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Biomedical subjects

D Franco

Publications and source records attributed to D Franco.

At least 109 records · Page 6Linked to original sources

Effects of bile acids and cholestasis on major histocompatibility complex class I in human and rat hepatocytes.

BACKGROUND/AIMS: Major histocompatibility complex (MHC) class I molecules, which are normally poorly expressed on the surface of hepatocytes, are overexpressed during cholestasis. The mechanisms responsible for this overexpression were examined. METHODS: The expression of class I molecules, assessed by flow cytofluorimetry, and the class I messenger RNA (mRNA) transcripts, assessed by Northern blot analysis, were measured on normal human hepatocytes in primary culture. RESULTS: Chenodeoxycholic acid induced an overexpression of MHC class I molecules, whereas ursodeoxycholic acid did not. The level of class I mRNA closely reflected that of the membrane protein. Moreover, cholestasis, induced in the rat by ligation-section of the common bile duct, increased the MHC class I mRNA level. Actinomycin D inhibited bile acid-induced class I transcription of rat hepatocytes in primary culture, whereas cycloheximide did not. Finally, class I mRNA expression was induced in hepatocytes by phorbol myristate acetate and by forskolin. This hyperexpression, as well as that observed with chenodeoxycholic acid, was suppressed by an inhibitor of protein kinase C and protein kinase A. CONCLUSIONS: Taken together, these results suggest that chenodeoxycholic acid, as interferon, activates protein kinase C and protein kinase A, resulting in the induction of MHC class I expression.

Adult↗

Mucoid dysplasia of tricuspid and congenital bicuspid aortic valves in Syrian hamsters (Mesocricetus auratus).

A histological study was made of the aortic valves of 141 Syrian hamsters aged between 35 and 657 days, belonging to an inbred laboratory colony with a high incidence of congenital bicuspid aortic valves. A tricuspid aortic valve was found in 81 specimens, whereas the remaining 60 possessed a bicuspid aortic valve. In all bicuspid valves there were two aortic sinuses, a ventral and a dorsal, each supporting one cusp. Thirty-three (23.4%) of the 141 specimens showed mucoid dysplasia of the aortic valve. The defect was characterized by thickening of the valve cusps and disruption of the fibrosa layer accompanied by an increased amount of glycosaminoglycans. Ten (12.3%) of the 81 tricuspid aortic valves and 23 (38.3%) of the 60 bicuspid aortic valves were dysplastic. This difference was statistically significant (P < 0.001). The findings indicate that, in the Syrian hamster, the simultaneous occurrence of bicuspid aortic valve and aortic valve dysplasia is not a random event. However, the fact that these valve defects also occur independently suggests that there is no primary morphogenetic dependence between them, but that some other cause predisposes to their concurrence.

Animals↗

Cartilage in the aortic valve and its relationship with the aortic valve morphology in Syrian hamsters.

We conducted a light-microscopic histologic study of the aortic valves of 224 Syrian hamsters aged between 1 and 771 days. Most of the hamsters examined belonged to a single laboratory-inbred family with a high incidence of bicuspid aortic valves (BAVs). In 146 specimens the aortic valve was tricuspid, and in 107 of them the ventral commissure was more or less fused. The remaining 78 specimens showed a BAV with the aortic sinuses oriented ventrodorsally. In 33 BAVs a raphe was located in the ventral aortic sinus. Cartilaginous foci were present in the aortic valves of 86 specimens, 40-771 days old. The foci were located at two different sites, namely in the ventral wall of the valve and/or in the dorsal aortic sinus. Statistical analyses substantiate that (1) chondrogenesis begins earlier in BAVs, and especially in those having a raphe, than in tricuspid aortic valves and (2) the location of the cartilaginous foci is significantly associated with the morphology of the aortic valve. The present findings support the hypothesis that, in the Syrian hamster, cartilage forms in the aortic valve as a response to locally intense mechanical stimulation.

Animals↗

[Training of surgeons for laboratory research].

A degree in surgical research has been set up in 1986 in France. It includes a one-year full time work in a research laboratory, and seminars (one to three days long, each). General surgical research objectives are gathered in a first seminar. Then, candidates select one among four optional subjects: biomaterials-artificial organs, transplantation, oncology, and neurosciences. Two prerequisites are necessary in order to register. The first is to write a research project according to standardized rules, and the second is to attend two seminars, one dealing with scientific communication and the other with methodology in clinical research. A nation-wide valid Academic degree is delivered to candidates who pass an oral presentation of their research report and who attended all seminars according to the optional subject that they selected. From 1986 to 1993, 434 students attended the formation. They came from different regions of France, proving the nation-wide characteristic of the degree, and some from foreign countries. Seminars were held in different French University towns. An increasing number of students become Ph.D.

