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Biomedical subjects

R Gallo

Publications and source records attributed to R Gallo.

At least 73 records · Page 4Linked to original sources

High levels of fetal membrane activin beta A and activin receptor IIB mRNAs and augmented concentration of amniotic fluid activin A in women in term or preterm labor.

The aim of the present study was to evaluate whether spontaneous labor at term and pathological preterm labor are associated with changes in the expression of activin A and activin receptor mRNAs in fetal membranes. In addition, amniotic fluid activin A concentration in women delivering at term or undergoing preterm labor was also measured. The expression of activin beta A subunit and activin receptor type II and type IIB mRNAs was assessed by reverse transcriptase-PCR on specimens of amnion and chorion collected from patients delivering at term or undergoing preterm labor. Control specimens were collected from women delivered by elective cesarean section who had not experienced labor. A specific two-site ELISA was used to measure activin A concentrations in the amniotic fluid. A cross-sectional study of amniotic fluid retrieved by amniocentesis from 109 pregnant women was carried out. Patients were classified into the following groups: (1) healthy controls at term but not in labor (n = 25); (2) healthy controls at term in spontaneous labor (n = 40); (3) healthy controls between 23 and 36 weeks of gestation (n = 12); (4) patients in preterm labor responding to tocolytic treatment (n = 19); (5) patients in preterm labor with subsequent delivery (n = 13). Activin beta A subunit and activin receptor type IIB mRNA levels in both the chorion and amnion in women delivering at term or after preterm labor were significantly higher than in women delivering without undergoing labor (P < 0.01). Expression of activin receptor type II mRNA in membranes did not differ among the three groups of women. Amniotic fluid activin A concentration in patients in labor was significantly higher than in those at term but not in labor (P < 0.01). Patients in preterm labor had significantly higher amniotic fluid activin A concentrations than women at the same stage of gestation (P < 0.01). The highest values were found in women undergoing preterm labor and subsequent delivery. In conclusion, spontaneous labor and preterm labor are characterized by increased synthesis and release of activin A from amniotic and chorionic cells and by an augmented expression of activin type IIB receptor.

Activin Receptors↗

Rapamycin inhibits vascular smooth muscle cell migration.

Abnormal vascular smooth muscle cell (SMC) proliferation and migration contribute to the development of restenosis after percutaneous transluminal coronary angioplasty and accelerated arteriopathy after cardiac transplantation. Previously, we reported that the macrolide antibiotic rapamycin, but not the related compound FK506, inhibits both human and rat aortic SMC proliferation in vitro by inhibiting cell cycle-dependent kinases and delaying phosphorylation of retinoblastoma protein (Marx, S.O., T. Jayaraman, L.O. Go, and A.R. Marks. 1995. Circ. Res. 362:801). In the present study the effects of rapamycin on SMC migration were assayed in vitro using a modified Boyden chamber and in vivo using a porcine aortic SMC explant model. Pretreatment with rapamycin (2 ng/ml) for 48 h inhibited PDGF-induced migration (PDGF BB homodimer; 20 ng/ml) in cultured rat and human SMC (n = 10; P < 0.0001), whereas FK506 had no significant effect on migration. Rapamycin administered orally (1 mg/kg per d for 7 d) significantly inhibited porcine aortic SMC migration compared with control (n = 15; P < 0.0001). Thus, in addition to being a potent immunosuppressant and antiproliferative, rapamycin also inhibits SMC migration.

Administration, Oral↗

Syndecans-1 and -4 are induced during wound repair of neonatal but not fetal skin.

