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Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 199 records · Page 11Linked to original sources
PubMed1993

A single amino acid substitution in elongation factor Tu disrupts interaction between the ternary complex and the ribosome.

Elongation factor Tu (EF-Tu).GTP has the primary function of promoting the efficient and correct interaction of aminoacyl-tRNA with the ribosome. Very little is known about the elements in EF-Tu involved in this interaction. We describe a mutant form of EF-Tu, isolated in Salmonella typhimurium, that causes a severe defect in the interaction of the ternary complex with the ribosome. The mutation causes the substitution of Val for Gly-280 in domain II of EF-Tu. The in vivo growth and translation phenotypes of strains harboring this mutation are indistinguishable from those of strains in which the same tuf gene is insertionally inactivated. Viable cells are not obtained when the other tuf gene is inactivated, showing that the mutant EF-Tu alone cannot support cell growth. We have confirmed, by partial protein sequencing, that the mutant EF-Tu is present in the cells. In vitro analysis of the natural mixture of wild-type and mutant EF-Tu allows us to identify the major defect of this mutant. Our data shows that the EF-Tu is homogeneous and competent with respect to guanine nucleotide binding and exchange, stimulation of nucleotide exchange by EF-Ts, and ternary complex formation with aminoacyl-tRNA. However various measures of translational efficiency show a significant reduction, which is associated with a defective interaction between the ribosome and the mutant EF-Tu.GTP.aminoacyl-tRNA complex. In addition, the antibiotic kirromycin, which blocks translation by binding EF-Tu on the ribosome, fails to do so with this mutant EF-Tu, although it does form a complex with EF-Tu. Our results suggest that this region of domain II in EF-Tu has an important function and influences the binding of the ternary complex to the codon-programmed ribosome during protein synthesis. Models involving either a direct or an indirect effect of the mutation are discussed.

Anti-Bacterial Agents↗
PubMed1993

Electroconvulsive therapy.

Modern ECT practice has evolved far from its beginnings more than 50 years ago. ECT is effective, safe, and rewarding in the clinical setting. This discussion complements the 1990 APA Task Force report and elaborates on some of the clinical and scientific factors that could not be fully addressed by the report. The future of ECT lies in understanding the mechanisms by which it relieves depressive symptoms and causes amnesia and related cognitive deficits.

Combined Modality Therapy↗
PubMed1992

Comparison of the complete sequence of the str operon in Salmonella typhimurium and Escherichia coli.

The nucleotide (nt) sequences of the str operon in Escherichia coli K-12 and Salmonella typhimurium LT2 were completed and compared at the nt and amino acid (aa) level. The order of conservation at the nt and aa level is rpsL greater than tufA greater than rpsG greater than f usA. A striking difference is that the rpsG-encoded ribosomal protein, S7, in E. coli K-12 is 23 aa longer than in S. typhimurium. The very low (0.18) codon adaptation index of this part of the E. coli K-12-encoding gene and the unusual stop codon (UGA) suggest that this is a relatively recent extension. A trend towards a higher G+C content in fusA (gene encoding elongation factor (EF)-G) and tufA (gene encoding EF-Tu) in S. typhimurium is noted. In fusA, nt substitutions at all three positions in a codon occur at a much higher frequency than expected from the number of nt substitutions in the gene, assuming they are random and independent events. An analysis of substitutions in this and other genes suggests that the triple substitutions in fusA, and some other genes, are the result of the sequential accumulation of individual mutations, probably driven by selection pressure for particular codons or aa.

Amino Acid Sequence↗
PubMed1992

Judgement day.

Explore the source record for details and available documents.

Community Participation↗
PubMed1992

Transient neonatal denervation alters the proliferative capacity of myosatellite cells in dystrophic (129ReJdy/dy) muscle.

