The effect of 15-deoxyspergualin, a newly developed anti-tumor agent, on the development of spontaneously occurring lupus glomerulonephritis in male BXSB and MRL/lpr mice was examined. The prophylactic effect of 15-deoxyspergualin was evaluated using 8-week-old male BXSB mice. Its therapeutic effect was estimated using male BXSB and MRL/lpr mice of 13 weeks of age. Treatment with 15-deoxyspergualin at a dose of 5 mg/kg for 5 weeks suppressed the increment of IgG-producing cells in the spleen, decreased serum levels of circulating immune complexes assessed by solid-phase C1q-binding assay and effectively prevented the deposition of immune complexes in renal glomeruli estimated by immunofluorescent studies in both strains of mice. 15-Deoxyspergualin was also effective in preventing the massive lymphoproliferation characteristic of MRL/lpr mice as assessed by the weight of mesenteric lymph nodes. It seemed quite valuable that 15-deoxyspergualin drastically suppressed the progress of polyclonal B cell activation in both strains of autoimmune mice, which have different mechanisms leading to B cell activation. These results suggest that 15-deoxyspergualin might be used as a therapeutic agent for human erythematosus.

Animals↗

PubMedDate not supplied

Immunosuppressive activities of deoxyspergualin. II. The effect on the antibody responses.

We examined the suppressive effect of a newly developed antitumor agent, 15-deoxyspergualin (DSP), on the plaque-forming cell responses to various antigens. The intraperitoneal injections of DSP at a dose of 5.0 mg/kg body weight suppressed drastically the development of plaque-forming cells in the spleen of C57BL/6 mice immunized with sheep red blood cells (0.2 ml of a 5% suspension), trinitrophenyl-lipopolysaccharide (1 microgram/mice) and trinitrophenyl-Ficoll (100 micrograms/mice). These suppressive effects were observed when the administration of DSP was started after the injection of antigens. The responsiveness of spleen cells from DSP-treated mice was also checked in in vitro culture. Responsiveness to lipopolysaccharide in vitro was not reduced. Furthermore DSP did not significantly suppress the responsiveness of spleen cells to succinylated concanavalin A or production of interleukin-1 or -2. The results are discussed with regards to the mode of action of DSP on immune responsiveness.

Animals↗

PubMedDate not supplied

Toxicological and immunological evaluation of the immunosuppressant 15-deoxyspergualin in BALB/c mice: an in vivo and in vitro study.

The toxicological aspects as well as the immunosuppressive mechanism of 15-deoxyspergualin (DSP) were studied using BALB/c mice. Five-week-old animals were subcutaneously given phosphate-buffered saline (PBS; Group 1) or DSP at 0.5 (Group 2) to 5.0 mg (Group 4) per kg body weight daily for 1 to 3 months. They were sacrificed to obtain blood for hematology and liver function studies. The spleen, taken simultaneously, was histologically examined, the T cell surface markers of splenocytes were flow cytometrically measured, and their interleukin 2 (IL-2) production induced in vitro by Enterotoxin A (Ent A) was assayed using CTLL cells. Additionally, the in vitro effect of DSP on IL-2 generation and plaque forming cell (PFC) production was studied using splenocytes of non-treated mice. During the 3 months of treatment, the body weight slowly increased in Groups 1 and 2, while the body weight of the 2.5-mg DSP mouse group (Group 3) was significantly lower on days 28 and 56 of treatment compared with Group 1 of the same age (P less than 0.05). The administration of DSP at 5.0 mg/kg (Group 4) caused marked reduction in body weight of the animals. They were sacrificed on day 28 because of their worsening general condition. WBC and RBC counts decreased in Group 3 on days 57 and 93, and the platelet number increased on day 57. A liver function test was not affected by DSP treatment except for an elevated SGOT in Group 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Role of insulin resistance in heart and skeletal muscle F-18 fluorodeoxyglucose uptake in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: Altered heart and skeletal glucose usage has been reported in patients with non-insulin-dependent diabetes mellitus (NIDDM). Although elevations in plasma free fatty acid (FFA) concentrations have been implicated in reduced myocardial 18fluorine-fluoro-2-deoxy-D-glucose uptake (MFU), the specific role of whole-body insulin resistance in MFU in patients with NIDDM compared with skeletal muscle metabolism remains controversial. PURPOSE: MFU and skeletal muscle 18fluorine-fluoro-2-deoxy-D-glucose uptake (SMFU) were compared with positron emission tomography and the whole-body glucose disposal rate (GDR) during hyperinsulinemic euglycemic clamping in 26 normotensive asymptomatic patients with NIDDM who were not taking medication. These factors were also compared in 12 age-matched control subjects to increase the knowledge of the influence of whole-body insulin resistance on MFU. In addition, independent factors for both SMFU and MFU were investigated. RESULTS: GDR in control subjects (10.0 +/- 2.97 mg/min per kilogram) was significantly higher than in patients with NIDDM (4.05 +/- 2.37 mg/min per kilogram, P < .01). SMFU in patients with NIDDM (0.826 +/- 0.604 mg/min per 100 g) was significantly lower than that in control subjects (1.86 +/- 1.06 mg/min per 100 g, P < .01). MFU in patients with NIDDM (5.35 +/- 2.10 mg/min per 100 g) was also significantly lower than that of control subjects (7.05 +/- 1.66 mg/min per 100 g, P = .0182). SMFU significantly correlated with GDR (r = .727, P < .01) and FFA (r = -.52, P < .01) in patients with NIDDM. MFU also correlated with GDR (r = .778, P < .01) and FFA (r = -.72, P < .01) in patients with NIDDM. Multivariate stepwise regression analysis showed that GDR (F = 36.8) was independently related to MFU (r = .85, P < .01) whereas FFA was not (F = 1.763), where F is the value for statistical analysis of multivariate stepwise regression analysis. CONCLUSION: Insulin resistance is the most essential factor for both heart and skeletal muscle FDG uptake in patients with NIDDM.

