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Protein identification and peptide sequencing by tandem mass spectrometry requires knowledge of how peptides fragment in the gas phase, specifically which bonds are broken and where the charge(s) resides in the products. For many peptides, cleavage at the amide bonds dominate, producing a series of ions that are designated b and y. For other peptides, enhanced cleavage occurs at just one or two amino acid residues. Surface-induced dissociation, along with gas-phase collision-induced dissociation performed under a variety of conditions, has been used to refine the general 'mobile proton' model and to determine how and why enhanced cleavages occur at aspartic acid residues and protonated histidine residues. Enhanced cleavage at acidic residues occurs when the charge is unavailable to the peptide backbone or the acidic side-chain. The acidic H of the side-chain then serves to initiate cleavage at the amide bond immediately C-terminal to Asp (or Glu), producing an anhydride. In contrast, enhanced cleavage occurs at His when the His side-chain is protonated, turning His into a weak acid that can initiate backbone cleavage by transferring a proton to the backbone. This allows the nucleophilic nitrogen of the His side-chain to attack and form a cyclic structure that is different from the 'typical' backbone cleavage structures., (Copyright 2000 John Wiley & Sons, Ltd.)

Psychologic factors may play a significant role in acne in at least three ways. First, as many patients readily report, emotional stress can exacerbate acne. Second, it is common for patients to develop psychiatric problems as a consequence of the conditions, such as those related to low self-esteem, social phobias, or depression. Finally, primary psychiatric illnesses such as obsessive-compulsive disorder and psychosis may be based on a complaint that is focused on acne. In this review we hope to facilitate an understanding of how emotional factors and acne connect, and aid the dermatologist in identifying the possible presence of psychiatric problems stemming from or contributing to the disorder.

Childhood and adolescent obsessive-compulsive disorders are sometimes seen in dermatology practice. When present, OCD is most frequently manifested in younger patients as trichotillomania, onychotillomania, onychophagia, and acne excoriée. In addition to these disorders, obsessive hand washing, AIDS phobia, and other psychosomatic dermatoses characterized by obsessive-compulsive tendencies are seen in all age groups. It is important to define the nature of any underlying psychiatric disorder before beginning drug treatment of these patients. With the availability of new medications, most notably, clomipramine and fluoxetine, there is reason for optimism regarding the treatment of OCD. Whenever feasible, the dermatologist should not hesitate to involve a psychiatrist to help with diagnosis and treatment when the diagnosis of OCD is being considered.

Rats were exposed for a single 6-h period to varying concentrations of aerosols of the polyamine, spermidine trihydrochloride. They were subsequently killed at 6 h, 1, 2, 5, 9 and 14 days after the start of exposure. The lungs were examined for histopathological alterations at both light and electron microscopic level and assays of lung spermidine burdens performed. In rats killed at the 6-h termination period, lung spermidine levels had increased approximately 1.5-fold although concentrations in animals killed on days 1 and 2 showed only marginal increases. Concentrations peaked again on day 5 and henceforth decreased until control spermidine levels were again achieved on day 14. Exposure of rat lungs to spermidine resulted in a specific dose-dependent necrosis of Clara cells of the bronchiolar epithelium and alveolar Type II cells. At the lowest dose used (6 mg/m3) specific necrosis of the Clara cells was seen at the earliest time interval studied, i.e. 6 h, but these cells were rapidly lost and subsequently replaced without evidence of significant cell proliferation by the 2-day sacrifice period. At all higher dose levels additional necrosis of the alveolar Type II cells occurred which was not reversible but which progressed through alveolitis to a fully developed subchronic pneumonitis by 14 days.

After the administration of paraquat to rats the lung is the organ most severely damaged. The pathology in the lung can be divided into two distinct phases: (1) a destruction phase lasting a few days with damage to the type I and type II alveolar epithelial cells, oedema and haemorrhage (most of the rats which die after dosing with paraquat do so during this phase); (2) a reparative phase with regeneration of the epithelium and, in areas of severe damage, a characteristic proliferation of fibroblasts. In both phases of the lesion the death of the rats results from anoxia. Paraquat is selectively accumulated by the rat lung in comparison with other tissues and this accounts, at least in part, for the specific toxic effect in this organ. The accumulation into the lung was shown by in vitro studies to depend on energy and is inhibited by various endogenous and exogenous compounds. This uptake process is not that which has been described for 5-hydroxytryptamine and evidence is presented to suggest that the type I and type II alveolar epithelial cells are sites of accumulation. When paraquat is present in lung cells, it undergoes a cyclical reduction and oxidation with the production of superoxide anion. This radical may lead directly or indirectly to the formation of lipid peroxides and hence to cell death. However, paraquat stimulates the pentose-phosphate pathway and both reduces the level of NADPH and inhibits fatty acid synthesis in the lung. These effects occur when there is only minimal ultrastructural damage to the lung cells. It is suggested, therefore, that the primary mechanism of toxicity of paraquat is the extreme oxidation of NADPH which inhibits vital physiological processes and renders the cell more susceptible to attack from lipid hydroperoxides.