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R A Gardiner

Publications and source records attributed to R A Gardiner.

At least 19 recordsLinked to original sources

An immunohistological demonstration of c-erbB-2 oncoprotein expression in primary urothelial bladder cancer.

Sections of formalin-fixed, paraffin-blocked tissue from 116 primary transitional cell carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining of cell membranes, known to correlate with gene amplification, was seen in 22 (19%) of the 116, with variable staining from tumour to tumour and within tumours themselves. Consistent with its mooted value as a prognosticator in bladder cancer, the c-erbB-2 oncoprotein was detected in 13 (of 40) grade III and 9 of the 26 muscle-invasive tumours examined compared to 1 (of 25) grade I and 6 (of 66) mucosa only (pTa) lesions. These results support further examination of c-erbB-2 expression in bladder cancer.

Aged

Evaluation of a bladder advancement extension graft technique.

A bladder advancement extension technique was developed to provide a reliable method for creating an extra length of bladder in continuity, so that Boari flap and psoas hitch procedures, with or without the extension grafts, would reach sufficiently high routinely to permit these procedures to become the preferred practical options for accommodating significant proximal ureteric deficiencies or for replacing the whole of the ureter. In addition, an omentally supported bladder graft was established separately for use in a "retrieval" procedure should extension graft stenosis develop subsequently. Of 10 dogs studied for 6 months, 2 required "retrieval" pedicled island patch grafts for stenoses at extension graft/upper ureteric junctions. Healthy urothelium with muscle in the walls was seen in grafts resting on their supporting omental beds. At the time of sacrificing, none of the operated upper tracts was obstructed.

Animals

Transferrin receptor expression in primary superficial human bladder tumours identifies patients who develop recurrences.

A group of 65 patients with superficial bladder carcinoma was followed for 2 years and tumour recurrence rate was correlated both with transferrin receptor status of the initial primary tumour and with the results of voided urine cytology. Nine of 24 patients with transferrin receptor negative tumours had recurrences compared with 30 of 41 patients with transferrin receptor positive tumours. This difference was highly significant. Urine cytology at presentation was also predictive of further tumour formation: of 30 patients who were transferrin receptor positive and had positive urine cytology, 25 developed recurrences.

Adult

Application of the invaginated sleeve technique to form a continent ileal urostomy.

The invaginated sleeve technique has been adapted to produce a continent urostomy, able to be catheterised, from a length of canine ileum measuring less than 10 cm. Of the 4 dogs catheterised twice daily up to 13 weeks, narrowing was present in the extra-ileal segment in 2, but all intra-ileal double-barrelled lumina remained healthy with preservation of bowel mucosa.

Animals

RAS oncogene product expression in normal and malignant oral mucosa.

Proto-oncogenes are important in both normal cellular differentiation and in carcinogenesis. The majority of transforming genes belong to the ras family and the ras gene product has been shown to be elevated in some oral carcinomas. RAP-5 monoclonal antibody was used to determine the expression of the p21ras protein in normal and neoplastic oral mucosa in an immunohistological study. The expression of p21ras protein was generally restricted to acanthous cells with strong staining in normal oral mucosa and well-differentiated carcinomas. In contrast, the p21ras protein was not detected in significant amounts in severely dysplastic lesions and poorly differentiated carcinomas. These results suggest that expression of p21ras is a normal feature of more fully differentiated tissues, both normal and neoplastic, and is not useful as an indicator of cell proliferation or 'malignant potential'.

Antibodies, Monoclonal

An immunohistological examination of inflammatory cell infiltration in primary testicular seminomas.

Inflammatory cell infiltration was characterized in five classical seminomatous testicular tumours using immunohistochemical techniques. These cells of immunological lineage were sited mostly around vessels. Lymphocytes were the most numerous, T cells outnumbering B cells in all sections studied. The helper/inducer subgroup predominated in the T cell family with suppressor cells more common than cytotoxic cells. Plasma cells constituted only a small percentage of this population as did natural killer cells. No Langerhans cells were identified. Phagocytic macrophages were twice as common as antigen-presenting macrophages yet T lymphocytes were 15 times more common than these antigen-presenting macrophages.

