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Biomedical subjects

I Roth

Publications and source records attributed to I Roth.

At least 19 recordsLinked to original sources
PubMed2000

Transverse instability of magnetized electron holes

We study a transverse instability of the nonlinear equilibria known as electron phase-space holes in the presence of a magnetic field. The instability is intrinsically two dimensional and is determined by the dynamics of the trapped electrons. It depends on hole amplitudes, ambient magnetic fields, and the perpendicular velocity spread. The long-standing hole stability problem in multiple dimensions can be characterized by the gyro-to-bounce frequency ratio. A low ratio associated with a small perpendicular velocity spread results in a disintegration of the positive potential spikes.

Journal Article↗
PubMed1999

IL-10 is an autocrine inhibitor of human placental cytotrophoblast MMP-9 production and invasion.

During human placentation, fetal cytotrophoblast stem cells differentiate and then invade the uterine wall and its associated spiral arteries. This process anchors the placenta to the uterus and supplies maternal blood to the fetus. Cytotrophoblast invasion in vitro requires the expression of matrix metalloproteinase-9 (MMP-9). Recently, we showed that cytotrophoblasts produce interleukin-10 (IL-10), a potent immunomodulatory cytokine that could have paracrine effects on the maternal immune system. IL-10 synthesis is dramatically downregulated after the first 12 h of culture, while MMP-9 secretion is rapidly upregulated and the cells acquire an invasive phenotype. These observations prompted us to investigate whether IL-10 is an autocrine regulator of cytotrophoblast MMP-9 production. We found that the cells expressed IL-10 receptor mRNA, suggesting that autocrine effects are possible. Adding recombinant IL-10 to cytotrophoblast cultures significantly decreased the cells' MMP-9 expression at both protein and mRNA levels, but did not affect mRNA levels of the tissue inhibitor of metalloproteinase-3. Thus, IL-10 may alter the proteinase/inhibitor balance. IL-10 treatment further caused a net decrease in MMP activity, thereby reducing cytotrophoblast invasiveness. An antibody that neutralized endogenous IL-10 function had the opposite effect in all experiments. Together, these data suggest that IL-10 is an autocrine inhibitor of cytotrophoblast MMP-9 activity and invasiveness.

Cell Differentiation↗
PubMed1996

Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10.

The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus.

Base Sequence↗
PubMed1994

Human cytotrophoblast invasion is up-regulated by epidermal growth factor: evidence that paracrine factors modify this process.

Formation of the human placenta requires a subset of cytotrophoblast stem cells to acquire an invasive phenotype. We examined the effect on cytotrophoblast invasiveness of growth factors that control the differentiation of other cells. Exogenous TGF-beta 1, PDGF-AA, PDGF-BB, and TNF-alpha affected neither cell morphology nor the rate of cytotrophoblast invasion in vitro. In contrast, addition of EGF to first trimester cytotrophoblast cultures produced dramatic changes in morphology and a severalfold increase in invasive capacity. The effects of EGF on later gestation cytotrophoblasts, whose invasive capacity is diminished, were much less pronounced. Next we investigated whether cytotrophoblasts themselves produce ligands that interact with the EGF receptor. A radioimmunoassay and a radioreceptor assay failed to detect EGF receptor ligands in cytotrophoblast-conditioned medium. Likewise, by RT-PCR cytotrophoblasts expressed neither EGF nor TGF-alpha mRNA. In contrast, EGF receptor mRNA was expressed and its protein levels remained constant during the experiment. Immunolocalization using F(ab') fragments of an anti-human EGF antibody failed to detect this growth factor in the chorionic villus. We conclude that maternal ligands that interact with the EGF receptor could play an important role by up-regulating trophoblast invasion, particularly during the early stages of pregnancy.

Becaplermin↗
PubMed1993

The patterns of gene expression in the tomato shoot apical meristem.

In this paper, we describe the synthesis of a cDNA library from the vegetative shoot apical meristem and the analysis of clones selected from it. Using in situ hybridization, we characterized the patterns of expression of these genes in the tomato shoot apical meristem, as well as the patterns obtained from other sources. The results from the analysis of 15 cDNAs indicated the following six main patterns of gene expression in the shoot apical meristem: overall expression, zero expression, expression limited to the epidermis, expression excluded from the epidermis, punctate expression, and expression elevated in the flanks of the meristem. The patterns observed and the nature and number of the genes showing these patterns necessitate a reinterpretation of the models of meristem structure and function. In particular, the data suggest a compartmentation within the shoot apical meristem based on the spatial expression of particular subsets of genes. This paper also reports on the specific and precise criteria essential for the correct identification of meristem-specific gene expression. The data give new insight into the molecular organization of the shoot apical meristem and provide the framework for a detailed dissection of the factors controlling this organization.

