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Biomedical subjects

R F McMahon

Publications and source records attributed to R F McMahon.

At least 37 records · Page 2Linked to original sources
PubMed1994

Altered saccharide sequences in two groups of patients with metastatic prostatic carcinoma.

OBJECTIVE: To investigate the hypothesis that primary prostatic carcinomas with metastases to different sites (lymph nodes or bone) show varying expression of cell surface and cytoplasmic glycoconjugates. PATIENTS AND METHODS: A group of 14 patients with primary prostatic carcinoma with lymph node metastases but no bone metastases has previously been shown to have an increased survival time. This group was compared with a control group of 14 patients with lymph node-negative, bone metastasis-positive primary prostatic carcinoma using a panel of biotinylated lectins revealed by the avidin-biotin peroxidase complex method. The results were analysed semi-quantitatively and differences in binding patterns between the two groups were sought. RESULTS: No significant differences were seen using the LCA, LTA, UEA-1, WFA, VVA or SBA lectins. The group with bone metastases but no lymph node involvement showed significantly increased binding for the ECA and AHA lectins, both before and after neuraminidase pre-treatment, compared with the lymph node-positive group. CONCLUSIONS: These results suggest that tumours lacking or having a reduced affinity for binding sites for both Gal beta 1-3GalNac (Type I oligosaccharide structures--AHA) and Gal beta 1-4GlcNac (Type II oligosaccharide structures--ECA) sequences are more likely to develop lymph node metastases and less likely to develop bone metastases and thereby increasing the patient's chances of survival. This is further evidence that the metastatic potential of tumours per se and the ultimate site of distal metastases from such tumours is affected in part by the glycoconjugates expressed on their cell surfaces and indicates that metastatic phenotypes for prostatic carcinoma exists.

Aged↗
PubMed1994

Acid-base transport systems in a polarized human intestinal cell monolayer: Caco-2.

Acid-base transport systems have been incompletely characterized in intact intestinal epithelial cells. We therefore studied the human cell line Caco-2, cultured on Teflon membranes to form confluent monolayers with apical microvilli on transmission electron microscopy and progressive enrichment in microvillar hydrolases. Monolayers (16- to 25-day-old), loaded with the pH-sensitive dye BCECF-AM (2',7'-bis (carboxyethyl)-5-carboxyfluorescein), were mounted in a spectrofluorometer cuvette to allow selective superfusion of apical and basolateral surfaces with Hepes- or HCO(3-)-buffered media. Intracellular pH (pHi) was measured by dual-excitation spectrofluorimetry; calibration was with standards containing nigericin and 110 mM K+ corresponding to measured intracellular [K+] in Caco-2 cell monolayers. In HCO(3-)-free (Hepes-buffered) media, bilateral superfusion with 1 mM amiloride or with Na(+)-free media reversibly inhibited pHi recovery from an intracellular acid load (NH4Cl pulse) by 86 and 98% respectively. Selective readdition of Na+ to the apical or basolateral superfusate also induced a pHi recovery, which was inhibited by ipsilateral but not by contralateral amiloride (1 mM). The pHi recovery induced by apical Na+ readdition had a Michaelis constant (Km) for Na+ of 30 mM and a relatively high inhibitor constant (Ki) for amiloride of 45.5 microM. Initial pHi in HCO(3-)-buffered media was lower than in the absence of HCO3- (7.35 vs. 7.80). pHi recovery from an acid load in HCO3- was Na- dependent but was inhibited only 18% by 1 mM amiloride. The amiloride-independent pHi recovery was inhibited 49% by pre-incubation of cells in 5 mM DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid). These data suggest that Caco-2 cells possess: (a) both apical and basolateral membrane Na(+)-H+ exchange mechanisms, the apical exchanger being relatively resistant to amiloride, similar to apical Na(+)-H+ exchangers in several normal epithelia; and (b) a Na(-)-dependent HCO3- transport system, either Na(+)-HCO3- cotransport or Na(-)-dependent Cl(-)-HCO3- exchange.

