The agarose gel electrophoretic analysis of molluscum contagiosum virus (MCV) DNA obtained from 92 Japanese patients revealed the presence of four different BamHI cleavage patterns of MCV DNAs, classified as MCV-1,2,3 and 4. MCV-1 was found in 69% of the patients, MCV-2 in 4%, MCV-3 in 25%, and MCV-4 in 2%. Almost all the isolates from children and all female adult cases were infected with either MCV-1 or 3. No obvious clinical differences were seen between these two types. MCV-4 was found in only two adult male cases. The sizes of the lesions induced by MCV-4 appeared to be larger than those of other types. Six sets of siblings were shown to be infected with the same types, whereas two sets were infected with the different types. Some different MCV types were found in the cases attending the same swimming pools.
A 15-month-old girl had an asymptomatic eruption of yellowish-brown flat papules of 12 months' duration. Those papules were seen multiply on her face and in a small number on her neck and trunk. Skin biopsy showed a massive infiltrate of histiocytic cells in the upper and middle dermis. Electron microscopically, these cells had comma-shaped bodies in the cytoplasm, and formed desmosome-like junctions at the cell peripheries. A diagnosis of benign cephalic histiocytosis was made on the basis of these clinical, histological, and ultrastructural findings. To the best of our knowledge, this is the first report of benign cephalic histiocytosis in Japan.
A 22-year-old woman, whose first infant had died of lethal junctional epidermolysis bullosa (JEB), requested prenatal diagnosis for her third pregnancy. At 20 weeks gestation, fetal biopsy was performed under direct vision by fetoscopy. A semithin section of epon-embedded skin showed dermo-epidermal separation at the light microscopic level. Electron microscopy revealed the site of separation to be within the lamina lucida of the epidermal basement membrane (EBM). Indirect immunofluorescence on a 5 microns cryostat specimen of skin showed a complete absence of GB3 monoclonal antibody immunostaining at the EBM compared with a control 18 week old normal fetal skin sample. The diagnosis was therefore made that the fetus was affected with lethal JEB and a prostaglandin termination performed. The diagnosis was confirmed by further studies on the aborted fetus. 54 cases of prenatal diagnosis of various types of epidermolysis bullosa performed at Institute of Dermatology over the last 10 years are briefly reviewed. Several social and practical problems to launch prenatal diagnosis in Japan are also discussed.
Recently, it has been shown that 1,25 (OH)2 Vitamin D3 (VD3) shows growth inhibition and enhances differentiation of keratinocytes in vitro. To elucidate the further effect of VD3 on keratinocytes, we studied the effect of recombinant human gamma interferon (IFN-gamma) and VD3 on the expression of HLA-DR antigen and MHC class I antigen on 3 normal and 6 transformed keratinocytes by means of FACS analysis. IFN-gamma (500 JRU/ml, 72 hr) induced the expression of HLA-DR antigen on 3/3 normal keratinocytes, 3/4 trichilemmoma and 1/2 squamous cell carcinoma cell lines. When these cells were cultured with both IFN-gamma and VD3 at the same time, the expression of HLA-DR antigen was significantly decreased. Sequential treatment of these cells with IFN-gamma and VD3 (each 72 hr), or vice versa, showed significant suppression of HLA-DR antigen expression. The fluorescens intensity of class I antigen was increased after IFN-gamma treatment, however, this effect is inhibited when the cells were treated with combination of IFN-gamma and VD3.
Blood Group related antigens Lewis A, Lewis B, CA 19-9, and sialyl SSEA-1 were examined in normal human skin and oral mucosa, using monoclonal antibodies to the respective antigen immunohistochemically. These antigens were not expressed on normal keratinocytes but Lewis A and Lewis B were expressed on oral mucous epithelium. Lewis A, Lewis B, and CA 19-9 were expressed clearly on intraepidermal and dermal eccrine duct, but sialyl SSEA-1 was poorly expressed in some cases. In secreting portion of eccrine gland, Lewis A was expressed in 20%, Lewis B was expressed in 70%, and CA 19-9 was expressed in 10%, and sialyl SSEA-1 was expressed weakly in 20% of cases. It's noteworthy that sialyl SSEA-1 was expressed on dendritic cell in epidermis and some infiltrated small round cell in dermis. There is no correlation between patient's peripheral blood type (Lewis) and expression of Lewis antigen in normal skin.
