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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.

A classification of the different types of osteogenesis imperfecta is proposed. There are 3 main groups: the lethal type, the severe type and the so-called regressive type, with a more favorable course. This classification was established to allow for a more precise definition of the prognosis at the time of birth, or even in utero when diagnosis is made by ultrasonography. It should also allow for better classification of the data obtained by the study of the molecular collagen. This project is different from Sillence's one by the exclusion of type II B lethal types, which are often compatible with survival. In view of the frequent occurrence of a dominant mutation in the type II A, the more generally accepted recessive transmission is discussed.

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.

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.

The nature of spleen cells in Fischer rats bearing a large size (greater than 1 cm diameter) mammary adenocarcinoma 13762A (MAC) which block the immunostimulating capacities of MTP2 (a synthetic immunomodulator) and suppress proliferation in vitro of splenic T and B lymphocytes by their respective mitogens was investigated. Splenic macrophages were recognized as the suppressor cells by (a) restoration of mitogenic responses by depletion of macrophages from spleen cell suspensions and (b) continued suppressor activity in spleen cell suspensions of tumor bearers devoid of viable T lymphocytes. Macrophage contact with T lymphocytes was required for the inhibition of T lymphocyte proliferation by concanavalin A as shown by (a) the absence of suppressor activity in supernatants derived from cultured suppressor macrophages, (b) lowering of the suppressor activity of intact macrophages after treatment with neuraminidase, (c) lowering of the suppressor activity of macrophages by addition of red cells to spleen cultures of tumor bearers indicating red cell interference with macrophage-T cell interaction and (d) lack of inhibiting action of suppressor macrophages on allogenic T lymphocyte proliferation showing macrophage T cell recognition for suppression. Animals bearing a large size tumor exhibited spleen hypertrophy and an increase in macrophage: lymphocyte ratio and a decrease in red cell: lymphocyte ratio. Splenic macrophages did not appear to be implicated in blocking antitumor immunity induction since (a) suppressor macrophages were absent in spleens during the inductive phase of the immune response and (b) MAC implanted in allogenic Wistar rats grew to about 2 cm diameter, induced splenic suppressor macrophages but the tumor was later rejected by the animals. Collectively the results suggest that suppressor macrophages are the result of increasing tumor volume rather than its cause.

The effects of porcine interleukin-1 (IL-1) alpha on collagen production were studied in cultured human rheumatoid synovial cells. Addition of 0.05-5 ng of IL-1/ml into the cultures resulted in a dose-dependent decreased rate of collagen released into the medium over 24 h. To determine whether this inhibition was due to secondary action of prostaglandin E2 (PGE2) secreted in response to IL-1, cultures were incubated in presence of various inhibitors of arachidonate metabolism. Depending on the cell strains, these inhibitors were able to suppress or diminish the effect of IL-1, suggesting that PGE2 is involved in the mechanism. Depression of collagen production caused by IL-1 mainly affected type I collagen and therefore led to a change in the type I/type III collagen ratio in the extracellular medium. Steady-state levels of mRNA for types I and III procollagens were estimated by dot-blot hybridization and compared with the amounts of respective collagens produced in the same cultures. IL-1 generally increased procollagen type I mRNA, but to a variable extent, as did indomethacin (Indo). Depending on the cell strain, the combination of indo and IL-1 could elevate the mRNA level of type I procollagen compared with Indo alone. These results did not correlate with the production rate of collagen in the medium, which was diminished by exposure to IL-1. The level of mRNA for collagen type III was not greatly changed by incubation with IL-1, and a better correlation was generally observed with the amount of type III collagen found in the medium. These data suggest that an additional control mechanism at translational or post-translational level must exist, counterbalancing the stimulatory effect of IL-1 on collagen mRNA transcription. It is likely that IL-1 could modulate the production of collagen in synovial cells by an interplay of different mechanisms, some of them limiting the effect of primary elevation of the steady-state mRNA level.