Acid-Base Equilibrium↗
PubMed1993

Pelvic ileo-anal reservoirs: a lectin histochemical study.

Pelvic ileo-anal reservoir (ileal pouch) formation is now a common surgical approach to the management of long-standing inflammatory bowel disease. The ileal mucosa in this new environment responds with changes in morphology and histochemical reactivity, as shown by conventional techniques. In this study, pre-pouch ileum and pouch ileal mucosa from 20 patients have been examined with a large panel of lectins using an avidin-biotin-peroxidase technique, with appropriate negative controls and sugar-inhibition studies. Changes were noted between pre-pouch ileum and the pouch mucosa which were complex, and no single alteration was seen in every case. Most variations related to saccharide sequences near the non-reducing termini of O- and N-linked glycans. Many of these were seen with lectins having requirements for terminal fucosyl residues, and to a lesser extent for galactosyl sequences, and were most obvious in the epithelium. Some of the changes occurred with such frequency as to suggest a direct response to surgery, but many of the variations were likely to be adaptive responses, possibly related to inflammation or infection. The changes in glycans were largely additive and could not be explained as a consequence of the actions of bacterial glycosidases. These alterations suggest that reservoir mucosa undergoes an adaptive response to the new intraluminal environment, without frank colonic metaplasia, and some changes occur to a greater degree in patients with pouchitis.

Adult↗
PubMed1993

Foreign body giant cell reactions and ossification associated with benign melanocytic naevi.

AIMS: To assess the incidence of foreign body giant cell reactions and ossification in benign/melanocytic naevi; and to examine their pathological features to gain an insight into their pathogenesis. METHODS: Intradermal (n = 185) and compound naevi (n = 110) from a routine histology service, together with 60 naevi submitted to an ophthalmic pathologist, were examined for foreign body reactions and ossification. Additional cases were identified prospectively in the course of routine reporting. The clinical and pathological features of positive cases were assessed. RESULTS: Foreign body reactions were identified in nine (4.9%) intradermal and four (3.6%) compound naevi, but in none of the naevi from around the eye. One intradermal naevus showed ossification. A further 11 naevi showing foreign body reaction and five showing ossification alone were identified prospectively. The 24 naevi showing a foreign body reaction had a similar age and sex distribution to controls but were more likely to occur on the head and neck. The reaction usually occurred deep to the naevus, sometimes in relation to a hair follicle, and fragments of hair or keratin were identified in most. Osteoid or bone was present within the reaction in five. In six other naevi, all from the head and neck of women, osteoid or mature bone was present deep to the naevus in the absence of a giant cell reaction. CONCLUSIONS: Foreign body giant cell reactions occur not uncommonly in relation to benign naevi, as a result of follicular damage, possibly due to trauma. The similar siting of foci of bone suggests that ossification occurs as a secondary phenomenon in these cases.

Adult↗
PubMed1993

Lipomatous hamartoma of the interatrial septum.

Four cases of lipomatous hamartoma of the interatrial septum (LHIAS) were diagnosed at autopsy, three in elderly women, two of whom were morbidly obese. One patient had signs of congestive cardiac failure, without other significant cardiopulmonary disease, which was thought to be a result of the interatrial lipomatous hamartoma, while in the others, the LHIAS was considered an incidental finding. This condition, previously considered a hypertrophic phenomenon, is now best described as hamartomatous, and is being recognized more frequently both by clinicians and pathologists.

Aged↗
PubMed1992

Inhibition of Clostridium perfringens phospholipase C by ammonium and sulfonium dications.

