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Biomedical subjects

J G Williams

Publications and source records attributed to J G Williams.

At least 19 recordsLinked to original sources
PubMed1992

Chemotactic sorting to cAMP in the multicellular stages of Dictyostelium development.

Dictyostelium transformants that overproduce the extracellular form of cyclic nucleotide phosphodiesterase and so accumulate a reduced amount of cAMP are blocked in development after aggregation in the form of a tight mound, prior to formation of the apical tip. In such mounds, prespore cell differentiation is repressed, and the apical accumulation of prestalk cells is greatly retarded. When a source of cAMP is placed below the arrested mounds, prestalk cells that would normally migrate in an apical direction instead sort downwards to the substratum. Thus, by acting as the chemoattractant that draws prestalk cells to the apex, cAMP signaling directs the formation of a patterned structure.

Animals↗
PubMed1992

Culmination in Dictyostelium is regulated by the cAMP-dependent protein kinase.

We placed a specific inhibitor of cyclic AMP-dependent protein kinase (PKA) under the control of a prestalk-specific promoter. Cells containing this construct form normally patterned slugs, but under environmental conditions that normally trigger immediate culmination, the slugs undergo prolonged migration. Slugs that eventually enter culmination do so normally but arrest as elongated, hairlike structures that contain neither stalk nor spore cells. Mutant cells do not migrate to the stalk entrance when codeveloped with wild-type cells and show greatly reduced inducibility by DIF, the stalk cell morphogen. These results suggest that the activity of PKA is necessary for the altered pattern of movement of prestalk cells at culmination and their differentiation into stalk cells. We propose a model whereby a protein repressor, under the control of PKA, inhibits precocious induction of stalk cell differentiation by DIF and so regulates the choice between slug migration and culmination.

Animals↗
PubMed1992

Cloning and characterization of the Dictyostelium discoideum rasG genomic sequences.

A Dictyostelium discoideum genomic DNA clone containing the ras-related gene, rasG was isolated using the rasG cDNA as a probe. The genomic clone encompasses the entire coding region of the gene and 1.5 kb of 5' flanking region. The rasG gene contains a single intron as determined by sequence comparison with the cDNA, whereas the highly related rasD gene contains three introns. Primer extension analysis showed that transcription of the rasG gene initiates at multiple sites. Sequence analysis of the 5' flanking region of the gene revealed a stretch of thymine residues upstream from the transcription start sites but there is no evidence for a TATA box sequence.

Animals↗
PubMed1992

Global and local genome mapping in Arabidopsis thaliana by using recombinant inbred lines and random amplified polymorphic DNAs.

A population of Arabidopsis thaliana recombinant inbred lines was constructed and used to develop a high-density genetic linkage map containing 252 random amplified polymorphic DNA markers and 60 previously mapped restriction fragment length polymorphisms. Linkage groups were correlated to the classical genetic map by inclusion of nine phenotypic markers in the mapping cross. We also applied a technique for local mapping that allows targeting of markers to a selected genome region by pooling DNA from recombinant inbred lines based on their genotype. We conclude that random amplified polymorphic DNAs, used in conjunction with a recombinant inbred population, can facilitate the genetic and physical characterization of the Arabidopsis genome and that this method is generally applicable to other organisms for which appropriate populations either are available or can be developed.

Chromosome Mapping↗
PubMed1992

Macrophage priming by interferon gamma: a selective process with potentially harmful effects.

The tissue-fixed macrophage is a key cellular element in the initiation and regulation of inflammation. Understanding the regulation of macrophage activation may provide valuable clues to the mechanisms involved in both beneficial and deleterious effects of inflammation. The lymphokine interferon-gamma (IFN-gamma) is capable of producing paradoxical immunoinflammatory effects. In the immunocompromised host it up-regulates a variety of immune functions and improves survival, but it is also capable of producing harmful effects by sensitizing immunocompetent animals to subclinical doses of endotoxin. These paradoxical effects suggest that the state of activation or priming of the host immune system is a key determinant of its response to endotoxemia. Because tumor necrosis factor (TNF) and procoagulant activity (PCA) elaboration by the tissue-fixed macrophage play a central role in the host response to endotoxin, we asked whether the paradoxical effects of IFN-gamma may be caused by priming of the macrophage for TNF and/or PCA production. In vitro, IFN-gamma produces a marked augmentation in TNF but does not alter PCA elaboration in response to endotoxin, demonstrating the selectivity of IFN-gamma priming of the macrophage. In vivo, IFN-gamma pretreatment followed by an established subclinical endotoxin exposure enhances toxicity while simultaneously increasing peak serum TNF levels. Exogenous priming by IFN-gamma alters the activation state of the macrophage and modifies the host response to endotoxin. Because this response is also dependent on the host's underlying immune state, IFN-gamma treatment in the immunocompetent host has the potential to produce deleterious effects by eliciting an exaggerated TNF response during endotoxemia.

