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Biomedical subjects

F Nobili

Publications and source records attributed to F Nobili.

At least 73 records · Page 4Linked to original sources

Human colonocytes in primary culture: a model to study epithelial growth, metabolism and differentiation.

The purpose of this work was to set up an in vitro model for the study of normal and pathological functions of the colonic epithelium. We have isolated colonic crypts by mild proteolytic digestion and mechanical dissociation of human biopsy material obtained during colonoscopy. The crypts, free of connective tissue, when placed in culture rapidly attached to the substrate and formed colonies containing over 95% of epithelial cells. Histochemical and ultrastructural characterization of the colonies showed the presence of both absorptive and secretory cells, exhibiting a high degree of differentiation. Proliferative activity occurred mostly during the first 24 h and progressively declined thereafter. The cells survived and maintained differentiated characteristics for at least three days in culture. This method can be used to study normal functions of the colonic epithelium. It may also be employed to investigate both noxious and protective factors in pathological conditions such as inflammatory bowel disease and colorectal neoplasia.

Cell Differentiation↗

First-trimester human trophoblast is class II major histocompatibility complex mRNA+/antigen.

Lack of expression of the polymorphic class I and class II MHC antigens in the cytotrophoblast is one of the major factors determining the privileged immunologic status of the placenta. In this report, we show that first-trimester human placental cytotrophoblast cells display moderate to strong expression of class II MHC (HLA-DR alpha and -DR beta) and Ii chain transcripts, apparently in absence of detectable class II antigens and Ii chain. In addition, DR alpha, DR beta, and Ii mRNAs, but not antigens, are consistently upregulated by IFN-gamma. Constitutive expression and upregulation of mRNAs are detectable in trophoblast cells kept in short term as well as prolonged (2-3 weeks) culture. These results are reminiscent of an analogous mRNA+/antigen- dissociation occurring, in the case of class I MHC gene products, in a subpopulation of first-trimester cytotrophoblast cells. Thus, analogous mechanisms prevent the expression of potentially hazardous class I and II allodeterminants at early stages of semiallogeneic pregnancy.

Blotting, Northern↗

Cerebral blood flow and somatosensory evoked response changes induced by spinal cord stimulation: preliminary follow-up observations.

A group of 6 patients undergoing cervical spinal cord stimulation (SCS) because of different pathologies was studied. Multipolar leads (QUAD-Medtronic) were inserted percutaneously; following an SCS test period, leads were connected to a multiprogrammable, fully implantable generator (ITREL II). Neither surgical nor other side effects were found. Regional cerebral blood flow (rCBF) (xenon-133 inhalation) was determined in the basal condition and after 30 min of SCS. Somatosensory-evoked potential (SSERs) from the legs were recorded in basal conditions and after 45 min of SCS. In 2 patients SSERs could not be evaluated due to electrical noise from SCS. CBF increased mainly in anterior regions in 4/6 patients (P300 improved in 1 of them and in another case), and was unchanged in 2 patients. rCBF was retested after a mean of 9.5 months of continuous SCS with the same parameters. rCBF returned to basal values in the 4 patients showing an early flow increase; in contrast, rCBF increased in the other 2 cases without early flow changes. These preliminary data seem to support the view of an acute effect of SCS on rCBF as well as on SSER, at least in some patients. Differences in long-term rCBF modifications might depend on either the underlying pathology or on the different neuronal system involved by SCS.

Adolescent↗

Regional cerebral blood flow in familial hypercholesterolemia.

