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Biomedical subjects

C J Kirkpatrick

Publications and source records attributed to C J Kirkpatrick.

At least 163 records · Page 9Linked to original sources
PubMed1982

Lipid storage in cultured articular chondrocytes due to prostanoid precursors and a prostanoid synthesis inhibitor.

Lapine articular chondrocytes were subcultured in the presence or absence of the prostanoid precursors, arachidonic acid or dihomo-gamma-linolenic acid, and the cyclooxygenase inhibitor indomethacin. Lipid storage was studied microscopically using the Sudan black staining method. Control chondrocyte cultures showed a weakly positive staining reaction until confluence was reached, at which point the intra-cytoplasmic lipid content decreased. Both arachidonic acid and dihomo-gamma-linolenic acid at 100 mumol/l caused a marked increase in lipid storage which continued even after confluence was achieved. 1 mumol/l concentrations were indistinguishable from controls, whereas 10 mumol/l concentrations elicited a slight increase in lipid storage compared with controls. The prostaglandin cyclooxygenase inhibitor indomethacin did not affect chondrocyte lipid storage. However, administration of a prostanoid precursor in the presence of indomethacin caused a massive increase in intra-cytoplasmic storage of lipid, eventually leading to cell death. A possible explanation is that indomethacin may alter chondrocyte lipid metabolism in the presence of substrate molecules by rechanneling lipid synthesis away from the prostaglandin pathway to other lipid synthetic pathways.

8,11,14-Eicosatrienoic Acid↗
PubMed1982

Alterations in articular chondrocyte growth and proteoglycan synthesis due to prostanoid precursors.

The effects of the prostaglandin precursors, dihomo-gamma-linolenic acid and arachidonic acid, on chondrocyte proliferation, proteoglycan synthesis and morphological structure were studied using lapine articular chondrocytes in vitro. Neither substance exerted a cytotoxic effect on chondrocytes. Dihomo-gamma-linolenic acid caused a dose-dependent inhibition of chondrocyte proliferation (8% and 35% reduction at 10 and 100 mumol/l respectively) (P less than 0.01), whereas arachidonic acid failed to cause any significant alteration: 10 mumol/l of dihomo-gamma-linolenic acid stimulated proteoglycan synthesis by 14% (P less than 0.01), whilst 100 mumol/l elicited a reduction of 14% (P less than 0.01); 100 mumol/l of arachidonic acid also caused a statistically significant inhibition (31%) (P less than 0.001) of 35SO4 incorporation into proteoglycans. The inhibitory effects on proteoglycan synthesis may be mediated by intracellularly synthesized prostaglandins, which are known to exert this effect. This may also help explain the susceptibility of articular cartilage to damage with increasing age, as arachidonic acid is found in increasing concentrations in the superficial layers of articular cartilage.

8,11,14-Eicosatrienoic Acid↗
PubMed1982

The effects of nickel ions on articular chondrocyte growth in monolayer culture.

Monolayer cultures of lapine articular chondrocytes were used to study the effects of nickel ions (Ni++) on chondrocyte proliferative capacity, proteoglycan synthesis and cellular morphology. Nickel depressed chondrocyte proliferation at the highest concentration tested (100 mumol/l; P less than 0.01) and also exerted a dose-dependent inhibition of proteoglycan synthesis (50 and 100 mumol/l; P less than 0.01). Despite both these effects, no evidence of chondrocyte damage was detectable at the light-microscopical level. The possible significance of the nickel-induced reduction of articular chondrocyte proteoglycan synthesis for the functional integrity of the residual cartilage following hemiarthroplasty operations is discussed.

Animals↗
PubMed1982

Fatal Clostridium perfringens infection after normal term pregnancy.

We describe a case of fatal gas gangrene of the uterus after an apparently normal term pregnancy in a 22-year-old woman. The patient died less than 15 h after the onset of symptoms, which consisted of a single episode of vomiting and increasing hypogastric pain. Hypotension, tachycardia and renal failure were the dominant clinical features. The pathogenesis, diagnosis and treatment of uterine gas gangrene are discussed.

Adult↗
PubMed1982

Alterations in chondrocyte morphology, proliferation and binding of 35SO4 due to Fe(III), Fe(II), ferritin and haemoglobin in vitro.

