Synthesis and biological evaluation of a new class of vaccine adjuvants: aminoalkyl glucosaminide 4-phosphates (AGPs).

A novel series of acylated omega-aminoalkyl 2-amino-2-deoxy-4-phosphono-beta-D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toxoid-specific antibodies in mice and augment vaccine-induced cytotoxic T cells against EG.7-ova target cells.

Early undifferentiated connective tissue disease. V. An inception cohort 5 years later: disease remissions and changes in diagnoses in well established and undifferentiated connective tissue diseases.

OBJECTIVE: To review the diagnoses after 5 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD); to examine death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients was identified in 10 academic rheumatology practices. They had less than one year of signs and/or symptoms of CTD. Diagnoses of specific well established CTD were made using accepted diagnostic and classification criteria. The diagnoses after 5 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The progression of unexplained polyarthritis to rheumatoid arthritis occurred infrequently. Ten percent of patients with isolated Raynaud's phenomenon progressed to systemic sclerosis (SSc). The 5 year survival was over 90% in all diagnostic categories, with the exception of SSc, in which it was 64%. CONCLUSION: Patients with a well established CTD usually continued with the same diagnosis. Patients with undifferentiated CTD tended to remain undifferentiated or to remit.

TJ-114 (Sairei-To), an Herbal Medicine in Rheumatoid Arthritis.

The search for better treatments for malignancies has been enhanced by use of a relatively inexpensive clinical protocol that encourages the preliminary screening of a large number of potential anticancer drugs with early elimination of those that are clearly ineffective, preserving resources for more intensive evaluation of those that show some evidence of benefit. We adapted this method to determine whether the herbal medicine TJ-114 was worthy of further study for the treatment of rheumatoid arthritis (RA) patients. TJ-114 is a traditional herbal medicine that has been used extensively in Japan for the treatment of RA, Reports suggest that it may be a useful second-line agent, well-tolerated and safe. For these reasons, a 6-month, open prospective pilot study to evaluate the efficacy, safety and tolerability of TJ-114 in United States RA patients was undertaken. Thirty patients were enrolled; 18 completed the study. There were five responders by predefined composite criteria. Twelve patients withdrew from the trial, six for lack of efficacy, four for non-compliance, one for diarrhea and one for constipation and abdominal pain. The anti-cancer drug screening protocol stipulates that the drug be discarded if there are no responders among the first 14 patients and only 1 or 2 among the first 30 patients. Using this approach, the response rate found in this study justifies placebo-controlled, double-blind studies to determine the relative efficacy and toxicity of TJ-114 in a more definitive manner.

Arthritogenic effects of Mycoplasma arthritidis T cell mitogen in rats.

The intraarticular injection of Mycoplasma arthritidis T cell mitogen (MAM) produced significant joint swelling with inflammation in DA rats. Histologic examination of the joint initially showed edema below the synovial surface layer with light polymorphonuclear and focal lymphoid cell infiltration. Widespread but incomplete shedding of the surface layer of the synovial membrane and hypertrophy and hyperplasia of the subsynovium with fibroblasts and macrophages were observed subsequently. The hyperplastic process began to resolve by Day 5 and almost completely disappeared by Day 7 with healing of the surface layer, leaving virtually no trace of the preceding acute episode. Arthritis in animals with previous adjuvant induced arthritis was not exacerbated by the intraarticular injection of MAM.

Chronic arthritis of rabbits induced by mycoplasmas. I. Clinical microbiologic, and histologic features.

Mycoplasma arthritidis and Mycoplasma pulmonis induced chronic arthritis in rabbits on intraarticular injection, characterized by joint swelling and histologic evidence of chronic active inflammation persisting at least one year. Cartilage and bone destruction was a prominent late feature of M arthritidis but not M pulmonis disease. Despite the progressive nature of the disease and persistence of active inflammation for many months after inoculation, mycoplasmas and mycoplasma antigens were not found in joint tissues after 7 weeks.

Mycoplasma-dependent activation of normal lymphocytes: mitogenic potential of mycoplasmas for mouse lymphocytes.

Nonviable preparations of a wide variety of glucose-utilizing mycoplasma species, including Acholeplasma laidlawii and Spiroplasma citri, were found to be mitogenic for mouse lymphocytes. Particularly strong reactions were obtained with Mycoplasma synoviae, M. gallisepticum, M. pneumoniae, S. citri, and a strain of M. fermentans that was previously isolated from a leukemic patient. Nonviable preparations of arginine-utilizing mycoplasmas inhibited the uptake of [3H]thymidine by lymphocytes, but this effect could be reversed by heat treatment or arginine supplementation, and a stimulatory effect was then observed. Viable M. arthritidis was also found to have a mitogenic effect, as detected by an increased uptake of [3H]thymidine by normal lymphocytes and by autoradiographic techniques in which an increase in the numbers of transformed cells was seen. These observations provide the potential for enhanced immunological responsiveness or lymphokine-mediated inflammation in mycoplasma-infected hosts.

Mycoplasma-dependent activation of normal lymphocytes: role of arginine and nonviable mycoplasma antigen in the induction of lymphocyte-mediated cytotoxicity for syngeneic mouse target cells.

The ability of arginine supplementation to abrogate or potentiate Mycoplasma arthritidis-mediated cytotoxicity induction by normal CBA mouse lymphocytes was investigated. Also, nonviable antigens of M. arthritidis were assayed for their ability to induce a cytotoxic response. The presence of additional arginine in the culture medium had no significant effect on the amount of cytotoxicity produced. In some cases, an increase in cytotoxicity was seen in the presence of additional arginine. Amino acid analysis of the culture supernatants showed that the arginine in the nonsupplemented medium was exhausted during the assay, whereas ample amounts of arginine were present in the supplemented medium. However in both cases the amount of cytotoxicity was comparable. Nonviable antigens of M. arthritidis were unable to induce a significant cytotoxic response in the presence of normal lymphocytes. The same antigens exhibited a suppressive response when tested for blastogenesis in the presence of normal lymphocytes. A discussion of lymphocyte involvement is presented.

Arthritis of mice induced by Mycoplasma arthritidis. Humoral antibody and lymphocyte responses of CBA mice.

Peak arthritis occurred 7 days after intravenous injection of CBA mice with Mycoplasma arthritidis and persisted in some animals for 84 days. A marked leucocytosis was apparent for the first 21 days. Complement-fixing antibodies reached a peak 14 days after injection of the organisms and persisted at high levels for 84 days. Metabolic-inhibiting and mycoplasmacidal antibodies were present but at much lower titres.

Chronic proliferative arthritis of mice induced by Mycoplasma arthritidis: demonstration of a cell-mediated immune response to mycoplasma antigens in vitro.

Lymphocytes taken from mice chronically infected with Mycoplasma arthritidis exhibited a significant blastogenic response as measured by (3H)thymidine uptake when exposed in vitro to M. arthritidis antigens. The lymphocytes taken from 9 of 12 control mice of similar age exhibited an inhibition of (3H)thymidine uptake when exposed to M. arthritidis antigens.