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S Bernasconi

Publications and source records attributed to S Bernasconi.

At least 19 recordsLinked to original sources
PubMed1998

Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line.

Induction of chemokine gene expression from peripheral blood mononuclear cells (PBMCs) stimulated by proinflammatory cytokines plays an important role in both wound repair and response to infectious agents. In the present study, we show that the proinflammatory cytokine interleukin-6 (IL-6) potently induced mRNA expression and secretion of the CC chemokine monocyte chemotactic protein 1 (MCP-1) in PBMCs. In addition, because human immunodeficiency virus (HIV) infection in vivo and in vitro has been shown to dysregulate the production of and/or the response to cytokines, PBMCs from both healthy uninfected and HIV-infected individuals were studied for their constitutive and IL-6-induced expression of MCP-1. No substantial differences were observed between the two groups of individuals. In addition, IL-6 upregulated MCP-1 expression in the promonocytic cell line U937 and in its chronically HIV-infected counterpart, U1. In these cell lines, IL-6 selectively induced MCP-1 and not other chemokines, including regulated upon activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and IL-8. IL-6 induction of MCP-1 was partially inhibited by hydrocortisone in U1 cells. Thus, IL-6 activates PBMCs to secrete MCP-1, a CC chemokine pivotal for monocyte recruitment in tissue and organs in which important inflammatory events occur.

Anti-Inflammatory Agents↗
PubMed1998

IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages.

Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dendritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology, cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation, occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocytosis was mostly mediated via the mannose receptor, as demonstrated by blocking with unlabeled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.

Antigen Presentation↗
PubMed1998

Neurotransmitter-hormonal responses to psychological stress in peripubertal subjects: relationship to aggressive behavior.

The relationship between different degrees of normal aggressiveness (low, medium, high) and neurotransmitter-neuroendocrine responses to the administration of psychologically stressful tests (Mental Arithmetic, Stroop Color Word Interference task, Trial Social Stress test) was examined in thirty male peripubertal junior school adolescents. Plasma concentrations of norepinephrine (NE), epinephrine (EPI), ACTH, cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (T) were measured immediately before the beginning of the tests and at their end, 30 min later. High-normal aggressiveness have been found associated with significantly higher basal concentrations of NE, ACTH, PRL, and T and with a significant increase of GH responses to the stressful stimuli.

Adolescent↗
PubMed1997

MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression.

Monocyte chemotactic protein-1 (MCP-1) interacts with the chemokine receptor CCR2. Two CCR2 cDNAs have been described. Sequence analysis as well as Northern blotting and RNase protection with different probes revealed that the CCR2 gene is expressed in activated natural killer (NK) cells and mononuclear phagocytes as a predominant long transcript (3.4 kb) consisting of CCR2B followed by a novel sequence (X), corresponding to an intron in the genome, and by a CCR2A specific portion. The predominant long transcript is polyadenylated and present in the cytoplasm. We found that bacterial products and cytokines affect CCR2 expression. Interleukin-2 (IL-2) augmented CCR2 mRNA in monocytes and NK cells. The augmented migratory capacity of IL-2-activated versus resting NK cells was associated with increased CCR2 transcript levels. Lipopolysaccharide (LPS) and other microbial agents caused a rapid and drastic reduction of CCR2 mRNA levels. The rate of nuclear transcription of CCR2 was not affected by LPS, whereas the mRNA half life was reduced. These results suggest that regulation of receptor expression, in addition to agonist production, is probably a crucial point in the regulation of the chemokine system. Down-regulation of chemokine receptor expression may play a role in the modulation of HIV infection in macrophages by LPS. Levels of MCP-1 were markedly elevated in the cerebrospinal fluid (CSF) but not in blood of HIV-infected patients with cytomegalovirus (CMV) encephalitis. The CSF levels of MCP-1 in CMV encephalitis were markedly higher than those found in the CSF of HIV-infected patients with or without unrelated neurological diseases. IL-8, the prototype of C-X-C chemokines and RANTES and macrophage inflammatory protein-1 alpha (C-C chemokines) were not substantially increased in the liquor of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurological disorders associated with HIV.

AIDS Dementia Complex↗
PubMed1997

Final height in non-growth hormone deficient children treated with growth hormone. The Italian Multicentre Study Group.

