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Introduction: Mastitis is the inflammation of the mammary gland that mainly occurs during the lactation period and requires antibiotic treatment with little evidence for its efficacy. We investigated the effect of the National Action Plan for antimicrobial resistance aiming for appropriate antimicrobial stewardship on broad-spectrum antibiotics administration for mastitis despite the lack of a disease-specific antimicrobial agents manual., Methods: Using a large nationwide database, an interrupted time-series analysis was performed using data from 34,340 female patients who received antibiotics for mastitis between April 2012 and March 2020. This study compared the trend of outcomes before and after the publication date of the National Action Plan (April 2016). The outcomes were the proportion of broad-spectrum and first-choice narrow-spectrum antibiotic administration and surgical drainage within 30 days after the administration., Results: Broad-spectrum antibiotics were administered in 70% of the cases before and 67% of the cases after the National Action Plan publication date. The trend of broad-spectrum antibiotics administration significantly changed at the publication (-2.6% [95% confidence interval, -3.9% to -1.3%], p < 0.001) and the administration decreased after the publication (1.9% annual decrease, P trend < 0.001). The trend of first-choice antibiotics administration also changed at the publication (1.3% [0.1-2.4%], p = 0.028) and the administration increased after the publication (1.3% annual increase, P trend < 0.001). The occurrence of surgical drainage was stable during the study period., Conclusion: Despite the lack of a disease-specific antimicrobial manual, the publication of the National Action Plan improved antimicrobial stewardship for mastitis without any impact on a surgical treatment course., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

Background/aim: Currently, there are no established biomarkers to differentiate between glucocorticoid (GC)-resistant and GC-sensitive ulcerative colitis (UC); however, interleukin (IL)-1β could be one such candidate biomarker. The aim of this study was to investigate whether mucosally expressed IL-1β could predict the response to GC in patients with UC., Methods: A total of 27 mucosal tissue samples from 10 patients with GC-resistant UC (GC-resistant group), 9 patients with GC-sensitive UC (GC-sensitive group), and 8 control patients (control group) were analyzed by qRT-PCR for the expression of IL-1β, GC receptor α (GRα), GRβ, and other inflammatory mediators. Rachmilewitz endoscopic index (REI) between the GC-resistant and GC-sensitive groups was matched to avoid any potential influence of inflammation., Results: The REI did not significantly differ between the GC-resistant and GC-sensitive groups. Mucosally expressed IL-1β levels in the GC-resistant group were significantly higher than those in the GC-sensitive group. However, there were no significant differences in the expression levels of GRα, GRβ, and other inflammatory mediators between the 2 groups. We could distinguish between the GC-resistant and GC-sensitive groups with a sensitivity of 90.0% and specificity of 77.8% based on mucosally expressed IL-1β., Conclusions: Mucosally expressed IL-1β can be used as a predictor of GC response in patients with UC., (© 2020 S. Karger AG, Basel.)

Background/aims: Mutations in the presenilin 2 (PSEN2) gene cause familial Alzheimer's disease (AD). Common polymorphisms affect gene activity and increase the risk of AD. Nonsynonymous polymorphisms in the PSEN2 gene showed Lewy body dementia (LBD) phenotypes clinically. Therefore, we aimed to investigate whether PSEN2 gene polymorphisms were associated with AD or LBD., Methods: Seven single nucleotide polymorphisms (SNPs) of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBD patients, and 105 age-matched controls., Results: Linkage disequilibrium (LD) examination showed strong LD from rs1295645 to rs8383 on the gene in our cases from Japan. There were no associations between the SNPs studied here and AD onset, and haplotypic analyses did not detect genetic associations between AD and the PSEN2 gene. Although the number of the cases was small, the SNPs studied did not modify the risk of developing LBD in a Japanese population., Conclusion: The common SNPs of the PSEN2 gene did not affect the risk of AD or LBD in a Japanese population. Because genetic variability of the PSEN2 gene is associated with behavioral and psychological symptoms of dementia (BPSD) in AD and LBD, further detailed analyses considering BPSD of both diseases would be required.

