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Biomedical subjects

G Neri

Publications and source records attributed to G Neri.

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

Effects of galanin on the secretion and proliferative activity of the immature and regenerating adrenal glands of rats.

The effects of galanin and the galanin-receptor antagonist (galanin-A) [D-Thr(6),D-Trp(8,9),15-ol]-galanin(1-15) on the immature and regenerating rat adrenal glands have been investigated in vivo. Adult female rats with adrenal regeneration and their offpring (20-day-old) were given three subcutaneous injections (28, 16, and 4 h before being killed) of 2 nmol/100 g galanin and/or galanin-A, and 0.1 mg/100 g vincristin 3 h before being killed. Plasma corticosterone concentration was measured by radioimmunoassay, and the mitotic index ( per thousand of metaphase-arrested cells) was evaluated. In immature rats, galanin increased plasma corticosterone concentration, without affecting mitotic index; the secretagogue effect was reversed by galanin-A, which alone was ineffective. In rats with regenerating adrenal, galanin-A increased both blood level of corticosterone and mitotic index; galanin was ineffective, but blocked the effects of galanin-A. These findings allowed us to draw the following conclusions: 1) galanin exerts a moderate glucocorticoid secretagogue action on immature rat adrenals, but endogenous galanin does not play a major physiological role in the functional control of the gland; and 2) endogenous galanin exerts a maximal tonic inhibitory control on both glucocorticoid secretion and proliferative activity of regenerating rat adrenals, whose physiological relevance remains to be investigated.

Adrenal Glands↗
PubMed2000

Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis.

Secretin, glucagon, gastric inhibitory polypeptide (GIP), and parathyroid hormone (PTH) belong, together with vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase (AC)-activating polypeptide, to a family of peptides (the VIP-secretin-glucagon family), which also includes growth hormone-releasing hormone and exendins. All the members of this peptide family possess a remarkable amino-acid sequence homology, and bind to G-protein-coupled receptors, whose signaling mechanism primarily involves AC/protein kinase A and phospholipase C/protein kinase C cascades. VIP and pituitary AC-activating polypeptide play a role in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and in this review we survey findings that also other members of the VIP-secretin-glucagon family may have the same function. Secretin and secretin receptors are expressed in the hypothalamus and pituitary gland, and secretin inhibits adrenocorticotropic hormone (ACTH) release. No evidence is available for the presence of secretin receptors in adrenal glands, but secretin selectively depresses the glucocorticoid response to ACTH of dispersed zona fasciculata-reticularis (ZF/R) cells. Glucagon and glucagon-like peptide-1 are contained in the hypothalamus, and all the components of the HPA axis are provided with glucagon and glucagons-like-1 receptors. These peptides exert a short-term inhibitory effect on stress-induced pituitary ACTH release and depress the ZF/R cell response to ACTH by inhibiting the AC/protein kinase A cascade; they also stimulate hypothalamic arginine-vasopressin release. GIP receptors are present in the ZF/R of the normal adrenals, and are particularly abundant in some types of adrenocortical adenomas and hyperplasias. GIP, through the activation of the AC/protein kinase A cascade, evokes a sizeable glucocorticoid secretagogue effect, leading to the identification of a food/GIP-dependent Cushing's syndrome. PTH and PTH-related protein are expressed in the hypothalamus and pituitary gland, and PTH and PTH-related protein receptors in all the components of the HPA axis. Both peptides enhance ACTH and arginine-vasopressin release, as well as stimulate aldosterone and glucocorticoid secretion of dispersed zona glomerulosa and ZF/R cells, respectively. The involvement of growth hormone-releasing hormone and exendins in the functional regulation of the HPA axis has not yet been extensively investigated.

Amino Acid Sequence↗
PubMed2000

Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome.

The Aarskog syndrome or facio-genital dysplasia (FGDY, MIM No. 305400) is an X-linked condition characterized by short stature, macrocephaly, facial, genital and skeletal anomalies. It is caused by mutation of the FGD1 gene mapped to the Xp11.21 region. To date, only one point mutation has been reported in an affected family, consisting of the insertion of an additional guanine residue at nucleotide 2122 of exon 7, which causes premature translational termination. We now report the finding of two novel FGD1 mutations, a missense mutation in a family of Italian origin and a deletion of 3 exons in a sporadic case from Germany. These mutations confirm the role of FGD1 as the gene responsible for the Aarskog syndrome.

