PubMed Health⌕ Search

Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 217 records · Page 12Linked to original sources
PubMed1993

Local protective effects of nerve growth factor-secreting fibroblasts against excitotoxic lesions in the rat striatum.

Neurotrophic factors, such as nerve growth factor (NGF), in addition to their role in neuronal development, have protective effects on neuronal survival. Intracerebral implantation of cells genetically altered to secrete high levels of NGF is also found to promote neuronal survival in experimental lesioning models of the brain. The range of activity for such biological delivery systems has not yet been well described either spatially or temporally. Therefore, the authors chose to study the local and distant protective effects of an NGF-secreting rat fibroblast cell line implanted in an excitotoxic lesion model of Huntington's disease. They found that preimplantation of NGF-secreting fibroblasts placed within the corpus callosum reduced the maximum cross-sectional area of a subsequent excitotoxic lesion in the ipsilateral striatum by 80% when compared to the effects of a non-NGF-secreting fibroblast graft, and by 83% when compared to excitotoxic lesions in ungrafted animals (p < 0.003). However, NGF-secreting cells placed in the contralateral corpus callosum failed to affect striatal lesion size significantly when compared to contralateral or ipsilateral non-NGF-secreting cell implants. Of note, fibroblasts were clearly visible within the graft site at 7 and 18 days after implantation; however, few cells within the grafts stained positively for NGF peptide or for the messenger ribonucleic acid (mRNA) encoding the transfected NGF gene-construct at either time point. These results show that biological delivery systems for NGF appear to have a profound but local effect on neuronal excitotoxicity, which will necessitate careful neurosurgical placement for maximum effect. Furthermore, the ability of this genetically altered cell line to synthesize NGF mRNA and peptide appears to decrease spontaneously in vivo, a characteristic that will need to be addressed before this method of biological delivery can be utilized as a treatment for chronic degenerative diseases.

Animals↗
PubMed1993

Biocompatibility of hemodialysis membranes: evaluation in an ovine model.

We studied the cardiopulmonary, hematologic, and inflammatory response to hemodialysis with seven different membranes in sheep. We also compared acetate dialysate with bicarbonate dialysate and evaluated the role of thromboxane in mediating these responses to dialysis with Cuprophan membranes (Baxter Healthcare Corp., Renal Division, Deerfield, Ill.) in sheep. The data generated in these studies indicate that dialyzer membranes can be divided into three major categories, defined by propensity to activate complement. High complement activators such as Cuprophan (low surface-area CF-1511 and high surface-area ST-25 dialyzers) produced dramatic neutropenia and hypoxemia and significant (p < 0.01) increases in the plasma concentration of thromboxane and in mean pulmonary artery blood pressure. The magnitude of these effects appeared to be surface area related. The low-flux Fresenius F-6 polysulfone membrane (Fresenius USA Inc., Concord, Calif.) also resulted in the generation of significant levels of C3a. In contrast, low complement activators such as polyacrylonitrile (AN-69; Gambro Hospal, Inc., Lakewood, Colo.) and cellulose triacetate (CT-110G; Baxter) produced little or no neutropenia, small transient increases in thromboxane, and no rise in mean pulmonary artery pressure. Dialyzers with intermediate complement-activating potential such as cellulose acetate (CA-110; Baxter) and Hemophan (HT-100; Baxter) produced small to moderate degrees of neutropenia and small increases in thromboxane and mean pulmonary artery pressure. Treatment of sheep with sodium ibuprofen before dialysis with Cuprophan CF-1511 membranes prevented the initial increases in mean pulmonary arterial pressure and thromboxane generation and the decrease in arterial oxygen tension, but did not affect the degree of complement activation or neutropenia. In sheep undergoing Cuprophan dialysis, bicarbonate dialysate did not prevent the increase in circulating complement and the associated neutropenia otherwise seen during the early portions of dialysis with acetate dialysate. Bicarbonate dialysate did, however, reduce (not prevent) the initial increases in thromboxane and mean pulmonary arterial pressure, and the magnitude of the hypoxemia seen with the use of acetate dialysate. The results of these experiments therefore indicate that (1) reactions in sheep correlate well with data collected in human beings and the model can be an effective means for comparing novel dialysis membranes and pharmacologic interventions during dialysis and (2) although complement appears to be the transducer of the hematologic and immunologic response, thromboxane appears to be the final effector of the cardiovascular responses to hemodialysis with Cuprophan membranes.

