Search PubMed⌕ Search

Biomedical subjects

S J Thorpe

Publications and source records attributed to S J Thorpe.

At least 73 records · Page 4Linked to original sources
PubMed1989

Blood group antigen expression in frozen sections of presenting bladder cancer: 3-year prospective follow-up of prognostic value.

Blood group antigen (BGA) expression was studied on frozen sections from the initial, presenting, transitional cell bladder cancers of 73 patients. Clinical follow-up was prospective and, after 3 years, 59 patients were available for assessment. Of 32 tumours that retained substantial BGA (BGA+ and BGA +/- ), 11 progressed. Of 27 tumours with less than 5% or undetectable BGA expression (BGA-), 14 did not progress. Of 24 pTa tumours, 17 had substantial BGA expression and 7 were BGA-; 5 patients progressed, 4 substantially BGA positive and 1 BGA-, all to category pT1; 15 tumours were category pT1, 7 substantially BGA positive and 8 BGA-; 7 patients progressed, 1 substantially BGA positive and 6 BGA-, all of whom died from bladder cancer; 20 were pT2 or deeper, 8 substantially BGA positive and 12 BGA-; 12 patients progressed, 6 substantially BGA positive and 6 BGA-, all of whom died from bladder cancer. Despite improved understanding of the biochemistry and techniques of detection of BGA, these results preclude the use of BGA determination as a guide to prognosis in individual transitional cell carcinoma, whether used alone or in combination with pT category.

ABO Blood-Group System↗
PubMed1988

Developmental patterning of carbohydrate antigens during early embryogenesis of the chick: expression of antigens of the poly-N-acetyllactosamine series.

This report describes a striking temporal and spatial patterning of specific carbohydrate sequences in the developing chick embryo. By using oligosaccharide sequence-specific monoclonal antibodies as immunohistochemical reagents in conjunction with neuraminidase, it was possible to visualize the occurrence, as well as the changes in distribution, of oligosaccharides of the poly-N-acetyllactosamine series. These were (a) long-chain unbranched sequences reactive with anti-i Den, (b) long-chain branched sequences reactive with anti-I Step and (c) short-chain branched sequences reactive with anti-I Ma and (d) their sialylated forms. The salient observations with serial sections of embryos from the unincubated to the 17th stage were as follows. (1) A pronounced anteroposterior patterning appeared during neuroectodermal development, such that the long-chain unbranched and long-chain branched sequences, which were abundant on the ectoderm of the earlier stages, were replaced by short-chain branched sialo-oligosaccharides in the developing brain and anterior neural tube. (2) A striking anteroposterior and mediolateral patterning developed in the subectodermal extracellular spaces. The long-chain linear and short-chain non-sialylated sequences demarcated regions favourable for migration of the lateral plate mesoderm. (3) A distinction was made between the dorsal and ventral routes of the trunk neural crest in that the extracellular matrix of the dorsal route only was associated with long-chain linear and short-chain sialylated branched sequences. (4) A circumscribed perinotochordal distribution of the short-chain sialylated branched sequences was observed in the region of the future centra of the vertebrae. (5) An abundance of long-chain linear and long-chain sialylated branched structures was detected in primordial germ cells which permitted their identification during migration. These observations suggest that oligosaccharides of the poly-N-acetyllactosamine series may have roles as short-range, region-specific information factors during morphogenetic events that take place in the developing embryo, and they open the way to the search for recognition proteins (e.g. endogenous lectins) specific for each of these oligosaccharide structures.

Animals↗
PubMed1986

Blood-group-related carbohydrate antigens are expressed on human milk galactosyltransferase and are immunogenic in rabbits.

Immunochemical evidence is presented for the presence of blood-group-related carbohydrate structures on human milk galactosyltransferase and for the occurrence of the corresponding specificities among rabbit antibodies to this enzyme. Although these carbohydrate specificities constitute minor populations among antisera and affinity-purified antibodies to galactosyltransferase, their presence is important in the immunohistochemical approach to enzyme localization, since they give rise to strong reactivities with epithelial cells of the gastrointestinal tract.

