Biomedical subjects

J E Jordan

Publications and source records attributed to J E Jordan.

At least 37 records · Page 2Linked to original sources

PubMed1996

Cost-effectiveness of endovascular therapy in the surgical management of cerebral arteriovenous malformations.

PURPOSE: To determine the economic effect of endovascular therapy in conjunction with surgery for cerebral arteriovenous malformations. METHODS: Twenty-five patients with arteriovenous malformations treated with embolization and surgical excision or embolization alone were compared with reported results in 475 patients who underwent surgery only. Respective mean morbidity and mortality rates were calculated and a cost-effectiveness analysis was performed in terms of costs of hospitalization, professional fees, and other direct procedural and indirect costs. Quality-adjusted life-years saved were also calculated. RESULTS: The net effective treatment cost per cure was $71 366 (in 1992 dollars) for embolization and surgery compared with $78 506 for surgery alone. This resulted in a 9% average savings per treated patient. Cost per quality-adjusted life-year calculations resulted in a cost of $6734 for embolization and surgery and $9814 for surgical treatment alone, with savings as high as 34% when endovascular therapy was used. CONCLUSION: Endovascular therapy in conjunction with surgery resulted in significant economic benefits for treatment of cerebral arteriovenous malformations.

Adult↗

PubMed1995

Cost effectiveness and outcome assessment of magnetic resonance imaging in diagnosing cord compression.

BACKGROUND: This study was designed to investigate the costs associated with the use of magnetic resonance imaging (MRI) in the workup of spinal cord compression caused by metastatic disease, an area in which it has proven to be diagnostically useful. METHODS: The study was divided into two parts. Part 1 consisted of a retrospective review of the hospital charts of 46 patients, half of whom were diagnosed with cord compression in the pre-MRI era and the other half diagnosed after MRI availability; costs for these two groups were compared. Part 2 consisted of a review of several major studies comparing the sensitivities and specificities of MRI with alternative imaging techniques, usually myelography. Cost effectiveness and cost/cost ratios were derived for diagnostic usefulness using prevalence, sensitivity, specificity, and cost estimates of MRI and its alternatives, including costs of false-negative and false-positive testing. RESULTS: Our hospital-based experience yielded an average cost of $ 3664 per patient without MRI and $ 2283 per patient when MRI was available (1991 dollar amounts). The cost of diagnosis was 65% more expensive without MRI. Use of the literature-based experience demonstrated that the cost of diagnosis was at least 82% more costly without MRI than when it was available. However, when key variables were altered during sensitivity analysis, this difference of increased cost of diagnosis without MRI ranged from 25% to 98%. CONCLUSION: This work suggests that MRI may result in significant economic benefits in diagnosing metastatic cord compression, but further work is needed on physician behavior and referral patterns with MRI versus myelography as is long term follow-up for potential reductions in patient debility using MRI.

Cost-Benefit Analysis↗

PubMed1995

Erythropoietin stimulates transcription of the TAL1/SCL gene and phosphorylation of its protein products.

Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia. The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers. TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation. Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus (FVA cells). Epo elicited a rapid, dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs. An Epo-inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein. Induction of DNA binding activity was associated temporally with Epo-induced phosphorylation of nuclear TAL1 protein. These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages.

Animals↗

PubMed1995

Suspected multiple sclerosis: MR imaging with a thin-section fast FLAIR pulse sequence.

PURPOSE: To compare thin-section, sagittal, fast fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) imaging with conventional axial spin-echo (SE) imaging for early detection of multiple sclerosis (MS) in the brain. MATERIALS AND METHODS: Conventional 5-mm axial proton-density- and T2-weighted SE images and sagittal 2-mm fast FLAIR images of the brain in five healthy volunteers and 25 patients with clinically suspected MS were evaluated and graded as normal or as showing possible or probable MS in a double-blind study. RESULTS: Fast FLAIR was judged better than SE in 37% of cases, equal to SE in 63%, and never worse than SE. In 43% of patients considered to have normal SE images, fast FLAIR images showed abnormalities consistent with MS. A subependymal striated appearance observed in several cases is believed to represent early inflammation and/or demyelination around subependymal veins in MS. CONCLUSION: Sagittal thin-section fast FLAIR is superior to conventional axial proton-density- and T2-weighted SE pulse sequences for detection of MS plaques in the brain.

Adult↗

PubMed1995

Hypertonicity, but not hypothermia, elicits substance P release from rat C-fiber neurons in primary culture.

