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Biomedical subjects

B Sweeney

Publications and source records attributed to B Sweeney.

9 recordsLinked to original sources

Cancer-associated changes in glycosylation of fibronectin. Immunohistological localization of oncofetal fibronectin defined by monoclonal antibodies.

The extracellular matrix adhesion molecule fibronectin exhibits different isoforms derived by alternative splicing as well as recently demonstrated variation in O-glycosylation. Although fibronectin is widely distributed in normal tissues, the individual isoforms have been found to show restricted tissue distribution and association with malignancies. The monoclonal antibody FDC-6 defines a cancer-associated de novo glycosylation of a specific threonine residue in the C-terminal region of the fibronectin molecule termed oncofetal fibronectin. Here we report an immunohistological study of oral squamous cell carcinomas (n = 33), premalignant lesions (n = 15), and normal oral mucosa (n = 10) using the FDC-6 antibody. A selective expression of the oncofetal fibronectin epitope was demonstrated in close relation to the invading carcinoma, whereas no staining was observed in premalignant lesions without epithelial dysplasia, or in normal epithelium. Furthermore, we attempted to identify additional carbohydrate-related epitopes distinguishing fibronectin of human hepatoma cell line HUH-7 from plasma fibronectin. No novel epitopes were identified, as all generated monoclonal antibodies lacking reactivity with plasma fibronectin showed the same specificity as FDC-6. Previous studies have indicated that the de novo glycosylation is induced by a novel transferase activity only found in fetal and carcinoma cell lines, placenta and hepatoma tissues. Here we provide further evidence that a purified UDP-GalNAc:peptide N-acetylgalactosaminyltransferase from normal bovine thymus and human placentae is incapable of utilizing the hexapeptide VTHPGY as a substrate. The results demonstrate that oncofetal fibronectin is highly associated with malignancy, and appears to be induced by expression of a unique glycosyltransferase or modification of the specificity of the normally expressed transferase.

Aged

Immunochemical detection of a small cell lung cancer-associated ganglioside (FucGM1) antigen in serum.

Recently, the ganglioside FucGM1 (Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4[NeuAc alpha 2-3]-Gal beta 1-4Glc beta 1-1 Cer) was identified as a small cell lung cancer (SCLC) marker both in chemical and histochemical studies. In order to further determine whether the FucGM1 ganglioside is shed from the tumor site and consequently is present in the serum of SCLC patients, we produced a series of new monoclonal antibodies raised against FucGM1 and related glycolipids. Shedding of the FucGM1 ganglioside was studied both in vitro and in vivo using SCLC cell lines and nude mice xenografts of SCLC cells as model systems, and finally immunochemical analyses were performed on serum samples from patients with SCLC. High-performance thin-layer chromatography immunostaining demonstrated the presence of FucGM1 in conditioned culture media obtained from FucGM1-positive SCLC cell lines. Furthermore, tumor extracts of SCLC cell line xenografts in nude mice were positive for the FucGM1 marker, and more importantly the marker was also present in serum samples from these mice. Twenty serum samples were obtained from patients with histologically verified SCLC. Eight patients had localized disease, and the remaining patients had disseminated cancer involving metastases to other organ sites. Sera from 4 of these patients were clearly positive, and 2 additional cases were found to be weakly positive. The positive patient sera were all from patients with extensive disease. Sera from 12 patients with non-SCLC and 20 healthy individuals were all found to be negative. These results clearly establish the FucGM1 glycolipid as a potential serum marker of SCLC for which a sensitive immunoassay should be developed and tested using a larger series of serum samples.

Adult

Decay of nitroprusside. II: In vivo.

Clinical experience suggests that nitroprusside (SNP) concentrations decay more rapidly in vivo than in vitro. Plasma concentrations of SNP were measured therefore in 20 patients at the end of an infusion, with mean arterial pressure (MAP) and cyanide (HCN) concentrations. Plasma SNP concentrations (20-243 micrograms litre-1; mean = 123.5 micrograms litre-1), were related to infusion rate (r = 0.66, P less than 0.001), and declined rapidly to a mean (SD) of 7.7 (4.5) micrograms litre-1 in 15 min. The decay of SNP correlated closely with the increase in arterial pressure (mean MAP vs log mean plasma SNP concentrations: r = -0.993, P less than 0.001), and was probably biphasic: mean (SD) T1/2 alpha = 0.89 (0.62) min, T1/2 beta = 14.3 (12) min. Mean plasma HCN and mean plasma SNP concentrations decreased together (r = 0.955, P less than 0.001), thus confirming that in vivo decomposition of the drug is the source of HCN.

Adult

Literature and medicine: a short course for medical students.

A course on literature and medicine for medical students is described. A wide range of books, plays and poems were used with medical and non-medical themes. Students enjoyed the course and particularly welcomed the non-medical components. The staff learned at least as much as the students. Several book lists were developed with input from the students. Such a course might have a part to play in several parts of the medical course, such as in the teaching of ethics.

Attitude of Health Personnel

The use of antacids as a prophylaxis against Mendelson's syndrome in the United Kingdom. A survey.

Maternal mortality from aspiration of gastric contents still remains unacceptably high, despite various recommended prophylactic measures. In order to establish which forms of antacid prophylaxis are currently being used, a questionnaire was sent to anaesthetists working in obstetric units in the United Kingdom. Despite its limitations, magnesium trisilicate remains the most popular antacid during labour and before Caesarean section.

Anesthesia, Obstetrical

Toxicity of bone marrow in dentists exposed to nitrous oxide.

The morphology of the bone marrow of 21 dentists who habitually used nitrous oxide in their surgeries was investigated. Exposure to nitrous oxide was measured with an atmospheric sampling device, and each dentist was invited to fill in a questionnaire giving details of medical history, diet, and intake of alcohol. During the trial a full neurological and haematological investigation was carried out and a bone marrow aspirate was examined both morphologically and by the deoxyuridine suppression test. Mean exposures to nitrous oxide ranged from 159 to 4600 parts per million. In all subjects serum vitamin B12 and folate concentrations were within normal limits. Abnormal results of deoxyuridine suppression tests were obtained in three of the 20 dentists tested; two of these three had abnormal white cells in their peripheral blood films. This study provides direct evidence that occupational exposure to nitrous oxide may cause depression of vitamin B12 activity resulting in measurable changes in bone marrow secondary to impaired synthesis of deoxyribonucleic acid.

Anesthesia, Dental

Franz Kuhn. His contribution to anaesthesia.

The history of tracheal intubation has been described before, but earlier accounts have overlooked several aspects and, in particular, the part played by Kuhn, who also deserves to be recognised for a number of other original contributions to anaesthesia.

Anesthesia, Inhalation