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Biomedical subjects

S Bernasconi

Publications and source records attributed to S Bernasconi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Listeriosis in recipients of allogeneic bone marrow transplants from unrelated donors.

Two cases of listeriosis in patients submitted to matched unrelated donor bone marrow transplantation are reported. The patients developed listerial septicemia and listerial septicemia with meningitis and encephalitis 39 and 29 days after transplantation, respectively. Including the present two cases, 19 Listeria monocytogenes infections in related and unrelated donor allogeneic bone marrow transplant recipients have been reported to date. Infection occurred earlier in unrelated donor transplant recipients. Listeriosis is a rare complication in allogeneic bone marrow transplant recipients; however, the widespread practice of performing transplants from a donor-alternative to a human leukocyte antigen-compatible sibling and, in this setting, the need for intensified immunosuppression may predict an increasing and earlier occurrence of listeriosis.

Adult↗
PubMed2000

Distribution of catabolic pathways in some hydrocarbon-degrading bacteria from a subsurface polluted soil.

Enrichment cultures on naphtha solvent were used to select aromatic hydrocarbon-degrading bacteria from a BTEX (benzene, toluene, ethylbenzene, xylene)-contaminated subsoil obtained from beneath a paint factory located in Milan, Italy. Fifteen isolated strains were studied for their different biodegradative capacities. Among these, 13 were able to grow on naphtha solvent. Ten were identified as Pseudomonas putida and three as Pseudomonas aureofaciens. Two other degraders were identified as Pseudomonas aeruginosa and Alcaligenes xylosoxidans subsp. denitrificans. Further molecular characterization of the isolates was carried out by randomly amplified polymorphic DNA analysis to ascertain that all the studied strains belonged to different haplotypes. The isolates were characterized for the presence of genes encoding for toluene dioxygenase, xylene monooxygenase and catechol 2,3-dioxygenase by polymerase chain reaction analysis and by Southern analysis. P. putida strain CM23, which showed homology with xylA,M, xylE and todC1C2BA genes, possessed multiple pathways which enabled the strain to grow on benzene, toluene and m-xylene.

Alcaligenes↗
PubMed2000

Detection of genes for alkane and naphthalene catabolism in Rhodococcus sp. strain 1BN.

Rhodococcus sp. 1BN was isolated from a contaminated site and showed various biodegradative capabilities. Besides naphthalene, strain 1BN degraded medium- (C6) and long-chain alkanes (C16-C28), benzene and toluene, alone or when the hydrocarbons were mixed in equal proportions. The nucleotide sequence of an alk polymerase chain reaction (PCR) fragment revealed a 59% nucleotide homology to the Pseudomonas oleovorans alkB gene. The nar fragments were highly homologous to genes coding for large and small subunits of cis-naphthalene 1,2-dioxygenase (narAa and narAb) and to cis-naphthalene dihydrodiol dehydrogenase (narB) from other rhodococci. The oxidation of indene to cis-(1S,2R)-1,2-dihydroxyindan by toluene-induced cells allows to hypothesize that strain 1BN also carries a toluene dioxygenase-like system.

Alkanes↗
PubMed2000

Neuroendocrine responses to psychological stress in adolescents with anxiety disorder.

Neurotransmitter-neuroendocrine and cardiovascular responses to the administration of a psychologically stressful mixed-model test (Mental Arithmetic, Stroop Color Word Interference Task, Trier Social Stress Test) were examined in 20 male peripubertal subjects affected by anxiety disorder (group A: 14 with generalized anxiety disorder, 6 with generalized anxiety disorder and separation anxiety disorder) and 20 junior school adolescents, matched for age, without overt psychological disorders (group B). Plasma levels of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (Te) were measured immediately before the beginning of the tests and 30 min later at their end. Mean prestress values of GH, PRL, beta-EP and ACTH were significantly higher in anxious subjects than in controls. There was no difference in NE, EPI, CORT and Te prestress levels in the two groups. After the psychological stress session NE, GH and Te concentrations increased significantly in anxious subjects (A), but not in controls. In contrast, beta-EP and PRL decreased significantly during the psychological stress session in anxious subjects, and were unaffected by stress in the subjects without anxiety. No significant changes were found in ACTH, CORT and EPI during the challenge either in anxious subjects or in controls, which may be attributed to the late time of poststress blood sampling. In contrast to controls, heart rate and systolic blood pressure increased significantly in anxious subjects after psychological stress testing. Our data support the hypothesis that the hyperactivity of the noradrenergic system in response to stress is associated with anxiety disorders in adolescents and might influence the responses of GH and Te. High prestress basal values of stress hormones seem to be induced in anxious subjects by the anticipation of the task or by a persistent hyperactivity of the noradrenergic system. Further studies are needed to investigate in more detail the involvement of the HPA axis in anxious adolescents by a more refined resolution of time points of blood sampling.