Lapine articular chondrocytes in vitro were used to study the effects of Fe3+, Fe2+, ferritin and haemoglobin on cell proliferation, synthesis of proteoglycans and morphological structure. Fe3+ (10, 100 and 500 micrograms/ml) reduced the DNA content of cultures by approximately 35% as well as inhibiting proteoglycan synthesis. Chondrocytes showed positive cytoplasmic staining for both ferric and ferrous ions at the 500 micrograms/ml concentration. Fe2+ (100 micrograms/ml) also decreased DNA content and proteoglycan synthesis, although no iron uptake by the chondrocytes could be detected. Ferritin (1.0, 0.5 and 0.1 micrograms/ml) elicited a significant inhibition of proteoglycan synthesis without affecting cellular DNA synthesis. 1 and 5 micrograms/ml of haemoglobin each reduced the DNA content of cultures by 60%, whilst markedly inhibiting proteoglycan synthesis (75 and 99% respectively). None of the substances tested caused chondrocyte toxicity. The ability of Fe3+, Fe2+, ferritin and, in particular, haemoglobin to inhibit chondrocyte proteoglycan synthesis may represent a pathway whereby cartilage is susceptible to destruction in the haemophilic joint.

Animals↗
PubMed1982

Influence of zinc and copper on lapine articular chondrocytes in monolayer culture: morphology, proliferation and proteoglycan synthesis.

The effects of zinc and copper ions on the structure, proliferative capacity and proteoglycan metabolism of lapine articular chondrocytes were studied in a monolayer culture system. Zn++ was cytotoxic at a concentration of 100 mumol/l, whereas 50 mumol/l caused a stimulation of chondrocyte proliferation with simultaneous reduction (p less than 0.01) in macro-molecular binding of 35 SO4. 10 mumol/Zn++ failed to evoke any alteration in these parameters. Cu++ concentrations of 100 and 50 mumol/1 significantly reduced cell proliferation (p less than 0.01) with a concomitant stimulation of 35 SO4 uptake into proteoglycans 10 mumol/Cu++ did not significantly alter chondrocyte multiplication nor binding of 35SO4. It is proposed that Zn++ may play a role in chondrocyte damage in joint disease. Furthermore, the possible therapeutic efficacy of copper in maintaining cartilage integrity is supported.

Animals↗
PubMed1981

The effect of soluble sodium urate on the proliferation and proteoglycan synthesis of lapine articular chondrocytes in monolayer culture.

The effects of soluble monosodium urate (350, 50, and 5 mumol/l) on the proliferation and proteoglycan synthesis of lapine articular chondrocytes were studied in a monolayer culture system. Cellular proliferation in vitro was unaffected by urate treatment. Chondrocytes treated with 50 mumol/l sodium urate showed a 26% reduction in binding of 35SO4 to matrix macromolecules. However, this reduction did not achieve statistical significance. The 350 and 5 mumol/l concentrations did not alter 35SO4 binding. It is proposed that monosodium urate has no marked direct effect on chondrocyte viability, proliferation and proteoglycan synthesis.

Animals↗
PubMed1980

The effects of prostaglandin A1 and prostaglandin B1 on the differentiation of cartilage in the chick embryo.

In organ cultures of chick embryonic limb rudiments the mean length of explants treated with 25 microgram/ml prostaglandin B1 (PGB1) was significantly smaller than that of paired controls (P < 0.001) after 4, 6 and 8 days in vitro. The deceleration of linear growth was constant during 8 days in vitro. Growth inhibition was confirmed by a statistically significant decrease in explant dry weight after 8 days of culture. However, PGB1 caused no observable alteration in the histological structure of the explants. The possible role of PGB1 in the physiological control of cartilage growth is postulated. Explants similarly treated with prostaglandin A1 (PGA1) at concentrations of 15 microgram/ml for 8 days or 20 microgram/ml for 4 and 8 days exhibited "comma" and "inverted commas" phenomena, caused by the intermingling of chondroblasts from the epiphyseal and flattened-cell zones, which thus ceased to be distinct entities. Adenylate cyclase in the plasma membrane may be involved in this disturbance of cartilage differentiation.

Animals↗
PubMed1980

Cartilage growth inhibition and necrosis in vitro caused by prostaglandin A1.