OBJECTIVE: To evaluate the final height of nongrowth hormone deficient (N-GHD) children treated with growth hormone (GH). DESIGN: Multicentre retrospective study. PATIENTS: 71 (54M/17F) N-GHD children (peak GH after pharmacological stimulation > 14-24 mU/l) who had been treated for 4.19 +/- 0.14 years with GH (0.69 +/- 0.02 IU/kg/week). MEASUREMENTS: Height (H) and height velocity (HV) expressed as standard deviation score (SDS) for chronological age (CA) and bone age (BA), BA/CA ratio, and predicted adult height (PAHSDS) were evaluated before and during treatment, and at each pubertal stage. Target height (TH), and final height (FH) were also calculated, and expressed as SDS. RESULTS: In the whole group, HSDS for CA increased significantly after the first year on GH, and remained significantly increased for 4 years. This did not occur to HSDS for BA, owing to a significant increase in BA/CA after the first year of therapy. In addition, this increase coincided with stages 4 and 5 of puberty. HVSDS for CA and BA also increased significantly after the first year of treatment, and remained significantly elevated for 4 years. PAHSDS did not change significantly during treatment. FHSDS (-1.69 +/- 0.07) was similar to PAHSDS (-1.6 +/- 0.12) and target height (THSDS) (-1.46 +/- 0.08). FHSDS was > or = THSDS in 36.6% of the patients, and > or = initial PAHSDS in 34.5%. Male patients were subdivided into 2 groups (A and B). Patients in Group A (n = 26) started treatment at puberty, while group B (n = 28) consisted of subjects who started therapy during prepubertal years. Height, height velocity and predicted adult height showed the same pattern as in the whole group, in each subgroup. BA/CA advanced significantly in group A after the second year on GH and in group B, after at least 3 years of therapy. FHSDS, THSDS, and PAHSDS were similar in both groups (-1. 7 +/- 0.13, -1.29 +/- 0.2 and -1.39 +/- 0.15 in group A and -1.48 +/- 0.11, -1.85 +/- 0.15 and -1.36 +/- 0.12 in group B, respectively). However, in group B (prepubertal), FHSDS was > or = initial PAHSDS in 60% of the patients and > or = THSDS in 40.7%, while in group A (pubertal), FHSDS was > or = initial PAHSDS only in 22.7% of the patients and > or = THSDS in 34.6%. FHSDS was found to be correlated with THSDS, PAHSDS at the onset of treatment, and after 1 year of treatment. The age at the beginning of puberty, and the duration of puberty were appropriate in all groups. CONCLUSIONS: GH treatment was effective in increasing height velocity of short non-GH-deficient children, but final height was not definitely improved with respect to initial predicted adult height.

Adolescent↗
PubMed1997

Triggering of beta 1-integrin chain induces platelet adhesion to cultured endothelium.

We report here that platelets adhere to cultured endothelial cells (EC) on exposure to the integrin beta 1 activating monoclonal antibody (mAb) BV7. The effect of BV7 is exerted mostly on platelets rather than EC. BV7 does not induce platelet aggregation or 5-hydroxytyptamine (5-HT) release and does not increase platelet adhesion to matrix proteins. Another activating beta 1 mAb, Lia1/2, triggers an effect similar to BV7. Blocking antibodies to alpha 2 and beta 1, but not to other integrin chains, are able to inhibit BV7-mediated adhesion. Moreover, the effect of BV7 requires active cellular metabolism and is not inhibited by platelet treatment with aspirin, by the PAF receptor antagonist BN50730, the phosphokinase C inhibitor staurosporin, or by the cAMP or cGMP enhancers prostaglandin E1 and sodium nitroprusside, respectively. Finally, BV7-mediated adhesion was enhanced by the endoperoxide analogue U46619. These data describe a novel mechanism of platelet adhesion to endothelial cells. This adhesion pathway appears to be mediated by alpha 2 beta 1-integrin on platelets and a still-undefined endothelial counter receptor.

Alprostadil↗
PubMed1997

A general strategy for isolation of endothelial cells from murine tissues. Characterization of two endothelial cell lines from the murine lung and subcutaneous sponge implants.

