Hypersensitivity pneumonitis (HP) is a granulomatous interstitial lung disease resulting from an immunologic reaction to the repeated inhalation of organic dusts and active chemicals. There are 50 or more groups of HP, but the prevalence varies from country to country, and even within a country, depending on a variety of occupational or environmental inhalants. In Western coutries farmer's lung, bird fancier's disease, humidifier lung, and air-conditioner disease are common, but in Japan summer-type HP is the most prevalent group. Summer-type HP is a house-related illnes induced by Trichosporon asahii and Trichosporon mucoides which contaminate the patients' home environments in hot and humid conditions. The polysaccharide antigen contains mannan backbone attached with short side chains consisting of mannose, xylose, and glucuronic acid residues. Both immune complex-mediated and T cellmediated immune responses to the yeast are involved in the induction and development of the disease. Host factors such as HLA-DQw3 and cigarette smoking also play an important role in the development or suppression of the disease. An assay for serum anti-Trichosporon antibody by a Triko Kit is very useful for the serodiagnosis, and sanitization by cleaning, disinfecting, and removing from the colonizing location of Trichosporon prevents recurrence of the disease. Summer-type HP induced by Trichosporon is a new type of HP. It can be found in other countries including most Western countries, because Trichosporon asahii and Trichosporon mucoides distribute in the temperate and subtropical areas of the world.

View full abstract

Adhesion molecules play crucial roles in a variety of in vivo responses such as development of various tissues in embryos and also in the body defence mechanism in the postnatal period. Defects in adhesion molecules thus result in various pathological disorders. Recent investigation has identified a large number of novel adhesion molecules, particularly those involved in the extravasation of leukocytes including lymphocytes. However, there still appears to be a substantial number of unidentified adhesion molecules. In addition, signal transduction as well as regulatory mechanisms of adhesion molecules remain not fully explored. I will herein describe general characteristics of adhesion molecules and also discuss issues that need to be urgently resolved in the field of cell adhesion.

View full abstract

Fungus is known to be one of the causative allergens inducing bronchial asthma as are housedustmites, pollen and pet dander. Outdoor airborne fungi such as Cladosporium, Alternaria, Penicillium and Aspergillus are important inducing IgE antibody formation. In addition to these common fungi, the indoor fungi Aspergillus restrictus, Neurospora and Eurotium are important allergenic fungi which have recently been identified. The yeast Candida albicans, is a common commensal of the human oral and vaginal mucosae and gastrointestinal tract and part of the normal flora, is known as one of the main allergens causing bronchial asthma. We examined the allergenicity of mannan (Mn) as a cell-wall constituent and acid protease (CAAP) as a secreted enzyme of C. albicans. We previously reported cases of atopic asthma caused by CAAP and stressed the role of CAAP as an important allergen in mucosal allergy to C. albicans.
The levels of the antibodies to these antigens in the sera of asthmatic patients who showed positive immediate intradermal response to crude C. albicans (n=86) were measured. Anti-Mn IgE and IgG antibody levels were measured by liquid-phase assay (AlaSTAT). Anti-CAAP and anti-crude C. albicans IgE and IgG antibody levels were measured by RAST and AlaSTAT. Anti-Mn A and anti-Mn B IgE antibody titers were strongly correlated (r=0.87), while anti-Mn A and anti-CAAP IgE titers were not correlated. However, all of the anti-Mn A IgE positive sera and all of the anti-CAAP IgE positive sera were positive for IgE to crude-C. albicans. This indicates that both Mn and CAAP are C. albicans-related allergens. Titers of IgG antibodies to Mn A and crude C. albicans were highly correlated (r=0.90).
Results of inhibition assays performed using other fungal antigens as inhibitors showed that Mn is a cross reactive allergen among different fungi and that CAAP is a C. albicans specific allergen causing human mucosal allergic reaction.

