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Biomedical subjects

K A Gilbert

Publications and source records attributed to K A Gilbert.

11 recordsLinked to original sources

Parenteral nutrition for the acutely ill.

Parenteral nutrition (PN) is one of the most sophisticated forms of intravenous therapy in use today. Intravenous feeding is a life-saving technology for patients unable to maintain their nutritional status using the gastrointestinal tract. Although PN has become an integral component of patient care, the risks associated with this therapy must be weighed against the potential benefits. Comprehensive clinical management includes selection of candidates, implementation and monitoring of therapy, and ensuring a seamless transition when PN is no longer required. Optimal parenteral nutrition demands expertise in caring for vascular access devices. A collaborative approach to care minimizes the risks associated with PN and ensures positive patient outcomes.

Acute Disease↗

Inhibition of gap junction communication in alveolar epithelial cells by 18alpha-glycyrrhetinic acid.

Cultured alveolar epithelial cells exhibit gap junction intercellular communication (GJIC) and express regulated levels of connexin (Cx) 43 mRNA and protein. Newly synthesized radiolabeled Cx43 protein equilibrates with phosphorylated Cx43 isoforms; these species assemble to form both connexons and functional gap junction plaques. The saponin 18alpha-glycyrrhetinic acid (GA) rapidly and reversibly blocks GJIC at low concentrations (5 microM). Extended exposure to 18alpha-GA at higher concentrations causes inhibition of GJIC and time- and dose-dependent reductions in both Cx43 protein and mRNA expression. The latter toxic effects are paralleled by disassembly of gap junction plaques and are reversed less readily than acute effects on GJIC. These observations demonstrate 18alpha-GA-sensitive regulation of intercellular communication in epithelial cells from the mammalian lung and suggest a role for Cx43 expression and phosphorylation in acute and chronic regulation of GJIC between alveolar epithelial cells.

Animals↗

Isolation, cloning, and characterization of a novel rat lung zinc finger gene, RLZF-Y.

Zinc-finger (ZF) proteins are widely distributed. The current study reports isolation, cloning and characterization of a novel ZF gene, RLZF-Y. Total RNA from rat lung was reverse transcribed. The 5' and 3' ends were isolated by rapid amplification of cDNA ends (RACE) using primers derived from a previously isolated partial clone. RACE products of 1.5 and 1.1 kb were cloned and sequenced. Identical overlapping sequence of 70 base pairs confirmed representation of the same cDNA approximately 2.5 kb in length. Probes derived from both 5' RACE and 3' RACE products independently hybridized to a 2.5 kb mRNA from rat lung. RLZF-Y mRNA is expressed in lung, brain, heart and kidney; expression is low in liver. Predicted amino acid sequence analysis defined three regions of similarity to known C2H2 ZF proteins: a region containing seven ZF structures characteristic of the Krüppel-like subfamily of ZF genes; a region with sequence similarity to the Krüppel-associated box A (KRAB-A) domain at the amino end; an amino-terminal leucine-rich region (LeR) adjacent to KRAB-A. The presence of KRAB-A and the adjacent LeR implies RLZF-Y protein may function as a transcriptional repressor.

Amino Acid Sequence↗

Increased lung inflation induces gene expression after pneumonectomy.

Rapid hyperplastic growth of the remaining lung is initiated by partial pneumonectomy in many mammalian species. The response restores normal tissue structure and function. Although physiological control of compensatory lung growth is documented, little is known about the molecular mechanisms that underlie the process. The aim of this study was to investigate the role of mechanical signals in the induction of immediate-early gene (IEG) expression after pneumonectomy. Expression of c-fos and junB increased nine- and fourfold, respectively, in the right lung within 30 min after left pneumonectomy in rats. In contrast, changes in expression of c-jun and c-myc were not observed. When isolated lungs were subjected to elevated airway pressures in vitro, expression of c-fos and junB was induced in a time- and dose-dependent manner similar to that observed in vivo. Similarly, in vitro lung perfusion induced c-fos and junB expression in the absence of increasing lung inflation. These results support the premise that rapid changes in IEG expression after pneumonectomy are initiated by mechanical signaling in the remaining lung. Elevated IEG expression may contribute to initiation of compensatory lung growth.

Animals↗

Targeted identification of zinc finger genes expressed in rat lungs.

Control of alveolar cell growth and differentiation after pneumonectomy likely involves changes in expression of regulatory genes, including those encoding zinc finger (ZF) proteins. To explore this premise, total RNA from the lungs of control and pneumonectomized rats was reverse transcribed; PCRs were performed with degenerate primers corresponding to amino acid sequences HTGEKP and CPECGK(N), which are evolutionarily conserved among ZF genes. Reaction products corresponding to three and four ZF units were isolated and cloned. Sixteen clones were sequenced and found to represent rat lung ZF genes: six clones were highly similar or identical to known ZF genes and ten clones showed lower homology to known ZF genes and thus appear to represent new members of the ZF family. Northern analysis demonstrated differential expression of some ZF genes after pneumonectomy. Thus a PCR-based strategy with primers derived from evolutionarily conserved ZF protein sequences efficiently identifies ZF genes expressed in lung, some of which may play a role in cellular growth and differentiation.

Amino Acid Sequence↗

Pontine cholinergic reticular mechanisms cause state-dependent changes in the discharge of parabrachial neurons.

