PubMed Health⌕ Search

Biomedical subjects

M Fazi

Publications and source records attributed to M Fazi.

At least 19 recordsLinked to original sources

[Sarcoidosis and clear cell carcinoma of the kidney: the sixth case?].

The Authors report a very rare case of clear cell renal cancer associated with sarcoidosis, incidentally discovered in a 39 year-old man, admitted for a not correlated pathology (multiple left rib fractures due to automobile crash). Problems related to a proper assessment of sarcoidosis are discussed as well as potential arising of a neoplasm during the entire follow-up period: for that, it must always be complete and accurate.

Adenocarcinoma, Clear Cell↗

Syngeneic consecutive rat spleen transplantation bearing infantile testis.

Seventy-seven Lewis adult rats received autologous testicular implants in the spleen. These spleens were retransplanted in a consecutive transplant fashion as we described earlier. Some were observed as long as 26 to 27 months. Although earlier splenic-testicular transplants showed benign granulosa cell tumors, some of the long-term follow-ups showed a seminoma-like transformation.

Animals↗

Update on sequential isologous rat organ transplantation: pancreaticoduodenal and kidney transplantations.

This periodic report includes intermittent results of consecutive pancreaticoduodenal (Pd) and kidney (Kt) transplants in inbred rats and results on double kidney transplants that did not follow sequential transplant protocol. Eight 24-month-old Lewis pancreas, kidney, and aorta served histological controls showing normal histological architecture with no atherosclerosis developed in the aorta. Thirty-four month old pancreas and thirty-two month old kidneys, which resided in young hosts for at least three occasions, appeared as youthful Pd and Kt grafts. They show normal histological appearance for more than the expected life span of a Lewis rat. The fact that not only pancreases but also kidneys outlived their host leads to the study of other different organs' viability as aged valuable grafts. Nevertheless, the threats by the development of atherosclerosis in graft-associated aortas resulted in slow progression of the follow-ups.

Animals↗

Extracellular signal-regulated kinase activation differentially regulates platelet-derived growth factor's actions in hepatic stellate cells, and is induced by in vivo liver injury in the rat.

Upon liver injury, hepatic stellate cells (HSC) show increased proliferation, motility, and extracellular matrix (ECM) production. The extracellular signal-regulated kinases (ERK) control different functions in a cell-specific manner. In this study, we evaluated the role of ERK activation in cultured HSC stimulated with platelet-derived growth factor (PDGF) and after induction of liver injury in vivo. HSC were isolated from normal human liver tissue, cultured on plastic, and used in their myofibroblast-like phenotype. In in vivo experiments, HSC were isolated from normal rats or at different time points after a single intragastric administration of CCl(4). Nontoxic concentrations of PD98059, a specific inhibitor of ERK activation, reduced PDGF-induced activation of ERK in a dose-dependent fashion. Suppression of ERK activation was associated with complete inhibition of HSC proliferation and with a 57% reduction in chemotaxis. In the presence of the ERK inhibitor, binding of the AP-1 complex and of STAT1 to the related regulatory elements was inhibited. The inhibition of the DNA binding activity of STAT1 was mediated by a reduction in PDGF-induced tyrosine phosphorylation. Expression of c-fos in response to PDGF was also reduced, but not suppressed, by treatment with PD98059. In HSC isolated from CCl(4)-treated rats, ERK activity increased as early as 6 hours following liver damage, and declined thereafter. The results of this study indicate that ERK activation regulates proliferation and chemotaxis of HSC, and modulates nuclear signaling. Acute liver damage in vivo leads to activation of ERK in HSC.

Animals↗

Migration of mesothelioma cells correlates with histotype-specific synthesis of extracellular matrix.

