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Biomedical subjects

E Sweeney

Publications and source records attributed to E Sweeney.

At least 37 records · Page 2Linked to original sources

Immunocytochemical localization of c-erbB-2 protein in transitional cell carcinoma of the urinary bladder.

The level of expression and cellular localization of the c-erbB-2 gene product in transitional cell carcinoma of the urinary tract is controversial. Analysis of the c-erbB-2 gene structure and comparison of its expression in the same cells by Southern, Northern and immunoblotting, and by immunocytochemistry minimize the errors of interpretation inherent in one technique. Such a 'correlative study' has been performed on tumours from 82 patients. c-erbB-2 gene amplification was detected in 14 per cent of initial tumours and was associated with grade (P < 0.001). Raised levels of mRNA were seen in those tumours with increased gene copy number and in 13 per cent of the remainder. Immunoblotting detected the expected 185 kD immunoreactive protein and a 155 kD protein associated with high gene copy number. Immunocytochemistry localized c-erbB-2 immunoreactivity to the cell membrane and cytoplasm, and the latter predominated. Four antibodies to c-erbB-2 (AB-3, 21N, pAb 1, and NCL CB11) were compared on contiguous sections of the same tumour and showed the same pattern of immunoreactivity. Similarly, analyses carried out in three independent laboratories identified the same cellular localization. Membrane and cytoplasmic immunoreactivity was demonstrated in all tumours with gene amplification or increased mRNA levels and in 40 per cent of the remaining tumours. We showed that immunocytochemistry requires careful standardization of techniques and quantitation between different groups. However, despite variations in the intensity of immunoreactivity, the total number of positive cells remained constant. Therefore quantitation must be based on the number of positive cells and, ideally, their immunoreactive content relative to normal and positive tissue controls.

Biomarkers, Tumor↗

Localised histiocytic lipofuscinosis. An unusual pigmented lesion.

We report a case in an 86-year-old woman, of a localised aggregate of lipofuscin-laden histiocytes presenting as a pigmented lesion with local itching. Histologically, there was a diffuse dermal infiltrate of mononuclear cells, predominantly histiocytes containing golden-brown pigment shown to be lipofuscin. The typical ultrastructural appearance of this pigment was demonstrated on electron microscopy, and adjacent iron deposition was confirmed. The etiology of this rare lesion is unclear. Clinical distinction from pigmented cutaneous malignancies may be difficult.

Aged↗

The incidence and role of actinomyces in recurrent acute tonsillitis.

Although actinomyces has been identified in between 1.77% and 37% of resected tonsils its possible role in recurrent acute tonsillitis has received little attention. A histological and bacteriological study of 129 pairs of tonsils from patients with recurrent acute tonsillitis showed actinomyces to be present in 29.5%. The organism, however, was also present in 40% of tonsils from 10 patients with no history of tonsillar disease. In neither of these groups was there any specific evidence of tissue reaction to actinomyces nor was there a male preponderance as in clinical actinomycosis. The presence of actinomyces in the tonsil was not favoured by the concurrence of beta-lactamase producing bacteria. These data indicate that actinomyces does not have a causal role in recurrent acute tonsillitis.

Actinomyces↗

Proliferating cell nuclear antigen (PCNA) expression in Hodgkin's disease.

Previous studies of the proliferating cell fraction in Hodgkin's disease (HD) have been directed towards the classical Hodgkin and Reed-Sternberg cells (HRS) to the exclusion of the background population and have not included cases of nodular lymphocyte predominant Hodgkin's disease (NLPHD). Using an antibody to proliferating cell nuclear antigen (PCNA), we have determined the growth fraction of HRS cells and L&H cells in paraffin sections of 15 cases of classical HD [12 nodular sclerosis (NS), 3 mixed cellularity (MC)] and eight cases of NLPHD. By double staining with anti-PCNA and antibodies to B cells (CD20) and T cells (CD45RO), we also determined the growth fraction and immunophenotype of the background population in each case. In classical HD, 50.4 per cent of HRS cells were PCNA-positive and judged to be proliferating, which is comparable to previous studies, while in NLPHD 76.9 per cent of L&H cells were PCNA-positive. In both classical HD and NLPHD, the majority of PCNA-positive cells in the background were T cells, which showed a growth fraction of 57.8 and 68.5 per cent, respectively; in comparison, only 4 per cent of B cells were PCNA-positive in each type of HD. L&H cells are widely accepted to be B cells and there is growing evidence that HRS cells are also B cell-derived. Our results underline a relationship between classical HD and NLPHD and suggest that the characteristic histological features of both diseases may be caused by the production and release of cytokines from altered B cells.