Polyamines, alkyldiammonium and alkyldisulfonium salts, inhibit the Clostridium perfringens phospholipase C-catalyzed hydrolysis of 1-S-phosphocholine-2-O-hexadecanoyl-1-mercapto-2-ethanol (1) at pH 7.5, 37 degrees C, mu = 1.0 with KCl. Simple saturation kinetics are observed as both 1 and [Ca2+] are varied and simple linear inhibition is observed. The data are consistent with a non-competitive mechanism that involves binding of the inhibitors to free enzyme, E.[Ca2+] and E.[Ca2+].[S]; the inhibition constants for decamethylenebis(trimethylammonium) and decamethylenebis(dimethylsulfonium) bromides are 90 and 0.28 mM, respectively. It is suggested that the enhanced inhibition by the alkyldisulfonium salts results from more favorable equilibrium constants for contact ion-pair formation or from the formation of tetracoordinate sulfuranes.

Ammonia↗
PubMed1992

Renal carcinoma in patients undergoing nephrectomy: analysis of survival and prognostic factors.

A series of 155 patients who underwent nephrectomy for renal carcinoma between 1965 and 1985 at Manchester Royal Infirmary were analysed for survival in relationship to presenting features, surgical staging and histopathology. Univariate and multivariate analyses were carried out. Five-year survival estimates for stage 1 disease were 81%, for stage 2 disease 65%, for stage 3 disease 39% and for stage 4 disease 6%. An erythrocyte sedimentation rate (ESR) greater than 30 mm/h was associated with worse survival and a history of hypertension was associated with better survival. Renal vein invasion alone was related to worse survival. Perinephric fat invasion was also associated with worse survival and this association in the multivariate analysis was more significant than expected, suggesting that the principles of radical surgery should be observed. The presence of granular cells as opposed to clear cells worsened survival. Patients with papillary tumours had a better survival than those with solid tumours.

Adult↗
PubMed1992

Evaluation of three techniques for differential diagnosis of prostatic needle biopsy specimens.

AIMS: To determine whether acidic mucin staining, lectin histochemistry using Wisteria floribunda agglutinin, and immunohistochemistry using the monoclonal antibody EAB 903 are of benefit in distinguishing between hyperplastic and carcinomatous prostatic glandular tissue in needle biopsy specimens. METHODS: Formalin fixed, paraffin wax embedded prostatic needle biopsy specimens of benign and malignant tissue were examined. Alcian blue-periodic acid Schiff staining was performed on 33 benign and 34 malignant cases. Wisteria floribunda agglutinin (WFA) binding sites were demonstrated by the avidin-biotin peroxidase (ABC) technique with and without neuraminidase pretreatment on 34 benign cases and 32 malignant cases. EAB903 anticytokeratin antibody binding sites were demonstrated using both an indirect immunoperoxidase (IIP) technique and an avidin-biotin peroxidase complex method on seven benign and 31 malignant cases. RESULTS: Acidic mucin staining was found in 17 of 34 malignant glands and was weakly positive in five of 33 benign glands. WFA positivity before neuraminidase pretreatment was present in 29 of 32 malignant glands and in 19 of 34 benign glands. After neuraminidase all benign and malignant cases showed positivity. EAB 903 positivity was seen in 11 of 31 malignant glands using the IIP technique and in two of 31 malignant glands using the ABC technique. In seven benign cases there was positivity in all glands using the IIP method with predominant basal cell staining in three and superficial cell staining in four. In benign cases using the ABC method two cases were negative. CONCLUSIONS: None of the three methods studied showed sufficient sensitivity and specificity to allow their recommendation for routine diagnostic use.

Agglutination Tests↗
PubMed1991

Kinetic mechanism of Clostridium perfringens phospholipase C. Hydrolysis of a thiophosphate analogue of lysophosphatidylcholine.