It has been previously shown that transiently denervated, neonatal dystrophic muscle fails to undergo the degeneration-regeneration cycle characteristic of murine dystrophy (Moschella and Ontell, 1987). Thus, the myosatellite cells (myogenic stem cells) in these muscles have been spared the mitotic challenge to which dystrophic myosatellite cells are normally subjected early in the time course of the disease. By in vitro evaluation of the proliferative capacity of myosatellite cells derived from extensor digitorum longus (EDL) muscles of 100-day-old genetically normal (+/+) and genetically dystrophic [dy/dy (129ReJdy/dy)] mice and from muscles of age-matched mice that had been neonatally denervated (by sciaticotomy) and allowed to reinnervate, it has been possible to directly determine whether the cessation of spontaneous regeneration in older dy/dy muscles in vivo, is due to an innate defect in the proliferative capacity of the myosatellite cells or exhaustion of the myosatellite cells' mitotic activity during the regenerative phase of the disease. This study demonstrates that transient neonatal denervation of dystrophic muscle (Den.dy/dy) increases the number of muscle colony-forming cells (MCFs) per milligram of wet weight muscle tissue, increases the plating efficiency, and significantly increases the in vitro mitotic activity of dystrophic myosatellite cells toward normal values. The increased mitotic capability of myosatellite cells derived from Den.dy/dy muscle as compared to unoperated dy/dy muscle suggests that there is no innate defect in the proliferative capacity of the myosatellite cells of dy/dy muscles and that the cessation of spontaneous regeneration in the dy/dy muscles is related to the exhaustion of their myosatellite cells' mitotic capability.

Animals↗
PubMed1992

The effect of per-item fees on the behaviour of general practitioners.

The recent government White Paper 'Working for Patients' emphasised the use of financial incentives as a means of altering the behaviour of general practitioners (GPs) in the U.K. This paper examines the impact of financial incentives on GPs' behaviour with respect to maternity care and cervical cytology. Changes in per-item fees over the period 1966-89 appear to have had little effect on the numbers of treatments; rather service provision was related to patient demand and the availability of GPs. However, target payments for cervical cytology introduced in 1990 appear to have had a major impact.

Fees, Medical↗
PubMed1992

Macrophages in tissues and in vitro.

Macrophages have specialized functions in different tissue microenvironments such as lymphohaemopoietic organs and the nervous system. Recently, progress has been made in defining cellular and molecular properties of isolated and tissue macrophages in the developing and adult animal.

Animals↗
PubMed1992

Verrucous carcinoma (epithelioma cuniculatum) plantare.

A case of plantar verrucous carcinoma is described. The lesion was treated as an ischaemic ulcer before the true nature was recognised. Prior to the diagnosis the patient had a femoro-popliteal arterial bypass graft performed. An amputation was undertaken once the diagnosis was established.

Aged↗
PubMed1992

Spontaneous release of interleukin-I and interleukin-6 by peripheral blood mononuclear cells after oophorectomy.

1. We studied the changes in interleukin-1 and interleukin-6 secretion by peripheral blood mononuclear cells from 12 premenopausal women after oophorectomy and seven premenopausal women who had undergone simple hysterectomy. 2. The results showed that 1 month after surgery interleukin-1 secretion increased by 414 +/- 171% (mean +/- SEM) and interleukin-6 secretion increased by 1354 +/- 481% in oophorectomized women, whereas only non-significant fluctuations in the secretion of both cytokines (-9% +/- 29% for interleukin-1 and -31% +/- 19% for interleukin-6) were seen in the women who had undergone simple hysterectomy. The difference between the two groups was significant (P = 0.035 for interleukin-1 and P = 0.003 for interleukin-6). In addition, oophorectomy, but not simple hysterectomy, was followed by significant increases in plasma ionized calcium concentration (P < 0.05), plasma alkaline phosphatase activity (P < 0.01) and plasma osteocalcin concentration (P < 0.02), and a reduction in plasma parathyroid hormone level (P < 0.01). 3. We conclude that ovary ablation may modify cytokine secretion by peripheral blood mononuclear cells. If this phenomenon occurs in the bone microenvironment, it could be important in the loss of bone observed after oophorectomy. However, the possibility of an independent alteration induced by the lack of gonadal hormones but unrelated to bone turnover cannot be excluded.

Adult↗
PubMed1992

Screening for mutations in the open reading frame and promoter of the beta-amyloid precursor protein gene in familial Alzheimer's disease: identification of a further family with APP717 Val-->Ile.