Abnormalities, Multiple↗
PubMed2000

Effects of recombinant murine leptin[1-147] and leptin fragment 116-130 on steroid secretion and proliferative activity of the regenerating rat adrenal cortex.

Leptin, the product of the ob gene, is a hormone mainly secreted by the adipose tissue, which acts through specific receptors (Ob-R) widely distributed in the body tissues. Ob-Rs are present in the mammalian hypothalamo-pituitary-adrenal axis, and evidence indicates that leptin regulates adrenocortical secretion. Moreover, leptin is known to act as a growth promoting factor in some tissues, including the endocrine ovary. We have investigated the effects of three subcutaneous injections of 2 nmol/100 g of native murine leptin[1-147] and of its biologically active fragment 116-130 on the secretory and proliferative activity of the regenerating rat adrenal cortex. Leptin[1-147] increased plasma aldosterone concentration at day 8 and plasma corticosterone concentration (PBC) at day 5 of regeneration, without affecting mitotic index. In contrast, leptin[116-130] lowered PBC and mitotic index at both times of adrenal regeneration. In light of the fact that adrenal regeneration is at least in part dependent on the pituitary ACTH, we conclude that: (i) native leptin moderately stimulates steroid secretion, acting directly on the adrenal cortex, through signaling mechanisms other than those involved in the ACTH action; (ii) native leptin is unable to enhance the proliferative activity of regenerating adrenals, which conceivably is maximally stimulated by ACTH; (iii)leptin[1-147] and leptin[116-130] differently interact with Ob-Rs or interact with different receptors; and (iv) leptin[116-130] inhibits the signaling pathways mediating both the secretagogue effect of native leptin and the proliferogenic effect of ACTH.

Adrenal Cortex↗
PubMed2000

Prolonged kallikrein inhibition does not affect the basal growth and secretory capacity of rat adrenal cortex, but enhances mineralo- and glucocorticoid response to ACTH and handling stress.

The effects on the pituitary-adrenocortical functions of the prolonged (7-day) blockade of endogenous bradykinin (BK) synthesis, obtained by the administration of the kallikrein inhibitor (K-I) cyclohexylacetyl-Phe-Arg-Ser-Val-Gln amide, were investigated in the rat. K-I treatment did not cause significant changes in the (i) body and adrenal weights; (ii) basal plasma levels of ACTH, aldosterone and corticosterone; and (iii) average volume of adrenocortical cells and their basal secretory capacity. Conversely, K-I administration induced a significant magnification of the in vivo mineralo- and glucocorticoid responses to the intraperitoneal (i.p.) bolus injection of ACTH. Moreover, K-I-treated rats, but not control ones, displayed a moderate and short-term adrenal secretory response to the mild stress evoked by the placebo i.p. injection. Collectively, these findings rule out the possibility that endogenous BK plays a relevant role in the control of adrenocortical function under basal conditions. However, they suggest that endogenous BK may be involved in quenching exceedingly high adrenocortical responses to ACTH and stresses.

Adrenal Cortex↗
PubMed2000

Tyrphostin-23 enhances steroid-hormone secretion from dispersed human and rat adrenocrotical cells.

