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Biomedical subjects

J Ferluga

Publications and source records attributed to J Ferluga.

At least 19 recordsLinked to original sources
PubMed2000

Heterogeneous recognition of beta 2-glycoprotein I by antibodies from antiphospholipid syndrome patients.

Beta 2-glycoprotein I plays a pivotal role in the binding of antiphospholipid antibodies to phospholipid in patients with antiphospholipid syndrome. In this study the nature of the epitopes on beta 2-glycoprotein I (beta2-GPI) recognised by sera from antiphospholipid syndrome (APS) patients (n = 15) was investigated and compared to rabbit polyclonal and mouse monoclonal anti-beta2-GPI antibodies. beta2-GPI was only recognised when bound to a high affinity binding support. The antigenic epitope on beta2-GPI recognised by all APS patients was also dependent on disulphide bond integrity. Digestion of beta2-GPI with elastase rapidly destroyed the epitope(s) on beta2-GPI recognised by antibodies in 91% of APS patients. The main cleavage occurred at tryptophan316-lysine317 in the fifth domain. Digestion with staphylococcal V8 protease resulted in a 50% reduction in antibody binding in 81% of patients and the cleavage sites mainly involved the first domain of the molecule. There was considerable variability in the recognition of six different species of beta2-GPI by serum from APS patients. The epitopes on beta2-GPI bound by APS sera appear conformationally determined in all patients but are quite heterogeneous in the regions of beta2-GPI that are recognised.

Adsorption↗
PubMed1990

Potential role of anti-oncogenes in aging.

Some observations on cellular senescence are discussed regarding the possibility that the postulated genes, which bring about the DNA synthesis block of senescent fibroblasts, might be similar to those designated as anti-oncogenes or tumour suppressor genes. The latter genes have been defined by tumorogenicity tests of hybrids from fused tumour and normal cells, of which the retinoblastoma (RB) gene is a prototype. Similarities between the two systems are considered, which are consistent with the assumption that senescent growth arrest, like the suppression of tumorogenicity of the hybrids, might be effected by anti-oncogenes via inhibition of cellular oncogenes in their growth signal transduction functions. A link may be provided by the finding of a direct interaction of certain DNA tumour virus oncoproteins with the RB gene product p105-RB, together with observations that the tumour viruses are also able to reinitiate DNA synthesis in growth arrested senescent fibroblasts. The possibility is also discussed that some silent retinoblastoma-like genes might become aberrantly expressed in senescent cells owing to a progressive loss of 5-methyl cytosine residues of DNA.

Aging↗
PubMed1989

Possible organ and age-related epigenetic factors in Huntington's disease and colorectal carcinoma.

It is hypothesized that the expression of Huntington's disease and the development of sporadic colorectal carcinomas may largely depend on age-related epigenetic defects in methylation pattern of DNA at the disease associated loci. In the former case the potential defects may be coupled with a DNA demethylation and activation in the brain of a silent growth factor-like gene that may induce an abnormal cell differentiation. In the development of colon carcinomas the age-related process may affect potential growth regulatory genes that may normally become demethylated and active in the colon as part of their differential expression. In such a state and possibly also due to their structure, they may be especially prone to the epigenetic defects that may lead in this case to gene point mutation and deletion.

Aging↗
PubMed1988

Is all genetic (hereditary) hemochromatosis HLA-associated.

1. GH in Australia is significantly associated with the HLA-A3 antigen, which is the only independent marker for the disease (B7 in linkage disequilibrium with A3). 2. The haplotype A3, B7, DR2 is the only one with increased prevalence in this disease, presumably due to its being the predominant haplotype among early immigrants. 3. Exceptions to HLA association in GH are rare and can be explained by: (1) incorrect HLA serotyping, (2) chromosomal recombination, or (3) rare homozygous-homozygous mating. 4. These data are consistent with GH being due to a mutant gene or genes in close proximity to HLA-A. 5. Heavy alcohol ingestion does not lead to expression of hemochromatosis in heterozygous subjects.

Alcohol Drinking↗
PubMed1987

Genetic hemochromatosis and HLA linkage.

