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M Kaplan

Publications and source records attributed to M Kaplan.

At least 109 records · Page 6Linked to original sources
PubMed1998

Unconjugated and conjugated bilirubin pigments during perinatal development. V. Effect of phototherapy on serum conjugated bilirubin in hyperbilirubinemic neonates.

OBJECTIVE: To determine the effect of phototherapy on serum conjugated bilirubin fractions, an index of bilirubin conjugation, in hyperbilirubinemic neonates. METHOD: Serum was sampled from 21 jaundiced (serum diazo total bilirubin > or = 274 micromol/l), term, otherwise healthy neonates prior to starting phototherapy, and 24 h after the commencement of treatment. Alkaline methanolysis followed by reverse-phase, high-performance liquid chromatography, specific for determination of unconjugated bilirubin and the monoconjugated and diconjugated fractions of total conjugated bilirubin in serum, was used for the analysis. Prephototherapy values were compared to those at 24 h. RESULTS: Serum total bilirubin and total conjugated bilirubin values decreased during the study period, from 220 (211-239) to 177 (157-213) micromol/l (median (25-75% range)) p = 0.001, for the former, and from 1.4 (0.87-1.57) to 0.93 (0.69-1.84) micromol/l, p = 0.005, for the latter. These parameters decreased by a similar percentage (-16.6+/-14.8% and - 14.0+/-23.4%, respectively; p > 0.05). Both monoconjugated and diconjugated bilirubin, calculated as a percentage of total conjugated bilirubin, remained constant over the study period (88.2 (72.2-96.4)% before phototherapy and 92.5 (87.3-96.8)% after 24 h, p > 0.05, for monoconjugated bilirubin, and 11.8 (3.6-27.8)% and 7.5 (3.2-12.7)%, respectively, p > 0.05, for diconjugated bilirubin). CONCLUSIONS: Serum total conjugated bilirubin values decreased in parallel to serum total bilirubin levels during phototherapy, maintaining a constant relationship between these two parameters. The ratios of monoconjugated and diconjugated bilirubin to total conjugated bilirubin remained constant. These findings imply that phototherapy does not alter bilirubin conjugation in hyperbilirubinemic neonates.

Bilirubin↗
PubMed1998

HHV-6 infection in HIV-infected asymptomatic and AIDS patients.

In order to investigate the levels of HHV-6 infection and elevated antibodies to HHV-6 in HIV-1-infected asymptomatic and symptomatic patients, peripheral blood mononuclear cells were (PBMC) cultured. As patients progressed from asymptomatic HIV infection to AIDS, there was a concurrent increase in replicating HHV-6. Plasma obtained from several of these patients showed the presence of IgM antibody and a significantly elevated level of HHV-6 IgG antibody. Serial samples of plasma from 10 AIDS patients collected over a period of 4 years were assayed for the detection of HHV-6 core protein (gp116/64/54) by antigen capture ELISA. The results demonstrated that either a persistent infection or reactivation can occur based on the degree of fluctuation in HHV-6 antigen detected. ELISA to HHV-6 purified viral proteins, i.e., early (p41/38) and late (gp110), demonstrated that IgG antibody to gp110 did not differentiate between HIV-1-infected and healthy donors. IgG and IgM antibody to p41/38, however, showed a significantly higher prevalence in HIV-1-infected individuals (56.7-85.3%) than in normal healthy donors (19.0%), suggesting virus activation. PBMC culture from the AIDS patients expressing significant peaks of HHV-6 core antigen (gp116/64/54) in their plasma showed that in most cases, HHV-6 early and late antigens were detectable; however, those patients with consistently low antigen peaks had no detectable antigens in their PBMC. Only 55% of PBMC cultures established from IgM antibody-positive HIV-1-infected asymptomatic and AIDS patients expressed HHV-6 antigens in the short-term cultures, but HHV-6 antigens could not be demonstrated in PBMC culture from 4 IgM-antibody-positive healthy donors. HHV-6 isolates obtained from the HIV-1-positive patients were predominantly HHV-6 variant A, compared to healthy donors. Based on the data presented here, it is evident that the levels of HHV-6 infection increased in HIV-1-infected asymptomatic individuals as they progressed to AIDS. Our immunovirological data on HHV-6-infected individuals with HIV infection support a role for HHV-6 in the pathogenesis of AIDS. We believe that simultaneous active infection with HIV-1 and HHV-6 may contribute to enhanced immune suppression perhaps leading to disease manifestations.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Role of macrophage glycosaminoglycans in the cellular catabolism of oxidized LDL by macrophages.

