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Biomedical subjects

J Morgan

Publications and source records attributed to J Morgan.

At least 19 recordsLinked to original sources
PubMed1999

Indications for cholesterol-lowering medication: comparison of risk-assessment methods.

BACKGROUND: Recommendations for the prescription of lipid-lowering drugs emphasise the importance of an assessment of absolute coronary heart disease (CHD) risk based on all risk factors, rather than simply the serum cholesterol concentration. If, however, the methods recommended for risk assessment are inaccurate, recommended prescribing will not occur. We compared several sets of guidelines for such treatment in a series of patients referred to a lipid clinic, to assess the difference in degree of risk of CHD at which lipid-lowering medication is recommended by each set of guidelines. METHODS: For a series of 570 patients (50% men) without pre-existing clinical evidence of atherosclerosis referred to a lipid clinic, we compared the algorithms, charts, and tables used by the US National Cholesterol Education Program (NCEP), the joint guidelines of the European Society of Cardiology, the European Atherosclerosis Society, and the European Society of Hypertension, and the report of the UK Standing Medical Advisory Committee with the Framingham risk equation programmed into a computer. FINDINGS: In 386 patients for whom the NCEP and UK guidelines could be compared, 62% of the men and 72% of the women met NCEP criteria for lipid-lowering medication, whereas only 9% of the men and less than 1% of the women met the UK criteria. The Framingham equation estimated a CHD risk of more than 3% per year in 22% of the men and 7% of the women, which shows that the UK tables underestimated CHD risk. European guidelines could be applied to only 261 patients, and were reasonably accurate in assessment of a CHD risk of 2% per year. INTERPRETATION: Guidelines for the use of statin treatment in patients with CHD differ in their assessment of CHD risk. The method of risk assessment recommended in future guidelines for CHD prevention should be critically tested in relevant groups of patients.

Algorithms↗
PubMed1998

"Depression" increases "craving" for sweet rewards in animal and human models of depression and craving.

This study consisted of two experiments, one in rats and one in human volunteers, that used the identical progressive ratio (PR) operant procedure. In both experiments, responding was reinforced under a progressively increasing work requirement, and different groups of subjects received reinforcers that varied in sweetness. In experiment 1, rats were subjected to chronic mild stress, a well-validated animal model of depression. Performance under the PR schedule increased in subjects reinforced with conventional precision pellets (which contain 10% sucrose) or very sweet pellets, but not in subjects reinforced with sugar-free pellets. In experiment 2, volunteers were subjected to a depressive musical mood induction. Performance under the PR schedule increased in subjects reinforced with chocolate buttons, but not in subjects reinforced with with buttons made from the relatively unpalatable chocolate substitute carob. In experiment 2, depressive mood induction also increased chocolate craving, as measured by a novel questionnaire, and there were significant correlations between chocolate craving and chocolate-reinforced PR performance. These results suggest that performance under the PR schedule provides a measure of craving rather than reward, and that craving for sweet rewards is increased by depressive mood induction in both animal and human models. Implications for the interpretation of pharmacological studies using the PR procedure are also discussed.

Adult↗
PubMed1998

Influence of coping style and precolonoscopy information on pain and anxiety of colonoscopy.

BACKGROUND: This study assessed the relationship between patient coping style, precolonoscopy information, and anxiety and pain associated with colonoscopy. METHODS: Eighty consecutive adult patients undergoing initial colonoscopy were classified into two groups on the basis of coping style: information seekers or information avoiders. All were given standardized information about colonoscopy. Half of each group was randomly assigned to receive additional sensory information describing what they could expect to feel. Self-report, physiologic, and behavioral indices of anxiety and pain were measured. RESULTS: Patients given information congruent with coping style experienced significantly less self-report anxiety immediately after the information intervention and spent less time in recovery. In contrast, patients given information not congruent with coping style maintained their pre-intervention anxiety level. Patients given information congruent with coping style scored lower on behavioral indices of pain, but there were no differences with respect to patient perception of pain or the dosage of sedative drugs. Most patients reported that the bowel preparation was the most distressing part of the colonoscopy. CONCLUSIONS: Assessment of coping style and provision of congruent information reduces anxiety, recovery time, and observed behavioral indices of pain of colonoscopy but has no effect on sedation dose or patient perception of pain.