Syndecans are a family of four cell surface proteoglycans that bind to various components of the extracellular environment and can regulate many cellular behaviors including growth, adhesion, and movement. To determine whether syndecans can function during wound repair, we have examined expression of the syndecans during wound repair of adult mouse and neonatal or fetal human skin. Syndecan-1 and -4 were induced in the dermis within 12 h after incisional injury of murine or neonatal human skin. Syndecan-1 was induced primarily on endothelium, and syndecan-4 was present throughout the dermis at the site of injury. Following re-epithelialization, expression of the syndecans return to their baseline level. In marked contrast to these observations, wounded human fetal skin showed no increase in expression of syndecans. This lack of increase in the expression of syndecans by cells of the dermis correlates with prior observations that fetal skin heals without a polymorphonuclear cell infiltrate, appreciable fibrosis, or clinically apparent scar. Thus, induced expression of syndecans is not an absolute requirement for wound repair but does correlate with the occurrence of fibrosis in mature skin. These findings support the role of syndecans as regulators of cell behavior and suggest that syndecan-1 and -4 induction in the dermis may contribute to events that lead to inflammation and fibrosis.

Animals↗

Corticotropin-releasing factor-binding protein: origins and possible functions.

Corticotropin-releasing hormone-binding protein (CRFBP) is a 37-kD protein of 322 amino acids, containing one putative N-glycosylation site and 11 cysteines, 10 of which remain in the mature molecule (298 amino acids) and result essential for the action. CRFBP protein gene has been cloned and mapped to the distal region of chromosome 13 and loci5q in the mouse and human genomes. CRFBP is the only example of a neuropeptide-binding protein. It is produced in human and rat brain, and in human liver and placenta. In brain, the central distribution of CRFBP shares some regional overlap with CRF receptor-bindings sites. Additionally, in hypothalamic and limbic structures, CRFBP has been identified in association with CRF-expressing cell groups. CRFBP has been also demonstrated in the human placenta and related membranes. Indeed, amniotic epithelium, chorionic cytotrophoblast, and maternal decidua also show intense positive CRFBP mRNA signals. Circulating CRFBP levels in healthy nonpregnant individuals show the same range values as in maternal plasma collected during the first and second trimesters of pregnancy. A rise in CRFBP levels at 30-35 weeks of pregnancy with a dramatic decrease at 38-40 weeks have been shown. At postpartum, CRFBP levels in maternal plasma reach the nonpregnant concentrations. Recombinant and native CRFBP neutralize the ACTH-releasing activity of human CRF in cultured pituitary or placental cells and, additionally, may block the activity of CRF on human pregnant endometrium prostaglandin release and on human myometrium contractility in vitro. These findings suggest that CRFBP may play a role in modulating the functions of CRF in human pregnancy.

Body Fluids↗

Human placenta and fetal membranes express human urocortin mRNA and peptide.

Recently a new member of the corticotropin-releasing factor (CRF) family has been cloned and named urocortin. It has been localized in rat brain and to human chromosome 2. The present study investigated whether human placenta and related tissues express mRNA and immunoreactive urocortin. Using specific oligonucleotide primers, reverse transcriptase-polymerase chain reaction experiments were performed on total RNA isolated from human placenta and decidua collected both at early stage of gestation (8-11 weeks) and at term (39-40 weeks). In addition, experiments were also done on specimens of amnion and chorion collected at term. Independently from the gestational age, placental and decidual cells expressed urocortin mRNA, with a 145 bp DNA band corresponding to the expected length. The expression of urocortin mRNA was also found in amnion and chorion. Using specific antiserum and an immunoperoxidase technique, immunoreactive urocortin was then localized in syncytiotrophoblast cells and in some extent in cytotrophoblast cells of placental villi at term, as well as in fetal membranes and maternal decidua. The present findings revealed that human placenta and gestational related tissues express human urocortin gene and localize immunoreactive urocortin, supporting the concept that these tissues are capable of expressing a large number of neuroendocrine peptides.

Amnion↗

Remodeling of cytoskeleton and triads following activation of v-Src tyrosine kinase in quail myotubes.