Adolescent↗
PubMed2000

Long-term results with growth hormone therapy in idiopathic hypopituitarism.

More than 30 years after its introduction, growth hormone (GH) treatment is well established in children with GH deficiency. Nevertheless, the long-term results of this therapy, expressed as height, are generally considered unsatisfactory. We report on results obtained in a group of GH-deficient children who were treated with daily injections of recombinant GH within the first 5 years of life and who reached an adult height very close to their target height. The full catch-up growth to the target height demonstrated in these patients suggests that replacement therapy should be started early and continued until adulthood. Height at onset of puberty is an important variable which might significantly influence the adult height. The significant and prolonged influence of birth weight on growth response to GH therapy underlines the important role of fetal growth in planning early treatment of GH-deficient children.

Body Height↗
PubMed2000

Diagnosis of central precocious puberty: endocrine assessment.

The new methods which are currently available have provided substantial help in performing the differential diagnosis of CPP, especially in detecting very early modifications of gonadotropin secretion. Nocturnal sampling is not a practical tool and generates discomfort for patients, and daytime samples do not yet have sufficient sensitivity; thus, determination of LH levels after GnRH stimulation is the most important test. We emphasize that the use of the GnRH agonist test improves the discrimination of the endocrine investigation, making it easier to differentiate CPP from other conditions, such as thelarche. Determination of sex steroids is necessary, but its use in isolation is not recommended.

Brain Diseases↗
PubMed2000

[A case of female pseudohermaphroditism caused by maternal androluteoma].

Female pseudohermaphroditism is a condition characterized by various degree of external genitalia virilization in a patient with female internal genitalia and karyotype (XX). External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment. Fetal metabolic abnormalities, like congenital adrenal hyperplasia, are the most common causes of female pseudohermaphroditism, however there is a low incidence of gestational hyperandrogenism caused by maternal pathology. We report a case of female pseudohermaphroditism secondary to a maternal ovarian luteoma of pregnancy producing androgenic hormones. The newborn presented a severe degree of external genitalia virilization with high urogenital sinus (stage Prader V). Moreover we describe the main steps of diagnostic iter that are necessary both to exclude other causes of virilization and to study all anatomical aspects in view of the surgical correction. The operation consists in two phases of action: an early clitorisvulvoplasty according to Passerini-Glazel and a late vaginal pull-through with anterior saggital transanorectal approach (ASTRA).

Disorders of Sex Development↗
PubMed1999

Up-regulation of CCR2 chemokine receptor expression and increased susceptibility to the multitropic HIV strain 89.6 in monocytes exposed to glucocorticoid hormones.

Glucocorticoid hormones (GC) are potent antiinflammatory agents widely used in the treatment of diverse human diseases. The present study was aimed at assessing the effect of GC on chemokine receptor expression in human monocytes. Dexamethasone (Dex) up-regulated mRNA expression of the monocyte chemotactic protein (MCP-1, CCL2) chemokine receptor CCR2. The effect was selective in that other chemokine receptors were not substantially affected. Stimulation by Dex was observed after 4 h of exposure at concentrations of 10(-7) to 10(-5) M. Steroids devoid of GC activity were inactive, and the GC receptor antagonist, RU486, inhibited stimulation. Dex did not affect the rate of nuclear transcription, but augmented the CCR2 mRNA half-life. Augmentation of CCR2 expression by Dex was associated with increased chemotaxis. Finally, Dex treatment induced productive replication of the HIV strain 89.6, which utilizes CCR2 as entry coreceptor, in freshly isolated monocytes. Together with previous findings, these results indicate that at least certain pro- and antiinflammatory molecules have reciprocal and divergent effects on expression of a major monocyte chemoattractant, MCP-1, and of its receptor (CCR2). Augmentation of monocyte CCR2 expression may underlie unexplained in vivo effects of GC as well as some of their actions on HIV infection.

Cell Membrane↗
PubMed1999

Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcripts.