Adaptation, Psychological↗
PubMed1998

Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia.

We have investigated the effects of two fibric acid derivatives, bezafibrate mono (400 mg daily) and gemfibrozil (600 mg b.d.), in 29 patients with type IIb hyperlipoproteinaemia. All patients received placebo and each drug for 8 weeks in randomised order in a double-blind, cross-over study designed to evaluate any different effects of the drugs on serum lipoproteins, cholesteryl ester transfer protein (CETP), cholesteryl ester transfer activity (CETA), plasma fibrinogen, plasminogen activator inhibitor-I (PAI-1) or paraoxonase. Serum cholesterol decreased (P < 0.05) with gemfibrozil, but the effect of bezafibrate on serum cholesterol did not achieve statistical significance (placebo 8.34 +/- 1.05 (mean +/- S.D.), gemfibrozil 7.70 +/- 1.23 and bezafibrate 7.8 +/- 1.37 mmol/l). Both drugs decreased the serum triglyceride concentration (both P < 0.001) (placebo 4.39 (3.13-5.75) (median (interquartile range)), bezafibrate 2.26 (1.89-3.89) and gemfibrozil 2.00 (1.30-3.30) mmol/l) and very low density lipoprotein (VLDL) cholesterol (both P < 0.001) (placebo 1.18 (0.74-2.30), bezafibrate 0.59 (0.34-0.85) and gemfibrozil 0.48 (0.34-0.68) mmol/l). Discontinuous gradient ultracentrifugation (DGU) revealed that Sf 60-400 (large VLDL) decreased by more than 50% and Sf 20-60 (small VLDL) by more than 30% with each of the drugs (both P < 0.001), neither of which affected the composition of these lipoproteins. Gemfibrozil decreased the concentration of Sf 12-20 lipoprotein (intermediate density lipoprotein; IDL) by 23% (P < 0.01), whereas the effect of bezafibrate on this lipoprotein did not achieve statistical significance. Neither drug altered the concentration of apolipoprotein B or of total Sf 0-12 lipoproteins (low density lipoprotein, (LDL)). Both, however, significantly increased the quantity of free cholesterol in Sf 0-12 lipoproteins (P < 0.05). Overall the concentration of triglycerides decreased significantly in all lipoproteins isolated by DGU (Sf 0-12, Sf 12-20, Sf 20-60, Sf 60-400) on gemfibrozil treatment, but only in Sf 20-60 and Sf 60-400 on bezafibrate (all P < 0.05). Both drugs also increased serum high density lipoprotein (HDL) cholesterol (placebo 1.15 +/- 0.29, bezafibrate 1.27 +/- 0.38 (P < 0.01) and gemfibrozil 1.26 +/- 0.49 (P < 0.05) mmol/l) and HDL3 cholesterol concentration (placebo 0.59 +/- 0.12, bezafibrate 0.72 +/- 0.23 (P < 0.001) and gemfibrozil 0.70 +/- 0.24 (P < 0.01) mmol/l). Serum apolipoprotein A1 (apo A1) was increased (P < 0.05) by bezafibrate compared to gemfibrozil (placebo 103 +/- 26, bezafibrate 111 +/- 28 and gemfibrozil 102 +/- 25 mg/dl) and CETA from HDL to VLDL and LDL was decreased (P < 0.05) by bezafibrate compared to placebo, but the apparent decrease with gemfibrozil did not achieve statistical significance (placebo 39.6 +/- 17.7, bezafibrate 32.3 +/- 14.7 and gemfibrozil 33.8 +/- 15.0 nmol/ml/h). Neither drug affected the circulating concentration of CETP. Plasma fibrinogen was increased (P < 0.05) by gemfibrozil (placebo 4.16 (3.38-4.71) and gemfibrozil 4.65 (4.05-5.77) g/l) and was significantly lower (P < 0.001) on bezafibrate (3.60 (3.18-4.54) g/l) than on gemfibrozil treatment. There was a significant (P < 0.05) increase in PAI-1 activity with bezafibrate and a similar trend with gemfibrozil (placebo 41.2 (25.6-64.5), bezafibrate 50.5 (35.1-73.9) and gemfibrozil 48.5 (31.5-5.4 U/l). Neither fibrate influenced plasma concentrations of PAI-1 nor were the activities of lecithin:cholesterol acyl transferase or paraoxonase affected. The major difference in the action of the two drugs on lipoprotein metabolism was the greater effect of gemfibrozil in decreasing the overall serum concentration of Sf 12-20 lipoproteins and the triglycerides in Sf 12-20 and 0-12 lipoproteins. Bezafibrate, however, increased serum apo A1 concentration and significantly decreased CETA. The two drugs also had different effects on the plasma fibrinogen levels, which increased with gemfibrozil and tended to decrea

