Biomedical subjects
Publications and source records attributed to P Jones.
A new cyanoacrylate adhesive developed for orthodontic use was subjected to a controlled in vitro trial of ultimate shear bond strength. Performance deteriorated on storage in saline, rendering the material unsuitable for clinical use. Other alternatives to conventional acid-etch retained composite resin bonding agents are discussed.
Prepared samples of light-activated composite were cured by transillumination of tooth tissue in healthy volunteers. Positioning of the samples and the direction of illumination was designed to simulate curing during direct bonding. The effectiveness of curing was investigated by determination of surface microhardness. The degree of polymerization of the specimens cured by transillumination was found to be reduced compared to the control samples cured by direct exposure to the light source.
The evolution of modern communications, in particular by satellite, has enabled the development of a Global system for the alerting and coordination of search and rescue organisations in the event of maritime disaster. A brief overview of the components of the system is given after a review of the various official bodies involved in its inception.
Two dosing regimens of cefoperazone plus mezlocillin were compared in a prospective, randomized trial for therapy of febrile cancer patients. The two regimens were 5 g mezlocillin plus 2 g cefoperazone intravenously every four hours (higher dose) or 3 g mezlocillin plus 1 g cefoperazone intravenously every four hours (lower dose). Although the overall response rate was higher with the higher dose regimen (78 percent versus 66 percent, p = 0.04), the two regimens were comparable in patients with documented infections (72 percent versus 68 percent). Likewise, the two regimens were equally effective against those infections in which the pathogen could be determined (82 percent versus 82 percent). Serum bactericidal titers of at least 1:32 against a known pathogen were associated with a higher response rate than were titers of less than 1:32, but the higher dose regimen did not result in higher serum bactericidal titers. Hypoprothrombinemia was a side effect, especially with the higher dose regimen, before prophylactic vitamin K was routinely administered to patients. Since there were no major benefits with the use of the higher dose regimen of mezlocillin plus cefoperazone, the lower dose regimen is more appropriate for routine usage.
The two markers most closely linked to the myotonic dystrophy (DM) locus on chromosome 19 are the gene that codes for apolipoprotein CII (APOC2) and the anonymous probe D19S19 (LDR152). Both of these markers show tight linkage to DM, with maximum lod scores of greater than 20 at recombination fractions of less than 0.05. We have identified, in a family in which DM segregates, an affected individual where a meiotic recombination event has occurred in which both of these linked markers have crossed over with the gene defect. This demonstrates that APOC2 and D19S19 are probably on the same side of DM.
We have investigated the use of in situ hybridisation together with immunocytochemistry for the study of endocrine cell function, using as an example the expression of prolactin messenger RNA (mRNA) in pituitaries of rats under various endocrinological conditions. In situ hybridisation using a 32P-labelled cRNA probe for rat prolactin was carried out on sections of 4% paraformaldehyde-fixed pituitaries from prepubertal, pubertal, pregnant, lactating and ovariectomised rats and adjacent sections were immunostained for prolactin. Northern gel analysis was performed on total RNA extracts of pregnant, lactating and control pituitaries. While in ovariectomised rat pituitaries both prolactin immunoreactivity and prolactin mRNA were decreased, no differences in prolactin immunostaining were seen between prepubertal, pubertal, pregnant or lactating rats and controls, even when the supra-optimal dilution technique was used. However, using in situ hybridisation, prolactin mRNA signal was increased in prepubertal rats, and with hybridisation and northern gel analysis the signal was reduced in pregnant rats and markedly increased in lactating rats. The combined use of in situ hybridisation and immunocytochemistry provides morphological information concerning endocrine gene expression and protein synthesis in the pituitary gland.
PURPOSE: Physicians increasingly prescribe cyclosporine as an immunosuppressive agent for both organ-transplant and non-organ-transplant recipients. Investigators have reported a high incidence of drug-induced hypertension even when clinical nephrotoxicity was not present. We wanted to determine the reason. PATIENTS AND METHODS: A comparison was made of hypertension in 15 cyclosporine-treated transplant recipients with that in a similar group of 15 azathioprine-treated transplant recipients. RESULTS: Hypertension in the cyclosporine group responded differently from that seen in the azathioprine group and from previously described forms of post-transplantation hypertension. Hypertensive cyclosporine-treated patients show a sodium acquisitive renal state that responds to sodium restriction. Unlike rat models, which suggest cyclosporine-induced stimulation of the renin-angiotensin system, or previous forms of post-transplant hypertension in humans, plasma renin levels were not elevated and blood pressure did not respond to a test dose of captopril. CONCLUSION: Hypertension in cyclosporine-treated patients is an iatrogenic form of hypertension that may be associated with an early, subtle, renal defect in sodium excretion, a genesis of hypertension that is consistent with Guyton's view of essential hypertension.
Ten isolates of Bradyrhizobium spp. which form two colony types were studied; the isolates originated from a range of legume species. The two colony types differed in the amount of gum formed or size or both, depending on the strain. Whole 7-day-old colonies of each type were subcultured to determine the proportion of cells which had changed to the other type. An iterative computerized procedure was used to determine the rate of switching per generation between the two types and to predict proportions reached at equilibrium for each strain. The predicted proportions of the wetter (more gummy) or larger colony type at equilibrium differed significantly between strains, ranging from 0.9999 (strain CIAT 2383) to 0.0216 (strain CIAT 2469), because some strains switched faster from dry to wet (or small to large) and others switched faster from wet to dry (or large to small). Predicted equilibrium was reached after about 140 generations in strain USDA 76. In all but one strain (CIAT 3030) the growth rate of the wetter colony type was greater than or similar to that of the drier type. The mean difference in generation time between the two colony types was 0.37 h. Doubling times calculated for either colony type after 7 days of growth on the agar surface ranged from 6.0 to 7.3 h. The formation of two persistent colony types by one strain (clonal or colony dimorphism) may be a common phenomenon among Bradyrhizobium strains.
