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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 559 records · Page 31Linked to original sources
PubMed1994

A role for cAMP-dependent protein kinase in determining the stability of prespore cell differentiation in Dictyostelium.

When Dictyostelium slugs are disaggregated and shaken in suspension prespore mRNAs disappear from the cells very rapidly but in the presence of extracellular cAMP the loss of prespore mRNA sequences is retarded. In a mutant which lacks a functional regulatory subunit of the cAMP-dependent protein kinase (PKA), and where the catalytic subunit is thereby rendered constitutively active, two prespore mRNA sequences persist for extended times after cellular disaggregation. Thus PKA is a component of the signaling pathway that allows prespore cells rapidly to dedifferentiate when extracellular cAMP signaling is disrupted. Analysis of cells expressing a dominant inhibitor of PKA shows there to be both a PKA-requiring and a non-PKA-requiring intracellular signaling pathway directing prespore-specific gene transcription and suggests that there may also be post-transcriptional regulation by PKA.

Animals↗
PubMed1994

Disruption of the gene encoding the EcmA, extracellular matrix protein of Dictyostelium alters slug morphology.

The ecmA and ecmB genes of Dictyostelium are expressed in prestalk and stalk cells. They encode components of the slime sheath, the extracellular matrix that surrounds the migrating slug, and the stalk tube, the matrix that encases stalk cells. We have generated, by homologous gene disruption, a mutant in which the ecmB gene is inactivated but the strain develops normally. In contrast, ecmA null mutant strains develop to form abnormally long and thin standing slugs. While the slime sheath of mutant slugs appears to be normal in electron microscopic observations, the sheath material remaining on the substratum after the slug travels through it is abnormally susceptible to breakage. After a short period of migration the axial ratio of mutant slugs decreases to that of normal slugs and, at culmination, normal fruiting bodies are produced. These data suggest that the EcmA protein has its primary role during slug formation, where it contributes to the strength of the slime sheath, and that the function of the EcmB protein is dispensible.

Animals↗
PubMed1994

Inhibition of cAMP-dependent protein kinase in Dictyostelium prestalk cells impairs slug migration and phototaxis.

Dictyostelium slugs expressing a dominant inhibitor of the cAMP-dependent protein kinase (PKA) selectively in prestalk cells are insensitive to the environmental signals that normally induce culmination (Harwood et al., 1992a). When such slugs do, eventually, attempt to culminate they are unable to activate stalk-specific gene expression and they become arrested in their development. We show here that they are also about half the size of normal slugs and that they move at about half normal speed, even after their size difference has been taken into account. They are also less accurate in orienting their direction of movement towards the light. Thus, in addition to its role in cellular differentiation, PKA is required for several important aspects of slug behaviour.

Animals↗
PubMed1994

Regulation of cell proliferation and estrogen synthesis by ovine LH, IGF-I, and EGF in theca interstitial cells of the domestic hen cultured in defined media.

There is relatively little information on the factors which regulate the proliferation and alterations in the steroidogenic capacity of avian theca cells during follicular maturation. The development of culture conditions for these cells to determine the effects of gonadotrophin (LH) and the growth factors epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) on DNA synthesis and estrogen production is reported. Cultures were established in serum-supplemented (with fetal calf serum or chicken serum) or ITS+ (insulin, transferrin, and selenium plus additives) supplemented serum-free media. Cell replication occurred throughout the 72-hr culture period as indicated by a linear increase in the DNA content of the culture dishes. Aromatase activity of the cells as defined by conversion of androstenedione to estrogen was best maintained in serum-free medium while sera inhibited this activity. Ovine LH enhanced the aromatase activity of cultured cells from medium and small-sized follicles, while IGF-I and EGF inhibited both basal and LH-stimulated aromatase activity. LH, IGF-I, and EGF all stimulated cell proliferation as reflected by increased DNA. The responses of cells to these peptides varied with the size of the follicle, with the greatest effects on cells from F4/5.