Adult↗
PubMed1998

Mice deficient for 5-lipoxygenase, but not leukocyte-type 12-lipoxygenase, display altered immune responses during infection with Schistosoma mansoni.

Periovular granuloma formation during Schistosoma mansoni infection is a complex, multifaceted immunologic response. Products of arachidonic acid metabolism have been shown to contribute to this response through studies in which general inhibitors of lipoxygenase function reduce granulomatous inflammation. To determine which lipoxygenases are important for granuloma development in schistosomiasis, wild type mice or mice deficient for 5-lipoxygenase (5-LO) or "leukocyte-type" 12-lipoxygenase (12-LO) were infected with S. mansoni and studied for responses to schistosome eggs and egg antigens. At the acute stage of infection, when granuloma formation is usually maximal, 5-LO deficient mice developed smaller granulomas around liver-deposited schistosome eggs compared with wild type or 12-LO deficient mice. 5-LO mice also displayed less antibody-mediated (5 h) and cell-mediated, delayed-type (24 h) hypersensitivity to schistosome egg antigens than did the other two infection groups. In an attempt to determine possible mechanisms for the reduced inflammatory responses, we also measured hepatic mRNA levels of cytokines that have been shown to influence granuloma size (IL-4, IL-10, and IFN-gamma). The mRNA levels for IL-10 were significantly lower in 5-LO-deficient mice, but SEA-stimulated spleen cells did not demonstrate a significant difference in IL-10 production between wild type and 5-LO mice. These data suggest that 5-LO plays a role in host responses to schistosomiasis via a mechanism that cannot be explained solely by changes in expression of these cytokines.

Animals↗
PubMed1998

Antigen specific and nonspecific modulation of the immune response by aminolevulinic acid based photodynamic therapy.

Photosensitizers used normally in treating cancers have considerable potential for treatment of other diseases. One such photosensitizer is the endogenously synthesized photosensitizer protoporphyrin IX (PpIX). To better understand how protoporphyrin might be used in transplantation or in treating autoimmune diseases, information must be obtained on how the photosensitizer affects all immune cells. We used a combination of flow cytometry and in vitro activation assays (recall assays and mixed-lymphocyte reactions) to examine the effects of PpIX on the antigen specific component, lymphocytes and the non-antigen specific component, the macrophages/monocytes and dendritic cells of the immune system. Whereas, lymphocytes accumulate PpIX only when activated, both macrophages and dendritic cells accumulated PpIX immediately, without in vitro activation, as measured by flow cytometry. ALA-PDT (aminolevulenic acid-photodynamic therapy) treated adherent cells in the recall assay had a decreased capability to activate lymphocytes. By increasing the light dose in the recall assay, antigen primed lymphocytes were selectively eliminated from a population of cells. Stimulator cells in an MLR had a decreased stimulatory capacity following ALA-PDT treatment. Functional alterations are seen in both the antigen specific

Aminolevulinic Acid↗
PubMed1998

Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles.

Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle disease characterized by a lack of dystrophin expression. Myoblast transplantation and gene therapy have the potential of restoring dystrophin, thus decreasing the muscle weakness associated with this disease. In this study we present data on the myoblast mediated ex vivo gene transfer of full-length dystrophin to mdx (dystrophin deficient) mouse muscle as a model for autologous myoblast transfer. Both isogenic primary mdx myoblasts and an immortalized mdx cell line were transduced with an adenoviral vector that has all viral coding sequences deleted and encodes beta-galactosidase and full-length dystrophin. Subsequently, these transduced myoblasts were injected into dystrophic mdx muscle, where the injected cells restored dystrophin, as well as dystrophin-associated proteins. A greater amount of dystrophin replacement occurred in mdx muscle following transplantation of mdx myoblasts isolated from a transgenic mouse overexpressing dystrophin suggesting that engineering autologous myoblasts to express high amounts of dystrophin might be beneficial. The ex vivo approach possesses attributes that make it useful for gene transfer to skeletal muscle including: (1) creating a reservoir of myoblasts capable of regenerating and restoring dystrophin to dystrophic muscle; and (2) achieving a higher level of gene transfer to dystrophic muscle compared with adenovirus-mediated direct gene delivery. However, as observed in direct gene transfer studies, the ex vivo approach also triggers a cellular immune response which limits the duration of trans-gene expression.

Adenoviridae↗
PubMed1998

Cytokine mRNA levels in the hearts of inbred mice that develop different degrees of cardiomyopathy during infection with Trypanosoma cruzi.

Profiles of cytokine mRNA expression were examined by semiquantitative RT-PCR in the hearts of DBA/2 (pathopermissive) and B10.D2 (pathoresistant) mice during infection with the Brazil strain of Trypanosoma cruzi. The levels and time-course profiles of IFNgamma, IL-1beta and IL-10 mRNA expression were similar in each strain. TNFalpha, iNOs, and IL-13 mRNA expression peaked at comparable levels and times after infection in each strain, but declined more rapidly in B10.D2 than in DBA/2 mice. Peak IL-2 mRNA levels were also similar between the two strains, but occurred earlier in DBA/2 than in B10.D2 mice. Levels of IL-4, IL-6 and IL-12 mRNA were significantly higher in DBA/2 than in B10.D2 mice from day 10 through day 50 of infection. With the exception of IL-1beta, which was expressed constitutively in both strains, the levels of mRNA of all other cytokines examined reached their peak no later than day 20 and declined significantly by day 50 after infection. The inflammatory infiltrate paralleled the latter cytokines; starting at day 10 in DBA/2 mice and at day 15 in the B10.D2 s, peaking between days 20 and 30 in both strains, decreasing to minimal levels by day 50 in the pathoresistant mice, but maintaining a mild amount through day 70 in the pathopermissive strain. The inflammation was composed mostly of lymphocytes and histiocytes throughout the entire process. These data demonstrate differences in the profiles of cytokine mRNA that may be related to the differential degree of cardiac pathology that develops in these two strains of mice upon infection with T. cruzi.

Age Factors↗
PubMed1998

The use of a back class teaching extension exercises in the treatment of acute low back pain in primary care.

BACKGROUND: Back extension exercises are commonly recommended to treat acute low back pain. Evidence of their beneficial effect is, however, weak. OBJECTIVES: We aimed to demonstrate a benefit of teaching back extension exercises in addition to usual GP care for acute low back pain. METHODS: Patients with acute simple low back pain of less than 28 days duration, presenting to a GP, were randomized either to attend a back class or to receive conventional management. Outcome was measured using changes in the Oswestry disability score and visual analogue pain scale (VAS) on six occasions during 1 year and also a VAS and patient assessment of degree of disability during the previous 6 months at 1 year. RESULTS: Seventy-five patients were recruited. The principal outcome measures showed no difference between the two groups. The treatment group reported less chronic disability at 1 year (50% versus 14%, P < 0.007). CONCLUSIONS: A treatment effect has not been demonstrated, but some patients who would otherwise have reported mild pain were pain free after 1 year. This approach to treating back pain has not been shown to be effective. More much larger studies, with more intensive treatment, are required in order to decide whether physical therapy in primary care is beneficial as treatment for acute back pain.