Amino Acid Sequence↗
PubMed1992

CD59 (homologous restriction factor 20), a plasma membrane protein that protects against complement C5b-9 attack, in human atherosclerotic lesions.

Blood cells express a cell membrane protein, termed homologous restriction factor 20 (HRF20) and identical to CD59, that can inhibit complement C5b-9 insertion into their membranes. In this report, we investigated by immunohistochemistry whether CD59 was present on cells in human atherosclerotic lesions since membranous C5b-9(m) has been found in lesions. Using a monoclonal anti-CD59 antibody, a cellular CD59 staining pattern was apparent in nearly all lesion specimens. CD59 stain co-localised with macrophage (CD14), T lymphocyte (CD7), endothelial cell (anti-factor VIII related antigen) and smooth muscle cell cytoskeletal-specific antigens (anti-alpha actin and muscle myosin). Endothelial cells always exhibited a more intense stain than the other cell types. CD59 antigen was not localised to any one area of the lesions. Usually CD59-positive cells occurred in clusters rather than as randomly spaced individual cells. CD59 did not stain all cells of the lesion and in particular did not appear to stain all smooth muscle cells. Areas of CD59-negative cells were sometimes observed to exhibit a cellular C5b-9 staining pattern. C5b-9 deposits were also observed in CD59-positive regions. Normal saphenous vein stained strongly for CD59 at the endothelial lining and weakly in the media. Capillaries in atherosclerotic intima always stained strongly for CD59. We conclude that HRF20 is constitutively expressed on endothelium and is under regulatory control in smooth muscle cells. Cellular C5b-9 attack in atherosclerotic lesions is therefore most likely to occur on smooth muscle cells.

Actins↗
PubMed1992

The apolipoprotein(a) moiety of lipoprotein(a) interacts with the complement activation fragment iC3b but does not functionally affect C3 activation or degradation.

A previous study has shown that complement component C3 binds to recombinant apolipoprotein(a) (r-apo(a)). In the present report we have investigated the interactions between lipoprotein(a) (Lp(a)), r-apo(a) and C3 in relation to complement activation and degradation. Neither Lp(a) nor r-apo(a) affected complement activation as indicated by sheep and rabbit red blood cell hemolytic assays, and by assessment of the amount of C3a generated in zymosan-activated human serum in the presence or absence of Lp(a). Crossed immunoelectrophoretic analyses indicated that Lp(a) retarded the migration of iC3b in complement-activated serum but had no effects on C3, C3b, C3c or C3dg. Recombinant apo(a) exhibited the same properties as intact Lp(a) indicating that it is the apo(a) portion of Lp(a) that mediates this effect and not the lipid moiety. Low density lipoprotein had no effect on the migration of C3 cleavage fragments. Treatment of Lp(a) or apo(a) with neuraminidase abolished their capacity to alter iC3b migration. SDS-PAGE immunoblotting analysis of C3 activation fragments generated in the presence of Lp(a) demonstrated the usual physiologic C3 cleavage fragments. Rocket intermediate gel immunoelectrophoresis of complement-activated serum demonstrated that Lp(a) did not hinder or accelerate the generation of C3c and C3dg breakdown fragments of iC3b. The results indicate that the apo(a) moiety of Lp(a) alters the migration of iC3b in an electric field but does not affect complement activation or degradation of activated C3. The sialic acid residues on apo(a) are necessary for the apo(a)-iC3b interaction.

Apolipoproteins↗
PubMed1991

Analysis of complement C3 activation products in human atherosclerotic lesions.

Cleavage of the complement C3 protein is essential for complement activation. Saline extracts of human atherosclerotic lesions were examined by various techniques for the presence of C3 cleavage fragments. Crossed intermediate gel immunoelectrophoresis revealed that native C3 was the predominate C3 protein in extracts and that the C3dg fragment was also detected. SDS-PAGE/Western blot analyses of lesion extracts employing monoclonal antibodies directed at C3c and C3dg fragment determinants demonstrated molecular weight bands corresponding to the known molecular weights of all the physiologic C3 cleavage fragments, except C3b which is known to have a short half-life. After C3, the two most common fragments observed were C3c and C3dg. No bands other than those corresponding to known C3 cleavage fragments were observed and control antibody stains were always negative. In some blots bands with a greater molecular mass than C3 were evident, indicating that some of the C3 in lesions may be covalently bound to an activator. We have previously identified a large (100-500 nm) nonapoprotein containing lipid particle (LCA) as a major complement activating structure in human atherosclerotic lesions. Fractionation of lesion extracts by molecular sieve chromatography and sucrose density gradient centrifugation failed to reveal a concordance between LCA and C3 antigens. The results indicate that complement activation, i.e. C3 convertase formation, takes place in human atherosclerotic lesions and that activated C3 is degraded according to normal complement regulatory mechanisms.

