Expression of MAGE-1, MAGE-2 and MAGE-3 genes in human gastric carcinomas; lack of evidence for cytotoxic effects in cases with simultaneous expression of MAGE-3 and HLA-A2.

The human MAGE gene products are recognized by major histocompatibility complex-restricted cytotoxic T lymphocytes. We analyzed by RT-PCR the expression of MAGE-1, MAGE-2, MAGE-3 and HLA-A2 genes in 10 human gastric cancer cell lines and 46 human stomachs removed due to advanced gastric carcinomas. All the cell lines expressed MAGE genes, except for MKN-45 and -74 which lacked the expression of MAGE-1 and -3 genes in this study. Of the 46 gastric carcinomas, MAGE-1, -2 and -3 genes were expressed in 14 (30%), 10 (22%) and 26 (57%) cases, respectively, regardless of histological type. Normal gastric mucosa and intestinal metaplastic mucosa showed no expression of these genes. HLA-A2 gene expression was noted in 14 both normal and carcinoma cases. Simultaneous expression of MAGE-3 and HLA-A2 genes was noted in 7 cases. Mean apoptotic and Ki-67-labeling indices (AI and KI) of carcinoma cells were 2.3 +/- 0.5 and 48.1 +/- 6.0 in 7 cases, and 2.8 +/- 0.2 and 47.3 +/- 2.7 in the other 39 cases lacking the expression of MAGE-3 and/or HLA-A2 genes, respectively. The two-year survival rate did not differ between the two groups. Although this study confirmed the relatively higher expression of the MAGE gene family in human advanced gastric carcinomas, it might suggest that simultaneous expression of MAGE-3 and HLA-A2 genes does not necessarily imply the induction of cancer cell apoptosis by CTL.

The ultrastructural histopathology of eosinophilic pustular folliculitis.

The follicular skin lesions of a patient with eosinophilic pustular folliculitis were investigated by electron microscopy. Pustules in the outer root sheath contained acantholytic keratinocytes with numerous microvilli and features of desmosomal cleavage. The infiltrating eosinophils and neutrophils exhibited autolytic or degenerative changes rather than degranulation. The aggregated tubulo-vesicular structures were associated with the debris of autolytic eosinophils. Multiple, tiny, bubble-like structures enclosed within a membrane were frequently seen in the intercellular space. The intercellular space of the outer root sheath was widened with decreased desmosomal adhesion between the keratinocytes, but no intracellular edema was detectable. The infiltrating lymphocytes, predominantly T-cells with convoluted nuclei, extended cytoplasmic processes to adjacent keratinocytes. Apposition of T-lymphocytes and Langerhans cells was noted. Some keratinocytes in the outer root sheath contained large, sebaceous lipid droplets. No obvious virus particles or other pathogenic agents were detected. It is possible that T-lymphocytes and other immunosurveillance cells are involved in the pathomechanism of eosinophilic pustular folliculitis.

Papuloerythroderma.

The main macroscopic features of 4 cases presented here are erythroderma-like lesions and solid papules. The former covers extensive areas over entire trunk and extremities, especially extensor surfaces. The latter is observed mainly on flexor surfaces of extremities and around the former. The axillae, inguinal regions, cubital and popliteal fossae, and big furrows on abdomen are spared from these lesions. Rashes appear first as papules and form erythroderma-like lesions through their assembly and confluence. Histologically, both show almost the same findings. Patients are older males with no general symptoms except itching. Although the course is chronic, lesions improve slowly and heal only after years.

Assessment of anti-stratum corneum antibody titres in pustulosis palmaris et plantaris.

Titres of anti-stratum corneum (SC) antibodies, determined by an indirect immunofluorescence (IF) technique, were significantly higher on average in pustulosis palmaris et plantaris (PPP) and pompholyx than in normal controls. By a complement IF technique, the antibodies fixed complement (C3) in high titer in PPP, but to a much lesser degree in pompholyx and normal controls. Direct IF microscopy studies showed the deposition of IgG and C3 in the SC in some of the biopsy specimens of the pustular lesions. These findings suggest that in PPP anti-SC antibodies may be involved at least in part in activation of the complement system and the subsequent accumulation of polymorphonuclear leukocytes.

Dyskeratotic degeneration of epidermal cells in pityriasis rosea: light and electron microscopic studies.

We studied biopsies from twenty-nine patients with pityriasis rosea. All specimens showed features of subacute or chronic dermatitis as previously reported, but sixteen cases (55%) had dyskeratotic cells within the epidermis. Ultrastructurally, these cells contained an aggregation of tonofilaments, many vacuoles and intracytoplasmic desmosomes. Previously, only non-specific histological changes had been described in pityriasis rosea, but the presence of dyskeratotic cells seems to be a significant feature.

Potassium iodide in the treatment of erythema nodosum and nodular vasculitis.