Background/aims: It has recently been shown that the neuronal sortilin-related receptor (SORL1) plays an important role in the pathogenesis of Alzheimer's disease (AD)., Methods: To investigate whether variations around the SORL1 gene are associated with AD, 7 single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan technology with 180 AD patients and 130 age-matched controls., Results: Our results confirmed the strong linkage disequilibrium among the 7 SNPs studied. However, our study failed to detect any association between the SNPs and AD. We could not confirm any synergetic interaction between the SNPs and apolipoprotein E in our AD patients either., Conclusion: Further genetic studies are needed to clarify the relationship between the SORL1 gene and AD., (Copyright 2008 S. Karger AG, Basel.)

Background: Although dermatomyositis (DM)-associated facial erythema was noted in the nasolabial folds of Japanese patients, DM-associated facial erythema other than heliotrope rash has drawn little attention in previous studies., Objectives: To characterize phenotypical features and frequencies of erythema, especially those in the seborrheic area of the head, in DM patients., Methods: A retrospective study on skin manifestations in 33 DM patients followed up at our department during the past 15 years was conducted., Results: Macular violaceous erythema (MVE) in the seborrheic area of the face was most frequent (67%). Patients with facial MVE had also MVE in the scalp significantly more frequently than those without facial MVE. The pathology of the facial MVE was dominated by DM-associated changes with slight changes compatible with seborrheic dermatitis (SD)., Conclusions: Japanese DM patients had MVE frequently in the seborrheic area of the head. Its phenotypical features suggested that it might be triggered by SD., (2008 S. Karger AG, Basel.)

Background: Nodular scleroderma is a fibrosing reaction, presenting well-defined, firm, raised nodules, which resembles keloid. Recent studies suggest that connective tissue growth factor (CTGF) is involved in the fibrotic process, and its expression is increased in many fibrosing diseases., Objective: In this study, we report 3 cases of nodular scleroderma, and the expression of CTGF is also investigated., Methods: Three patients who developed nodular scleroderma are described. Expression of CTGF protein and transcripts in nodular scleroderma was examined by immunohistochemistry and in situ hybridization., Results: Patients were 1 female and 2 males, and all cases were associated with diffuse systemic sclerosis. Nodular lesions were found on the chest (2 cases), back (1 case), upper arm (1 case) and nape (1 case). Histology of the nodular lesions showed thickened collagen bundles in the dermis. Results of immunohistochemistry showed that expression of CTGF was detected on the sclerotic fibroblasts in the lesions of nodular scleroderma, while it was not detected in fibroblasts in normal skin. In situ expression of CTGF transcripts was abundantly detected on the fibroblastic cells in nodular scleroderma., Conclusion: Our data showed increased expression of CTGF in the sclerotic fibroblasts of nodular scleroderma, suggesting that CTGF plays an important role in its pathogenesis., (Copyright 2005 S. Karger AG, Basel.)

Objective: To understand the autoimmunity associated with chronic hepatitis C (CHC), we investigated autoantibodies (autoAbs) to CD69., Methods: With this aim, we tested the reactivity of serum samples from patients with CHC and asymptomatic carriers of hepatitis C virus (HCV), as well as from patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH), to recombinant CD69 molecules., Results: Frequencies of anti-CD69 autoAbs were 38.7% in CHC, 15.8% in AIH and 12.3% in CHB. None of the tested asymptomatic HCV carriers had autoAbs to CD69. It is important clinically that the presence of anti-CD69 autoAbs was found to be associated with a poor response to interferon-alpha (IFN-alpha) therapy. In the epitope analysis, multiple epitopes were mapped on CD69, indicating antigen-driven production of the autoAbs., Conclusion: We evidenced existence of anti-CD69 autoAbs in patients with CHC, and found that the anti-CD69 autoAb may have potential for predicting responses to IFN-alpha therapy., (Copyright 2003 S. Karger AG, Basel)

