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Biomedical subjects

G Nanni

Publications and source records attributed to G Nanni.

At least 37 records · Page 2Linked to original sources
PubMed2001

Kaposi's sarcoma associated with previous human herpesvirus 8 infection in kidney transplant recipients.

This study investigates the prevalence of human herpesvirus 8 (HHV-8) infection in kidney transplant patients, evaluating the risk of HHV-8 transmission via transplantation and the association between pre- and posttransplantation HHV-8 infection and the subsequent development of Kaposi's sarcoma (KS). Immunofluorescence and an enzyme immunoassay were used to determine HHV-8 seroprevalence in 175 patients awaiting kidney transplantation and 215 controls who were attending our clinic for other reasons. All patients in the study came from central or southern Italy. Seroprevalence was similar in both groups (14.8 versus 14.9%), with no significant difference between the rates for male and female patients. Of the 175 patients, 100 were tested for anti-HHV-8 antibodies at various times during follow-up. During follow-up, seroprevalence increased from 12% on the date of transplantation to 26%. This increase was paralleled by an age-related increase in seroprevalence in the control group. During follow-up from 3 months to 10 years after transplantation, KS was diagnosed in seven patients (4.0%). Six of these patients were positive for HHV-8 prior to transplantation. Overall, 23.0% of patients who were HHV-8 positive before transplantation developed KS, whereas only 0.7% of seronegative patients developed the disease (relative risk, 34.4; 95% confidence interval, 4.31 to 274.0). This finding suggests that the key risk factor for KS is infection prior to transplantation and that antibody detection in patients awaiting transplantation could be useful in identifying patients at high risk for KS. In patients from geographic areas with a high prevalence of HHV-8, serological tests on donors may be less important.

Adult↗
PubMed2001

Interaction between monensin and CCl4 after chronic treatment: dolichol and retinol content of rat liver sinusoidal cells.

The aim of this investigation was to study retinol, which is known to decrease in hepatic stellate cells during fibrogenesis, and dolichol, which influences membrane fluidity and decreases in liver injury, in freshly isolated liver parenchymal and nonparenchymal cells after intoxication of rats with CCl4 combined with the ionophore monensin for 3, 5 and 7 weeks. To study the interrelationship between dolichol and vitamin A transport, a load of vitamin A was given to batches of rats 3 days before sacrifice. Monensin did not modify the action of CCl4 in hepatocytes. On administration of CCl4 and CCl4-monensin, dolichol decreased independently of vitamin A load, while retinol increased, especially when a load of vitamin A was given to rats 3 days before sacrifice. Hepatocytes appeared to no longer be able to export or metabolize vitamin A. In a subfraction of hepatic stellate cells (Ito-1 cells) dolichol always decreased, while retinol was no longer stored after each treatment; dolichol and retinol showed the same behavior but the decrease was more pronounced in monensin after vitamin A load and after 3 weeks. These data support the hypothesis that by modulating membrane characteristics, dolichol might be involved in intracellular or intercellular retinol transport and that altered transport between hepatocytes and Ito-1 cells might accompany liver injury. The data regarding another subfraction, Ito-2 cells, partly resemble those for the Ito-1 fraction and are in agreement with the heterogeneity of hepatic stellate cells. In Kupffer and sinusoidal endothelial cells, dolichol and retinol content was not homogeneous and was only slightly altered after the treatments. Monensin and CCl4 are not interactive. Although both drugs alter membrane lipids, their association allows some sinusoidal cell responses to be differentiated.

Animals↗
PubMed2000

Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registry-based study.

BACKGROUND: Organ transplant recipients are at an increased risk of nonmelanoma skin cancer. Few data concern heart transplantation and populations from southern Europe. METHODS: A total of 1,329 patients who received their first kidney (1,062 subjects) or heart allograft (267 subjects) were included in a partly retrospective cohort study to evaluate the risk of skin cancer. The incidence rate per 1,000 person-years and the cumulative incidence were computed. Standardized morbidity ratio was estimated by comparison with Italian cancer registry data. To analyze the role of potential prognostic factors, Cox's regression method was used. RESULTS: The overall incidence rate of nonmelanoma skin cancer was 10.0 cases per 1,000 posttransplant person-years (95% confidence interval 8.2-11.7). This estimate was far higher than expected in the general population. The overall risk of developing skin cancer increased from a cumulative incidence of 5.8% after 5 posttransplant years to an incidence of 10.8% after 10 years of graft survival. In a Cox proportional hazard risk model, the most important factors that appeared to favor the development of skin cancer were age at transplantation and sex. After adjustment for age at transplantation and sex, no definite increased risk was documented among heart as compared with kindney transplant recipients. CONCLUSIONS: Our study confirms the increased risk of nonmelanoma skin cancer among organ transplant recipients in a southern European population.

