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C J Kirkpatrick

Publications and source records attributed to C J Kirkpatrick.

At least 145 records · Page 8Linked to original sources
PubMed1988

An ultrastructural study of the morphology and lectin-binding properties of human mast cell granules.

The morphological characteristics and lectin-binding properties of mast cell granules from four human neurofibromata are described. Ultrastructural examination of the granules revealed that some contained dense cores, others had membranous configurations and some forms were intermediate between the two. A round electron-lucent area was present in some granules. After treatment with biotinylated lectins (10 micrograms ml-1) followed by an avidin-peroxidase revealing system (5 micrograms ml-1 in 0.125 M Tris-buffered saline with 0.347 M NaCl, pH 7.6), mast cell granules strongly bound Concanavalin A, garden pea, lentil, wheatgerm, erythro- and leuco-kidney bean lectins. This indicated the presence of abundant N-linked complex-type saccharide sequences. Soybean and peanut lectins showed only weak binding, while the presence of sparse alpha-L-fucosyl terminals was indicated by the weak binding of winged pea lectin. The staining intensity of wheatgerm lectin was considerably reduced when incubated in the presence of its specific competing sugar tri-N-acetylchitotriose. Despite a wide variety of morphological differences between granules, all showed similar staining patterns and all granules within a single cell shared the same binding characteristics.

Cytoplasmic Granules↗
PubMed1988

Lectin histochemistry of the mast cell: a light microscopical study.

The purpose of this study was to determine if human mast cell granules contain non-repeating oligosaccharide sequences. The binding of lectins to human mast cell granules was studied using a panel of 11 lectins variously selective for both N- and O-linked oligosaccharide sequences. The tissues were principally derived from cutaneous neurofibromata and benign and malignant breast diseases, that is, readily available human material with a known high content of mast cells. Lectin-binding sites in the formalin-fixed paraffin-embedded or resin-embedded material was visualized by means of biotinylated lectins and an avidin-peroxidase technique for light microscopy. The results indicate that human mast cell granules contain abundant N-linked sequences, but few or no O-linked residues. These sequences appear to be mostly in the form of non-bisected highly branched or smaller biantennate sequences, although variable positive binding with erythrophytohaemagglutinin was observed, indicating some degree of bisection.

Histocytochemistry↗
PubMed1988

Interaction between mast cells and perineurial fibroblasts in neurofibroma. New insights into mast cell function.

Transmission electron microscopy was performed on seven neurofibromata to study the relationship between the frequently occurring mast cells and the other cell types present in the tumour. Intimate association was observed between mast cells and perineurial fibroblasts, but not between mast cells and Schwann cells. At the contact interface between mast cells and perineurial fibroblasts, numerous vesicle-like structures were observed with corresponding endocytotic vesicles in the fibroblast plasma membrane. The authors regard this close morphological relationship as in vivo evidence for a possible role of mast cells in fibroblast metabolism, a conclusion which has already been drawn from in vitro studies, but until now inadequately supported by observations in vivo.

Cell Communication↗
PubMed1987

Studies on the adhesion of protoscoleces from Echinococcus multilocularis and E. granulosus to artificial substrates and human endothelial cells in vitro.

This paper describes experiments in vitro to investigate the interaction between isolated protoscoleces from Echinococcus granulosus and E. multilocularis and human endothelial cells in monolayer culture. During a maximum coculture period of 48 h neither protoscoleces nor endothelial cells showed evidence of cytotoxicity. However, protoscoleces adherent to either endothelial cells or artificial substrata developed a glycocalyx-like coat. Adherence of protoscoleces to endothelial cells requires serum (pooled human serum or foetal calf serum) in a dose-dependent fashion. However, protoscolex adhesion to artificial substrates such as glass with or without gelatin coating was markedly inhibited by serum. Thus, even 0.001% serum reduced adhesion by 46% compared with the control value. Whilst the chemical nature of the serum components have not been identified, these experiments show that serum contains both inhibitory and promoting factors for protoscolex adhesion, a finding of possible significance for the therapeutic prevention of systemic spread of established Echinococcus infections.

Animals↗
PubMed1986

Cholesterol synthesis in cultured human peripheral lymphocytes. Influence of LDL, HDL, cholesterol/phosphatidylcholine liposomes and complete serum.