Education, Medical, Graduate↗

The Sugiura procedure: a prospective experience.

BACKGROUND: The Sugiura procedure, which includes esogastric devascularization, splenectomy, and esophageal transection, aims to suppress esophageal varices without exposing the patient to hepatic encephalopathy, because the operation does not alter hepatic blood flow. METHODS: From May 1978 to March 1989, 39 patients (79% with cirrhosis) with previous variceal bleeding underwent an elective Sugiura procedure. Thirteen of them (33%) had recurrent bleeding despite medical therapy. RESULTS: There were neither operative deaths nor intraoperative complications. Eighteen patients (46%) had 19 postoperative complications, which were severe in 7 cases. During the second postoperative month, 68% of the patients had no visible varices at endoscopy. There was no alteration of liver function at 1 year after operation. Ninety-five percent, 85% and 76% of patients were free of recurrent variceal bleeding at 1, 3, and 5 years, respectively. None of the patients had chronic encephalopathy. One-, 3-, and 5-year survival rates were 95%, 70%, and 70%, respectively. Survival curves were not different in patients with and without cirrhosis. CONCLUSIONS: The Sugiura procedure carries a low operative risk and results in good prevention of recurrent variceal bleeding. Moreover, the liver function remains stable after operation and there is no significant risk of hepatic encephalopathy. This procedure should be reserved for failure of medical therapy.

Adult↗

[Cystadenoma of the liver. Clinical, radiological and anatomopathological study of 5 cases, one associated with cystadenocarcinoma].

We describe the clinical, radiological and pathological features of 5 cases of cystadenoma, one associated with cystadenocarcinoma. In 3 of these patients, the presence of thick wall, endoluminal buds and septations at imaging investigations was suggestive of the diagnosis of cystadenoma or cystadenocarcinoma. In 2 of these patients, these imaging features were lacking. In 2 of these patients, partial surgical resection was performed and was followed by recurrence of the tumor. In all cases, the diagnosis was confirmed by pathology examination of the resection specimen. In conclusion, this study shows that diagnosis of cystadenoma or cystadenocarcinoma may be very difficult because of the absence of suggestive imaging features in some cases, and confirms that complete resection of the tumor, allowing pathology confirmation, is needed for the optimal treatment of cystadenoma or cystadenocarcinoma.

Adult↗

MDR1 (multidrug resistance) gene expression in human primary liver cancer and cirrhosis.

MDR1 RNA levels were analysed in patients with hepatocellular carcinoma (HCC), benign liver tumors or cirrhosis. None of the patients with HCC had received chemotherapy. MDR1 RNA levels were increased relative to a normal liver specimen in 15/26 liver cancers, 2/6 benign liver tumors and 0/8 tumor-free cirrhotic livers. MDR1 was also overexpressed in cirrhotic non-tumorous liver tissues of some patients with HCC. The results indicate that the MDR1 gene is overexpressed in liver tumors and some preneoplastic lesions and that might account for the very poor response of primary liver cancers to chemotherapy.

Carcinoma, Hepatocellular↗

The coronary arteries of the Syrian hamster, Mesocricetus auratus (Waterhouse 1839).

Bearing in mind that the Syrian hamster provides an animal model for the study of congenital coronary artery anomalies, we decided to undertake a definition of its normal coronary artery pattern. The sample examined consisted of 1204 specimens. They were studied both histologically and by means of a corrosion-cast technique. The course of the coronary arteries in this species is intramyocardial. The right coronary artery has two principal branches: the right circumflex branch and the dorsal interventricular branch. The conal branch usually originates from the main trunk of the right coronary artery. The main branches of the left coronary artery are the obtuse marginal branch, the left circumflex branch, and usually a dorsal ventricular branch as well. The ventral interventricular branch is often absent. When it is present, it always originates from the left coronary artery and seldom reaches the apex of the heart. The interventricular septum is principally supplied by one, or rarely two, septal arteries arising from the right and/or left coronary arteries. According to the number and origin of these vessels, three septal coronary artery patterns were established; namely, the right, the left, and the right-left septal patterns. In the Syrian hamster, the left septal pattern is the most frequent (70.4%). The right septal pattern occurred in 28.1% of the specimens studied, whereas the right-left septal pattern was only found in 1.5% of them.