Animals↗
PubMed1986

Sensory-specific satiety: food-specific reduction in responsiveness of ventral forebrain neurons after feeding in the monkey.

It has been shown previously that some neurons in the lateral hypothalamus and substantia innominata respond to the sight of food, others to the taste of food, and others to the sight or taste of food, in the hungry monkey. It is shown here that feeding to satiety decreases the responses of hypothalamic neurons to the sight and/or taste of a food on which the monkey has been satiated, but leaves the responses of the same neurons to other foods on which the monkey has not been satiated relatively unchanged. This suggests that the responses of these neurons in the ventral forebrain are related to sensory-specific satiety, an important phenomenon which regulates food intake. In sensory-specific satiety, the pleasantness of the sight or taste of a food becomes less after it is eaten to satiety, whereas the pleasantness of the sight or taste of other foods which have not been eaten is much less changed; correspondingly, food intake is greater if foods which have not already been eaten to satiety are offered.

Animals↗
PubMed1986

Expression of blood group antigens in urinary tract tumours: prospective fluorescence study using cryostat sections of fresh frozen tissues.

Cryostat sections of fresh frozen tissues were used in a prospective study of blood group H and A antigen fluorescence in 73 transitional cell carcinomas of the bladder. The aim was to evaluate antigen expression without subjecting the tumour tissues to organic solvents that extract blood group active glycolipids. Deletion of the genetically predicted antigen was twice as common in tumours of pT1 or greater stage than those of pTa stage and also twice as common in poorly differentiated than in moderately well differentiated tumours. The considerable heterogeneity and overlap, however, in patterns of reactivity in tumours of various histopathological stages and grades and the effect of secretor status on antigenicity meant that there was no obvious antigenic feature that correlated precisely with invasive stage or differentiation grade. It remains to be determined whether the antigen positive and antigen negative tumours represent different disease entities with differing clinical courses. Our results indicate, however, that studies of the blood group antigens in urinary tract tumours are more likely to be of value in research into biochemical disorders in the neoplastic process than in routine clinical assessment as a guide to treatment.

ABO Blood-Group System↗
PubMed1985

Transformation and growth related changes in levels of nuclear and cytoplasmic proteins antigenically related to mammalian beta-galactoside-binding lectin.

Immunofluorescence and immunoblotting experiments, using a monoclonal antibody to the 13 kDa mammalian beta-galactoside-binding lectin have shown that human lymphocytes contain nuclear and cytoplasmic proteins of apparent molecular masses of 130, 80, 65 and 13 kDa that are antigenically related to the lectin and whose levels and patterns of expression change in association with transformation, or after stimulation with mitogens. These observations, together with the finding that the myeloid cell line K562 is also rich in the 130 kDa component, whereas the mature granulocytes of normal donors and of patients with chronic myeloid leukaemia are lacking in all of the immunoreactive forms, raise the possibility that this family of lectin-related proteins may be components of growth regulatory systems that are variously elicited in the transformed and stimulated cells.

Antibodies, Monoclonal↗
PubMed1985

Cell interactions in preimplantation embryos: evidence for involvement of saccharides of the poly-N-acetyllactosamine series.

Roles of cell surface carbohydrates containing the 3-fucosyl-N-acetyllactosamine and poly-N-acetyllactosamine sequences (SSEA-1 and I antigens, respectively) in the compaction of mouse embryos have been investigated using the endo-beta-galactosidase of Bacteroides fragilis to modify the surface of cleavage-stage embryos. Treatment with this enzyme abolished SSEA-1 activity and diminished I antigen activity on the embryonic cell surface. Embryos cultured in the presence of endo-beta-galactosidase from the 2- to 4-cell stage onwards, or treated with the enzyme at the compacting 8-cell stage, continued to compact and proceeded to form blastocysts at the normal rate. However, when compacted 8- to 16-cell embryos were experimentally decompacted in calcium-free medium, treated for 1 h with endo-beta-galactosidase and returned to normal culture medium, the time taken for 50% of the embryos to recompact was prolonged five-fold. There was an even greater delay if these embryos were maintained in culture medium containing the enzyme. Blastocysts were eventually formed under both conditions. Thus, endo-beta-galactosidase did not affect compaction unless the embryos were first decompacted. On the assumption that recompaction and de novo compaction occur by similar mechanisms, we propose that carbohydrate-binding molecules are involved which have high affinities for poly-N-acetyllactosamine structures and protect them from digestion by endo-beta-galactosidase.

