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Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Effect of titanium surface roughness on chondrocyte proliferation, matrix production, and differentiation depends on the state of cell maturation.

Although it is well accepted that implant success is dependent on various surface properties, little is known about the effect of surface roughness on cell metabolism or differentiation, or whether the effects vary with the maturational state of the cells interacting with the implant. In the current study, we examined the effect of titanium (Ti) surface roughness on chondrocyte proliferation, differentiation, and matrix synthesis using cells derived from known stages of endochondral development. Chondrocytes derived from the resting zone (RCs) and growth zone (GCs) of rat costochondral cartilage were cultured on Ti disks that were prepared as follows: HF-HNO3-treated and washed (PT); PT-treated and electropolished (EP); fine sand-blasted, HCl-H2SO4-etched, and washed (FA); coarse sand-blasted, HCl-H2SO4-etched, and washed (CA); or Ti plasma-sprayed (TPS). Based on surface analysis, the Ti surfaces were ranked from smoothest to roughest: EP, PT, FA, CA, and TPS. Cell proliferation was assessed by cell number and [3H]-thymidine incorporation, and RNA synthesis was assessed by [3H]-uridine incorporation. Differentiation was determined by alkaline phosphatase specific activity (AL-Pase). Matrix production was measured by [3H]-proline incorporation into collagenase-digestible (CDP) and noncollagenase-digestible (NCP) protein and by [35S]-sulfate incorporation into proteoglycan. GCs required two trypsinizations for complete removal from the culture disks; the number of cells released by the first trypsinization was generally decreased with increasing surface roughness while that released by the second trypsinization was increased. In RC cultures, cell number was similarly decreased on the rougher surfaces; only minimal numbers of RCs were released by a second trypsinization. [3H]-thymidine incorporation by RCs decreased with increasing surface roughness while that by GCs was increased. [3H]-Uridine incorporation by both GCs and RCs was greater on rough surfaces. Conversely, ALPase in the cell layer and isolated cells of both cell types was significantly decreased. GC CDP and NCP production was significantly decreased on rough surfaces while CDP production by RC cells was significantly decreased on smooth surfaces. [35S]-sulfate incorporation by RCs and GCs was decreased on all surfaces compared to tissue culture plastic. The results of this study indicate that surface roughness affects chondrocyte proliferation, differentiation, and matrix synthesis, and that this regulation is cell maturation dependent.

Animals↗
PubMed1996

Surface roughness modulates the local production of growth factors and cytokines by osteoblast-like MG-63 cells.

Titanium (Ti) surface roughness affects proliferation, differentiation, and matrix production of MG-63 osteoblast-like cells. Cytokines and growth factors produced in the milieu surrounding an implant may also be influenced by its surface, thereby modulating the healing process. This study examined the effect of surface roughness on the production of two factors known to have potent effects on bone, prostaglandin E2 (PGE2) and transforming growth factor beta 1 (TGF-beta 1). MG-63 cells were cultured on Ti disks of varying roughness. The surfaces were ranked from smoothest to roughest: electropolished (EP), pretreated with hydrofluoric acid-nitric acid (PT), fine sand-blasted, etched with HCl and H2SO4, and washed (EA), coarse sand-blasted, etched with HCl and H2SO4, and washed (CA), and Ti plasma-sprayed (TPS). Cells were cultured in 24-well polystyrene (plastic) dishes as controls and to determine when confluence was achieved. Media were collected and cell number determined 24 h postconfluence. PGE2 and TGF-beta 1 levels in the conditioned media were determined using commercial radioimmunoassay and enzyme-linked immunosorbent assay kits, respectively. There was an inverse relationship between cell number and Ti surface roughness. Total PGE2 content in the media of cultures grown on the three roughest surfaces (FA, CA, and TPS) was significantly increased 1.5-4.0 times over that found in media of cultures grown on plastic or smooth surfaces. When PGE2 production was expressed per cell number, CA and TPS cultures exhibited six- to eightfold increases compared to cultures on plastic and smooth surfaces. There was a direct relationship between TGF-beta 1 production and surface roughness, both in terms of total TGF-beta 1 per culture and when normalized for cell number. TGF-beta 1 production on rough surfaces (CA and TPS) was three to five times higher than on plastic. These studies indicate that substrate surface roughness affects cytokine and growth factor production by MG-63 cells, suggesting that surface roughness may modulate the activity of cells interacting with an implant, and thereby affect tissue healing and implant success.

Biocompatible Materials↗
PubMed1996

Proliferation, differentiation, and protein synthesis of human osteoblast-like cells (MG63) cultured on previously used titanium surfaces.