The IL-1 type I receptor (IL-1RI) is part of a signaling complex together with the IL-1R accessory protein, whereas available information is consistent with a "decoy" model of function for the IL-1 type II receptor (IL-1RII). The present study was designed to investigate the effect of bacterial LPS on IL-1R in human monocytes. LPS causes rapid release of the IL-1RII, an effect blocked by a metalloprotease inhibitor. Subsequently, LPS-treated monocytes showed a drastic reduction of IL-1RII mRNA. In contrast, LPS induced IL-1RI and, to a lesser extent, IL-1AcP expression. LPS-induced augmented expression of the canonical 5-kb IL-1RI mRNA was accompanied by the appearance of 2.4-kb IL-1RI transcripts. The use of probes representative of different regions of the IL-1RI mRNA, as well as cDNA cloning, revealed that the 2.4-kb inducible band includes incompletely spliced, polyadenylated transcripts potentially encoding truncated versions of the receptor. The observation that the prototypic proinflammatory molecule LPS has divergent effects on IL-1Rs, with inhibition of IL-1RII and stimulation of IL-1RI and IL-1R accessory protein, is consistent with the view that these molecules subserve opposite functions in the pathophysiology of the IL-1 system. The rapid shedding of IL-1RII by monocytes early in recruitment may serve to buffer the systemic action of IL-1 leaking from sites of inflammation. This early event, followed by prolonged inhibition of IL-1RII expression and up-regulation of IL-1RI, may render monocytes more responsive to IL-1 at sites of inflammation.

Base Sequence↗
PubMed1999

Up-regulation of CCR1 and CCR3 and induction of chemotaxis to CC chemokines by IFN-gamma in human neutrophils.

Human neutrophils (polymorphonuclear leukocytes; PMN) respond to some CXC chemokines but do not migrate to CC chemokines. Recent work has shown that chemokine receptors can be modulated by inflammatory cytokines. In this study, the effect of IFN-gamma, a prototypic Th1 cytokine, on chemokine receptor expression in PMN was investigated. IFN-gamma caused a rapid (approximately 1 h) and concentration-dependent increase of CCR1 and CCR3 mRNA. The expression of CCR2, CCR5, and CXCR1-4 was not augmented. IFN-gamma-treated PMN, but not control cells, expressed specific binding sites for labeled monocyte-chemotactic protein (MCP)-3 and migrated to macrophage-inflammatory protein (MIP)-1alpha, RANTES, MCP-3, MIP-5/HCC2, and eotaxin. 7B11, a mAb for CCR3, inhibited the chemotactic response of IFN-gamma-treated PMN to eotaxin, and aminoxypentane-RANTES blocked PMN migration to RANTES. These results suggest that the selectivity of certain chemokines for their target cells may be altered by cytokines produced within an inflammatory context. Since PMN may play a role in orienting immunity toward Th1 responses, it is possible to speculate that IFN-gamma not only promotes Th1 differentiation directly, but also reorients the functional significance of Th2 effector cytokines by broadening the spectrum of their action to include PMN.

Antigens, CD↗
PubMed1999

Differential responsiveness to constitutive vs. inducible chemokines of immature and mature mouse dendritic cells.

Upon exposure to immune or inflammatory stimuli, dendritic cells (DC) migrate from peripheral tissues to lymphoid organs, where they present antigen. The molecular basis for the peculiar trafficking properties of DC is largely unknown. In this study, mouse DC were generated from CD34+ bone marrow precursors and cultured with granulocyte-macrophage-CSF and Flt3 ligand for 9 days. Chemokines active on immature DC include MIP1alpha, RANTES, MIP1beta, MCP-1, MCP-3, and the constitutively expressed SDF1, MDC, and ELC. TNF-alpha-induced DC maturation caused reduction of migration to inducible chemokines (MIP1alpha, RANTES, MIP1beta, MCP-1, and MCP-3) and increased migration to SDF1, MDC, and ELC. Similar results were obtained by CD40 ligation or culture in the presence of bacterial lipopolysaccharide. TNF-alpha down-regulated CC chemokine receptor (CCR)1, CCR2, and CCR5 and up-regulated CCR7 mRNA levels, in agreement with functional data. This study shows that selective responsiveness of mature and immature DC to inducible vs. constitutively produced chemokines can contribute to the regulated trafficking of DC.

Animals↗
PubMed1999

Circulating antibodies recognizing oxidatively modified low-density lipoprotein in children.