View full abstract

It has been recognized that there are considerable variations in their skin reactivity to environmental allergens as well as in immunoreactivities, even in AD patients with similar signs and symptoms. Some AD patients have high serum IgE antibody levels, while others show low levels. There are also differences in the kinds of triggering factors that are related to the development and maintenance of AD, e. g., allergic or non-allergic. Even among AD patients with high titers of serum IgE antibodies, the kinds and number of allergens involved in the exacerbation of AD are different and can change with time. The types of the underlying allergic reactions vary as well, i. e., some show immediate reactions, while others show delayed type hypersensitivity responses to environmental allergens. Thus, even AD patients diagnosed by the established criteria may have remarkably different backgrounds. When we looked over our published data, we noticed that there were differences in levels of IgE RAST and skin reactions between AD with atopic respiratory diseases (ARD) and pure AD without ARD. Levels of IgE RAST against airborne allergens, which come into the body mainly through the respiratory tract, were higher in AD with ARD, while those against allergens such as Candida albicans and Malassezia furfur, which can colonize on the skin, were higher in pure AD. In addition to these Th2-mediated immunological abnormalities, Th 1-mediated DTH reaction and lymphocyte proliferation indices against airborne allergens were remarkably low in AD with ARD, whereas those against Candida albicans and Malassezia furfur were relatively preserved, although they were lower than those found in normal subjects. We understand from these findings that routes of allergen entry are important for the outcome of the resultant allergic reactions. This point of view is important answering questions such as how AD develops and how it can be prevented from the insults of each allergen.

View full abstract

We examined the ploidy of C. neoformans strains using both laser scanning cytometry and a fluorescence microscope equipped with a photomultiplier. Haploid strains consisted of normal-sized cells with a haploid DNA amount. In the cell population there were also large-sized cells with a diploid DNA amount. These large cells in haploid strains were isolated using a Skerman micromanipulator, cultivated, and were able to generate diploid clones. Even after only 3-5 transfers on slants, haploid cells were present in all the diploid clones examined. Conversely, haploid clones obtained by single-cell-isolation of normal-sized cells from haploid strains were also shown to contain diploid cells after 3-5 transfers. Fresh haploid isolates from the environment similarly contained diploid cells after 3-5 transfers. Thus, a cellular ploidy shift was shown to occur widely in C. neoformans strains.

View full abstract

We clinically evaluated three commercially available (1→3)-β-D-glucan measurement methods for the diagnosis of fungal infections: the kinetic turbidimetric, the end-point chromogenic, and the kinetic chromogenic Limulus tests. For the kinetic turbidimetric assay, we examined a dilution and heating pretreatment method at 70°C for plasma to eradicate irregular (1→3)-β-D-glucan values caused by changes in the nonspecific turbidity of the reaction mixture, a problem occasionally encountered when the ordinary method is used (pretreated at 80°C). With the 70°C-pretreatment method, the nonspecific turbidity was eradicated and the values of (1→3)-β-D-glucan were lower than those obtained by the ordinary method. Thus, the 70°C-pretreatment method was less sensitive than the ordinary method, but its specificity was higher. The overall agreement rates between the kinetic turbidimetric assay and chromogenic assay were near 90%. Some samples in the control group showed unexpectedly high (1→3)-β-D-glucan values with the kinetic chromogenic assay. The measurement with the end-point chromogenic assay was influenced by sulfa drugs. In the kinetic turbidimetric method, the 70°C-pretreatment method is more effective than the ordinary method.

View full abstract

Candida dubliniensis is a newly-recognized Candida species and an important infectious pathogen, particularly for HIV-positive patients. From oral smear samples from the radix linguae of 173 HIV-positive children, we obtained four yeast isolates which took a blue-green color on CHROMagar Candida plate at 37°C for 48 hours from one HIV-positive 3-year-old boy in Brazil. The isolates were difficult to grow on potato dextrose agar plate at 42°C, produced abundant chlamydospores on a cornmeal agar plate with Tween 80, and sprouted germ tubes in saline with horse serum, and the antigenic profile by CANDIDA CHECK test was useless. Carbohydrate assimilation tests by ID32C showed no reference code number in the reference book. The isolates were subjected to molecular biological assay of the DNA sequence of the large-subunit ribosomal DNA region (D1/D2) and randomly amplified polymorphic DNA (RAPD). The DNA sequence agreed with those of standard C. dubliniensis strains, and therefore, the isolates were identified as C. dubliniensis. RAPD band pattern analysis indicated that the clinical isolates might summarize one genotype. Although the child did not present oral lesions, the fungus might be latent for opportunistic infection.