A rapid, reproducible method for the isolation of murine endothelial cells (ECs) has been developed. Murine ECs were highly enriched by collagenase digestion of mechanically minced lung and subcutaneous sponge implants followed by specific selection with rat anti-mouse CD31 (i.e., PECAM-1) monoclonal antibody-coated magnetic beads (Dynabeads). Pure EC populations were isolated from primary cultures by a second cycle of immunomagnetic selection. The cells from the lung were then cloned by a limiting-dilution method to exclude the possibility of nonendothelial cell contamination. Of the 300 cells plated, 29 clones (approximately 10%) were obtained. The clones were positive for CD31 as measured by flow cytometry, and one clone from the lungs (1G11) and the cells from sponge implants (designated as SIECs) were then subjected to subsequent culture in vitro for 40 and 30 passages (up to 5 months), respectively. Characterization was performed on cells between passage 3 and 10. Both cell types formed contact-inhibited monolayers on gelatin and capillary-like "tubes" on Matrigel. However, 1G11 cells exhibited a "cobblestone" morphology, whereas SIECs had a fibroblast-like appearance at confluence. By flow cytometry and enzyme-linked immunosorbent assay, these cells constitutively expressed CD31, VE-cadherin (cadherin-5), CD34, ICAM-1, VCAM-1, and P-selectin. After stimulation with 30 ng/mL of tumor necrosis factor-alpha, the cells became positive for E-selectin (at 4 hours poststimulation) and the expression of ICAM-1, VCAM-1, and P-selectin was upregulated (after 24 hours of stimulation). The presence of VE-cadherin in 1G11 cells and SIECs was confirmed by fluorescence microscopy and Northern blot analysis. The phenotype and morphology of both cell types were stable during 5 months of culture, and there was no evidence of overgrowth by contaminating cells. Taken together, the approach outlined herein may provide a general strategy for the isolation and culture of ECs from a variety of murine tissues. The general strategy outlined here is simple, effective, and flexible, allowing the inclusion of further positive or negative selection steps.

Animals↗
PubMed1997

Corticotropin-releasing hormone (CRH) inhibits steroid biosynthesis by cultured human granulosa-lutein cells in a CRH and interleukin-1 receptor-mediated fashion.

The presence of immunoreactive CRH was recently demonstrated in human ovaries. CRH immunoreactivity was localized by immunohistochemistry in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in large granulosa-derived luteinized cells of developing corpora lutea. Also, CRH and its receptors were identified in Leydig cells of the testis where CRH was shown to inhibit testosterone biosynthesis. To examine the role of CRH in the ovary, we studied its effect on estradiol (E2) and progesterone (P4) release by human granulosa cells obtained from women undergoing in vitro fertilization for male factor infertility or uni- or bilateral tubal impatency. In all subjects, superovulation was induced by treatment with gonadotropins. The effects of graded doses of ovine CRH (10[-11]-10[-6] mol/liter) were evaluated in the conditioned medium obtained after 24 h incubation of the cells. All CRH concentrations employed except for the lowest one (10[-11] mol/liter) caused a significant decrease of media E2 and P4 levels. Maximal inhibition for both E2 and P4 production was obtained by 10[-6] mol/liter CRH concentration, which decreased hormone production by 39% and 34%, respectively. The alpha-helical CRH9-41 antagonist at 10(-6) and 10(-7) mol/liter blocked the suppressive effect of 10(-9) mol/liter CRH on both E2 and P4 secretion, while it had no effect when added to the culture media without CRH. Since interleukin (IL-1)-1 mediates certain actions of CRH on leukocytes, we examined whether the CRH effect on ovarian steroidogenesis was IL-1-mediated. Interleukin-1 receptor antagonist at 10(-7) and 10(-6) mol/liter blocked the inhibitory effects of CRH on E2 and P4 secretion, while it had no effect in the absence of CRH. In conclusion, CRH exerts a CRH- and IL-1 receptor-mediated inhibitory effect on ovarian steroidogenesis and might be actively involved in the still enigmatic processes of follicular atresia and luteolysis.

Adult↗
PubMed1997

Autosomal dominant neurohypophyseal diabetes insipidus associated with a missense mutation encoding Gly23-->Val in neurophysin II.

Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is an inherited disease caused by progressive degeneration of the magnocellular neurons of the hypothalamus leading to decreased ability to produce the hormone arginine vasopressin (AVP). Affected individuals are not symptomatic at birth, but usually develop diabetes insipidus at 1-6 yr of age. The genetic locus of the disease is the AVP-neurophysin II (NPII) gene, and mutations that cause ADNDI have been found in both the signal peptide of the prepro-AVP-NPII precursor and within NPII itself. An affected girl who presented at 9 months of age and her similarly affected younger brother and father were all found to have a novel missense mutation (G1758-->T) encoding the amino acid substitution Gly23-->Val within NPII. The mutation was confirmed by restriction endonuclease analysis. A T1-weighted magnetic resonance imaging of the father's pituitary gland demonstrates an attenuated posterior pituitary bright spot. This mutation may be valuable for developing models of dominantly inherited neurodegeneration, as the early age of onset of symptoms suggests that this mutation may be particularly deleterious to the magnocellular neuron.