Macrophage binding sites for oxidized LDL (Ox-LDL) include class A scavenger receptors (SR-As), the CD-36 molecule, and an additional but hitherto unidentified binding site. Because cell-surface glycosaminoglycans (GAGs) were previously shown to be involved in the cellular uptake of native LDL and lipoprotein(a), several strategies to assess the participation of heparan sulfate (HS) and chondroitin sulfate (CS) in macrophage catabolism of Ox-LDL were used. First, incubation of J-774 A.1 macrophage-like cells with either heparinase or chondroitinase, or with both enzymes together, reduced the binding, uptake, and degradation of 125I-Ox-LDL by 20% to 45%, in comparison with control nontreated cells, while catabolism of 125I-labeled acetylated LDL (Ac-LDL) and native LDL were unaffected. Second, the proteoglycan (PG) cellular content was increased by cell enrichment with exogenous GAGs or by using human monocyte-derived macrophages from two patients with Sanfilippo mucopolysaccharidosis, which are characterized by cellular HS accumulation. In these macrophages, cellular uptake of 125I-Ox-LDL increased, while catabolism of 125I-Ac-LDL and native LDL were unaffected. Experiments using conditioned media from control, heparinase-digested, or chondroitinase-digested macrophages indicated that neither secreted GAGs nor released digestion products played any role in Ox-LDL catabolism. To evaluate potential interactions between cell-surface GAGs and known receptors for Ox-LDL, we used excess unlabeled Ac-LDL to block SR-As or anti-CD-36 antibodies to block CD-36, and then examined the catabolism of 125I-Ox-LDL by GAG-enriched or -depleted macrophages. Both excess unlabeled Ac-LDL and anti-CD-36 antibodies reduced 125I-Ox-LDL catabolism, but only excess unlabeled Ac-LDL completely abolished the increase in 125I-Ox-LDL catabolism on GAG enrichment of the cells, indicating a cooperation between exogenous GAGs and cell-surface SR-As in the catabolism of OX-LDL. Moreover, the addition of GAGases to macrophages that were preincubated with anti-CD-36 antibodies and excess Ac-LDL further reduced macrophage degradation of Ox-LDL in comparison with cells that were pretreated only with anti-CD-36 antibodies and Ac-LDL, indicating a more complex role for endogenous GAGs. Overall, these studies demonstrate a substantial contribution of macrophage-associated GAGs in the catabolism of Ox-LDL, which is mediated in part by a cooperation between GAGs and cell-surface SR-As.

Acetylation↗
PubMed1998

Human Herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report.

We examined cerebral spinal fluid (CSF) from multiple sclerosis (MS) patients and patients with other neurological diseases (OND) for antibody specific for Human Herpesvirus-6 (HHV-6) and for HHV-6 DNA detectable by PCR. CSF from MS patients had a higher frequency of IgG antibody to HHV-6 late antigens (39.4%) compared with CSF from OND (7.4%). In contrast, the frequency of detectable IgG antibody in CSF from MS patients specific for Epstein-Barr Virus (EBV) (12.1%) and Human Cytomegalovirus (HCMV) (6.1%) was much lower. Two of 12 MS CSFs (16.7%) also contained HHV-6 DNA detected by PCR. None of four OND CSF were positive for HHV-6 DNA. Plasma from 16 patients with MS, eight with OND and 72 healthy donors were tested for antibodies by ELISA to HHV-6 early (p41/38) and late (gp110) proteins. Although no differences in anti-gp110 IgG antibody were detected between MS patients, patients with other neurological diseases, and normals, IgG antibody to early protein p41/38 was detected in > 68% of the plasma from MS patients, 12.5% from OND patients and 27.8% of the controls. IgM antibody to p41/38 was present in > 56% of MS patients, 12.5% of OND patients, and 19% of controls. These data suggest that more than half of the MS patients had active, ongoing HHV-6 infections. HHV-6 was also isolated from peripheral blood mononuclear cells (PBMC) from 3/5 MS patients who were in relapse or had progressive disease and was identified as HHV-6 Variant B. These preliminary results support the hypothesis that HHV-6 may be a co-factor in the pathogenesis of some cases of MS.