This paper details experiments using the Fell technique of organ culture of 8-day chick embryo femoral and tibial rudiments to test the effects of prostaglandin A1 (PGA1) on cartilage growth. Growth was studied during 8 days in vitro by measurement of rudiment length and wet and dry weight, and by histology. PGA1 inhibited explant growth in a dose-related manner. Linear growth was significantly decreased by 20 and 25 microgram/ml PGA1 at 2, 4, 6 and 8 days, and by 15 microgram/ml at 6 and 8 days. Linear growth was unaffected by 1 and 10 microgram/ml doses. Weight measurements were significantly reduced by 25 microgram/ml PGA1 (2, 4 and 8 days) and by 20 microgram/ml (8 days). Chondroblast degeneration was caused by doses of 15, 20 and 25 microgram/ml PGA1. Progressive degeneration was seen at the 25 microgram/ml concentration after 2 days in vitro. Cellular changes as early as 27 h in vitro were seen using electron microscopy. Tritiated thymidine autoradiography confirmed reduced chondroblast proliferation in the presence of PGA1 (25 microgram/ml). The mechanisms of prostaglandin-induced changes in embryonic cartilage remain uncertain. The possible role of intracellular cyclic nucleotides in the reaction is discussed.

Animals↗
PubMed1980

The effect of vagotomy on the distribution of sulphomucin-containing cells in the rat pyloric antrum.

The present histological investigation showed that bilateral truncal vagotomy (with accompanying pyloroplasty) reduced the sulphomucin-containing cell population of the pyloric antral mucosa of the rat stomach. Although this did not reach statistical significance (95% confidence limits), study of the absolute distribution of the sulphomucin-containing cells showed that significantly fewer of these cells were situated in the basal third of the mucosa as a result of the operation. A study of the percentage distribution revealed that a much higher percentage of sulphomucin-containing cells was present in the middle third of the mucosa in vagotomized rats than in the corresponding regions of the control stomachs. Thus, vagotomy and pyloroplasty had effected a redistribution of the sulphomucin-containing cells in the pyloric antrum. The possible explanation and significance of this finding are discussed.

Animals↗
PubMed1977

Reactivity and antibody response to vaccination with bivalent influenza A/Victoria/75-A/New Jersey/76 vaccines in children with chronic pulmonary diseases.

Reactogenicity and antibody responses of high-risk children and adolescents (aged three to 18 years) to bivalent influenza A/Victoria/75-A/New Jersey/76 virus vaccine from nine participating centers were compared to the response of the total population of vaccinees in the multicenter study of the National Institute of Allergy and Infectious Diseases. Split-product vaccines given in two doses four weeks apart offered protection without a significant risk of side effects. Patients with chronic pulmonary disease did not differ from the total study population to antibody response or reactivity to vaccination with A/New Jersey strains.

Adolescent↗
PubMedDate not supplied

Effectiveness and safety of ultrasonic atherosclerotic plaque ablation: in vitro investigation.

Ultrasound energy was applied to 137 segments of human cadaver atherosclerotic arteries, 90 with calcified and 47 with noncalcified atheromatous plaque, and to 100 segments of healthy swine aorta. The average depth of penetration was dependent on the forward force of the ultrasonic probe, the duration of treatment, and the degree of atherosclerosis. There was one perforation of a fibrous plaque using a forward force of 2 Newton and 45 sec of application time. Injury of healthy intima was minimal. It is concluded that catheter-delivered ultrasound is effective and safe for the disintegration of atherosclerotic plaques. Presently, the main limitations of the system are the lack of flexibility and steerability.

Angioplasty, Balloon↗
PubMedDate not supplied

Endothelial cell cultures as a tool in biomaterial research.

Progress in biocompatibility and tissue engineering would today be inconceivable without the aid of in vitro techniques. Endothelial cell cultures represent a valuable tool not just in haemocompatibility testing, but also in the concept of designing hybrid organs. In the past endothelial cells (EC) have frequently been used in cytotoxicity testing of materials, especially polymers, used in blood-contacting implants, as well as for investigating seeding technologies for vascular prostheses. At present the exponential development both in theory and practice of cell and molecular biology of the endothelium offers great promise in the biomaterial field. Up until now this EC research field has mostly been non-biomaterial orientated. Nevertheless, the relevance for biomaterial research is apparent. Four aspects will be concisely reviewed under the headings inflammation, with special reference to cell adhesion molecules (CAMs) and cytokines, angiogenesis, focusing on the healing response, signal transduction, presenting examples from cytokine- and metal ion-induced up-regulation of genes coding for CAMs, and, finally, endothelial functionality, with emphasis on the principal characteristics of the physiological endothelial phenotype. Finally, the application of these fields to three foci of biomaterial research will be discussed, emphasizing the role of EC culture techniques in controlling the host response to biomaterials (microvascular EC), controlling EC functionality (promoting positive effects and down-regulating negative effects), and tissue engineering (integration of EC into hybrid organs/biosensors). The need for more co-culture and three-dimensional models will be stressed and data from the authors' laboratory presented to illustrate these principles.

