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Biomedical subjects

P H Lambert

Publications and source records attributed to P H Lambert.

At least 19 recordsLinked to original sources
PubMed1992

Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire.

We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.

Adolescent↗
PubMed1992

Synthesis and ACE inhibitory activity of the stereoisomers of perindopril (S 9490) and perindoprilate (S 9780).

Perindopril, a powerful ACE inhibitor contains 5 chiral carbons, thus there is the possibility of 2(5) = 32 stereoisomers for the general structure 1. These 32 stereoisomers were synthesized by cross-coupling the 8 stereoisomers of perhydroindole 2-carboxylic acid benzylester with the 4 stereoisomers of 2-(1-carbethoxybutylamino) propionic acid 4, then hydrogenating the resulting benzylesters. Each stereoisomer of perindopril furnished by saponification the corresponding diacid stereoisomer 2 of perindoprilate which is the active form of perindopril. For each of the 32 stereoisomers 2 the in vitro ACE inhibitory potency (IC50) was determined. Four of them, including perindoprilate, had activities in the nanomolar range, and four more were ca. 10 x less active. The four acid esters 1 corresponding respectively to the four most active diacids 2 in vitro were studied (1 mg/kg via the oral route) for their in vivo activity in dogs. It could be concluded that p.o. absorption of the active acid esters 1 and their activation to the active diacid 2 depended only on the chiralities of the two ring junction carbons of the perhydroindole ring.

Administration, Oral↗
PubMed1979

[Demonstration of soluble parasite antigens, the corresponding antibodies and immune complexes in acute malaria].

Serum levels of malaria antigens, antimalaria antibodies, immune complexes and complement components have been followed up in 23 patients suffering from acute malaria infection and recovering under therapy. Malarial antigens in serum were detected by counterimmunoelectrophoresis: the peak was observed before therapy started and their levels rapidly decreased. Specific antimalarial antibodies became detectable 5--7 days after starting treatment in patients with a first infection. Immune complexes were detected in 21 of 23 sera with a peak level between days 5 and 9. A marked decrease of C4 and C3 was observed in the presence of normal levels of factor B.

Antibodies↗
PubMed1979

Induction of thymocytotoxic autoantibodies after injection of bacterial lipopolysaccharides in mice.

The injection of bacterial lipopolysaccharides (Salmonella typhimurium and Escherichia coli LPS) has been shown to induce thymocytotoxic autoantibodies in various strains of mice (C57BL/6, BALB/c, DBA/2, AKR, A/J and C3HeB/FeJ). Titers up to l:16 were observed. Such antibodies did not develop in C3H/HeJ mice which are low responders to LPS. The thymocytotoxic antibodies had the following characteristics: (a) 2-mercaptoethanol sensitivity, (b) optimal reactivity at 4 degrees C, (c) cytotoxicity for autologous and syngeneic thymocytes but not for spleen cells. The cytotoxicity decreased after absorption with thymocytes, spleen cells or brain tissue but not with kidney or liver homogenates. These LPS-induced thymocytotoxic antibodies were similar to the natural thymocytotoxic antibody occurring in NZB mice.

Animals↗
PubMed1979

Relevance of polyclonal antibody formation to the development of autoimmunity : the model of African trypanosomiasis.

There is an induction of anti-DNA antibodies in mice following the administration of bacterial lipopolysaccharides, Dextran sulfate and PPD, which is closely associated with the property of these substances to trigger a polyclonal B cell activation. In the experiments model of African trypanosomiasis there is also an intense polyclonal antibody synthesis paralleled by the formation of several autoantibodies: anti-DNA, anti-bromelain treated mouse red blood cells and antithymocyte antibodies.

Animals↗
PubMed1979

Complement activation in pneumonia.

Complement analyses performed on serially collected plasma samples from 10 patients during acute infectious pneumonia or bronchopneumonia showed normal or increased values for hemolytic activity and Clq, C4, C3, and factor B levels. However, the levels of C3 breakdown products (C3d) were significantly (greater than 2 SD) increased in six patients during the first three days of observation, suggesting that hypercatabolism of complement components may occur during the acute phase of infectious pneumonia concomitant with a hypersynthesis of some complement components. Evidence of circulating immune complexes was obtained only in two patients with the 125I-Clq Binding Test.