Lipoprotein-deficient milieu, freshly isolated human peripheral blood lymphocytes lose about 50% of their membrane cholesterol into the medium within 8 h. The cholesterol loss is counter-regulated by de novo synthesis commencing after a lag phase of 8-12 h, and reaching a steady state within 24 h at a diminished membrane cholesterol level. About 50 micrograms free cholesterol/ml, offered in the form of low-density lipoproteins (LDL) and cholesterol/phosphatidylcholine liposomes, suppressed cholesterol synthesis to about 20% of that controls (lipoprotein-deficient culture). By contrast, pure phosphatidylcholine liposomes enhanced cholesterol synthesis to about 150% of control values. High-density lipoproteins (HDL) exerted a slightly suppressive effect on cholesterol synthesis only at high concentrations (greater than 100 micrograms HDL cholesterol/ml). HDL added to cultures containing fixed concentrations of LDL led to a dose-dependent neutralization of LDL suppression of cholesterol synthesis. Culture medium containing complete serum caused a suppression of cholesterol synthesis to about 50% of the control. The lesser reduction in cholesterol synthesis caused by complete serum compared with LDL or cholesterol/phosphatidylcholine liposomes can be explained by the presence of HDL in the former. Our results support the view that the cholesterol requirement of blood lymphocytes in their lipid-rich milieu is met by cholesterol neosynthesis as well as an exchange mechanism with surrounding lipoproteins. In our system, the cholesterol neosynthesis appears to be controlled by the ratio of LDL to HDL in the surrounding medium.

Acetates↗
PubMed1986

Systemic kappa light chain deposition and amyloidosis in multiple myeloma: novel morphological observations.

Light and transmission electron microscopic studies as well as immunohistochemical investigations were performed on a case of multiple myeloma in a 40-year-old female with systemic kappa light chain deposition. The latter took the form of extensive deposits in the liver, spleen and bone marrow. Amyloid was not found in these deposits, although it was present in the wall of branches of the portal vein. Conversely, amyloid but not light chain deposition was found in the tongue, synovial membrane from the knee and myocardium. The kidney was the only organ to show both amyloid and light chain deposits intimately associated with each other in and around tubules and collecting ducts. Ultrastructurally the light chain deposits were seen to be biphasic, having two granular components of different electron density. In the spleen and bone marrow, but not in the liver, the kappa light chain deposits were surrounded by multinucleated giant cells. This is the first report of light chain deposition disease associated with a foreign body type of giant cell reaction. The morphological variability of organ involvement suggests that the molecular structure and conformation of the deposited light chains are heterogeneous and may reflect a broad spectrum of metabolism of these deposits in various organs.

Adult↗
PubMed1985

Comparative effects of trypsin, collagenase and mechanical harvesting on cell membrane lipids studied in monolayer-cultured endothelial cells and a green monkey kidney cell line.

Experiments are presented in which membrane lipids of endothelial cells in monolayer culture were labelled with [14C]linoleic acid. Approx. 90% of the radioactive label were incorporated into phospholipids. A comparison of various harvesting methods showed that during the disruption of the labelled endothelial cell monolayer, 0.25% trypsin and 0.125% trypsin (+0.01% EDTA) released 650 and 470% more radioactivity, respectively, than did 0.01% collagenase (+0.01% EDTA). Parallel studies were performed on a green monkey kidney cell line. In this case, 0.25% trypsin released 520% more radioactivity than did 0.1% collagenase (+0.01% EDTA), although 0.125% trypsin in the presence of EDTA (0.01%) was much less traumatic than trypsin alone, the released radioactivity being of the same order of magnitude as that for collagenase. Morphological studies on endothelial cell cultures failed to reveal any distinctive differences in surface morphology following the various enzyme treatments. The results suggest that collagenase treatment of endothelial cell monolayers is the least traumatic harvesting or subculturing method as far as the integrity of the lipids in the cell membrane is concerned.

Animals↗
PubMed1985

Morphogenesis and possible precursor lesions of invasive carcinoma of the papilla of Vater: epithelial dysplasia and adenoma.

Surgical specimens from 58 invasive carcinomas of the papilla of Vater were studied histomorphologically. Tubular or villous adenomas, adenomatous residues, and microadenomas were found in the vicinity of the carcinomas in 91.4 per cent of the cases; moderate or severe epithelial dysplasia in adenomatous structures or in surface and ductal epithelium was present in 81 per cent of the cases. The results of the present histomorphologic study support the hypothesis that invasive carcinomas arise from pre-existing mucosal lesions, such as adenoma or dysplasia.

