repeated studies on the same person. It may become the method of choice for studies of mental and cognitive processes, presurgical mapping, monitoring recovery from stroke or head injuries, exploration of seizure disorders, or monitoring the effects of neuropharmaceuticals.

Animals

Callosal efficiency is related to sustained attention.

The purpose of this study was to determine whether there is a relationship between the efficiency of interhemispheric communication (IHC) and the ability to sustain attention. Children were tested on a vigilance task in which the amount of time between target presentations (interstimulus intervals; ISI) was varied. IHC was assessed by comparing within-field and between-field matches on a tachistoscopic task. Subjects who showed better IHC had faster RTs on the long ISI trials of the vigilance task, suggesting callosal involvement in the ability to sustain attention over a long period of time in the absence of sensory input.

Arousal

Magnetic resonance imaging functional activation of left frontal cortex during covert word production.

Six normal volunteers underwent 4-T functional magnetic resonance imaging while performing a covert letter fluency task. An echo planar imaging sequence was utilized to detect activation based on deoxyhemoglobin contrast. All 6 subjects showed consistent activation in the frontal operculum and premotor and primary motor cortices. Activation was also detected in the supramarginal gyrus and the posterior part of the superior temporal gyrus. These results show that magnetic resonance functional neuroimaging can be used to investigate cerebral activity noninvasively during performance of complex cognitive tasks.

Adult

Hand posture in writing: possible artifacts from self report.

Seven hundred forty undergraduate students were asked to report the hand posture they used during writing and the presence or absence of left-handedness in the immediate family. Drawings were provided of prototypical "normal" and "inverted" posture and subjects were also given the option of reporting that their hand posture was somewhere between the two illustrated positions. The incidence of reporting "between" was 17% for left-handers and 46% for right-handers. These results suggest that experimenters should exercise caution when categorizing subjects on the basis of self-report forms that include only two choices: normal posture and inverted posture.

Adult

Small subunit contacts in ribulose-1,5-bisphosphate carboxylase.

The arrangement of subunits of ribulosebisphosphate carboxylase in solution has been studied by exposing the enzyme to the cross-linking agents tetranitromethane, dimethyl suberimidate, and dimethyl adipimidate, and the cleavable cross-linking agent, methyl 4-mercaptobutyrimidate followed by gel electrophoresis in the presence of dodecyl sulfate. All these agents caused the formation of dimers of the enzyme's small subunit, independently of protein concentration. In addition, trimers and tetramers of small subunit were detected in the mercaptobutyrimidate-treated enzyme. The data show that small subunits are closely paired in the native enzyme and may be in layers of four, or a ring of eight.

Carboxy-Lyases