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Biomedical subjects

F Nobili

Publications and source records attributed to F Nobili.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of retinoids on gene expression in different epithelial models in vivo and in vitro.

We have previously reported that the induction of Vitamin A deficiency results in a threefold decrease in the hepatic expression of cellular retinol binding protein I (CRBP I) mRNA in vivo and that the treatment of intestinal cell lines in vitro with retinoids leads to the induction of CRBP I transcription. In the present paper we extend the analysis to retinoid-dependent gene expression in the testicular epithelium in vivo and in the intestinal cell line FRIC B. In rat testis excess Vitamin A results in the reduced production of mature spermatozoa and in the premature release of immature germ cells in the lumen, while Vitamin A deficiency leads to almost complete degeneration of the germinal epithelium. We show reduced level of expression of CRBP I mRNA in vitamin A deficient testis. Retinoid treatment of cultured intestinal cells, which induces a reorganization of the actin cytoskeleton, has no effect on the expression of the differentiation induced gene Dri 42. The results show that even though unable to trigger by themselves the differentiation process, retinoids exert a direct effect on the expression of specific genes.

Animals↗
PubMed1997

Impaired quantitative cerebral blood flow in scleroderma patients.

Systemic Sclerosis (SSc) is a multisystem disease characterised by proliferation of vascular tissue, obliterative microvascular lesions and diffuse organ fibrosis. Despite widespread vascular disease, Central Nervous System complaints are only infrequently reported and it is uncertain whether they merely derive from systemic complications or whether they may be also caused by a primary vascular process within the brain. Regional cerebral blood flow (rCBF) was quantitatively measured by the 133Xenon clearance technique in twenty-seven consecutive SSc patients without relevant systemic complications and with different severity of vascular involvement, as staged by nailfold capillary videomicroscopy (NCV). Absolute, percent, and asymmetry rCBF values were compared (z-statistics) with age- and sex-matched healthy controls. Cerebral MRI and Mini-Mental State Examination (MMSE) were also performed. Doppler sonography of neck vessels and Transcranial Doppler sonography (TCD) were performed in patients presenting rCBF reduction. Cerebral hypoperfusion was found in the 52% of patients, i.e.: in 33% of patients with the 'early' NCV pattern, in 56% of patients with the 'active' pattern, and in 67% of patients with the 'late' NCV pattern. Thirty percent were the MRIs showing focal and/or diffuse signal abnormalities in the white matter of both hemispheres with the highest rate (44%) in the 'late' NCV pattern. MMSE disclosed mild dementia in one patient in the 'late' NCV group and some mistakes in 6 more patients, in the 'active' or 'late' NCV groups, whereas TCD failed to find significant stenosis of Willis' arteries. Cerebral hypoperfusion is shown for the first time in a substantial part of SSc patients without either neurological symptoms or relevant systemic complications. It is suggested that the rCBF reduction might be related to the systemic scleroderma microangiopathy although, probably due to the paucity of connective tissue in cerebral vessels, the vast majority of patients remains in a subclinical phase.

Adult↗
PubMed1997

Survey of the deliveries of immigrant women from developing countries in the 2nd Institute of Gynaecology and Obstetrics, University of Rome, 'La Sapienza', Italy.

Five hundred and forty-four immigrant women, admitted from 1983 to 1993 to the 2nd Institute of Obstetrics and Gynaecology of Rome University, were enrolled in the study. Africa and East Europe were the most common places of birth. Seventy-five per cent of women gave birth spontaneously, and a caesarean section was performed in 22.2%. The frequency of spontaneous delivery and caesarean section was about the same among Italian and immigrant women.

Journal Article↗
PubMed1997

Treatment of rats with dexamethasone or thyroxine reverses zinc deficiency-induced intestinal damage.

