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Biomedical subjects

A Stern

Publications and source records attributed to A Stern.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alpha-tocopherol modulates tyrosine phosphorylation in human neutrophils by inhibition of protein kinase C activity and activation of tyrosine phosphatases.

Alpha-tocopherol augmentation in human neutrophils was investigated for effects on neutrophil activation and tyrosine phosphorylation of proteins, through its modulation of protein kinase C (PKC) and tyrosine phosphatase activities. Incubation of neutrophils with alpha-tocopherol succinate (TS) resulted in a dose-dependent incorporation into cell membranes, up to 2.5 nmol/2x10(6) cells. A saturating dose of TS (40 micromol/l) inhibited oxidant production by neutrophils stimulated with phorbol myristate acetate (PMA) or opsonized zymosan (OZ) by 86 and 57%, as measured by luminol-amplified chemiluminescence (CL). With PMA, TS inhibited CL generation to a similar extent to staurosporine (10 nmol/l) or genistein (100 micromol/l), and much more than Trolox (40 micromol/l). With OZ, TS inhibited CL to a similar extent to Trolox. Neutrophil PKC activity was inhibited 50% or more by TS or staurosporine. The enzyme activity was unaffected by genistein or Trolox, indicating a specific interaction of alpha-tocopherol. TS or Trolox increased protein tyrosine phosphorylation in resting neutrophils, and as with staurosporine further increased tyrosine phosphorylation in PMA-stimulated neutrophils, while the tyrosine kinase (TK) inhibitor genistein diminished phosphorylation. These effects in resting or PMA-stimulated neutrophils were unrelated to protein tyrosine phosphatase (PTP) activities, which were maintained or increased by TS or Trolox. In OZ-stimulated neutrophils, on the other hand, all four compounds inhibited the increase in tyrosine-phosphorylated proteins. In this case, the effects of pre-incubation with TS or Trolox corresponded with partial inhibition of the marked (85%) decrease in PTP activity induced by OZ. These results indicate that alpha-tocopherol inhibits PMA-activation of human neutrophils by inhibition of PKC activity, and inhibits tyrosine phosphorylation and activation of OZ-stimulated neutrophils also through inhibition of phosphatase inactivation.

Chromans↗
PubMed2001

Worsening of macrophage activation syndrome in a patient with adult onset Still's disease after initiation of etanercept therapy.

The macrophage activation syndrome (MAS) is a rare, potentially fatal, clinical syndrome, which has been described in childhood rheumatic disorders. MAS is defined by a prolonged period of fevers, pancytopenia, and hypertriglyceridemia (with or without hypofibrinogenemia). Histopathological examination of bone marrow, spleen, or lymph nodes shows hemophagocytosis by mononuclear phagocytes. In patients with Still's disease, observed triggering events for MAS have included both infectious processes and pharmacological agents, such as parenteral gold and nonsteroidal anti-inflammatory drugs. We report the case of a young woman with adult-onset Still's disease (AOSD), complicated by an Epstein-Barr virus infection and subsequent MAS, whose course worsened after administration of the soluble tumor necrosis factor-alpha receptor, etanercept. Subsequent treatment with pulse corticosteroids and cyclosporine A induced a dramatic clinical improvement. Treatment data regarding the use of etanercept in AOSD are lacking; given our experience and recent reports in children with Still's disease, we would suggest caution using this agent in patients with AOSD, particularly when complicated by MAS.

Journal Article↗
PubMed2001

Continuous intra-articular patient-controlled analgesia in a cancer patient with a pathological hip fracture. A case report.

Pain management is one of the major goals to achieve in treating terminal patients. Managing severe pain with drug therapy by using a combination of narcotics, non-narcotics, and adjuvant drugs provides the best results for most patients. In patients with fractures due to bone metastases there is a relative indication for operative treatment if the patient is expected to survive the operation and to recover in the postoperative period. In this case report a terminal 48 year-old female with a pathological femoral neck fracture is presented. No operative treatment was offered because of her bad general status. Pain control was maintained by continuous administration of local analgesics directly into the intra-articular femoral space, through a system of patient-controlled analgesia (PCA). The visual-analogue pain scale (VAS), which was maximal before beginning of this treatment, was markedly reduced during the treatment, and was again elevated to maximum after the intra-articular catheter was removed. Although continuous regional analgesia to a fractured bone which involves the joint is not a generally acceptable method and carries some risks it has a role in a selected group of patients.