Arginine Vasopressin↗
PubMed1997

Spontaneous thyrotropin and cortisol secretion interactions in patients with nonclassical 21-hydroxylase deficiency and control children.

Both exogenous and endogenous hypercortisolism result in reduced TSH secretion and mild hypothyroidism. However, little is known about the relation between endogenous TSH and cortisol secretion under physiological or slightly disturbed conditions. To examine this, we evaluated the pulsatility and circadian rhythmicity and time-cross-correlated the 24-h secretory patterns of cortisol and TSH in eight prepubertal children with nonclassical congenital adrenal hyperplasia (NCCAH) and eight age-matched short normal children. In both groups, TSH and cortisol were secreted in a pulsatile and circadian fashion, with a clear nocturnal TSH surge. Although no difference in mean 24-h TSH levels was observed between the two groups, daytime TSH levels were lower in the NCCAH group than in control children (P < 0.05). The cross-correlation analysis of the 24-h raw data showed that TSH and cortisol were negatively correlated, with a 2.5-h lag time for both groups, with cortisol leading TSH. This correlation might reflect a negative glucocorticoid effect exerted on the hypothalamic-pituitary-thyroid axis under physiological conditions. A significant positive correlation with TSH leading cortisol was observed at 8.5 and 5.5 h lag times for the control and NCCAH groups, respectively. The substantially shorter lag time of this positive correlation in NCCAH children than in controls suggests that in the latter, the nocturnal TSH peak occurs temporally closer to their compromised morning cortisol peak. These data indicate that the hypothalamic-pituitary-adrenal axis has a primarily negative influence on endogenous TSH secretion and that even mild disturbances in cortisol biosynthesis are associated with slight alterations in TSH secretion.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Changes of dimeric inhibin B levels in maternal serum throughout healthy gestation and in women with gestational diseases.

Human placenta expresses subunit messenger RNAs for synthesizing inhibin A and B. Experimental studies have shown an effect of inhibins on placental hormone secretion, but an endocrine function is suggested by the high levels in maternal circulation. Although information is available on the changes of inhibin A in serum of healthy pregnant women, data on inhibin B levels are limited to early gestation. The aim of the present study was to investigate the changes of inhibin B levels in maternal circulation in healthy pregnant women throughout gestation, and to evaluate whether early pregnancy disturbances or gestational diseases are characterized by abnormal inhibin B levels. The protocol included various groups of pregnant women. A longitudinal evaluation of serum inhibin B levels was done at specific intervals (8-12, 13-18, 19-24, 25-28, 29-33, and 34-40 weeks) in the following groups: 1) healthy pregnant women (n = 13); 2) women at risk of hypertension who did not develop hypertension (n = 8); and 3) women with chronic hypertension (n = 13). In women in group 1, a blood sample was also obtained in the postpartum period (12, 24, and 48 h after delivery). Other pregnant women with abnormal bleeding in the first trimester were studied; they were subdivided into women with ongoing pregnancy (n = 12); and women with miscarriage (n = 22); a control group of healthy pregnant women at the same gestational age was also included (n = 18). A final group of women with gestational diseases (n = 34) was included in the study and included women with: 1) pregnancy-induced hypertension (n = 10); 2) preeclampsia (n = 17); and 3) intrauterine fetal growth retardation (n = 7). A group of healthy nonpregnant women (n = 9) was used as controls, and a blood specimen was collected during both the early- to midfollicular and midluteal phases of the menstrual cycle. Serum dimeric inhibin B levels were measured by using a double-antibody enzyme-linked immunoadsorbent assay. Early gestation inhibin B levels were similar to those of nonpregnant controls and showed a significant rise during the third trimester (P < 0.01). The highest maternal serum inhibin B levels were found at term (P < 0.01). Values significantly returned to control levels within 12-48 h (P < 0.01) after placental delivery. Women at risk of hypertension showed a similar gestational-related increase of inhibin B levels during the third trimester, without any significant difference when compared with healthy women. Women with chronic hypertension showed significantly lower levels at term (P < 0.01). Women with pregnancy-induced hypertension or preeclampsia, or who were carrying a fetus with intrauterine growth retardation showed serum inhibin B levels during the third trimester of gestation consistently lower than in control healthy women at the same gestational age (P < 0.001, mean +/- SEM). Maternal serum inhibin B levels in women with early pregnancy bleeding or miscarriage were similar to those of healthy pregnant women at the same gestational age, independent from the outcome of gestation. The present study showed that maternal serum inhibin B levels increase in the last trimester of normal pregnancy, with low levels in women with hypertensive disturbances or intrauterine growth retardation.