Animals↗
PubMed1992

Liposome-encapsulated hemoglobin inhibits tumor necrosis factor release from rabbit alveolar macrophages by a posttranscriptional mechanism.

Macrophages contribute to the systemic inflammatory response that characterizes the sepsis syndrome through the production of inflammatory cytokines such as tumor necrosis factor (TNF). Liposome-encapsulated hemoglobin (LEH), a potential red cell substitute, is cleared by fixed tissue macrophages. In these studies, in vitro incubation of alveolar macrophages with stored LEH was shown to inhibit the expression of TNF induced by endotoxin (lipopolysaccharide, LPS) stimulation. This effect was dependent on LEH dose but independent of the period of exposure to the LEH. Despite inhibition of TNF expression, Northern blot analysis of total cellular RNA from LPS-stimulated macrophages revealed accumulations of TNF-specific transcripts in cells treated with or without LEH. Thus the mechanism of LEH inhibition of TNF expression appears to involve a posttranscriptional event. Although these results suggest a potential advantage of resuscitation with LEH when sepsis complicates hemorrhagic shock, immunomodulation in vivo remains to be defined.

Animals↗
PubMed1992

Treatment of rectal prolapse in the elderly by perineal rectosigmoidectomy.

The results and complications of perineal rectosigmoidectomy for complete rectal prolapse in 114 patients have been reviewed. Most patients were elderly and high risk by virtue of other concurrent medical conditions. Fourteen patients (12 percent) developed significant postoperative complications. Hospital stay was short (median, four days). Ten patients were lost to follow-up. The remaining 104 patients were followed for 3 to 90 months. Eleven patients (10 percent) developed recurrent full-thickness rectal prolapse, six of them underwent repeat perineal rectosigmoidectomy. Sixty-seven patients had fecal incontinence prior to surgery. Eleven patients underwent concomitant levatoroplasty; 10 of them either improved or regained full continence of feces postoperatively. Twenty-six of the 56 patients who underwent perineal rectosigmoidectomy alone improved or regained full continence. Rectal prolapse can be successfully treated by perineal rectosigmoidectomy in elderly, high-risk patients with minimal morbidity. Levatoroplasty dramatically improves fecal incontinence occurring in association with rectal prolapse.

Adult↗
PubMed1992

The relationship between adenoma weight and intact (1-84) parathyroid hormone level in primary hyperparathyroidism.

The relationship between preoperative serum levels of intact parathyroid hormone (PTH), serum calcium, and the weight of parathyroid adenoma has been investigated in 44 patients undergoing surgery for primary hyperparathyroidism due to single gland disease. There was no significant correlation between preoperative serum calcium and either intact PTH concentration or adenoma weight (r = 0.465 and 0.381, respectively). Although there was a significant correlation between PTH concentration and adenoma weight (r = 0.850, p less than 0.0005), this correlation was lost when two unusually heavy adenomas weighing 10.98 and 15.23 g were removed from the analysis. Clearly, a preoperative direct prediction of gland weight determined from PTH level was not possible. Patients with adenomata heavier than 750 mg had a significantly lower circulating PTH level per mg of adenoma than patients with glands lighter than 750 mg. PTH secretion in vitro in low calcium medium by adenoma cells from glands weighing less than 1 g was higher than secretion by cells from adenomas heavier than 1 g. Larger parathyroid adenomata appear to secrete less PTH per unit weight in vivo and per unit cell in vitro under conditions of maximal stimulation.

Adenoma↗
PubMed1992

A G-rich sequence element common to Dictyostelium genes which differ radically in their patterns of expression.

Removal of a G-rich element from the DIF-inducible, prestalk-, and stalk-specific ecmB gene reduces expression but cell-type specificity is retained. The ecmB element will functionally substitute for a homologous sequence upstream of CP2, a cAMP-inducible gene and is bound by GBF, the factor which interacts with the CP2 G box. These results suggest that the G box may play a similar stimulatory role in these two independently regulated genes where it presumably interacts with different ancillary promoter elements.

