Search PubMed⌕ Search

Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 109 records · Page 6Linked to original sources
PubMed1996

The University of Toronto liver transplant program.

The University of Toronto liver transplant program began in 1985 at a time when the procedure had already evolved from an experimental form of surgery to an accepted treatment for many forms of liver failure. The program was established not only to provide clinical care for patients but also to address academically the barriers which impeded success. The program brought together experts in medicine, surgery, pathology, and the basic sciences of immunology, virology and molecular biology. Our group has had a special interest in transplantation for viral hepatitis. We demonstrated the role of HBV DNA as a prospective factor in both viral recurrence and survival. We further studied a number of agents to prevent re-infection including PGE, HBIG and more recently lamivudine. Although the short-term results of transplantation for HCV appear excellent, reinfection of the graft and development of chronic hepatitis and cirrhosis may make long-term results problematic. Therefore, we have directed attention to studies of pathogenesis and treatment of HCV in liver transplantation. Our studies have demonstrated a unique role for ribavirin as an immunomodulatory agent which can benefit the course of posttransplant HCV. Future studies will examine combination therapy in an attempt to eradicate the virus. Our group also has been interested in PNF and FHF and have demonstrated a positive effect of PGE in this setting. As we look to the future, the greatest challenges facing transplantation are the shortage of organ donors and the toxic effects of long-term immunosuppression. Our group now has established research efforts both in tolerance induction and xenotransplantation which we feel are necessary to make transplantation an effective, universal treatment for end stage organ failure.

Adult↗
PubMed1995

MHV-3 induced prothrombinase is encoded by musfiblp.

Previously, we demonstrated induction of a unique macrophage prothrombinase, PCA, in MHV-3 infected BALB/cJ mice. By immunologic screening, a clone representing PCA was isolated from a cDNA library and sequenced. The sequence identified this clone as representing part of a gene, musfiblp, that encodes a fibrinogen-like protein. Six additional clones were isolated, and one clone, p11-3-1, encompassed the entire coding region of musfiblp. Murine macrophages did not constitutively express musfiblp, but when infected with MHV-3, synthesized musfiblp-specific mRNA. Musfiblp mRNA induction was earlier and significantly greater in BALB/cJ than A/J macrophages. Prothrombinase activity was demonstrate when musfiblp was expressed from p11-3-1 in RAW 264.7 cells. These data suggest that musfiblp encodes the MHV-induced prothrombinase.

Animals↗
PubMed1995

Manipulation of skin graft rejection in alloimmune mice by anti-VCAM-1:VLA-4 but not anti-ICAM-1:LFA-1 monoclonal antibodies.

C3H mice were immunized by repeated skin grafting with B10.BR tail skin. Ten days after the last immunization mice received 100 micrograms (intravenously) of a variety of different monoclonal antibodies (mAbs: anti-ICAM-1, -LFA-1, -VCAM-1, -VLA-4), alone or in combination, followed by further B10.BR skin grafts. Control animals received injections of saline only. Skin graft survival was monitored daily in all groups. Further injections of antibody were given every second day until graft rejection occurred. In separate studies lymphoid cells were harvested from various tissues of the grafted mice at 6 and 20 days post grafting. Aliquots of each sample were analysed by polymerase chain reaction for mRNA for different cytokines (interleukins IL-2, IL-4, IL-10 and IFN gamma (gamma-interferon)) believed to be important in the regulation of graft rejection. In addition, lymphoid cells were restimulated in vitro with irradiated B10.BR or third-party stimulator cells in the presence or absence of monolayers of C3H-derived endothelial cells (EC), in an attempt to mimic the in vivo environment of the interactions of cells engaged in alloreactivity in these mice. Only anti-VCAM-1 caused significant prolongation of graft survival in immune mice, while in contrast only the combination of anti-ICAM-1 and anti-LFA-1 produced enhanced survival in naive animals. In each case increased survival was associated with decreased activation of Th1 cells (diminished IL-2, IFN gamma) and increased activation of Th2 cells (increased IL-4, IL-10).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pharmacokinetics of a new oral formulation of cyclosporine in liver transplant recipients.

Trough concentrations of cyclosporine can be highly variable because of its poor bioavailability in current oral formulations, Sandimmune (SIM). Neoral (N-SIM) a new microemulsion of cyclosporine is more readily absorbed than SIM in healthy controls. The present study compared the pharmacokinetic profiles of SIM and N-SIM following orthotopic liver transplantation. In 16 patients with partial biliary diversion, 1 week after transplantation, the bioavailability and peak concentration of a single 300 mg dose of N-SIM were greater than SIM by 724% (p = 0.0019) and 800% (p = 0.0001), respectively. In 39 patients who were on stable doses of cyclosporine 1 month after transplantation, the bioavailability of N-SIM was higher than that of SIM under both fasting (+64%, p = 0.001) and fed (+37%, p = 0.004) conditions. Trough concentrations were similar for the two formulations. However, peak concentrations were higher for N-SIM in both fasting (+119%, p = 0.003) and fed (+53%, p = 0.003) patients. Also, time to peak was shorter for N-SIM in both fasting (-21%, p = 0.027) and fed (-59%, p = 0.0001) patients. The correlation between trough concentrations and bioavailability was greater for N-SIM than for SIM in fasted (r = 0.80, p = 0.0001 versus r = 0.75, p = 0.0001) and fed patients (r = 0.65; p = 0.002 versus r = 0.55; p = 0.012). We conclude that the rate of absorption and the bioavailability of N-SIM is significantly and consistently better than SIM and may, therefore, improve the therapeutic index of cyclosporine after liver transplantation.

Administration, Oral↗
PubMed1995

Association of mouse fibrinogen-like protein with murine hepatitis virus-induced prothrombinase activity.