Tyrphostin-23 is commonly used as inhibitor of tyrosine kinase (TK). We found that tyrphostin-23 concentration-dependently increased basal steroid-hormone secretion from dispersed human and rat adrenocortical cells, the maximal effective concentration being 10(-5) M. Tyrphostin-23 (10(-5) M) enhanced 10(-9) M angiotensin-II- and endothelin-1-stimulated secretion of human and rat adrenocortical cells, but not the secretory response to 10(-9) M ACTH However, it increased the response to lower concentrations (10(-12) or 10(-11) M) of ACTH. The secretagogue effect of tyrphostin-23 on dispersed rat adrenocortical cells was abolished by either the adenylate cyclase inhibitor SQ-22536 (10(-4) M) or the protein kinase A (PKA) inhibitor H-89 (10(-5) M). Tyrphostin-23 (10(-5) M) raised basal cyclic-AMP release by dispersed rat adrenocortical cells, but in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 10(-3) M) it was ineffective. Both tyrphostin-23 and IBMX increased cyclic-AMP release by rat adrenocortical cells in response to 10(-10) M ACTH, and their effects were not additive. Taken together, our findings suggest that tyrphostin-23, acting as an inhibitor of phosphodiesterases in adrenocortical cells, increases the intracellular concentration of cyclic-AMP available for PKA activation thereby stimulating steroid-hormone secretion. They also stress that caution must be used in interpreting the results of studies aimed at investigating the possible cross-talk between adenylate cyclase- and TK-dependent signaling cascades.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Endothelin-1 stimulates aldosterone synthesis in Conn's adenomas via both A and B receptors coupled with the protein kinase C- and cyclooxygenase-dependent signaling pathways.

BACKGROUND: The mechanisms and factors leading to enhanced aldosterone secretion and ultimately to neoplastic transformation of the adrenal cortex are poorly defined. Angiotensin-II (Ang-II) and endothelin-1 (ET-1) have emerged as likely candidates among potential aldosterone secretagogues and adrenocortical growth-promoting factors. We therefore compared the effects of Ang-II and ET-1 on steroid hormone secretion of Conn's adenomas. METHODS: Ten Conn's adenomas that showed responsiveness to Ang-II blockade in vivo were recruited. Fragments of the tumors were collected immediately after surgical excision, and dispersed cells were obtained by collagenase digestion and mechanical disaggregation. Steroid hormones secreted by dispersed Conn's adenoma cells were assayed by quantitative high-performance liquid chromatography or radioimmunoassay. RESULTS: Both Ang-II and ET-1 (10(-9) mol/L) similarly enhanced the overall steroid hormone production. ET-1 raised the release of pregnenolone (as evaluated by blocking its further metabolism by cyanoketone), corticosterone, 18-hydroxycorticosterone, and aldosterone, without affecting that of 11-deoxycortisol, cortisol, and 11-deoxycorticosterone. The hormonal responses to ET-1 were partially reversed by 10(-7) mol/L of either the ETA-receptor antagonist BQ-123 or the ETB-receptor antagonist BQ-788 and were abolished when both antagonists were used together. The aldosterone response to the selective activation of ETA and ETB receptors was studied in three Conn's adenomas by exposing dispersed cells to ET-1 (10(-9) mol/L) plus BQ-788 (10(-7) mol/L) and to the ETB-receptor agonist BQ-3020 (10(-8) mol/L). Both treatments raised aldosterone output by about 2-fold. ETA receptor-mediated aldosterone response was abolished by the protein kinase (PK) C inhibitor calphostin C (10(-5) mol/L). ETB receptor-mediated secretory response was lowered by either calphostin C and the cyclooxygenase (COX) inhibitor indomethacin (10(-5) or 10(-4) mol/L) and was completely suppressed when these two were combined. The PKA inhibitor H-89 and the lipoxygenase inhibitor phenidone were ineffective. CONCLUSIONS: Collectively, our findings indicate that Ang-II and ET-1 equipotently stimulate both early and late steps of aldosterone synthesis in Conn's adenoma cells. The secretagogue effect of ET-1 occurs via the activation of ETA and ETB receptors, which are coupled with the PKC-dependent and the PKC- and COX-dependent signaling pathways, respectively.

Adrenal Cortex Hormones↗
PubMed2000

Absence of Helicobacter pylori in tonsillar swabs from dyspeptic patients.

Aim of this study was to evaluate whether tonsils might be a potential reservoir for Helicobacter pylori (H. pylori) infection. A total of 72 consecutive dyspeptic patients undergoing endoscopy for the first time were studied. For each patient, a bilateral tonsillar swab was performed, before endoscopy, for microbiological culture and immunochemical analysis. Antral biopsies were also collected at endoscopy for microbiological culture, rapid urease test, and histological examination. Helicobacter pylori infection was detected in 42 of 72 (58.3%) patients. All tonsillar specimens were negative for H. pylori on both microbiological culture and immunochemical analysis, suggesting that the tonsils are not an extragastric reservoir for H. pylori infection.

