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Biomedical subjects

D Samuel

Publications and source records attributed to D Samuel.

At least 91 records · Page 5Linked to original sources
PubMed1997

Evidence for selection of hepatitis B mutants after liver transplantation through peripheral blood mononuclear cell infection.

BACKGROUND/AIMS: Despite anti-HBs immunoglobulin therapy, hepatitis B virus (HBV) infection recurs in a high proportion of patients transplanted for HBsAg positive and serum HBV DNA negative chronic liver disease. The contribution of HBV genetic variability to disease recurrence has not been yet thoroughly addressed. We have therefore undertaken a detailed comparison of preS/S and preC/C sequences in two selected patients with recurrence of HBsAg and HBV DNA after transplantation. METHODS: PreS/S and preC/C regions were amplified by PCR from the serum, peripheral blood mononuclear cell (PBMC) and liver tissues of two patients transplanted for end stage HBV-related cirrhosis. Samples were taken both pre- and post-transplantation. HBV-sequences from four to nine clones were determined and compared. RESULTS: A mixing of different HBV DNA molecules was observed within and between serum, liver and PBMC samples. Sequences from both patients showed mutations in the preC region which abolished HBeAg secretion, and in the preS2 initiation codon which prevented preS2 envelope protein production. In addition, for both patients, deletions in the preS2 domain (3 and 21 base pairs) led to the expression of modified preS1 envelope protein. For one patient, the predominant HBs protein sequence found in the PBMC before transplantation showed four specific mutations. One of these mutations was in the "a" determinant (codon 144, asparagine to glycine change) of the major envelope protein. These mutations were not detected, as predominant mutations, in the liver and serum pre-orthotopic liver transplant samples. In contrast, after liver transplantation, this was the major form identified in serum, liver and PBMC. CONCLUSIONS: Our results have shown the selection of different HBV DNA molecules in liver and mononuclear cells. In addition, they provide direct evidence for the role of PBMC in the infection of liver grafts and support the hypothesis that infection of PBMC might lead to selection of HBV variants which would escape immune therapy. Finally, we provide in vivo evidence for reinfection of the liver by HBV particles lacking preS2 envelope protein expression.

Hepatitis B Surface Antigens↗
PubMed1997

De novo and apparent de novo hepatitis B virus infection after liver transplantation.

BACKGROUND/AIMS: The aim of this study was to clarify the aetiology of apparent de novo HBV infection after liver transplantation. METHODS: Twenty out of 570 HBsAg negative patients (3.5%) became HBsAg positive after transplantation and were studied. Donor and recipient sera were retrospectively tested for HBsAg, anti-HBs, anti-HBc, and HBV DNA by PCR. Donor and recipient livers were tested for HBV DNA by PCR on paraffin-embedded tissue. RESULTS: Group 1: HBV infection of donor origin (eight patients): one donor serum was HBsAg positive, three were serum HBV DNA positive, four were liver HBV DNA positive. Group 2: reactivation of latent HBV infection (eight patients) with detection of HBV DNA in pretransplant serum (seven patients) or in native liver (one patient): three were anti-HBs positive, two anti-HBc positive, and three with fulminant hepatitis had no serological HBV markers. Group 3: undetermined origin (four patients) defined by absence of HBV DNA in pretransplant donor and/or recipient sera and liver; however, acquired infection was suspected from two anti-HBs and anti-HBc positive donors. Two patients became HBsAg negative, and five HBV DNA negative. One died from HBV-cirrhosis and two were retransplanted. In the others, the last histology showed cirrhosis (three), chronic hepatitis (nine), acute hepatitis (one), and non-specific change (four patients). CONCLUSIONS: The prevalence of de novo HBV infection in liver transplant patients was 3.5%; the aetiology was determined in 16/20 patients: from the donor in eight, and from the recipient in eight. One should be cautious when donors or recipients are anti-HBc or both anti-HBs and anti-HBc positive.

Adult↗
PubMed1997

Long-term longitudinal study of intrahepatic hepatitis C virus replication after liver transplantation.

