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Herpes simplex virus type 1 (HSV-1) induces an immediate-early (IE) polypeptide IE 12. An equivalent polypeptide coded by HSV-2 which migrated slightly more slowly on SDS-polyacrylamide gels was identified and designated IE 12.3. Analysis of the serotype of the IE polypeptide induced by five HSV-1/HSV-2 intertypic recombinants when correlated with their genome structures showed that IE 12/IE 12.3 mapped in the region spanning the TRs/Us junction. Unlike four other IE polypeptides induced by HSV-1 (IEs 175, 110, 68 and 63), IE 12 was not detectably phosphorylated. more...

The terminal stages of erythropoietic protoporphyria are recorded. The observations are related to the site of the fundamental lesion and the nature of the biochemical defect. The possibly ominous prognosis in this usually mild condition is emphasized. Apart from congenital porphyria, the porphyrias do not usually confer severe cutaneous lesions. These diseases present to dermatologists because of moderate photosensitivity and are not usually regarded as a risk to life. Dangerous central nervous system involvement may occur, however, in acute intermittent, variegate and hereditary coproporphyrias, while in acquired symptomatic porphyria severe underlying liver dysfunction may occur. Probably the most common familial photosensitizing porphyria is erythropoietic protoporphyria. Recently some deaths from severe liver involvement have been reported in this disease. more...

Frozen tissue sections from the lesions of five patients with histologically proven mycosis fungoides were examined using a specific antihuman T-cell antiserum and an indirect peroxidase staining technique. The dermal and epidermal infiltrates were shown to comprise predominantly cells bearing the specific T-cell antigen, HTLA. Two of the patients exhibited characteristic Pautrier microabscesses whose cells were exclusively T lymphocytes. more...

Immunofluorescence studies were carried out on 47 patients with primary localized cutaneous amyloidosis. The majority had the macular, maculopapular or papular forms of lichen amyloidosus, although 3 patients had the nodular type. All biopsies fluoresced positively for immunoglobulins or complement, particularly IgM and C3. Staining for kappa and lambda light chains was positive. The consistent immunofluorescent patterns observed were similar in some respects to lichen planus, suggesting that colloid bodies and amyloid may share similar properties in acting as a filamentous sponge on to which immunoglobulins and complement are absorbed. The pathogenesis of lichen amyloidosus is compared with that of lichen planus. more...

A sensitive immunoperoxidase method employs a new chicken anti-B2-microglobulin (B2M) antibody for use on paraffin sections. The method demonstrates the loss of B2M from the cell membranes of malignant eccrine poromas , and this is correlated with the histopathologic and clinical criteria of malignancy. more...

The presence of natural killer (NK) cells, as defined by reactivity with the monoclonal antibodies Leu 7, Leu 11 and Leu 19 was assessed in the inflammatory infiltrate around epidermal neoplasms and compared with findings in a range of inflammatory dermatoses. HNK-1+ (Leu 7) cells were present in a wide range of malignant, pre-malignant and inflammatory disorders. Cells positive for the more specific NK cell antigens CD16 (Leu 11)/NKH-1 (Leu 19) had a distribution mainly restricted to cases of squamous cell carcinoma (five of nine) and keratacanthoma (three of seven). The variability in distribution between the different antibodies suggests that the majority of cutaneous HNK-1+ cells are not NK cells, but represent cross-reacting T lymphocytes. The qualitatively distinct distribution of CD16+ and NKH-1+ cells around some cases of squamous cell carcinoma and keratoacanthoma is of interest but their absence from a number of such cases calls into question a specific effector role for natural killer cells in these squamoproliferative tumours. more...

A case of malignant bronchial carcinoid with multiple cutaneous metastases is reported. Despite the extremely aggressive behavior of the disease and the presence of multiple hepatic metastases, the patient did not exhibit the usual clinical features of the carcinoid syndrome. The relevance of the finding of elevated 24-hour urinary vanillylmandelic acid levels in patients with carcinoid tumors is discussed. more...

The clinical and histopathological features of 12 female patients with Flegel's disease were studied. The onset of this dermatosis was delayed until adulthood. The eruption consisted of scaly papules 1-5 mm in diameter which developed principally on the lower legs, upper arms and pinnae. Histopathologically there were discrete foci of hyperkeratosis with some parakeratosis over an attenuated and partially spongiotic epidermis. A genetic influence in this disorder was suggested by its occurrence in sisters in two families and in a mother and daughter. Immunohistochemical and biochemical studies suggested that there is a disorder of keratinocyte proliferation in the disease. more...

The time-course of cutaneous inflammatory responses to LTB4 and PGE2 both alone and in combination has been studied in 10 healthy volunteers. LTB4 induced a transient wheal and flare response in some subjects, maximal at 15 minutes and succeeded by an erythematous, indurated lesion at 2-4 hours. PGE2 elicited a wheal and erythema response which resolved within 1-2 hours. Combination of LTB4 and PGE2 produced acute wheal and erythema responses which did not differ significantly from the summation of responses to the individual constituents of the mixture or from responses to a two-fold increase in the concentration of either component. Wheal and erythema responses persisted, however, with significant potentiation of responses 4 hours after injection. As both leukotrienes and prostaglandins are generated in acute allergic reactions, the effects of these mediators in combination could contribute to persisting and late-onset responses to allergen, in both the skin and lung. In particular, sustained responses to the combination of LTB4 and PGE2 might be important in the pathogenesis of inflammatory skin diseases such as psoriasis. more...