Anthralin (dithranol) is frequently used for the treatment of psoriasis. However, the mode of action of anthralin has not been completely elucidated as yet. Recent findings suggest that psoriatic keratinocytes are resistant to the apoptotic process. In this study, we examined the immunohistochemical expression of apoptosis-regulated protein in the involved psoriatic skin following topical anthralin therapy. Biopsy specimens were obtained from back skins treated with topical anthralin or white petrolatum (control) in 4 patients with psoriasis vulgaris. Immunohistochemical examination revealed that psoriatic keratinocytes expressed high levels of Bcl-x, which was significantly reduced after anthralin treatment. Bax was not detected in the epidermal keratinocytes in the petrolatum-treated skin, while it was present in the upper keratinocytes after anthralin therapy. Bcl-2 was detected only in basal layers of psoriatic epidermis following both petrolatum and anthralin application. Psoriatic keratinocytes expressed higher levels of Fas in the lower epidermis, while only weak expression was detected in anthralin-treated plaques. On the other hand, hyperproliferative keratinocytes strongly expressed Fas ligand (FasL) on their plasma membranes as well as infiltrating lymphocytes in the upper dermis. Furthermore, anthralin-treated psoriatic epidermis did not express FasL. In normal skin, keratinocytes expressed low to absent levels of Bcl-x and Bax, while Bcl-2 was detected only in melanocytes in basal layers. Neither Fas nor FasL were detected in the epidermis of normal skin. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed positive labeling on the majority of psoriatic keratinocytes through the epidermis in petrolatum-treated skin, whereas anthralin treatment markedly reduced TUNEL-positive keratinocytes. These in vivo results may reflect improvement of the psoriatic skin following effective anthralin therapy., (Copyright 2003 S. Karger AG, Basel)

Background: Interleukin (IL)-13 is a T-cell-derived cytokine that shares several functions with IL-4, including the induction of immunoglobulin E synthesis. Recent studies suggest that cytokines expressed locally in the skin play several critical roles in atopic dermatitis (AD), however, little is known about the role of IL-13 in AD lesions., Objectives: The present study was designed to characterize the involvement of IL-13 in AD in the skin and peripheral blood mononuclear cells (PBMC)., Methods: Using lesional and nonlesional skin from adult AD patients and normal skin from healthy volunteers, we performed RT-PCR, in situ RT and immunostaining to determine the IL-13 expression at the mRNA and protein levels. The actual numbers of IL-13 expressing cells in biopsy specimens were counted under the microscope. IL-13 mRNA expression in PBMC from AD patients and healthy volunteers was examined by RT-PCR analysis., Results: IL-13 mRNA expression was detected by RT-PCR in lesional and nonlesional skin and in PBMC from AD patients, but not in normal skin or PBMC from healthy volunteers. In AD lesional skin, numerous IL-13 mRNA-positive cells were demonstrated by in situ RT, and similar numbers of IL-13-positive cells were also detected immunohistochemically. Smaller numbers of IL-13-positive cells were observed in AD nonlesional skin and in normal skin. The differences in the numbers of IL-13-expressing cells between lesional and nonlesional skin were statistically significant. Double immunostaining revealed that IL-13 was produced in approximately 40% of T cells and 20% of mast cells in AD lesional skin, suggesting that T cells and mast cells are major sources of IL-13 in AD lesions., Conclusion: IL-13 may play a local as well as a systemic role in the development of AD lesions., (Copyright 2002 S. Karger AG, Basel)

The first nationwide nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type 1 (HIV-1) of voluntarily donated blood after serological pre-screening and before release of cellular components and plasma for fractionation was implemented by the Japanese Red Cross Blood Transfusion Services. The NAT screening assay using multiplex reagent is time-saving, cost effective, and labour-saving procedure for all blood and blood products including short-shelf life platelets. During the 50-mini-pool NAT screening of serologically negative donations (February 1, 2001-April 30, 2001), we were able to screen out 112 HBV-positive, 25 HCV-positive, and 4 HIV-1 positive units from blood and blood components.

