Psoriasis vs allergic contact dermatitis in palms and soles: a quantitative histologic and immunohistochemical study

Cesinaro AM, Nannini N, Migaldi M, Pepe P, Maiorana A. Psoriasis vs allergic contact dermatitis in palms and soles: a quantitative histologic and immunohistochemical study. APMIS 2009; 117: 629–34. A systematic histologic and immunohistochemical study of cases of psoriasis (PSO) and allergic contact dermatitis (ACD) in palmo‐plantar skin was performed to find differences between these two diseases that usually show overlapping features in these specific sites. Skin biopsies from 42 (22 female, 20 male) patients were evaluated for several histopathologic parameters and immunohistochemistry was applied to quantify keratinocytic proliferation, the number of dendritic cells (DCs) and the phenotype of the mononuclear cell infiltrate. Regular epidermal hyperplasia and marked parakeratosis were found to be more frequent in PSO than in ACD cases, but only the first parameter reached the level of significance (p = 0.03). The number of S100 protein‐positive DCs was significantly higher in ACD (p = 0.006), whereas keratinocytic proliferation, studied with Mib‐1, was found to be higher in PSO than in ACD, but the difference was not statistically significant. No significant difference was detected in the number of CD4⁺, CD8⁺ and bcl2⁺ lymphocytes in PSO and ACD cases. In the palms and soles, the finding of irregular epidermal hyperplasia and the detection of a higher number of S100 protein‐positive DCs favor the diagnosis of ACD over PSO. The differential diagnosis between PSO and ACD can be practically approached using a histopathologic parameter and a commercially available antibody.     

Enzymatic methyl esterification of a deamidated form of mouse epidermal growth factor

The enzyme S-adenosylmethionine:protein carboxyl-O-methyl-transferase, type II (EC2.1.1.77; PCMT) from eukaryotes methyl esterifies peptides containing isoAsp residues, which can arise from spontaneous deamidation of labile Asn residues. We report here a study on in vitro methyl esterification of mouse EGF by bovine brain PCMT. This peptide contains two Asn in the sequences Asn¹-Ser² and Asn¹⁶-Gly¹⁷. It is known from the literature that the presence of a small residue on the carboxyl side of asparaginyl makes this residue susceptible to deamidation through the spontaneous formation of a succinimide intermediate. Therefore EGF was incubated under deamidating conditions (pH9.0, 37° for 48 h) and the extent of deamidation monitored by enzymatically measuring the NH₃ produced during the alkali treatment: a release of 0.80 mol NH₃/mol EGF was calculated. The alkali-treated EGF, analyzed by anion-exchange chromatography, shows two major components identified as native EGF (nEGF) and its deamidated form (dEGF). When incubated in the presence of purified PCMT neither nEGF nor dEGF showed any methyl accepting capability. Since it is known that the three-dimensional structure of a protein may hinder the methyl esterification of a potential ethyl accepting site, dEGF was unfolded by reducing and alkylating the intrachain disulfide bridges. Only a slight increase in the methyl accepting capability could be observed. Conversely, when EGF was deamidated after its unfolding, the resulting protein was stoichiometrically methylated by PCMT, presumably at level of isoAsp¹⁶. Our findings strongly suggest that the three-dimensional structure of a protein is a major specificity determinant for both deamidation and methyl esterification processes.     

Women's paid and unpaid work and pregnancy outcome: a discussion of some open questions

Empirical results in the last 20 years have shown that employedwomen, on the whole, have a better perinatal outcome than full-timehousewives. The possible reasons for this difference are presentedand discussed Despite the consistency of the data, current thinkingin this area is still influenced by the idea that being outsidethe labour market may represent a protective factor in pregnancy.The obvious resistance, on the part of researchers, to fullyacknowledging results based on empirical data indicates thepersistence of the prejudice that sees housewives as women whodo not work. The fact of the matter is that they work full-time,often in poor conditions, and without a salary. The possibleconsequences of this prejudice for perinatal health are outlined.     

Relationship between body weight and blood pressure and some metabolic parameters in psoriatic patients

The relationship between body weight and blood pressure, total serum cholesterol, triglycerides, uric acid and glucose was investigated in 203 psoriatic patients in comparison with 904 healthy controls. In the psoriatic patients, these parameters were clearly related to their body weight. Those psoriatic patients of normal weight exhibited lower mean values of all the parameters compared with overweight psoriatic patients while they did not differ from control subjects of normal weight. Our results suggest that only overweight psoriatic patients exhibit the metabolic abnormalities frequently reported in the literature, while psoriatic patients of normal weight do not differ from the general population in this respect.     

LACK OF ENDOGENOUS OPIOID INHIBITORY TONE ON LH SECRETION IN EARLY PUBERTY

Thirteen normal children, seven males and six females, during early puberty (I-II according to Tanner), have been studied. Each subject was injected at weekly intervals and in random order with 100 micrograms of LHRH, 0.2 mg/kg of naloxone and 0.9% saline in single bolus. The gonadotrophin response was evaluated. The administration of naloxone failed to elevate LH levels in any of the subjects studied, even in those who showed a clear gonadotrophin response to LHRH. Unlike the response noted in adults, endogenous opiates do not appear to exert a tonic inhibitory influence on LH secretion during early puberty.     

Probing the structure of human growth hormone by limited proteolysis

Digestion of human growth hormone (hGH) with the Glu-specific protease from Staphylococcus aureus V8 was performed at 20-22°C or 37°C at a 1:20 ratio (by weight) at pH 7.8 with or without 0.2% SDS. There are 14 Glu-residues evenly distributed along the polypeptide chain of hGH as possible sites of proteolytic cleavage of V8-protease. The pattern of fragmentation of hGH was analyzed by electrophoresis and reversed-phase HPLC, and the identity of the proteolytic fragments isolated to homogeneity was established by their partial sequencing and amino acid analysis after acid hydrolysis. Kinetic analysis of the proteolytic digestion process allowed to establish that initial nicking of the protein occurs at Glu³³ and subsequently at Glu⁵⁶ and Glu⁶⁶. Much slower cleavages occur at G1u³⁰ and Glu¹⁸⁶. These cleavage sites are located at chain loops in the hGH molecule, and in particular outside the helical segments of the four-helix bundle of the crystal structure of hGH. Fragments 1-33 and 67-191 comprising entirely the N-terminal helix and the three C-terminal helices of hGH, respectively, were isolated to homogeneity in amounts useful for subsequent conformational and functional studies. The results of this study and of previous ones [Li, C.H. (1982) Mol. Cell. Biochem. 46 , 31-41] describing limited proteolysis of hGH by various proteases have been interpreted on the basis of the three-dimensional structure and dynamics of hGH. Overall, it is shown that proteolytic enzymes preferentially cleave hGH at exposed and flexible loops only, thus emphasizing the fact that proteases can be used as reliable probes of protein structure and dynamics. © Munksgaard 1995.