Antibodies, Viral↗
PubMed1998

Bilirubin conjugation, reflected by conjugated bilirubin fractions, in glucose-6-phosphate dehydrogenase-deficient neonates: a determining factor in the pathogenesis of hyperbilirubinemia.

BACKGROUND AND OBJECTIVE: Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, which in severe cases may cause kernicterus and death. Because G-6-PD-deficient individuals frequently undergo acute, trigger-induced hemolytic episodes, increased hemolysis has frequently been implied in the pathogenesis of this neonatal hyperbilirubinemia. However, in Sephardic Jewish G-6-PD-deficient neonates, the rate of hemolysis, reflected by blood carboxyhemoglobin values corrected for inspired carbon monoxide, has been shown to be elevated, not only in those who developed hyperbilirubinemia, but also, to a similar extent, in those who remained only moderately jaundiced. Because at any point, serum total bilirubin values reflect a balance between bilirubin production on the one hand and bilirubin conjugation and elimination on the other, we suspected bilirubin conjugation to be a key factor in the pathogenesis of the hyperbilirubinemia. Physiologically, a fraction of conjugated bilirubin refluxes from the hepatocyte to the serum, and accurate determination of serum conjugated bilirubin fractions can be used to mirror intrahepatocytic bilirubin. Using this principle, we previously demonstrated a decreased diconjugated bilirubin fraction in hyperbilirubinemic G-6-PD-deficient neonates compared with hyperbilirubinemic G-6-PD-normal controls, suggesting diminished bilirubin conjugation. This conjugated bilirubin pattern probably reflects the recently described interaction between G-6-PD deficiency and the variant promoter for the gene encoding the bilirubin conjugating enzyme UDP glucuronosyltransferase, as seen in Gilbert's syndrome. Therefore, we postulated that efficiency of bilirubin conjugation is a crucial factor in the development of hyperbilirubinemia in G-6-PD-deficient neonates. We hypothesized that those G-6-PD-deficient neonates who develop hyperbilirubinemia would have decreased bilirubin conjugation ability, whereas those with a more efficient conjugating system would have a lesser degree of bilirubinemia. METHODS: Term, healthy, male, G-6-PD-deficient neonates with no other obvious predisposing cause for hyperbilirubinemia were selected at random when their serum diazo total bilirubin values ranged from 171 to 254 micromol/L (10-14.9 mg/dL). At this point, simultaneous with the diazo bilirubin determination, serum was collected and frozen for high-performance liquid chromatography (HPLC) measurement of serum bilirubin fractions. The infants were followed clinically and with serum diazo bilirubin determinations until they either did not exceed a serum diazo bilirubin value of 254 micromol/L (14.9 mg/dL) (nonhyperbilirubinemic) or until bilirubin values rose above this level (hyperbilirubinemic), by a process of self-selection. A method of alkaline methanolysis, followed by reverse-phase HPLC, was used to measure unconjugated bilirubin and the mono- and diconjugated fractions of serum conjugated bilirubin. Total HPLC bilirubin and total conjugated bilirubin values were calculated from these measured bilirubin fractions. Patients also were classified according to the serum total conjugated bilirubin value as low bilirubin conjugators (serum total conjugated bilirubin less than median) or as high bilirubin conjugators (serum total conjugated bilirubin greater than median). The data were analyzed by comparing serum conjugated bilirubin fractions between the hyperbilirubinemic and nonhyperbilirubinemic groups and the risk of developing hyperbilirubinemia in the low bilirubin conjugators, relative to that of the high bilirubin conjugators. RESULTS: Neonates were sampled at 53 +/- 12 and 58 +/- 12 hours for the subsequently hyperbilirubinemic and nonhyperbilirubinemic groups, respectively (NS). Initial (ie, at the time of sampling) serum total diazo bilirubin values (mean +/- SD) were almost identical for the subsequently hyperbilirubinemic and nonhyperbilirubinemic groups (214 +/