Animals↗
PubMed1992

Multiple roles for cAMP-dependent protein kinase during Dictyostelium development.

The cAMP-dependent protein kinase (PKA) holoenzyme of Dictyostelium comprises a single regulatory (R) and catalytic (C) subunit, and both proteins increase in concentration during cellular aggregation. In order to determine the role of the kinase, we have constructed mutants of the R subunit that are defective in cAMP binding, in inhibition of the C subunit, or in both functions. Analysis of these mutants suggests that overexpression of the unmutated R subunit, which is known to block development, occurs by direct inactivation of the C subunit rather than by an effect on intracellular cAMP levels. Cells with an inactive C subunit (PKA- cells) are defective in cAMP relay, the production of cAMP in response to extracellular cAMP stimulation. This presumably accounts for their inability to undertake aggregation. When mixed with wild-type cells, PKA- cells migrate toward the signalling centre but remain confined to the periphery of the tight aggregate and are lost from the back of the migratory slug. This suggests that PKA may be required during the late, multicellular stages of development. Consistent with this, we find that a number of postaggregative genes are not expressed in PKA- cells, even when they are allowed to synergise with normal cells.

Animals↗
PubMed1992

Absorption of non-haem iron in normal women measured by the incorporation of two stable isotopes into erythrocytes.

1. Iron absorption has been quantitatively measured as the incorporation of physiological doses of stable iron isotopes into erythrocytes. Five milligrams of 57Fe (orally) and 250 micrograms of 58Fe (intravenously) were given to five healthy women on 2 consecutive days. Fourteen days later the changes in the 57Fe/56Fe and 58Fe/56Fe ratios in the erythrocytes of each subject were measured using an inductively coupled plasma mass spectrometer. Isotope ratios were also measured in two subjects who were not given any enriched isotope. Concomitant measurements of plasma volume using a dye-dilution technique enabled the estimation of body iron mass and the calculation of iron absorption. 2. The mean coefficients of variation for the 57Fe/56Fe ratio and the 58Fe/56Fe ratio were 0.22% and 0.47%, respectively. This precision allowed enrichments of basal ratios to be reliably detected in all cases. The mean change in the 57Fe/56Fe ratio was 0.00116 (SD 0.00052, P < 0.001) and the mean change in the 58Fe/56Fe ratio was 0.00035 (SD 0.00004, P < 0.001). Control subjects showed no enrichment. 3. The calculated iron absorption ranged from 10% to 34%, and the amount of absorption was related to the iron stores of the subjects. Percentage iron absorption was identical when estimates of the plasma volume (derived from a body mass equation) were used instead of the plasma volume determined by dye-dilution measurements. Incorporation of intravenous iron into erythrocytes was on average 81% (range 68-93%). 4. The method is especially applicable to the study of iron absorption during pregnancy when incorporation into erythrocytes cannot be predicted.

Absorption↗
PubMed1992

Inducible expression of calmodulin antisense RNA in Dictyostelium cells inhibits the completion of cytokinesis.

The single gene encoding calmodulin in the eukaryotic microorganism Dictyostelium discoideum was cloned and sequenced. The gene was found to contain three introns, one lying immediately after the translation initiation codon. The deduced amino acid sequence indicated that Dictyostelium calmodulin contains 19 amino acid differences from vertebrate calmodulin, including extensions at both termini. Northern blot analysis showed that similar levels of calmodulin mRNA are present throughout growth and development of wild-type cells. A complete copy of the calmodulin cDNA was prepared, and an 87-base pair fragment complementary to the 5'-end of the calmodulin mRNA was subcloned into the Dictyostelium transformation vector pVEII, such that expression of the antisense transcript was driven by the discoidin I gamma promoter. Transformed cells were selected and maintained at low cell density, a condition resulting in minimal activity of the discoidin I promoter. High level expression was induced by allowing the transformants to reach high cell density or by growing them in the presence of medium conditioned by high density cells. Under these conditions, in which calmodulin mRNA and protein levels were reduced about twofold, the calmodulin antisense transformants lost the ability to complete cytokinesis. A contractile ring formed and constricted, but the midbody linking daughter cells failed to break. The resulting cell population contained multinucleated cells and networks of cells connected by cytoplasmic bridges. Normal cell division was restored when the cells were diluted to low density. These observations have identified a new point at which calmodulin may regulate cell cleavage.