Three human pleural malignant mesothelioma cell cultures (MM) of epithelioid (E1), fibrous (F1) and byphasic (B1) histotype were studied in their synthesis of the extracellular matrix (ECM) components laminin (LM), fibronectin (FN), type IV collagen (cIV), and in their chemotactic and haptotactic migration towards the ECM produced proteins. MM-B1 showed the highest FN synthesis and release; MM-E1 produced the highest quantity of basement membrane constituents LM and cIV; MM-F1 weakly produced and released FN, LM and cIV. MM-B1 had the highest chemotactic and haptotactic motility, MM-F1 migrated toward the lowest concentration of LM while had reduced chemotactic activity toward FN and cIV; MM-E1 had the lowest migratory activity toward each ECM substrate. We demonstrated that three MM of different histotype are characterized by different ECM production and that these differences determine a variable ability of each MM to spread and migrate towards ECM substrates.

Cell Movement↗

Mutations of the Apc gene in experimental colorectal carcinogenesis induced by azoxymethane in F344 rats.

We investigated in the rat the role of the Apc gene, which is mutated in familial adenomatous polyposis and sporadic colon cancer in the process leading from normal colonic mucosa to aberrant crypt foci (ACF) and finally to adenomas and adenocarcinomas. We analysed mutations in exon 15 of the rat Apc gene using in vitro synthesized protein assay in 66 ACF and in 28 colon tumours induced by azoxymethane. No Apc mutations were found in ACF, whereas five mutations were found in the tumours. The data suggest that mutations of the Apc gene are associated with the transition from ACF to adenoma and adenocarcinoma and not from normal mucosa to ACF.

Adenocarcinoma↗

Modification of azoxymethane intestinal carcinogenesis in rats by feeding sucrose boluses, pasta, and glucose.

We studied whether repeated boluses of sucrose or diets containing carbohydrates with a variable glycemic index (GI) affect intestinal carcinogenesis in rats. Male F344 rats were treated twice (1 wk apart) with 15 mg/kg sc azoxymethane (AOM) and then divided into four experimental dietary groups with different carbohydrate composition and administration schedules: the sucrose group was fed 44% (wt/wt) sucrose (GI = 65), the bolus group was fed sucrose as carbohydrate and 43 boluses of sucrose (10-15 g/kg) at various time intervals, the pasta group was fed pasta [77% (wt/wt) cooked pasta, GI = 55], and the glucose group was fed 44% (wt/wt) glucose (GI = 97). All nutrients, including carbohydrates, were provided in similar amount to the different groups. The experiment was terminated between Day 230 and Day 245 after AOM administration. At this time the pasta group had significantly higher cecal short-chain fatty acids than the other groups. Intestinal adenomas and cancers occurred with the same frequency in the bolus, sucrose, and glucose groups. On the contrary, we observed a significant decrease (p = 0.03) in the cumulative incidence of intestinal adenomas, but not adenocarcinomas, in the pasta group compared with the sucrose group (intestinal adenoma incidence in the pasta group was 31% compared with 63% in the sucrose group, 46% in the bolus group, and 37% in the glucose group). In conclusion, these results do not support the hypothesis that sucrose boluses or carbohydrates with a high GI stimulate colon carcinogenesis, but they indicate that foods such as pasta may exert a protective effect.

Adenoma↗

Aberrant crypt foci in human colon carcinogenesis.

We developed a procedure for the endoscopic visualization in humans of aberrant crypt foci (ACF), preneoplastic lesions of the colon mucosa, and we determined the frequency of ACF in resected sections of human colon. For the endoscopy we studied 12 consenting adults (6 controls and 6 colon cancer cases) by dyeing colon mucosa with 0.5% methylene blue and searching ACF with a magnifying endoscope. ACF of varying dimensions were visualized in all subjects. We also studied colon surgical specimens from patients with colon cancer or diverticulitis. After staining the mucosa with 2% methylene blue, we found approximately the same density of ACF in the colon mucosa of the patients with colon cancer as in that of patients with diverticulitis (ACF/cm2 were 0.124 +/- 0.143 [N = 14] and 0.108 +/- 0.210 [N = 4], respectively [mean +/- SD]). In conclusion, the visualization of ACF with methylene blue in humans does not identify groups at low and high risk of colon cancer.

Adult↗

Effects of GM1 ganglioside on cardiac function following experimental hypoxia-reoxygenation.

