Biomedical subjects

D Jaeck

Publications and source records attributed to D Jaeck.

At least 181 records · Page 10Linked to original sources

PubMedDate not supplied

Multiplication of human immunodeficiency virus in primary cultures of human Kupffer cells--possible role of liver macrophage infection in the physiopathology of AIDS.

In primary cultures of Kupffer cells obtained from surgical biopsies of human liver by collagenase perfusion followed by centrifugal elutriation and infected with HIV, the virus multiplied abundantly, as attested by the appearance of a reverse transcriptase activity in the medium. Examined by electron microscopy, the cells were found to contain viral particles with typical features of Lentivirinae. Furthermore, the virus could be revealed by immunofluorescence using an HIV+ patient serum. HIV antibodies also neutralized the infectivity of the Kupffer cell-produced virus. Our results demonstrate that the cells constituting the largest fraction of fixed macrophages in the body may be infected by HIV, thereby suggesting that the Kupffer cells may play a role in the physiopathology of the disease, namely as a reservoir for the virus.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Morphine stimulates HIV replication in primary cultures of human Kupffer cells.

Intravenous drug abusers represent a high risk group for HIV infection in Europe and North America. Although the use of blood-contaminated needles undoubtedly constitutes the main factor of transmission of the virus, an effect of the drug itself either on the immune system or on virus replication, thus favouring the initiation of the infection, may not be excluded. We have formerly established that primary cultures of human Kupffer cells (KC) are permissive for HIV1. In this paper, we describe the effect of morphine hydrochloride on the multiplication of different isolates of HIV1 in cultured human KC. KC were obtained by dissociation of human liver fragments with collagenase and purified by centrifugal elutriation. Five-day-old KC were infected with HIV1; at different intervals, the production of virus was quantitated by the reverse transcriptase activity associated with the particles present in the culture medium. In primary cultures of KC preincubated for 48 h and maintained in the presence of morphine, the production of viral particles was increased. This enhancing effect was found with 3 different HIV1 isolates. Treatment of KC with morphine prior to infection was not required for the stimulation to take place, which indicated that the enhancing effect was not related to a more efficient adsorption of the virus to the KC plasma membrane. Stimulation of HIV1 production was observed for all the concentrations of morphine used (0.05 to 0.5 mg/ml). These results, if confirmed in vivo, may shed new light on the risk factors related to the intravenous administration of heroin.

Cells, Cultured↗

PubMedDate not supplied

[Technique of surgical ampullectomy].

We describe the technique of surgical ampullectomy, which consists of complete resection of the papilla of Vater, including the sphincter, the distal part of common bile duct and Wirsung duct, and the duodenal wall around the papilla. Limits of resection are assessed by frozen section, particularly on both biliary and pancreatic ducts which are sutured together and reinserted on the duodenal wall. Surgical ampullectomy, combined with frozen section, is associated with a low morbidity, and represents a valid alternative to pancreaticoduodenectomy and endoscopic ampullectomy for presumed-benign ampullomas.

Ampulla of Vater↗

PubMedDate not supplied

Human endothelial cells isolated from the hepatic sinusoids and the umbilical vein display a different permissiveness for HIV1.

Endothelial cells are now considered as potential targets for HIV infection, together with other non-lymphoid cells. We previously demonstrated that endothelial cells isolated from the human liver sinusoids (SEC) are permissive for HIV1 in vitro (Steffan et al., 1992), whereas human umbilical vein endothelial cells (HUVEC) do not allow replication of seven HIV1 and HIV2 strains under the same infection conditions (Lafon et al., 1992). The aim of our work was to compare the permissiveness of SEC and HUVEC and to determine whether the lack of HIV replication in HUVEC, which do not possess CD4 receptors (Lafon et al., 1992), could be related to the absence of virus penetration. The bypass of the early events in the virus life cycle, including the stage of fusion, by transfection of HUVEC with the HTLV-IIIB provirus led to one cycle of viral replication. Moreover, a low level of viral replication was observed in HUVEC infected with the NDK HIV strain, known to penetrate its target cell in a CD4-independent fashion. These results indicate that the block of infection in HUVEC takes place during the early stages of the viral replicative cycle. However, given the low level of NDK replication in HUVEC (0.02% infected cells) in comparison with NDK-infected SEC (30 to 50% infected cells), the absence of the CD4 receptor on HUVEC may not be the only limiting factor for viral growth. Although these two types of endothelial cells display a very different permissiveness for HIV, the present data suggest that they could both serve as a viral reservoir.