Previously, we demonstrated induction of a unique macrophage prothrombinase during infection of BALB/cJ mice by mouse hepatitis virus strain 3 (MHV-3). By immunologic screening, a clone representing this prothrombinase was isolated from a cDNA library and sequenced. The sequence identified this clone as representing part of a gene, musfiblp, that encodes a fibrinogen-like protein. Six additional clones were isolated, and one clone, p11-3-1, encompassed the entire coding region of musfiblp. Murine macrophages did not constitutively express musfiblp but, when infected with MHV-3, synthesized musfiblp-specific mRNA. musfiblp mRNA induction was earlier and significantly greater in BALB/cJ than A/J macrophages. Prothrombinase activity was demonstrated when musfiblp was expressed from p11-3-1 in RAW 264.7 cells. These data suggest that musfiblp encodes the MHV-induced prothrombinase.

Amino Acid Sequence↗
PubMed1995

Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension.

Obliterative lesions in portal veins (PVs) and hepatic veins (HVs) of all sizes are known to occur in cirrhotic livers. PV lesions have generally been attributed to thrombosis, but the pathogenesis of the HV (veno-occlusive) lesions is unknown. We have studied 61 cirrhotic livers removed at transplantation to clarify the prevalence, distribution, and pathogenesis of venous lesions, as well as the association of these lesions with other morphological features and clinical morbidity. Intimal fibrosis that is highly suggestive of healed HV or PV thrombosis was found in at least 70% and 36% of livers, respectively. The distribution of HV lesions was patchy and largely confined to veins between 0.1 and 3 mm in diameter, suggesting multifocal origin in small veins. PV lesions were more uniform throughout the liver, suggesting origin in large veins with propagation to the small veins. HV lesions were associated with regions of confluent fibrosis (focal parenchymal extinction), and PV lesions were associated with regional variation in the size of cirrhotic nodules and a history of bleeding varices. These observations suggest that thrombosis of medium and large PVs and HVs is a frequent occurrence in cirrhosis, and that these events are important in causing progression of cirrhosis.

Budd-Chiari Syndrome↗
PubMed1995

[Prenatal diagnosis of a small intestinal volvulus].

Ninety-five percent of the neonatal cases of bowel atresia result from jéjuno-ileal obstructions. Frequency is estimated from 1/3,000 to 1/5,000. We observed a case of small bowel volvulus secondary to jejunal atresia diagnosed at 35 weeks gestation. The ultrasound examination was performed due to decreased perception of active fetal movements. Fetal extraction was successful before perforation and meconial peritonitis.

Adult↗
PubMed1994

Prolongation of rat small bowel or renal allograft survival by pretransplant transfusion and/or by varying the route of allograft venous drainage.

Lewis rats show prolongation of survival of LBNF1 renal allografts when those grafts are drained by the portal vein, or if recipients are treated with LBNF1 bone marrow cells infused via the portal venous route peritransplantation. The longest survival was seen in animals in which both portal venous transfusion and graft drainage by the portal route were performed. When the same manipulations were performed for Lewis rats receiving heterotopic small bowel transplants, only in the "combined treatment" group was there significantly enhanced graft or animal survival relative to control rats. In separate studies, we examined the mixed leukocyte proliferation response in vitro, and IL-2 production, from rats treated as above and receiving renal or small bowel transplants. In both organ transplant models, there was a good correlation between enhanced graft survival in vivo and decreased in vitro responses to specific allostimulation.

Animals↗
PubMed1994

[Laparoscopic colpo-suspension by the Burch technique].

The Burch technique is the reference method for the treatment of exertion incontinence related to cervicocystoptosis. We present an original laparoscopic technique equivalent to the classical open approach. This technique is particularly interesting because a wide pneumoretzius allows adequate access for instruments without being hindered by intestinal loops and the free border of the bladder. Suspension is achieved with non-absorbable mesh bands which are attached to the vagina and Cooper ligaments with staples. The anchoring point is thus larger and the space remains blood free. Fifty nine operations were performed with this technique at the Department of Gynaecology of the University Hospital at Caen, France. No failures have been observed.

Female↗
PubMed1994

Kinetics of drug action in disease states. XLIII: Potentiating effect of L-tryptophan on the hypnotic action of phenobarbital and ethanol in rats.

The essential amino acid L-tryptophan has been widely used as a sleeping aid because it can produce drowsiness and decrease sleep latency. Its concentrations in plasma and brain and its binding to plasma protein are markedly altered in hepatic encephalopathy and renal failure. The purpose of this investigation was to determine if L-tryptophan can enhance the sensitivity of the central nervous system to the hypnotic actions of a barbiturate and an alcohol. Female rats weighing approximately 200 g received an intravenous infusion of L-tryptophan (0.8 or 0.08 mg/min) for 30 min and then an infusion of phenobarbital (0.824 mg/min) with L-tryptophan (0.8 or 0.08 mg min-1) until the onset of loss of righting reflex (LRR). Control animals received an infusion of saline solution for 30 min and then phenobarbital without the amino acid. Similar experiments were performed with ethanol (16.3 mg/min), with and without L-tryptophan (0.8 mg/min). L-Tryptophan infused alone at a rate of 3.8 mg/min for 84 min did not cause LRR. Administration of L-tryptophan at a rate of 0.8 mg/min with phenobarbital was associated with statistically significant reductions in the total dose and concentrations of phenobarbital in serum, serum water, brain, and cerebrospinal fluid (CSF) at onset of LRR. The 0.08 mg/min infusion of L-tryptophan had a less pronounced effect, with statistically significant reductions of phenobarbital concentrations at onset of LRR in brain and CSF. L-Tryptophan also significantly reduced the total dose and the concentrations of ethanol in serum, brain, and CSF required to produce LRR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