Recurrence of hepatitis C after liver transplantation is common and can lead to severe liver diseases. Although immunosuppression and high levels of viremia suggest a direct pathogenicity of hepatitis C virus (HCV), the relations between viral replication and long-term histological course are still unknown. Thirty-three patients with a mean histological follow-up of 3.5 years (3 months - 8.6 years) were analyzed. Nineteen patients were infected by genotype 1b. Liver HCV RNA was determined in parallel with the quantitation of an internal control (28S ribosomal RNA) by competitive polymerase chain reaction (PCR). Lobular hepatitis (LH) and chronic active hepatitis (CAH) occurred in 27 and 19 patients, respectively. Levels of liver HCV RNA determined in 84 biopsies were higher in cases of LH than in the other patterns (82 +/- 123 vs. 19 +/- 38; P < .01) and were unrelated to the genotype. Progression from LH to CAH was associated with a highly significant decrease of liver HCV RNA (P = .006), which was not observed in patients with stable histology. Among patients with CAH, those infected by genotype 1b had more severe liver damage and lower levels of liver HCV RNA than others (P = .04). Multivariate analysis showed that high levels of liver HCV RNA at the time of the first posttransplantation biopsy was an independent predictor of CAH (P = .01). After liver transplantation, the progression to CAH together with a decrease of liver HCV RNA suggests that a host's response is involved in the long-term viral pathogenicity. This response may be stronger and liver disease more severe in patients with high levels of replication at the time of LH and in those infected by genotype 1b.

Adult↗
PubMed1997

Snake venom cardiotoxins-structure, dynamics, function and folding.

Snake cardiotoxins are highly basic (pI > 10) small molecular weight (approximately 6.5 kDa), all beta-sheet proteins. They exhibit a broad spectrum of interesting biological activities. The secondary structural elements in these toxins include antiparallel double and triple stranded beta-sheets. The three dimensional structures of these toxins reveal an unique asymmetric distribution of the hydrophobic and hydrophilic amino acids. The 3D structures of closely related snake venom toxins such as neurotoxins and cardiotoxin-like basic proteins (CLBP) fail to show similar pattern(s) in the distribution of polar and nonpolar residues. Recently, many novel biological activities have been reported for cardiotoxins. However, to-date, there is no clear structure-function correlation(s) available for snake venom cardiotoxins. The aim of this comprehensive review is to summarize and critically evaluate the progress in research on the structure, dynamics, function and folding aspects of snake venom cardiotoxins.

Amino Acid Sequence↗
PubMed1997

Proline is a protein solubilizing solute.

The effect of proline on the prevention of trichloroacetic acid (TCA)-induced protein precipitation is studied. It is found that proline at high concentrations (> 4.0 M) completely prevents TCA-induced precipitation of hen egg white lysozyme. Other osmolytes such as ethylene glycol, glycerol and sucrose fail to prevent the TCA-induced precipitation of lysozyme. Viscosity and 1-anilino-8-naphthalene sulphonic acid binding experiments suggest that proline at high concentration forms an ordered supramolecular assembly. Proline is shown to increase the solubility of protein due to formation of such higher order assemblies. A model of the supra-molecular assembly of proline is proposed and a possible in vivo role of the increased levels of proline under water stress is discussed.

Animals↗
PubMed1997

Prolonged interferon-alpha therapy of hepatitis B virus-related decompensated cirrhosis.

Interferon alpha therapy of hepatitis B virus-related decompensated cirrhosis with the dose and the duration generally used is frequently associated with severe side-effects and reactivations. Between 1989 and 1996, 15 patients with hepatitis B virus-related decompensated cirrhosis received prolonged (3-48 months) low-dose (3 million units) IFN-alpha therapy. Ten patients (66%) had a sustained loss of serum hepatitis B virus DNA and hepatitis Be antigen (if present initially) associated with a decrease of aminotransferase levels into the normal range. During follow-up of these 10 patients, seven had a marked clinical improvement and are alive and fully active. One has an hepatocellular carcinoma, and two died without reactivation. Among the five other patients, two had a transient loss of serum HBV DNA followed by reactivation and three did not respond to therapy. During follow-up, one of these five patients died and one underwent liver transplantation. Severe complications, possibly related to interferon were uncommon and included bacterial infection in one case and variceal bleeding in two cases. Eleven of the 15 patients treated are alive after 1.5-7 years of follow-up. Hence, in patients with hepatitis B-related cirrhosis, prolonged low-dose IFN-alpha therapy is relatively well tolerated and may induce a sustained inhibition of hepatitis B virus replication with marked clinical improvement.

Adult↗
PubMed1997

Hepatitis viruses and liver transplantation.