Acute Disease↗
PubMed1998

Validation of air as an equilibration medium in gastric tonometry: an in vitro evaluation of two techniques for measuring air PCO2.

This laboratory-based bench study was undertaken to evaluate the accuracy and equilibration characteristics of air and saline respectively as CO2 equilibrating media in the silicone balloon of a gastric tonometer and to compare two methods of measuring air PCO2. Two gastric tonometers were suspended in a bath containing 0.9% saline maintained at 37 degrees C. Certified calibration gases at three different CO2 concentrations were bubbled into the bath. When the bath PCO2 measurement was stable the tonometers were primed with 5 ml of air and 2.5 ml normal saline respectively and allowed to equilibrate for 30 and 90 minutes. Following equilibration, samples were aspirated and analysed in duplicate in a blood gas analyser. Bias and precision were calculated from the measured and expected PCO2 values. A consistent negative bias (21-23%) was seen with air at all three CO2 concentrations at 30 and 90 minutes with a coefficient of variation between 2.7 and 3.3%. Imprecise data were obtained with saline at different levels of CO2. A similar experimental set-up was used to compare air PCO2 measurement by a blood gas analyser and an infra-red analyser (Tonocap). Similar bias was obtained with the blood gas analyser with respect to air PCO2 measurement as in experiment 1. The infra-red analyser measurement was highly precise with negligible bias. Air appears to be a better CO2 equilibration medium during bench testing of tonometry producing a systematic negative offset and requiring a uniform correction factor of 1.25. This correction factor is independent of equilibration time and equilibrating CO2 concentration. The use of the infra-red analyser eliminates any bias in the measurement of air PCO2 and obviates the need for a correction factor.

Air↗
PubMed1998

Constitutional WT1 mutations in Wilms' tumor patients.

PURPOSE: Patients with Wilms' tumors (WT) who carry constitutional mutations in the WT1 gene have been described in case reports and small case series. We sought to determine the frequency of constitutional WT1 mutations in a larger cohort, and to identify clinical manifestations associated with the risk for carrying a WT1 mutation. METHODS: We collected clinical data and blood samples from 201 patients with a history of WT. Southern blot analysis, single-strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing were performed on DNA isolated from peripheral-blood lymphocytes from each patient. Odds ratios (ORs) for the carriage of a germline mutation of the WT1 gene were calculated for patients who had specific clinical risk factors compared with those who did not. RESULTS: Of 201 patients with WT in the cohort, eight patients were carriers of mutations in the WT1 gene. Six of the eight mutations were protein-truncating nonsense mutations. None of 56 patients with isolated unilateral WT was a carrier. The OR of carrying a WT1 mutation was elevated for patients with genitourinary anomalies (OR19.3; P < .002). Seven of 28 boys with WT with cryptorchidism carried WT1 mutations. No increased risk was observed for patients with nephrogenic rests, bilateral tumors, history of secondary cancers, or family history of WT. CONCLUSION: Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias. Patients with WT and no genitourinary anomalies are at low risk for carrying a WT1 mutation. Constitutional WT1 mutations that encode truncated WT1 proteins may predispose to the development of cryptorchidism, hypospadias, and WTs.

Adolescent↗
PubMed1998

Gestational changes in the levels of transforming growth factor-beta1 (TGFbeta1) and TGFbeta receptor types I and II in the human myometrium.