To study the cellular signals underlying the regulatory mechanisms involved in maintenance of sarcomeric integrity, we have used quail skeletal muscle cells that reach a high degree of structural maturation in vitro, and also express a temperature-sensitive mutant of the v-Src tyrosine kinase that allows the control of differentiation in a reversible manner. By immunofluorescence and electron microscopy we show that v-Src activity in myotubes leads to an extensive cellular remodeling which affects components of the sarcomeres, the cytoskeleton network and the triad junctions. We have previously shown that activation of v-Src causes a selective dismantling of the I-Z-I segments coupled to the formation of aggregates of sarcomeric actin, alpha-actinin and vinculin, called actin bodies. We now show that intermediate filaments do not participate in the formation of actin bodies, while talin, a component of costameres, does. The I-Z-I segments are completely dismantled within 24 hours of v-Src activity, but the A-bands persist for a longer time, implying distinct pathways for the turnover of sarcomeric subdomains. Immunofluorescence labeling of markers of the triad junctions demonstrates that the localization of the alpha 1 subunit of the dihydropyridine receptor is disrupted earlier than that of the ryanodine receptor after tyrosine kinase activation. Furthermore, the location of junctional sarcoplasmic reticulum and transverse tubule membranes is maintained in myotubes in which the I-Z-I have been removed and the regular disposition of the intermediate filaments is disrupted, supporting a role for sarcoplasmic reticulum in the proper positioning of triad junctions. Altogether these results point to a tyrosine kinase signaling cascade as a mechanism for selectively destabilizing sarcomere subdomains and their tethering to the cytoskeleton and the sarcolemma.

Actins↗

Episodic secretion of activin A in pregnant women.

The aim of the present study was to determine the characteristics of activin A secretion in women with normal and abnormal pregnancy. With this purpose, a prospective study was done to evaluate the putative pulsatile pattern of serum activin A in serial specimens of blood collected during a certain amount of time (every 15 min for 3 h). A group of pregnant women (N = 24) participated in a cross-sectional study. They were subdivided into three groups: healthy pregnant women (N = 8), patients with preterm labor (N = 8) and patients with gestational diabetes (N = 8) before and after insulin therapy. Secretory pulses of serum activin A were determined in all patients with a specific frequency and amplitude by using two different computerized analyses, i.e. DETECT and CLUSTER. Mean +/- SEM values of serum activin A were significantly higher in patients with preterm labor and gestational diabetes than in controls (p < 0.01), showing a significant decrease following insulin therapy in diabetic patients (p < 0.01). Specific pulses of serum activin A levels were observed in all women. The mean pulse frequency did not change significantly between healthy controls and the different pathological groups. Patients with gestational diabetes after insulin therapy showed a pulse frequency that was significantly higher than in controls (p < 0.05). When the mean peak amplitude of activin A pulses was evaluated, patients with preterm labor or gestational diabetes showed values that were significantly higher than in healthy pregnant women (p < 0.01) A significant, inverse correlation between pulse frequency and amplitude was found both in healthy pregnant women (p < 0.05) and in patients with gestational diabetes (p < 0.001). The present study showed that circulating activin A levels in pregnant women change in a pulsatile pattern whose pulse amplitude is modified in the presence of gestational diseases, such as preterm labor or gestational diabetes.

Activins↗

Allopregnanolone concentration in hippocampus of prepubertal rats and female rats throughout estrous cycle.

Hippocampus plays an important role in cognition, neuroendocrine function and sexual behaviour. Changes of hippocampal neuropeptide and neurotransmitter concentrations are associated to behavioural changes occurring throughout reproductive life. The present study focused the attention on the presence of a neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one (termed allopregnanolone) in hippocampus. In particular, hippocampal allopregnanolone concentration in male and female prepubertal rats and in female rats throughout estrous cycle were evaluated. Hippocampal extracts were eluted on high pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Prepubertal male and female rats (15 days old) showed highest values which significantly decreased with advancing age (25 and 60 days) (p < 0.01); the lowest hippocampal concentration of allopregnanolone was found in adult rats. Female rats on proestrus morning and afternoon showed an hippocampal allopregnanolone concentration significantly higher than on diestrus or on estrus (p < 0.01), while rats on estrus showed hippocampal allopregnanolone concentration significantly lower than during other days of estrus cycle (p < 0.01). These data indicate differences in hippocampal concentration of allopregnanolone between prepubertal and adult rats and throughout estrous cycle in female rats. This finding suggest a putative role of neurosteroids in the modulation of behavioral changes occurring throughout reproductive life.