Bilirubin↗
PubMed1998

Indomethacin tocolysis increases postnatal patent ductus arteriosus severity.

UNLABELLED: Postnatally, therapeutic indomethacin administration is usually effective in mediating patent ductus arteriosus (PDA) constriction in premature infants. There are infants, however, who remain resistant to indomethacin and require more aggressive surgical intervention to facilitate ductal closure. Indomethacin tocolysis has been reported to increase the incidence of persistent PDA in premature infants. It was our impression that infants exposed to antenatal indomethacin not only suffered from an increased incidence of PDA, but that they were more symptomatic from PDA and that for them, PDA was more resistant to medical closure. It is this observation that we sought to examine in this study. METHODS: Medical records of all mothers and premature neonates with birth weight </=1500 g, admitted to the neonatal intensive care unit of the Shaare Zedek Medical Center during 1996 and 1997, who survived for at least 1 week, were reviewed retrospectively. Data on maternal indomethacin and steroid exposure, birth weight and gestational age, and ductus status and treatment were analyzed. In our obstetrics department, indomethacin is the medication of choice to inhibit premature labor. Mothers who arrive in premature labor are started on indomethacin therapy, if delivery is not imminent. All infants </=1500 g were studied by a pediatric cardiologist between 24 and 72 hours of life using two-dimensional echocardiography with color flow mapping to assess ductal patency. Decisions to treat were based on echocardiographic evidence of PDA, along with any of the following clinical signs: bounding pulses, diastolic pressure of </=25 mm Hg, pulmonary plethora and/or cardiomegaly on chest x-ray, or increasing oxygen requirement with no other explanation. Initial treatment is with indomethacin, if there are no contraindications. Our general approach is to begin therapy with a continuous indomethacin infusion, followed by a course of bolus indomethacin if the infant does not respond. However, each attending neonatologist may treat according to his/her preference (ie, bolus vs continuous). All infants with PDA are followed with serial echocardiographic examinations until the ductus is closed. RESULTS: A total of 105 premature infants met the above criteria. Thirty-six of these 105 infants had echocardiographic signs of a PDA (34.3%). Those with PDA were less mature (gestational age, 28.9 +/- 2.6 vs 30.3 +/- 2.6 weeks, respectively) and tended to be smaller (1060 +/- 270 vs 1166 +/- 261 g). Of the 36 infants with PDA, 15 (42%) resolved spontaneously and 21 (58%) were symptomatic and required treatment with indomethacin. There were no differences in gestational age or birth weight between infants whose PDA resolved spontaneously and those requiring indomethacin therapy. Four of the 21 (19%) treated infants remained unresponsive to indomethacin and required ductal ligation. Of 17 infants with PDA who responded to indomethacin therapy, 1 (6%) was treated with a single course of bolus indomethacin, to which he responded, and 16 (94%) were treated with continuous indomethacin and responded promptly. The differences in therapeutic responsiveness to initial treatment with continuous vs bolus indomethacin were not significant. Of the 105 infants, 29 were exposed to indomethacin tocolysis. Those who were exposed to antenatal indomethacin and those who were not were well-matched with respect to birth weight and gestational age. Fifteen (52%) of the 29 exposed infants versus 18 (24%) of the 76 infants not exposed to antenatal indomethacin developed a PDA postnatally (relative risk = 2.1; 95% confidence interval: 1.22-3.74), and 45% of the antenatally exposed infants versus 12% of the nonexposed infants were symptomatic and required indomethacin (relative risk = 1.9; 95% confidence interval: 1.17-3.20). Four of the exposed infants versus none of the unexposed infants required surgical ligation. (ABSTRACT TRUNCATED)

