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Biomedical subjects

M Rawlings

Publications and source records attributed to M Rawlings.

11 recordsLinked to original sources
PubMed2001

Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study.

Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.

Adolescent↗
PubMed1998

European network for the case-population surveillance of rare diseases (Euronet). A prospective feasibility study.

OBJECTIVE: Euronet, a case-population surveillance scheme, aims to estimate the risk of certain rare conditions which are commonly iatrogenic, by comparing drug use amongst non-selective cases with overall drug use in the general population. METHODS: The method is based on three provisos: (1) all incident cases (irrespective of suspected aetiology) should be ascertained and studied; (2) a full drug history should be obtained from cases by direct interview; and (3) drug-use data for the products of interest should be available for this population from which cases are chosen. The feasibility of this problem-oriented approach for the identification of new signals of adverse drug reactions and for risk estimation will be tested in relation to agranulocytosis, Stevens-Johnson syndrome and toxic epidermal necrolysis in four defined areas in Europe, totalling 19 x 10(6) inhabitants, with these latest two outcomes being studied in only three regions. The design, methods and main limitations of this case-population surveillance approach are described.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

A bacterial basic region leucine zipper histidine kinase regulating toluene degradation.

The two-component signal transduction pathways in bacteria use a histidine-aspartate phosphorelay circuit to mediate cellular changes in response to environmental stimuli. Here we describe a novel two-component todST system, which activates expression of the toluene degradation (tod) pathway in Pseudomonas putida F1. The todS gene is predicted to encode a sensory hybrid kinase with two unique properties--a basic region leucine zipper dimerization motif at the N terminus and a duplicated histidine kinase motif. Evidence from a synthetic peptide model suggests that TodS binds as a dimer to a pseudopalindromic sequence (5'-TGACTCA), which resembles the recognition sequence of the eukaryotic transcription factors Fos and Jun. These results provide additional evidence that bacteria and eukaryotes share common regulatory motifs. The todT gene product, a response regulator, was overproduced as a fusion protein in Escherichia coli, and the purified protein was found to bind specifically to a 6-bp palindromic DNA structure in the tod control region. The phosphorylated form of TodT appears to be the activator of tod structural genes. This is the first report of a two-component system that regulates aromatic metabolism in bacteria.

Amino Acid Sequence↗
PubMed1995

Identification of a membrane protein and a truncated LysR-type regulator associated with the toluene degradation pathway in Pseudomonas putida F1.

A 3 kb DNA region upstream of the toluene degradation (tod) genes, todFC1C2BADEGIH, in Pseudomonas putida F1 (PpF1) was sequenced. Two divergently arranged open reading frames, todR and todX, were identified. A toluene-inducible promoter was localized in front of todX, and the transcription start point was mapped. This promoter is probably responsible for the expression of all tod structural genes. TodX was found to be a membrane protein. Its predicted amino acid sequence (453 residues; M(r) 48,265) exhibits considerable similarity with the FadL protein of Escherichia coli, an outer membrane protein required for binding and transport of long-chain fatty acids. An apparent function of TodX is likely to be involved in facilitating the delivery of exogenous toluene inside the PpF1 cells. The sequence of TodR (100 residues) exhibits extensive homology with the DNA-binding domain of transcriptional activators of the LysR family, but todR was found to have a negligible role in tod gene regulation.

Amino Acid Sequence↗
PubMed1992

The gene encoding Escherichia coli acyl carrier protein lies within a cluster of fatty acid biosynthetic genes.

The gene encoding Escherichia coli acyl carrier protein (ACP) has been isolated and sequenced. The ACP gene (called acpP) was located on the genetic map between fabF and fabD which encode two fatty acid biosynthetic enzymes, 3-ketoacyl-ACP synthase II and malonyl CoA-ACP transacylase, respectively. An open reading frame between acpP and fabD encodes a 26.5-kDa protein that has significant sequence identity (greater than 40%) with two acetoacetyl-CoA reductases and thus is believed to encode a 3-ketoacyl-ACP reductase. This gene (called fabG) is cotranscribed with acpP. Thus, the gene encoding ACP, the key carrier protein of fatty acid synthesis, is located within a cluster of fatty acid biosynthetic genes.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗
PubMed1988

Insertional restoration of beta-galactosidase alpha-complementation (white-to-blue colony screening) facilitates assembly of synthetic genes.

The assembly of synthetic genes from oligodeoxynucleotides can be an inefficient process. Upon ligation of a synthetic assembly into a plasmid vector and transformation of an Escherichia coli host, it is often found that only a minor fraction of the putative recombinant plasmids contains synthetic sequences. Moreover, the synthetic sequences cloned are often altered versions of those originally designed. We have designed a biological test to detect those plasmids that contain synthetic sequences of the proper length, termini and reading frame. The test is the reversal of the beta-galactosidase alpha-complementation (blue-to-white) test used to detect the insertion of DNA segments into the polylinker sequences of the phage M13 mp, plasmids pUC, and related vectors. We begin with a modified vector defective in alpha-complementation and use insertion of the synthetic DNA segment to restore alpha-complementation. The alpha-complementation activity of the original vector (e.g., pUC18) was first abolished by a frameshift or DNA insertion within the polylinker sequence of the lacZ' gene segment. The alpha-complementation was then restored by insertion of the synthetic DNA sequence between the cohesive ends generated by digestion of two polylinker restriction sites. Formation of blue colonies requires the insertion of a DNA segment of appropriate length and termini to reconstruct the lacZ' open reading frame and thus is much more selective than the usual insertional inactivation strategy. We show that this 'insertional restoration' screening method markedly enhances the proper assembly of synthetic genes and describe manipulations to readily and reliably frameshift various polylinker sequences.

Amino Acid Sequence↗
PubMed1988

Hepatocellular carcinoma: importance of histologic classification as a prognostic factor.

The characteristics and clinical courses of 15 patients with fibrolamellar carcinoma have been compared to 62 patients with hepatocellular carcinoma treated over the same time period. Marked differences were found in patient, tumor, and treatment characteristics. Survival rates in these two groups of patients have been compared by univariate analysis of the subsets of those patient, tumor, and treatment characteristics. The longer survival of the group of patients with fibrolamellar carcinoma could not be accounted for by the prevalence or absence of any of these characteristics. Comparison of subsets of patients with documented noncirrhotic livers or those having complete resection of their tumors revealed a significantly prolonged survival in patients with the fibrolamellar variant. The 5 year survival rate of the patients with fibrolamellar carcinoma who had complete tumor resection was 45 percent, with a median survival time of 50 months. The 5 year survival of patients with hepatocellular carcinoma who had complete tumor resection was 0 percent, with a median survival time of 22 months.

Adolescent↗