Adenoma↗
PubMed1985

Interaction between enteroviruses and human endothelial cells in vitro. Alterations in the physical properties of endothelial cell plasma membrane and adhesion of human granulocytes.

Fluorescent molecular probes were used for study of the interaction between enteroviruses (Echo 9, Echo 12, and Coxsackie B3 virus) and human endothelial cells in monolayer culture. With the use of the monomer-excimer method with pyrene decanoic acid it was shown that a marked dose-dependent restructuring of the plasma membrane occurred following addition of virus to the endothelial cells. This took the form of an increase in the lipid surface available to the lipophil reporter molecules, probably due to an alteration in the domain structure of the plasma membrane caused by insertion of virus capsid proteins. Experiments with diphenylhexatriene indicated that the enteroviruses had only a slight tendency to make the plasma membrane of the endothelial cell more fluid. Concomitant with these alterations in the biophysical properties of the membrane, a virus-induced increase in granulocyte adherence to the endothelial cells was observed for all three enteroviruses studied. Possible mechanisms for this elevated adherence are discussed, as well as the significance of the results for the phenomenon of virus-induced granulocytopenia.

Cell Adhesion↗
PubMed1984

Alterations in the biophysical properties of the human endothelial cell plasma membrane induced by a chemotactic tripeptide: correlation with enhanced adherence of granulocytes.

Human umbilical vein endothelial cells in monolayer culture were used to study the effects of the chemotactic tripeptide, N-formylmethionylleucylphenylalanine (FMLP), on structure and function of the endothelium. Endothelial cell morphology was unaffected by concentrations of 10(-8)-10(-4)M. No effect on endothelial cell proliferative capacity, as measured by the DNA content of cultures, was seen at the FMLP concentrations studied (10(-8)-10(-6)M). Using fluorescent molecular probes to investigate FMLP-induced alterations in membrane structure, it was shown using the monomer-excimer method with pyrene decanoic acid that FMLP caused a marked restructuring of the plasma membrane. This took the form of a restriction of the surface available to the lipophile reporter molecules, probably caused by a molecular reorganization of the membrane protein component. Experiments with diphenylhexatriene indicated that FMLP did not make the plasma membrane of the endothelial cell more fluid. Concomitant with these changes in the physical properties of the membrane, an FMLP-induced increase in granulocyte adherence to the endothelial cells was observed. A theoretical model is presented correlating granulocyte adherence with the lateral mobility of lipids in the endothelial cell membrane. The significance of the FMLP-induced increase in granulocyte adherence to endothelial cells for the pathogenesis of sepsis is discussed.

Cell Adhesion↗
PubMed1984

Effect of piroxicam on structure and function of joint cartilage.

In vitro experiments were performed on isolated articular chondrocytes under the influence of piroxicam. It was demonstrated that this non-steroidal anti-inflammatory agent affected neither cell proliferation nor the incorporation of 35SO4 into matrix macromolecules. Dogs were treated with piroxicam for 8 weeks. Morphological studies were performed on the tissues of the knee joints. Macroscopic and light microscopic investigations revealed no structural differences between the tissues (synovial membrane and articular cartilage) of control and treated dogs. Even at the ultrastructural level no alterations in the cartilage were observed. The capacity of chondrocytes to incorporate 35SO4 under in vitro conditions was identical in control and experimental animals. It is concluded that piroxicam has no adverse effect on chondrocytes under in vitro conditions or on articular cartilage structure in the in vivo model.

Animals↗
PubMed1984

Experimental studies on the pathogenesis of ochronotic arthropathy. The effects of homogentisic acid on adult and fetal articular chondrocyte morphology, proliferative capacity and synthesis of proteoglycans in vitro.

Lapine adult and fetal articular chondrocytes in monolayer culture were employed as an experimental model for studying the effects of homogentisic acid on chondrocyte morphology, proliferation and synthesis of proteoglycans. Concentrations of homogentisic acid in the range from 0.1 to 100 micrograms/ml were investigated and a cytotoxic effect was detected with concentrations of 5 micrograms/ml and above. Thus, with adult articular chondrocytes this effect was seen between 36 and 48 h of subculture with 5 micrograms/ml or more of homogentisic acid present from the beginning of subculture. In fetal articular chondrocyte cultures a concentration of 1 microgram/ml elicited a statistically significant reduction (13%) in cell proliferation without altering sulphated macromolecular synthesis. Experiments with 3H-thymidine autoradiography to measure the pulse labeling index (LI) in fetal chondrocytes in vitro showed that the 5 micrograms/ml concentration of homogentisic acid present for 21 h from the beginning of subculture gave a LI of 2%, compared with 25% for controls. Thus, homogentisic acid can reduce chondrocyte proliferative capacity before morphological alterations can be detected by light microscopy. No significant alterations in the synthesis of proteoglycans were detected at concentrations below the cytotoxic level. The homogentisic acid-induced cytotoxicity and reduction of proliferation in chondrocytes represents a possible pathway by which cartilage is damaged in ochronotic arthropathy.