The anticentromere antibody is considered to be a useful serologic marker for the CREST syndrome. But this antibody also appears in other related conditions less frequently. We classified 29 patients with anticentromere antibodies into 3 groups: (1) 16 patients with systemic sclerosis or Raynaud's phenomenon alone; (2) 7 patients with other connective tissue diseases; (3) 6 patients with other conditions. Ig class reactivities and complement-fixing abilities of anticentromere antibody were measured by the indirect immunofluorescence test. The whole Ig titers were high (1025 or more) in all patients belonging to group 1. However, the properdin-fixing anticentromere antibody titers of these patients were relatively low (256 or less). In contrast, the patients in group 2 and 3 were shown to have higher C3- and properdin-activating abilities which were determined by the ratios of the titers of C3- and properdin-fixing anticentromere antibody to the IgG titers although the whole Ig titers of these patients were widely distributed. These data suggest that the patients who have low whole Ig titers and/or high properdin-fixing titers do not belong to the scleroderma spectrum and that the patients without clinical features of scleroderma have high C3- and properdin-activating abilities.
A 35-year-old male from Kagoshima prefecture developed nodules with asymptomatic erythema on both upper eyelids, both hands and upper right leg in April 1986. On April 10, 1987, biopsy of skin lesions revealed numerous atypical CD4 positive lymphocytes which had invaded the dermis around the vessels. Analysis of serum showed positive antibody titer (X40) against the human T lymphotropic virus type I (HTLV-I) with some flower cells evident in peripheral blood; however, no infiltration into bone marrow or lymph nodes could be seen. Lymphocytes from peripheral blood and from the skin lesion of the right leg showed monoclonal integration of HTLV-I proviral DNA. Chronic active hepatitis B virus (HBV) was also a complicating factor. Familial study revealed all three family members to be infected with HTLV-1 as well as HBV. Proviral integration of HTLV-I was the intermediate type in two out of the three. From the results, a diagnosis of smoldering adult T cell leukemia-lymphoma (ATLL) was made in this patient with high risk to family members. Herein we discuss the development of ATLL in this case and infection among family members.
Abnormalities of triglyceride (TG) metabolism are considered to play an important role in pathogenesis of psoriasis. Two psoriatic patients with hypertriglycemia were treated with 750 mg of oral Clofibrate daily. While they were treated, both patients showed improvement of psoriasis. Upon cessation of treatment the lesions returned. During the treatment, levels of serum TG, apolipoprotein C-III (apo C-III), and apo E were reduced significantly. The analysis of serum fatty acids revealed a change in the level of linoleic acid. The serum linoleic acid level, which had been low in both cases before the treatment, increased in one case and decreased in other during the treatment. In the biopsy specimen from the post-treatment plaque, both capillary proliferation and endothelial swelling in the dermis were less prominent. There was a moderate reduction in the number of lymphocytic cells, and an increase in that of histiocytic cells. Clofibrate treatment improved TG metabolism and the histological and clinical findings in the psoriatic lesion.
To investigate the influence of ursodesoxycholic acid (URSO) on griseofulvin (GF)-induced protoporphyria mice, analysis of hepatic, erythrocytic, and fecal porphyrin levels and histopathological examinations were performed in dd-Y strain mice treated with 0.5% GF and/or 0.5% URSO. We observed no difference of hepatic and fecal porphyrin levels between the GF group and GF with URSO group, although an elevation of erythrocytic porphyrin levels was seen in the GF with URSO group. However, remarkable hepatic atrophy revealed in the GF with URSO group. Furthermore, a strong emission of red fluorescence was observed in the liver under long wave ultraviolet. Histopathologically, many focal necrosis was found in the liver specimen treated with GF and URSO. We expected that URSO might facilitate the excretion of porphyrin from bile to feces because of suppression of transfer from serum to erythrocyte like cholic acid (CA). But, the action of URSO appears to be different from that of CA. We consider that the 0.5% concentration of URSO plays a role in the cytotoxic effect to the liver.
A case of Malignant Hemangioendothelioma (MHE) effectively treated with intra-arterial continuous infusion of recombinant interleukin-2 (rIL-2) was experienced. The Pt, a 82-year-old women, presented herself in our hospital with a complaint of the tumor in right-frontal region. Based on clinical and pathological findings, the Pt, was diagnosed as MHE. Increase of LAK (Lymphokine activated killer cell) activity was observed during treatment with intra-arterial continuous infusion of rIL-2. In addition, decrease of tumor was started when LAK activity showed high value. We mainly discussed about treatments for MHE and mechanism of these therapies by use of data of this case and other autho's papers.