Arteries↗
PubMed1985

[Prognosis and indications of corticosteroid treatment of intrathoracic sarcoidosis--conclusions from a prospective study].

Preliminary results of a prospective clinical trial to evaluate the value of corticosteroid therapy of intrathoracic sarcoidosis had demonstrated that there were no differences between treated and untreated patients with regard to the clinical, radiological and functional outcome after several years. In one hundred and seventy two patients we could check the former results by identical tests after a longer follow-up period (mean 8,9 years) and by additional physiological assessments, i.e. Cstat, DLCO, DM, VC, which seem to be more significant for early detection of functional disorders in sarcoidosis. Again the findings showed no significant differences neither between patients treated with prednisolone for 12 or 6 months respectively nor when compared to the untreated group. In conclusion we do not treat patients with asymptomatic intrathoracic sarcoidosis and without extrapulmonary manifestations before the disease shows no regressive course within one year or when a progressive course is observed.

Adult↗
PubMed1977

Corticosteroid therapy of intrathoracic sarcoidosis stages I and II--results of a controlled clinical trial.

It is difficult to evaluate the efficacy of sarcoidosis therapy. There are high rates of spontaneous remission, frequently pushing course and tendency to relapses after treatment. 280 patients with histologically confirmed mediastino-pulmonary sarcoidosis in stage I and II without extrapulmonary manifestations have been admitted until now in a controlled clinical trial. More than 150 of them have been analysed after a follow-up of 3 to 5 years, in 40 cases already to 7 years. The patients have been treated by prednisolone and isoniazide for six and 12 months respectively and compared with a non-treated control group. 6 and 12 months after the start of observation X-ray regression has been more often observed in the treated than in the non-treated patients. However, the results after 3 and 5 years were nearly similar in all groups: improvement in 75% and complete resolution in 60% respectively. It seems to us therefore that prednisolone shows only an effect on the early stage of sarcoidosis but is without any influence on the late X-ray results. In consequence corticosteroid therapy is clearly indicated only in patients with progressive course of the disease.

Adrenal Cortex Hormones↗
PubMed1975

Determination of total insulin (TIRI) in plasma of insulin-treated diabetics and newborn infants of insulin-treated diabetic mothers.

Plasma of insulin-treated diabetics and of newborn infants of insulin-treated diabetic mothers contains insulin antibodies which invalidates the radioimmunoassay of insulin. Therefore, the endogenous insulin antibody complex must be splitted at a pH lower than 5 and the total IRI (TIRI) is separated by ethanol extraction. It was investigated the recovery rate in dependence upon plasma volume used for extraction. By reduction of used plasma volume from 500 to 200 mul per extraction the recovery rate was increased from 65.1 +/- 8.4 to 88.3 +/- 4.2% (mean +/- SEM). The low plasma volume of 200 mul for TIRI extraction made it possible to determine TIRI during glucose loads of newborn infants. To eliminate different conditions of incubation for standard and unknown plasma samples the TIRI levels were computed by means of so-called "extracted" standard curve, obtained with extracted insulin from standard insulin dilution in insulin-free pooled human plasma. Using the described method a temporary regeneration of insulin secretion of a newly diagnosed juvenile diabetic after insulin treatment could be shown. In contrast to newborn infants of healthy mothers a biphasic/insulin release was found during the intravenous glucose loads in newborn infants of insulin-treated diabetic mothers.

Adult↗
PubMed1975

[Erster Bericht über eine kontrollierte klinische Untersuchung zur Prednisolon-Behandlung der thorakalen Sarkoidose].

117 patients with histologically confirmed mediastino-pulmonary sarcoidosis stage I and II without extrapulmonary manifestations were included in a controlled therapeutic trial. 92 patients remained for analysis. Among these 54 were treated for 6 or 12 months with prednisolone and isoniacid; 38 were not treated. 6 and 12 months after beginning the observation, improvement was more frequent in the treated group. After 3 years and 5 years (45 patients only) however differences were no more evident: improvement was observed in about 80 per cent, complete remission in about 65 per cent in treated and untreated patients. In both groups, patients presenting dissemination in the lungs had worse results than those with hilo-mediastinal adenopathy associated or not with pulmonary dissemination. Prednisolone seems to have effects in the early phase of sarcoidosis but is apparently not so effective in respect to the general development of the illness and in preventing pulmonary fibrosis. Therefore strict indication for therapy with corticosteroids of sarcoidosis exist when progressive pulmonary dissemination and/or reduction of pulmonary function is evident.

Adolescent↗