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Biomedical subjects

A P Wilson

Publications and source records attributed to A P Wilson.

At least 19 recordsLinked to original sources

Evidence that leukosialin, CD43, is intensely sulfated in the murine T lymphoma line RDM-4.

Metabolic labeling of the murine T lymphoma cell line RDM-4 with [35S] sulfate results in intense incorporation into a cell-retained component of apparent Mr approximately 100,000. This macromolecule is identified as a glycoprotein by lectin chromatography. The sulfate is not incorporated as tyrosine sulfate. Release of the radiolabel by alkaline beta-elimination but not by endoglycosidase F is consistent with the sulfation of O- rather than N-linked oligosaccharides. The sulfated glycoprotein displays anomalous migration on SDS-PAGE in two respects: 1) the apparent Mr shifts from 115,000 to 87,000 on increasing the acrylamide concentration from 7 to 12%, and 2) on neuraminidase digestion migration is substantially reduced (apparent Mr 140,000). These properties indicate that the sulfated protein is both heavily glycosylated and extensively sialylated, and are characteristic of the lymphoid mucin, leukosialin (sialophorin, CD43). Specific labeling of the sialoglycoproteins of RDM-4 cells indicates that leukosialin, the most intensely labeled protein, comigrates with the sulfated protein on SDS-PAGE at varying acrylamide concentrations. Our data are therefore consistent with sulfation of at least some of the numerous O-linked oligosaccharides of this abundant glycoprotein in RDM-4 cells. No sulfation of CD43 in resting splenic T cells is observed.

Animals

Coxiella burneti endocarditis in a patient with positive chlamydial serology.

A 41-year-old man who habitually slept in a car park presented with a culture-negative endocarditis. Serological tests indicated infection with both Coxiella burneti and Chlamydia psittaci. He was treated with doxycycline and clindamycin and required aortic valve replacement. Culture of the excised value for both agents was negative but electron microscopy was suggestive of coxiella endocarditis.

Adult

A meta-analysis of the use of amoxycillin-clavulanic acid in surgical prophylaxis.

The efficacy of amoxycillin-clavulanic acid as antibiotic prophylaxis in surgery has been assessed in numerous clinical studies, chiefly in abdominal and gynaecological surgery. A meta-analysis of 21 trials covering 2685 patients given amoxycillin-clavulanic acid and 2220 patients given comparator regimens is presented. Monotherapy with amoxycillin-clavulanic acid was as effective as the comparators, including combination regimens utilizing gentamicin or metronidazole, in preventing wound infections (median wound infection rates were 6% and 10% respectively). The antibacterial activity of amoxycillin-clavulanic acid covers the broad range of aerobic Gram-negative and anaerobic organisms that have a major role in postoperative infections. In addition, amoxycillin-clavulanic acid may have benefits in terms of convenience, tolerance and cost.

Abdomen

Enterococcus species in urinary tract infection.

Significant urinary isolates have been prospectively recorded since 1971. Enterococcus species, a common cause of nosocomial urinary tract infection, have been identified, and susceptibilities to a range of antibiotics have been determined. In addition, isolates in 1988 were tested for breakpoint susceptibility to vancomycin and teicoplanin. Despite changes in the hospitals covered, isolation of Enterococcus species rose steadily from 4% in 1971 to 12.6% in 1990 in hospital patients and from 2% to 5.6% in general-practice patients (P less than .01). All isolates of Enterococcus species were sensitive to ampicillin. Teicoplanin inhibited all 526 strains tested at a concentration of 2 micrograms/mL, but the same concentration of vancomycin inhibited only 370 (70%). The increased prevalence of enterococcal urinary tract infection is probably the result of increasing use of catheterization and broad-spectrum antibiotics. Glycopeptides reach high levels in the urine, and teicoplanin might be an alternative for the treatment of urinary tract infections due to enterococci.

Anti-Bacterial Agents

Screening for Corynebacterium diphtheriae.

A throat swab from a 9 year old girl with pharyngitis yielded a non-toxigenic strain of Corynebacterium diphtheriae var mitis and Streptococcus group G. C pseudodiphtheriticum was isolated from the throats of two of her four brothers. In each case the isolate was sent to the reference laboratory before full identification. The growth was found to be mixed for one brother; the other isolate being a toxin producing C diphtheriae var gravis. The child was asymptomatic and the case proves that all colonial types on the Hoyles plate should be identified.