We report a case of unusual annular erythema associated with myelodysplastic syndrome (MDS). A 58-year-old male with MDS developed annular erythema on his back, scaly erythema on the dorsa of hands, and exudative erythema on his eyelids. Histological examination revealed a mononuclear cell infiltrate around vessels and follicles in the mid- to lower dermis. He had no history of treatment with granulocyte-colony-stimulating factor (G-CSF). Serum granulocyte-macrophage-colony-stimulating factor (GM-CSF) level was slightly elevated (5.84 pg/ml, normal < 2.0 pg/ml), whereas other cytokines including G-CSF, IL-6, and IL-8 were within normal limits. Skin manifestations were much improved by systemic mepitiostane, and serum GM-CSF level returned to normal levels.

Purpose: To characterize T cells infiltrating into the ocular tissues of mice with experimental autoimmune uveoretinitis (EAU) immunized with interphotoreceptor retinoid-binding protein (IRBP)., Methods: The T cell receptor (TCR) repertoire on T cells obtained from ocular lesions of EAU mice was analyzed by reverse transcriptase-polymerase chain reaction. The clonotype of the T cells was examined by the single-strand conformation polymorphism (SSCP) method, followed by sequence analysis of the TCR beta-chain complementarity-determining region 3 (CDR3)., Results: The repertoire of the TCR BV gene in T cells from inflamed lesions was heterogeneous. SSCP analysis showed accumulation of multiple T cells specifically in ocular tissues of EAU mice, suggesting that these cells were expanded by an antigen-driven stimulation. Junctional sequence analysis demonstrated the presence of highly conserved amino acid sequence motifs (AGTGG, AGD) in CDR3 of BV2-positive T cells., Conclusions: Our findings suggest that T cells infiltrating into ocular lesions of EAU mice recognize restricted T cell epitopes of IRBP, resulting in autoimmune uveoretinitis.

The recurrence of invasive thymoma is often observed; however, no accepted treatment of recurrent invasive thymoma has yet been established. We herein report a 41-year-old woman with invasive thymoma and pleural dissemination who demonstrated long-term survival after undergoing 4 operations. Based on our findings, reoperation is thus suggested in patients with intrathoracic recurrence and long-term survival can be expected.

We report a case of direct skin invasion by Hodgkin's disease from a left supraclavicular lymph node. Clinical and pathological presentations mimicked infectious disease such as scrofuloderma. The nodule later developed a fistula following a biopsy that never healed despite numerous antibiotic treatments. Ten months later, other nodules with spontaneous fistula formation appeared on the anterior neck. A diagnosis of Hodgkin's disease was then made. Subsequent COPP cytostatic therapy remarkably improved the skin lesions and lymph nodes achieving complete remission.

Background: Interferon-gamma (IFN-gamma) is used in the treatment of tumor stage mycosis fungoides (MF), whereas its mechanism is still unknown. We have previously shown that treatment with intralesional IFN-gamma induced tumor regression., Objective: To explore the possibility that IFN-gamma may alter the cytokine expression by tumor cells, we studied cytokine gene expression in a tumor nodule of MF., Methods: By using the reverse transcriptase-polymerase chain reaction, Th1- and Th2-type cytokine mRNA expression was examined before and after intralesional IFN-gamma therapy. Additionally, we examined bel-2 protein expression on tumor cells., Results: We found weak mRNA expression of interleukin-4 (IL-4) and IL-5, and strong expression of IL-6, IL-10 and IFN-gamma before therapy. After successful treatment of intralesional IFN-gamma, mRNA expression of IL-5, IL-6 and IL-10 were significantly reduced and IL-2 mRNA was mildly induced. Culture for 24 h of tumor cells with IFN-gamma showed upregulation of IL-2 mRNA and downregulation of IL-6 mRNA expression. bcl-2 expression was significantly decreased after successful intralesional IFN-gamma therapy, photochemotherapy (PUVA) and radiation therapy., Conclusion: These data suggest that IFN-gamma induces tumor regression by affecting cytokine gene expression in MF tumor lesions. The reduced bcl-2 expression did not seem to be induced by a direct immunological affect of IFN-gamma, but to represent a nonspecific result of tumor regression after successful treatment.