Animals↗

[Ciliated cysts of the liver. 2 cases].

We report herein two cases of ciliated hepatic cysts. These exceptional lesions belong to the category of solitary nonparasitic cysts. They are probably dysembryoplastic and appear to derive from the embryonic foregut. Diagnosis is based on microscopic examination of the surgical specimen. The role of aspiration cytology in the preoperative diagnosis of this lesion has not yet been defined.

Adolescent↗

[Giant cell chondroma of soft tissues. Apropos of a case and review of the literature].

Soft tissue chondroma is a benign cartilaginous tumour most often located at the extremity of the upper limbs. We report a very unusual case of soft tissue chondroma due to its location in the sole of the foot resulting in delayed diagnosis. Diagnosis of soft tissue chondroma was confirmed by microscopic examination and by immunohistochemistry showing S 100 protein in the cells of mature and immature areas. The presence of numerous giant cells is exceptional. Labelling of the giant cells by KP 1 protein in the present case suggest that they are derived from macrophages.

Adult↗

Persistence of hepatitis B and hepatitis C viral genomes in primary liver cancers from HBsAg-negative patients: a study of a low-endemic area.

The role of HBV and HCV in the course of primary liver cancer in patients who are negative for HBsAg has been debated. Using a combination of serological and polymerase chain reaction assays, we investigated the association between HCV and HBV infections and primary liver cancer in 24 HBsAg-negative patients living in France. The presence of HCV RNA and HBV DNA sequences was tested for in serum and in tumorous and nontumorous liver samples. Twelve patients had anti-HCV, and 11 patients had anti-HBs and/or anti-HBc. HCV RNA sequences were found in the serum samples of all anti-HCV-positive patients and none of the patients who were negative. Patients with HCV viremia had HCV RNA genomic sequences and presumed replicative intermediates in both tumorous and nontumorous specimens. Sequence analysis of a hypervariable region in the E2/NS1 gene of HCV showed significant variations between the viral molecules isolated from the nontumorous, tumorous and serum samples. This eliminated the hypothesis of the contamination of the tumor by nontumorous cells and serum particles and assessed that liver tumor cells did contain HCV RNA genomes. Eleven of 22 patients tested had HBV DNA in the serum; 5 patients were anti-HBc positive and anti-HBs positive. Patients with HBV viremia had HBV DNA sequences in both tumorous and nontumorous liver specimens. Selective loss of part of the HBV genome in the tumorous tissue of two of these patients suggested HBV DNA persistence in clonally expanded malignant cells. Only 4 of the 22 patients were negative for both viruses. Our results show that HBsAg-negative hepatocellular cancer in France is associated with chronic HBV or HCV infection and, in some cases, both; these findings are consistent with an etiological role for HBV and HCV in HCC that develops in cirrhotic patients living in areas of low prevalence.

Base Sequence↗

Peritoneovenous shunting of intractable ascites in patients with cirrhosis: improving results and predictive factors of failure.

BACKGROUND: The clinical results of peritoneovenous shunting have not been entirely satisfactory in spite of dramatic improvement of renal function and decrease of ascites. The purpose of this study is to determine whether certain modifications improved our results. METHODS: A modified LeVeen shunt was electively inserted in 56 patients who had cirrhosis with intractable ascites. In 24 patients (42.9%) the Child-Pugh's score was less than 9, and in 32 patients the score was 9 or above. Fourteen patients (25%) had previous variceal bleeding, and 15 patients (26.8%) had previous spontaneous bacterial peritonitis (SBP). LeVeen shunt was modified by the addition of a titanium venous catheter tip. Prophylactic antibiotic therapy was administered to all patients. RESULTS: No operative deaths occurred, and one patient had severe postshunt coagulopathy. Five patients (8.9%) experienced recurrent ascites resulting from blockage from the shunt. The cumulative rate of shunt blockage was 5.6% at 1 year and 12% at 2 years. Seventeen patients (30.3%) have recently had variceal bleeding. The cumulative risk of variceal bleeding was significantly higher in patients with a previous hemorrhage than in those patients without (p < 0.05). Eight patients (14.3%) had SBP after operation. The cumulative risk of SBP was higher in patients with a history of SBP than in those patients without, although the difference was not significant. Fifty-five percent of late deaths were related to variceal bleeding or to SBP. Overall cumulative 1- and 2-year survival rates were 67.2% and 55.2%, respectively. It was 82% and 71% in patients without previous variceal bleeding or SBP. CONCLUSIONS: These data suggest that peritoneovenous shunting might be beneficial only in selected patients. Previous variceal bleeding and/or SBP indicate liver transplantation in suitable patients.