Twenty-nine patients with erythema nodosum, nodular vasculitis, or erythema nodosum-like lesions associated with Behçet's syndrome were treated with potassium iodide. Administration of the drug for systemic effect showed a substantial effect in 11 of 15 patients with erythema nodosum, seven of ten with nodular vasculitis, and one of four with leg lesions of Behçet's syndrome. Relief of subjective symptoms, including tenderness, joint pain, and fever, occurred within 24 hours. Substantial improvement in the eruption occurred within a few days, and the lesions disappeared completely ten to 14 days after therapy was initiated. The patients to whom the medication was administered shortly after the initial onset of erythema nodosum seemed to respond most satisfactorily. The effect of the drug was marked in the patients with positive C-reactive protein reactions, joint pains, and/or fever. Possible mechanisms by which potassium iodide exerts its effect are discussed.

Ultrastructural studies of spontaneously regressing plane warts. Macrophages attack verruca-epidermal cells.

Plane warts were examined at the earliest phase of spontaneous involution using an electron microscopy. Macrophages outnumbered lymphocytes in invading the epidermis. Lymphocytes exhibited pseudopods on the surface which occasionally reached into the epidermal cells. The cell membranes of both macrophages and epidermal cells frequently disappeared on the contacting surface and on occasion part of the cytoplasm and even the nucleus of macrophages invaded the epidermal cells. The macrophages showed an independent partial loss of their cell membranes with a subsequent outpour of their contents. This ultrastructural feature indicates that in spontaneously regressing plane warts the depressed membrane stability of macrophages as observed in BCG and other-induced tumor cell destruction also occurs in the presence of lymphocytes. Therefore, the spontaneous involution may represent a rejection phenomenon.

Ultrastructural studies of spontaneously regressing plane warts. Langerhans cells show marked activation.

Ultrastructural changes in Langerhans cells during spontaneous involution of plane warts were examined. In areas with activated macrophages and epidermal cell interaction, Langerhans cells showed signs of enhanced cellular activity with an increased number of Langerhans cell granules, as in contact dermatitis. The fine structure of Langerhans cell granules, however, was unusual in that the vesicular portion was surrounded by a membrane, and this portion frequently occurred independently taking the shape of a loop.

The phenomenon of spontaneous regression of numerous flat warts: immunohistological studies.

The phenomenon of systemic regression of numberous flat warts takes place within one month after the sudden onset of spontaneous inflammation in them. In other types of warts, we have never observed such a dramatic regression. We performed a histological study in a total of 51 cases showing this spontaneous inflammation in their flat warts and found a massive mononuclear cell infiltration in all. In 9 cases, a histological study for basophils was carried out but failed to show them among the infiltrating cells despite the strong histological resemblance to contact allergy. An immunofluorescence technique performed in 16 cases demonstrated no specific deposits of immunoglobulins and complement in such inflamed wart tissues except for those which appear to be only a secondary event to inflammation per se. These immunopathological findings further substantiate the concept that cell-mediated mechanisms rather than humoral immunity play a major role in this phenomenon of sudden regression of numerous flat warts.

Erythema multiforme: demonstration of immune complexes in the sera and skin lesions.

In twenty patients with erythema multiforme we investigated circulating immune complexes and their deposition in the skin lesions. CIq-binding activity was elevated in ten of twenty patients, and the platelet aggregation titre was high in three of twelve tested sera. Decreased levels of C3 were seen in two and of C4 in one out of eighteen patients. Direct immunofluorescence showed a deposition of C3, IgM or IgG in the blood vessel walls of the upper dermis in four of twelve patients. These findings may suggest that transient production of circulating immune complexes and their deposition play an important role in the pathogenesis of this disease.

Benign and neoplastic eosinophilic staining cells: an immunofluorescence study.

Deposition of immunoglobulins, complement and fibrinogen on eosinophilic staining cells was investigated using direct immunofluorescence techniques. Serum factor deposition was detected on benign epidermal eosinophilic cells seen in pityriasis lichenoides et varioliformis acuta, sunburn erythema and, in addition, on subepidermal hyaline bodies in lichen planus; no such deposition occurred on neoplastic eosinophilic cells in Bowen's disease and squamous cell carcinoma. The qualitative findings of immunofluorescence microscopy seem to be different in inflammatory and malignant dermatoses.

Ultrastructural studies of allergic contact dermatitis in man. Epidermal cell changes at 3, 6, and 12 h after application of DNCB.

Early epidermal lesions of allergic contact dermatitis were examined by electron microscopy. Normal human volunteers were sensitized to DNCB, and contact reactions were elicited sequentially. Epidermal cell changes at 3 h included: the occurrence of small vacuoles with or without membrane, focal dilatation of intercellular spaces, and the alteration of tonofilaments into short, aggregated bundles. Non-sensitized skin to which DNCB was applied also showed small vacuoles with or without membrane. Monocytes infiltrated into the intercellular spaces which were not dilated, and the neighboring tonofilaments of keratinocytes remained normal.