Animals↗
PubMed1984

Blood group-active carbohydrate chains on the receptor for epidermal growth factor of A431 cells.

The antigens expressed on the carbohydrate chains of the receptor for epidermal growth factor of A431 cells were studied by immunoblotting with monoclonal antibodies. Blood group A and the Type 1 based blood group ALeb and Lea antigens were detected as well as antigens associated with unsubstituted, monofucosylated and difucosylated Type 2 blood group chains. The Lea and the difucosylated Type 2 antigen activities were abolished by treating the blotted receptor with endo-beta-galactosidase, indicating that they are expressed on backbone structures of poly-lacto/neolacto type. (The term 'poly-lacto/neolacto' is used here to describe oligosaccharide backbone structures consisting of repeating Type 1, Gal beta 1-3GlcNAc (lacto) or Type 2, Gal beta 1-4GlcNAc (neolacto) sequences.) The glycosidic linkage of oligosaccharides to protein was investigated using Pronase digests of the receptor biosynthetically labelled with [3H]glucosamine or [3H]fucose. The oligosaccharides were alkali-resistant, consistent with N- rather than O-glycosidically linked chains. A proportion of [3H]fucose-labelled glycopeptides was susceptible to endo-beta-galactosidase, confirming the immunoblotting experiment using antibodies against the Lea and the difucosylated Type 2 antigenic determinants. Oligosaccharides were released from the [3H]fucose- and [3H]-glucosamine-labelled glycopeptides by hydrazinolysis. Chromatography of the oligosaccharides on Bio-Gel P6 and Concanavalin A columns indicated a spectrum of oligosaccharides which include those of high mannose type labelled with [3H]glucosamine, and a mixture of oligosaccharides labelled with [3H]fucose and [3H]glucosamine of bi- and multiantennary complex types of which a subpopulation is susceptible to digestion with endo-beta-galactosidase.

ABO Blood-Group System↗
PubMed1984

Species differences in the expression of carbohydrate differentiation antigens on mammalian blood cells revealed by immunofluorescence with monoclonal antibodies.

Following recent observations using monoclonal antibodies that carbohydrate structures behave as differentiation antigens of man and mouse, we have made a preliminary survey of the expression of 8 monoclonal antibody-defined carbohydrate antigens on blood cell smears of man, baboon, mouse, rat, rabbit, pig, and dog. There are considerable species differences in the patterns of antigen expression. However, certain generalizations can be made as follows: the i and I antigens, associated with linear and branched carbohydrate chains consisting of repeating N-acetyl-lactosamine sequences (Gal beta 1-4GlcNAc, termed Type-2 backbone sequences) are widely distributed among granulocytes and lymphocytes of all the species studied, and on erythrocytes, monocytes, and platelets of some of them. Substantial amounts of Type-1 backbone sequences (Gal beta 1-3GlcNAc) may occur on rabbit lymphocytes. The N-acetylneuraminic acid-containing antigens, Pr2 and Gd, are also expressed to varying degrees on blood cells. On the other hand, antigens based on mono- and difucosylated N-acetyllactosamine, termed SSEA-1 (or X-hapten) and C14 (or Y-hapten) are predominantly granulocyte/monocyte-associated antigens. The former antigen is expressed in overt form only on untreated human granulocytes but occurs in cryptic state, masked by sialic acid, on human monocytes, and on the granulocytes and monocytes of baboon, rabbit, and dog but not on those of mouse, rat, and pig. The latter antigen is expressed on human granulocytes and on neuraminidase-treated monocytes and granulocytes of dog. Lymphocytes of dog are unusual in their expression of C14 antigen, in cryptic state, masked by sialic acid residues. Although the physiological roles of these various carbohydrate structures, in vivo, are not yet known, they seem excellent candidates as determinants of species and cell-type differences in susceptibilities to infective agents.