Analgesia, Patient-Controlled↗
PubMed2001

Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.

Excessive production of hydroxyl radicals in blood and liver has previously been demonstrated by us in rats with obstructive jaundice induced by common bile duct ligation (CBDL). In this study, we demonstrate overproduction of superoxide radicals in circulating blood of CBDL rats by the lucigenin-amplified chemiluminescence technique. To pinpoint the molecular agents that mediate these processes, we measured circulating proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ( IL-1beta), and interleukin-6 (IL-6) in controls and CBDL rats. Concentrations of these cytokines in blood of CBDL rats were markedly elevated when compared to the controls (TNF-alpha: 36.7 +/- 5.0 vs 13.8 +/- 0.5 pg/mL; IL-6: 2,814 +/- 1,740 vs 0 pg/mL; IL-1beta: 11.9 +/- 2.6 vs 0 pg/mL). The overproduction of free radicals triggered by elevated cytokines in CBDL rats was correlated with the activation of NF-kappaB in hepatic tissue. Using the TdT-mediated dUTP nick-end label staining technique, we showed that hepatic tissue sections from CBDL rats had an increase in the apoptotic index (AI). Based on these findings, we propose that the severe hepatic injury in CBDL rats is mediated by a cycle that involves the activation of NF-kappaB by combined action of proinflammatory cytokines and reactive oxygen species (ROS). NF-KB, in turn, initiates the transcription of cytokine genes (eg, IL-6, IL-8, TNF-alpha), which triggers hepatic injury, at least in part, by a free radical-mediated apoptotic mechanism. Elevated ROS may be as a positive-feedback signal that triggers NF-KB reactivation; the severe hepatic injury of CBDL rats may result from perpetuation of this vicious cycle.

Animals↗
PubMed2000

Evolution of quasiparticle charge in the fractional quantum hall regime

The charge of quasiparticles in a fractional quantum Hall (FQH) liquid, tunneling through a partly reflecting constriction with transmission t, was determined via shot noise measurements. In the nu = 1/3 FQH state, a charge smoothly evolving from e(*) = e/3 for t(1/3) congruent with 1 to e(*) = e for t(1/3)<<1 was determined, agreeing with chiral Luttinger liquid theory. In the nu = 2/5 FQH state the quasiparticle charge evolves smoothly from e(*) = e/5 at t(2/5) congruent with 1 to a maximum charge less than e(*) = e/3 at t(2/5)<<1. Thus it appears that quasiparticles with an approximate charge e/5 pass a barrier they see as almost opaque.

Journal Article↗
PubMed2000

Dual instantons

We show how to map the Belavin-Polyakov instantons of the O(3)-nonlinear sigma model to a dual theory where they then appear as nontopological solitons. They are stationary points of the Euclidean action in the dual theory, and moreover, the dual action and the O(3)-nonlinear sigma model action agree on shell.

Journal Article↗
PubMed2000

Enhanced oxidative stress and accelerated cellular senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts.

Glucose-6-phosphate dehydrogenase (G6PD) is involved in the generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and the maintenance of the cellular redox balance. The biological effects of G6PD deficiency in nucleated cells were studied using G6PD-deficient human foreskin fibroblasts (HFF). In contrast to that of normal HFF, the doubling time of G6PD-deficient cells increased readily from population doubling level (PDL) 15 to 63. This was accompanied by a significant increase in the percentage of G(1) cells. The slow-down in growth preceded an early entry of these cells into a nondividing state reminiscent of cellular senescence. These cells exhibited a significant increase in level of senescence-associated beta-galactosidase (SA-beta-gal) staining. The importance of G6PD activity in cell growth was corroborated by the finding that ectopic expression of active G6PD in the deficient cells prevented their growth retardation and early onset of senescence. Mechanistically, the enhanced fluorescence in dichlorofluorescin (H(2)DCF)-stained G6PD-deficient cells suggests the possible involvement of reactive oxygen species in senescence. Taken together, our results show that G6PD deficiency predisposes human fibroblasts to retarded growth and accelerated cellular senescence. Moreover, G6PD-deficient HFF provides a useful model system for delineating the effects of redox alterations on cellular processes.

Cell Cycle↗
PubMed2000

Cellular glucose-6-phosphate dehydrogenase (G6PD) status modulates the effects of nitric oxide (NO) on human foreskin fibroblasts.

Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in cellular redox homeostasis, which is crucial for cell survival. In the present study, we found that G6PD status determines the response of cells exposed to nitric oxide (NO) donor. Treatment with NO donor, sodium nitroprusside (SNP), caused apoptosis in G6PD-deficient human foreskin fibroblasts (HFF1), whereas it was growth stimulatory in the normal counterpart (HFF3). Such effects were abolished by NO scavengers like hemoglobin. Ectopic expression of G6PD in HFF1 cells switched the cellular response to NO from apoptosis to growth stimulation. Experiments with 1H-¿1,2,4ŏxadiazolo¿4, 3-aquinoxalin-1-one and 8-bromo-cGMP showed that the effects of NO on HFF1 and HFF3 cells were independent of cGMP signalling pathway. Intriguingly, trolox prevented the SNP-induced apoptosis in HFF1 cells. These data demonstrate that G6PD plays a critical role in regulation of cell growth and survival.

Apoptosis↗
PubMed2000

Interband scattering and the "Metallic Phase" of two-dimensional holes in GaAs /AlGaAs

The "metallic" characteristics of high density holes in GaAs/AlGaAs heterostructures are attributed to inelastic scattering between the two split heavy hole bands. Landau fan diagrams and weak field magnetoresistance are employed to measure the interband scattering rate. The inelastic rate is found to depend on temperature with an activation energy similar to that characterizing the longitudinal resistance. It is argued that acoustic plasmon mediated Coulomb scattering might be responsible for the Arrhenius dependence on temperature. The absence of standard Coulomb scattering characterized by a power-law dependence upon temperature is pointed out.

Journal Article↗
PubMed2000

MAPK-dependent expression of p21(WAF) and p27(kip1) in PMA-induced differentiation of HL60 cells.

Treatment of HL60 cells with phorbol 12-myristate 13-acetate (PMA) results in growth arrest and differentiation towards the macrophage lineage. PMA-induced changes are easily monitored by morphological changes while cells in suspension start adhering onto substrate. PMA induces rapid activation of the extracellular signal-regulated kinases (ERKs). Activation of the ERK pathway is essential to PMA-induced differentiation of HL60 cells. PMA also induces the expression of the cyclin-dependent kinase inhibitors p21(WAF) and p27(kip1), which is modulated by the use of an inhibitor of the ERK cascade. This implies that a link exists between ERK activation and p21(WAF) and p27(kip1) induction in the process of terminal differentiation.

Cell Cycle Proteins↗
PubMed2000

Differentiation status modulates transcription factor NF-kappaB activity in unstimulated human hepatocellular carcinoma cell lines.

We report herein a novel finding that under an unstimulated condition, a group of four human hepatocellular carcinoma (HCC) cell lines with varying degrees of differentiation, can spontaneously activate NF-KB. The propensity of activation coincided inversely with the differentiation status, with order being SK-Hep-1 > J5 > Hep3B > HepG2. Further studies indicate that this pattern of activation correlates excellently with the descending order of intracellular GSH/GSSG ratios as well as with the ascending order in the ability of these cells to generate hydrogen peroxide. Taken together, our data suggest that differentiation status may play a pivotal role in modulating intracellular thiol redox status and the extent of catalase expression, which may be crucial in the control of NF-kappaB activity in these HCC cells.

Carcinoma, Hepatocellular↗
PubMed2000

Conductivity tensor of striped quantum hall phases

We study the transport properties of pinned striped quantum Hall phases. We show that, under quite general assumptions, the macroscopic conductivity tensor satisfies a semicircle law. In particular, this result is valid for both smectic and nematic stripe phases, independent of the presence of topological and orientational defects such as dislocations and grain boundaries. As a special case, our results explain the experimental validity of a product rule for the dissipative part of the resistivity tensor, which was previously derived by MacDonald and Fisher (cond-mat/9907278) for a perfect stripe structure.

Journal Article↗
PubMed2000

Nitric oxide stimulates tyrosine phosphorylation of focal adhesion kinase, Src kinase, and mitogen-activated protein kinases in murine fibroblasts.

