PubMed Health⌕ Search

Biomedical subjects

D Childs

Publications and source records attributed to D Childs.

16 recordsLinked to original sources

A role for guanylate cyclase C in acid-stimulated duodenal mucosal bicarbonate secretion.

Luminal acidification provides the strongest physiological stimulus for duodenal HCO3- secretion. Various neurohumoral mechanisms are believed to play a role in acid-stimulated HCO3- secretion. Previous studies in the rat and human duodenum have shown that guanylin and Escherichia coli heat-stable toxin, both ligands of the transmembrane guanylyl cyclase receptor [guanylate cyclase C (GC-C)], are potent stimulators for duodenal HCO3- secretion. We postulated that the GC-C receptor plays an important role in acid-stimulated HCO3- secretion. In vivo perfusion studies performed in wild-type (WT) and GC-C knockout (KO) mice indicated that acid-stimulated duodenal HCO3- secretion was significantly decreased in the GC-C KO animals compared with the WT counterparts. Pretreatment with PD-98059, an MEK inhibitor, resulted in attenuation of duodenal HCO3- secretion in response to acid stimulation in the WT mice with no further effect in the KO mice. In vitro cGMP generation studies demonstrated a significant and comparable increase in cGMP levels on acid exposure in the duodenum of both WT and KO mice. In addition, a rapid, time-dependent phosphorylation of ERK was observed with acid exposure in the duodenum of WT mice, whereas a marked attenuation in ERK phosphorylation was observed in the KO animals despite equivalent levels of ERK in both groups of animals. On the basis of these studies, we conclude that transmembrane GC-C is a key mediator of acid-stimulated duodenal HCO3- secretion. Furthermore, ERK phosphorylation may be an important intracellular mediator of duodenal HCO3- secretion.

Acids↗

Cortisol response to two different doses of intravenous synthetic ACTH (tetracosactrin) in overweight cats.

Fifteen middle-aged to older, overweight cats attending a first-opinion clinic were investigated to rule out hyperadrenocorticism as a cause of their weight problem, using two different protocols for the adrenocorticotropic hormone (ACTH) stimulation test. The cats received intravenous synthetic ACTH (tetracosactrin) at an initial dose of 125 microg; a second test was performed between two and three weeks later, using a dose of 250 microg intravenously. The mean basal serum cortisol concentration was 203 nmol/litre (range 81 to 354 nmol/litre). The highest mean serum cortisol concentration occurred at 60 minutes following the 125 microg dose and at 120 minutes following the 250 microg dose. There was, however, no statistically significant difference between these peak cortisol concentrations attained using either dose of tetracosactrin. A significantly higher mean serum cortisol concentration was attained after the higher dose at the 180 minutes time point, indicating a more prolonged response when compared with the lower dose. The cats were followed up for one year after the initial investigations and none were found to develop hyperadrenocorticism during this time.

Adrenocorticotropic Hormone↗

Identification of novel temperature-sensitive lethal alleles in essential beta-tubulin and nonessential alpha 2-tubulin genes as fission yeast polarity mutants.

We have screened for temperature-sensitive (ts) fission yeast mutants with altered polarity (alp1-15). Genetic analysis indicates that alp2 is allelic to atb2 (one of two alpha-tubulin genes) and alp12 to nda3 (the single beta-tubulin gene). atb2(+) is nonessential, and the ts atb2 mutations we have isolated are dominant as expected. We sequenced two alleles of ts atb2 and one allele of ts nda3. In the ts atb2 mutants, the mutated residues (G246D and C356Y) are found at the longitudinal interface between alpha/beta-heterodimers, whereas in ts nda3 the mutated residue (Y422H) is situated in the domain located on the outer surface of the microtubule. The ts nda3 mutant is highly sensitive to altered gene dosage of atb2(+); overexpression of atb2(+) lowers the restrictive temperature, and, conversely, deletion rescues ts. Phenotypic analysis shows that contrary to undergoing mitotic arrest with high viability via the spindle assembly checkpoint as expected, ts nda3 mutants execute cytokinesis and septation and lose viability. Therefore, it appears that the ts nda3 mutant becomes temperature lethal because of irreversible progression through the cell cycle in the absence of activating the spindle assembly checkpoint pathway.

