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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 289 records · Page 16Linked to original sources
PubMed1992

Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced alpha-amino acids as competitive N-methyl-D-aspartic acid antagonists.

A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([3H]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [45Ca2+] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2 microM) was retained for analogues (31 and 32, Table I; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper.

Amino Acids↗
PubMed1992

Enteric Clostridium perfringens infection associated with parvoviral enteritis in dogs: 74 cases (1987-1990).

Parvovirus infection was confirmed by fluorescent antibody staining of or viral isolation from specimens of small intestine in 181 (17%) of 1,110 dogs necropsied between July 1, 1987 and Dec 31, 1990. Clostridium perfringens was isolated from 74 (69%) of 108 dogs with parvovirus infection from which specimens of jejunum also had been obtained for culture of anaerobic bacteria. Gram-positive bacilli in association with focal to diffuse necrosis of the superficial portions of the villi were observed in histologic sections of specimens of small intestine from 56 (98%) of 57 dogs from which parvovirus and C perfringens had been identified. These findings indicate that C perfringens frequently proliferates in dogs with parvovirus infection.

Animals↗
PubMed1992

Beta-proline analogues as agonists at the strychnine-sensitive glycine receptor.

3-Carboxy-3,4-dehydropyrrolidine was found to bind with affinity equal to that of glycine in a [3H]strychnine binding assay. Simple substitution of the 1-, 2-, 4-, or 5-position resulted in marked loss of affinity. A decline in affinity was also found upon enlargement, contraction, or saturation of the 5-membered ring. However, beta-proline and azetidine-3-carboxylic acid retained significant binding affinity. Despite its good affinity in [3H]strychnine binding, 3-carboxy-3,4-dehydropyrrolidine showed only weak agonist activity in intracellular recordings of cultured murine spinal cord neurons. This apparent lack of correlation between binding and functional results is discussed in light of the current models of the strychnine-sensitive glycine receptor.

Animals↗
PubMed1992

Role of serum vitronectin and fibronectin in adhesion of fibroblasts following seeding onto tissue culture polystyrene.

The suitability of polymeric biomaterials as surfaces for the attachment and growth of cells has often been investigated in tissue culture. In this study the contribution that adsorption of serum fibronectin (Fn) or vitronectin (Vn) make to the attachment and spreading of fibroblast cells during the first 90 min following seeding was determined for two modified tissue culture polystyrenes, as model biomaterial surfaces. The amount of serum Vn and Fn which adsorbed onto tissue culture grade polystyrene (TCP) from different serum concentrations over the range of 0.1-30% (v/v) were determined and compared to attachment of cells of the BHK-21 and HT1080 fibroblast lines. There was no simple correlation between the amount of Fn or the amount of Vn adsorbed and cell attachment and spreading. The requirement for Fn or Vn for attachment and spreading of BHK-21 or HT1080 cells onto modified polystyrene (either TCP or to Primaria) during the first 90 min of cell culture was directly tested by selective removal of Fn or Vn from the serum prior to addition to the culture medium. Attachment and spreading of BHK-21 or HT1080 cells onto TCP or Primaria surfaces were reduced in a concentration-dependent manner when the cells were seeded in medium containing 2% (v/v) or higher concentrations of Vn-depleted serum. BHK-21 cells or HT1080 cells seeded in medium containing Fn-depleted serum (which contained Vn) attached and spread onto TCP or Primaria. Both BHK-21 cells and HT1080 cells failed to attach to TCP or Primaria when seeded in medium containing serum depleted of both Vn and Fn. The requirement for serum Vn or Fn for fibroblast attachment to TCP was also tested using cells of a human dermal fibroblast strain. The attachment of the dermal fibroblasts to TCP during the first 90 min of culture was not decreased by depletion of Vn from the 15% (v/v) serum, but there was a reduction in the proportion of the attached cells which had spread. Selective depletion of serum Fn did not have any effect on either cell attachment or spreading. Our results show that for fibroblast cells, particularly with cell lines such as BHK-21 or HT1080 but also with cell strains, the first binding of cells onto tissue culture polystyrene when plated in medium containing serum is a result of adsorption onto the surface of serum Vn. The adsorption of serum Vn onto the surface overcomes the effect of serum components which tend to decrease cell attachment.

Adsorption↗
PubMed1992

Technical artifact simulating "motor axonopathy".

We describe 3 patients, referred for other problems, whose nerve conduction studies revealed low compound motor amplitudes, normal motor conduction velocities and normal sensory nerve studies, consistent with a motor axonopathy. EMG was normal. The unexpected nature of these findings precipitated a search for technical artifact. A partial transection of the active electrode was found. After replacement, repetition of the motor studies was normal. Our explanation was of a normal "reference" signal being subtracted from a present but diminished "active" signal.