Sephadex G-75 gel filtration of murine anagenic hair bulb extracts (HBE) showed two peaks with chemotactic activity. Peak I (m.w. 63 +/- 4.6 KD) was chemotactic for both neutrophils and lymphocytes, and Peak II (m.w. 47 +/- 5.6 KD) was chemotactic for lymphocytes only. The neutrophil related chemotactic activity was sensitive to treatments by trypsin, pronase, neuraminidase, or heating at 100 degrees C for 10 min. With Peak I, lymphocyte related chemotactic activity was sensitive to treatments by pronase, trypsin or neuraminidase, but was unaffected by heating at 100 degrees C for 10 min. On the other hand, the same aforementioned treatments all individually inactivated the Peak II lymphocyte related chemotactic activity. Intradermal injection of Peak I fractions into guinea pigs induced infiltration of neutrophils and mononuclear cells, and that of Peak II induced the infiltration of mononuclear cells. These findings suggest that normal C3H murine anagenic hair bulb contains three different chemotactic factors related to neutrophils and lymphocytes.
Localization of HTLV-I-associated antigens was studied in adult T cell leukemia (ATL) cells and HTLV-I-infected cell line cells using monoclonal and human polyclonal antibodies against the viral-related antigens. Two monoclonal antibodies that we obtained by hybridoma technique reacted with HTLV-I-virus core antigens, P19 and P24, respectively. Human anti-HTLV-I-antibodies, which were purified from sera from ATL patients reacted with not only HTLV-I virus particles but also their precursors located in the cytoplasm. In tumor cells freshly isolated from ATL patients, no expression of the virus antigens was observed. When the cells were cultured for several days, the virus antigens were defined in about 3-5% of the cultured cells by the monoclonal antibodies, and in 5-10% by the purified human anti-HTLV-I antibodies. Addition of 5-iodo-2'-deoxyuridine to the culture inhibited cell growth, and at the same time, increased the percentage of the virus antigen-positive cells. Established HTLV-I-infected cell lines showed different cytological profiles from the original ATL cells in the viral replication and morphology.
In attempt to prove the hypothesis that corneocyte surface area in diabetics is larger than that in age-matched non-diabetics, we collected corneocytes from 50 diabetics and 43 non-diabetics in different decades of life. We measured surface areas of 27 +/- 3 corneocytes in each subject, utilizing an image analyser (Kontron MOP-10), then we counted mean number of corneocytes collected in 7 diabetics and 7 non-diabetics. There was a significant correlation between corneocyte surface area and chronological age in non-diabetics, whereas there was no significant correlation in diabetics. Corneocyte surface area of diabetics was larger than that of non-diabetics in every decades of life. The differences were statistically significant in 4th, 7th and 8th decades of life. Mean number of corneocytes collected in non-diabetics was 2.21 +/- 0.47 (X 10(5)), whereas that in diabetics was 2.49 +/- 0.55 (X 10(5)). The present study suggested that turnover time of corneal layer of the skin might be delayed in diabetics.
To investigate alterations in the basement membrane (BM) components around tumor nests, Bowen's disease (BD), actinic keratosis (AK), basal cell epithelioma (BCE), squamous cell carcinoma (SCC) were studied by double immunofluorescent staining with antibodies to laminin (LN), type IV collagen (CIV), heparan sulfate proteoglycan (HSPG), and chondroitin 6-sulfate glycosaminoglycan (C6S). In BD, all BM components were continuous on the dermo-epidermal junction. In AK, C6S was partially disrupted, but the other components were continuous. In BCE, LN and CIV were continuous around the tumor nests, but HSPG and C6S were varied. SCCs were divided into two groups by the patterns of LN, CIV, and HSPG; SCC with continuous BM components or disrupted ones. The former SCC had a tendency to show the more infiltrative growth. C6S was detected partially on the BMs of SCCs which have cytological characteristics of BD, while it was absent on those of other SCCs. The difference in the patterns of the BM components suggests variation of tumor invasion.
Case 1 was a 20-year-old male with a nodule on the scrotum. Case 2 was a 14-year-old female with a dome-shaped, reddish-brown nodule on the nose. Case 3 was a 30-year-old male with a dome-shaped, reddish-brown nodule on the forearm. All of the excised specimens showed typical features of solitary reticulohistiocytic granuloma. There were histiocytes and multi-nucleated giant cells in the dermal tumorous nests. They were stained positively with PAS reaction and anti-lysozyme antibody, but were stained negatively with S-100 protein antibody. To clarify the nosology of the reticulohistiocytic granuloma, we reviewed the literatures of multicentric reticulohistiocytosis and adult xanthogranuloma. Multicentric reticulohistiocytosis was considered to be a systemic disease and different from solitary reticulohistiocytic granuloma. However, adult xanthogranuloma showed clinical similarities to solitary reticulohistiocytic granuloma instead of the differences in the histopathologic features.