Androstenedione↗
PubMed1994

Chicken granulosa cell proliferation and progesterone production in culture: effects of EGF and theca secretions.

Paracrine/autocrine factors like epidermal growth factor (EGF) and transforming growth factor (TGF alpha) produced in the mammalian ovary modulate ovarian functions such as cell proliferation, differentiation, and steroidogenesis. To study similar activities in the avian ovary, we have developed a culture system for chicken granulosa cells using either serum containing or serum-free media. In the defined medium, granulosa cells for the F1, F2, and F3 follicles of the chicken ovary proliferated as indicated by enhanced levels of DNA, synthesised progesterone in similar amounts to those observed in acute experiments, and responded to luteinizing hormone (LH) during and after the culture period. The morphology of the cells and profile of growth in both media (although better in serum than in serum-free medium) are similar to those reported for mammalian cells. EGF stimulated granulosa cell proliferation over 72 hr in culture while inhibiting basal and LH-stimulated progesterone production; these effects were greatest in the less mature cells taken from the F3 follicles. Theca-conditioned medium (TCM) from chicken ovarian theca cell cultures mimicked the effects of EGF when cultured with granulosa cells. Taken together, these results suggest that EGF/TGF alpha-like peptides have a role in avian ovarian function. Moreover, the effects observed for TCM suggest that these peptides may be present in the theca layer with a paracrine function in the adjacent granulosa.

Animals↗
PubMed1994

Characterization of a cDNA from Arabidopsis thaliana encoding a potential thiol protease whose expression is induced independently by wilting and abscisic acid.

The sequence and expression characteristics are described of a wilt-inducible gene in Arabidopsis thaliana. A1494 encodes a potential thiol protease whose mRNA accumulates rapidly in shoot tissue upon the loss of turgor. A1494 mRNA levels peaked after ca. 4 h and declined thereafter. Dehydration also induced rapid biosynthesis of the phytohormone abscisic acid (ABA), which continued for at least 9 h. Exogenous ABA induced the accumulation of A1494 mRNA, with kinetics similar to those after wilting. Rehydration of wilted shoots led to a rapid decline in the content of both ABA and A1494 mRNA. Wilting and ABA independently induced A1494 expression as evidenced by the effects of ABA and wilting on the ABA-deficient aba-1 and ABA-insensitive abi-1 and abi-3 genotypes. A1494 mRNA was not detectable in aba-1 shoots but accumulated rapidly after either wilting or ABA treatment, whereas the shoot ABA content was increased only by ABA treatment. ABA had no effect on A1494 mRNA levels in the abi-1 and abi-3 mutants but wilting did result in enhanced A1494 expression. Heat shock had only a minor effect on A1494 mRNA levels, whereas exposure to low temperature resulted in substantial accumulation of A1494 mRNA in wild-type shoots. However, this latter response, unlike that to drought, was mediated exclusively via ABA synthesis as demonstrated by the lack of A1494 mRNA accumulation in cold-treated aba-1 shoots.

Abscisic Acid↗
PubMed1994

Prevalence and first-line treatment of diarrhoeal symptoms in the community.

By systematically sampling patient registers in two socio-economically contrasting Scottish urban general practices, 440 households were selected and contracted by a research health visitor who interviewed a household member in 425 of them (response rate = 97%). Information was obtained on the point and period prevalence of diarrhoeal symptoms in all household members (n = 1,335), and on the knowledge, attitudes and behaviour of the respondents. While the point prevalence was low (under 1% of the household members), around 12% were reported to have experienced symptoms in the three-month period prior to the interview, and these were associated with a small but far from negligible loss of time from school or work. There were no significant seasonal differences in prevalence rates, nor were there significant differences between the two practices. Knowledge about appropriate treatment was high, but there was some confusion about the administration of liquids (especially milk) other than water, and a high level of ignorance about the existence and purpose of oral rehydration solutions. These findings have implications for public education about the initial management of acute diarrhoeal symptoms.

