Characterization of a leukotactic factor derived from psoriatic scale

A study was made on the in vitro characteristics and in vivo biological activities of a leukotactic factor derived from psoriatic scale (PLF). Sephadex G-75 chromatography showed that PLF eluted in the region of the 12,500 dalton protein marker. It resisted heating, lyophilization, acidity (pH 3) and alkalinity (pH 11), but was destroyed by trypsin digestion. The substance attracted polymorphonuclear leukocytes (PMNs) in vitro; this ability was inhibited by antiserum to C3a and was partially reduced by antiserum to C5. Although PLF showed strong chemotactic activity for PMNs, its activity for mononuclear cells was only mild. Intradermal injection of PLF into man or guinea-pig produced an erythematous response with dense tissue neutrophilia, the time course of which was similar to that of the Arthus response. PLF also provoked increased vascular permeability in guinea-pig skin. Moreover, repeated intradermal injection of PLF to the same site in guinea-pigs led to moderate acanthosis of the overlying epidermis. These observations strongly suggest that transepidermal migration of leukocytes in psoriatic lesions is provoked by PLF, whose activity appears to reflect that of complement cleavage products, particularly C3a, presumably produced by complement activation in the subcorneal region of the epidermis. Furthermore, it is postulated that PLF may be a factor which plays a crucial role in the production of typical psoriasiform tissue changes.     

Eosinophilic pustular folliculitis. Studies on possible chemotactic factors involved in the formation of pustules

Eosinophilic pustular folliculitis (EPF) is a dermatosis of unknown aetiology, characterized by repeated development of pruritic follicular papulopustules with a tendency to form an annular configuration on the face and other seborrhoeic areas, and by palmoplantar pustular lesions in one-fifth of the patients. Both types of lesions are infiltrated mainly by eosinophils with some polymorphonuclear leukocytes (PMN). To elucidate the mechanisms underlying pustule formation, we studied the chemotactic activity for leukocytes of the skin surface lipids (SSL) obtained from seborrhoeic areas. No specific chemotactic activity was detectable in stored SSL from patients with EPF. However, fresh SSL collected from the seborrhoeic areas of normal adults contained chemotactic substances for eosinophils and PMN which were labile on storage in air. In stratum corneum extracts from palmoplantar lesions of patients with EPF we demonstrated the presence of a 13000 molecular weight chemoattractant factor for PMN, the activity of which was partially inhibited by antiserum against C5a, and a low molecular weight lipid-soluble chemotactic factor for eosinophils, the activity of which was also lost on storage in air. Our findings suggest that these chemotactic factors play a role in the production of the characteristic pustular lesions of EPF.     

Leukotactic properties of soluble substances inpsoriasis scale

In an attempt to elucidate the mechanicms underlying the production of transepidcrmal migration of leukocytes toward the stratum corneum in psoriatic lesions, the chcmotactic properties of soluble substances in psoriasis scales were examined by a modified Boydm's chamber. All crude extract of horny tissues studied, i.e. callus, scales of exfoliative dermatitis and of psoriasis vulgaris, showed chcmotactic activity for human peripheral blood leukwyta. But only the chemotactic activity of the psoriasis scale extract was highly potent. This was greatly reduced after dialysis. Fresh strum was not required to manifest thechemotactic activity. By Sephadex G-200 chromatography, the scale extracts from psoriasis vulgaris and pustular psoriasis had potent activity cluted near the cytochrome C marker. The same fractions of other horny tissue extracts, bacterial filtrate prepared from cultured psoriasis scale fragments, and serum did not show such potent activity. On the basis of analysis by gel tiltration and recent tindings of immunopathological studies, a postulate was made that a complement derived cbemotactic factor, possibly a C₅ cleavage product, developed as a result of antigen—antibody reaction in the stratum corneum of psoriatic lessions.     