Background and Objective: Mast cells are thought to play an important role in the pathogenesis of systemic sclerosis (SSc), although their significance is still unknown. As mast cells are increased in number in the lesional skin of the early stage of scleroderma, we addressed the question whether expression of stem cell factor (SCF), a mast cell growth factor, is upregulated in the lesional skin., Methods: Immunohistochemical analysis of SCF was performed in paraffin-embedded skin sections from the lesions of 18 patients with SSc (13 in the edematous and 5 in the sclerotic phase) and from normal skin of 5 subjects. SCF messenger RNA expression was also examined on cultured fibroblasts derived from SSc by using reverse-transcriptase polymerase chain reaction., Results: Immunostaining showed focal expression for SCF in fibroblast-like spindle-shaped cells, mast cells, keratinocytes and endothelial cells. SCF-positive spindle-shaped cells were significantly increased in the reticular dermis in the early edematous stage of SSc (33.7 +/- 13.0/mm2) as compared with normal skin (18.3 +/- 4. 2/mm2; p <0.05); however, there was no significant difference between the sclerotic phase (18.9 +/- 6.9/mm2) and normal skin. mRNA expression of SCF was detected both in cultured scleroderma-derived and normal skin-derived fibroblasts., Conclusion: These results may suggest that SCF plays a role in the fibrotic process in early-stage SSc.

We describe the case of a 69-year-old man with malignant lymphoma who developed granuloma annulare on his fingers. The number of cutaneous nodules increased when a recurrence of lymphoma was demonstrated during the course of disease. Granulomatous lesions disappeared after the fifth cycle of chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisolone). The coexistence of these two diseases is relatively rare. The clinical features seen in this case, however, might suggest that granuloma annulare is a generalized granulomatous reaction induced by malignant lymphoma.

A 51-year-old woman underwent a bilateral wedge resection of lung metastases through a median sternotomy 10 months after an initial operation for synovial sarcoma of the left lower extremity. Since then, five right and two left posterolateral thoracotomies have been performed over a 6-year period. The patient is presently doing well 7 years after the initial operation of the left lower extremity without any evidence of recurrence.

A 66-year-old woman with CD8+ chronic lymphocytic leukaemia developed multiple indurated erythema or plaques. A skin biopsy specimen showed dense infiltration of leukaemia cells in the dermis and subcutaneous tissue. Most of the infiltrating cells were CD8 + cells. To our best knowledge, leukaemia cutis such as this case showing plaques with diffuse infiltration of CD8 + cells has not been reported previously.

A 73-year-old man was admitted to our hospital to undergo treatment for right lung cancer (large cell carcinoma) which had directly invaded the liver through the diaphragm, and presented with T3N0M0, stage IIIa disease. A right lower lobectomy was performed with lymph node dissection, combined with a partial resection of the diaphragm and the liver, as well as a reconstruction of the diaphragm using the latissimus dorsi muscle. The patient had an uneventful postoperative course and was free of disease 1 year later at the time when this paper was written.

In a patient with both lichen planus and psoriasis, and suffering from hepatitis C virus infection, we examined the T cell receptor (TCR) Vb repertoire by reverse transcriptase polymerase chain reaction in skin lesions from psoriasis and lichen planus. A variety of rearranged variable TCR genes was found in the skin lesions, and the TCR Vb repertoire of the infiltrating T cells was not restricted. Although different patterns of expression were observed in the two lesions, TCR Vb 2 and 7 were commonly found.

A 58-year-old male presented multiple papules on the nose for over 10 years. Excisional biopsy revealed angiofibroma with perivascular fibrosis and coarse collagen fibers. Investigation for internal malignancies revealed gastric cancer. Messenger RNA for HER-2/neu and c-ras were found both in the lesions of the skin and stomach. We propose the term, fibropapule multiplex of the nose, which may be a variant of Cowden's disease associated with occult internal malignancy.

