Organizing pneumonia associated with T-cell lymphoma.

A 61-year-old male with a history of coeliac disease was diagnosed with organizing pneumonia (OP) on transbronchial and transthoracic lung biopsies. He then developed refractory coeliac disease type II and haemophagocytic lymphohistiocytosis. Nine months after his initial diagnosis of OP and after multiple biopsies of the lung, duodenum, and bone marrow, he was diagnosed with enteropathy-associated T-cell lymphoma (EATL). Although OP in patients with lymphoma is most commonly attributed to chemotherapeutic agents or bone marrow transplant, it may be seen in the absence of prior anticancer treatment. The mechanism linking OP and lymphoma is unclear but OP could represent a syndrome of T-cell dysfunction or develop as a direct reaction to malignant infiltration of the lung. In patients with atypical presentations, exclusion of an alternate diagnosis must be pursued using surgical lung biopsy, wherever possible. This is the first reported case of OP associated with EATL.

The role of steric effects in the direct mutagenicity of N-acyloxy-N-alkoxyamides.

Electrophilic N-acyloxy-N-alkoxyamides are mutagenic in Salmonella typhimurium TA100 without the need for S9 metabolic activation and they react with DNA at guanine-N7 at physiological pH. Since these are direct-acting mutagens, structural factors influence binding and reactivity with DNA. Mutagenicity in TA100 can be predicted by a QSAR incorporating hydrophobicity (logP), stability to substitution reactions at nitrogen (pK(a) of the leaving acid) and steric effects of para-aryl substituents (E(s)). A number of mutagens exhibit activities that deviate markedly from the predicted values and they fall into two classes: di-tert-butylated N-benzoyloxy-N-benzyloxybenzamides, which--because of their size--are most probably excluded from the major groove or are unable to achieve a transition state for reaction with DNA, and N-benzoyloxy-N-butoxyalkylamides with branching alpha-to the amide carbonyl, which are resistant to S(N)2 reactions at the amide nitrogen.

Crystal structures and properties of mutagenic N-acyloxy-N-alkoxyamides--"most pyramidal" acyclic amides.

X-Ray data for two N-acyloxy-N-alkoxyamides, a class of direct-acting mutagens, indicate extreme pyramidalisation at the amide nitrogen in keeping with spectroscopic and theoretically determined properties of amides with bisoxosubstitution at nitrogen. The combined electronegativity of two oxygens leads to average angles at nitrogen of 107.8 and 108.1 degrees and [chiN] of 66 degrees and 65 degrees. The sp3 nature of nitrogen results in negligible amide resonance as evidenced by long N-C(O) bonds, high IR carbonyl stretch frequencies, carbonyl 13C NMR data and very low amide isomerisation barriers. In addition, conformations in the solid state support a strong n(O)-sigma*(NOAc), anomeric interaction as predicted by molecular orbital theory. HF/6-31G* calculations on formamide, N-methoxyformamide and N-formyloxy-N-methoxyformamide support these findings.