Acute Disease↗
PubMed1979

Decreased heat-labile opsonic activity and complement levels associated with evidence of C3 breakdown products in infected pleural effusions.

Heat-labile opsonic activity was measured simultaneously in serum and pleural fluid of patients with transudates, infectious exudates (with positive or negative bacterial culture) and neoplastic exudates, using two different complement-dependent phagocytic tests: the killing of Staphylococcus aureus Wood 46 variant strain (K50 opsonic titers) and the assessment of ingestion rate of endotoxin-coated paraffin particles (Oil Red 0 uptake test). K50 opsonic titers were lower in culture-positive pleural effusions as compared to culture-negative (P < 0.002) or neoplastic effusions (P < 0.002). These results were corroborated by the Oil Red 0 uptake test. The data obtained with the two assays showed a significant correlation (P < 0.001). The hemolytic activity of complement (CH50) as well as the levels of C3 breakdown product, C3d, were measured in the same sera and pleural fluid samples and in an additional group of patients with pleural effusions of the same etiology. Effusions with positive cultures showed lower CH50 values (P < 0.01) and higher C3d values (P < 0.05) when compared to culture-negative pleural fluids. Finally, evidence for immune complexes in pleural effusions and sera was looked for by determination of Clq binding activity. Levels were higher in culture-positive effusions when compared to culture-negative fluids (P = 0.005).K50 opsonic titers showed a positive correlation with CH50 values (P < 0.001) for all fluids tested. Similarly Clq binding activity correlated with C3d levels in effusions of infectious origin (P = 0.05). Recovery experiments using the various bacterial species isolated from culture-positive pleural effusions showed evidence of complement inactivation upon incubation with pooled sera at concentrations of 10(7)-10(8) microorganisms/ml. These results indicate that one important reason for bacterial persistence in empyema may be decreased opsonization secondary to local consumption of complement.

Adult↗
PubMed1979

Circulating and tissue-bound immune complex formation in murine malaria.

Immune complex formation during Plasmodium berghei infection of OF1 mice was investigated. Circulating immune complexes (CIC) were detected by the Clg-binding assay and the conglutinin-binding solid-phase assay in lethal or drug-limited infections. CIC appeared on day 9 of infection, peaked on day 11, and disappeared only after complete cure of the infection. Analysis of the immune complexes detected by the Clq-binding assay revealed the following characteristics: sedimentation coefficients of 13S to 21S, resistance to DNAse, and selective removal by filtration through protein A bound to Sepharose. Glomerular deposits of IgM preceded the appearance of CIC, whereas deposits of IgG and C3 were concomitant with the appearance of CIC. Tissue-bound immunoglobulins were also found in the choroid plexus. The appearance of anti-malarial antibodies and malarial antigens in the serum was closely associated with a depression of C3 levels and the presence of CIC. Drug treatment was followed by normalization of C3 levels, and clearance of both CIC and malarial antigens.

Animals↗
PubMed1979

Purification of soluble immune complexes from serum using polymethylmetacrylate beads coated with conglutinin or C1q. Application to the analysis of the components of in vitro formed immune complexes and of immune complexes occurring in vivo during leishmaniasis.

A procedure for the isolation of immune complexes from human sera has been developed. Two steps are involved: (1) lipid-free serum is precipitated by polyethylene glycol; (2) the solubilized precipitate is absorbed on a column of polymethylmethacrylate beads coated with conglutinin (K) or C1q; the column is washed, the complexes are then eluted, using 0.02 M EDTA (for K column) or 0.5 M NaCl (for C1q column). This procedure permitted the purification and the characterization of soluble 125I-BSA-anti-BSA, 125 I-tetanus toxoid-anti-tetanus toxoid, and 125-I-HBsAg-anti-HBsAg complexes made in vitro in the presence of fresh human serum. The isolated complexes were shown to contain antigen, antibody, C1q, C1r, C1s and C3. When normal human serum was submitted to such a procedure, no detectable amount of protein was present in the final eluted fraction. Immune complexes formed in vivo were also purified by conglutinin column from the serum of a patient with disseminated leishmaniasis. The isolated material was found to contain IgM, IgG, C1q, C1r, C1s, C3c and C3d. The purified complexes dissociated at acid pH were found to contain anti-IgG and anti-leishmania antibodies.

Adult↗
PubMed1979

Immune complexes and complement in rheumatoid arthritis.