Animals↗
PubMed1983

A comparison of the effects of two gold-containing therapeutic agents on articular chondrocyte growth in vitro.

Chondrocyte structure and function under the influence of two gold-containing therapeutic agents, aurothioglucose and triethylphosphine gold, were studied in a monolayer culture system for cultivating lapine articular chondrocytes. The functional parameters investigated were chondrocyte proliferation and the incorporation of 35SO4 as indicator of glycosaminoglycan synthesis. Aurothioglucose (0.2, 1 and 10 micrograms/ml) failed to affect either parameter and caused no cytotoxic effect detectable with the light microscope. Triethylphosphine gold (1.5 and 3 micrograms/ml) prevented subcultured chondrocytes from forming monolayers and was cytotoxic to chondrocytes present in established monolayers, studied with the light and scanning electron microscope. A 0.3 microgram/ml concentration did not alter chondrocyte proliferation or sulphate incorporation and was not cytotoxic.

Animals↗
PubMed1983

Effects of prostanoid precursors and indomethacin on chick embryonic cartilage growth in organ culture.

Using the Fell technique of organ culture of 8-day chick embryo femoral and tibial rudiments, the effects of indomethacin, dihomo-gamma-linolenic acid and arachidonic acid on limb rudiment linear growth and differentiation were investigated. Indomethacin (50 and 100 mumol/l) elicited a statistically significant decrease in rudiment linear growth without affecting differentiation or cell structure. Dihomo-gamma-linolenic acid and arachidonic acid, both at 100 mumol/l, exerted no effect on limb rudiment linear growth or differentiation. From previous work, it has been shown that PGA1 and PGB1 caused a marked inhibition of linear growth, PGA1 being cytotoxic. The failure of the prostaglandin (PG) precursors to reproduce these effects suggests that PGA or PGB biosynthesis in embryonic chondrocytes plays no significant role in cartilage growth regulatory mechanisms. Moreover, the growth inhibitory effect of the PG cyclooxygenase inhibitor, indomethacin, suggests that a product of arachidonic acid metabolism via the cyclooxygenase pathway may promote cartilage growth.

8,11,14-Eicosatrienoic Acid↗
PubMed1983

Myocardial infarction, cardiac rupture, and coronary insufficiency in the industrialised Ruhr valley. An autopsy study.

A retrospective study of autopsies was performed on patients who died of ischaemic heart disease (IHD) in the industrialised Ruhr valley of West Germany. Groups were classified on the basis of the presence or absence of cardiac scar tissue, acute myocardial infarction and cardiac rupture. Severe coronary atherosclerosis was not a constant finding in IHD, and ranged from 57% of acute coronary insufficiency cases in women to 86% of recurrent infarction cases in men. During the period 1970 to 1979 recurrent infarction decreased in frequency, whilst hearts with scar tissue in the absence of fresh infarction (chronic progressive coronary insufficiency) became increasingly common. These two groups accounted for 72% of IHD deaths and were more common in men than in women. However, the incidence of first-time acute myocardial infarction and acute coronary insufficiency was higher in women than in men. The frequency of clinically known diabetes mellitus and/or hypertension was higher in women with IHD than in controls. Systemic hypertension was not commoner in cardiac rupture cases than in other cases of acute myocardial infarction. Cardiac rupture increased markedly in the latter half of the last decade so that since 1974 20% of all acute myocardial infarcts showed cardiac rupture. The incidence of first-time infarction as well as anterior infarction was significantly higher in cases of cardiac rupture than in acute infarction without rupture. The incidence of recent coronary thrombosis was low in recurrent myocardial infarction (23%), higher in first-time infarction (39%) and highest in cardiac rupture (59%). In men, this finding was significantly higher in acute infarction with rupture than in acute infarction without rupture (p less than 0.001). The view of coronary thrombosis as a secondary phenomenon in acute myocardial infarction is supported.

Adult↗