Basal Cell Carcinoma↗
PubMed2000

Action of chronic CC14 on the retinol and dolichol content of rat liver parenchymal and non-parenchymal cells.

We studied dolichol, on account of its role in membrane fluidity and fusion, and retinol, on account of its behaviour in liver fibrosis, in isolated parenchymal and sinusoidal rat liver cells after CCl4 treatment for 3, 5 and 7 weeks. Retinol uptake was also investigated by administering a load of retinol three days before sacrifice. In hepatocytes, dolichol decreased and seemed to be the preferred target of lipid peroxidation by CCl4; indeed, retinol increased especially after vitamin A load. Two subfractions of hepatic stellate cells were obtained: in the subfraction called Ito-1, dolichol decreased, while the supplemented retinol was no longer stored; in the subfraction called Ito-2, the values were intermediate. In Kupffer and endothelial cells dolichol was higher after three weeks, in agreement with fibrogenesis. Retinol increased after retinol load, in Kupffer and endothelial cells, in agreement with their scavenger function. The different behaviour of dolichol content in parenchymal and non-parenchymal cells suggests that dolichol may have different functions in liver cells. Since it has been ascertained that, in liver fibrosis, stellate cells gradually lose retinol, the inability of HCs to send retinol to Ito-1 subfraction or the inability of Ito-1 subfraction to take up and store vitamin A might induce or contribute to the transformation of these cells into a different phenotype. This behaviour is discussed regarding the role of cellular and retinol binding proteins in intracellular retinol content. Moreover a role of dolichol in membrane fluidity and retinol traffic is hypothesised.

Animals↗
PubMed2000

Effects of vitamin E on dolichol content of rats acutely treated with 1,2-dichloroethane.

Previous investigations have demonstrated that 1,2-dichloroethane (DCE) poisoning affects dolichol (Dol) concentration in rat liver. Dol, a long-chain polyprenol, is considered an important membrane component: as dolichyl phosphate, it is rate limiting for the synthesis of glycoprotein; as free or fatty acid, it is highly concentrated in the Golgi apparatus (GA) where it can increase membrane fluidity and permeability, required glycoprotein maturation and secretion. DCE biotransformation may stimulate pro-oxidant events through hepatocellular glutathione depletion. Since the molecules of Dol are susceptible to oxidative degradation, the aim of this investigation is to verify whether vitamin E (vit. E) supplementation in rats is able to prevent Dol breakdown during acute DCE treatment. Before acute DCE administration (628 mg/kg body weight), a group of male Wistar rats were pretreated with vit. E (33 mg/kg body weight) for 3 days. High-performance liquid chromatography analysis has shown that within 5-60 min after DCE administration, the Dol concentration decreased in liver homogenate, cytosol, microsomes and GA. Particularly, 60 min after the treatment, Dol levels in the trans Golgi fraction were 71% lower than in controls. Rat pre-treatment with vit. E prevented the DCE-induced decrease in Dol concentrations of all liver fractions considered, in particular the reduction of total-Dol observed in the trans Golgi fraction 60 min after treatment was only 40%. These data suggest that hepatic metabolism of DCE is able to promote peroxidative attacks which lead to the degradation of Dol molecules. The pre-treatment of rats with vit. E results in a good, although not complete, prevention of total-Dol depletion after DCE poisoning.

Animals↗
PubMed2000

HHV8 in renal transplant recipients.

Human herpevirus 8 (HHV8) DNA sequences have been found in lesions from patients with Kaposi's sarcoma (KS) in several forms including immunosuppressed transplant patients. We wanted to study the transmission of HHV8 in kidney transplant recipients and to assess the risk of development of KS related to the viral infection in this group of patients. We tested sera of 120 renal transplant recipients with serological assay for antibodies to HHV8 antigens before transplantation and then we tested sera of 66 patients of the same group after transplantation. Antibodies were detectable in 27.5% of the patients before transplantation. In the seropositive population 15.1% developed KS and in the negative group 1.1%. Analysing 66 posttransplant sera we noticed that 24% of the seronegative patients became positive after transplantation. Our data suggest that being positive for HHV8 before transplantation could be an important risk factor for the development of KS.

Antibodies, Viral↗
PubMed1999

Dolichol and retinol content of rat liver sinusoidal cells after chronic monensin treatment.