Adult↗

[Management of asymptomatic lithiasis].

A careful analysis of the series of patients with asymptomatic gallstones suggests that prophylactic cholecystectomy is not necessary. The purpose of this work was to try to detect subgroups of asymptomatic patients with factors predictive of symptoms or of severe complications such as acute cholecystitis, pancreatitis, or gallbladder carcinoma. Among local factors, neither the size, number or nature of gallstones, nor alterations of the walls or contractility of the gallbladder were predictive of symptoms or complications. Among general factors, neither the age or sex of patients nor associated diseases such as diabetes mellitus or recent organ transplantation were predictive of symptoms or complications. Only the few patients with a porcelain gallbladder were at high risk for gallbladder carcinoma requiring prophylactic cholecystectomy. In all other patients treatment of asymptomatic gallbladder stones is unnecessary as well as any surveillance.

Cholelithiasis↗

Overexpression of p53: a rare event in a large series of white patients with hepatocellular carcinoma.

Mutant p53 has been found in a wide variety of human malignancies including carcinomas of the lung, breast and colon. Because of the controversial mutational rate of the p53 gene in hepatocellular carcinoma, a large series of liver tumors from white patients with different risk factors was examined immunohistochemically for expression of the p53 mutant to assess its prevalence and the relationships between p53 overexpression and clinicopathological data. Nine of 58 specimens were found to have detectable evidence of p53 gene mutation by virtue of the immunohistochemical detection of mutant p53 protein. The p53 mutation was more frequent in patients with serological hepatitis B and C markers than in patients without these markers (p = 0.046). The prevalence of p53-positive tumors was also significantly higher in the group of tumors with invaded portal branches than in the group without (p = 0.02). Our results showed that p53-positive hepatocellular carcinoma is a rare finding in patients exposed to a low dietary aflatoxin intake and that p53 mutation seems to occur at a late stage of the tumoral process and could contribute to an aggressive tumoral phenotype.

Adult↗

Hepatic activity and mRNA expression of aspartate aminotransferase isoenzymes in alcoholic and nonalcoholic liver disease.

In liver and serum, AST activity is dependent on two isoenzymes, which are mitochondrial and cytosolic in nature. In an attempt to explain the well-known increase of serum mitochondrial AST-to-total AST ratio in chronic alcoholism (which is due to a specific increase of the mitochondrial isoenzyme), we analyzed: (a) liver and serum AST, ALT and glutamate dehydrogenase activities in 23 active drinkers with minimal liver changes, 11 alcoholic patients with cirrhosis who had stopped drinking, 18 nonalcoholic patients with viral chronic hepatitis and 11 subjects with normal livers; and (b) the expression of messenger RNAs for AST isoenzymes in the corresponding liver samples. Enzymatic activities were decreased in the liver irrespective of the origin of the liver disease. In patients with viral chronic hepatitis (or in those with alcoholic cirrhosis when abstinent), variations in liver proteins and messenger RNAs paralleled significant decreases in mitochondrial AST, ALT and glutamate dehydrogenase and a nonsignificant decrease of cytosolic AST. In alcoholic patients with minimal liver changes, the significant decrease of hepatic cytosolic AST, ALT and glutamate dehydrogenase activities contrasted with a close-to-normal liver mitochondrial AST activity; the increased amounts of mitochondrial AST messenger RNA give evidence for a pretranslational mechanism of regulation, indicating a possible increase in the total production of mitochondrial AST in the liver. The decrease of hepatic cytosolic AST activity was statistically significant only in alcoholic patients without cirrhosis who had a normal cytosolic AST mRNA level, thus suggesting a contributory role of translational or posttranslational regulation. In conclusion, regulation of AST isozymes during liver disease is complex, including differential, pretranslational and translational or posttranslational mechanisms.

Aspartate Aminotransferases↗