This study compared osteoblasts proliferation, differentiation, and protein synthesis on new and used titanium (Ti) disks to test the hypothesis that cleaning and resterilization of previously used Ti disks does not alter cell response to a particular surface. Ti disks of varying roughness were prepared by one of five different treatment regimens. Standard tissue culture plastic was used as a control. Human osteoblast-like cells (MG63) were cultured on the Ti disks and cell proliferation, cell differentiation, RNA synthesis and matrix production (collagen and noncollagen protein; proteoglycans) measured. After their first use, the disks were cleaned, resterilized by autoclaving, and MG63 cells cultured on them as before. At confluence, the same parameters were measured and cell behavior on new and used disks compared. When confluent cultures of cells on plastic were compared to those cultured on new Ti surfaces, cell number was reduced on the roughest surfaces and equivalent to plastic on the other surfaces. Cell number was further reduced when disks with the roughest surfaces were re-used; no differences in cell number could be discerned after cleaning and resterilization. Cell proliferation was inversely related to surface roughness and was less than seen on tissue culture plastic. Re-use of the Ti disks resulted in no change in cell proliferation rate. Alkaline phosphatase specific activity in isolated cells was lowest on the rougher surfaces; no differences between new and used disks were observed. Similarly, enzyme activity in the cell layer was decreased in cultures grown on rougher surfaces, with no effect of prior disk use being noted. RNA synthesis was decreased with respect to plastic in cultures on smoother surfaces and increased on rougher surfaces; prior disk use did not alter RNA synthesis. Collagen production by the cells was decreased on smoother surfaces, but was comparable to tissue culture plastic when grown on rougher surfaces. Non-collagen protein production was unaffected by culture surface and whether or not the disk had been previously used. Proteoglycan synthesis by cells was decreased on all surfaces studied and comparable on both new and used disks. The results of this study indicate that Ti implant surfaces are unaffected by cleaning and resterilization, although rougher surfaces may require more extensive cleaning than smoother ones. This suggests the possibility that implants, in the same patient, could be safely reused. In vivo studies in animals, however, need to be performed before clinical application can be considered.

Alkaline Phosphatase↗
PubMed1996

Non-islet cell tumour-associated hypoglycaemia: 111In-octreotide imaging and efficacy of octreotide, growth hormone and glucocorticosteroids.

A patient presented with frequent episodes of spontaneous hypoglycaemia due to a solitary fibrous tumour of pleural origin, secreting incompletely processed pro-insulin-like growth factor II (big IGF-II). Somatostatin receptors were demonstrated in the tumour by 111 inlabelled octreotide scintigraphy, but despite maximal doses of octreotide, there was no suppression of big IGF-II secretion and the hypoglycaemia persisted. The combination of GH and glucocorticoid therapy abolished the hypoglycaemia.

Aged↗
PubMed1996

The role of cytology in the diagnosis of Paget's disease of the nipple.

Although rare, eczematous skin changes ascribed to Paget's disease of the nipple nevertheless warrant timely diagnosis. However this may occasionally be delayed due to a reluctance to proceed to traditional diagnostic techniques of wedge biopsy, surgical excision or punch biopsy. In this communication we describe 11 cases of unilateral mammary Paget's disease, in which an unequivocal cytodiagnosis was made from nipple scrapings. In five of these cases an underlying ductal carcinoma of the breast was simultaneously diagnosed by fine needle aspiration (FNA) cytology of a palpable breast lump. All 11 cases were subsequently proven histologically to be Paget's disease. Despite the fact that the use in dermatology of scrape smears and fine needle aspiration cytology remains somewhat unpopular, it is suggested that the screening of any eczematous skin change of the nipple should be considered using the simple, reliable and non-invasive technique of scrape cytology.

Adult↗
PubMed1996

Invasive pneumococcal infections in children infected with HIV are not associated with splenic dysfunction.