Adult↗
PubMed1997

[Conservative therapy in renal carcinoma: follow-up].

Due to the increasing use of sophisticated imaging techniques, up to 30% of diagnosed renal cell carcinoma (RCC) are asymptomatic and diagnosed incidentally. Getting the cue from our personal survey of conservative renal surgery for renal cell carcinoma with a cancer specific survival of 95.5% after a mean follow up of 32.7 months, a review of the literature is illustrated: numerous studies have documented the technical success rate with this approach as well as long term disease free survival, comparable to that obtained by radical nephrectomy, in patients with unilateral, small, low stage tumors and normal opposite kidney. Patient selection is of extreme importance in case of partial resection in the presence of a normal contralateral kidney. The tumor must be < 3-4 cm, solitary, well delineated on CT, without invasion of the perinephric far or pyelocaliceal system (T1 and T2), easily resectable with at least 1 cm of healthy parenchyma. Only well informed patients who agree on a careful follow up after surgery can be candidates for kidney sparing surgery. In case of imperative surgery the follow up must be strict and personified for every single patient. Those patients who underwent a partial nephrectomy in presence of a normal contralateral kidney should be monitored with a conventional follow up monitored in order to detect an eventual local recurrence: 12 monthly ultrasonography and contrast enhanced CT scan alternately every 6 months for the first five years after surgery and then lifelong once a year by echography and/or CT scan.

Adult↗
PubMed1997

Persistent high MR signal of the posterior pituitary gland in central diabetes insipidus.

We describe three cases of central diabetes insipidus, each with a different pathogenesis, in which unexpected hyperintensity of the posterior pituitary gland was seen on T1-weighted MR images obtained at the time of presentation. In the first case (idiopathic), the posterior pituitary signal persisted more than 10 years; in the second case (Langerhans cell histiocytosis), the signal disappeared within 3 months, despite early specific chemotherapy with etoposide; and in the third case (transient), the posterior signal disappeared within 1 year, but it was documented at the time of spontaneous reversal of polyuria and polydipsia.

Adolescent↗
PubMed1996

Stimulating properties of 5-oxo-eicosanoids for human monocytes: synergism with monocyte chemotactic protein-1 and -3.

The newly described products of 5-hydroxyeicosanoid dehydrogenase, 5-oxo-6,8,11,14-eicosatetraenoic acid (ETE) and 5-oxo-15(OH)ETE, induced directional migration and actin polymerization of human monocytes in vitro. At peak concentrations, the two eicosanoids had a chemotactic activity of about 40% of that observed in the presence of an optimal concentration of FMLP and twice the activity elicited by the related eicosanoid 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE). 15-Oxo-ETE showed a very low but detectable chemotactic activity. All of these chemotactic responses were blocked by Bordetella pertussis toxin, but were resistant to LY255283, a leukotriene B4 (LTB4) receptor antagonist. 5-Oxo-ETEs and 5-HETE induced homologous desensitization of chemotactic response, but did not cross-desensitize to other chemotactic agonists (e.g., monocyte chemotactic protein (MCP)-1 and LTB4). 5-Oxo-ETEs increased in a synergistic fashion the monocyte migration to MCP-1 and MCP-3. In the same range of concentrations, 5-oxo-ETE increased MCP-1-induced release of arachidonic acid from labeled monocytes. No synergistic interaction was observed when FMLP was used as chemoattractant. Thus, this study identifies monocytes as cells responsive to 5-oxo-ETEs and shows that monocyte activation by 5-oxo-ETEs occurs through an LTB4 receptor-independent mechanism that associates with pertussis toxin-sensitive G proteins. The synergistic interaction between 5-oxo-ETEs and C-C chemokines, two families of mediators both synthesized by phagocytic cells, may be relevant in vivo for the regulation of monocyte accumulation at sites of allergic and inflammatory reactions.

Actins↗
PubMed1996

IL-1alpha gene-transfected human melanoma cells increase tumor-cell adhesion to endothelial cells and their retention in the lung of nude mice.