Acute Disease↗
PubMed1992

The Ku complex is modulated in response to viral infection and other cellular changes.

The complex of Ku with DNA is demonstrated to have multiple forms as assayed by gel retardation analysis. In CV1 cells this variation of complex can be modulated in response to viral infection with SV40. By Western blot analysis, a correlation can be made between modification of the complex formed on DNA in response to viral infection with variation of the 85 kDa subunit of Ku. Modification of the 85 kDa subunit can also be seen when cells are exposed to various extracellular stimuli including variation in serum levels, PMA and CaPO4.

Amino Acid Sequence↗
PubMed1992

Aspiration cytodiagnosis of breast carcinoma in pregnancy and lactation with immunohistochemical and electron microscopic study of an unusual mammary malignancy with pleomorphic giant cells.

We have reviewed our experience with 8,706 needle aspiration cytology (NAC) of the breast which were done from January 1983 to June 1991. During our study we diagnosed four cases of breast carcinomas (three ductal type and one with pleomorphic giant cells) in pregnant or lactating women; in all of these the cytologic findings corresponded with the subsequent tissue diagnosis and cell block preparations. Considering that carcinoma of breast during pregnancy and lactation is rare and is second only to cervical cancer, it was felt that its diagnosis by NAC was useful for timely management. In the case in which pleomorphic giant cells were present as an integral component of the tumour, immunohistochemical and electron microscopic study was done. This is discussed in view of our recent experience with this unusual tumour.

Adult↗
PubMed1992

Characterization of DNA sequences that mediate nuclear protein binding to the regulatory region of the Pisum sativum (pea) chlorophyl a/b binding protein gene AB80: identification of a repeated heptamer motif.

Two protein factors binding to the regulatory region of the pea chlorophyl a/b binding protein gene AB80 have been identified. One of these factors is found only in green tissue but not in etiolated or root tissue. The second factor (denominated ABF-2) binds to a DNA sequence element that contains a direct heptamer repeat TCTCAAA. It was found that presence of both of the repeats is essential for binding. ABF-2 is present in both green and etiolated tissue and in roots and factors analogous to ABF-2 are present in several plant species. Computer analysis showed that the TCTCAAA motif is present in the regulatory region of several plant genes.

Base Sequence↗
PubMed1992

FMLP causes eicosanoid-dependent vasoconstriction and edema in lungs from endotoxin-primed rats.

Recruitment of inflammatory cells to the lung capillaries has been proposed as an important step in the sequence of events that lead to acute lung injury. Frequently, in the clinical setting, bacteremia and sepsis syndrome precede the acute lung failure and endotoxin priming may represent a comparable paradigm, useful for experimental pursuit. Following addition of the chemotactic tripeptide FMLP (10(-9) to 10(-6) M) to the cell-free, salt solution perfusate of isolated rat lungs, only a small degree of vasoconstriction was observed. However, in lungs isolated from rats that received 2 mg/kg intraperitoneal Salmonella enteritidis endotoxin 2 h before lung perfusion, FMLP dose dependently caused a large, transient pulmonary pressor response, edema formation, and release of large amounts of thromboxane and leukotriene B4. Since in vitro priming with endotoxin, direct vascular injury by neutrophil elastase, nor direct stimulation with FMLP of pulmonary artery rings from endotoxin-pretreated rats, mimicked the effects of in vivo endotoxin priming, we conclude that the presence of inflammatory cells in the lung capillaries accounted for the large amount of eicosanoids produced by the lungs after FMLP stimulation. In fact, by retrograde lavage of the lung circulation with a collagenase solution, previously adherent cell clumps were mobilized and identified. These cell clumps, composed of red blood cells, neutrophils, and platelets, were not seen in the vascular lavage sediment obtained from unprimed control lungs. Indomethacin, a thromboxane antagonist, AA861, a 5-lipoxygenase inhibitor, and WEB 2086, a platelet-activating factor (PAF) antagonist, reduced the thromboxane synthesis and release after FMLP (10(-7) M) in in vivo endotoxin-primed lungs. None of the inhibitors employed exclusively inhibited only one particular eicosanoid mediator but rather affected the release of several mediators, suggesting a close link between the different synthetic arachidonic acid pathways. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate), NCDC, but not an inhibitor of phospholipase D (Wortmannin) or of protein kinase C (staurosporine) inhibited the FMLP-stimulated pulmonary pressure rise and eicosanoid release in endotoxin-primed lungs in vivo. Our data suggest that eicosanoids (in particular thromboxane) released from cells trapped in the lung circulation, but not from constitutive lung cells, contribute to vasoconstriction and edema formation caused by the chemoattractant FMLP in endotoxin-primed lungs.