Antigens, CD↗

Imaging of medullary carcinoma of the thyroid using 111In-labelled anti-CEA monoclonal antibody fragments.

The distribution of 111In-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody fragments [F(Ab')2] was studied in five patients either with known inoperable medullary carcinoma of the thyroid (MCT) or evidence of recurrence/metastases based on elevated calcitonin (hCT) levels. All five cases had elevated serum CEA levels and positive immunohistochemical stains for both hCT and CEA prior to scintigraphy. In two patients with identified inoperable disease both planar and SPECT scans were positive. In the remaining three patients, where the recurrence/metastatic sites were unknown, SPECT images were positive in two. Of these, only one had positive planar images. These results indicate that 111In-labelled anti-CEA F(ab')2 scintigraphy, especially in conjunction with SPECT, is useful for the diagnostic evaluation of patients with MCT. The limiting factor of this technique is the high level of non-specific uptake, particularly in the liver, but improvements in the specificity of newer anti-CEA antibodies and the ability to label these with 99Tcm is addressing this problem.

Adult↗

AUA1: new immunocytochemical marker for detecting epithelial cells in body cavity fluids.

Further to detailed genetic and biochemical characterisation of AUA1 as a surface glycoprotein present on epithelial cells, the antibody against AUA1 was used as an immunocytochemical marker of epithelial cells in body cavity fluids in an attempt to improve the diagnosis made on routine staining. AUA1 was initially tested in 144 morphologically clear cut effusions. It was positive in 46 of 52 (88%) carcinomas and negative in 82 of 84 (98%) benign effusions, including technically inadequate or poorly cellular preparations. There were no false positive results. AUA1 was subsequently used more selectively--that is, in 42 of 175 (24%) of morphologically difficult fluids. AUA1 provided essential diagnostic information in 15 of 42 (36%) and confirmed diagnosis in 17 of 42 (40%), thus enabling accurate diagnosis in a further 32 of 42 (76%) of the difficult cases. The total diagnostic accuracy was therefore 94.3%. AUA1 is a reliable immunocytochemical marker for detecting epithelial cells in body fluids. Its use improves diagnostic accuracy of morphological assessment in difficult cases.

Antibodies, Monoclonal↗

Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder.

The structure and expression of the proto-oncogene c-erbB-2 was studied in 86 patients with transitional cell carcinoma. Initial tissue samples comprised 37 grade 1, 32 grade 2 and 13 grade 3 tumours and four cases of carcinoma in situ. At the time of this first tumour sample, amplification of the c-erbB-2 gene was demonstrated by Southern blotting in 1/37 grade 1, 5/32 grade 2 and 6/13 grade 3 tumours (0.005 less than P less than 0.01). Tumour 're-occurrences' were obtained from 23 of these patients on one or more occasions. Amplification was detected in re-occurrences from seven of these 23, none of whom showed amplification in the first tumour sample. DNA was also extracted from exfoliated cells in urine collected from five cases of carcinoma in situ and c-erbB-2 amplification was demonstrated in one of these. No gene amplification was identified in patients' lymphocytes, ten biopsies of normal urothelium and 22 various intravesical pathologies. Increased expression of c-erbB-2 mRNA correlated with amplification of the gene. In addition, raised levels of mRNA were seen in the absence of gene amplification in six tumours. Immunoblotting using the polyclonal antibody 21N, raised against the c-terminus of the c-erbB-2 protein demonstrated increased amounts of a 185 kD immunoreactive protein in tumours with increased c-erbB-2 gene copy number compared with control tissues. In some tumours with high c-erbB-2 gene copy number, a 155 kD immunoreactive protein not detected in controls was expressed at higher level than the 185 kD protein. Immunocytochemistry using a monoclonal antibody AB-3, raised against the c-terminus of the c-erbB-2 protein, showed a positive reaction in the cytoplasm and cell membrane of tumours with gene amplification and in 40% of tumours with no amplification. An association was found between c-erbB-2 amplification and over-expression and the development of tumour re-occurrences. We suggest that c-erbB-2 amplification and over-expression may provide a useful molecular marker in transitional cell carcinoma of the bladder and merits further investigation as a potential prognostic indicator.

Blotting, Northern↗

Dosage of colloidal bismuth subcitrate in duodenal ulcer healing and clearance of Campylobacter pylori.

Sixty consecutive patients with endoscopically proven duodenal ulcers were given colloidal bismuth subcitrate tablets either as 120 mg q.d.s. or 240 mg b.d., in a randomized single-blind study. The efficacy of each regimen was determined by endoscopic examination and antral biopsy at 4 weeks; if the ulcer remained unhealed, treatment was continued and endoscopy repeated at 8 weeks. The ulcer-healing efficacy of the two regimens was identical; however, in the four times daily group only 27% remained Campylobacter pylori positive after 8 weeks of treatment compared with 58% of the twice-daily group. Similarly, only 21% of twice daily patients were free of histological gastritis compared with 42% of the four times daily patients.