Isocapnic dry gas hyperventilation provokes hyperpnea-induced bronchoconstriction in guinea pigs by releasing tachykinins from airway sensory C-fiber neurons. It is unknown whether dry gas hyperpnea directly stimulates C-fibers to release tachykinins, or whether this physical stimulus initiates a mediator cascade that indirectly stimulates C-fiber tachykinin release. We tested the hypotheses that mucosal hypothermia and/or hyperosmolarity--physical consequences of airway heat and water loss imposed by dry gas hyperpnea--can directly stimulate C-fiber tachykinin release. Neurons isolated from neonatal rat dorsal root ganglia were maintained in primary culture for 1 wk. Cells were then exposed for 30 min at 37 degrees C to graded concentrations of NaCl, mannitol, sucrose, or glycerol (0-600 mOsm) added to isotonic medium, or to isotonic medium at 25 degrees C without or with 462 mOsm mannitol added. Fractional release of substance P (SP) was calculated from supernatant and intracellular SP contents following exposure. Hyperosmolar solutions containing excess NaCl, mannitol, or sucrose all increased fractional SP release equivalently, in an osmolarity-dependent fashion. In marked contrast, hypothermia had no effect on fractional SP release under isotonic or hypertonic conditions. Thus, hyperosmolarity, but not hypothermia, can directly stimulate tachykinin release from cultured rat sensory C-fibers. The lack of effect of glycerol, a solute which quickly crosses cell membranes, suggests that neuronal volume change represents the physical stimulus transduced by C-fibers during hyperosmolar exposure.

Animals↗

PubMed1995

Conspicuity of tumors of the head and neck on fat-suppressed MR images: T2-weighted fast-spin-echo versus contrast-enhanced T1-weighted conventional spin-echo sequences.

OBJECTIVE: The purpose of this study was to compare the conspicuity of tumors of the head and neck on MR images acquired with T2-weighted fat-suppressed fast-spin-echo and contrast-enhanced T1-weighted fat-suppressed conventional spin-echo sequences. MATERIALS AND METHODS: The MR images of 29 patients with 36 pathologically proved tumors of the head and neck were retrospectively analyzed. The conspicuity of these tumors was assessed on the T2-weighted sequence (4700/108 [TR/TE]) and on the contrast-enhanced T1-weighted sequence (500/16) with a 1.5-T system. Qualitative tumor-to-background contrast was graded separately against background muscle, fat, and mucosa (0 = not visualized, 1 = poorly visualized, 2 = fairly well visualized, 3 = well visualized), and the best overall sequence was noted for each tumor. Quantitative tumor-to-background ratios were measured for 10 of the tumors by using the same background markers. RESULTS: The mean overall qualitative tumor-to-background contrast grades for the T2-weighted sequence were tumor/muscle = 2.84, tumor/fat = 2.20, and tumor/mucosa = 1.23, and for the contrast-enhanced T1-weighted sequence, they were tumor/muscle = 2.02, tumor/fat = 1.58, and tumor/mucosa = 0.73. Overall, 86% of the tumors were better or equally well visualized on the T2-weighted images. The mean overall quantitative tumor-to-background ratios for the T2-weighted sequence were tumor/muscle = 7.93, tumor/fat = 3.34, and tumor/mucosa = 0.68, and for the contrast-enhanced T1-weighted sequence, they were tumor/muscle = 2.43, tumor/fat = 2.28, and tumor/mucosa = 0.85. CONCLUSION: The T2-weighted fat-suppressed fast-spin-echo sequence offers better contrast between tumors and adjacent muscle, fat, and mucosa than does the contrast-enhanced T1-weighted fat-suppressed spin-echo sequence and thus improves overall tumor conspicuity. In addition, the T2-weighted sequence does not require IV contrast material and can be performed more rapidly than can the contrast-enhanced T1-weighted sequence. The contrast-enhanced T1-weighted sequence may offer complementary information on the precise characterization of complex tumors and on the potential determination of tumor extent.

Adipose Tissue↗

PubMed1994

The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis.