Adult↗
PubMed1999

Syndromal (and nonsyndromal) forms of male pseudohermaphroditism.

The term sex determination refers to the genetic events that bring about male or female gonadal development; sex differentiation to all subsequent morphogenetic and physiological events that establish functional sexuality, sexual dimorphism and the secondary sexual characteristics. Virtually all of the steps of sex differentiation are under genetic control; consequently each one of them can fail as result of mutation of the corresponding genes. We shall be concerned with those genes and their mutations that cause pseudohermaphroditism in males and more rarely in females (with the exception of congenital adrenal hyperplasia). Special emphasis will be placed on Swyer, Denys-Drash, RSH, GBBB, campomelic and ATR-X syndromes, whose genes were recently identified.

Animals↗
PubMed1999

Partial duplication of the long arm of chromosome 15: confirmation of a causative role in craniosynostosis and definition of a 15q25-qter trisomy syndrome.

A syndrome of mental retardation and multiple congenital anomalies, including craniosynostosis and overgrowth, was observed in two related individuals from a large kindred. Both of them carried a 15q25.1-qter trisomy associated with a subtle 13qter monosomy resulting from unbalanced segregation of a familial t(13;15)(q34;q25.1) translocation. Reportedly, a further individual in this kindred has the same condition. The present report confirms previous claims that gene(s) in the distal 15q region play a role in suture formation. At the same time it adds new data to the delineation of a 15q25-qter trisomy syndrome.

Adolescent↗
PubMed1999

Infrared photodetection for the in vivo localisation of phage-derived antibodies directed against angiogenic markers.

Angiogenesis, the formation of new blood vessels from pre-existing ones, is a characteristic process which underlies many diseases, including cancer, rheumatoid arthritis and blinding ocular disorders. Antibodies capable of selective targeting and occlusion of neovasculature would open diagnostic and therapeutic opportunities. We have recently demonstrated that phage-derived human antibody fragments with high affinity for the extra-domain B (ED-B) of fibronectin, a marker of angiogenesis, selectively localise in new-forming blood vessels upon intravenous injection. Here, we show that infrared fluorescence methodologies nicely complement radioactive techniques for the study of the antibody-mediated targeting of angiogenesis in a variety of animal models. Methods are presented for the construction and use of infrared fluorescence imagers, as well as for the production and characterisation of recombinant antibodies labeled with infrared fluorophores.

Animals↗
PubMed1999

Mosaicism for the full mutation and a microdeletion involving the CGG repeat and flanking sequences in the FMR1 gene in eight fragile X patients.

The molecular mechanism of the fragile X syndrome is based on the expansion of an unstable CGG repeat in the 5' untranslated region of the FMR1 gene in most patients. This expansion is associated with an abnormal DNA methylation leading to the absence of production of FMR1 protein (FMRP). Such expansion apparently predisposes the repeat and flanking regions to further instability that may lead to mosaic conditions with a full mutation and a premutation or, rarely, with normal or reduced alleles that can sometimes be transcriptionally active. In this study we describe eight unrelated fragile X patients who are mosaic for both a full mutation and an allele of normal (four cases) or reduced size (four cases). Sequencing analysis of the deletion breakpoints in 6 patients demonstrated an internal deletion confined to the CGG repeat in four of them, which represents the most likely explanation for the regression of the full mutation to a normal sized allele. In two patients with a reduced allele, the deletion encompassed the entire CGG repeat and part of the flanking regions. Analysis of FMRP by Western blot was performed in one of the mosaics with a normal sized allele and in three of those with a reduced allele. In the first patient's lymphocytes FMRP was detected, whereas in the three other patients the deletion is likely to impair transcription as no FMRP was present in their lymphocytes.

Base Sequence↗
PubMed1999

Association of trisomy 9p and band heterotopia.

Patients with the trisomy 9p syndrome and CNS abnormalities have been poorly assessed. We report a patient with trisomy 9p who showed band heterotopia on MRI. Abnormal neuronal migration is sufficiently frequent in patients with the trisomy 9p syndrome that brain MRI should be routinely considered in all patients with this syndrome.