Child

A comparison of the growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian tumours.

The growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian malignancy, benign ovarian tumours and non-tumour related gynaecological conditions have been investigated using an ovarian carcinoma cell line (OAW 42), mesothelial cells (58MC) and rat kidney cells (NRK-49F). Colony stimulating activity (CSA) for tumour cells and transforming activity (TA) for mesothelial cells were weakly correlated, but whereas elevated TA was tumour-associated, CSA was not. However, TA was not cancer-associated and, although the difference between the mean TA values of benign and malignant cyst fluids was of borderline significance, some benign cyst fluids from cystadenomas showed high TA values. Higher levels of TA in the cystadenomas showed a significant correlation with the menopausal status of the patient and higher levels of TA in the malignant cyst fluid/peritoneal fluid groups were associated with more advanced disease. Results indicated that some fluids contained TGF-beta-like activity, but there was no direct evidence for the presence of TGF-alpha/EGF-like activity in the fluids. Heparin inhibited clonogenic growth of tumour cells but not mesothelial cells. The reduced CSA which was observed after treatment of fluids with both heparin and thrombin implicated coagulation factors in the manifestation of CSA. It was concluded that CSA in the fluids was due, at least partly, to fibrin coagulation, and TA was due to unknown growth factor(s) which may include TGF-beta-like activity. The results are discussed in the context of the aetiology of ovarian carcinoma, and the possible clinical significance of TA.

Animals

Murine T lymphocytes and T-lymphoma cells produce chondroitin sulphate and heparan sulphate proteoglycans and free heparan sulphate glycosaminoglycan.

Normal murine splenic T lymphocytes and T-lymphoma cells were incubated with [35S]sulphate in low-sulphate medium for 4 hr. Gel filtration and SDS-PAGE revealed that the radiolabelled macromolecules secreted by these cells were almost exclusively chondroitin sulphate and heparan sulphate proteoglycans of relatively low molecular weight (MW), 100,000-200,000. Triton X-100 extracts of the cells contained similar proteoglycans. Under the conditions employed the incorporation of radiolabel by cells grown in vivo was equally distributed between cell-retained and secreted fractions, whereas cells grown in vitro retained some 75% of incorporated label. In general heparan sulphate predominated over chondroitin sulphate in both secreted and cell-retained fractions. Cell extracts also contained a minor proportion of free glycosaminoglycan, which is almost exclusively heparan sulphate. These chains, like those incorporated into the proteoglycan, were around 12,000 MW. The T-lymphoma cells RDM-4, whether grown in vitro or in vivo, also incorporated a substantial proportion of [35S]sulphate into a single, cell-retained protein, 100,000 MW. No such radiolabelled protein was detectable in T cells.

Animals

A comparative study of the interaction of oestradiol and the steroidal pure antioestrogen, ICI 164,384, with the molybdate-stabilized oestrogen receptor.

The kinetics of binding of oestradiol and the steroidal pure antioestrogen ICI 164,384 to the molybdate-stabilized oestrogen receptor, partially purified from pig and human uterine tissue, were determined. ICI 164,384 bound directly to the oestrogen receptor protein and the kinetic parameters of this interaction were, in general, similar to those for the binding of oestradiol, regardless of the source of the receptor protein. However, the rate of association of oestradiol, regardless of the source of the receptor protein. However, the rate of association of the antagonist with the receptor protein was slower when compared to that of oestradiol. Furthermore, the concentration of binding sites for the two ligands was of the same order. The binding of oestradiol resulted in a steroid-receptor complex which could be transformed in vitro, to a form with increased affinity for DNA-cellulose. However, the complex formed between ICI 164,384 and the receptor protein did not show increased affinity for DNA-cellulose when exposed to conditions that transformed agonist-receptor complexes. Therefore, the binding of ICI 164,384 to the oestrogen receptor protein results in a suppression of the transformation process. A similar suppression in vivo may account for the pure antagonist properties of ICI 164,384.

Animals

The use of the wound scoring method 'ASEPSIS' in postoperative wound surveillance.