Journal Article↗
PubMedDate not supplied

Induction of apoptosis in human microvascular endothelial cells by divalent cobalt ions. Evidence for integrin-mediated signaling via the cytoskeleton.

Wound healing following implantation is characterized by an acute inflammatory reaction and a subsequent reorganizing phase in which angiogenesis is involved. Endothelial cells (EC) participate in both inflammation and angiogenesis. Thus, the effects on functions of EC exerted by implanted materials could affect the progression of wound healing. The corrosion of metallic implants can cause high concentrations of heavy metal ions in the peri-implant tissues. The purpose of the present study was to test the effects of possible corrosion products on the function and viability of human EC in vitro. Long-term exposure of EC to CoCl2 and NiCl2 (3 days, 0.7 mM) leads to a decrease of cell number and changes in cellular morphology. However, the morphological changes between CoCl2- and NiCl2-treated cells differ significantly. The changed morphology of CoCl2-treated EC and the fragmented DNA pattern indicates apoptosis. Nickel-treated cells demonstrated necrosis. The activity of integrins was tested by an assay of cellular adhesion on collagen-coated surfaces. It was shown that the number of adherent cells significantly decreased upon exposure to CoCl2. Our studies suggest that induction of cell death in EC upon exposure to CoCl2 could be attributed to impaired integrin signaling, which leads to a damaged cytoskeleton and culminates in apoptosis.

Journal Article↗
PubMedDate not supplied

[Determination of bone quality before spinal instrumentation--value of different in vivo methods].

OBJECTIVE: The present investigation should elucidate which assessment technique for bone quality is most appropriate to estimate preoperatively fixation strength of instrumental spine fusions. METHODS: VDS-screw fixation strength in 50 human cadaveric vertebral bodies was approximated by means of pullout force assessment. Bone quality was assessed by Dual Energy X-ray Absorptiometry (DEXA), Quantitative Computed Tomography (QCT), MRT and histomorphometry. For each of these techniques, correlation with axial pull out force strength was investigated. RESULTS: Highest correlation was found for cancellous bone density (QCT) (r = 0.72; p < 0.001) and DEXA (r = 0.70; p < 0.001). MRT, cortical bone density (QCT) and histomorphometry just slightly correlated with pullout force strength. CONCLUSIONS: Absorptiometrical techniques like QCT and DEXA are most appropriate to estimate VDS-screw fixation strength preoperatively.

Adult↗
PubMedDate not supplied

Comparative analysis of the reactivity of human umbilical vein endothelial cells in organ and monolayer culture.

Endothelial monolayer cell cultures have been used to study pathomechanisms under standardized in vitro conditions. These results can only be regarded as valid as long as phenomena studied in vitro are comparable to findings in situ, e.g. in organ culture. The aim of the present study was to examine the reliability and comparability between human umbilical vein endothelial cells (HUVEC) in a monolayer cell culture model and endothelial cells (EC) in organ culture, as well as in the native umbilical cord. Our results prove the reliability of HUVEC as a model for standardized investigations of EC. The differences found suggest that gradual differences in antigen expression in vitro and in situ become apparent by comparing in situ and in vitro investigations.

Antigens, CD34↗
PubMedDate not supplied

Endothelial accumulation of hydroxyethyl starch and functional consequences on leukocyte-endothelial interactions.

To date, accumulation of hydroxyethyl starch (HES) has been studied mainly in skin specimens, but there are no detailed reports available regarding starch accumulation in the endothelium. Because endothelial cells play an essential role during shock, we studied the accumulation of HES in human umbilical venous endothelial cells (HUVEC). HUVEC (n = 9) were incubated with a fluorescein-conjugated HES 200/0.5 (FITC-HES) at 0.5-20 mg/ml for 1-72 h. FITC-HES was internalized dose- and time-dependently by pinocytosis into secondary lysosomes. Asymptotic elimination curves showed that 50% of the formerly ingested molecules could not be eliminated. Despite accumulation, starch molecules did not attenuate the expression of E-selectin, ICAM-1 or VCAM-1 on TNF-alpha-activated HUVEC. However, apart from adhesion molecule expression, perfusion studies showed that HES reduced neutrophil adhesion by direct inhibition of integrin-mediated interactions.

Cell Adhesion↗