Amino Acid Sequence↗
PubMed1992

Reducing distress associated with pelvic examinations: a stimulus control intervention.

The effect of a new pelvic examination gown on patients' experienced discomfort during pelvic examination was tested. It was hypothesized that a better designed gown would reduce reported distress. Subjects were 87 patients at a private gynecology clinic. Age ranged from 17 to 72. Informed consent was obtained and patients were randomly assigned to either the experimental gown or the standard drape condition. Following examination, subjects completed questionnaires assessing demographic characteristics, state and trait anxiety, desired changes in pelvic examination procedures, and reactions to the examination. The attending nurse recorded heart rate and blood pressure. Results supported the hypotheses. Experimental subjects rated the gown as more comfortable than control subjects rated the drape. Experimental subjects desired fewer changes in exam procedures than control subjects, indicating that the gown provided them with an overall more comfortable experience.

Adolescent↗
PubMed1992

Reducing distress associated with pelvic examinations: a replication.

A previous study of the effect of a new examination gown on patients' experienced discomfort during pelvic examination demonstrated that the gown was effective. This study replicated the previous study with a younger group of subjects. It was hypothesized that the new gown would reduce reported distress. Subjects were 147 patients at a university student health center. Age ranged from 18 to 31. Informed consent was obtained and patients were randomly assigned to either the experimental gown or the standard drape condition. Following examination, subjects completed questionnaires assessing demographic characteristics, state and trait anxiety, desired changes in pelvic examination procedures, and reactions to the examination. The attending nurse recorded blood pressure. Results supported the hypotheses. Experimental subjects rated the gown as more comfortable than control subjects rated the drape. Results indicate that this simple stimulus control intervention reduces one source of distress associated with pelvic examinations.

Adolescent↗
PubMed1992

Histamine H2-receptor antagonists in peptic ulcer disease. Efficacy in healing peptic ulcers.

Duodenal ulcer healing depends on the degree and length of inhibition of gastric secretion and upon the duration of therapy, while gastric ulcer healing is dependent mainly on the duration of therapy. Currently marketed doses of the histamine H2-receptor antagonists heal between 77 and 92% of duodenal ulcers at 4 weeks, and adjuvant treatment to eradicate Helicobacter pylori increases this rate. Once-daily administration is as effective as more frequent dosing regimens and may even result in higher healing rates. Gastric ulcers heal more slowly, but 75 to 88% of ulcers heal after 8 weeks of treatment. While newer more potent acid suppressors such as omeprazole heal ulcers slightly more quickly, the H2-receptor antagonists have an unparalleled safety record of over 15 years. It is unlikely that the prostaglandin analogues can improve on the efficacy of the H2-receptor antagonists with as low an incidence of side effects.

Drug Administration Schedule↗
PubMed1992

Catching action: visuomotor adaptations in children.

Videotapes of the catching action of 28 children aged 4 to 10 years were carefully observed from simultaneous frontal and lateral perspectives. For both one- and two-handed ball catching, three discernible modes of visual attention and limb movement spaced along a maturity continuum were determined. Only for the ten-year-olds catching two-handed did strategies of visual attention (predicting where the ball would be) and limb usage (grasping with the fingers) couple exclusively as in skilled, adult catching. Success in two-handed catching improved exponentially with age from 77% to 96%. For one-handed catching the success rate was 40% at ages 4, 5, and 6 years, 7.5 and 30% at 7 and 8 years, improving steadily to 92% at 10 years. In the middle of age range the drop in performance coincided with the highest incidence of mixed strategies. No gender differences on either strategy or performance were evident.

Attention↗
PubMed1992

Effects of instruction and practice on ball catching skill: single-subject study of an 8-year-old.

An eight-year-old boy learned to make one-handed catches by involvement in three 30-min. periods of instruction and practice consisting of modelling, videotape-based performance feedback, and variable practice interspersed with videotaped assessments on seven consecutive days. An adult-like catching action (both hands) emerged in the second session and was used exclusively thereafter. Catching success at the second and third assessments improved from 40% (preferred hand) and 30% (non-preferred) to over 90% (both hands) on the final assessment. Following the intervention, success and the catching action were similar to those of skillful ten-year-old subjects observed in a previous study.

Attention↗