We describe a patient with incontinentia pigmenti who developed the clinical picture of intestinal Behçet's disease. Diagnosis of Behçet's disease was base on a recurrent genital and oral ulcer and a positive HLA-B51. Impaired neutrophil chemotactic activity and an elevated plasma IL-6 level were found. Chromosomal study revealed no abnormality in the patient or her family. We discuss the possibility that there are common immunological abnormalities in the two syndromes.

Background: Multiple dermatofibromas (DFs) are often associated with systemic lupus erythematosus (SLE). An increased number of mast cells is observed in the upper portion or over the lesion of DF., Objective: To investigate the role of the serum of a patient with multiple DFs, we examined its growth effects on fibroblasts., Method: 3H-Thymidine incorporation was used to examine the effects of the serum of an SLE patient with multiple DFs on fibroblasts derived from DF and normal skin., Results: The serum of the SLE patient with multiple DFs exhibited a stronger growth-stimulatory activity on normal and DF-derived fibroblasts in a dose-dependent manner, compared to that of SLE without DFs or normal sera. The growth effects were inhibited in 40% by antiplatelet-derived-growth-factor antibody and almost completely inhibited by antibody against basic fibroblast growth factor. Cultured fibroblasts derived from the upper portion of the DF lesion, which included most of the numerous mast cells, demonstrated a higher level of 3H-thymidine uptake after stimulation of autologous serum compared to that from the mid and lower portions of DF., Conclusion: These results suggested the existence of various fibroblast growth factors derived from the mast cells in SLE patients with multiple DFs.

Background: Multiple dermatofibromas (DFs) have been reported to develop in various disorders, especially in systemic lupus erythematosus (SLE)., Objective: To investigate the role of mast cells in the formation of multiple DFs in association with autoimmune disorders, we quantified the number of mast cells., Methods: Three cases who developed multiple DFs with positive antinuclear antibodies are described; a 54-year-old woman with a 10-year history of SLE with 13 lesions, a 33-year-old woman with 11 lesions and a 46-year-old woman with SLE and Sjögren syndrome with 10 nodules. Distribution and number of mast cells were examined in the removed lesions of DFs., Results: In 2 cases, mast cells in the upper portion of the lesions were increased in number in comparison with the solitary DF, nevocellular nevus and normal skin. These 2 cases had early DFs from the onset; in the remaining case in which mast cell number was not increased, they were old or fading lesions., Conclusion: It is suggested that mast cells may play a role in induction and exacerbation of the fibrotic process of multiple DFs, and they are supposed to be a reactive hyperplasia in association with systemic autoimmune disorders.

A patient with psoriasis vulgaris developed verruciform xanthoma (VX) on the scrotum during psoralen photochemotherapy (PUVA). Although it is uncertain whether VX was induced by PUVA therapy, we report the first case of VX which appeared in a patient with psoriasis during PUVA therapy. We speculate that UV light may be one of the etiologic factors triggering VX in this case.

We describe a case of primary multiple cutaneous plasmacytosis successfully treated by intralesional steroid therapy. Plasma interleukin-6 (IL-6) levels reduced in parallel with the disease activity. Intralesional steroid reduced IL-6 production by peripheral blood mononuclear cells, while neither PUVA therapy nor intralesional recombinant interferon-gamma resulted in a benefit and plasma IL-6 levels did not decrease. It was suggested that IL-6 might play an important role in the pathogenesis of this condition.

Chronic actinic dermatitis (CAD) has distinct clinical features different from polymorphous light eruption (PLE). In order to clarify the difference between CAD and PLE, not only in clinical histories and findings but also in photobiological and histopathological reactions to phototests, we investigated 6 Japanese patients with CAD and performed provocative phototests which are our standardized methods in diagnosing PLE. On provocative phototests in CAD, pruritic papules were reproduced with smaller doses of UVB, at longer hours after irradiation (48-72 h) and they lasted for more days than in patients with PLE. Our study demonstrated that although milder cases of CAD and severe cases of PLE could not be distinguished clearly based on photobiological reactions alone, typical cases of CAD showed completely different provocative phototest results from those of PLE.