The occurrence of circulating antibodies (IgG) against oxidatively modified LDL was investigated in a group of normocholesterolemic, healthy, cardiovascular risk-free children and in a comparable group of normal adults. An increased titer of IgG recognizing Cu++-oxidized or malondialdehyde (MDA)-derivatized LDL (MDA-LDL) was a constant feature in children. The antigenic epitopes recognized by these antibodies were generated rather late in the process of copper-mediated LDL oxidation, concomitantly with the formation of fluorescent adducts between reactive aldehydes (including MDA) and apo B100. MDA-LDL was not the only antigen recognized: derivatization of other structurally unrelated proteins, such as HDL, serum albumin, fibrinogen, and transferrin with MDA led to generation of recognizable epitopes. However, among the various modified proteins, LDL exhibited the highest binding activity for IgG present in the group of children. This was associated with an enhanced propensity of LDL isolated from children to undergo in vitro oxidation, despite normal levels of the endogenous antioxidant alpha-tocopherol. These findings indicate that circulating antibodies recognizing proteins modified with end-products of lipid peroxidation (including LDL) are present in healthy cardiovascular risk-free children. The possibility that LDL oxidation occurs in vivo already in childhood and may act as the real immunogen is an attractive but still unproven hypothesis.

Adolescent↗
PubMed1999

Changes of serum allopregnanolone levels in the first 2 years of life and during pubertal development.

Allopregnanolone is the best characterized among neurosteroids, and its role in the control of neuroendocrine axes has attracted increasing interest recently. However, there is no available information about circulating levels of allopregnanolone during infancy, childhood and puberty. We studied two groups of children: 1) those aged between 0 and 2 y (n = 72), and 2) those aged between 6 and 18 y, at different Tanner's stages (n = 82). In each of these patients, serum allopregnanolone, progesterone, cortisol, and dehydroepiandrosterone levels were evaluated after informed consent; allopregnanolone was measured by RIA after acid extraction on cartridge. There was no significant variation of serum allopregnanolone levels either in male and female children during the first 2 y of life. Furthermore, although serum dehydroepiandrosterone levels showed a significant decrease, inversely correlated with age of the children (p < 0.01), serum cortisol and progesterone levels showed a significant age-related increase during the first 2 y of life. Cortisol and allopregnanolone levels were positively correlated (p < 0.01). During puberty, we observed a progressive increase in serum allopregnanolone levels in both boys and in girls, which were higher at Tanner' s stage IV-V (0.7+/-0.01 nM; mean +/- SEM) than at stages I-II (0.32+/-0.02 nM; p < 0.01); mean levels were significantly higher at puberty than in the first 2 y of life (p < 0.01). Furthermore, during puberty, serum progesterone and dehydroepiandrosterone levels also increased progressively with age in both boys and girls. Allopregnanolone and dehydroepiandrosterone levels were positively correlated throughout puberty. The present results indicate that serum allopregnanolone levels do not change during the first 2 y of life but increase during pubertal development, suggesting that this steroid may be involved in the adaptive neuroendocrine mechanisms related to puberty.

Adolescent↗
PubMed1999

Acquired inhibitor against factor IX in a child: successful treatment with high-dose immunoglobulin and dexamethasone.

The occurrence of acquired inhibitor against factor IX:C is infrequent in haemophilia B patients and is very rare in previously healthy subjects, in whom it is often related to underlying diseases. We describe the case of a 2-year-old girl, who was referred to our hospital with haematomas, without previous bleeding history. Prolonged APTT, normal PT and a factor IX:C level below 1% were found. An inhibitor against factor IX:C was detected (5.5 U mL(-1)). Her father and mother showed normal factor IX:C levels. Treatment with high-dose immunoglobulin (400 mg kg(-1) day(-1) for 5 consecutive days by intravenous infusion) and dexamethasone (4 mg three times a day by intravenous injection for 4 consecutive days) normalized factor IX:C levels and overcame the inhibitor. In conclusion, high-dose immunoglobulin and high-dose dexamethasone are a successful and safe immunosuppressive approach for recovery from inhibitor occurrence.

Child, Preschool↗
PubMed1999

A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1.

Blocking chemokine production or action is a major target for pharmacological intervention in different human diseases. Bindarit (2-methyl-2-[[1-(phenylmethyl)-1H-indazol-3yl]methoxy]propan oic acid) dose-dependently inhibited MCP-1 and TNF-alpha production induced in vitro in monocytes by LPS and Candida albicans. It did not affect the production of the cytokines IL-1, IL-6, or the chemokines IL-8, MIP-1alpha and RANTES. In the air pouch model in mice, oral treatment reduced monocyte recruitment and local MCP-1 production, induced by carrageenan or IL-1 injection. In NZB/W mice, a model of lupus nephritis, oral treatment prolonged survival and delayed the onset of proteinuria. The results presented here show that bindarit is a preferential inhibitor of the production of MCP-1 in vitro and in vivo and suggest that its beneficial effects in models of joint and kidney inflammation are related to its anti-MCP-1 action. It is therefore possible to selectively and differentially regulate chemokines by targeting their production with small synthetic molecules.

Animals↗