OBJECTIVES: Children infected with HIV-1 are more likely to acquire infections associated with the encapsulated bacterial pathogens of childhood than their non-HIV-infected peers. The goal of the current study was to determine what proportion of community-acquired, invasive pneumococcal disease in HIV-infected children could be attributed to splenic dysfunction, as measured by enumerating the number of pocked red blood cells (RBCs) in peripheral blood. METHODS: Splenic reticuloendothelial function was assessed semiquantitatively by examining the morphology of the RBCs of 84 children born to HIV-infected mothers using phase interference microscopy. Surveillance of medical records, and a review of the Yale-New Haven Hospital Clinical Microbiology computerized database, revealed that all of the bacterial cultures of blood and cerebrospinal fluid from these patients were positive. RESULTS: Of the 84 children assessed, 70 were infected with HIV (median age 66 months) and 14 were uninfected seroreverters (controls). Sixty-one of the 70 HIV-infected children met the CDC criteria for moderate or severe immunodeficiency and/or moderate or severe symptomatic conditions. Seventeen of the 70 HIV-infected children experienced 23 invasive bacterial infections. Streptococcus pneumoniae was responsible for all 23 infections. The median age at the time of first infection among these 17 subjects was 20 months (range, 10-58 months). There were no episodes of invasive bacterial infections in the remaining 53 HIV-infected children nor among the 14 controls. All 84 children studied, including those with invasive pneumococcal disease, had normal proportions (i.e., < 2%) of pocked erythrocytes in peripheral blood. CONCLUSION: Splenic dysfunction, as measured by the pocked RBC count, does not account for the increased occurrence of invasive pneumococcal disease found in children infected with HIV.

AIDS-Related Opportunistic Infections↗
PubMed1996

Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies.

The objective was to determine whether the frequency of flare in systemic lupus erythematosus (SLE), patients is increased during pregnancy and the puerperium. Seventy-eight pregnancies in 68 SLE patients attending the lupus pregnancy clinic, at St. Thomas' Hospital, during the last 5 yr were included. The pregnancy period and 8 weeks post-delivery were considered. This group was compared with a control group of 50 consecutive, non-pregnant, age-matched SLE patients attending our weekly lupus clinic. Additionally, 43 of the pregnant patients carried on attending the lupus clinic for the year after puerperium, and their course was compared with themselves during pregnancy. SLE activity was assessed using the Lupus Activity Index (LAI) score. An increase > or = 0.26 in the score was considered as a flare of the disease. Pregnancy and control groups were homogeneous for age, race, disease duration and distribution of autoantibodies. Sixty-five per cent of the patients flared during pregnancy and/or the puerperium and 42% flared in the control group (P = 0.015). The rates of flare per patients/month were 0.082 +/- 0.004 for the pregnancy group and 0.039 +/- 0.003 for the control group (P < 0.001). The 43 patients whose course was controlled after the puerperium flared more frequently during pregnancy that thereafter (McNemar test, P = 0.003). The rates of flare per patient/month were 0.093 +/- 0.006 during pregnancy and the puerperium, and 0.049 +/- 0.004 after the puerperium (P = 0.0015). Kidney and central nervous system involvement was not different between the pregnancy and control groups. In terms of frequency of flares, there was no difference in any of the groups between patients taking and not taking steroids. We conclude that SLE tends to flare during pregnancy. Flares are maximal during the second and third trimester and the puerperium. Flares are not more severe than in non-pregnant patients, and most of the flares can be managed conservatively. Prednisolone does not prevent flares.

Adult↗
PubMed1996

Reduction in humidity as a method of controlling mites and mite allergens: the use of mechanical ventilation in British domestic dwellings.

BACKGROUND: Low humidity is an important limiting factor for mite population growth. Reducing humidity can therefore be used as a method to control mites within the home. OBJECTIVE: This study investigated the effect of mechanical ventilation heat recovery (MVHR) units on house dust mites and mite allergen Der p 1 in typical homes in the North-West of England. METHODS: Mite counts and Der p 1 levels were measured at 3-monthly intervals over a period of 1 year in 18 houses (nine with MVHR units and nine architecturally matched control houses). Paired dust samples were collected using a vacuum cleaner with an air-flow rate 451/sec, adapted to collect the sample onto a preweighed filter paper. A 1 m2 area of bedroom carpet, living room carpet and mattress was sampled for 2 min. Indoor temperature and relative humidity (RH) levels were recorded for a period of 1 week before and after the winter period (November and February: 3 and 6 months data sets). The environmental questionnaire was completed at the beginning and at the end of the study. RESULTS: No difference in either Der p 1 concentrations or mite counts in any of the sampling sites at 3, 6, 9 and 12 months as compared with the baseline values was found, both within and between the groups (P > 0.01). The measured levels of RH performed in autumn and winter were found to be lower in the MVHR houses compared to the architectural controls. The indoor temperature during each period did not differ between the groups. Questionnaire data showed that the severity of condensation improved in the MVHR homes, whilst during the winter period, the severity of condensation had increased in the architectural control group. CONCLUSIONS: The MVHR unit does not reduce indoor humidity to levels capable of retarding the mite population growth and decreasing mite allergens in the type of houses predominantly found in the mild and humid climate of the North-West of England.