Highly sensitive and specific tests for HCV infection are now available for epidemiological studies. These include: (1) the second-generation ELISA or agglutination technique with supplemental testing; (2) serotyping of antibody; (3) detection of HCV-RNA by RT-nested double PCR with the 5' noncoding region for the highest sensitivity; (4) quantitation of HCV-RNA; (5) genotyping using specific primers in the core region, and (6) sequence analysis of E2/NS1 hypervariable region 1 to identify homology among HCV isolates. Transmission of HCV is commonly done by percutaneous routes, although the route in a significant proportion of sporadic infections is unknown. Sexual transmission and perinatal transmission appear to be relatively infrequent.

Clinical and immunopathological analysis was performed on 24 cases of Sjögren syndrome with annular erythema (AESjS). AESjS predominantly appears on the cheek of the face where skin temperature is relatively low in comparison with other sites. VCAM-1 and ICAM-1 were strongly expressed on endothelial cells of AESjS, while epidermal expression of ICAM-1 was focal and weak. VCAM-1 mRNA expression was also much more intense compared to systemic lupus erythematosus. The lymphocyte response to staphylococcal enterotoxin B was higher in AESjS than that of controls, and cells positive for T cell receptor V beta 6,9,12 were expanded after the culture. Superantigen-driven endothelial-cell-dependent T cell infiltration to the skin plays a crucial role in AESjS.

To break the vicious circle between malnutrition and severe infection which has been linked to the great magnitude of infant deaths worldwide, we have been searching by means of clinical and experimental studies for measures which provide for rapid enhancement of body defenses. Based on clinical observations of malnourished children and the sequence of recovery during nutritional rehabilitation, it is suggested that the complement system is a more important factor during the early stage of nutritional recovery than CMI. In animal experiments using malnourished rats, nutritional deprivation affected various components of the body defense system to various extents, CMI being the most susceptible to influence. The complement system acted to maintain host defense even when CMI was impaired. Also observed was the earlier recovery of serum complement to normal or higher levels as compared with that of CMI. The complement system responded to bacterial infection much earlier than other immunologic responses, even in malnourished rats with depressed CMI. The infected rats showed a much higher rate of de novo synthesis of complement proteins than noninfected rats, and this effect was predominant in the malnourished group. Based on these animal experiments, we attempted to induce rapid heightened resistance to infection in malnourished rats by enhancing the complement system. After administration of proper doses of lentinan or Zn-chlorophyllin, which are known to activate C3 in vitro, to malnourished rats, heightened resistance against bacterial infection was induced together with a heightened complement response. In contrast, after administration of cobra venom factor, which is known to reduce C3 activity both in vitro and in vivo, resistance against bacterial infection was reduced, even in well-nourished rats. In summary, we have analyzed in the malnourished state the mechanism of heightened resistance against bacterial infection after activation of C3 by lentinan or Zn-chlorophyllin. These C3 activators enhanced C3b formation and iC3b formation in vivo, eventually resulting in enhanced interaction of iC3b present on invaders with CR3 on phagocytic cells.

Biphasic skin reaction with peak response at 1 and 24 h with prominent mast cell degranulation was induced by intravenous application of a monoclonal anti-DNP IgE antibody and subsequent skin test. This reaction was hapten-specific and mast-cell-dependent because no reaction was observed when oxasolone was used as an elicitation antigen or skin test was elicited in genetically mast-cell-deficient mice (W/Wvv). A partial spongiotic reaction and mononuclear cell infiltration into the epidermis were observed in mice with hyperplastic epidermis induced by topical retinoic acid. Cotransfer of DNFB-sensitized lymph node cells with anti-DNP IgE antibodies failed to enhance the skin test reaction in unsensitized mice. These results suggest that, to some degree, IgE antibody may play some role in the development of eczematous skin lesions in the rodent system without the involvement of cellular hypersensitivity.