Structural and functional damage to the intestine and the potential beneficial effects of dexamethasone (Dex) and thyroxine (T4) were examined in zinc-deficient rats. Rats were assigned to zinc deficient (ZD), control (C) or pair-fed (PF ) groups and fed for 40 d a zinc deficient (1 mg/kg) diet (ZD rats) or a similar diet supplemented with 50 mg Zn/kg (C and PF rats). Some rats of the ZD group were treated for the last 10 d with low (250 mg/kg) or high (5 mg/kg) doses of Dex or with T4 (100 mg/kg). Serum corticosterone of T4-treated ZD rats did not differ from untreated ZD rats. Serum T4 of T4-treated ZD rats did not differ from C rats. ZD rats developed ulcerations, inflammation and edema in the small intestine, particularly in the jejunum. PF rats did not show mucosal changes relative to C rats. ZD rats showed significantly lower crypt cell production rate (CCPR) and labeling index (LI) in the three intestinal regions, and lower cell migration rate and higher turnover time in the duodenum relative to C rats. Sucrase and maltase activities of ZD rats were significantly lower than C rats in the three mucosal regions. Treatment with the low dose of Dex resulted in fewer ulcerations compared with ZD rats. In rats administered the high dose of Dex or T4, all morphological alterations disappeared; the CCPR, LI, cell migration rate, cell turnover time and disaccharidase activities did not differ from C rats. In conclusion, Dex and T4 exert beneficial effects on zinc deficiency-induced intestinal alterations in rats.

Animals↗
PubMed1997

Transcellular metabolism of leukotriene A4 by rabbit blood cells: lack of relevant LTC4-synthase activity in rabbit platelets.

The objective of this study was to determine the transcellular metabolism of leukotriene A4 by rabbit blood cells. mixed peripheral blood leukocyte preparations with and without platelets in a ratio of 1:40 were challenged with the Ca(2+)-ionophore A23187. 5-Lipoxygenase metabolites production was assessed by RP-HPLC coupled with diode-array UV detection. In light of the observation that leukotriene C4 production in leukocyte-platelet coincubation was the same as with leukocytes alone, mixed coincubation of human and rabbit blood cells was tested. Rabbit leukocytes with human platelets resulted in a significant increase of leukotriene C4 production, while no changes were observed in human leukocytes with or without rabbit platelets. In agreement with these results, intact rabbit platelets or rabbit platelet lysates, unlike human platelets, were not able to convert synthetic leukotriene A4 free acid to leukotriene C4. These data provide evidence that rabbit leukocytes are able to make a significant amount of leukotriene A4 available for transcellular metabolism, while rabbit platelets, unlike human platelets, lack leukotriene C4-synthase activity.

Animals↗
PubMed1997

[Congenital deformities of the chest wall. Surgical treatment].

BACKGROUND AND AIMS: Malformations of the front chest wall are congenital defects that have been reported since the seventeenth century and which include the clinical syndromes of funnel chest, pigeon chest and Poland's syndrome. Although they have been reported for such a long time, their pathogenesis is in many ways still unknown and the theories proposed up until now reveal uncertain and unsatisfactory findings. Attempts to gather precise information regarding their real incidence are equally ineffective given that frequently those cases which are not particularly severe are not referred for specialist care. These malformations usually involve severe psychological problems caused by the deformity and, in more severe cases, may lead to alterations in normal cardiac and respiratory function which are above all evident during intense physical effort. METHODS: The authors critically review the cases of chest malformation corrected by the Department of Pediatric Surgery at the G. Gaslini Institute during the period from 1986 to date. They describe the surgical techniques used, justifying their choice and discussing any postoperative complications. RESULTS: This experience shows that there is a clear preference for less invasive surgery for the correction of funnel chest compared to the technique proposed by Ravitch in which the sternum was totally mobilised following its extensive detachment from the other bone and muscular structures of the thoracic cage, with a high risk of damaging the internal mammary artery. The operation that was felt to be most suitable for correcting this defect was that described by Wesselhoett and De Luca in 1982. It is easier to perform and less invasive: it eliminates the detachment phase by inserting a support in titanium alloy through the sternal frame. Autologous grafts taken from the bottom contralateral ribs to the defect were used to treat Poland's syndrome in line with the technique suggested by Ravitch, thus achieving good stability of the whole chest; in view of the young age of the patients undergoing correction, it was not thought appropriate to proceed with the cosmetic reconstruction of the pectoral muscles using a peduncled flap of latissimus dorsi. A total of 70 patients were operated in this way; the cosmetic results were very satisfactory, whereas complications were limited to 5 cases of intraoperative pneumothorax, 5 cases of serohematic subcutaneous collection which were treated conservatively, and 1 case of hypertrophic scarring.

Child↗
PubMed1996

The Dri 42 gene, whose expression is up-regulated during epithelial differentiation, encodes a novel endoplasmic reticulum resident transmembrane protein.