Antibodies, Monoclonal

Development of the invaginated sleeve technique for continent cystostomies in dogs.

Two studies were undertaken in dogs to evaluate oblique tunnels through bladder walls lined by urothelium for use in continent cystostomies. In the first study, the tracts were lined completely by urothelium by 10 weeks, but tract calibre reduced considerably after stent removal and periluminal fibrosis was a prominent feature. In the second study a tubularised partial-thickness pedicle graft was invaginated through an oblique tunnel in the bladder wall, with the graft extending extravesically and then being wrapped in omentum. This technique provided complete urothelial covering by 2 weeks with much less periluminal fibrosis. In the 3 dogs catheterised daily up to 120 days, this technique afforded continence with generous tracts for catheterisation.

Animals

Immunocytochemical demonstration of p21ras in normal and transitional cell carcinoma urothelium.

Activation and/or overexpression of the protein product of the ras gene family (p21ras) has been implicated in the development of various cancers, including bladder carcinoma. We have used the anti-p21ras monoclonal antibody, RAP-5, to assess the level and pattern of expression in formalin-fixed, paraffin-embedded tissue sections of both normal and malignant urothelium. All 14 random normal bladder biopsies and 67 of 68 transitional cell carcinomas of the urinary bladder were positively stained with the RAP-5 antibody. In normal urothelium, p21ras staining tended to be localized to the superficial cell layer. With increasing histological grade and/or depth of invasion of the tumour, a greater proportion of tissue sections demonstrated a staining pattern which was more uniform with respect to the different epithelial cell types. Serially diluting the primary antibody did not reveal any significant differences in the staining patterns observed. Despite the change in staining pattern with increasing grade, these results suggest that p21ras expression by itself is not a useful indicator of the malignant phenotype.

Adult

An immunohistopathological characterisation of mixed non-seminomatous germ cell tumors.

Immunohistological techniques were used to characterise inflammatory cell infiltrates in mixed germ cell tumours. The distribution of these infiltrates was much more variable than in pure seminomas but could not be related accurately to any particular tumour type. There were approximately equal numbers of B and T cells in these areas and helper/inducer T cells were more common than suppressor/cytotoxic lymphocytes. Within these areas of inflammatory cells, the subtype composition was similar to that seen in pure seminomas.

B-Lymphocytes

c-Ha-ras-1 alleles in bladder cancer, Wilms' tumour and malignant melanoma.

Polymorphism of the human c-Ha-ras-1 gene has been analysed in DNA from 168 individuals using the enzymes MspI and HpaII. In all, 35 bladder cancer patients, 28 melanoma patients, 22 Wilms' tumour patients, 24 first-degree relatives of Wilms' tumour or melanoma patients and 59 unaffected controls were studied. A total of 13 different fragment sizes was detected, 4 "common" and 9 "unusual". Of the latter, 4 were observed only in cancer patients or their first-degree relatives. The frequency of unusual alleles was significantly greater in bladder cancer patients and in the combined tumour group than in controls, thus providing support for the association of unique Ha-ras alleles and cancer. Some unaffected relatives of patients carried unusual alleles, and thus there is no absolute relationship between Ha-ras genotype and disease.

Alleles

Replacement of excised segments of proximal ureters by tubularised bladder grafts vascularised by previously established omental pedicles.

This article reports the final study of experiments in which autologous bladder grafts have been used to replace excised segments of ureters in dogs. The technique described involves the use of bladder grafts on previously established omental pedicles as replacements for proximal ureters. Grafts were tubularised over silastic stents, then completely covered with secondary wrappings of omentum. Operated upper tracts were compared to control sides up to 12 months, then, at one year, intravenous urography was repeated at which time inspection was made of operated upper tracts (and contralateral controls) using an image intensifier prior to recording renal pelvic pressure responses to increasing perfusion rates and, finally, pathological examination. Only two of 14 upper tracts with pedicle grafts were failures radiologically and no upper tract was obstructed urodynamically. This approach is recommended for consideration as a treatment option in managing longitudinal defects in ureters in humans.