Rat hearts made hypoxic for 20 min by perfusion with 95% N2/5% CO2 and reoxygenated for 20 min in a Langerdorff apparatus showed a dose-dependent reduction of lactate dehydrogenase release when incubated with ganglioside GM1 (0.1-10 microM). The decline of contractile force during hypoxia was also reduced dose dependently in the presence of GM1. Similar effects were observed in hearts obtained from animals treated i.p. with 40 mg/kg GM1 for 14 days. The levels of Na+,K(+)-ATPase in ventricular tissue were also reduced after hypoxia-reoxygenation and the reduction was prevented in hearts from GM1-treated animals. GM1 (1-30 microM) reduced the functional response to field stimulation of adrenergic nerve terminals in isolated atria. Rat atria made hypoxic in glucose-free media maintained normal stores of tissue noradrenaline in the presence of 1 microM GM1. In the rabbit, GM1 (40 mg/kg i.p. for 4 days) reduced the alterations of the ST segment of the ECG during acute occlusion of the left descending and circumflex coronaries artery. In conclusion, ganglioside GM1 reduces some effects of hypoxia-reoxygenation in the heart, through still unknown mechanisms.

Animals↗

Effect of caval-portal shunt on ovarian tissue in rats: I. Histological observation.

Forty-three female Sprague Dawley rats were divided into five groups, with groups 1-4 subjected to end-to-side caval-portal shunt (CPS). In addition to CPS, group 1 (n = 13), group 2 (n = 10), and group 3 (n = 7) rats had undergone removal of the right ovary and one-half of the left ovary, the left ovary, and one-half of the left ovary, respectively. Group 4 (n = 6) rats were not subjected to ovariectomy. Group 5 (n = 7) animals were not subjected to CPS but underwent left ovarian hemiresection. The ovarian volume of the hemiresected ovaries increased to 393.00 +/- 4.83 mm3 and 126.00 +/- 44.3 mm3 from 18.40 +/- 0.54 mm3 and 18.40 +/- 0.59 mm in groups 1 and 3, respectively, at the end of three postoperative months. The nonresected ovaries enlarged to 339.98 +/- 5.09 mm3 and 226.3 +/- 46.2 mm3 from 36.79 +/- 1.09 mm3 in groups 2 and 3, respectively. When no ovaries were resected, the CPS animals in group 4 showed an increment of ovarian volume of 1.75-2.2 times as much as the preoperative ones. In the animals that had undergone simple hemiovariectomy (group 5), the contralateral ovaries showed a significant increase in volume (40.2 +/- 8.3 mm3 to 243.1 +/- 114.8 mm3) at 3 months. The hemiresected ovarian volume increased from 27.1 +/- 5.5 mm3 to 44.1 +/- 11.8 mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Protective effect of gangliosides on myocardial hypoxic damage in the rat.

The size of the infarct produced by ligation of the left coronary artery in the rat was decreased significantly in animals treated i.p. with 40 mg/kg per day of a ganglioside mixture (GMIX) for 7 days after surgery. Rats treated with GMIX had lower ventricular myeloperoxidase activity, indicating a lower leukocyte infiltration after infarction. The underperfused zone was also smaller in animals treated daily with GMIX 30 days after surgery. Control hearts, but not hearts obtained from animals pretreated for 15 days with 40 mg/kg per day of GMIX, released lactate dehydrogenase (LDH) during perfusion in a Langerdorff apparatus after ligation and reperfusion of the left coronary artery in vitro. Hearts made hypoxic in vitro by changing the perfusion gas to nitrogen for 20 min and later reoxygenating with 95% O2 -5% CO2 released LDH in the perfusate, but did not do so in the presence of 10 microM monosialotetraesosylganglioside. Gangliosides, therefore, seem to protect the rat heart against hypoxic damage.

Animals↗

Gastric hyperplastic changes and thymidine uptake after partial gastrectomy in rats.