Adolescent↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor stimulates macrophages to respond to IgE via the low affinity IgE receptor (CD23).

We have found increased concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid of 11 patients with nocturnal asthma (15.3 +/- 4.6 pg/ml) compared with normal subjects (2.3 +/- 6.1 pg/ml) (p = 0.03). In contrast to patients with asthma, low affinity IgE receptors (Fc epsilon RII or CD23) are not expressed on monocytes obtained from healthy, nonatopic donors. Fc epsilon RII expression was induced by the cytokines GM-CSF and interleukin (IL)-4 either alone or in combination. As assessed by flow cytometry, the combination of IL-4 and GM-CSF was found to be synergistic, inducing up to 54.8% +/- 4.6% Fc epsilon RII-positive monocytes compared with a maximum of 27.4% +/- 5.0% and 30.0% +/- 4.0% with IL-4 and GM-CSF alone, respectively (p < 0.05 compared with either cytokine alone). Human monocytes from the peripheral blood of seven normal subjects were cultured for 24 hours with and without IL-4 or GM-CSF. With IL-4, addition of IgE/anti-IgE complexes failed to induce IL-1 secretion and inhibited IL-1 secretion induced by lipopolysaccharides. The addition of GM-CSF or IgE immune complexes alone resulted in no additional IL-1 secretion in supernatants of the untreated monocytes, whereas the IgE complexes did stimulate IL-1 secretion by monocytes cultured in GM-CSF, as measured by ELISA (from 0.7 +/- 0.2 ng/ml to 2.3 +/- 0.5 ng/ml; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1994

Intracranial hemorrhage as a predictor of occult cervical-spine fracture.

STUDY OBJECTIVE: To determine whether intracranial hemorrhage is a predictor of occult cervical-spine fracture. DESIGN: A prospective, cross-sectional study. SETTING: University-affiliated Level I trauma center. PARTICIPANTS: Ninety-three blunt trauma victims with a Glasgow Coma Scale score of 12 or less. Exclusion criteria were incomplete radiographic evaluation caused by hemodynamic instability, death, or other reasons. INTERVENTIONS: The study protocol required that all patients undergo a five-view cervical-spine trauma series, head computed tomography (CT), and upper cervical-spine CT. Cervical-spine radiographs and CT scans were read by two radiologists blinded to each other's interpretations. The results were compared with each patient's head CT diagnosis. Medical records were reviewed for demographic information and mechanism of injury. RESULTS: Of the 93 patients, 54 had intracranial hemorrhage noted on CT scan; two of these patients had an upper cervical-spine fracture, but only one was an occult cervical-spine fracture. Thirty-nine patients had no intracranial hemorrhage; two patients had an upper cervical-spine fracture, but only one had an occult cervical-spine fracture. Fisher's exact test showed no significant difference between the rate of occult cervical-spine fracture between patients with and without hemorrhage. CONCLUSION: Despite a high percentage of patients with traumatic intracranial hemorrhage, our study failed to demonstrate that intracranial hemorrhage is predictor of occult cervical-spine fracture.

Adolescent↗
PubMed1994

Relating health education research to health policy.

This paper argues that research in health education is being driven by a set of implicit values that emphasize formality, rigor and objectivity, and that relatively little attention is being paid to the ways in which research findings are subsequently used. A critique of a detached and formal research perspective is developed around the problems of 'pure' knowledge and the potential incompatibility between this and policy-making processes. In this light, it is suggested that the pursuit of academic research rigor at the expense of practical utility is hindering the development of a stronger research-policy link. The paper then goes on to suggest that in adopting a sharper political orientation, health education research could legitimately become less concerned with the restrictive nature of academic formalism with research. The nature of this type of research, the potential it has as well as its limitations are subsequently explored.