CD4 Antigens↗

PubMedDate not supplied

Hepatocyte ploidy in regenerating livers after partial hepatectomy, drug-induced necrosis, and cirrhosis.

The hepatocyte ploidy was investigated by flow cytometry in regenerating Sprague-Dawley rat livers following either drug-induced acute necrosis (single sublethal doses of D-galactosamine or thioacetamide) or drug-induced chronic cirrhosis (repeated thioacetamide injections for 10-18 weeks) and in regenerating livers following 70% partial hepatectomy and was compared with that of normal hepatocytes. Twenty-four hours after partial hepatectomy, a significant decrease in 2n (1 diploid nucleus) hepatocytes and a significant increase in 8n (1 octoploid nucleus) hepatocytes occurred. In contrast, 24 h following induction of acute hepatic failure by single D-galactosamine or thioacetamide injections, a significant increase in 2n hepatocytes was observed, whereas the proportion of 8n hepatocytes remained unchanged. The liver ploidy returned to basal values within 21 days in all cases. In cirrhotic livers induced by chronic thioacetamide injections, the rate of 2n hepatocytes was about ten times that of the controls having the same age, while 4n (1 tetraploid nucleus) and 8n hepatocytes were one third of controls. The binucleation rate was also significantly decreased.

Animals↗

PubMedDate not supplied

Amelioration of hepatocellular integrity and inhibition of sinusoidal oxidative stress by N-acetylcysteine pretreatment in cold ischemia-reperfusion injury of rat liver.

Further improvements of donor liver preservation are still required in liver transplantation. In the present study, we investigated whether intraportal injection of N-acetylcysteine (NAC) 15 min before flush-out of UW solution (NAC pretreatment) improves liver dysfunction after cold preservation or has a protective effect on sinusoidal oxidative stress. The effect of NAC pretreatment was examined using an isolated perfused rat liver model. The NAC pretreatment significantly reduced sinusoidal oxidative stress relative to a control dextrose 5% injection. Under a glutathione-depleted condition produced by L-buthionine-[S-R]-sulfoximine, the NAC pretreatment also significantly reduced hepatocellular as well as sinusoidal oxidative stress, resulting in improvement of hepatocelllar integrity relative to a control dextrose 5% injection.

Acetylcysteine↗

PubMedDate not supplied

Lobular carcinoma in situ of the breast: results of a radiosurgical conservative treatment.

From 1980 to 1992, 17 women underwent lumpectomy (13) or quadrantectomy (4) and whole breast irradiation (median dose: 52 Gy) for pure lobular carcinoma in situ (LCIS). Three cases correspond to palpable lesions and 14 were discovered only by mammography. Twelve women also received tamoxifen at 20 mg/day for two years. With a median follow-up of 88 months, no local or regional recurrences have been recorded. The global rate of bilateral carcinoma was 17.6% (2 synchronous and one metachronous). In the literature, only eight other cases of LCIS were treated by lumpectomy and radiation therapy, but without details and data on long-term results. After biopsy alone for LCIS subsequent infiltrating carcinoma occurred in about 15% of the cases. Thus, the classical radiosurgical association should represent an interesting alternative both for biopsy alone and radical surgery until now only proposed to treat LCIS.

Aged↗

PubMedDate not supplied

Gemcitabine and protracted 5-FU for advanced pancreatic cancer. A phase II study.