We previously reported five families with primary, genetic (idiopathic) hemochromatosis in whom HLA typing of subjects indicated that a homozygous-heterozygous mating had almost certainly occurred and in whom inheritance of the disease trait was best explained by an autosomal recessive mode of inheritance. However, in one family, two children apparently homozygous for hemochromatosis did not manifest overt evidence of the disease, and alternative explanations were postulated, including autosomal dominant inheritance in this family. Subsequent study of the family members, including repeat HLA-DR serology with more recently defined antisera and DNA genotyping at the HLA-DR locus has, we believe, provided the true explanation for the previous apparent anomaly and adds further evidence for the tight linkage of the disease to the HLA-A locus.

Female↗
PubMed1985

Identification of murine H-2Db histocompatibility antigens in cells transfected with cloned H-2 genes.

Clones of mouse L-cells transformed with 21 cosmids containing 15 major histocompatibility complex class I genes of C57BL10 (H-2b) sperm cell DNA were analyzed for the expression of their transfected H-2 and Qa/Tla genes. Three cosmids contained a single gene, mapping to the H-2D region. This gene encodes the H-2Db alloantigen: mouse L-cells transfected with cosmids containing this gene reacted with monoclonal antibodies and alloantisera specific for the H-2Db antigen and expressed a 46-kd H-2 heavy chain associated with beta 2-microglobulin in their cell membranes. Furthermore, these transfected cells were stimulators of, and targets for, anti-H-2Db cytotoxic T-lymphocytes. Eighteen cosmids contained 14 different genes mapping to the Qa and Tla regions. L-cells transfected with these genes did not express class I genes reacting with alloantisera or monoclonal antibodies against Qa2, Qa4 or TL differentiation antigens. In particular, the Qa2,3 gene of C57BL10 was not identified.

Animals↗
PubMed1984

Lipopolysaccharide hyperreactivity of animals infected with Trypanosoma lewisi or Trypanosoma musculi.

Rats and mice infected with Trypanosoma lewisi and Trypanosoma musculi, respectively, showed hyperreactivity to lipopolysaccharide (LPS) from gram-negative bacteria. Fatal shock could be precipitated with a dose of LPS 100 to 1,000 times less in infected compared with noninfected animals. In trypanosome-infected rats and mice, extensive liver damage was evident after LPS challenge. These animals showed a pronounced hypoglycemia, marked elevation of blood aspartate transaminase level, and diffuse severe degeneration and total depletion of glycogen in hepatocytes. Only minor changes were observed in noninfected animals given the same dose of LPS. No mononuclear phagocytic cell infiltration was observed in the liver of infected animals. The most striking change was the great increase in size and the probable increase in phagocytic activity and number of sinusoidal Kupffer cells. We suggest that elevated Kupffer cell activity in trypanosome-infected animals may play a role in LPS-induced hepatotoxicity.

Animals↗
PubMed1984

Suppressor cells induced by BCG release non-specific factors in vitro which inhibit DNA synthesis and interleukin-2 production.

Mice injected intravenously with a high dose (5 X 10(7) ) of BCG fail to develop delayed hypersensitivity to BCG and are described as anergic or unresponsive. Spleen cells from these mice release factors on culture which suppress DNA synthesis induced by concanavalin A in vitro. Cell separation experiments showed that both macrophages and T cells produce inhibitory factors. However, the macrophage factor has a molecular weight 10,000-30,000, while the T cell factor has a molecular weight of 50,000-70,000. Further evidence that these two factors are different is provided by the kinetics of their action. The T cell factor only acts when given within 12 hr of stimulation with concanavalin A, while the macrophage factor acts even when given at 48 hr. In the case of the T cell factor, the inhibition of DNA synthesis may be attributed to its ability to block the interleukin-2 production induced by Con A. As similar T cell and macrophage factors are produced in mice responding to simple chemically reactive haptenes (contact sensitizers), it is possible that a similar suppressor circuit is involved in the control of the response to contact sensitizers and in the production of unresponsiveness (anergy) in mice given large doses of BCG.

Animals↗
PubMed1982

Expression of murine H-2Kb histocompatibility antigen in cells transformed with cloned H-2 genes.

Cosmids containing H-2 histocompatibility antigen genes of the H-2b haplotype have been isolated. One of these genes expresses a 45,000 molecular weight protein, indistinguishable from H-2Kb when introduced into mouse L cells. These H-2Kb transformed L cells can be killed by allospecific anti-H-2Kb cytotoxic T cells. Moreover, when infected with influenza virus, they can be killed by an H-2Kb-restricted, influenza virus-specific cytotoxic T cell line. These results show that expression of the H-2Kb gene product on the L-cell surface is sufficient to make it a target for specific T-cell killing.