The interleukin-1alpha(IL-1) gene was introduced by retroviral gene transfer into the A375P human melanoma cell line. Two hygromycin-resistant colonies, colony 3 and colony 6, which respectively do not and do express and release IL-1, were selected on the basis of Northern blot and ELISA. Both colonies adhered to resting human endothelial cells (EC) to the same extent. Pre-treatment of EC for 6 hr with conditioned medium (CM) from colony 6, but not from colony 3, increased the adhesion of A375P melanoma and HT-29 colon-carcinoma cells to EC. This increase was blocked by adding interleukin-l-receptor antagonist (IL-1ra) to the EC monolayer. Treatment of EC with colony-6-CM increased the expression of intercellular-adhesion molecule I (ICAM-1), vascular-cell-adhesion molecule I (VCAM-1) and E-selectin. Co-cultivation of colony-6 but not colony-3 melanoma cells with EC caused time-dependent increased expression of these adhesion proteins, reflecting their kinetics of expression on EC. Treating the EC with monoclonal antibodies to VCAM-1 and E-selectin abolished the colony-6-CM-induced increase in adhesion respectively to A375P melanoma and HT-29 colon-carcinoma cells. In vivo, i.v. injection of colony-6 cells in nude mice increased the expression of VCAM-1 on lung microvascular EC. The retention of radiolabeled A375P melanoma cells in the lung was increased in nude mice primed with colony-6 cells, but not with colony-3 cells, injected 6 hr earlier. These results demonstrate that IL-1 produced constitutively by transformed A375P melanoma cells is functionally active, inducing adhesion molecules on EC that enhance their adhesiveness for tumor cells and increase tumor-cell retention in the lung of nude mice.

Animals↗
PubMed1996

Beta-amyloid (25-35) peptide and IFN-gamma synergistically induce the production of the chemotactic cytokine MCP-1/JE in monocytes and microglial cells.

The molecular mechanisms involved in the development of senile plaques characteristic of aging and Alzheimer's disease are poorly understood. In this study, we examined whether human monocytes and murine microglial cells stimulated with the active fragment of amyloid beta-protein (Abeta(25-35)) express the monocyte chemotactic protein-1 (MCP-1)/JE. We show that upon incubation with Abeta(25-35), human monocytes accumulate MCP-1 mRNA and produce significant amounts of MCP-1. The effect of Abeta(25-35) on MCP-1 secretion was neither mimicked by a scrambled analogue nor affected by polymyxin B sulfate, even though the latter almost completely abolished the effect of LPS on MCP-1 expression. Murine microglial cells stimulated with Abeta(25-35) also expressed high levels of JE mRNA (the murine counterpart of MCP-1) and released bioactive chemotactic factors. In addition, we report that IFN-gamma significantly synergizes with Abeta(25-35) either in human monocytes or in murine microglial cells, and that Abeta(25-35) plus/minus IFN-gamma-mediated early induction of MCP-1 mRNA does not require new protein synthesis. Finally, we provide evidence that the Abeta(25-35)- and Abeta plus IFN-gamma-induced production of MCP-1 is, in large part, mediated in an autocrine fashion by endogenous TNF-alpha. Taken together, our findings uncover another novel biologic action of Abeta(25-35) and might help in better understanding the mechanisms underlying mononuclear phagocyte recruitment and activation into amyloid deposits.

Amyloid beta-Peptides↗
PubMed1996

Initial steps in the degradation of 3,4-dimethylbenzoic acid by Pseudomonas putida strain DMB.

Pseudomonas putida strain DMB capable of growing on 3,4-dimethylbenzoic acid as the only C and energy source was isolated by enrichment techniques. It does not utilize for growth or cooxidize the other dimethylbenzoate isomers tested. 3,4-Dimethylsalicylic acid, 3,4-dimethylphenol and 3,4-dimethylcatechol were isolated and identified by nuclear magnetic resonance and mass spectra in the reaction mixture of P. putida washed cells. The detection of the two first metabolites suggests that the initial step in the degradation of 3,4-dimethylbenzoic acid is the formation of 3,4-dimethylcyclohexa-3,5-diene-1,2-diol-1-carboxylic acid which underwent an acid-catalyzed dehydration yielding 3,4-dimethylsalicylic acid and 3,4-dimethylphenol. Further degradation proceeds through 3,4-dimethylcatechol via the meta pathway.

Benzoates↗