Cutaneous basophil hypersensitivity (CBH)-inducing factor was demonstrated in immune sera obtained from dinitrofluorobenzene (DNFB)-sensitized animals 2 weeks after sensitization (DNP-GPS-2W). It showed hapten specificity and worked dose dependently. It was fractionated into a non-gamma-globulin fraction by Sephadex G-150 gel filtration following ammonium sulfate desalting and CM-cellulose chromatography. The factor was eluted into a fraction of a little smaller molecular weight than bovine serum albumin on Sephadex G-150 gel filtration. It passed through an antiguinea pig IgG1 column and was absorbed to a DNP-BGG column. On SDS-PAGE it failed to show any staining band because of low protein concentration. From these results CBH factor appearing in circulation in contact-sensitized animals was thought to be a somewhat different molecule from that of Askenase's factor, i.e. IgG1 antibody.

It was recently demonstrated that there was a specific activity to induce basophil-rich skin reaction in the sera of contact-sensitized guinea pigs (CBH factor, CBH-F). In the in vitro chemotactic assay system, CBH-F was shown to have weak basophil chemotactic activity but enhanced its activity in the presence of corresponding antigen(s). Furthermore, basophil chemotaxis in reaction to the antigen(s) was observed when the cells were preincubated with CBH-F. It worked mainly for Percoll-separated bone marrow basophils but not for oil-induced peritoneal macrophages. Immunological analysis revealed that CBH-F was a protein with a small molecular weight (MW 4-6 X 10(4] with an antigen binding site and isoelectric point of between 4.5 and 5.0. It did not show any characteristics of IgG1 or IgG2 on immunoadsorbent column and immunoelectrophoresis. Enzyme treatment with insoluble trypsin eliminated the chemotactic activity but this was not the case with neuraminidase treatment.

The differentiation of photoallergic contact dermatitis by 3,3', 4', 5-tetra-chlorosalicylanilide from phototoxic contact dermatitis by 8-MOP in guinea pigs was studied by skin window technique. Based upon the results, it may be concluded that the photoallergic reaction can be differentiated from phototoxic reaction by the appearing pattern of basophilic leukocytes.

A 30-year-old male taxi driver developed extensive purpuric necrotic lesions all over his body. He had a consolidated shadow in the right upper lung field, proteinuria with microscopic hematuria, and granulomatous change in the nasal mucosa. The standard regimen of prednisolone alone or in combination with cyclophosphamide showed only a limited effect on the lesion. However, weekly intravenous injections of a high dose of cyclophosphamide (500 mg/week) in combination with 60 mg/day of prednisolone exhibited dramatical suppression of the disease activity.

The case of a 56-year-old female with coexisting aspergillosis and squamous-cell carcinoma in the maxillary sinus is reported. The diagnosis was established by cytologic study of washings of the sinus before and after admission and was confirmed by exploratory antrotomy. To our knowledge, this is the first case in which the coexistence of fungus and neoplasm in the paranasal sinus was established by preoperative cytologic diagnosis.

Sera obtained from guinea pigs sensitized with 2,4-dinitrofluorobenzene (DNFB) showed suppressive activity on the migration inhibitory factor (MIF) production by the lymph node cells obtained from DNFB-contact-sensitized guinea pigs. A similar suppressive effect was achieved by the sera of 2,4,6-trinitrochlorobenzene- (TNCB-)sensitized guinea pigs. The suppressive factor in the sera was found to be IgG1 antihapten antibody. It suppressed MIF production dose-dependently during a period between 3 h before and 1 h after the antigen stimulation. Pretreatment of macrophages with IgG1 antihapten antibody abolished the MIF production of the lymph node cell. The antibody lost its suppressive activity after splitting off its Fc portion, and pretreatment of macrophages with Fc fragments of normal IgG1 interfered with the action of the IgG1 antibody. Therefore, the IgG1 antihapten antibody in the sera of contact-sensitized guinea pigs acted on macrophages through its Fc portion to inhibit MIF production by lymph node cells.