Aim of this study was to ascertain whether an impairment of communication between parenchymal and non-parenchymal liver cells involves vitamin A intercellular transport. The following approach was adopted: liver cells were isolated from rats treated chronically with the hydrophobic ionophore monensin i.p. for 3, 5, and 7 weeks and their retinol and dolichol content was assessed. Monensin, which alters membrane flow, was used because it had previously been reported to induce liver steatosis, cholestasis and glycogenolysis after acute treatment and, by preliminary morphological examination, to impair vitamin A transport between stellate cells and hepatocytes. Dolichol was chosen as a biochemical marker because it is a membrane lipid that modulates the fluidity and permeability of the membranes that retinol must cross. After monensin treatment, a load of vitamin A was given to rats three days before sacrifice, to ascertain whether its uptake by sinusoidal liver cells was altered. The main result was a dolichol decrease in hepatocytes and in the Ito-1 subfraction. In this latter, monensin induced a decrease in dolichol content only after vitamin A load. Moreover, while the hepatocytes were able to take up a load of vitamin A normally, the Ito-1 subfraction was no longer able to store retinol. Therefore the polarised transport of retinol between hepatocytes and stellate cells seemed impaired. The behaviour of sinusoidal endothelial cells and Kupffer cells might be ascribed to the functions of these cells and is not significantly modified by monensin. In conclusion, the altered cross-talk between sinusoidal cells in liver pathology might involve retinol as well as cytokines. Different pools of dolichol might have a role in this membrane process in a hydrophobic environment.

Animals↗
PubMed1998

1,1,2,2-Tetrachloroethane-induced early decrease of dolichol levels in rat liver microsomes and Golgi apparatus.

Dolichols are long-chain polyprenols containing 14-22 isoprene units, present in mammalian tissues as free dolichol (Free-Dol), fatty acyl dolichyl esters (Dol-FA), and dolichyl phosphate (Dol-P). The hepatic level of Dol-P seems to be a rate-limiting factor for glycosylation processes. Previous studies from our laboratory demonstrated the susceptibility of the dolichol molecule to undergo radical attacks. Since the toxicity of 1,1,2,2-tetrachloroethane (TTCE)is dependent on the free-radical production during hepatic biotrasformation, it was of interest to determine whether this haloalkane might affect glycosylation mechanisms by changing dolichol levels and distribution in rat liver microsomes and Golgi apparatus (GA). Male Sprague-Dawley rats received a single dose of TTCE (574 mg/kg body weight) and were then sacrificed at different times (5, 15, 30, or 60 min). In the TTCE-treated rats both serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and hepatic triglycerides (TG) were significantly higher than control, while microsomal glucose 6-phosphatase (G6Pase) activity was decreased. In total microsomes Dol-P levels considered rate-limiting for the biosynthesis of the N-glycosylated proteins were significantly lower than in the control group 15 min after TTCE treatment. In normal rat liver, F1 secretory fraction of CA is 60-fold enriched in total dolichol content with respect to microsomes. In this compartment the total dolichol content, essential for the increase in membrane fluidity and permeability required for glycoprotein maturation and secretion, decreased significantly 5 min after TTCE treatment. Our results suggest that TTCE may affect dolichol functions in rat liver.

Animals↗
PubMed1998

Human herpesvirus 8 in Italian HIV-seronegative patients with Kaposi sarcoma.

OBJECTIVE: To evaluate the prevalence of human herpesvirus 8 (HHV-8) DNA detection in a large series of human immunodeficiency virus-seronegative patients with and without Kaposi sarcoma (KS) from the central and southern regions of Italy where classic KS is prevalent. DESIGN: Samples of lesional, peripheral unaffected, and distant normal skin and peripheral blood mononuclear cells (PBMCs) from 33 patients with KS and PBMCs from 42 control subjects were analyzed using single and nested polymerase chain reaction techniques for the presence of HHV-8 DNA. PATIENTS: A total of 33 patients with KS not related to acquired immunodeficiency syndrome (26 patients with classic KS and 7 patients with iatrogenic KS) were studied. Furthermore, 2 control groups were enrolled. The first group consisted of 13 healthy volunteers, the second of 29 patients affected by different dermatological diseases. RESULTS: Human herpesvirus 8 sequences were found in 100% of lesional and perilesional specimens, in 33% of the distant normal skin samples, and in 69.6% of the PBMCs from patients with KS. A possible correlation between HHV-8 DNA in PBMCs and the clinical stage of the disease was observed. Moreover, the prevalence of viral DNA in PBMCs from the total control group was 23.8%. No viral DNA was detected in tissue biopsy specimens taken from the control group. CONCLUSIONS: Our data suggest that HHV-8 could be a widespread virus, at least in Mediterranean regions where KS is more prevalent, such as southern and central Italy. As with other herpesviruses, it may be present lifelong in latent form somewhere in the body and may contribute to the pathogenesis of KS when other predisposing conditions are present.

Aged↗
PubMed1998

Content of dolichol and retinol in isolated rat non-parenchymal liver cells.