BACKGROUND/AIMS: Although chemotherapy in advanced pancreatic cancer procures dismal results, both 5-fluorouracil and gemcitabine have shown a modest activity. We report a phase II study of gemcitabine combined with protracted 5-fluorouracil. METHODOLOGY: Gemcitabine was given at 1000 mg/m2/week intravenously, in combination with concomitant 5-fluorouracil 200 mg/m2/day as a protracted venous infusion, both 3 out of 4 weeks in patients with locally advanced or metastatic pancreatic adenocarcinoma. Twenty-nine patients were enrolled, among whom 27 were metastatic. Response rate, overall and progression-free survival were endpoints, as well as tolerance and clinical benefit. RESULTS: We observed 3 (10%) partial responses, and 12 (42%) stabilizations within which the median disease control was 5.6 months. The median progression-free and overall survivals were 2.8 and 4 months, respectively. A clinical benefit was observed in 39% of patients. Myelosuppression was the main toxicity, but no grade 4 was observed. Other toxicities were mild. CONCLUSIONS: This combination chemotherapy was well tolerated in advanced pancreatic cancer patients.

Adenocarcinoma↗

PubMedDate not supplied

Engraftment and albumin production of intrasplenically transplanted rat hepatocytes (Sprague-Dawley), freshly isolated versus cryopreserved, into Nagase analbuminemic rats (NAR).

Banking of cryopreserved hepatocytes is a prerequisite for large-scale hepatocyte transplantation in the clinic. We compared the efficacy of intrasplenic transplantation into Nagase analbuminemic rats (NAR) of freshly isolated (FIH) and cryopreserved (CH) hepatocytes. Hepatocytes were cryopreserved using a controlled rate freezing protocol. Albumin production of thawed CH and FIH was measured in vitro in culture by ELISA and by Western blot. After in vivo intrasplenic transplantation of NAR with either FIH or CH we assessed 1) albumin in the serum of recipients by ELISA and by Western blotting analysis at different time intervals, and 2) hepatocyte engraftment by albumin immunohistochemical staining into spleens and livers at euthanasia. In vitro, albumin was produced up to day 4 of culture in both CH and FIH. In vivo, no intrasplenic engraftment of hepatocytes occurred. Intrahepatic engraftment of CH (cell number/mm2) was significantly (twofold) lower than that of FIH and appeared only as isolated cells and small (<10 cells) clusters, while bigger clusters (>10 cells) were observed with FIH. In the FIH group, serum albumin production was observed up to 32-49 days posttransplantation while in the CH group no serum albumin production was detected. Our results emphasize the need to improve 1) hepatocyte transplantation procedures either by repeated hepatocytes injections and/or by transplantation under a regeneration response, and 2) the freeze/thaw protocols of hepatocytes.

Animals↗

PubMedDate not supplied

Randomized trial of 5-fluorouracil, leucovorin and cisplatin in advanced pancreatic cancer.

BACKGROUND/AIMS: Phase II trials of combined 5 fluorouracil, leucovorin and cisplatin have demonstrated an 18-28% response rate in advanced pancreatic carcinomas. We investigated the effect of this chemotherapy regime on patients' survival. METHODOLOGY: Patients included gave informed consent. They had an advanced and proven pancreatic adenocarcinoma. The trial was multicentric, prospective and randomized. It compared a 5-day course of leucovorin (200 mg/m2/day), 5-fluorouracil (375 mg/m2/day) and cisplatin (15 mg/m2/day) repeated every 21 days (23 patients) with a control group (22 patients). The main end points were survival time (Kaplan-Meier and log-rank methods) a[not readable: see text]side effects of chemotherapy. RESULTS: Association of leucovorin, 5-fluorouracil and cisplatin failed to demonstrate any advantage of this regimen compared with supported care alone. Median survival times were 8.6 months (SD +/- 1.8) and 7.0 months (SD +/- 0.6), respectively. The modulation of 5-fluorouracil by leucovorin and cisplatin was well tolerated with moderate toxic effects. CONCLUSIONS: This multicentric trial failed to demonstrate any advantage of the evaluated chemotherapy regime in the palliative treatment of cancer of the exocrine pancreas. Other trials including gemcitabine and/or radiotherapy are needed in advanced pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMedDate not supplied