Epidemiology and prognosis of subungual melanoma in 34 Japanese patients

The incidence of malignant melanoma is much lower in the Japanese than in Caucasians. However, amongst the various types of malignant melanoma, the subungual and periungual sites are commonly found in the Japanese. One hundred and fifty-one cases of cutaneous malignant melanoma were seen over a 25-year period at our hospital. We found that. In 34 patients (23%). the subungual region was involved, a high frequency for one institution. We have analysed these patients and looked at their treatment. The finger nails were affected in 21 cases (62%) and the toe nails in 1 3 cases (38%). The thumb nails or great toe nails were at tecled in 25 of the 34 patients (73%). In 25 patients, histopathological features of acral lentiginous melanoma were found, with four cases of superficial spreading melanoma and five of nodular amelanotic melanoma. Of the latter group, four mimicked tibrous histiocytic tumour, and one was a desmoplastic malignant melanoma. I he proportion of patients presenting with stage III disease decreased after 1982. with a corresponding increase in patients whose tumour thickness was less than 4 mm (stage II). Concurrently, the prognosis for subungual malignant melanoma improved. The 5-year survival rate in each of the periods 1969–82 and 1981—93 was 5 3 and 87%. respectively. This is similar to that found in plantar malignant melanoma and is fell to be due to a greater public awareness of the condition and to the introduction of effective chemotherapy (the DTIC-AC nitro surear vincristine (OAV) regimen). Although the frequency of malignant melanoma is rather low in the Japanese, our data indicate that there is a high incidence of subungual malignant melanoma. Public awareness of the early stage of malignant melanoma seems to have improved prognosis.     

Mechanisms of pustule formation in cutaneous bacterial and viral infections: alterations of neutrophil membrane surface receptors

Changes in membrane surface receptors have been demonstrated by rosetting methods in polymorphonuclear leukocytes obtained from the pustules of different infectious dermatoses. There was a distinct difference in numbers of receptors in neutrophils from bacterial and viral pustules, i.e., C3b receptors were decreased on neutrophils from both bacterial and viral pustules, whereas IgG-Fc receptors were decreased only in neutrophils from viral pustules. The difference appears to be due to variations in the defence mechanisms against the invading micro-organisms.     

Stratum corneum hydration and amino acid content in xerotic skin

The relationship between clinical severity, the hydration state of the skin surface as assessed by a conductance with a 3.5 MHz high frequency impedance meter, and the amino acid content of the stratum corneum (SC) of six patients with ichthyosis vulgaris and 30 elderly persons with varying degrees of xerosis was investigated. With an increase in the severity of xerosis the SC showed a decrease in hydration and in its extractable amino acid content. There was a significant correlation between the hydration state and amino acid content of the SC. Although there was a significant correlation between the amino acid content of the lower leg SC and that of the forearm SC in the same subject, the former was generally lower, corresponding to the greater incidence of xerosis on the lower leg. These results suggest that a decreased amount of amino acids may be the result of low profilaggrin biosynthesis in the epidermis and that this is involved in the pathogenesis of these xerotic skin conditions. Clinical improvement of the xerosis following treatment with a urea-containing cream was not accompanied by any significant change in the amino acid content of the SC.     

Lack of an Effect of Madopar on the Disposition of Tolcapone and its 3-O-Methylated Metabolite in Rats

The effect of Madopar (benserazide and l -dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. There was no statistically significant difference in the pharmacokinetic parameters of tolcapone in the presence or absence of Madopar except for a change in the mean residence time after oral administration. Thus, we rejected the hypothesis that the consumption of S-adenyl-l -methionine by Madopar would change the disposition of tolcapone. There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar. We concluded that there was no interaction between tolcapone and Madopar.     

Aβ induces endoplasmic reticulum stress causing possible proteasome impairment via the endoplasmic reticulum–associated degradation pathway

Background: Accumulation of β‐amyloid is a major pathology of Alzheimer’s disease (AD). As in other neurodegenerative diseases, it is also reported that proteasome activity is deteriorated in post‐mortem brains of AD patients. However, the mechanism of proteasomal dysfunction in AD remains unexplained. There is, however, increasing reported evidence that the unfolded protein response (UPR) is involved in AD pathology. Here we show that Aβ causes not only the UPR leading to endoplasmic reticulum (ER) stress mediated cell death, but also proteasomal dysfunction in cultured cells. Methods: Mouse primary cultured neurons and other cultured cells such as HEK 293T or SH‐SY5Y were treated with Aβ or other reagents, such as thapsigargin and lactacystin, to study UPR or proteasome activity. The UPR was investigated using proteins or mRNA expression. To ascertain proteasome activity, we also recruited SH‐SY5Y cells stably transfected with GFP^u. Results: In vitro study showed that UPR, phosphorylation of eIF‐2α and BiP degradation preceded proteasome dysfunction. It is known that the UPR of ER occurs with the assistance of proteasome as ER‐associated protein degradation (ERAD). Conclusion: This evidence, taken together, suggests that Aβ may induce proteasome dysfunction by preceding the UPR through ER‐associated protein degradation.     

Tuberculosis verrucosa cutis in a tumour-like form

An unusual case of tuberculosis verrucosa cutis that presented with a tumour-like lesion on the heel is described. This responded rapidly to treatment with isoniazid.