As term approaches, a number of key proteins [contraction-associated proteins (CAPs)] are expressed within the human myometrium that are essential for the activation of powerful coordinated contractions during labor. The nature of the signals that switch on the synthesis of CAPs in vivo is not known. The ryanodine-sensitive intracellular Ca2+ release channel (RyR2) is a CAP whose expression in vitro is activated by transforming growth factor-beta (TGFbeta). The present experiments were performed to determine whether TGFbeta and TGFbeta receptors are present in the human myometrium at term and to explore the idea that they might form part of a signaling system in vivo. TGFbeta receptor types I and II, but not III, were demonstrated in myometrial smooth muscle in tissue taken from nonpregnant, pregnant nonlaboring, and spontaneous laboring women. Western blotting was used subsequently to determine the relative expression of TGFbeta receptor types I and II. Using nonpregnant myometrium as a baseline control the levels of expression of receptor types I and II were significantly increased by 168 +/- 19% (n = 6) and 162 +/- 22% (n = 7) in pregnant nonlaboring myometrium. In spontaneous laboring myometrium the levels of TGFbeta receptor type I and II expression were 93 +/- 12% (n = 6) and 85 +/- 11% (n = 7), respectively, compared to nonpregnant control values and were significantly lower than levels in pregnant nonlaboring tissues. The total TGFbeta1 levels in the myometrial tissues were 334 +/- 10, 534 +/- 73, and 674 +/- 106 pg/g tissue wet wt in nonpregnant, pregnant nonlaboring, and spontaneous laboring myometrium (n = 3 in each group), respectively. Thus, the TGFbeta signaling system appears to be up-regulated in the myometrium before the onset of parturition. The apparent loss of receptors in the spontaneous laboring samples in the presence of elevated total levels of TGFbeta may be indicative of agonist-induced receptor down-regulation. These observations support the idea that cytokines, in particular TGFbeta1, may play a role in the normal processes that prepare the myometrium for parturition at term.

Blotting, Western↗
PubMed1998

GRP78 induction by calcium ionophore potentiates photodynamic therapy using the mitochondrial targeting dye victoria blue BO.

The cationic photosensitizing triaryl methane dye Victoria Blue BO (VBBO) localizes in mitochondria and causes oxidative damage to this organelle during photodynamic therapy (PDT). Oxidative stresses from other photosensitizers induce a variety of stress proteins. The endoplasmic reticulum (ER)-based, calcium-binding stress protein GRP78 is a putative protective factor for photosensitizers such as Photofrin that damage multiple intracellular sites and for several cytotoxic agents. In the current study VBBO-PDT was found to induce glucose-regulated protein (GRP)78. However, in contrast to other drugs, rather than being protected, human squamous carcinoma cells (FaDu) induced to express GRP78 by calcium ionophore A23187 became more sensitive to PDT. A line of Chinese hamster ovary cells (C-1) constitutively overexpressing GRP78 also were more sensitive. Cytotoxicity of the A23187 treatment and VBBO was synergistic, with more than 11-fold potentiation with light irradiation, but was only additive in the dark. The increased cell killing was not due to differences in VBBO uptake or to changes in the intracellular localization of VBBO caused by calcium ionophore or GRP78. Thus, GRP78 appears to enhance rather than protect against VBBO-induced mitochondrial photodamage and contributes to cell death. This novel finding possibly may stem from the effects of GRP78, ER Ca2+ stores and ATP consumption on the Ca2+ and ATP-dependent mitochondrial permeability transition that may be evoked by PDT damage to the mitochondrial respiratory chain. The work suggests interventions that may potentiate PDT with mitochondrial targeting sensitizers and potential enhancements in efficacy when GRP78 is upregulated biologically or pharmacologically.

Animals↗
PubMed1998

Early undifferentiated connective tissue disease. V. An inception cohort 5 years later: disease remissions and changes in diagnoses in well established and undifferentiated connective tissue diseases.

OBJECTIVE: To review the diagnoses after 5 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD); to examine death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients was identified in 10 academic rheumatology practices. They had less than one year of signs and/or symptoms of CTD. Diagnoses of specific well established CTD were made using accepted diagnostic and classification criteria. The diagnoses after 5 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The progression of unexplained polyarthritis to rheumatoid arthritis occurred infrequently. Ten percent of patients with isolated Raynaud's phenomenon progressed to systemic sclerosis (SSc). The 5 year survival was over 90% in all diagnostic categories, with the exception of SSc, in which it was 64%. CONCLUSION: Patients with a well established CTD usually continued with the same diagnosis. Patients with undifferentiated CTD tended to remain undifferentiated or to remit.