Animals↗
PubMed1984

Responses of striatal neurons in the behaving monkey. 3. Effects of iontophoretically applied dopamine on normal responsiveness.

In order to analyse the functions of dopamine, the effects of the iontophoretic application of dopamine on the responsiveness of striatal neurons to their normal inputs were investigated in the behaving monkey. It was shown that many neurons in the putamen had responses related to movements, of for example the mouth. Iontophoretically applied dopamine decreased the spontaneous firing rates of 178 of 267 neurons (67%) tested in the putamen, caudate nucleus, and the adjacent prefrontal cortex which also receives a dopaminergic projection. Trifluoperazine, applied iontophoretically to block dopamine receptors, increased the spontaneous firing rates of some of the neurons in the prefrontal cortex, suggesting that under normal conditions in the behaving animal the release of dopamine holds the firing rates of these neurons at a low level. The median was 9 spikes/s in the present sample of striatal neurons. Application of dopamine decreased the magnitude of the movement-related responses of the striatal neurons; this decrease in the responses was of approximately the same magnitude in spikes per second as the decrease in the spontaneous firing rate of the neurons produced by the same current of dopamine. It is suggested that this type of effect of dopamine could influence the signal to noise ratio of processing within the striatum, and that changes in this signal to noise ratio produced by disturbances of dopaminergic function could contribute to the behavioral disorders produced by dysfunctions of the dopaminergic systems.

Animals↗
PubMed1984

Tumour-associated and differentiation antigens on the carbohydrate moieties of mucin-type glycoproteins.

In this report the carbohydrate antigens expressed on the three oligosaccharide domains, core, backbone and peripheral, of mucin-type glycoproteins are briefly reviewed in the light of recent observations with monoclonal antibodies. These have revealed that a number of cell-surface antigens which behave as tumour-associated and differentiation antigens of man or mouse are abundantly expressed on the carbohydrate chains of a variety of secreted mucins of human and animal origins and they belong to an antigen system which also includes the major blood group antigens. Examples are given of the use of well-characterized anti-carbohydrate antibodies to derive structural information on (a) mucin-type glycoproteins of human B lymphocyte membranes, (b) the high molecular weight glycoproteins of the normal human gastric and distal-colon mucosae and (c) tumour-derived glycoproteins from these two organs. Major differences between the antigenicities of the normal stomach and distal-colon, and between their tumour-derived glycoproteins, and the important effect of the secretor status in the expression of these antigens are described. These observations have enabled a better understanding of the individual and tissue differences in the expression of tumour-associated antigens. The possibility is raised that these carbohydrate structures (many of which also occur on certain N-linked oligosaccharides and glycolipids) are components of receptor systems for endogenous ligands. More tangible evidence is cited for the role of certain structures in this family of saccharides as receptors for infective agents.

ABO Blood-Group System↗
PubMed1983

Marker of peripheral blood granulocytes and monocytes of man recognized by two monoclonal antibodies VEP8 and VEP9 involves the trisaccharide 3-fucosyl-N-acetyllactosamine.

Two hybridoma antibodies (VEP8 and VEP9) raised against the promyelomonocytic leukemia cell line HL60 have previously been shown to distinguish human granulocytes and monocytes from other cells of the peripheral blood. We report here that both antibodies recognize the carbohydrate structure 3-fucosyl-N-acetyllactosamine with the following sequence: (formula; see text) This structure is the same as that recognized by a hybridoma antibody against mouse teratocarcinoma cells (anti-SSEA-1) which recognizes an early embryonic antigen in the mouse. Until recently this carbohydrate structure was considered to be rare among glycoproteins and glycosphingolipids. However, there is a growing list of human and animal glycoproteins in which this sequence has been detected by chemical and immunochemical methods. In this article we survey this information and discuss how this and other carbohydrate structures behave as differentiation- or tumor-associated antigens.