A search for novel genes that are up-regulated during development and differentiation of the epithelial cells of the intestinal mucosa led us to the isolation of the Dri 42 cDNA clone (Dri, differentially expressed in rat intestine). The nucleotide sequence of the full-length cDNA has shown that it encodes a 35.5-kDa protein with one consensus sequence for N-linked glycosylation and alternating hydrophilic and hydrophobic domains. To determine the intracellular localization of Dri 42 we have raised polyclonal antibodies in hens against a bacterially produced Dri 42-glutathione S-transferase fusion protein. Immunofluorescence detection with these antibodies has shown specific staining of the endoplasmic reticulum (ER) in the relatively undifferentiated fetal rat intestinal cell line FRIC B and in sections of rat small intestine. ER membrane localization of Dri 42 was confirmed by laser confocal microscopy of polarized Madin-Darby canine kidney cells overexpressing a Dri 42-chloramphenicol acetyltransferase (CAT) fusion protein by transfection. Pulse labeling experiments on transiently transfected cells demonstrated that the protein does not acquire Golgi modifications up to 4 h after synthesis, thus indicating that Dri 42 is an ER resident protein. The transmembrane disposition of Dri 42 was studied using in vitro insertion of Dri 42-CAT fusion proteins into microsomal membranes. The fusion proteins consisted of several different lengths of truncated Dri 42 and a reporter protein, CAT, that was linked in-frame after each hydrophobic segment. We found that hydrophobic segments H1, H3, and H5 had a signal/anchor function, and that membrane insertion of Dri 42 was achieved co-translationally by the action of a series of alternating insertion signals and halt transfer signals, resulting in the exposure of both termini of the protein to the cytosolic side. The functional implications of the structure and localization of Dri 42, whose primary sequence does not share significant homology to any previously described protein, are discussed.

Amino Acid Sequence↗
PubMed1996

Cerebral haemodynamic changes induced by spinal cord stimulation in man.

Spinal cord stimulation (SCS) has been shown to influence cerebral perfusion in both experimental models and humans. With the aim of further verifying such an effect, twelve patients had an epidural (cervical or dorsal) lead inserted percutaneously and underwent regional cerebral blood flow (rCBF) examinations (133-Xenon inhalation method) before and during SCS. Mean blood velocity (MBV) in the middle cerebral artery was also measured in seven cases by means of transcranial Doppler. In the patients with a cervical lead, a symmetrical increase in rCBF was found, mainly in the anterior regions (from +8% to +21%). MBV increased in four cervical lead implants (from +16% to +20%) and in one case with a dorsal lead (+15%). These results suggest that cerebral perfusion may increase in patients undergoing SCS through a cervical lead. Although the mechanism involved in the increase in rCBF remains to be clarified, frontal lobe functional activation by the ascending reticular pathways through the thalamo-cortical projections might be hypothesised.

Adolescent↗
PubMed1996

Prognostic significance of quantitative electroencephalography in Alzheimer patients: preliminary observations.

In 31 Alzheimer outpatients followed up for a mean time of 26.4 months the hypothesis that quantitative electroencephalography (qEEG) could predict the loss of activities of daily living (ADL), the onset of incontinence, and death was tested by the Weibull proportional hazard model of 'lifereg' procedure of the Statistical Analysis System package. A central-posterior temporal region was considered in either side (power-weighted, log transformed relative values). Right delta predicted both the loss of ADL and death, whereas right theta predicted the onset of incontinence. Left values gave borderline significant results toward all end-points, whereas power-weighted mean frequency always gave borderline results. The curves calculated for predicted times may be a valid support for the clinician in attempting prognostic judgments of disease evolution.

Aged↗
PubMed1996

Cytokine gene expression in intestine of rat during the postnatal developmental period: increased IL-1 expression at weaning.