Arthritis↗
PubMed1998

Characterization of endogenous protoporphyrin IX induced by delta-aminolevulinic acid in resting and activated peripheral blood lymphocytes by four-color flow cytometry.

Lymphocytes treated with delta-aminolevulinic acid (ALA) can accumulate the photoactive, fluorescent heme precursor, protoporphyrin IX (PpIX). With visible light illumination, PpIX can be used in photodynamic therapy (ALA-PDT) to kill or functionally alter cells. The aim of this study was to characterize the effects of ALA and ALA-PDT on resting and activated human peripheral blood T lymphocytes. Accumulation of PpIX depends inversely on the rate of its iron-dependent conversion into heme. Activated replicating lymphocytes have low intracellular iron levels, with corresponding increases in the transferrin receptor (CD71). Thus, we expected activated lymphocytes would preferentially accumulate PpIX. Using four-color flow cytometry, we examined ALA-induced PpIX levels in T-cell subsets of resting and activated human peripheral blood mononuclear cells and the relationship between CD71 and PpIX. Peripheral blood mononuclear cells stimulated by phytohemagglutinin (PHA) were simultaneously phenotyped for PpIX, CD71 and the T-cell markers CD3 and CD4 or CD8. In activated cells treated with 0-6 mM ALA for 4 h, PpIX fluorescence was maximal at 1 mM ALA. On a single cell basis, there was a strong correlation between PpIX accumulation and CD71 expression. The ALA-treated, PHA-stimulated, CD71+ lymphocytes had an eight-fold greater mean PpIX fluorescence than nonactivated, CD71- cells. Approximately 87% of the CD4+ and 85% of the CD8+ T cells accumulated PpIX. The PpIX levels of CD8+ cells were about 5% greater than CD4+ cells. In addition, mixed lymphocyte reaction-stimulated cells treated with ALA accumulated more PpIX than controls. Thus, activated cells preferentially accumulate endogenous PpIX when exogenous ALA is administered. Cytotoxicity studies showed that the majority of the activated cells following ALA-PDT were killed but resting cells were spared. Also, in examining activation markers by flow cytometry the number of cells that were positive for activation markers CD38 or CD71 dramatically decreased after ALA and light treatment in activated populations. The data suggest a role for ALA-PDT as an immunomodulator or photocytotoxic agent targeting activated lymphocytes.

Aminolevulinic Acid↗
PubMed1998

Analysis of anti-Trypanosoma cruzi antibody isotype specificities by western blot in sera from patients with different forms of Chagas' disease.

Infection of humans with Trypanosoma cruzi leads to either a lifelong asymptomatic infection or to symptomatic presentations such as cardiomyopathy, mega-syndromes, or both. The reasons for the different clinical manifestations are not understood. We have previously studied a group of chronically infected individuals with different clinical forms of Chagas' disease and found that the levels of some anti-T. cruzi antibody isotypes, analyzed by enzyme-linked immunosorbent assay, differed among patients with different clinical presentations. We have expanded these studies to examine the antigen specificity of these patients' IgG1, 2, 3, IgM, and IgA by western blot. We observed that binding of particular antigens by some antibody isotypes were more prevalent in some clinical groups as compared to others. For example, IgG3 from 13 of 19 (68%) individuals with digestive manifestations bound a 68-kDa antigen, but only 3 of 31 (9%) individuals with cardiac involvement detected this same moiety. We also found that, regardless of the clinical group, the profiles of antigens recognized by each antibody isotype differs dramatically from the profiles recognized by each other isotype. Together with our previous observations demonstrating that the levels of anti-parasite antibody isotypes correlates with the clinical form, these data suggest that overall anti-T. cruzi antibody reactivities may indeed be skewed toward different antigens in individuals with different clinical presentations.

Adult↗