Nitric oxide (NO) can participate in cellular signaling. In this study, monoclonal antibodies against proteins from the growth factor-mediated signalling pathway were used to identify a set of 126-, 56-, 43-, and 40-kDa proteins phosphorylated on tyrosine at NO stimulation of murine fibroblasts overexpressing the human epidermal growth factor receptor. The band corresponding to the 126-kDa protein was FAK. The 56-kDa protein was Src kinase, and the doublet 43- and 40-kDa protein corresponded to the extracellular-regulated MAP kinases (ERK1/ERK2). The effects of NO on focal adhesion complexes were also investigated. FAK was constitutively associated with the adapter protein Grb2 in HER14 cells. Treatment of the cells with the NO donor, sodium nitroprusside, or with EGF did not change this association. We also detected a basal constitutive association of Src kinase with FAK in HER14 cells. In NO-treated cells, this association was stimulated. The doublet 43/40-kDa protein was identical to the ERK1/ERK2 MAP kinases. NO stimulated an increase in ERK1/ERK2 phosphorylation as assessed by a shift in its eletrophoretic mobility and by increased phosphotyrosine immunoreactivity. Furthermore, NO-dependent activation of ERK1/ERK2 depended on the intracellular redox status. Inhibition of glutathione synthesis was necessary to promote activation of the kinases.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Dissipationless transport in low-density bilayer systems

In a bilayer electronic system the layer index may be viewed as the z component of an isospin- 1 / 2. An XY isospin-ordered ferromagnetic phase was observed in quantum Hall systems and is predicted to exist at zero magnetic field at low density. This phase is a superfluid for opposite currents in the two layers. At B = 0 the system is gapless but superfluidity is not destroyed by weak disorder. In the quantum Hall case, weak disorder generates a random gauge field which probably does not destroy superfluidity. Experimental signatures include Coulomb drag and collective mode measurements.

Journal Article↗
PubMed2000

Successful treatment of occupational allergy to bumblebee venom after failure with honeybee venom extract.

BACKGROUND: Immediate-type allergies to bumblebee stings occur infrequently. Previous studies have demonstrated a high degree of cross-reactivity between honeybee venom (HBV) and bumblebee venom (BBV). It has been proposed that venom immunotherapy (VIT) with HBV is a therapeutic alternative for patients with BBV allergy. METHODS AND RESULTS: We present two cases of occupational immediate-type allergies to BBV. Although both nonatopic patients had a negative personal history of previous allergic reactions to honeybee sting, specific IgE antibodies and a positive intradermal reaction to HBV were detected. Despite VIT with HBV, the two developed another severe allergic reaction after incidental bumblebee stings. VIT with BBV, using in one patient a rush protocol and in the other a "conventional" regimen, with escalating doses of 0.01-100 microg of BBV, was performed. Before and during the VIT, the course of IgE and IgG specific antibodies to BBV was analyzed, demonstrating a significant decrease of BBV-IgE and an increase of BBV-IgG. The effectiveness of the treatment was also proven by an in-hospital sting challenge with a live bumblebee. CONCLUSIONS: Our data demonstrate that cross-immunotherapies with HBV do not protect BBV-allergic patients sufficiently. We conclude that BBV-allergic patients should be treated with BBV. A "rush" VIT with BBV is a safe alternative to a "conventional" protocol.

Adult↗
PubMed2000

Inhibition of cell proliferation in HCC-9204 hepatoma cells by a c-myc specific ribozyme.

A ribozyme (RZ) gene targeting c-myc mRNA was synthesized and cloned. Cleavage reaction showed that cleavage of the RZ was efficient and specific. The RZ gene-containing retrovirus vector pDOR-RZ was transfected into HCC-9204 hepatoma cells, which constitutively express high levels of c-myc using Lipofectamine. Positively transfected cells were selected using G418. In situ hybridization showed that both pDOR-RZ and pDOR vectors had been integrated into the chromosome of HCC-9204 cells. Dot blot hybridization indicated that expression of the RZ was only evident in pDOR-RZ-transfected HCC-9204 cells. Avidin-biotin complex enzyme-linked immunosorbent assay showed that c-myc expression was down-regulated. Chromatin aggregation into compact masses, cytoplasmic vacuole degeneration, and blurring of cytoplasm structure were observed by transmission electron microscopy in HCC-9204-RZ cells. These results suggest that the use of a c-myc mRNA cleaving enzyme could be most effective in tumor cells that are highly proliferative and constitutively express high levels of c-myc.

Carcinoma, Hepatocellular↗