Alkaloids↗
PubMed1991

Appraisal of a new scheme for prenatal screening for Down's syndrome.

OBJECTIVE: To appraise a new method of prenatal screening for Down's syndrome based on maternal serum concentrations of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin combined with maternal age--the "triple test." DESIGN: Examination of the cost effectiveness of the triple test relative to screening only by maternal age over a range of population detection rates. SETTING: Leicestershire Health Authority. MAIN OUTCOME MEASURES: Costs per affected fetus detected. RESULTS: The triple test is more cost effective than screening only by maternal age for risk cut off points for amniocentesis, resulting in a detection rate over 45%. The most efficient detection rate is around 60-65%, for which the cost per case detected is around 29,000 pounds, through screening with higher detection rates is still likely to be cost beneficial. CONCLUSIONS: Prenatal screening for Down's syndrome based on the triple test should replace screening based only on maternal age. Individual women's preferences should be elicited by the use of structured decision analysis in order to maximise utility and so increase the benefits of the screening programme.

Adult↗
PubMed1991

The effect of dibutyryl camp (dBcAMP) on morphological differentiation, growth and invasion in vitro of a hamster brain-tumor cell line: a comparative study of dBcAMP effects in 2- and 3-dimensional cultures.

The use of agents that stimulate cancer cells to differentiate is proposed as a potential approach to the treatment of malignancy. To evaluate the effects of a differentiation inducer on morphology, growth and invasion in vitro of brain-tumor cells, a diffusely invasive hamster glial cell line (CxT3C15) was treated with ImM dibutyryl cyclic adenosine monophosphate (dBcAMP). The efficacy of dBcAMP was tested in monolayer cultures, 3-dimensional static cultures (i.e., spheroids) and confrontation cultures with an embryonic chick heart. CxT3C15 cells exhibited increased numbers of long cellular processes (morphological differentiation) following treatment of monolayer cultures with ImM dBcAMP. One mM dBcAMP also altered the macroscopic and ultrastructural morphology of CxT3C15 grown as spheroids. These alterations were: (i) a fast transition of rough to smooth morphology macroscopically, and (ii) fading of the cell borders concomitant with the disappearance of cell-membrane excrescences, as seen by scanning electron microscopy. Exponential growth of CxT3C15 in monolayers was not changed following treatment with ImM dBcAMP. Treatment of CxT3C15 spheroids with the same dose of dBcAMP caused a reduction of relative volume increase (30-40%). Invasion of CxT3C15 in an embryonic chick heart in vitro was not altered after addition (prior to or at the time of co-culture) of ImM dBcAMP to the co-cultures. These results indicate that invasion of CxT3C15 is not necessarily linked to morphological differentiation or moderated by reduced proliferation.

Animals↗
PubMed1991

Retinal pigment epithelium response and the use of the EOG and Arden Ratio in depression.

Supersensitivity to light in depression has been observed with both neuroendocrine and ophthalmological assessment methods. The biological defect underlying this abnormality may be localized in either the photoreceptors, the retinal pigmented epithelium, or some interaction of the two. The present study assessed responses of the retinal pigmented epithelium (RPE). All subjects underwent thorough ophthalmological and mood assessments. The electrooculogram (EOG) was used to measure standing potentials of the RPE in response to light and dark in 20 normal controls and 20 unmedicated depressed patients. Both groups were matched for age, sex, time of day for the procedure, and prior lighting history. Reproducibility of the EOG measure on two independent occasions for 13 control subjects had an intrasubject reliability coefficient of 0.70. The mean +/- SD Arden Ratio (light peak/dark trough) of the control group (2.13 +/- 0.42) compared to the depressed group (2.28 +/- 0.72) showed no statistical difference. There was, however, a significant difference between groups in response to darkness; depressed patients had a lower standing potential in the dark compared to controls, suggesting supersensitivity to light. No difference between groups was detected in standing potentials at baseline or in response to light. Supersensitivity to light in depression may be related to abnormal function of the RPE, but the inherent reliability of the EOG precludes the use of this instrument in pursuing this hypothesis.

Adult↗