View full abstract

We studied the preventive effects of socks against dermatophyte infection. Wearing various socks (cotton socks, nylon stockings, wool socks and “tabi”), a healthy volunteer walked on a bath mat on which a patient with tinea pedis had stepped earlier. The volunteer pressed her right foot with socks onto large agar medium (Foot-press method), then, took off the socks and performed the Foot-press method again. The number of colonies of isolated dermatophytes on the medium was counted.
The number of isolated colonies from the sole after taking off the nylon stockings was larger than that from the foot wearing the stockings. Dermatophytes were also isolated from the sole after taking off cotton socks. In contrast, few dermatophytes were isolated from the sole after taking off wool socks or “tabi”.
On microscopic observation, fibers of the nylon stockings and cotton socks were seen to be loose enough for dermatophytes to pass through. In contrast with those socks, fibers of wool socks and “tabi” were tight or fluffy. In conclusion, the nylon stockings and cotton socks are unsatisfactory in preventing the adhesion of dermatophytes.

View full abstract

An epidemiological investigation on dermatophytoses in Japan for the year 1996 was carried out with the following results. The number of dermatomycoses patients visiting the fifteen cooperating institutes that year was 8, 402. New outpatients with this condition accounted for 13.1% of all new outpatients in these institutes. Dermatophytoses patients numbered 7, 395 and were composed of: tinea pedis 4, 764 (64.4%), tinea unguium 1, 487 (20.1%), tinea corporis 558 (7.5%), tinea cruris 369 (5.0%), tinea manuum 195 (2.6%), tinea capitis 11, kerion Celsi 7, tinea barbae 1 and other forms 3. Of these, 113 were children under 15 years of age. Species and incidences of the 2, 615 strains isolated from the patients with dermatophytoses were as follows: Trichophyton (T.) rubrum 1, 828 (69.9%), T. mentagrophytes 743 (28.4%) Epidermophyton floccosum 20 (0.8%), Microsporum (M.) canis 13 (0.5%), M. gypseum 5, T. violaceum 2, and 4 undetermined strains. Candidiasis was found in 722 individuals: intertrigo 299, erosio interdigitalis 95, erythema infantum 89, oral candidiasis 63, paronychia et onychia 56, genital candidiasis 56, onychomycosis 24, chronic mucocutaneous candidiasis 1 and other atypical forms of candidiasis 39. Patients with tinea versicolor numbered 265 and those with Malassezia folliculitis 15. There were five cases of deep dermal mycoses: three of sporotrichosis, one of chromomycosis and one of aspergillosis. The results of superficial dermatophytoses for the year 1996 differed from those of 1991-92 in the following points: Tinea corporis and tinea cruris were lower in number, while tinea unguium had increased in ratio and number. M. canis infection tended to decrease gradually. In the age-distribution of tinea, in every clinical form the peak of distribution curve shifted to a more elderly age group.

View full abstract

Dermatophytosis of the external auditory meatus is believed to be a fairly rare disease. In the past three and a half years we have had seven cases of dermatophytosis in the external auditory meatus. All cases except one were associated with tinea of other lesions.
Case 1: A 44-year-old man had tinea of the auricle, tinea pedis and tinea unguium.
Case 2: A 14-year-old boy, the son of case 1 had no tinea elsewhere on his body, including the auricle. He scratched the auditory meatus with an earpick which his father had used.
Case 3: A 62-year-old man had tinea of the auricle, tinea pedis and tinea unguium.
Case 4: A 50-year-old man had tinea of the auricle, tinea pedis and tinea unguium.
Case 5: A 36-year-old man had tinea of the auricle, tinea pedis, tinea unguium and tinea cruris.
Case 6: A 30-year-old woman had tinea of the auricle.
Case 7: A 68-year-old man had tinea of the auricle, tinea pedis, tinea unguium and tinea manuum.
Endoscopic examination (except for cases 4 and 7) revealed dry cerumen from cartilaginous to bony region of the external auditory meatus. Direct examination using KOH method of the cerumen in all cases demonstrated numerous fungal elements. Fungal cultures identified Trichophyton rubrum except for cases 3 and 6. All cases were successfully treated with oral itraconazole or terbinafine. We suggest that tinea of the external auditory meatus is frequently associated with that of the auricle.

View full abstract