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Biomedical subjects

J Bonaventure

Publications and source records attributed to J Bonaventure.

78 records · Page 5Linked to original sources

Induction of antitumor immunity employing live tumor cells and maltose tetrapalmitate.

Several protocols employing a new immunoadjuvant, maltose tetrapalmitate (MTP), were tried in an effort to obtain immunization against a weakly immunogenic transplantable mammary adenocarcinoma, 13762, in syngeneic Fischer rats. Effectiveness of immunization was measured by rejection of tumor or reduction in tumor growth, by alteration in survival time after tumor challenge, and by proliferation in vitro of spleen cells of animals tumor-sensitized by killed tumor cells and tumor extracts. No success in the induction of tumor rejection was achieved by employing killed tumor cells or 3 M KCl tumor extracts used in either the presence or absence of MTP. Only a low dose of viable tumor cells elicited tumor rejection immunity when combined with MTP treatment given three times weekly. Spleen cell proliferation of tumor-sensitized animals was obtained in the case of live cells and 3 M KCl extract immunization, and was specific for the type of antigen (killed cells or soluble) preparation employed.

Adjuvants, Immunologic↗

In vitro spleen cell proliferation following in vivo treatment with a synthetic glycolipid or lipid A in three mouse strains.

Synthetic glycolipid, maltose hexastearate (MHS), like LPS or lipid A is a B cell mitogen for outbred Swiss mice, inbred C3H/HeN and C3H/HeJ X C3H/HeN F1 hybrid but not for C3H/HeJ mice. MHS administered i.p. (10 micrograms) to Swiss, C3H/HeN, C3H/HeJ and C3H/HeJ X C3H/HeN F1 hybrid mice confers within 90 min an increased ability in the spleen cell populations such that they exhibit increased incorporation of 3H thymidine into cellular DNA in vitro. The spleen cells of MHS treated mice also respond in vitro more vigorously than controls to a T cell mitogen (Con A) but not at all differently from controls to a B cell mitogen (LPS). The stimulated cells are sensitive to anti theta serum + C' (experiment done with Swiss mice) and the Lyt 1,1 monoclonal antibody + C' (experiment done with C3H/HeN mice), indicating them functionally to be of T-helper variety. Unlike MHS, lipid A administration i.p. resulted in MHS like response in C3H/HeN but not in C3H/HeJ mice. MHS action has been traced to an induction of IL1 release by macrophages of MHS treated animals by chromatographic analysis of macrophage derived supernatants. IL1, in turn, according to the prevalent concepts would stimulate immature T cells to become mature IL2 producer cells, allowing T helper cell proliferation through IL2 release.

Adjuvants, Immunologic↗

Effects of structural variations in synthetic glycolipids upon mitogenicity for spleen lymphocytes, adjuvancy for humoral immune response and on anti-tumour potential.

Synthetic glycolipids prepared by esterification of various sugars and sorbitol, and containing various numbers of saturated or unsaturated fatty acid residues as well as bacterial lipid A and lipopolysaccharide, were tested for mitogenicity of splenic cells of Fischer rats and Swiss mice and for the augmentation of humoral immune response against sheep red blood cells in these species. Subsequently a few of the humoral immune-response-enhancing glycolipids were compared with non-enhancers in their anti-tumour activity against 13762 rat mammary carcinoma in inbred Fischer 344 rats and Ehrlich tumour in Swiss mice. They were given systemically after tumour inoculation and intratumourally in squalene and Tween emulsion after intradermal MAC tumour development. It was observed that certain structural characteristics in glycolipids with respect to the type of sugar, the type and number of fatty-acid residues were needed for their adjuvant action of the humoral arm of the immune response. Although humoral immune-response enhancers were somewhat superior to non-enhancers in their anti-tumour activity, the correlation coefficient demonstrated a lack of significant concordance. It is concluded that glycolipids selected for their ability to augment humoral immune responses against standard antigens need not be suspect as tumour-enhancers on the grounds that they would elicit blocking antibodies in vivo against tumour-associated antigens.

Adenocarcinoma↗

Linkage study in a large pedigree with Stickler syndrome: exclusion of COL2A1 as the mutant gene.

A three generation family with Stickler syndrome is reported. Affected patients exhibited myopia with frequent retinal detachment or glaucoma. Most of them had characteristic facial dysmorphism, the Pierre-Robin sequence being observed in four individuals. Neonatal radiological signs of the Weissenbacher-Zweymüller syndrome were also noticed but early arthopathy was not reported in adults. Restriction fragment length polymorphism studies with the type II collagen gene (COL2A1) showed a recombination event between the disease locus and COL2A1, thus excluding collagen type II as the candidate gene. Although the calculation of the likelihood of genetic heterogeneity versus homogeneity based on 10 families was not statistically significant, we suggest that a second locus is probably involved in this highly variable syndrome.

Abnormalities, Multiple↗

[Lethal syndromes with thin bones].

The authors report six cases from six different families of lethal brittle bone disease with narrow diaphyses and thin ribs. This phenotype should be dissociated from the lethal forms of osteogenesis imperfecta and encompass two diseases. In the first, autosomal recessive, the metaphyses of long bones are narrow, with a membranous ossification, without cartilagenous residue. Cultured fibroblasts demonstrate a marked increase in type V collagen. In the second type, the metaphyses are enlarged and the babies have a facial dysmorphism with hypoplasia of the eyebrows, frontal bossing and a small mouth.

Bone Diseases, Developmental↗

Combined radiotherapy, chemotherapy, and maltose tetrapalmitate immunotherapy in the treatment of 4'dimethylaminoazobenzene-induced liver cancer.

Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunotherapy alone and in combinations were tried against 4' dimethylaminoazobenzene (DAB) induced primary liver cancer in Wistar rats in three separate protocols. Rats were fed a low protein synthetic diet containing 0.06% DAB for 90-120 days. Around 90 days, liver cancers developed in all the animals. In the first protocol, animals were either left untreated or treated with cyclophosphamide (Cy), MTP (i.p. or oral) and Cy plus oral MTP. Rats in the MTP (i.p.) group maintained a steady liver weight but neither Cy nor Cy + MTP influenced the survival time or liver weight. In the second protocol, R as well as a 3-drug combination at 2 dose levels were tried alone and with MTP before or soon after cessation of DAB feeding. Survival times were decreased by R and chemotherapy due to combined toxicities of DAB and treatments and were partially restored by MTP. In the third protocol, MTP, R, and Cy were each tried alone and in combinations, 21 days after cessation of 100-day DAB feeding. Increase in survivals were obtained by each treatment, although tumor weight was best controlled by triple R+ Cy + MTP combination.

Animals↗