The liver sinusoids, that are considered as a functional unit, harbour four types of sinusoidal cells (Ito, Kupffer, endothelial and pit cells). Dolichol content has been determined in many tissues and subcellular compartments, alteration has been reported in many types of liver injury, but until now no data are available on its content in every type of sinusoidal non-parenchymal liver cells. Dolichol and retinol metabolism might intersect in their traffic in biological membranes. Intercellular as well as intracellular exchange of retinoids is an essential element of important processes occurring in liver cells. It has been suggested that the role of dolichol, besides being a carrier of oligosaccharides in the biosynthesis of N-linked glycoproteins, may be to modify membrane fluidity and permeability, and facilitate fusion of membranes. Dolichol in the membrane is intercalated between the two-halves of the phospholipid bilayer, but its exact disposition is not known and the movement and distribution of retinoid in membranes may vary with the geometry of the membranes. Therefore the aim of this study is to obtain a global understanding of the sinusoidal system regarding dolichol and retinol content in each type of isolated rat liver sinusoidal cell, in normal conditions and after vitamin A administration. The information that can be drawn from the present results is that with normal vitamin A status of the animal, the dolichol content is almost uniform in all liver cells. After vitamin A supplementation, a great increase of dolichol, together with the known increase of retinol, can be measured only in a subpopulation of the Ito cells, the Ito-1 subfraction. Therefore in the cells that are present in the hepatic sinusoid, different pools of dolichol may have separate functions. Because retinol traffic among cells, membranes and plasma still remains to be fully understood, roles of dolichol in the exchange of vitamin A among sinusoidal liver cells are discussed.

Animals↗
PubMed1998

Effect of ethanol administration on the level of dolichol in rat liver microsomes and Golgi apparatus.

Data obtained in our laboratory had suggested that acute ethanol administration (6 g/kg body weight) selectively and rapidly affects the intracellular system of protein glycosylation at the level of the Golgi apparatus. Dolichols are important membrane components, and dolichyl phosphate is a glycosyl sugar carrier for N-glycosylation of proteins in endoplasmic reticulum and is considered rate-limiting for this process. In this study, modifications in the concentration and distribution of liver microsomal dolichols after acute ethanol administration were investigated. Between 3 and 24 hr after ethanol administration, the microsomal dolichyl phosphate concentration was significantly lower than in control animals. The highest reduction was observed at 12 hr (-52%). An earlier and more marked reduction of total dolichol was observed in the Golgi apparatus, and, in particular, in the secretory fraction F1 (-70% at 6 hr). Ethanol treatment of isolated hepatocytes led to a significant reduction of the de novo synthesis of both dolichyl phosphate and free dolichol. Moreover, in vitro experiments have demonstrated that pro-oxidant agents lead to a significant decrease of both free dolichol and dolichyl phosphate. Our results suggest that acute ethanol administration induces a marked decrease of dolichols, probably by increasing the degradation and impairing the biosynthetic pathway of these molecules.

Animals↗
PubMed1997

Immunohistochemical analysis of p53 protein in transplant recipients with Kaposi's sarcoma.

PURPOSE: Kaposi's sarcoma (KS) is a proliferative process of suspected viral aetiology associated with immune deficiency. In transplanted patients, lesions regress on discontinuation of immunosuppressive therapy. The purpose of this work was to analyse the expression of the p53 oncosuppressor gene product, a proliferation regulator overexpressed in both malignant and non-malignant conditions, with the aim of better qualifying KS proliferation characteristics. METHODS: We analysed p53 expression in a group of transplanted, cyclosporin A-treated, KS patients by immunohistochemistry, utilizing the DO-7 (with and without the antigen retrieval pretreatment), and the PAb 240 monoclonal anti-p53 antibodies, the latter of which is able to detect a mutated epitope, and evaluating staining intensity and localization, whether cytoplasmic or nuclear. RESULTS: Seventy five percent of KS lesions from transplanted patients presented both nuclear and cytoplasmic positive p53 immunostaining with DO-7 antibody, thus demonstrating a presumably functional inactivation; one case also presented immunoreactivity with the PAb 240 antibody. CONCLUSIONS: On the basis of the results obtained and in the presence of lesion regression upon immunosuppression withdrawal, it may be concluded that KS in transplanted patients can be considered a non-malignant proliferative process, and that the cytoplasmic expression of p53 may stand for a functional inactivation pattern.

Female↗
PubMed1997

Dolichol and vitamin A content in rat liver Ito (perisinusoidal) cells.

Dolichol has been determined in many tissues but to date no data are available on liver Ito (fat storing) cells. In this note dolichol was determined in two subpopulations of liver Ito cells isolated from rats pretreated with vitamin A: Ito-1, vitamin A enriched and Ito-2, relatively poor of vitamin A. Differences were observed in the behaviour of the two fractions after vitamin A pretreatment of rats. In fact, in Ito-1 fraction dolichol increases with the increase of vitamin A, while in Ito-2 fraction it does not change significantly with the increase of vitamin A. These results, while confirming the heterogeneity of fat storing cells, are discussed as to the possible role of dolichol and vitamin A metabolism.

Animals↗