Immune complexes have been shown to occur frequently during rheumatoid arthritis. They have been found in blood, in the synovium and in other extravascular lesions. The recent development of methods for the quantitation of immune complexes provided new tools to evaluate the possible role of immune complexes in rheumatoid arthritis. Immune complexes which appear in synovial fluid are in higher concentration than in serum and have particular physicochemical properties. They likely result from a local formation in the synovium and seem to be directly involved in the generation of the local inflammation. High levels of circulating immune complexes are usually associated with the development of extra-articular vascular lesions. One of the major biological activity of immune complexes is to activate the complement system. There is indeed evidence of complement activation in circulating blood as well as in synovial fluid in patients with rheumatoid arthritis. The presence and the concentration of complement breakdown products in these fluids correlates with the clinical activity. Therefore, the analysis of immune complexes and of complement components appears useful for diagnosis and follow-up, and for the understanding of the pathogenesis of the disease.

Antigen-Antibody Complex↗
PubMed1978

[Specific cytolytic activity of human lymphocytes following vaccination with vaccinia virus and measles virus].

Human peripheral lymphocytes harvested 7 days after vaccination with vaccinia virus or measles virus lyse specifically target cells infected with the corresponding virus. This cytotoxic activity is found in a subpopulation of lymphocytes depleted of T-cells and containing lymphocytes bearing Fc receptor. The activity can also be transferred by supernatant of immune lymphocytes on addition of normal lymphocyte. These results suggest that two types of cell are involved: an antibody-secreting cell providing specific antiviral antibody (B-cells), and an effector cell bearing Fc receptor (K-cells).

Adult↗
PubMed1978

[Immunologic study of pleural neoplastic effusions: Detection of immune complexes and complement activation].

Occurrence of immune complexes in malignant pleural effusions has been investigated by the 125I-c1q binding test. 55% of the pleural effusions had C1q binding activity levels higher than those found in transudates used as controls. The levels of C1q binding activity in effusions were significantly higher than those found in the serum of the same cancer patients. High levels of C1q binding activity were found in malignant effusion independently of type or differentiation of the tumors involved. The C1q binding material had properties of immune complexes. The levels of CH50 and C3d, i.e. the degradation product of C3, in malignant effusion were similar to those of transudates. These observations show a high incidence of immune complexes in malignant effusions and a slight activation of complement inadequate for its local consumption. The persistence in major quantity of immune complexes in malignant effusion suggests local formation or decreased clearance.

Antigen-Antibody Complex↗
PubMed1978

[Incidence and specificity of circulating immune complexes in infectious mononucleosis (proceedings)].

Occurrence of immune complexes in infectious mononucleosis has been investigated by the 125I Clq binding assay. Increased serum Clq-binding activity was found in 87% of the 23 patients studied during the acute stage of the disease. The serum Clq-binding material detected has properties identical to those of immune complexes. IgG antibodies dissociated from the complexes at acid pH and F (ab)'2 fragments obtained after treatment by pepsin appeared to be directed against the viral capsid antigen of Epstein-Barr virus.

Antibodies, Viral↗
PubMed1978

[Immunopathology in a case of kala-azar (proceedings)].

A 33 year old woman was admitted to hospital for fever of unknown origin. Leishmania donovani was found in histological preparations from lymphnodes and by sternal puncture. Circulating immune complexes present in high concentration were isolated and characterized. The circulating immune complexes remained elevated two months after the disappearance of Leishmania from the bone marrow.

Antigen-Antibody Complex↗
PubMed1978

Quantitation of serum complement components and plasma C3d in patients with malignant lymphoma: relation to the stage of the tumor and circulating immune complexes.

Total hemolytic complement activity (CH 50) and complement component levels were measured in 27 patients with Hodgkin's disease and 31 patients with non-Hodgkin malignant lymphoma. CH 50 values were higher than normal in almost all the patients. Increased levels of serum C4, C3 and factor B were observed in 62%, 31% and 19% of these patients, respectively. However, plasma concentration of C3d, a breakdown product of C3, was elevated in 29% of the cases. The hypercatabolism of C3 was not closely associated with the presence of circulating immune complexes, as assessed by the C1q binding assay, nor with the presence of general symptoms in the patients. On the contrary, it appeared to be in relation with the extent of the malignant disease.

Adolescent↗