BACKGROUND AND PURPOSE: Although epidemiologic investigations are trying to clarify the role of plasma lipid concentrations (primarily cholesterol and its subfractions) as risk factors for both ischemic and hemorrhagic stroke, little information is available regarding the effect of sustained hypercholesterolemia on cerebral perfusion. METHODS: Regional cerebral blood flow (CBF) was measured by the 133Xe inhalation method in 25 heterozygous patients (four untreated) affected with familial hypercholesterolemia. In 15 patients regional CBF was repeated 20 minutes after intravenous administration of acetazolamide (10 mg/kg body wt) to evaluate cerebrovascular reactivity. Correlations among cerebral perfusion data, present or pretreatment plasma lipid concentrations, and certain other clinical features were assessed by ANOVA. RESULTS: Both basal regional CBF and cerebrovascular reactivity were normal in the vast majority of patients compared with age- and sex-matched normal control subjects. CBF was significantly dependent on pretreatment low-density lipoprotein cholesterol (LDL-C) concentration (P = .005) and the presence of symptomatic ischemic heart disease (P = .015). CBF was only slightly dependent on age (P = .05) and was not dependent on either lipoprotein(a) or present LDL-C concentration. CBF did not differ between treated and untreated patients, and the perfusional increase induced by acetazolamide was not related to any other variable. CONCLUSIONS: Cerebral perfusion and cerebrovascular reactivity were maintained within the normal range despite long-lasting, severe hypercholesterolemia, even if a somewhat lower CBF was found in those patients with the highest LDL-C pretreatment levels. These results are in accord with the epidemiologic data that implicate hypercholesterolemia as a minor risk factor, if a risk factor at all, for intracranial atherosclerosis and ischemic stroke.

Acetazolamide↗

Expression of epithelial markers and retinoid-binding proteins in retinol- or retinoic acid-treated intestinal cells in vitro.

This study was undertaken with the aim of investigating the effects of retinoids on the expression of differentiated traits in intestinal cell models. The cell lines used included epithelial cells isolated from fetal rat intestines (FRIC), displaying a relatively undifferentiated phenotype, and the human colon adenocarcinoma cell lines Caco 2 and HT29, which express some of the traits of the mature enterocytes under defined culture conditions. The effects of retinoids were also studied in organ cultures of fetal rat intestine, where the epithelial-mesenchymal interactions are preserved. All-trans-retinol and all-trans-retinoic acid treatments were compared in their ability to regulate the expression of genes coding for proteins involved in retinoid metabolism and for cytoskeletal proteins. The results have shown that the effects of the two retinoids were qualitatively similar. A specific induction of the cellular retinol-binding protein CRBP I mRNA was observed following retinoid treatment in one of the two FRIC lines examined (FRIC B) and in organ culture. The expression of the retinoic acid receptors RAR alpha and gamma was not affected by treatment in any of the cultures examined, while RAR beta was expressed only by the organ cultures and was transcriptionally induced by retinoic acid treatment. The retinoids also induced a reorganization of the actin cytoskeleton in the FRIC B cell line, accompanied by a decrease in the expression of two components of the microvillar cytoskeleton, ezrin and villin. The results obtained in both cell and organ cultures suggest that retinoids alone are not able to trigger the differentiation program in the intestinal epithelial cell, irrespective of the level of differentiation already achieved at the time of treatment.

Animals↗

Metallothionein gene is expressed in developing rat intestine and is induced by zinc but not by corticosteroids.

The expression of metallothionein (MT) mRNA during perinatal development of rat intestine and its induction by zinc and corticosteroids were studied. Pregnant rats from d 17 to 22 of gestation and rats at 2, 4, 13 and 21 d of postnatal life were injected with saline solution (control) or with zinc (10 mg/kg body wt) or corticosteroids (1 mg/kg body wt). After 6 h, tissues were removed for analysis. Northern hybridization of polyA + RNA to 32P-MT-cDNA revealed that MT was expressed already at d 17 of fetal life, increased afterwards (reaching the maximal expression around birth) and decreased soon after until weaning. Metallothionein mRNA was markedly induced by zinc at d 18 of fetal life to a level that remained constant throughout postnatal life. Corticosteroids were ineffective in inducing MT gene expression during prenatal and postnatal development. In 21-d-old adrenalectomized rats the level of MT mRNA was similar to that of control rats of the same age and was not changed by hormone treatment. The results indicate that MT gene expression can be induced by zinc during fetal life and that its expression without exogenous inducers cannot be ascribed to circulating corticosteroids.

Adrenal Cortex Hormones↗

Regional cerebral blood flow in chronic stroke patients.