Anti-Ulcer Agents↗

Adjuvant antibiotic therapy in duodenal ulcers treated with colloidal bismuth subcitrate.

Persistence of Helicobacter pylori after duodenal ulcer healing is associated with high rates of ulcer relapse. We compared colloidal bismuth subcitrate alone with CBS combined with one of four antibiotic regimens in the treatment of duodenal ulcers. Endoscopy and antral biopsies were performed before treatment and four weeks afterwards. Biopsy specimens were examined for histological evidence of gastritis and by Gram stain and culture for H pylori infection. Altogether 141 patients were allocated to one of five treatment groups. Giving CBS and metronidazole (400 mg tid for 7 days) with and without amoxycillin (500 mg tid) achieved higher clearance rates of H pylori than treatment with CBS alone (p less than 0.01). These two combinations also achieved higher rates of antral gastritis healing than CBS alone (p less than 0.01 and p less than 0.05 respectively). Susceptibility to metronidazole was tested in 29 isolates before and in seven isolates after treatment with metronidazole by disc diffusion test and minimum inhibitory concentration assay. Twenty seven (93%) of the isolates were sensitive before treatment while six of seven (86%) were resistant afterwards. Four of the six resistant strains had acquired resistance during treatment and one of these had acquired metronidazole resistance despite concomitant treatment with amoxycillin, to which it remained sensitive. CBS with adjuvant metronidazole at a dose of 400 mg tid for seven days significantly improves the eradication of H pylori compared with CBS alone. Acquired metronidazole resistance, however, seems to be an important cause of failure to eradicate H pylori.

Amoxicillin↗

Direct immunofluorescence testing of skin biopsies--an under-utilised diagnostic aid.

Direct immunofluorescence testing of skin biopsies is a simple inexpensive and relatively non-invasive diagnostic procedure currently widely used in dermatological practice for the investigation and diagnosis of dermatological and immunological disorders. This paper reviews the value and applicability of the procedure in a variety of disease states. The sensitivity and specificity of the test to a spectrum of clinical conditions should encourage its more widespread use in general medical and rheumatology practice.

Biopsy↗

Histological gastritis in duodenal ulcer: relationship to Campylobacter pylori and effect of ulcer therapy.

Antral gastritis has been described in up to 100% of patients with duodenal ulcer disease, and recently has been associated with Campylobacter pylori infection. The present study examines the effect of two ulcer therapies (cimetidine and colloidal bismuth subcitrate) on this lesion. Sixty-four consecutive patients with endoscopically diagnosed duodenal ulcer were randomized to treatment with either agent upon entry into the study. Antral biopsies were taken at both initial and final endoscopies for culture of C. pylori and assessment of degree of gastritis (as based on inflammatory cell infiltrate: grades 0 to 3). The organism was detected in 90% of the patients at initial biopsy, and grades 2 and 3 gastritis were documented in 76%. The presence of the organism and the gastritis were significantly correlated (p less than 0.001), and the bacterium was not cultured from histologically normal antral mucosa. Active chronic gastritis (grade 3) was seen in 65% of those with C. pylori, and was not found in any patient without the bacterium. Cimetidine had no effect on either the organism or the gastritis, whereas the bismuth preparation significantly (p less than 0.002) reduced the prevalence of both. The present study documents that therapy directed against C. pylori has a significant effect on the gastritis of duodenal ulcer disease and possible mechanisms for the observed effects are discussed.

Adult↗

Campylobacter pylori and recurrence of duodenal ulcers--a 12-month follow-up study.

In 39 patients with endoscopically healed duodenal ulcers repeat endoscopy and two antral biopsies after 1 year showed a relapse rate of 59%. Only post-treatment Campylobacter pylori status was a significant predictor of endoscopic relapse. 79% of patients who remained culture positive had a relapse, compared with 27% of culture-negative patients. Relapse was more likely (66%) in patients with a recurrence of C pylori after apparent eradication of the organism than in those who remained negative for C pylori (10%). No patient who remained negative for C pylori had histological gastritis, whereas all with recurrence of C pylori showed histological gastritis. These findings suggest an important role for C pylori in duodenal ulcer relapse in the year after treatment.

Adult↗

Mast cells in pulmonary haemosiderosis.

A case of childhood pulmonary haemosiderosis with a fourfold increase in mast cells in the lung is described. This finding is discussed in relation to the pathogenesis of the disease. Comparison is made with controls, and the use of disodium cromoglycate is advocated.

Cell Count↗