The human adult intraepidermal eccrine sweat duct (IESD) were studied by the transmission electron microscope. The formation of the intracytoplasmic cavities was demonstrated in the luminal cell of the adult IESD, and the relation between the intracytoplasmic cavities and the IESD formation was as follows. On the eccrine sweat duct ridge, these intracytoplasmic cavities enlarged, broke through the cell membrane and coalesced into the intercellular lumen. Furthermore, several intercellular lumina were merged into the intraepidermal ductal lumen. In the lower to upper squamous layers, small intracytoplasmic cavities were formed around the intraepidermal duct and were fused into the duct. Simultaneously, the contents of the intracytoplasmic cavities were discharged into the ductal lumen. Intracytoplasmic cavities in these layers were ordinarily formed and concerned in not only the reconstruction of the duct but also the secretory function. The intracytoplasmic cavities were surrounded with the same microvilli as lined the intraepidermal ductal lumen. Many clear vesicles (about 0.1 microns in diameter) were observed near the intracytoplasmic cavities, but multivesicular dense bodies (MDB) were not seen near the cavities. These vesicles were considered to participate in the formation of the intracytoplasmic cavities.
Twenty-seven cases of urticarial erythema with predominantly neutrophilic infiltration in the upper dermis were examined clinically, histologically and serologically. Their condition persisted longer than common urticaria, with transitory high fever and arthralgia being noted frequently. Based on histological examination results, the patients were divided into three groups. Ten patients with histological findings of leukocytoclastic vasculitis were diagnosed as urticarial vasculitis which was accompanied in 7 cases by systemic lupus erythematosus, Sjögren syndrome or viral hepatitis. This group frequently showed hypocomplementaemia and multiple organ involvement such as hepatitis and nephritis. An immunofluorescence study demonstrated immunoglobulin and/or complement components to be deposited in the vessel walls of upper dermis, thus implicating type III allergy in the pathogenesis. The second group consisted eight patients with moderate infiltration of neutrophils toward the vascular walls though vasculitic changes were not apparent. Systemic lupus erythematosus and Sjögren syndrome were noted in 5 of these patients but multiple organ involvement was relatively quite infrequent. Antihistamines and even systemic corticosteroids failed to have any effect in the majority of the patients on these two groups. The remaining nine patients constituting the third group showed neither neutrophilic infiltration toward vessel walls nor vascular damage and there was no multiple organ involvement. Bacterial infection of upper respiratory tract appeared to possibly be a trigger in most of these patients for whom antibiotics were effective as treatment. In conclusion, histological examination is particularly important for cases such as the present cases for accurate diagnosis and deciding appropriate treatment.
Skin penetration of various antimicrobial agents was studied in rats. Skin concentration/serum concentration ratios were classified into three groups, i.e. group I with ratio greater than or equal to 0.7, group II with the ratio 0.7-0.4 and group III with the ratio less than or equal to 0.4. The drugs of group I were OFLX, CPFX, LFLX, FLRX, SPFX, AMK, EM, RXM, CAM, CLDM. The drugs of group II were ABPC, CVA/AMPC, CVA/TIPC, CEX, CED, CXD, CTM-HE, CXM-AX, CPZ, CBPZ, TFLX, ASTM, MINO. The drugs of group III were AMPC, CCL, CDX, CPDX-PR, CFTM-PI, CTZ, CEC, CEZ, CTM, CMZ, CZON, MCR, IPM/CS. Factors which may influence the skin penetration were discussed, but no definite conclusion has not been obtained.
From 1975 to 1989, 12 patients with pemphigus vulgaris (PV) and 19 with pemphigus foliaceus (PF) were treated with systemic or topical corticosteroids at the Nara University Hospital. All 12 patients with PV were treated with oral corticosteroids (initial dose of prednisolone: 15-70 mg/day) and 4 of 12 patients showed prolonged clinical remission (up to 9 years) without corticosteroids. Of 19 patients with PF, 16 patients were treated with oral corticosteroids (initial dose of prednisolone: 8-40 mg/day) and 3 patients were treated with only topical application of corticosteroids. In PF, 7 of 16 patients treated with systemic corticosteroids and all 3 patients treated with topical corticosteroids also showed prolonged clinical remission (up to 10 years). These observations suggest that most of the patients with pemphigus respond well to the treatment of relatively small or moderate dosage of corticosteroids.