For the purposes of wound surveillance programmes and clinical trials, a wound scoring method, ASEPSIS, makes assessment of wound sepsis more objective and reproducible by allotting points both for the appearance of the wound in the first week and for the clinical consequences of infection. ASEPSIS was compared with other definitions of wound infection in 1029 surgical patients and its suitability for surveillance and detection of risk factors were examined. Satisfactory healing was recorded in 867 patients, disturbance of healing in 74 and minor, moderate and severe wound infection in 41, 24 and 23 patients respectively. An ASEPSIS score over 20 points was more sensitive and as specific as the presence of pus as an indicator of changes in management resulting from infection. Multiple regression analysis of ASEPSIS scores indicated that operation type, ward, degree of contamination, age, body mass index, and preoperative stay in hospital were significant risk factors. In matching 52 infected patients with uninfected controls, any wound score over 10 points was associated with a significant delay in discharge from hospital (median 3 days, P less than 0.0005).

Cross Infection

Preoperative screening cultures in the identification of staphylococci causing wound and valvular infections in cardiac surgery.

Cultures of nasal or presternal swabs form part of the routine preoperative screening of patients on the cardiac surgical ward. During a trial of antibiotic prophylaxis in 314 patients, preoperative isolates of Staphylococcus aureus and coagulase-negative staphylococci were compared with strains associated with postoperative sternal wound breakdown (24 patients) and prosthetic valve endocarditis (3 patients). Morphology, antibiotic sensitivity pattern, plasmid analysis and phage typing were used to differentiate strains. In only three cases of wound infection and one of prosthetic valve endocarditis were pathogenic staphylococci not distinguishable from preoperative isolates. The collection of superficial swabs for this purpose before cardiac surgery is therefore unlikely to be cost effective.

Cardiac Surgical Procedures

Aminoglycoside toxicity following antibiotic prophylaxis in cardiac surgery.

We have reviewed experience with aminoglycosides in cardiac surgical prophylaxis from 1984 to 1989. In the first two years, prospectively randomized trials (517 patients) allowed comparison of tobramycin (three-day course) with a non-toxic antibiotic, teicoplanin. A significant excess rise in serum creatinine was present at the end of the first postoperative week in patients given tobramycin (165 vs 149 patients, 95% CI 3-17 microM. P less than 0.01, which was most marked in ten oliguric patients with trough serum levels over 2 mg/l (95% CI 7-52 microM). However, no patient needed haemodialysis and only one case of possible ototoxicity was identified. During the next three years, of 912 patients given two to three days gentamicin, 29 patients were shown to have potentially toxic serum levels and oliguria. Three individual cases are described, including one of ototoxicity and one of nephrotoxicity neeeding haemodialysis. The hazards of aminoglycoside toxicity are probably small compared with the failure of other antibiotics to cover staphylococci that may later cause wound infection or endocarditis. However, surgeons should probably be advised to check the aminoglycoside level in all patients on the first post-operative day.

Aged

Biological properties of ten human ovarian carcinoma cell lines: calibration in vitro against four platinum complexes.

Ten human ovarian carcinoma cell lines have been studied as a potential in vitro screen for the development of novel anticancer platinum complexes. Lines have been established and developed both from solid and ascitic tumours, from pretreated and untreated patients, and are available at a range of in vitro passage numbers. The biological properties of the lines were consistent with them being human, epithelial and of ovarian carcinoma origin. Using a tritiated thymidine or leucine uptake method, and a 96 hour continuous drug exposure, the lines have been calibrated against four platinum-containing chemotherapeutic agents: cisplatin, iproplatin, carboplatin and tetraplatin. Striking differences in cytotoxicity were observed across the lines for each agent. Some lines were consistently resistant, others generally sensitive, whereas some showed clear evidence of differential sensitivity to a particular agent. Statistical analysis (Spearman rank correlation) involving the six possible pairings of drugs showed that cisplatin, iproplatin and carboplatin elicit a very similar pattern of response in these lines whereas tetraplatin elicits a completely different response pattern. Similar cytotoxicity values were obtained using a soft agar cloning assay. Results using a tetrazolium dye reduction assay, however, gave somewhat higher and more variable values, particularly with tetraplatin. The thymidine uptake assay will be adopted in further studies on a selected panel of six lines. This panel encompasses the spectra of sensitivities identified for each of the four agents against the original ten lines and may provide a useful screening facility for the development of novel platinum drugs, in that it detects both cell line-determined and structure-determined differences in cytotoxicity.

Antigens, Neoplasm