In the present study we have investigate whether cytokines are constitutively and differently expressed in intestine during the differentiative processes that take place at weaning. We have analyzed the expression of IL-1 beta, IL-2, IL-4 and IFN gamma by polymerase chain reaction in Peyer's patches (PP) and in intestine deprived of PP (I-PP) of rats from 16 to 30 days of age. The results showed a constitutive and marked expression of the cytokines already before weaning, with the exception of IL-2 in PP and IFN gamma in I-PP. IL-beta was the only cytokine to show a different expression at various ages with an initial increase at 19 days and a further elevation at 21 days when intestinal epithelium passes through major differentiative stages, suggesting an involvement of this cytokine in intestinal development. We have also tested whether treatment of rats with the immunosuppressor cyclosporin A (CsA) could affect intestinal differentiation. The results showed that only some markers of differentiation were affected (proliferation of staminal crypt cells and length of crypts). This was probably due to a direct effect rather than an immunomediated effect of CsA, since treatment of three intestinal cell lines (Caco-2, HT-29, FRIC) with CsA indicated that this drug can exert a cytostatic activity on intestinal cells.

Animals↗
PubMed1996

Cerebral blood flow reserve in patients with syndrome X.

BACKGROUND: Patients with syndrome X frequently show disorders of oesophageal motility, bronchial reactivity or impaired vasodilator capacity of peripheral vascular beds. For these reasons, it has been suggested that syndrome X may represent a generalized abnormality of vascular and non-vascular smooth muscle function, rather than an isolated coronary problem. OBJECTIVE: To measure the cerebral blood flow and cerebrovascular vasodilator reserve in syndrome X patients and in controls. METHODS: We measured the cerebral blood flow and cerebrovascular reserve in 16 patients with syndrome X [11 women, aged 59.5 +/- 10.8 years (mean +/- SD)] and in 16 age-matched healthy volunteers. No patients had evidence of stenoses of carotid and vertebral arteries on Doppler sonography. Cerebral blood flow was measured by the 133Xe inhalation method, using the initial slope index as the cerebral blood flow index. After a baseline measurement, a second cerebral blood flow measurement was performed 20 min after administration of 10 mg/kg acetazolamide intravenously. Acetazolamide is known to be a potent cerebral vasodilator. The percentage increase in cerebral blood flow after acetazolamide administration was considered an index of cerebrovascular vasodilator reserve. RESULTS: Under basal conditions, both regional and global cerebral blood flow were nearly identical in the control group and in the patient group (initial slope index 50.2 +/- 3.8 versus 50.3 +/-6.2, NS). After acetazolamide administration, the cerebral blood flow increase was 29.0 +/- 14% in the patient group and 29.5 +/- 11% in the control group (NS). CONCLUSIONS: Our data show that cerebral blood flow and cerebrovascular vasodilator reserve were preserved in a series of patients with syndrome X. These results are not consistent with the hypothesis of a diffuse smooth muscle disorder.

Acetazolamide↗
PubMed1996

Accuracy of 133-xenon regional cerebral blood flow and quantitative electroencephalography in systemic lupus erythematosus.

OBJECTIVE: Comparative assessment of sensitivity and specificity of regional Cerebral Blood Flow (rCBF) by 133-Xenon inhalation and quantitative Electroencephalography (qEEG) in patients with Neuropsychiatric Systemic Lupus Erythematosus (NP-SLE). METHODS: Sixty-two combined rCBF and qEEG examinations were performed in fifty-two SLE patients. Group A: 27 SLE patients without NP-SLE; group B: 17 patients with florid (within 1 month) NP-SLE; group C: 12 patients previous NP-SLE examined in the remission phase (four patients of which already considered in group B). The study also included data deriving from two sets of examinations in ten patients who were observed twice, in different phases of the clinical course of NP-SLE. RESULTS: In comparison to healthy controls, rCBF lower (p < .001) in group B only, whereas qEEG showed similar increases of both delta and theta relative powers together with a reduction of alpha relative power in groups A-C. As compared to group A, sensitivity and specificity in detecting cerebral abnormalities in group B were 76% and 78% for rCBF, and 59% and 44% for qEEG, respectively. In the ten patients examined twice, rCBF was consistent with clinical course in 90% of cases and qEEG in 60%. CONCLUSION: Total accuracy in detecting cerebral functional abnormalities during florid NP-SLE is better by rCBF than by qEEG. rCBF and, in selected cases, qEEG examinations are reliable markers of NP-SLE.

Adolescent↗
PubMed1995

Transcriptional regulation of the ezrin gene during rat intestinal development and epithelial differentiation.