Health Education↗
PubMed1994

Reduced virulence of rifampicin-resistant mutants of Francisella tularensis.

Rifampicin-resistant mutants of a live vaccine strain (LVS) of Francisella tularensis were produced and screened for virulence in mice; 4 avirulent clones with intraperitoneal (ip) LD50s > 10(6) cfu, compared with 10(2) cfu for LVS, were characterized. Growth characteristics at 37 degrees C, surface envelope proteins, and lipopolysaccharide profiles of resistant mutants were identical to those of LVS. Polymerase activity of the mutants was more resistant than the enzyme from LVS to the inhibitory action of rifampicin. Growth rates for mutants and LVS were similar during the first 5 h at 42 degrees C, but viability of the mutants decreased to < 0.01% at 24 h. LVS and mutants differed in their ability to grow in vitro in host macrophages: LVS increased 580-fold over 72 h; mutants increased 33-fold. After ip inoculation of the organisms into mice, increasing numbers of LVS from peritoneal cells were isolated; mutants decreased over 4 days.

Animals↗
PubMed1994

Cognitive and attitudinal impact of the Advanced Trauma Life Support program in a developing country.

Improvement in trauma patient outcome has been reported after Advanced Training Life Support training (ATLS) in the developing country of Trinidad and Tobago (T & T). The cognitive impact of ATLS training was assessed from pre-ATLS and post-ATLS performance of T & T physicians in multiple choice question tests and comparison with post-ATLS test performance among Nebraska physicians. Overall, improvement between the pre-test and post-test among the T & T physicians was 22.0% +/- 2.0%. All physicians including failures (199 out of 212 passed) improved in their post-test scores. Individual item analysis of the post-test, including the KR-20 determination, varied but the overall performance was similar for both physician groups with the T & T physicians performing slightly better in test 2 (6 of 16 vs. 25 of 100 failures, p < 0.05). Attitudinal impact was assessed through 87 questionnaires from 50 physicians (92% response) and 37 nurses (89% response). Physicians (97.8% compared with 69.7%) were more aware of the ATLS training, and both groups (physicians, 77.3%; nurses, 69.6%) differentiated ATLS-trained physicians based on better resuscitation, more timely and appropriate consultation, greater confidence in trauma management, and improvement in trauma mortality and morbidity; all respondents recommended ATLS training for all emergency room physicians. The demonstrated positive cognitive and attitudinal effects very likely contributed to the improved post-ATLS trauma patient outcome.

Attitude of Health Personnel↗
PubMed1994

Absence of an essential regulatory influence of the adenovirus E1B 19-kilodalton protein on viral growth and early gene expression in human diploid WI38, HeLa, and A549 cells.

Mutations in the gene encoding the adenovirus (Ad) early region 1B 19-kDa protein (the 19K gene) result in multiple phenotypic effects upon infection of permissive human cells. It has been reported, for example, that Ad type 2 (Ad2) and Ad5 with mutations in the 19K gene (19K-defective mutants) have a marked growth advantage compared with wild-type virus in human diploid WI38 cells (E. White, B. Faha, and B. Stillman, Mol. Cell. Biol. 6:3763-3773, 1986), and it was proposed that this host range phenotype stems from the large increase in viral early gene expression reported to occur in the mutant-infected cells. These observations gave rise to the hypothesis that the 19-kDa protein (the 19K protein) normally functions as a negative regulator of Ad early gene expression and growth. We have tested this hypothesis and find that Ad5 and Ad12 wild-type viruses grow as efficiently as their respective 19K-defective mutants, in1 and dl337 and pm700 and in700, in WI38 and other human cell types. Neither the accumulation of E1A cytoplasmic mRNAs nor the synthesis of E1A and other viral early proteins in these cells is altered as a result of these mutations in the 19K gene, and we conclude that the 19K protein does not play an essential role in regulating viral early gene expression or viral growth in human cells.

Adenoviridae↗