Activation of the SCL (or TAL-1) gene as a result of chromosomal translocation or deletion is a frequent molecular lesion in acute T-cell leukemia. By virtue of its membership in the basic helix-loop-helix family of transcription factors, the SCL gene is a candidate to regulate events in hematopoietic differentiation. We have used polyclonal antibody raised against a bacterial expressed malE-SCL fusion protein to characterize SCL protein expression in postimplantation embryos and in neonatal and adult mice. SCL protein was detected at day 7.5 post coitum at both embryonic and extraembryonic sites, approximately 24 hours before the formation of recognizable hematopoietic elements. Expression then localized to blood islands of the yolk sac followed by localization to fetal liver and spleen, paralleling the hematopoietic activity of these tissues during development. SCL protein was detected in erythroblasts in fetal and adult spleen, myeloid cells and megakaryocytes in spleen and bone marrow, mast cells in skin, and in rare cells in fetal and adult thymus. In addition, SCL protein was noted in endothelial progenitors in blood islands and in endothelial cells and angioblasts in a number of organs at times coincident with their vascularization. SCL expression was also observed in other nonhematopoietic cell types in the developing skeletal and nervous systems. These results show that SCL expression is one of the earliest markers of mammalian hematopoietic development and are compatible with a role for this transcription factor in terminal differentiation of the erythroid and megakaryocytic lineages. SCL expression by cells in the thymus suggests that the gene may be active at some stage of T-cell differentiation and may be relevant to its involvement by chromosomal rearrangements in T-lymphoid leukemias. Finally, expression of the gene in developing brain, cartilage, and vascular endothelium indicates SCL may have actions in neural development, osteogenesis, and vasculogenesis, as well as in hematopoietic differentiation.

Animals↗

PubMed1993

Stroke rates in patients with lacunar and large vessel cerebral infarctions.

A stroke registry was developed to determine the value of various clinical data in distinguishing lacunar from large vessel infarctions. Adequate localization was achieved in 98% of 246 patients with brain infarcts. These and 30 transient ischemic attack patients were followed for a median of 1082 days (range 2-1657). Follow-up data on TIA patients were invalidated by evidence of serious underreporting of TIAs in our general population. Among 212 male patients with cerebral infarcts not due to cardiogenic embolism, syphilis, migraine, vasculitis, or other unusual etiologies, 1-, 12-, and 36-month recurrence rates were 23%, 31% and 39% among patients with large vessel anterior circulation infarcts; 15%, 20% and 28% among patients with large vessel posterior circulation infarcts; and 8%, 16% and 21% among patients with lacunar anterior circulation infarcts, respectively. Six patients with posterior circulation lacunes did not experience recurrence. Comparative case fatality data were also compiled. Large vessel infarcts tended to be followed by further large vessel infarcts, usually in the same vascular distribution, whereas lacunar infarcts were not predictive of the type or location of subsequent events.

Cerebral Arteries↗

PubMed1993

Factors associated with occurrence of large vessel and lacunar cerebral infarctions.

A stroke registry was developed to determine the localizing value of various clinical data. Adequate localization was achieved in 98% of 246 patients with infarcts. Among 212 male patients with cerebral infarcts not due to cardiogenic embolism or an unusual etiology, there were 152 with large-vessel and 59 with lacunar infarcts. Logistic regression analysis of factors associated with large vessel and lacunar stroke identified myocardial infarction on ECG as the only statistically significant variable; its presence was associated with an odds ratio for lacunar infarction of 0.19 (95% confidence interval 0.06-0.66) (P = 0.009). Logistic regression analysis of factors associated with anterior and posterior circulation large vessel stroke identified pack years of smoking as the only statistically significant variable; the odds ratio for posterior circulation infarction for a 10-year increment in pack years of smoking was 0.83 (95% confidence interval 0.73-0.94) (P = 0.0035).

Age Factors↗

PubMed1993

Bone contusions of the knee: increased lesion detection with fast spin-echo MR imaging with spectroscopic fat saturation.

PURPOSE: To demonstrate that T2-weighted fast spin-echo (FSE) imaging with spectroscopic fat saturation (FS-FSE) increases the conspicuity between normal marrow and bone contusions in posttraumatic knees. MATERIALS AND METHODS: Seventy-six magnetic resonance (MR) studies of the knee were prospectively evaluated in 73 consecutive patients with knee pain. Conspicuity of regions of microtrabecular trauma (bone contusions) was evaluated with conventional T2-weighted imaging in the sagittal plane, T2-weighted FSE imaging in the coronal plane, T2-weighted FS-FSE imaging in the sagittal plane, and conventional T1-weighted imaging in the sagittal plane. RESULTS: Twenty-six foci of bone contusion were identified in 21 knees with the FS-FSE technique. Only 16 foci were demonstrated with conventional T2-weighted imaging. Six of the sites of bone contusion were not demonstrated with the FSE technique alone (without fat saturation). Four of the bone contusions were not seen on T1-weighted images; these sites of bone contusion were substantially more conspicuous on the FS-FSE images. In addition, FS-FSE imaging was more sensitive in demonstrating the extent of microtrabecular trauma. CONCLUSION: T2-weighted FS-FSE imaging is a sensitive and rapid method of identifying and assessing the extent of microtrabecular trauma about the knee.

Adult↗

PubMed1993

Role of eicosanoids in hyperpnea-induced airway responses in guinea pigs.