Allergens↗
PubMed1996

Ross River virus infection on the North Coast of New South Wales.

A retrospective follow-up survey was undertaken of residents of the North Coast of New South Wales infected with Ross River virus in 1992. The aims of the study were to describe the epidemiology and acute symptomatology of Ross River virus infection, its natural history during the first 12 months of infection, and its effects on those infected. Questionnaires were distributed to both cases and their medical practitioners. Of 129 people infected, aged between six and 85 years, 81 (63 per cent) were male and 48 (37 per cent) were female. The peak age-specific incidence was in the age group 50 to 59 years. The most common symptoms were arthralgia (95 per cent) and tiredness (91 per cent). Over 60 per cent took time off work. At 12 months follow-up, over 50 per cent reported persistent arthralgia, 35 per cent reported persistent tiredness and 15 per cent were still unable to carry out their normal activities. The median duration of symptoms was in the range 7 to 12 months, and of incapacity was in the range five weeks to three months. There were some differences from previous reports of Ross River virus outbreaks, in the incidence of major symptoms and the duration of illness and incapacity. These are likely to be at least partly due to inconsistent measurement methods. In this study, there were systematic differences between medical practitioners' and patients' estimates of periods of incapacity. Previous estimates of the direct economic costs and indirect human costs of infection based on data obtained from medical practitioners, although alarming, are almost certainly underestimates.

Adolescent↗
PubMed1995

Calcineurin feedback inhibition of agonist-evoked cAMP formation.

The effects of immunosuppressant blockers of calcineurin (protein phosphatase 2B) on cAMP formation and hormone release were investigated in mouse pituitary tumor (AtT20) cells. Immunosuppressants enhanced corticotropin-releasing factor- and isoproterenol-evoked cAMP production in proportion with their potency to block calcineurin. Further analysis of cAMP production revealed that intracellular Ca2+ derived through voltage-regulated calcium channels reduces cAMP formation induced by corticotropin releasing-factor or beta 2-adrenergic stimulation and that this effect of Ca2+ is inhibited by blockers of calcineurin. AtT20 cells were found to express at least three species of adenylyl cyclase mRNA-encoding types 1 and 6 as well as a novel isotype, which appeared to be the predominant species. In two cell lines expressing very low or undetectable levels of the novel cyclase mRNA (NCB20 and HEK293 cells respectively), corticotropin-releasing factor-induced cAMP formation was not altered upon blockage of calcineurin activity. These data identify calcineurin as a Ca2+ sensor that mediates the negative feedback effect of intracellular Ca2+ on receptor-stimulated cAMP production. Furthermore, the effect of calcineurin on cAMP synthesis appears to be associated with the expression of a novel adenylyl cyclase isotype, which is highly abundant in AtT20 cells.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in human malignancies.

Cyclin and cyclin-dependent kinase (CDK) complexes play important roles in controlling the cell cycle. The CDK inhibitors (CDKIs) inhibit the kinase activities of the complexes and block transitions of the cell cycle. Recently several CDKI genes have been cloned, and evidence suggests that at least a couple of these may be tumor suppressor genes. In this study, the partial structure of a CDKI gene, p27/Kip1, was determined. In addition, a large number of human cancers (432 cases) and cancer cell lines (20 lines) were analyzed for alterations of the p27/Kip1 gene by Southern blot analysis and PCR/single-strand conformation polymorphism. The coding region of the p27/Kip1 gene consists of at least two exons and an intron of about 600 bp. In 140 tumors of various tissues and 18 transformed cell lines, no deletions or rearrangements of the gene were detected by Southern blot analysis using a part of the coding sequence as a probe. One polymorphism and one silent mutation were detected by PCR/single-strand conformation polymoprhism. The polymorphism was a nucleotide substitution of guanine for thymine (GTC-->GGC) at codon 109, resulting in an amino acid substitution of glycine for valine (Val-->Gly). In summary, no abnormalities of the p27/Kip1 gene were detected in human malignancies. Now, two groups of CDKIs are classified based on the structure of the proteins. One group includes the p15, p16, and p18 CDKIs, which have ankyrin repeat motifs. The p15 and p16 CDKI genes are very frequently mutated in a variety of cancers. The p27/Kip1 and p21 CDKIs belong to the other group. We reported previously that abnormalities of the p21 gene were very rare. The latter group of the CDKIs, including p27/Kip1 and p21, are rarely mutated in human malignancies.

Base Sequence↗