The hydrolysis of S-[2-(hexadecanoyloxy)ethyl]thiophosphocholine (I), an analogue of lysophosphatidylcholine, by Clostridium perfringens phospholipase C, was followed at pH 7.5, 37 degrees C and I 1.0 (maintained with KCl), in a continuous assay, by monitoring the reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) at 412 nm. Simple saturation kinetics are observed with linear mixed-type slope-intercept effects for the hydrolysis of compound (I) with variable [Ca2+] at fixed concentrations of compound (I) and a simple slope effect as [compound (I)] is varied at fixed concentrations of Ca2+. These data are consistent with a simple ordered rapid-equilibrium mechanism in which Ca2+ binds to the enzyme first followed by substrate. The observed kinetic constants at pH 7.5, 37 degrees C and I 1.0 are K1 = 12.0 mM (Ca2+ dissociation), K2 = 36 microM [compound (I) dissociation] and Vmax. = 552 microM.min-1.mg-1. Alkane diammonium salts inhibit the enzyme by a non-competitive mechanism that involves binding to free enzyme, E.Ca2+ and E.Ca2+.S. The use of the simple micellarized substrate under these conditions allows the determination of kinetic and inhibition constants without complications arising from enzyme-micelle interactions.

Clostridium perfringens↗
PubMed1991

Inhibition of the Clostridium perfringens phospholipase C hydrolysis of a thiophosphate analog of lysophosphatidylcholine by micelle-bound ammonium and sulfonium cations.

Cetyltrimethylammonium and n-octadecyldimethylsulfonium bromides inhibit the Clostridium perfringens phospholipase C-catalyzed hydrolysis of 1-S-phosphocholine-2-O-hexadecanoyl-1-mercapto-2-ethanol (1) at pH 7.5, 37 degrees C, mu = 0.15 with KCl. Mixed micelles containing 1 and either inhibitor are substrates for the enzyme and the fraction of activity remaining is a monotonic, but non-linear function of the mole fraction of inhibitor. Simple saturation kinetics are observed as the concentration of 1 is increased in mixed micelles containing a constant mole fraction of inhibitor. Inhibition constants for cetyltrimethylammonium and n-octadecyldimethylsulfonium bromides are 0.66 +/- 0.04 and 0.25 +/- 0.02 mM, respectively. The data suggest that the significant inhibition previously observed for soluble alkyldisulfonium salts (K50 for dodecamethylene-bis(dimethylsulfonium) bromide, 27 microM) is dependent upon bifunctional cationic interactions rather than hydrophobic binding.

Cations↗
PubMed1991

Apoptosis in pancreatic allograft rejection--ultrastructural observations.

Transplantation of pancreaticoduodenal allografts in the PVG.RT1c----PVG.RT1u high responder rat strain combination led to the evolution of haemorrhagic pancreatic necrosis over a rejection course of 8d. A cellular infiltrate consisting mainly of monocytes and macrophages was detectable in the stroma while acinar cells showed degranulation and a progressive decrease in number. From day 4 on apoptotic bodies could be identified ultrastructurally within the exocrine tissue. Apoptosis during pancreas rejection, previously undescribed, contributes to acinar cell loss after transplantation in this model.

Animals↗
PubMed1991

Androgen associated hepatocellular carcinoma with an aggressive course.

The hepatocellular carcinomas that develop in patients treated with androgens have previously been associated with a benign clinical outcome. We describe a man who developed a hepatocellular carcinoma after 24 years of androgen treatment, whose tumour initially showed partial regression after withdrawal of androgens but subsequently pursued an aggressive and fatal course.

Carcinoma, Hepatocellular↗
PubMed1991

Pulmonary infarction, myocardial infarction, and acute disseminated intravascular coagulation.

Pulmonary and myocardial damage are frequently cited as manifestations of disseminated intravascular coagulation (DIC), but rarely as causes. Three elderly cases of severe DIC due to pulmonary and myocardial infarction are reported. All three patients died. Necropsy showed extensive pulmonary emboli in each case with large pulmonary infarcts in cases 1 and 2 and a ventricular aneurysm containing thrombus in cases 2 and 3. Early diagnosis and treatment of pulmonary embolism requires a high degree of clinical suspicion but may prevent progression to the irreversible stage of severe DIC.

Aged↗