Artifacts↗
PubMed1992

Relationship between septal perfusion, viability, and motion before and after coronary artery bypass surgery.

The etiology of abnormal interventricular septal motion occurring after open-heart surgery using cardiopulmonary bypass has not been clarified. Intraoperative ischemic septal injury has been proposed as one explanation for this finding. To examine this possibility, resting septal perfusion and viability were studied using rest and redistribution thallium-201 scintigraphy in 16 patients before and after coronary artery bypass surgery. The results were compared with septal motion on preoperative and postoperative resting gated blood pool scans. Preoperatively, septal thallium uptake was normal in 10 of 16 patients, and septal motion was normal in 14 of 16. Postoperatively, septal thallium uptake was normal in 11 of 16 patients, while septal motion was abnormal in all. Thus abnormal postoperative septal motion is usually associated with normal septal perfusion and viability on thallium scans and therefore is not the result of septal ischemic injury in a majority of patients.

Adult↗
PubMed1992

Flow cytometric analysis of organ preservation-induced endothelial cell membrane damage.

Organ preservation for transplantation is associated with endothelial cell damage. This vascular injury results in increased capillary permeability, graft edema, and early graft dysfunction. This damage may be the limiting factor in preservation of these organs. This study uses flow cytometric assessment of membrane integrity to examine the effects of various organ preservation solutions on human umbilical vein endothelial cell cultures. Confluent plates of human umbilical vein endothelial cells were incubated at 4 degrees C for 24, 48, and 72 hours in commonly used preservation solutions. After cold incubation, the cells were harvested and stained with propridium iodide and fluorescein diacetate. Cells were examined using a flow cytometer for membrane integrity and cytosolic activity. When examined after 24, 48, and 72 hours, cells stored at 4 degrees C in a 5% polyethylene glycol salt solution were significantly less damaged than those stored in any other solution (p less than 0.05). After 48 and 72 hours at 4 degrees C, cells stored in ViaSpan were significantly more intact than cells stored in EuroCollins and 0.9% saline solution (p less than 0.05). This study demonstrates that endothelial cell damage occurs during cold storage and that a polyethylene glycol-based solution showed superior cellular preservation.

Adenosine↗
PubMed1992

Managing strategic change--strategy, culture and action.

One of the major problems facing senior executives is that of effecting significant strategic change in their organizations. This paper develops a number of explanatory frameworks which address the links between the development of strategy in organizations, dimensions of corporate culture and managerial action. In considering such linkages, and by illustrating them with examples from work undertaken in companies, the paper also seeks to advance our understanding of the problems and means of managing strategic change.

Administrative Personnel↗
PubMed1992

Increased phosphorylation of elongation factor 2 in Alzheimer's disease.

Elongation factor 2 (EF-2) is a phosphoprotein that mediates the translocation step of elongation during protein synthesis. We investigated its phosphorylation to characterize translational regulation of gene expression in Alzheimer's disease. EF-2 was identified on two-dimensional (2D) gels of brain homogenates by analyzing immunoblots with EF-2-specific antibody (M(r) 96,000; pI 6.8). Four distinct charge variant isoforms were observed. We identified the two most acidic isoforms as being the phosphorylated forms by incorporation of radiolabeled phosphate. The phosphorylation of EF-2 in control and Alzheimer's disease (AD) brain was directly measured as the distribution of the four polypeptides on silver stained 2D gels. The ratio of the phosphorylated forms to unphosphorylated forms was elevated 45% in AD homogenates compared to controls (1.07 +/- 0.18; n = 9 vs 0.73 +/- 0.20; n = 6; P less than 0.004) which indicated an increased phosphorylation of AD EF-2. The phosphorylation exhibited specificity to the disease in that it was observed in affected areas (cortex and hippocampus) but not in an unaffected area (thalamus) of the same brains. Because phosphorylation of EF-2 inhibits protein synthesis, the observed AD-associated phosphorylation of EF-2 is consistent with the reduced in vitro activity of polysomes isolated from AD tissues that we have previously reported.

Adenosine Diphosphate Ribose↗
PubMed1992

Low doses of superoxide dismutase and a stable prostacyclin analogue protect in myocardial ischemia and reperfusion.