Ductus Arteriosus, Patent↗
PubMed1998

Severe neonatal hyperbilirubinemia. A potential complication of glucose-6-phosphate dehydrogenase deficiency.

G-6-PD deficiency is frequently associated with neonatal hyperbilirubinemia, which may be severe enough to cause kernicterus and death. Because of its association with acute trigger-induced hemolytic crises, G-6-PD deficiency-associated neonatal hyperbilirubinemia has been labelled as hemolytic in origin. In this article, the authors summarize recent evidence demonstrating that hemolysis cannot in and of itself be responsible for jaundice and that decreased bilirubin elimination plays a major role in its pathogenesis.

Bilirubin↗
PubMed1998

Ischemia and reperfusion injury. The ultimate pathophysiologic paradox.

It seems clear that the abundance of potential treatment options reflects the dearth of proved, effective options. Thus, although we appear to be on the brink of many potentially major breakthroughs in treatment, there currently remains a multitude of unanswered questions and the need for further study. At this point clinical recommendations must be limited to supportive care with moderation: oxygenation without hyperoxia; ventilation without hypocarbia; avoiding extremes of blood pressure, hematocrit, blood glucose, and body temperature. Unfortunately, data from human trials are extremely limited and often poorly controlled. Furthermore, even those few existing human studies have rarely--if ever--dealt with newborns infants (Table 2). In addition, many of the existing studies do not relate to generalized asphyxia but rather to single-organ reperfusion insults. Finally, there is the critical issue of timing. Unfortunately, much of the existing experimental data relate to prophylaxis rather than treatment, severely limiting their potential for clinical applicability. Interventions may have quite different effects when administered at different phases of this most intricate process. Hyperglycemia, for example, may be neuroprotective before an insult but detrimental if induced after an asphyxial episode. Conversely, the NMDA blocker MK-801 can adversely affect outcome when given before a global asphyxial insult but can reduce seizure-related damage when given during the hyperexcitability phase. Insulin-like growth factor is also neuroprotective only when given after an insult, but it is not helpful if given before. An intimate understanding of the pathophysiologic processes involved is essential before any attempts at applying the diverse data derived from numerous animal studies to the human situation in an intelligent manner. Future studies may focus on cocktails of different mixtures of the compounds discussed or on single multipotential drugs, which would make possible a multipronged approach. However, it is essential to investigate fully the potential for toxic drug interactions, as some combinations may be produce serious consequences. For example, Gluckman and Williams evaluated the potential of combining calcium channel blockers with NMDA receptor antagonists in hypoxic-ischemic rats and found that this combination led to rapid cardiovascular collapse. Other enticing approaches for future investigations will probably include some genetic-engineering-related studies in attempt to enhance endogenous antioxidant defenses with regulon stimulation or the administration of neurotrophic growth factors. Unavoidably, the trip from the laboratory to the bedside must of necessity be an arduous and rigorous one.

Animals↗
PubMed1997

Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia.