BACKGROUND AND PURPOSE: The aim of this study was to investigate regional cerebral blood flow parameters during the postacute phase of unilateral ischemic stroke and to correlate them with clinical data. METHODS: Regional cerebral blood flow was measured in 187 patients in the stabilized phase of stroke by the xenon-133 inhalation method with 32 extracranial detectors. Thirty-eight patients were reexamined after a mean +/- SD time of 32 +/- 21.4 months. RESULTS: The overall detection of hypoperfusion was 92.0%, with asymmetries as the most sensitive index, especially for patients with a lesser degree of neurological disability. Neurological disability score was strongly associated with regional cerebral blood flow in the affected hemisphere (p < 0.0001) and with asymmetries (p < 0.0001). The presence of carotid obstruction further decreased the regional cerebral blood flow in the affected hemisphere and significantly increased asymmetry (p < 0.0001). Subjects who had no hypoperfusion at absolute values analysis were more frequently free of carotid disease and had less severe disability than those who had bilateral or unilateral regional absolute cerebral blood flow reduction. In 38 patients without new cerebrovascular events, a significant (p = 0.005) reduction of hemispheric regional cerebral blood flow asymmetries was found on a follow-up examination. CONCLUSIONS: These data confirm the value of regional cerebral blood flow asymmetries in stroke detection and point out that important clinical information is also contained in absolute values analysis.

Adolescent↗

Regional cerebral blood flow in chronic hypertension. A correlative study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has occasionally been reported during essential hypertension. We explored regional cerebral blood flow in a large series of neurologically asymptomatic hypertensive patients to determine relations among cerebral blood flow, concomitant main vascular risk factors, and the most common signs of end-organ damage. METHODS: Regional cerebral blood flow was measured by the 133Xe inhalation method in 101 hypertensive patients without clinically apparent central nervous system involvement, including 39 mild to moderate untreated and 62 mild to severe treated patients. RESULTS: Compared with age- and sex-matched normal control subjects, cerebral blood flow was significantly reduced in untreated hypertensive patients (P < .01) and to a lesser extent in treated patients (P = .047). Both regional and global cerebral blood flow reductions were observed in approximately one third of patients in both groups. Analysis of variance failed to show significant correlations between cerebral blood flow and total cholesterol concentration, mean arterial blood pressure, duration of disease, or the presence of retinopathy or left ventricular hypertrophy. In the treated group, the quality of control of hypertension significantly influenced both global cerebral blood flow (P = .007) and cerebrovascular resistance (P < .0001). CONCLUSIONS: Focal or diffuse cerebral hypoperfusion is present even in neurologically asymptomatic hypertensive patients, especially when untreated; good control of blood pressure may preserve cerebral perfusion and reduce cerebrovascular resistance. Regional cerebral blood flow examination represents a relatively simple and low-cost technique to explore the perfusional condition of the brain, one of the main target organs of hypertensive disease.

Adult↗

Regional cerebral blood flow and cerebrovascular reactivity in IDDM.

OBJECTIVE: To investigate both rCBF and cerebrovascular reactivity, evaluated as pre- and post-ACZ rCBF differences in a group of IDDM patients with differences in duration of disease and severity of complications. RESEARCH DESIGN AND METHODS: rCBF was measured by the 133Xenon inhalation method in 20 IDDM patients and in 15 healthy control subjects before and after an intravenous injection of ACZ, a carbonic anhydrase inhibitor commonly used to assess cerebrovascular reactivity. RESULTS: Basal global CBF (the mean of 32 regional values) was within the normal range in all patients but 1, who showed slight hyperperfusion; moreover, in 3 patients with long-lasting disease, some hypoperfused regions were found. ANOVA showed an inverse correlation between basal global CBF (P < 0.01) and duration of diabetes, but no correlation with Hb, MABP, serum glucose concentration, or GHb. Compared with control subjects, the percentage of global CBF increment after ACZ administration was significantly impaired in 4 patients and gave a borderline response in 2 patients; 4 of these poor ACZ responders had retinopathy, and 1 had suffered from a TIA. Duration of diabetes, Hb, MABP, serum glucose concentration, and GHb did not correlate with the percentage of post-ACZ global CBF changes, and did not differ among the 6 poor ACZ responders and the other diabetic patients or control subjects. CONCLUSIONS: These results confirm that global CBF is within the normal range in most IDDM patients, although it is significantly influenced by the duration of diabetes; pathophysiological correlates of the altered cerebrovascular reactivity need to be further investigated. rCBF measurements, before and after ACZ administration, seem to represent a safe and reliable tool for assessing cerebrovascular function in IDDM.