Foveolar hyperplastic changes have been recently considered to be the most distinctive histological finding after partial gastrectomy, and their relationship with bile reflux has been proven. The present study was undertaken to establish whether an increase in 3H-thymidine uptake--which is an expression of increased gastric mucosal proliferative activity--might correspond to these hyperplastic changes. Histology and thymidine uptake values were assessed and compared in nineteen rats operated upon either by means of a Polya gastrectomy (11), or with a Roux-en-Y biliary diversion (8). Thymidine uptake values and the extent of gastric hyperplastic changes were greater in the Polya than in the Roux-en-Y group. Moreover, a significant correlation was found between thymidine uptake values and the extent of hyperplastic changes. The relationship between hyperplastic changes and post-gastrectomy increased mucosal proliferative activity would thus seem to have been demonstrated. Since bile acids have been shown to stimulate cell proliferation in ileal and colonic mucosa, a rôle for bile reflux can be hypothesized for the increased cell proliferation activity in the gastric stump.

Animals↗

Gastric hyperplastic changes and thymidine uptake after partial gastrectomy in rats.

Foveolar hyperplastic changes have been recently considered to be the most distinctive histological findings following partial gastrectomy, and their relationship to bile reflux has been proven. The present study was undertaken in order to determine whether an increase in 3H-thymidine uptake, which is an expression of increased gastric mucosal proliferative activity, might correspond to these hyperplastic changes. Histology and thymidine uptake values were assessed and compared in nineteen rats operated upon either with a Polya gastrectomy (11) or with a Roux-en-Y biliary diversion (8). Thymidine uptake values and the extent of gastric hyperplastic changes were greater in the Polya than in the Roux-en-Y group. Moreover, a significant correlation was found between thymidine uptake values and the extent of hyperplastic changes. Therefore, the relationship between hyperplastic changes and increased mucosal proliferative activity post-gastrectomy would seem to have been proven. Since bile acids have been shown to be able to stimulate cell proliferation in ileal and colonic mucosa, a role for bile reflux in the increased cell proliferation activity in the gastric stump can be hypothesized.

Anastomosis, Roux-en-Y↗

Non-acid gastroesophageal reflux. Detection and evaluation by means of combined esophageal and gastric pH-monitoring.

One hundred and fifteen partially-gastrectomized patients were submitted to combined gastric and esophageal pH-monitoring with the aim of studying non-acid gastroesophageal reflux (GER). Since the detection of non-acid GER seems to be linked to the possibility of detecting entero-gastric reflux, only those patients (61) in whom entero-gastric reflux could be evaluated were considered. 37.7% of the patients showed non-acid GER according to the personal definition of such a reflux (any sudden esophageal pH change of 0.5 or more with earlier or simultaneous entero-gastric reflux). On the contrary, with De Meester and coworkers' criteria, only 21.3% of the patients were considered alkaline refluxers. Slight symptoms and slight endoscopical/histological changes were present in 20-30% of both non-refluxers and refluxers (whichever method of GER evaluation was considered). Therefore, correlations between GER and symptoms, endoscopical changes and manometric findings seemed poor using either method of GER evaluation. However, since the theoretical basis of combined gastric and esophageal pH-monitoring seems correct and the application of new techniques and the development of the parameters of "normality" can hopefully increase our understanding, the routine use of gastric and esophageal pH-monitoring should not be abandoned.

Adult↗

Folate deficiency in operated terminal ileitis (Crohn's disease).

In a series of 39 subjects previous results for serum folate levels were confirmed while intraglobular folate did not differ from those in a control group. To verify the hypothesis that SASP administration could be responsible for serum folate deficiency three different sub-groups were considered. 11 patients had never taken SASP (sub-group I), 16 patients had taken SASP in the past but the treatment had been withheld at least 2 months before (sub-group II), 12 patients were still taking the drug at the time of the study (sub-group III). Differences in serum folate levels between each one of the three sub-groups and the control group were significant. The same was not true for the differences between each one of the three sub-groups and the other. These findings seem to confirm that SASP treatment is not the major cause of serum folate deficiency, but a multifactorial pathogenesis might account for it.

Adolescent↗