The present study examined the hypothesis that cholinoceptive reticular mechanisms in the gigantocellular tegmental field (FTG) of the medial pontine reticular formation cause state-dependent changes in the discharge of parabrachial neurons. In chronically implanted, unanesthetized cats, extracellular recordings were made from nonrespiratory and respiratory neurons in the parabrachial nuclear complex (PBNC) during the natural sleep-wake cycle and during the rapid eye movement (REM) sleeplike state caused by FTG microinjection of carbachol or neostigmine. PBNC cells that increased discharge during natural REM sleep (REM-on cells) revealed similar increased discharge during the carbachol-induced REM sleeplike state (DCarb). Cells that decreased discharge in natural REM sleep (REM-off cells) displayed decreased discharge during both DCarb and the neostigmine-induced REM sleeplike states. The limited sample of parabrachial respiratory neurons revealed significantly diminished discharge during the cholinergically induced REM sleeplike state. Thus cholinoceptive mechanisms localized to specific regions of the pontine reticular formation can cause state-dependent changes in the firing rates of respiratory and nonrespiratory neurons in the PBNC.

Animals↗

Pontomedullary neurons transsynaptically labeled by laryngeal pseudorabies virus.

The activity of the laryngeal abductor, the posterior cricoarytenoid (PCA) muscles, is diminished with the loss of wakefulness. During sleep, PCA muscles become hypotonic, suggesting that neural mechanisms which control states of consciousness also contribute to state-dependent changes in upper airway patency. The medial pontine reticular formation (mPRF) has long been known to play a key role in sleep control. Microinjection of cholinergic agonists into the mPRF produces a rapid eye movement (REM) sleep-like state and PCA muscle hypotonia, but the neuroanatomical pathways mediating this hypotonia are not clear. Therefore, the present study used retrograde transsynaptic viral labeling to define multisynaptic pathways from the PCA muscles to the mPRF. Pseudorabies virus was injected into the laryngeal PCA muscles of anesthetized rats. The distribution of retrogradely labeled neurons was studied in the brain stem 4 days post-inoculation. The results show that brain stem areas known to be involved in sleep cycle control are part of a multisynaptic pathway providing input to the laryngeal PCA muscles.

Airway Obstruction↗

Muscarinic cholinoceptive reticular mechanisms and parabrachial neuron discharge: a novel experimental approach.

This study examined the hypothesis that cholinergic receptor mechanisms within the gigantocellular tegmental field (FTG) of the medial pontine reticular formation can cause state-dependent changes in the firing rates of parabrachial nuclear complex (PBNC) neurons. Using intact, unanesthetized cats, long-term recordings were obtained from single PBNC neurons following FTG administration of cholinergic agonists and antagonists. We show that the state-dependent decrease in PBNC cell discharge reported in this study can be attributed to muscarinic mechanisms within the FTG. Our pharmacological blocking results further suggest that diminished PBNC discharge was mediated by non-M1 muscarinic receptors in the FTG. This study demonstrates the usefulness of combining long-term neuronal recordings in the PBNC with multiple pharmacological manipulations within the FTG.

Animals↗

Parabrachial neuron discharge in the cat is altered during the carbachol-induced REM sleep-like state (DCarb).

Pontine parabrachial neurons have been suggested to play a regulatory role in both respiratory and sleep cycle control. Encouraged by the finding that microinjections of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) of the cat produced respiratory changes paralleling those observed during rapid eye movement (REM) sleep (Neurosci. Lett., 102 (1989) 211-216), this study tested the hypothesis that cholinergic mechanisms in the mPRF can also cause state-dependent changes in the discharge of parabrachial neurons. This paper describes extracellular recordings of parabrachial neurons during REM sleep and during the carbachol-induced REM sleep-like state (DCarb). Cells which were activated (REM-on) or inactivated (REM-off) during REM maintained the same state-dependent firing patterns during the DCarb state. These results support the hypothesis that cholinergic mechanisms in the mPRF can cause state-dependent changes in the discharge of parabrachial neurons.

Animals↗

Environmental change and psycholinguistic ability of mentally retarded adults.

Effects on linguistic ability of transferring retarded adults from a large institution to small "family" bungalows were examined. Effects of environmental change on linguistic ability were assessed using the Illinois Test of Psycholinguistic Abilities (ITPA) and by video-tape recordings of subjects engaging in speech. Results indicated that the bungalows had more resident-oriented as opposed to institution-oriented practices and more staff-resident interaction than did the large institution. The residents to be transferred were matched with control subjects who remained in the large institution. The ITPA was administered and resident interviews were video taped for both groups immediately before the transfer date and 9 months later. Psycholinguistic ability improved significantly more for transferred residents than for control subjects. Transferred residents increased the number of words used in affirmative and negative replies to simple questions during the videotaped interview, but there were no indications of any progression from one language stage to the next. The findings are comparable to previous studies concerning environmental change and increase in language ability of retarded children.

Adult↗

Gaze patterns of mentally retarded adults in two contrasting environments.

Two matched samples of mentally retarded adults were video recorded on two occasions, before and after one group was transferred to a different type of hospital, and their gaze patterns analyzed. Overall, only slight changes after transfer were found, but analysis according to amount of looking at the interviewer on the first occasion showed that those transferred subjects who initially looked little of the time significantly increased their amount of looking after transfer. Some correlations with the Adaptive Behavior Scale were also reported.

Adult↗