Alleles↗

Keratan sulfate content in the superficial and deep layers of osteophytic and nonfibrillated human articular cartilage in osteoarthritis.

Very thin slices of the superficial and deep layers of osteophytic and apparently normal articular cartilage from six human osteoarthritic femoral heads were digested with papain. The digests were analyzed for keratin sulfate content using an enzyme-linked immunosorbent assay (ELISA) with inhibition step, and for chondroitin sulfate and collagen contents using biochemical assays. Although there were marked differences in Safranin-O staining of the superficial and deep layers of osteophytic cartilage, these two layers had identical high ratios of chondroitin sulfate/collagen. Keratan sulfate was present only in small amounts in osteophytic cartilage. However, the deeper layer contained significantly more of this glycosaminoglycan. The deeper layer of articular cartilage contained approximately twice as much chondroitin sulfate and six times more keratan sulfate relative to collagen than the superficial layer. The results of this study showed that this new sensitive approach, which requires as little as 200 micrograms wet cartilage as starting material, provides important qualitative and quantitative information about the major constituents of the matrix.

Cartilage, Articular↗

Peri-operative dreaming in paediatric patients who receive suxamethonium.

A prospective study is described of peri-operative dreaming in 144 paediatric patients aged 5-14 years who received suxamethonium for day case surgery. No case of awareness was elicited. One group received pretreatment with 80 micrograms/kg [corrected] tubocurarine. The incidence of dreaming in the 72 patients who were not pretreated was 16.7% compared with 2.8% in the patients pretreated with tubocurarine. This difference is statistically significant. The use of an intermittent suxamethonium technique gives a high incidence of dreaming which may be caused by muscle spindle discharge that produces cerebral arousal. Pretreatment with a non-depolarizing agent decreases this risk of dreaming.

Adolescent↗

Arterial oxygenation after major head and neck surgery involving tracheotomy.

Changes in vital capacity, and in arterial PO2 and PCO2, were studies after major head and neck surgery involving tracheotomy and after surgery on the upper abdomen. After major head and neck surgery, changes in vital capacity were comparable to those seen after upper abdominal operations, with a decrease on day 1 of 39% recovering to 78% of the preoperative volume by day 7. Arterial PO2 in both groups decreased on day 1 but whereas PaO2 after upper abdominal surgery was recovering by day 7, PaO2 in the head and neck group, at day 7, showed no sign of recovery. Arterial PO2 7 days after major head and neck surgery was 2.3 (+/- 0.4) kPa below the preoperative value (P less than 0.001).

Abdomen↗

Improved perinatal knowledge in community hospitals through a self-instructional program.

The Perinatal Continuing Education Program (PCEP) was conducted throughout South Carolina. The program was well received and greatly valued; however, participants requested more information covering obstetrics. To meet this need, we developed the Perinatal Education Program for Community Hospitals (PEPCH), patterned after and similar to PCEP, and tested it in South Carolina and southern California. In the South Carolina trial, the posttest was found reliable (Kuder-Richardson index = .77). In the California trial, the pretest/posttest reliability was confirmed. Learning for nurses was documented (pretest = 30.8 +/- 5.3, posttest = 36.8 +/- 5.5, P less than .001). Completion rate for this voluntary program was 84%. We conclude that a self-study program based in the community hospital can improve knowledge of perinatal professionals.

California↗

The analysis of interpersonal perceptions as a repertory grid.

In order to set goals and evaluate progress in therapy with couples it is important to begin with a clear formulation of the problem. The technique described provides quantitative data on three aspects of a relationship. Firstly, the extent to which a couple are in fact using a common language. Second, the extent to which they agree, understand each other's point of view, and realize how they are understood. Thirdly, the differences between their perception of the present and their goals for themselves and one another in the future. The investigation uses personal constructs elicited from the couple and the results are analysed as a repertory grid. Summary measures provided by the grid analysis organize the large amount of data and provide a general context for understanding the relationship within which particular aspects can be identified for more detailed analysis.

Adult↗