Animals↗
PubMed1981

Tuberculin hypersensitivity hepatitis in mice infected with Mycobacterium bovis (BCG).

A systemic BCG infection in mice induced multiple small granulomas located mainly in the periportal areas of the liver. Following systemic challenge of such mice with purified protein derivative of tuberculin (PPD), a rapidly developing hepatitis with diffuse intralobular mononuclear cell infiltration was precipitated, accompanied by high levels of aspartate transaminase in peripheral blood, hypoglycemia, focal hepatocyte necrosis, and accumulation of fibrinogen in liver. Bacterial lipopolysaccharide (LPS) also provoked acute hepatic damage both in BCG-infected mice and in mice pretreated with Corynebacterium parvum. PPD was not active in the latter. There were also lymphoid cell destruction and fibrinogen accumulation in the spleen of BCG-PPD-treated mice. Possible involvement of inflammatory and hepatotoxic mediators is suggested, and a T-lymphocyte-macrophage regulatory role in the pathogenesis of hepatitis is discussed.

Animals↗
PubMed1979

Protection of mice against endotoxin-induced liver damage by anti-inflammatory drugs.

Mice were injected with Corynebacterium parvum, which induces multiple granulomas in liver and renders animals hyper-reactive to the lethal effect of bacterial lipopolysaccharide (LPS). Such animals when challenged with LPS developed also extensive liver parenchymal cell damage as estimated by elevated blood asparate transaminase levels and a hypoglycaemia. Treatment with indomethacin, hydrocortisone, dexamethasone, promethazine, metiazinic acid and (+)-catechin ameliorated the liver damage. Hydrocortisone, dexamethasone, promethazine and metiazinic acid also reduced the mortality rate in mice challenged with LPS. Diarrhoea, accompanying the LPS-induced shock, was prevented by the drugs used. Possible agents mediating the hepatotoxic and shock effects of LPS are discussed.

Animals↗
PubMed1979

Increased hepatotoxicity of bacterial lipopolysaccharide in mice infected with Schistosoma mansoni.

Mice infected with Schistosoma mansoni were highly sensitive to the lethal effects of bacterial lipopolysaccharide (LPS). The hyper-reactive state of LPS coincided with the development around the parasite eggs of multiple granulomas in the liver. Elevated aspartate transaminase levels in blood and severe hypoglycaemia in LPS-challenged animals indicated extensive liver parenchymal cell damage. There was also a complete depletion of glycogen in hepatocytes of these animals. From this work and studies on other hepatitis models, it is suggested that individuals affected with granulomatous disorders may be at risk because of everyday exposure to LPS from the gut.

Animals↗
PubMed1979

Protection of pregnant mice with phospholipase C and with Arvin against foetal death induced by bacterial lipopolysaccharide.

Injection of bacterial lipopolysaccharide into pregnant mice resulted in fibrinogen accumulation, thrombosis and haemorrhage in the placental tissue and foetal death. Depletion of circulating fibrinogen by a thrombin-like enzyme from the venom of Malayan pit viper, Arvin, prevents foetal death. Foetal protection was also obtained by treating the mothers with a preparation of phospholipase C from Bacillus cereus known to inactivate tissue thromboplastin. It is suggested the lipopolysaccharide causes foetal death by inducing thrombosis as a consequence of activation of placental thromboplastin.

Ancrod↗
PubMed1979

The use of indium-111 for studies of cytotoxicity mediated by lymphocytes or by antibodies and complement.

Mouse P815 mastocytoma cells, Meth A sarcoma cells and human MRC5 fibroblasts and peripheral blood mononuclear cells were labelled with 111In, 51Cr or 125IUdR and their release from the cells measured. Spontaneous release of 111In from the cells in cultures was less than half that of 51Cr and was comparable to the release of 125I. When 111In-labelled P815 cells were lysed with antibodies and complement or with sensitized lymphocytes the label was released rapidly. 111In is a convenient label in short- as well as in long-term in vitro cytotoxicity studies because of its high labelling and detecting efficiency and its stable cell association.

Animals↗