Animals↗

Ultrasonographic bone characteristics during normal pregnancy: longitudinal and cross-sectional evaluation.

OBJECTIVE: We evaluated the pattern of bone density during pregnancy by radiation-free ultrasonographic densitometry. STUDY DESIGN: In a longitudinal study we measured bone mineral density in a group of 10 normal primiparous women, from the fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study bone mineral density was determined in a group of 85 normal primiparous women, in different weeks of pregnancy. RESULTS: In the longitudinal study ultrasonographic bone density was stable in the first part of pregnancy, whereas a significant (p < 0.05) decrease was evidenced during the third trimester. A negative correlation between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the cross-sectional study. CONCLUSION: During physiologic pregnancy the calcium mobilization from the maternal bone stores to accomplish the fetal needs can cause a significant decrease in maternal bone density in the last trimester of gestation.

Bone Density↗

Unstented semilunar homograft replacement of tricuspid valve in Ebstein's malformation.

Tricuspid valve pathology in Ebstein's malformation requires replacement when it is not possible to repair or reconstruct this valve. In smaller children, in whom the right-sided atrioventricular valve is severely dysplastic and right ventricular volume is prohibitive, prosthetic replacement is not always possible. We report here on 3 patients who underwent stentless semilunar homograft replacement (top-hat procedure) of tricuspid valve for Ebstein's anomaly with good short-term outcome. This provides an attractive alternative in the management of a certain difficult subset of patients, avoids long term anticoagulation and probably is more durable.

Child↗

From aortic cusp extension to valve replacement with stentless pericardium.

Between 1988 and 1994, 82 consecutive patients (median age 24 years) underwent reconstruction of the aortic valve with glutaraldehyde-treated pericardium. Simultaneously, 29 of 30 mitral valves were repaired. The first 27 patients underwent resection of the free edges and suture of a single strip of bovine pericardium. Transient ischemic changes suggested the need for a change in technique. The subsequent 55 patients underwent total valve reconstruction with an autologous pericardium fixed with glutaraldehyde in the appropriate shape and size according to the patient's aortic annulus. There were one in-hospital and three late deaths. No patient received anticoagulation, and no embolic events were detected. Nine patients required reoperation as a result of failure of mitral valve repair in 4 and severe aortic regurgitation in 5 (endocarditis [n = 2], commissural tear [n = 1], root dilation [n = 1], calcification of one bovine cusp [n = 1] at 58 months). There were no reoperative deaths. Complete linear echocardiographic follow-up of these patients showed low gradients, valve competence, and no progressive deterioration. No difference between techniques was detected.

Adolescent↗

Pulmonary autograft for aortic valve replacement in rheumatic disease: a caveat.

Pulmonary autograft replacement of the aortic valve offers an attractive option in the younger patient with growth potential and long-term survival. In our institution between January 1990 and August 1994, 78 patients have undergone this procedure. The mean age was 18.6 +/- 7.36 years (range, 1 to 41 years). The etiology was rheumatic in 63 patients (80.7%). Aortic regurgitation was the predominant lesion in 60 patients (76.9%). Significant mitral regurgitation requiring operation was present in 22 patients (28.2%). All patients underwent pulmonary autograft replacement of the diseased aortic valve and the mitral valve was repaired in 22 patients. There were no hospital mortality, endocarditis, or thromboembolism in the series up to date. There have been two late non-cardiac deaths. Five patients (6.4%) required reoperation, one for mitral repair failure and four for autograft failure. Acute rheumatic valvulitis was demonstrated in one of the reoperated patients. Echocardiography of 68 patients followed up more than 2 months show progression of aortic regurgitation more than 2/4+ in 12 patients (15.4%). Four of these patients have been reoperated without mortality. In conclusion, although the Ross procedure remains a safe and attractive alternative in aortic valve operation, the progression of aortic regurgitation, especially in the younger patient with rheumatic etiology, remains a concern.

Adolescent↗