Guinea pigs mechanically hyperventilated with dry gas exhibit hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH). Tachykinins released from airway C-fiber neurons are the central mediators of guinea pig HIB but play only a contributory role in HIBVH. Recent studies suggest that eicosanoid mediators can provoke bronchoconstriction and bronchovascular hyperpermeability, are released by dry gas hyperpnea, and can themselves elicit or modulate tachykinin release. We therefore hypothesized that eicosanoids may participate in HIB and/or HIBVH. To test these hypotheses, we analyzed respiratory system resistance changes and Evans blue-labeled albumin extravasation into the airways of 60 tracheostomized and mechanically ventilated guinea pigs. Animals were subjected to 10 min of isocapnic dry gas hyperpnea or to quiet breathing of humidified gas and received as pretreatment either piroxicam, a cyclooxygenase (CO) inhibitor; A-63162, a 5-lipoxygenase (5-LO) inhibitor; BW-755c, a combined CO and 5-LO inhibitor; ICI-198,615, a leukotriene D4 receptor antagonist; or no drug. HIB was substantially (50-80%) reduced by each of the four eicosanoid-modulating drugs. In contrast, HIBVH was reduced only by BW-755c, and this effect occurred only within the extrapulmonary airways (42% reduction). These data indicate that both CO and 5-LO products, including leukotriene D4, participate in the pathogenesis of HIB but that, like tachykinins, they play only a small contributory role in HIBVH. Together with our previous demonstration that sensory neuropeptide release is critical for the occurrence of HIB, we conclude that the roles of eicosanoids and tachykinins in guinea pig HIB are interdependent.

Animals↗

PubMed1993

Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs.

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.

Airway Resistance↗

PubMed1993

Diagnosis of carotid artery disease: preliminary experience with maximum-intensity-projection spiral CT angiography.

OBJECTIVE: Spiral CT allows continuous data to be acquired rapidly, and if a correctly timed IV bolus of contrast material is given, spiral CT angiography can be performed. This study was designed to evaluate spiral CT angiography with maximum-intensity-projection reconstructions for assessing the degree of carotid artery stenosis. SUBJECTS AND METHODS: Spiral CT angiography (of 28 carotid bifurcations in 14 patients) was compared in a blinded fashion with conventional angiography (of 28 bifurcations) and with two-dimensional time-of-flight MR angiography (of 12 bifurcations) to assess degree of stenosis. A nonblinded comparison of the contour of the lumen at the site of stenosis was then made between conventional angiography, spiral CT angiography, and MR angiography. The degree of stenosis was measured in each internal carotid artery and categorized as mild (< 30%), moderate (30-69%), or severe (70-99%) stenosis or as occlusion. Maximum-intensity-projection images were used for the evaluations; however, if calcification was circumferential and the lumen of the carotid artery could not be analyzed in the area of the calcification, the axial source images were used. RESULTS: The results of CT angiography and conventional angiography agreed overall in 25 (89%) of 28 cases (r = .921, p = .05, Spearman rank correlation). The presence of severe stenosis or occlusion was correctly identified in seven of seven cases. In the moderate and mild stenosis categories, 18 (86%) of 21 were correctly identified (r = .802, p = .122). Three internal carotid arteries (11%) had circumferential calcification that necessitated evaluation of the axial source images, and the measurements obtained from the axial images agreed well with angiographic findings. MR angiography correlated well with the various categories of stenosis. However, when we compared MR angiography directly with CT angiography and conventional angiography, we found that the degree of stenosis was overestimated when MR angiography was used. CONCLUSION: Our results show that spiral CT angiography shows normal and abnormal carotid anatomy well when compared with conventional angiography. The short examination time and clear depiction of arterial caliber in areas of stenosis are significant advantages of spiral CT angiography compared with MR angiography.

Aged↗

PubMed1992

Watershed infarction on computed tomographic scan. An unreliable sign of hemodynamic stroke.

We identified three patients with computed tomography-defined infarctions that were partly or exclusively located in watershed territories; clinical evaluation and cerebral angiography suggested that the infarcts were of embolic origin. In two patients, arteriography demonstrated minimal carotid plaque without evidence of significant stenosis. The third patient did have high-grade stenosis of the petrous portion of the ipsilateral internal carotid artery, but arteriography demonstrated a branch artery occlusion corresponding to the territory of the infarction. Although most authors suggest that watershed territory infarctions arise from hemodynamic events, cerebral embolization may be a common cause.

Aged↗

PubMed1992

Spicy meal disturbs sleep: an effect of thermoregulation?