Amyloid deposits were identified within the tumour mass of three melanocytic naevi. Amyloid in this situation is likely to be derived from degenerating naevus cells.

Peripheral blood lymphocyte cyclic AMP responses to isoprenaline, prostaglandin E2 and histamine were examined in patients with atopic eczema, in the presence and absence of a potent phosphodiesterase inhibitor (PDEI). Basal cyclic AMP levels were not significantly different in atopic and control groups. In the presence of the PDEI, there were impaired cyclic AMP responses to both isoprenaline and prostaglandin E2 in the atopic group. Differences between atopic and control cyclic AMP responses were exaggerated by the omission of the PDEI, when impaired responses to all agonists were observed in lymphocytes from atopic subjects. These results imply that, in atopic eczema, lymphocytes exhibit impaired responses not only at the beta-adrenoceptor site but at unrelated sites of adenylate cyclase activation, and these observations are consistent with increased leukocyte phosphodiesterase activity. more...

At rare intervals in the literature, reports have appeared of a skin tumour containing structures resembling Pacinian corpuscles. Four such tumours collected over the course of 20 years are described and the literature reviewed. more...

Four highly sensitive monoclonal antibodies were assessed for their use in an immunoperoxidase technic on cutaneous sections. Three, B2, C23, and 2A1, were found to discriminate basal cell carcinomas (BCCs) from benign proliferative disorders of skin, and 2A1, a monoclonal antibody against the heavy chain component of class 1 human leukocyte antigens (HLA) for the first time directly demonstrated the absence of this structure from the malignant cell membrane. However, the deeper portions of hair follicles were also found to be unlabeled, and further study of benign follicular tumors which may histologically mimic basal cell carcinomas is suggested. more...

A patient with profuse cutaneous pigmented lesions, subcutaneous myxoid neurofibromata and atrial myxoma is described. This is the second report of this syndrome, whose importance lies in the possibility of avoiding the potentially lethal consequences of a treatable cardiac tumour by recognition of distinctive cutaneous manifestations. more...

A study of dermatopathological specimens exhibiting parakeratosis has been made and the parakeratosis classified on morphological and topographical criteria. Twelve patterns of parakeratosis have been identified and their association with particular pathological conditions described. more...

Epidermal patterns of class II human lymphocyte antigen (HLA) expression in atopic and allergic contact dermatitis have been compared, using monoclonal antibodies recognizing each subregion. Expression of class II human lymphocyte antigens on keratinocytes has been confirmed in allergic contact dermatitis, while we have found them to be absent in atopic dermatitis. This finding argues that cell-mediated immune responses, possibly to epicutaneous contact with allergen, are not implicated in the pathogenesis of atopic dermatitis. more...

The effect of synthetic Paf-acether has been studied in guinea-pig skin, following intradermal injection, and in guinea-pig lung, following intravenous administration. Histopathological responses to Paf-acether were assessed by both light microscopy and electron microscopy. In addition, plasma protein extravasation and platelet accumulation were quantitatively assessed using radiolabelling techniques. Intradermal injection of Paf-acether, but not lyso-Paf, elicited acute increased vascular permeability, accompanied by intravascular accumulation of platelets and neutrophils. There was evidence, 2-8 h after intradermal injection of Paf-acether, of perivascular infiltration with neutrophils. At 24 h there was a mixed cellular infiltrate comprising mononuclear cells in addition to neutrophils. Following systemic administration of Paf-acether, aggregates of platelets in close association with neutrophils were evident within the pulmonary vasculature. Intravenous injection of Paf-acether, but not lyso-Paf, caused intrathoracic accumulation of radiolabelled platelets. These results suggest that Paf-acether has properties consistent with those of a mediator of inflammation. more...

Tissue from the cutaneous metastases of bronchial carcinoid was examined. Fine argyrophil secretory granules were demonstrated in the cytoplasm of the abnormal cells which showed positive labelling with neuron-specific enolase. Ultrastructural studies revealed numerous electron-dense membrane bound neuro-secretory granules, 50-300 nm in diameter. Other characteristic features included inter-digitating pseudo pod-like processes (up to 2 mu in size) in the cytoplasmic membrane, perinuclear filaments, a well-defined Golgi zone and numerous large mitochondria. more...

The previously unrecorded association of superficial bullous pyoderma and IgG-producing multiple myeloma is described. A rapid response of the cutaneous manifestations was achieved by treatment of the malignant paraproteinaemia. more...