Severe jaundice leading to kernicterus or death in the newborn is the most devastating consequence of glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G-6-PD) deficiency. We asked whether the TA repeat promoter polymorphism in the gene for uridinediphosphoglucuronate glucuronosyltransferase 1 (EC 2.4.1.17; UDPGT1), associated with benign jaundice in adults (Gilbert syndrome), increases the incidence of neonatal hyperbilirubinemia in G-6-PD deficiency. DNA from term neonates was analyzed for UDPGT1 polymorphism (normal homozygotes, heterozygotes, variant homozygotes), and for G-6-PD Mediterranean deficiency. The variant UDPGT1 promoter allele frequency was similar in G-6-PD-deficient and normal neonates. Thirty (22.9%) G-6-PD deficient neonates developed serum total bilirubin >/= 257 micromol/liter, vs. 22 (9.2%) normals (P = 0.0005). Of those with the normal homozygous UDPGT1 genotype, the incidence of hyperbilirubinemia was similar in G-6-PD-deficients and controls (9.7% and 9.9%). In contrast, in the G-6-PD-deficient neonates, those with the heterozygous or homozygous variant UDPGT1 genotype had a higher incidence of hyperbilirubinemia than corresponding controls (heterozygotes: 31.6% vs. 6.7%, P < 0.0001; variant homozygotes: 50% vs. 14.7%, P = 0.02). Among G-6-PD-deficient infants the incidence of hyperbilirubinemia was greater in those with the heterozygous (31.6%, P = 0.006) or variant homozygous (50%, P = 0.003) UDPGT1 genotype than in normal homozygotes. In contrast, among those normal for G-6-PD, the UDPGT1 polymorphism had no significant effect (heterozygotes: 6.7%; variant homozygotes: 14.7%). Thus, neither G-6-PD deficiency nor the variant UDPGT1 promoter, alone, increased the incidence of hyperbilirubinemia, but both in combination did. This gene interaction may serve as a paradigm of the interaction of benign genetic polymorphisms in the causation of disease.

Cohort Studies↗
PubMed1997

Oxidized LDL binding to a macrophage-secreted extracellular matrix.

Extracellular matrix (ECM), which was shown to be secreted by arterial wall cells, is a major part of the atherosclerotic lesion. ECM can contribute to low density lipoprotein (LDL) retention which can then lead to macrophage foam cell formation, the hallmark of early atherogenesis. The present study demonstrated that in addition to the known ability of endothelial cells and smooth muscle cells to produce ECM, macrophages can also secrete an ECM layer. The macrophage derived ECM was shown to contain the proteoglycans chondroitin sulfate, heparan sulfate and dermatan sulfate. Macrophage derived ECM can bind native LDL, as well as oxidized LDL (3 fold more than native LDL), and this binding is significantly increased in the presence of lipoprotein lipase. Glycosaminoglycans from the ECM (mainly chondroitin sulfate and heparan sulfate) participate in the binding of Ox-LDL to the macrophage derived ECM. These observations suggest that ECM is produced also by macrophages, and it can contribute to a specific and local delivery of atherogenic LDL to macrophages, leading to cellular cholesterol accumulation and foam cell formation.

Extracellular Matrix↗
PubMed1997

Short-range conformational energies, secondary structure propensities, and recognition of correct sequence-structure matches.

A statistical analysis of known structures is made for an assessment of the utility of short-range energy considerations. For each type of amino acid, the potentials governing (1) the torsions and bond angle changes of virtual C alpha-C alpha bonds and (2) the coupling between torsion and bond angle changes are derived. These contribute approximately -2 RT per residue to the stability of native proteins, approximately half of which is due to coupling effects. The torsional potentials for the alpha-helical states of different residues are verified to be strongly correlated with the free-energy change measurements made upon single-site mutations at solvent-exposed regions. Likewise, a satisfactory correlation is shown between the beta-sheet potentials of different amino acids and the scales from free-energy measurements, despite the role of tertiary context in stabilizing beta-sheets. Furthermore, there is excellent agreement between our residue-specific potentials for alpha-helical state and other thermodynamic based scales. Threading experiments performed by using an inverse folding protocol show that 50 of 62 test structures correctly recognize their native sequence on the basis of short-range potentials. The performance is improved to 55, upon simultaneous consideration of short-range potentials and the nonbonded interaction potentials between sequentially distant residues. Interactions between near residues along the primary structure, i.e., the local or short-range interactions, are known to be insufficient, alone, for understanding the tertiary structural preferences of proteins alone. Yet, knowledge of short-range conformational potentials permits rationalizing the secondary structure propensities and aids in the discrimination between correct and incorrect tertiary folds.