Animals↗
PubMed1983

The orbitofrontal cortex: neuronal activity in the behaving monkey.

Single unit recording of neurons in the orbitofrontal cortex of the alert rhesus monkey was used to investigate responses to sensory stimulation. 32.4% of the neurons had visual responses that had typical latencies of 100-200 ms, and 9.4% responded to gustatory inputs. Most neurons were selective, in that they responded consistently to some stimuli such as foods or aversive objects, but not to others. In a number of cases the neurons responded selectively to particular foods or aversive stimuli. However, this high selectivity could not be explained by simple sensory features of the stimulus, since the responses of some neurons could be readily reversed if the meaning of the stimulus (i.e. whether it was food or aversive) was changed, even though its physical appearance remained identical. Further, some bimodal neurons received convergent visual and gustatory inputs, with matching selectivity for the same stimulus in both modalities, again suggesting that an explanation in terms of simple sensory features is inadequate. Neurons were also studied during the performance of tasks known to be disrupted by orbitofrontal lesions, including a go/no go visual discrimination task and its reversal. 8.6% of neurons had differential responses to the two discriminative stimuli in the task, one of which indicated that reward was available and the other saline. Reversing the meaning of the two stimuli showed that whereas some differential units were closely linked to the sensory features of the stimuli, and some to their behavioural significance, others were conditional, in that they would only respond if a particular stimulus was present, and if it was the one being currently rewarded. Other neurons had activity related to the outcome of the animal's response, with some indicating that reinforcement had been received and others, that an error had been made and that a reversal was required. Thus, neurons in the orbitofrontal cortex possess highly coded information about which stimuli are present, as well as information about the consequences of the animal's own responses. It is suggested that together they may constitute a neuronal mechanism for determining whether particular visual stimuli continue to be associated with reinforcement, as well as providing for the modification of the animal's behavioural responses to such stimuli when those responses are no longer appropriate.

Animals↗
PubMed1983

A new approach for the antenatal diagnosis of beta-thalassaemia: a double labelling immunofluorescence microscopy technique.

A new approach to the antenatal diagnosis of beta-thalassaemia major (homozygous beta-thalassaemia) has been developed. Using rhodamine-labelled antibodies directed against gamma-globin, fetal erythrocytes can be identified in fetal blood samples contaminated with maternal cells, and using fluorescein-labelled antibodies directed against beta-globin, the presence of beta-chains (and thus Hb-A) may be determined in the same cells by double labelling immunofluorescence microscopy. The results obtained using this technique on blood samples from fetuses at risk for beta-thalassaemia major show that if fetal beta-chains are detected immunochemically the fetus is normal or heterozygous for beta-thalassaemia and over 85% of the fetuses unaffected by beta-thalassaemia major may be identified in this way. The technique is rapid, applicable to small numbers of fetal erythrocytes heavily contaminated with maternal cells and eliminates the necessity of determining chain synthesis ratios in those cases where beta-chains are detected immunochemically.

Antibody Specificity↗
PubMed1983

Blood group antigens in the normal and neoplastic bladder epithelium.

The indirect immunofluorescence technique was used to study the expression of the blood group A and H antigens in fresh-frozen and formalin-fixed paraffin-embedded sections of the bladder mucosa of 21 patients with non-neoplastic diseases of the bladder. Reliable assessment of these antigens could only be made using cryostat sections of fresh-frozen tissues. Also included in this study were tumour tissues of 5 patients with bladder cancer. The blood group A antigen was totally deleted in cryostat sections of the tumour of one patient with aggressive carcinoma and the appropriate antigens were diminished or focally deleted in the four patients with tumours that were non-invasive during one to three years of follow-up. It is concluded that sections of fresh-frozen tissues or sections processed in the absence of glycolipid-extracting solvents should be used for visualising the expression of blood group antigens in bladder tissues and assessing their value as prognosticators of the malignant potential of bladder tumours.

ABO Blood-Group System↗