Tabasco sauce and mustard taken with the evening meal markedly disturbed sleep of six, young, healthy male subjects; reducing slow wave and stage 2 sleep, increasing total time awake and tending to increase sleep onset latency. Whilst post meal effects on temperature and oxygen consumption were not significantly different from control meals the spicy food condition elevated body temperature during the first sleep cycle. The possibility that the spice principle capsaicin affects sleep via changes in body temperature is discussed.

Adult↗

PubMed1991

The quantitation of bovine embryo viability using a bioluminescent assay for lactate dehydrogenase.

Forty-seven bovine embryos, ranging from the four-cell to expanded blastocyst stage, with grades ranging from excellent to poor, were collected non-surgically from superovulated Holstein heifers. A viability assay based on the measurement of bioluminescent emission from the media surrounding an embryo was tested. This assay measured the activity of the enzyme lactate dehydrogenase (LDH) released into the media by the embryos. Lactate dehydrogenase has been reported to be released into media by nonviable embryos. The assay used is simple, rapid and nonsubjective, requiring approximately 5 min to complete. The LDH assay proved to be a practical method for distinguishing between nonviable and viable embryos. Viability was determined by the observation of embryo development in culture following the LDH assay. The activity of LDH in the media of nonviable embryos was consistently higher than for viable embryos (P<0.001), with no overlap between the two groups. Thus, the LDH assay was shown to be a reliable test of embryo viability.

Journal Article↗

PubMed1989

Cloning of the mRNA for the protein that crosslinks to the egg peptide speract.

An apparent receptor for the egg peptide speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) was identified by covalently coupling a radiolabeled speract analogue to intact spermatozoa and was then purified by DEAE-Sepharose chromatography and preparative gel electrophoresis after solubilization with Lubrol PX. The purified, crosslinked protein was digested with Staphylococcus aureus V8 protease and a resultant peptide, purified from polyacrylamide slab gel slices, was shown to have the amino acid sequence Val-Ser-Ala-Pro-Phe-Asp-Leu-Glu-Ala-Pro-Phe-Ile-Ile-Asp-Gly-Ile. Polyclonal antiserum, generated against a synthetic peptide that corresponded to the above sequence, immunoprecipitated the radiolabeled crosslinked protein and reacted with a Mr 77,000 protein on immunoblots, demonstrating that the sequenced peptide originated from the apparent receptor. A clone containing a 2.5-kilobase insert was subsequently isolated from a sea urchin testis cDNA library that contained DNA sequences encoding an open reading frame of 532 amino acids that included the above peptide sequence. The deduced amino acid sequence suggests that the protein contains a 26-residue amino-terminal signal peptide, a large extracellular domain relatively rich in cysteine (5%) that includes a four-fold repeat of about 115 amino acids, a single membrane-spanning region, and only 12 amino acid residues extending into the cytoplasm. Analysis of total RNA from Strongylocentrotus purpuratus testis by Northern blot revealed a 2.5-kilobase RNA. Preliminary data show the presence of hybridizing RNA of the same apparent size in other sea urchin species, including Arbacia punctulata, which does not respond to speract.

Amino Acid Sequence↗

PubMed1987

Lipid peroxidation in erythrocyte membranes: cholesterol product analysis in photosensitized and xanthine oxidase-catalyzed reactions.

The effects of singlet oxygen- and oxygen radical-induced lipid peroxidation on cell membrane integrity were compared, using the human erythrocyte ghost as a model system. Resealed ghosts underwent lipid peroxidation and lysis (release of trapped glucose-6-P) when irradiated in the presence of uroporphyrin (UP) or when incubated with xanthine (X), xanthine oxidase (XO) and iron. The UP-sensitized process was inhibited by azide but not by phenolic antioxidants, consistent with singlet oxygen (nonradical) involvement. This was confirmed by showing that the predominant photoproduct of membrane cholesterol was the 5 alpha-hydroperoxide. Total hydroperoxide (LOOH) content in UP-photooxidized ghosts increased linearly during the prelytic lag and throughout the period of rapid lysis. Unlike the photoreaction, X/XO/iron-dependent peroxidation and lysis was inhibited by catalase, superoxide dismutase and phenolic antioxidants, indicating O2-/H2O2 intermediacy and a free radical mechanism. Correspondingly, only radical reaction products of cholesterol were formed, notably the 7 alpha-, 7 beta-hydroperoxide pair. Membrane lysis had a distinct lag as in photooxidation; however, the LOOH profile was more complex, with an initial lag followed by a sharp increase and then slow decline. X/XO/iron-induced lysis commenced when LOOH levels were 2-3 times higher than in photosensitized lysis, suggesting that the pathways of membrane lesion formation are different in the two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic Acid↗