The effects of low dose human superoxide dismutase and low dose taprostene, a stable analogue of prostacyclin, were investigated separately and together in a model of myocardial ischemia (1.5 h) with reperfusion (4.5 h) in open chest, anesthetized cats. Taprostene (60 ng/kg per min), human superoxide dismutase (0.25 mg/kg per h), both agents together, or their vehicle, were infused intravenously in cats starting 0.5 h after occlusion of the left anterior descending coronary artery. Neither low dose taprostene nor low dose human superoxide dismutase exerted any endothelial or myocardial protection in this model. However, the two agents together showed a significant endothelial and myocardial protection in cats with myocardial ischemia and reperfusion. Compared with cats that were untreated or received only taprostene or human superoxide dismutase, cats receiving both agents exhibited a lower plasma creatine kinase activity at every time point observed after reperfusion, a reduced area of cardiac necrosis (7 +/- 2% vs. 21 +/- 5% area at risk, p less than 0.001), lower myeloperoxidase activity in the ischemic region (p less than 0.01) and a significant preservation of vasorelaxant responses of left anterior descending coronary rings to endothelium-dependent vasodilators, acetylcholine (p less than 0.001) and A-23187 (p less than 0.001). Taprostene appears to act additively with human superoxide dismutase to inhibit neutrophil adherence and activation and to inactivate superoxide radicals, and thus reduce cellular injury 4.5 h after reperfusion of the ischemic heart. Use of this agent may allow low doses of superoxide dismutase to be used more effectively in early myocardial ischemia.

Animals↗
PubMed1992

Descending thoracic aorta-to-iliofemoral artery bypass as an alternative to aortoiliac reconstruction.

During the last 3 decades subcutaneous extraanatomic bypass, despite its limited durability, has been the favored alternative to infrarenal aortofemoral bypass. Meanwhile, the descending thoracic aorta has been scarcely used as an inflow source for aortoiliac reconstruction. Over the past 8 years we performed 16 bypasses from the descending thoracic aorta to the iliofemoral vessels for occlusive disease. Our experience combined with that found in the English-language literature totaled 141 patients. In 79 patients (56%) the indication for surgery was failure or infection of an abdominal aortofemoral graft. Previous abdominal operations, sepsis, radiation therapy, the presence of abdominal stomas, or an unsuitable infrarenal aorta were the indications in the remaining cases. The combined operative mortality rate was 6.4%. The life-table primary graft patency was 98% at 1 year, 88% at 2 years, and 70.4% at 5 years. Bypass from the descending thoracic aorta to the iliofemoral artery uses an inflow source superior to other extraanatomic reconstructions, does not require aortic cross-clamping, avoids the abdominal cavity, and places the graft remote to the skin and intestine. The operative mortality and patency rates compare favorably to those of other extraanatomic or remedial aortic reconstructions. Descending thoracic aorta to iliofemoral artery bypass is a superb alternative to abdominal aortofemoral bypass, carries a low mortality rate, has an excellent short-term patency, and features unique characteristics for long-term durability.

Adult↗
PubMed1992

Misdiagnosis of ruptured abdominal aortic aneurysms.

Ruptured abdominal aortic aneurysm is a surgical emergency with a high mortality rate even when diagnosed and repaired immediately. We retrospectively reviewed 152 cases of ruptured abdominal aneurysms to identify the incidence of misdiagnosis leading to a delay in treatment, the most frequent misdiagnoses, and the outcome in this group of patients. Forty-six (30%) were initially misdiagnosed. The most common misdiagnoses were renal colic, diverticulitis, and gastrointestinal hemorrhage. The most common initial physical findings in misdiagnosed patients were abdominal pain (70%), shock (57%), and back pain (50%). A pulsatile abdominal mass was found in only 26% of misdiagnosed patients versus 72% of patients correctly diagnosed (p less than 0.005). Misdiagnosed ruptured abdominal aneurysm had a 44% mortality rate, which was not significantly different from patients correctly diagnosed (58%, p = 0.34). The lack of difference in mortality rates is most likely due to preselection of those misdiagnosed patients who were able to withstand the delay in diagnosis and survive to surgical treatment. The 30% incidence of misdiagnosis in this series suggests that it is frequently a difficult diagnosis to make and must be considered in elderly patients, especially men, who are admitted with abdominal pain and/or back pain.

Abdominal Pain↗
PubMed1992

Endothelial cell preservation using organ storage solutions.