Adult↗
PubMed1999

Pervasive developmental disorder and epilepsy due to maternally derived duplication of 15q11-q13.

Duplications of chromosome 15 have been reported in individuals with atypical autism, varying degrees of mental retardation, and epilepsy. The authors report the molecular analysis, neurophysiologic, and clinical evaluation of a 12-year-old boy with atypical autism and epilepsy due to a maternally derived 15q11-q13 duplication. Their findings suggest that this chromosomal region harbors genes for autism and possibly for partial epilepsy that may act in a dose-dependent manner.

Child↗
PubMed1999

Cardiac anomalies in the Simpson-Golabi-Behmel syndrome.

Diverse cardiac abnormalities have been reported in patients with the Simpson-Golabi-Behmel syndrome (SGBS), and it is suspected that they are related to the apparently high incidence of early death. To clarify the incidence and significance of the various cardiac abnormalities, we reviewed 101 SGBS patients (89 from the literature, 12 new). All were male, except for one clearly affected female patient with translocation X;1 [Punnett, 1994: Am J Med Genet 50: 391-393]. Ninety-six of 99 (97%) patients had the classic phenotype of macrosomia and typical "coarse" face. Thirty-six patients (36%) had a cardiac abnormality, of whom 26 (26%) had a cardiovascular malformation (CVM). After excluding 24 patients with insufficient clinical data, these percentages among the 77 informative cases were 47% and 34%, respectively. When grouped according to a mechanistic classification, most cases (20/ 26, or 77%) were class II CVMs (attributed to altered embryonic intracardiac flow). Other cardiac abnormalities included cardiomyopathy (n = 4) and electrocardiogram (ECG) conduction or rhythm abnormalities (n = 12); three of the affected patients (25%) also had a CVM. Among 92 informative cases, there were 29 (32%) deaths, a figure that excludes seven elective terminations. Among the 25 patients younger than 3 years, death was associated with a cardiac abnormality in six (23%). GPC3 mutation analysis using Southern blot testing and polymerase chain reaction amplification was performed for 37 of 101 (37%) patients. A mutation was detected in 26 of the 37 patients tested (70%), 12 of whom (46%) had a cardiac abnormality. We conclude that cardiac abnormalities of any type are common in SGBS (almost one-half of informative cases), with CVMs seen in one-third of cases. The heterogeneous ECG abnormalities in this survey must be viewed with caution, since they may represent a genuine component of the syndrome or reporting bias. Determining the true prevalence and natural history of cardiac abnormalities in SGBS will require a larger number of patients and more consistent prospective cardiac evaluations. There are sufficient data to recommend a baseline echocardiogram and ECG in SGBS patients. Data are insufficient to define a cardiac phenotype/molecular correlation.

Adolescent↗
PubMed1999

XLMR genes: update 1998.

Since the Seventh Fragile X and XLMR Mental Retardation (XLMR) Workshop in 1995, the genes for Coffin-Lowry, Mohr-Tranebjaerg, and Opitz G/BBB syndromes have been cloned. Jensen syndrome has been found to be allelic to Mohr-Tranebjaerg. Twenty new XLMR syndromes and metabolic or neuromuscular disorders have been reported. Twenty-four new localizations have been established, including five in previously reported conditions (FG, Carpenter, Arts, OPA2, and OFD1). The number of families with nonspecific XLMR that have been reported has continued to increase; 58 families or loci are now known. Eighteen new families with nonspecific mental retardation (MRX) have been reported. Two of them, however, were subsequently found to have mutations in the RABGDIA gene, which codes for a GDP-dissociation inhibitor for RAB proteins. In total, 41 more entries have been added to the X chromosome map of XLMR. The total number of known syndromes and MRX families has increased to 178. Of the 120 known XLMR disorders, 53 have been mapped, and 22 have been cloned. Assuming that at least 10 loci are necessary to account for the 58 families with MRX, the total number of XLMR loci counted so far would be 130. Although it is likely that many of the disorders will eventually prove to be allelic, it is not possible at present to determine the precise number of loci for nonspecific XLMR.

Humans↗