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Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) synergistically induce and sustain arthritis. Two competing hypotheses of arthritis induction are 1) that TNF preferentially mediates inflammation, whereas IL-1 impels bone destruction, or 2) that either cytokine controls the entire process. In this study, these propositions were tested in two experiments by instilling IL-1β or TNF-α into one knee of Lewis rats (n = 6/group) to incite arthritis, after which semiquantitative scores for inflammation, bone resorption, osteoclasts, and cartilage integrity were acquired. In the induction study, IL-1β or TNF-α (3, 10, or 30 μg) was given once to incite arthritis. After 2 days, IL-1β induced significant, dose-dependent increases in inflammation (mild to marked), bone resorption (minimal to moderate), and osteoclasts (minimal to moderate). In contrast, TNF-α induced minimal to mild inflammation but had little impact on resorption or osteoclasts. Both IL-1 and TNF (≥10 μg) yielded mild cartilage degeneration. Most lesion scores in TNF-treated rats were significantly lower than those in animals given the same dose of IL-1β. In the persistence study, rats were injected once with IL-1 or TNF (10 μg) and maintained for 2, 3, or 7 days. IL-1β significantly enhanced inflammation (all 3 days), bone resorption (days 2 and 3), osteoclasts (days 2 and 3), and cartilage matrix loss (days 2 and 3), whereas TNF-α augmented inflammation (days 2 and 3) and cartilage degeneration (day 2) but not bone resorption or osteoclasts. Thus, both IL-1β and TNF-α can launch inflammation, but IL-1β drives skeletal destruction.

This study defined the best site for quantifying osteoclasts in male Lewis rats with mycobacteria-induced adjuvant arthritis. Hind paw sections of normal and arthritic rats (n = 6 per group) taken 7 days after disease onset were stained for osteoclasts using an anti-human cathepsin K primary antibody. Erosions and osteoclasts were assessed using semiquantitative scores (entire section) and quantitative measures (in calcaneus, navicular tarsal, and tibia). Bone area in arthritic rats was significantly reduced (P ≤ 0.05) by 39–55%, with the greatest decrease in the tarsal. Osteoclasts in arthritic rats were significantly increased (P ≤ 0.05) relative to normal in calcaneus (sevenfold), tarsal (194-fold), and tibia (threefold). The most useful quantitative indices were bone area and total osteoclasts, both defined as a percentage of total area measured. Semiquantitative scores for bone erosion and osteoclasts paralleled the quantitative indices. These data show that the navicular tarsal is the most sensitive site at which to assess arthritis in rats with this variant of adjuvant-induced arthritis.

A new one-dimensional analysis of the collective interaction in a free-electron laser with combined helical wiggler and uniform axial magnetic fields is presented. Maxwell's curl relations and the cold-fluid equations are employed, with the appropriate form of solution for right and left circularly polarized electromagnetic waves and space-charge waves. A set of three linear homogeneous algebraic equations for the electric field amplitudes of the three propagating waves is derived. This set may be employed to obtain the general dispersion relation in the form of a tenth-degree polynomial equation. With the left circular wave assumed to be nonresonant, the dispersion relation reduces to a seventh-degree polynomial equation corresponding to four space-charge modes and three right circular modes. The results of a numerical study of the spatial growth rate and radiation frequency are presented.

This study describes the baseline haematology and serum chemistry values found in non-pregnant, pregnant (gestational days [GD] 2-21) and lactating (postnatal days 1-9) Sprague Dawley rats (n= 3-10/day) from the NCTR breeding colony of Cr1:COBS CD(SD)BR strain. Maternal body weights on GD0 ranged from 250 to 300 g. Multiple analytes were measured in both whole blood and serum of dams. Amniotic fluid, fetal serum, and postnatal pup serum analyte values were also acquired. Maternal blood was collected from the heart under sub-terminal carbon dioxide (CO2) anaesthesia. Most pregnant dam blood values were not appreciably different from values for non-pregnant dams until near term; near-term values for some analytes (red blood cells, haemoglobin, haematocrit, mean corpuscular haemoglobin concentration, alkaline phosphatase, albumin, total protein, glucose, total bilirubin, sodium, and chloride) decreased but returned to near-normal values soon after delivery. The most dramatic change was a three-fold elevation of serum triglyceride levels near term with a subsequent decrease at birth. Most serum chemistry analytes measured in progeny increased after birth except for alkaline phosphatase, calcium and potassium levels which decreased.

Primary dissociated mouse cerebrocortical cell cultures containing both neurons and glial cells were used as an experimental model to study the neurotoxic effects of formate, the putative toxic metabolite of methanol. Neural cells were isolated and prepared from the cerebral cortex of fetal CD-1 mice on Gestational Day 15. Mature 7- to 15-day-old monolayer cultures were exposed to formate (0 to 240 mM) for 8 hr at 37°C over a range of extracellular pH (6.0 to 7.6). Cytotoxicity was evaluated by histopathology, changes in membrane integrity (lactate dehydrogenase release, LDH; [14C]adenine nucleotide leakage), and mitochondrial metabolic activity [reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT]. Similar quantitative estimates of cell injury were obtained by LDH release or [14C]adenine nucleotide leakage from prelabeled cells. Exposure of neural cells produced time- and concentration-dependent toxic responses. The concentration of formate that resulted in 50% LDH leakage after an 8-hr incubation was estimated to be 45 mM. As determined by light microscopy, formate (20 to 60 mM) was specifically neuronotoxic, primarily affecting large polygonal neurons. Higher concentrations of formate (≥120 mM) induced nonspecific cytotoxicity. MTT reduction appeared to be a more sensitive endpoint by showing significant toxic effects at 20 mM (8-hr incubation), while significant leakage of LDH occurred only at formate concentrations ≥60 mM. Total intracellular ATP concentration was significantly decreased following a 20 or 40 mM formate exposure for 8 hr. These results are consistent with the hypothesis that formate may inhibit mitochondrial function resulting in decreased intracellular ATP and formate-induced neurotoxicity.Copyright 1993, 1999 Academic Press

The biologic behavior of 179 formalin-fixed, paraffin-embedded canine melanomas was correlated with their histologic appearance. In addition, flow cytometric analysis of DNA content was performed on 54 of these tumors. Histologic examination accurately predicted clinical course in 89% of the melanomas with known behavior. Flow cytometry accurately predicted behavior in 93% of tumors with diagnostic histograms and demonstrated malignant features in 100% of metastases from malignant oral tumors; histograms were nondiagnostic for 15% of tumors tested. Histologic examination, flow cytometry, and biologic behavior were in agreement for 93% of the tumors with diagnostic histograms. Interpretive problems were encountered in analyzing heavily pigmented melanomas using this flow cytometery technique.

Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for apical ectodermal ridge (AER) formation and acts epistatically upstream of Fgf-8, the earliest known AER marker in mice. Fgf-10(-/-) mice exhibited perinatal lethality associated with complete absence of lungs. Although tracheal development was normal, main-stem bronchial formation, as well as all subsequent pulmonary branching morphogenesis, was completely disrupted. The pulmonary phenotype of Fgf-10(-/-) mice is strikingly similar to that of the Drosophila mutant branchless, an Fgf homolog.