We present a first-principles study of stable configurations of single and multiple H atoms in a monovacancy in bcc transition metals and binding energies of the H atoms to the monovacancy. Typical bcc transition metals are group-V elements (V, Nb, and Ta), group-VI elements (Cr, Mo, and W), and Fe. The most stable site for an interstitial H atom in the intrinsic bcc transition metals is a tetrahedral interstitial site (T site). On the other hand, a single or a few H atoms trapped in a monovacancy in bcc metals occupy close to octahedral interstitial sites (O sites) next to the monovacancy. However, stable configurations of four and more-than-four H atoms in the monovacancy are various and different depending on the host metals. Stable sites for H atoms are usually shifted toward the T site or diagonal interstitial site (D site) as the number of H atoms increases in the monovacancy. As a result, a maximum of six H atoms can be accommodated in a monovacancy in V, Nb, Ta, Cr, and Fe, which is in good agreement with previous computational studies, while 10 and 12 H atoms can be accommodated in a Mo and W monovacancy, respectively.

Our results indicate the importance of PPAR gamma and C/EBP in adipocyte-like cell differentiation of FLS and that the process is influenced by inflammatory cytokines, and suggest that the proinflammatory character of FLS in patients with RA is diminished during adipocyte-like cell differentiation.

SUMMARY Peroxisome proliferator‐activated receptor γ (PPARγ) is a ligand dependent transcriptional factor known to be a regulator of adipogenesis. Recent studies have also shown that stimulation of PPARγ inhibits the transcriptional activities of other nuclear factors and down‐regulates proinflammatory cytokine synthesis in T cells and monocytes. We examined, in the present study, the functional significance of PPARγ expressed in fibroblast‐like synovial cells (FLS) isolated from patients with rheumatoid arthritis (RA). Incubation of FLS with a synthetic PPARγ ligand, troglitazone, inhibited endogenous production of TNF‐α, IL‐6 and IL‐8, as well as matrix metalloprotease‐3 (MMP‐3), without inducing apoptosis of the cells. The gelatinase activity of FLS culture media was also inhibited by troglitazone. Electrophoretic mobility shift assay (EMSA) showed a significant reduction in the DNA binding activity of NF‐κB in troglitazone‐treated FLS in response to TNF‐α or IL‐1β. Moreover, long‐term cultivation of FLS with troglitazone resulted in morphological changes with marked lipid accumulation in these cells. Our results show a negative regulatory function for PPARγ on cytokine and MMP production together with inhibition of cytokine‐mediated inflammatory responses in rheumatoid synovial cells. Our results also suggest that FLS could differentiate into adipocyte‐like cells in the presence of proper stimulatory signals including PPARγ.

It is unclear whether synchronous multiple tumors arise from multicentric or monoclonal origins. To verify the multicentric origin of synchronous colorectal carcinomas at a genetic level, immunohistochemical and molecular techniques were used to determine the p53 alterations in individual lesions of synchronous colorectal carcinomas. This study was based on a total of 32 colorectal tumors from 16 patients. Twenty-one of the 32 (66%) advanced tumors examined had positive staining for p53. Single-strand conformation polymorphism and polymerase chain reaction direct sequencing were carried out for exons 5 to 8 of p53. All cases had p53 mutations in one or more tumors of synchronous lesions. In nine patients in this series, individual lesions were found to carry a different mutated codon of the p53 gene. In the other seven patients, a p53 mutation was found in one tumor but not in another. These results indicate discordance of the mutation pattern of p53 in individual lesions of multiple colorectal carcinomas and support the idea that most synchronous colorectal carcinomas are genetically distinguishable and are multicentric in origin. We also confirmed the high frequency of p53 mutations in left-sided (71%) and rectal (91%) carcinomas, rather than right-sided (43%; P ‫؍‬ .04) carcinomas, suggesting that the molecular mechanism of synchronous colorectal carcinomas might differ between right-and left-sided tumors in the same patient.KEY WORDS: P53, Single-strand conformation polymorphism, Synchronous colorectal carcinomas.Mod Pathol 2000;13(2):131-139

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