Acute and chronic liver diseases related to hepatitis viruses are the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. The risk of viral B reinfection is: 80% in the absence of prophylaxis; is related to the presence of active viral B replication prior to transplantation; is higher in patients with chronic liver disease, rather than with fulminant hepatitis; and is higher in patients with hepatitis B virus (HBV)-related liver disease alone rather than in those with HBV-hepatitis delta virus (HDV) infection. Post-transplant long-term passive antibody to hepatitis B (anti-HB) immunoprophylaxis reduces the risk of HBV recurrence to 30% in patients with HBV cirrhosis, and to less than 10% in those with fulminant hepatitis B. Patients with HBV-HDV liver disease receiving passive anti-HB immunoprophylaxis are at low risk of HBV recurrence (10-15%), but at high risk of HDV recurrence (80%). However, HDV reinfection of the graft has no clinicopathological consequence in the absence of concomitant HBV reinfection. The five year survival of patients transplanted for HBV cirrhosis and for HDV cirrhosis at the Hepatobiliary Center, Hôpital Paul Brousse is 72% and 85%, respectively. Hepatitis B virus reinfection of the graft is characterized by a high level of viral replication, and a chronic outcome. Antiviral treatments such as ganciclovir, adenine arabinoside monophosphate, famcyclovir, and lamivudine have a place after transplantation and may stop HBV replication, ganciclovir, famcyclovir and lamivudine should be continued for several months and in some cases indefinitely. Hepatitis C virus reinfection is almost constant, assessed by the persistence of hepatitis C virus (HCV)-RNA in the serum in 90% of cases. Acute lobular hepatitis appeared in 75% of patients at a median of 4 months post transplantation with a range of between 23 days and 4 years. In our series, the 5 year actuarial rate of HCV acute hepatitis on the graft, chronic hepatitis, and cirrhosis, is 75, 60, and 8%, respectively. Hepatitis C virus RNA level is dramatically increased after transplantation and seems to correlate with the occurrence of acute hepatitis on the graft. A positive relation between genotype 1b and prevalence and severity of HCV hepatitis on the graft have been suggested in European series. There is no demonstrated way to prevent HCV reinfection. The use of interferon for the treatment of HCV hepatitis on the graft was disappointing due to a poor antiviral effect and the occurrence of chronic rejection episodes in some patients. Promising results of the combination of interferon and ribavirine have been reported and need confirmation. The 5 year survival of patients transplanted for viral C cirrhosis at the Hepatobiliary Center, Hôpital Paul Brousse is 78%. In conclusion, patients with HBV cirrhosis and without HBV replication are candidates for liver transplantation. Long-term passive anti-HB prophylaxis is the best way to prevent HBV recurrence. Patients with HBV replication should be included in protocols using combinations of antiviral treatments and passive anti-HB immunoprophylaxis. Viral C reinfection is frequent, but medium-term survival is good. However, long-term graft and patient survival remains unknown and methods to prevent and treat HCV reinfection on the graft are needed.

Antiviral Agents↗
PubMed1996

Involvement of the glutamatergic metabotropic receptors in the regulation of glutamate uptake and extracellular excitatory amino acid levels in the striatum of chloral hydrate-anesthetized rats.

The microdialysis technique was used to assess in vivo the putative functional role of metabotropic excitatory amino acid receptors in regulating extracellular levels of the excitatory amino acids glutamate and aspartate in the striatum of chloral hydrate-anesthetized rats. Addition of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) (10(-3) or 4 x 10(-3) M) in the dialysis probe did not modify the basal extracellular levels of glutamate and aspartate but induced a significant dose-dependent decrease in the KCl-elicited elevation of glutamate and aspartate extracellular levels. The effect of MCPG on glutamate extracellular concentration under K+ stimulation was reduced by the simultaneous superfusion of the metabotropic glutamate receptor agonist (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine) (L-CCG) (10(-3) M) which had no significant effect when tested alone. In contrast, L-CCG alone significantly potentiated the KCl-elicited elevation of aspartate extracellular concentrations but failed to modify the MCPG effect on this amino acid concentration. In a parallel series of experiments, high-affinity glutamate uptake was measured ex vivo 20 min after an in vivo injection of 10 pmol of MCPG in the striatum. MCPG was found unable to modify the glutamate uptake rate. In vitro, MCPG (1-1000 microM) again had no effect on glutamate transport rate. These data suggest that metabotropic excitatory amino acid receptors (1) may act to increase the extracellular levels of glutamate and aspartate under depolarizing conditions, and (2) may not have a major role in the regulation of high affinity glutamate uptake under basal conditions. In addition, it can be assumed that the control of glutamate and aspartate extracellular levels may involve different metabotropic receptors.