The development of organ preservation solutions has been primarily accomplished in whole organ animal models. This study examines the toxicity of commonly used organ preservation solutions on endothelial cells in vitro. Primary human umbilical-vein endothelial cell cultures were incubated at 4 degrees C in solutions of 0.9% saline (NS), EuroCollins, ViaSpan (Belzer UW) (VIA), or Hank's balanced salts with 5% polyethylene glycol (PEG). Endothelial cell viability was ascertained by colormetric measurement of mitochondrial reduction of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to purple 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan. After exposure to hypothermic storage, cells were incubated at 37 degrees C in media with MTT, and the amount of reduced formazan present was quantified using a micro-ELISA spectrophotometer. Higher absorbance values were indicative of better cellular preservation. Cells stored in PEG displayed the highest viability at all time periods. ViaSpan provided better cellular protection than EC at longer storage intervals. This model allows for rapid assessment of preservation-induced endothelial cell injury and may aid development of improved storage techniques.

Absorption↗
PubMed1992

Improvement of endothelial cell viability at 4 degrees C by addition of lazaroid U74500A to preservation solutions.

Lazaroids are potent inhibitors of lipid peroxidation. Endothelial cell damage has been shown to occur during cold storage preservation of lung and liver. This study examines the effects on endothelial cell viability of the addition of four lazaroids, U74006F, U78518F, U74500A, or U75412E to preservation solutions. Human umbilical vein endothelial cell cultures were stored at 4 degrees C for 48 and 96 hr in EuroCollins or 5% polyethylene glycol in buffered saline (PEG). U78518F, U74500A, U74006F, U75412E, or dexamethasone (each 50 microM) was added to EC (n = 32) or PEG (n = 32) and compared with control solutions of EC or PEG alone. Endothelial cell viability was determined by measuring cellular reduction of 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyltetrazolium bromide to a purple formazan dye. The reduction occurs only in viable cells and requires mitochondrial dehydrogenase activity. Results were quantified by measuring dye absorbance (Ab) with a micro-ELISA spectrophotometer. Absorbance values were compared by ANOVA and reported as mean values +/- standard deviation. Addition of U74500A to EC (Ab = 0.474 +/- 0.055) and PEG (Ab = 0.462 +/- .005) improved viability at 48 hr when compared with EC (Ab = 0.289 +/- 0.069) and PEG (Ab = 0.287 +/- 0.052) alone (P less than 0.05). At 96 hr, addition of U74500A resulted in improved viability in both EC (Ab = 0.377 +/- 0.068) and PEG (Ab = 0.195 +/- 0.09) or PEG alone (Ab = 0.212 +/- 0.1) (P less than 0.05). Other lazaroids tested were also effective in improving cellular viability, but to a lesser degree than U74500A. This study demonstrates that the addition of lazaroids to organ preservation solutions improves endothelial cell viability.

Absorption↗
PubMed1992

In vivo patency of endothelial cell-lined expanded polytetrafluoroethylene prostheses in an ovine model.

The performance of small-diameter vascular prostheses may be improved by implantation of grafts lined with endothelial cells. Expanded polytetrafluoroethylene (ePTFE) prostheses (4 mm x 40 mm) were coated with fibronectin (20 micrograms/ml), seeded with endothelial cells, and cultured for 48 h to produce a confluent, autologous endothelial cell lining. They were implanted as carotid interposition grafts in sheep. Seeded ePTFE grafts were compared with nonseeded ePTFE grafts and autologous carotid artery grafts. No anticoagulant or antiplatelet therapy was administered, making this a stringent test model for the thromboresistance of a small-diameter prosthesis. After 13 weeks the patencies of seeded, nonseeded, and autologous artery grafts were 16% (1/6), 0% (0/6), and 100% (6/6), respectively. The one seeded graft that was patent was fully lined with endothelial cells and showed no stenosis. The remaining five seeded grafts were occluded by fibrous tissue and displayed substantial spindle cell hyperplasia. There was no apparent difference between the autologous artery grafts and normal arterial tissue, and the anastomoses showed no stenosis. The ovine model provides a conservative test of prosthesis survival and may be useful for study of graft failure.

Anastomosis, Surgical↗
PubMed1992

The Milch technique for reduction of anterior shoulder dislocations in an accident and emergency department.

Following the introduction of the Milch technique as the preferred method of reduction of anterior shoulder dislocations in an A&E department, a retrospective study of the technique was carried out. A total of 187 patients with anterior shoulder dislocations were included. The Milch technique was attempted in 142 cases with a success rate of 86%. There was no statistical difference in the success rates of junior and senior staff. In 73% of the Milch cases either no analgesia or sedation or Entonox alone was used. This study shows that the Milch technique can successfully be used by inexperienced staff to reduce dislocated shoulders with a reduction in the requirements for sedation and anaesthetics.

Emergency Service, Hospital↗