Adult↗

PubMedDate not supplied

Salmonella typhimurium infection in domesticated fowl in a children's zoo.

Salmonella typhimurium infection occurred in a children's zoo where 11 fowl and 85 mammals were kept. Initially, the guinea pigs were infected and transmitted the infection to the fowl and rabbits. These mammals responded to medication and cleared of the infection; however, the birds were judged to contain excreters despite four regimens of treatment with antibiotics. Cloacal swabs were taken from all the birds. One turkey was positive for Salmonella and was destroyed. Pooled fecal samples from the birds were again positive. All the birds were tested serologically, and two birds, a goose and a turkey, were positive with Salmonella pullorum-gallinarum antigen, which was assumed to be a cross reaction with S. typhimurium antigen. The two birds were destroyed and the goose yielded Salmonella. The infection was finally eradicated, and the serologic examination was considered to be the most useful procedure for detection of the excreters.

Animals↗

PubMedDate not supplied

An occurrence of cardiac rupture in a capercaillie (Tetrao urogallus) probably induced by myocardial infarction.

A pair of capercaillies (Tetrao urogallus) were newly introduced from Austria into a museum in Japan, and the female bird died on the way to the museum. Autopsy revealed cardiac tamponade filled with a large quantity of blood coagulum in the pericardial cavity and cardiac rupture along the apex around 1.5 cm in length. Microscopically, myocardial necrosis associated with cellular infiltration was observed. The results indicated that the bird suffered from cardiac rupture on the way to the museum. Myocardial infarction was considered to be a predisposing factor for the incident.

Animals↗

PubMedDate not supplied

IL-1-mediated expression of membrane type matrix-metalloproteinase in rheumatoid osteoblasts.

OBJECTIVE: To determine whether the activation of metalloproteinases can be achieved by the interaction of the inflammatory cytokine, IL-1 beta, with rheumatoid osteoblasts. RESULTS: MMP-2 is not secreted by rheumatoid osteoblasts as a proenzyme; however, IL-1 beta stimulation induced the secretion of MMP-2 as an active form from rheumatoid osteoblasts. This MMP-2 activating activity was detected significantly in IL-1 beta-stimulated rheumatoid osteoblasts. In support of this result, IL-1 beta stimulation induced the expression of membrane type matrix-metalloproteinase (MT-MMP), a newly-identified MMP-2 specific activator, in rheumatoid osteoblasts. CONCLUSION: These results suggest that IL-1 beta induces MMP-2 activation in part by up-regulating MT-MMP expression and represents a new mechanism for cytokine-mediated articular destruction in RA.

Arthritis, Rheumatoid↗