Following the identification of mutations in the beta-amyloid precursor protein (APP) gene in familial, early onset Alzheimer's disease (AD), we have developed a screening protocol using single strand conformation analysis (SSCA) to screen exon 17 for the known mutations within APP. In addition, we used this protocol to screen the other seventeen exons of APP and a three hundred and thirty base pair regulatory region of the promoter for new mutations in 9 families with early onset AD. Exons 16 and 17, which encode the deposited beta-amyloid peptide, were screened in a further 10 families. Our screening procedure identifies all the reported mutations within APP. While we have identified a further family with APP717 Val-->Ile, we did not find any previously undescribed mutations. Screening of other exons of APP in 2 families in which we have previously reported mutations at APP717, failed to reveal other sequence abnormalities supporting the hypothesis that the mutations at APP717 cause the disease in these families. These data suggest that mutations in APP are a rare cause of familial early onset AD (3/21 families tested) and that within APP most, possibly all, mutations which cause AD are in exon 17.

Adult↗
PubMed1992

A prospective, randomized, blind comparison of three biopsy techniques in the management of patients after renal transplantation.

Although conventional histology (CH) of needle core biopsies has been accepted as the gold standard for diagnosis of renal allograft rejection, this assumption has never been tested. Fine-needle aspiration cytology (FNAC) and monoclonal antibody (panleukocyte) staining of needle core biopsies (MABS) have been suggested to be superior to CH. A total of 50 patients received a cadaveric renal transplant followed by immunosuppression with triple therapy. Biopsies were taken routinely at days 7,14,21,28, and 90, with additional biopsies taken between these times if rejection was suspected (total biopsy sessions = 219). Specimens were taken for CH, FNAC, and MABS at each biopsy session, but only the result of one technique (previously randomly allocated) was communicated back to the clinical team, using a standardized grading system. Subsequently the presence or absence of rejection was determined by retrospective analysis of the clinical and biochemical course by 4 clinicians, without reference to the biopsy result. Graft survival was not significantly different in the three groups. The sensitivities for CH, FNAC, and MABS were 75%, 59%, and 77%, respectively, while the specificities were 87%, 96%, and 80%, respectively. Inadequate samples for analysis occurred frequently with the MABS technique--and, to a lesser extent, with CH--and both techniques tended to overdiagnose rejection. FNAC most often gave an answer but did miss clinically important rejection episodes. Needle-core biopsy processed for CH remains the most reliable biopsy technique for the diagnosis of rejection of renal allografts. FNAC is a useful technique for monitoring grafts with stable function or nonfunction. MABS does provide information equivalent to CH, but, in this study, had a high incidence of inadequate samples.

Antibodies, Monoclonal↗
PubMed1992

Ceroid granuloma of the uterine cervix.

An excision biopsy was taken from a 59-year-old woman with a small dark-brown lesion on the anterior lip of the cervix. The histology revealed an ulcerated surface epithelium with a band-like infiltrate of pigment containing macrophages in the subepithelial zone. Histochemical examination of the specimen revealed that the pigment was ceroid. This is, to the best of our knowledge, the first case report of ceroid granuloma of the uterine cervix.

Ceroid↗
PubMed1992

Benign vaginal polyp: a histological, histochemical and immunohistochemical study of 20 polyps with comparison to normal vaginal subepithelial layer.

Twenty benign vaginal polyps from 18 patients, together with sections from normal vaginal epithelium, were studied histologically, histochemically using elastic van Gieson stain and immunohistochemically using monoclonal antibodies against vimentin, desmin and actin. The striking finding was the similarity, both histologically and immunohistochemically, of the stroma of vaginal polyps to that of the loose subepithelial layer found in normal vagina. The important difference was the marked degeneration of the elastic tissue, increased number of stellate and giant fibroblasts and subepithelial condensation of fibroblasts in the polyps. These findings support the hypothesis that vaginal polyps may represent a reactive hyperplasia of the loose subepithelial zone of the vaginal wall.

Adult↗
PubMed1992

Intradural bronchogenic cysts.

The pathological findings of an intradural and extramedullary cyst in the mid cervical spinal canal are described in a 55 year old woman who presented with a short history of pain and paraesthesia of the right arm. Intradural well defined solitary cystic lesions in the spinal canal are uncommon, their pathogenesis is poorly understood, and their nomenclature is confusing. In this case the cyst was a bronchogenic cyst; these are a rare form of such cysts and they are thought to be a malformation arising from a split notochordal syndrome and not a teratoma.

Bronchogenic Cyst↗