Anastomosis, Surgical

Elevated lactate dehydrogenase isoenzyme 1 as a tumour marker in patients with germ cell testicular tumours.

In a series of 50 patients with testicular tumours evaluated prior to orchidectomy, 12 out of 19 with pure seminoma and seven out of 31 with non-seminomatous or mixed seminomatous and non-seminomatous germ cell tumours had elevated plasma lactate dehydrogenase isoenzyme 1 concentrations. In contrast, seven of the 19 seminoma patients had elevated serum human chorionic gonadotrophin (hCG) concentrations and 25 of the 31 non-seminomatous and mixed seminomatous and non-seminomatous germ cell tumour patients had elevations of hCG and/or alpha-fetoprotein. Using these three markers, 12 out of 19 seminoma patients and 27 out of 31 non-seminomatous or mixed seminomatous and non-seminomatous tumour patients were positive for one or more of these tumour markers.

Biomarkers, Tumor

Transferrin receptor expression by human bladder transitional cell carcinomas.

The expression of transferrin receptors (TFR) by normal and neoplastic urothelial cells was studied in "control" patients and in patients with transitional cell carcinoma of the bladder. These tumours were graded independently and consisted of 19 grade I, 30 grade II and 19 grade III lesions. TFRs were identified using a monoclonal antibody specific for TFR (OKT9) in an immunofluorescent or avidin/biotin-immunoperoxidase technique on fresh frozen sections. TFRs were not detected on normal urothelium. However, positive staining was found to increase with increasing pathological grade and stage of the tumours, ranging from 31.6% of grade I to 78.9% of grade III tumours and 51.2% of pTa (mucosa only lesions) to 87.5% of pT2/pT2+ (muscle invasion +/- deeper) primary urothelial malignancies.

Adult

Genotoxicity of analgesic compounds assessed by an in vitro micronucleus assay.

Several analgesic compounds and mixtures of analgesics were examined for both cytotoxicity and ability to induce chromosomal damage in the normal rat-kidney cell line NRK-49F. Chromosomal damage was assessed using an in vitro micronucleus assay. Of all the compounds tested, only N-hydroxyparacetamol caused a high degree of cell death at the concentrations used. 4 analgesic compounds were found to be inducers of micronuclei in NRK cells; in order of decreasing potency these were: N-hydroxyparacetamol, N-hydroxyphenacetin, caffeine and paracetamol. An aspirin, phenacetin, caffeine mixture (APC) failed to induce micronuclei above the background level, and a paracetamol-codeine combination did not increase the level of micronuclei induction above that induced by paracetamol alone. This report suggests paracetamol and some related compounds are capable of inducing chromosomal damage in mammalian cells in vitro, which is consistent with recent reports of a possible paracetamol-DNA interaction.

Analgesics

Immunohistochemical analysis of the human bladder.

An immunohistochemical profile of cells in the mucosa and lamina propria of adult human bladders is described. Urothelial cells were HLA-DR-ve, ACP + ve and ATPase-ve. All lymphocytes in this layer were of the suppressor/cytotoxic T subgroup and dendritic cells with an identical phenotype to Langerhans cells were seen. In the lamina propria most lymphocytes were of the suppressor/cytotoxic type with some helper/inducer cells. An occasional natural killer cell and Langerhans cell was identified and large macrophage cells with a common phenotype to antigen presenting interdigitating (ID) cells were noted. Fibronectin staining was dense in the vicinity of basement membranes merging to form fine interconnecting latticework-like structures elsewhere in the lamina propria.

Acid Phosphatase

Endoscopic transvesical ureterotomy.

Endoscopic transvesical ureterotomy was used in 2 cases of lower ureteral stricture. Ureteral catheterization was performed after dilation. Then, with cutting diathermy a Colling's knife was directed so that an incision was made at the 12 o'clock position, cutting onto the catheter and, thus, completing the ureterotomy. In each case the incision extended outside the bladder through the strictured segment of the ureter and above to the dilated ureter proximal to the stenosis. Obstruction was relieved in both cases and, although vesicoureteral reflux was present during voiding, excretory urography at 12 months demonstrated acceptable tracts.

Aged