A variant of Southern Italian (delta beta)0-thalassemia is described in a women of Thai origin. The 3' breakpoint in Thai (delta beta)0-thalassemia is located about 1 kb upstream to that in Southern Italian (delta beta)0-thalassemia and produces a smaller deletion of approximately equal to 12.5 kb. Hematological phenotype, particularly Hb F output, is similar to that found in G gamma A gamma(delta beta)0-thalassemia despite the presence of a coexistent gamma-thalassemia effect.
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We have sequenced a cDNA, isolated from a chick embryo fibroblast lambda gt11 library, that encodes all 887 amino acids of alpha-actinin. Sequence from 10 different peptides from chick smooth muscle alpha-actinin was found to match that derived from the cDNA. The deduced protein sequence can be divided into three distinct domains: (a) the N-terminal 240 amino acid contains a highly conserved region (compared with Dictyostelium alpha-actinin) which probably represents the actin-binding domain, (b) amino acids 270-740 contain four repeats of a spectrin-like sequence, and (c) the C-terminal sequence contains two EF-hand Ca2+-binding sites. Each of these sites is defective in at least one oxygen-containing Ca2+-chelating amino acid side chain, suggesting that they are nonfunctional. Southern blots suggest that the alpha-actinin cDNA described here hybridizes to only one gene in chicken. Northern blots reveal only one size class of mRNA in fibroblasts and smooth muscle, but no hybridizing species could be detected in skeletal muscle poly(A+) RNA. The results are consistent with the view that smooth and skeletal muscle alpha-actinins are encoded by separate genes, which are considerably divergent.
To investigate whether the activated N-ras oncogene of HT1080 human fibrosarcoma cells contributes to the expression of the transformed phenotype, we have isolated flat revertants. In two independent revertant lines, an increase in chromosomal ploidy occurred without a concomitant increase in the number of copies of the N-ras transforming allele. Immunoprecipitation confirms that the level of the mutant N-ras p21 gene product in the revertants is correspondingly lower than in HT1080. Analysis of sporadic tumors derived from the revertant cells reveals an increased dosage of the transforming allele. The revertants also retransform after transfection of cloned activated ras oncogenes. These results imply direct participation of an N-ras oncogene in maintaining the transformed phenotype of a human tumor cell line.
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Imipenem/cilastatin was administered during 153 febrile episodes occurring in cancer patients and the response rate was 68%. Considering only documented infections the response rate was 71%. Patients who received imipenem as initial therapy had a higher response rate than patients who received it after failing other antibiotics (77% versus 68%). The overall response rates for septicemias and pneumonias were 75% and 58%. Among the 57 gram-negative infections 77% responded, but the response rate was substantially higher if imipenem was used as initial therapy (94% versus 69%). The poorest response rate was observed when imipenem was given as secondary therapy for Pseudomonas infections (50%), but most of these patients had failed to respond to other appropriate antibiotics. The only serious side effect was seizures which occurred in ten patients, although eight of them had other predisposing factors. Imipenem appears to be a useful antibiotic for treatment of infections, even in neutropenic cancer patients.
A chick-embryo fibroblast lambda gt11 cDNA library was screened with affinity-purified antibodies to chick gizzard vinculin. One recombinant was purified to homogeneity and the fusion protein expressed in Escherichia coli strain C600. The fusion protein was unstable, but polypeptides that reacted with vinculin antibodies, but not non-immune immunoglobulin, were detected by Western blotting. The recombinant contained a single EcoRI fragment of 2891 bp with a single open reading frame. The deduced protein sequence could be aligned with that of six CNBr-cleavage peptides and two tryptic peptides derived from chicken gizzard vinculin. AUG-247 has tentatively been identified as the initiation codon, as it is contained within the consensus sequence for initiation sites of higher eukaryotes. The cDNA lacks 3' sequence and encodes 74% of the vinculin sequence, presuming the molecular mass of vinculin to be 130,000 Da. Analysis of the deduced sequence showed no homologies with other protein sequences, but it does display a triple internal repeat of 112 amino acid residues covering residues 259-589. The sequences surrounding the seven tyrosine residues in the available sequence were aligned with the tyrosine autophosphorylation consensus sequence found in protein tyrosine kinases. Tyr-822 showed a good match to this consensus, and may represent one of the two major sites of tyrosine phosphorylation by pp60v-sre. Northern blots showed that the 2.89 kb vinculin cDNA hybridized to one size of mRNA (approx. 7 kb) in chick-embryo fibroblasts, chick smooth muscle and chick skeletal muscle. Southern blots revealed multiple hybridizing bands in genomic DNA.
We have isolated and sequenced a 2.1-kilobase cDNA encoding 86% of the sequence of alpha-actinin. The cDNA clone was isolated from a chick embryo fibroblast cDNA library constructed in the expression vector lambda gt11. Identification of this sequence as alpha-actinin was confirmed by immunological methods and by comparing the deduced protein sequence with the sequence of several CNBr fragments obtained from adult chicken smooth muscle (gizzard) alpha-actinin. The deduced protein sequence shows two distinct domains, one of which consists of four repeats of approximately 120 amino acids. This region corresponds to a previously identified 50-kDa tryptic peptide involved in formation of the alpha-actinin dimer. The last 19 residues of C-terminal sequence display an homology with the so-called E-F hand of Ca2+-binding proteins. Hybridization analysis reveals only one size of mRNA (approximately 3.5 kilobases) in fibroblasts, but multiple bands in genomic cDNA.
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