Amino Acids↗
PubMed1997

Increased uptake of LDL by oxidized macrophages is the result of an initial enhanced LDL receptor activity and of a further progressive oxidation of LDL.

Iron ions were recently shown to induce cellular lipid peroxidation in macrophages, and these oxidized cells can convert native low-density lipoprotein (LDL) to oxidized LDL (Ox-LDL). The present study demonstrates that deoxycholic acid (DCA) and angiotensin II (ANG-II) can also induce oxidative modification of macrophages via metal ions independent mechanisms. Furthermore, incubation of LDL (200 micrograms of protein/ml) for 24 h at 37 degrees C with DCA, ANG-II, as well as FeSO4-induced oxidized macrophages, resulted in oxidative modification of the lipoprotein as evidenced by increased TBARS formation in LDL (by 50, 105, and 258%, respectively), decreased TNBS reactivity (by 45, 56, and 42%, respectively), and increased cellular uptake (by 60, 166, and 230%, respectively). A positive correlation (n = .88) was found between the extent of the cellular lipid peroxidation and the increment in the cellular uptake of the LDL. The oxidative modification of LDL by oxidized macrophages was found to be a progressive process. Incubation of LDL with oxidized macrophages for increasing periods of time up to 24 h resulted in progressive increment in: (1) the electrophoretic mobility of the LDL; (2) the TBARS formation in LDL; (3) the cellular uptake of LDL by the oxidized macrophages via the Ox-LDL receptor. Upon fractionation on a heparin-sepharose column of LDL that was incubated for different periods of time with oxidized macrophages, a gradual increment in the unbound LDL fraction was obtained, up to 72% after 24 h of incubation. During the first hour of LDL incubation with the oxidized macrophages a twofold increase in the cellular uptake of LDL by these cells was detected, although no significant oxidation of the lipoprotein occurred during this short time period. This effect could be attributed to an increased number of LDL receptors on the cell surface of the oxidized macrophages. In conclusion, increased uptake of LDL by oxidized macrophages results from two routes: (1) enhanced uptake via the LDL receptor due to increased LDL receptor activity; (2) lipoprotein uptake via the Ox-LDL receptors due to cellular modification of LDL. Both of these processes lead to macrophage cholesterol accumulation and foam cell formation, and thus contribute to accelerated atherosclerosis under oxidative stress.

Angiotensin II↗
PubMed1997

Upregulation of human immunodeficiency virus (HIV) replication by CD4 cross-linking in peripheral blood mononuclear cells of HIV-infected adults.

This study was conducted with peripheral blood mononuclear cells from 67 human immunodeficiency virus (HIV)-infected adults. It supports the hypothesis that cross-linking of CD4 molecules by HIV gp120 can result in HIV upregulation and spread of infection. Underlying mechanisms include activation of latent infection by factors in addition to, or other than, tumor necrosis factor alpha.

Adult↗
PubMed1996

Rat eosinophils: isolation and characterization of superoxide production.

Studies with isolated cells are important to the understanding of mechanisms by which eosinophils participate in allergic inflammation. Due to species variability, isolation techniques and cell biology need to be defined for each source. We developed methods to obtain rat eosinophils with purity and viability exceeding 90%, characterized the superoxide anion production of these cells in response to standard activators, and compared these results with those previously obtained in our laboratories with the use of human eosinophils. Rat eosinophils responded vigorously to phorbol myristate acetate and poorly to platelet-activating factor and to N-formyl-methionyl-leucyl-phenylalanine, parallel to the responses of human eosinophils. In contrast, rat eosinophils responded unlike human eosinophils to other activators, having a larger response to calcium ionophore A23187, a smaller response to serum-treated or serum-opsonized zymosan, and a negative rather than positive modulatory effect of cytochalasin B. We conclude that rat eosinophils can be obtained in high purity and with intact responsiveness to a number of different activators.

Animals↗