Polarized intestinal epithelial cells are characterized by the presence of a brush border at their apical surface. The brush border cytoskeleton is assembled during cell differentiation and is composed of parallel actin bundles, held together by specific actin-binding proteins. Using specific cDNA probes we have studied the expression of the mRNAs encoding ezrin and moesin, two members of a class of proteins that connect the microvillar cytoskeleton to the plasma membrane, during the process of enterocyte maturation that occurs both in the embryonic and in the adult small intestine, along the crypt-villus axis. The steady state levels of ezrin mRNA were found to increase in the fetal gut epithelium between day 15 and day 20 of gestation and during the first week after birth, in parallel with the morphogenetic process that leads to cell polarization and brush border assembly. On the contrary, moesin mRNA is expressed at very low levels in the mature small intestine, with a sudden drop in transcription occurring at birth. In the continuously renewing epithelium of adult animals, ezrin mRNA levels are higher in the differentiated villus cells of the distal portions of the gastrointestinal tract and very low in undifferentiated crypt cells. These data demonstrate that the expression of the ezrin gene is regulated at the level of mRNA abundance during development and differentiation of the intestinal epithelium.

Amino Acid Sequence↗
PubMed1995

Assessment of regional cerebral blood flow during spinal cord stimulation in humans.

Increased cerebral perfusion has been reported in both animal models and humans undergoing spinal cord stimulation (SCS). However, this was an inconsistent finding and variables able to influence regional cerebral blood flow (rCBF) following SCS are poorly investigated. We report our experience on rCBF measurements by the xenon-133 inhalation technique in 20 patients receiving acute and chronic SCS for different pathologies in basal conditions. Neither acute nor chronic SCS induced significant rCBF changes in the group of patients as a whole. However females, non-atherosclerotic patients and patients with a cervical SCS lead, showed a trend (borderline statistical significance) toward a redistribution of rCBF with increased values in frontoprerolandic and decreased values in postrolandic regions. Although SCS appears to influence intracerebral distribution more than absolute changes in blood flow, the mechanisms underlying such a phenomenon remain unknown. Functional activation of frontal lobes by the ascending reticular pathways through the thalamofrontal projections could be one possible hypothesis which has to be confirmed by further studies.

Administration, Inhalation↗
PubMed1995

The expression of the Athb-8 homeobox gene is restricted to provascular cells in Arabidopsis thaliana.

We have characterized an Arabidopsis homeobox gene coding for a putative DNA binding protein that represents an early marker for vascular development. The full-length cDNA encodes a protein of 833 amino acids that we have designated Athb-8; it contains the conserved DNA binding domain that characterizes the HD-Zip family of transcription factors. RNA analysis showed that the Athb-8 gene is expressed during the vegetative and the reproductive phases of plant growth. A higher steady-state level of the Athb-8 mRNA was found in flowering stem and root. In situ mRNA analysis of Arabidopsis plants demonstrated that Athb-8 expression is restricted to the procambial cells of embryo and developing organs. Moreover, Athb-8-GUS expression was found in single parenchyma cells which are differentiating into tracheary elements in wounded tobacco transgenic plants. Finally, we showed that the auxin, indole-3-acetic acid, which is involved in vascular development and differentiation, modulates the expression of the gene. Taken together, these results suggest that Athb-8 might be a regulator of vascular development in Arabidopsis thaliana.

Amino Acid Sequence↗
PubMed1994

Subtractive hybridization cloning of novel genes differentially expressed during intestinal development.

Intestinal genes whose expression is regulated during development and differentiation were identified and cloned from a rat villi cDNA library using a subtracted cDNA probe. The isolated clones are transcribed in the fully differentiated intestinal epithelium 21 days after birth and absent or poorly expressed in the fetal gut at 15 days of gestation. Two of the DRI (differentially-expressed in rat intestine) genes are novel, while the others encode the microvillar protein ezrin and intracellular carrier proteins for retinol and fatty acids. Expression of the newly isolated DRI27 and DRI42 clones parallels epithelial differentiation during development and it is more pronounced in the distal portions of the small intestine. In situ hybridization experiments indicate that the DRI mRNAs are expressed in the differentiated cell types of the gut epithelium. Moreover, the expression of DRI27 and DRI42 is strongly related to the stage of epithelial differentiation during gut development. This relationship holds true also for the expression of DRI42 in other tissues. These clones will be a valuable tool to identify regulatory sequences and factors responsible for confining gene expression to the differentiated epithelial cell types in mammalian small intestine.

Animals↗