Acetazolamide↗

Protein starvation impairs the ability of activated lymphocytes to produce interferon-gamma.

The impairment of lymphocyte function in nutritionally deprived rats was studied. Lymphocytes from rats fed a diet lacking protein showed a severe decrease in their ability to proliferate when stimulated with mitogens. This was accompanied by a dramatic inhibition of interferon-gamma (IFN-gamma) production and a lesser decrease in the release of interleukin-2 (IL-2). Analysis of RNA levels by Northern blot hybridization confirmed that lymphocytes from protein-starved rats had lower levels of mRNAs for IFN-gamma, IL-2, and IL-2 receptor than those from control animals. Protein deprivation therefore leads to a modification of lymphocyte function such that IFN-gamma production in particular is severely impaired.

Animals↗

[Diagnosis and therapy of low-risk endometrial hyperplasia. Experience with LH-RH-A].

Endometrial hyperplasia is a endometrial condition often found in perimenopausal age. AUB is the most frequent symptom of endometrial hyperplasia. The combination of hysteroscopy and endometrial biopsy is the most suitable approach for the diagnosis of endometrial hyperplasia in symptomatic patients. The Authors have studied endometrial modifications due to LH-RH analogue, a depot formula, in 60 perimenopausal patients with AUB and with hysteroscopic and histologic picture of low-risk endometrial hyperplasia. They report the result of treatment efficacy (disappearance of symptoms and tendency to hypoatrophy of the mucosa). The use of LH-RH A seems to have a good result in the management of oestrogen-dependent gynaecological benign diseases.

Adult↗

[Locoregional anesthesia for surgical arthroscopy of the knee].

A new technique for regional anaesthesia for arthroscopy of the knee is presented. The method includes sciatic nerve block according to the technique proposed by Labat, through a posterior approach and the block of the femoral and lateral cutaneous nerves using a single anterior approach. Results obtained in 30 patients are presented: they include good stability of the cardiovascular and respiratory parameters, high efficiency and duration of anaesthesia resulting in a satisfactory surgical procedure.

Adult↗

Effects of beta-adrenoreceptor antagonists on cerebral blood flow of cirrhotic patients with portal hypertension.

The current study evaluated the effect of two beta adrenergic-blocking agents, propranolol (PRP) and atenolol (ATN), versus placebo on cerebral blood flow (CBF) of three homogeneous groups of cirrhotic patients with portal hypertension. CBF was measured by the noninvasive 133-Xenon inhalation method at rest and 1 hour after a single oral dose of PRP (40 mg), or ATN (100 mg), or placebo. Blood pressure and heart rate (HR) were measured at the beginning of each examination, and end-tidal pCO2(PeCO2) was monitored. The HR decreased significantly in both the PRP and ATN groups (P less than .01), whereas no changes were recorded for both PeCO2 and mean arterial blood pressure (MABP). The comparisons of the CBF differences among groups (ANOVA with the significance levels adjusted by the Bonferroni's correction) showed a significant increase in CBF after ATN as compared with both placebo (P less than .02) and PRP (P less than .01), whereas no significant differences were seen after PRP as compared with placebo. Our results confirm that PRP does not significantly affect CBF, whereas ATN induces an increase in CBF, although the underlying mechanism is difficult to explain.

Adrenergic beta-Antagonists↗

Regional cerebral blood flow asymmetries in a group of 189 normal subjects at rest.

Regional cerebral blood flow (rCBF) asymmetries were studied in 189 subjects (96 males and 93 females) at rest with the 133Xenon inhalation method using a fixed detector system. rCBF asymmetries in the resting condition were very small, nevertheless a significant (p less than 0.001) effect for their topographical distribution was present, reflecting higher rCBF in the right fronto-temporal and left parieto-occipital regions. rCBF asymmetries were not correlated with age, and there were no significant differences between males and females. Asymmetries are therefore useful from a statistical point of view in detecting rCBF abnormalities in the resting condition: they are more stable than absolute values in normal subjects and no matching according to age or sex is required when statistical comparisons are performed.

Adolescent↗