Amino Acids, Dicarboxylic↗
PubMed1996

Investigation of Ancient Egyptian Baking and Brewing Methods by Correlative Microscopy

Ancient Egyptian methods of baking and brewing are investigated by optical and scanning electron microscopy of desiccated bread loaves and beer remains. The results suggest that current conceptions about ancient Egyptian bread and beer making should be modified. Bread was made not only with flour from raw grain, but sometimes also with malt and with yeast. Brewing blended cooked and uncooked malt with water; the mixture was strained free of husk before inoculation with yeast.

Journal Article↗
PubMed1996

[Liver transplantation after exertion-induced heat stroke associated with fulminant liver failure].

OBJECTIVES: Describe the course of fulminant liver failure after exertional heat stroke. CASE REPORT: A 30-year-old man acclimated to the tropical climate, collapsed and became comatose with hyperthermia during a commando march in Gabon. Thirty-six hours later, the biological examination revealed moderate rhabdomyolysis and fulminant liver failure. An orthotoptic liver transplantation was performed at the 48th hour. Acute renal failure with severe rhabdomyolysis developed on the 4th day post-surgery while the patient was perfectly alert. His condition thereafter deteriorated and he died of chronic rejection 11 months after liver transplantation. DISCUSSION: In its most serious forms exertional heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. The reported case suggests that exertional heat stroke can cause fulminant liver failure, resulting either from the direct effect of heat on the hepatic parenchyma, or from acute hepatic ischemia due to blood redistribution made worse by the hypersecretion of antidiuretic hormone, a potent portal vasoconstrictor, which occurs in the heat acclimated subject.

Adult↗
PubMed1996

Urinary thromboxane B2 as an indicator of acute rejection in human liver transplantation.

Urinary thromboxane B2 (u-TXB2) was measured and analyzed after a human liver transplantation in 28 patients (30 transplantations) who underwent an orthotopic liver transplantation. Our results showed that the u-TXB2 levels exceeded 3.0 micrograms/mmol creatinine in only 2 of the 13 cases that had a favorable postoperative course. In 10 of the 11 episodes of acute rejection, the u-TXB2 levels exceeded 3.0 micrograms/mmol creatinine. In 6 episodes of acute rejection, the TXB2 levels were more than 5.0. In 4 out of 6 episodes of infection unassociated with rejection, the u-TXB2 values were between 3.0 and 4.9 micrograms/mmol creatinine. In 2 episodes of liver necrosis the TXB2 value reached 5.3 in one and 0.9 in the other. In conclusion, the u-TXB2 level was observed to be elevated in cases of acute rejection, infection, or necrosis. The diagnosis of acute rejection on the basis of u-TXB2 showed a sensitivity of 58.8%, a specificity of 93.3%, and an accuracy of 75.0% for a threshold level of 3.0 micrograms/mmol creatinine, and a sensitivity of 85.7%, a specificity of 79.2%, and an accuracy of 80.6% for a threshold level of TXB2 of 5.0 micrograms/mmol creatinine. These results indicate that the serial determination of u-TXB2 is a useful diagnostic means for predicting acute rejection after liver transplantation.

Adolescent↗
PubMed1996

Activation of the adenylate cyclase-dependent protein kinase pathway increases high affinity glutamate uptake into rat striatal synaptosomes.

This study examined the effects of various agents known to alter protein phosphorylation through protein kinase A or C on high affinity glutamate uptake measured in vitro on rat striatal homogenates. Incubation of synaptosomes with the phosphatase inhibitor, okadaic acid, dramatically increased glutamate uptake indicating that underlying phosphorylation mechanisms may be involved in the regulation of this transport process. The protein kinase C activator, phorbol-12,13-dibutyrate, or inhibitor, staurosporine, did not significantly modify glutamate uptake. In contrast, forskolin, which activates adenylate cyclase, induced a dose-dependent increase in glutamate uptake. Saturation kinetic analysis indicated that forskolin increased the Vmax without modifying the Km of the transport process as compared to control values. The effect of forskolin was mimicked by dibutyryl adenosine monophosphate, an analog of cAMP which activates protein kinase A, and counteracted by high doses of N-[2-(methylamino) ethy1]-5-isoquinoline sulfonamide, a protein kinase A inhibitor. These results suggest that an adenylate cyclase-dependent protein kinase may be involved in the post-translational regulation of glutamate transporters.

Adenylyl Cyclases↗