The light, polarization and electron microscopic changes in the liver of four cases of erythropoietic protoporphyria (EPP) are described. In one of these cases liver involvement resulted in death, whereas in the other three there were no symptoms of referable to hepatic disease. In two cases hepatic pigment was readily visible on light and polarization microscopy and corresponded to characteristic crystalline aggregates seen ultrastructurally. Pronounced micronodular cirrhosis and cholestasis were present in the fatal case, while in the other only mild periportal fibrosis and mononuclear inflammatory cell infiltrate occurred. The third and fourth cases showed no evidence of hepatic involvement on light microscopy. Electron microscopy, however, revealed characteristic crystal-containing vacuoles indicative of protoporphyrin deposition. The need for early detection of the hepatic lesion is emphasized. more...

The phospholipid PAF-acether is released from a range of inflammatory cell types and, in experimental animals, has properties appropriate to a mediator of inflammation. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early weal and flare response was succeeded, in a proportion of subjects, by an area of late-onset erythema at the site of the resolved weal, reminiscent of the dual response to allergen in sensitized individuals. The time-course and dose-response relationship of the early response has been determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. PAF-acether should therefore be considered as a potential mediator of both acute and persisting inflammation in man. more...

Biopsies from lesional skin of patients with histologically confirmed mycosis fungoides were embedded in resin and semi-thin ( I micrometer) sections were submitted to a variety of staining procedures, including Toluidine blue, Richardson's Huber, Giemsa, Paragon and Tribasic stains. The stained sections were examined with the light microscope and the quality of cellular morphological detail afforded by the different stains was assessed. The Toluidine blue, Richardson's and Paragon stains were found to be technically easy to perform and gave the best representation of nuclear and cytoplasmic detail Of these, the authors favoured Richardson's stain. The technique of processing the tissue, and staining a mounting procedures are detailed. more...

The presence of histiocytes in the epidermal and dermal infiltrate of mycosis fungoides was observed histochemically by revealing a diffuse pattern of acid alpha-naphthyl acetate esterase (ANAE) activity in the cytoplasm, and immunohistochemically by demonstrating the presence of histiocyte-specific 'enzymes', lysozyme, alpha-I-antitrypsin and alpha-I-antichymotrypsin. Histiocytes in the infiltrate of mycosis fungoides may be involved in antigen processing and interaction with T lymphocytes. more...

Epidermal mononuclear cell infiltrate from three patients with pagetoid reticulosis was examined for the presence of the cytoplasmic markers lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin, using specific antisera and a peroxidase-antiperoxidase technique. Many of the infiltrating cells possessed these markers, indicating that they belonged to the monocyte-macrophage-histiocyte series. more...

Beta 2-microglobulin (beta 2M) is part of the HLA molecule, and is found on the cell surface of human nucleated cells. In certain skin tumors, malignant change has been associated with a loss of this surface beta 2M, indicating a possible diagnostic value for this marker. At present beta 2M is best identified in paraffin-embedded tissue by means of a triple-layer peroxidase-antiperoxidase technique, using mammalian polyclonal antisera. Recently a polyclonal antiserum against human beta 2M has been produced in chickens. Because of the phylogenetic differences between the species, the resulting antiserum is likely to recognize more epitopes on the beta 2M and show greater sensitivity than antisera raised in mammalian species. To confirm this hypothesis, the avian antiserum was compared to both mammalian polyclonal (rabbit) and monoclonal (mouse) antibody in vitro. beta 2M fixed to plastic surfaces combined with more avian than mammalian antibody. Furthermore, insolubilized chicken antibody could bind more secondary antibody-horseradish peroxidase conjugate than could insolubilized mammalian antibody, thus showing even greater enhancement with this system. Immunohistochemical analysis of these systems confirmed that the chicken strategy has greater sensitivity, and can be used in an indirect system with consequent reduction in nonspecific background activity. It is the most suitable technique for the investigation of the distribution of beta 2M in paraffin-embedded tissue. more...

The development of a cutaneous nodule at the site of friction of spectacles has been discussed by several authors. In all but one case the lesion occurred behind the ears. The only previous report of this acquired tumour occurring on the nose is that of Farrell & Wilson (4). It is suggested that this problem is relatively common and most frequently presents when mistaken for basal cell epithelioma or when identified in medical personnel. A further six cases of this neglected tumour occurring on the nose are described. more...

It has been proposed that immune dysfunction in psoriasis is a consequence of aberrant cyclic nucleotide metabolism. We have examined cyclic AMP responses to isoprenaline, histamine, and prostaglandin E2 in peripheral blood mononuclear leukocytes from patients with psoriasis, in the presence and absence of a potent cyclic AMP phosphodiesterase inhibitor. Stimulated and basal cyclic AMP levels in mononuclear leukocytes from psoriatics did not differ from those observed in mononuclear leukocytes from normal subjects, irrespective of the stimulant employed, either in the presence or in the absence of the phosphodiesterase inhibitor. These findings do not support the hypothesis that psoriasis is associated with either impaired beta-adrenergic reactivity or a more generalized abnormality of mononuclear leukocyte cyclic nucleotide metabolism. more...