Lack of association of the interleukin-1 receptor antagonist gene with palmoplantar pustulosis in Japanese.

We analysed a polymorphism of the interleukin (IL)-1 receptor antagonist (IL1RN) gene in 93 Japanese patients with palmoplantar pustulosis (PPP). None of the IL1RN alleles was significantly increased in the patients compared with controls. Because PPP has been reported to be associated with the tumour necrosis factor (TNF) region, we examined the association between the TNF and IL1RN genes. There was a difference in IL1RN*2 positivity between patients with and without the AA genotype of the TNF gene. In contrast, such a difference was not found in controls. These data indicate a possible epistatic effect between TNF and IL1RN linked genes for susceptibility to the pathogenesis of PPP.

Polymorphisms in the TNFA promoter region is not associated with palmoplantar pustulosis.

Polymorphisms of the 5'-flanking promoter/enhancer region of the TNAFA gene were determined in 80 Japanese patients with pulmoplantar pustulosis (PPP). The 5'-flanking region of the TNFA gene from -1107 to 66 was amplified by polymerase chain reaction (PCR) method. Nucleotide sequencing data from the PCR products revealed that 5 single nucleotide polymorphisms at position 1031, -863, -857, -307 and -237. None of the nucleotide substitutions were significantly increased in PPP patients when compared with those in controls. To clarify the linkage among the neighboring genetic marker, we analyzed the association between the polymorphisms in the TNFA promoter region and the NcoI polymorphism in the first intron of the TNFB gene as well as HLA-DR9. The genotype at 1031C is strongly associated with TNFB1 and negatively associated with TNFB2 which is reported to be associated with PPP. These data indicate that TNFA gene centromeric to TNFB is not associated with PPP and the susceptible gene of PPP is located between TNFB and HLA-B.

Frontal mucocele presenting as a subcutaneous tumour on the forehead.

A 57-year-old Japanese woman had a 3-month history of an asymptomatic subcutaneous tumour on the forehead. The patient presented a slightly elevated, elastic soft subcutaneous mass, 3 cm in diameter, on the mid to left-side forehead. Slight swelling of the left upper eyelid was observed. CT scanning and magnetic resonance images revealed a sharply demarcated cystic mass from the subcutaneous area on the forehead expanding into the frontal sinus and intracranial space. The tumour was diagnosed as a frontal mucocele and combined external and endoscopic approaches were performed. It is rare that a patient with a frontal mucocele is initially referred as a case of a subcutaneous tumour because most of the patients complain primarily of the ophthalmic symptoms. However, the present case reminds us that frontal mucocele is one of the differential diagnoses for a subcutaneous mass on the forehead.

Polymorphism in the tumor necrosis factor B gene is associated with Palmoplantar pustulosis.

We investigated the allele and genotype distribution of a polymorphism of the tumor necrosis factor (TNF) B gene and the frequency of HLA-DR9 in 49 patients with Palmoplantar pustulosis (PPP) and 51 healthy controls. We found that the frequency of TNFB2 in the PPP patients was significantly higher than that in the controls. Furthermore, the DR9-TNFB2 haplotype was significantly more frequent in the PPP patients (P=0.0045). These results suggest that TNFB2 may confer susceptibility to PPP.

[Efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin in healthy volunteers].

We conducted a field trial to evaluate the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in preventing or attenuating influenza among volunteers during the winter season of 1994-1995. A trivalent inactivated influenza vaccine, composed of A/Yamagata/32/89 (H1N1), A/Kitakyusyu/159/93 (H2N2) and B/Mie/1/93 influenza virus strains, was administered intranasally together with recombinant LTB containing 1% recombinant LT (LTB*). Vaccination was done twice 4 weeks apart. Salivary secretory IgA and serum HI antibodies were measured before and 8 weeks after the primary vaccination. Thirty-two volunteers were enrolled in this study; 18 volunteers (mean age 37.7 +/- 11.3) were given LTB*-combined vaccine and 14 volunteers (mean age 44.1 +/- 11.3) given placebo. Outbreaks of H3N2 subtype and B type virus were observed during this study period. Six (42.9%) of the 14 volunteers in the placebo group and 3 (16.7%) of the 18 receiving the LTB*-combined vaccine contracted influenza. There was no statistically significant difference between the two groups, because the number of subjects was small. Higher percentage of positive IgA and HI antibody responses among vaccines given vaccine with LTB* were observed as compared with those in the placebo group. Positive IgA antibody response to all vaccine strains were observed in 46.7% (7/15) of the vaccine group. On the other hand, none of the placebo group showed positive IgA antibody response to all vaccine strains. These results suggest that nasal influenza vaccine with LTB* appears to be effective in preventing influenza.

Antibody responses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin.

Evaluation of the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in inducing antibody responses among volunteers, which was conducted during the winter season of 1993-1994, is reported. A trivalent inactivated vaccine, composed of A/Yamagata/32/89 (H1N1), A/Kitakyusyu/159/93 (H3N2) and B/Bangkok/163/90 influenza virus strains, was used alone or together with the adjuvant, recombinant LTB supplemented with 0.5% recombinant LT (LTB*). The volunteers were divided into two groups: 73 volunteers (mean age 35.0 +/- 12.0 years) inoculated intranasally (i.n.) with LTB*-combined vaccine and 49 volunteers (37.9 +/- 11.3) inoculated i.n. with the vaccine alone. Vaccination was done twice 4 weeks apart. Salivary secretory IgA and serum hemagglutination-inhibiting (HI) antibodies were measured before and 8 weeks after the primary vaccination. For the sake of convenience, more than a 1.4-fold rise in IgA antibody response (units of specific IgA antibody per microgram of total IgA) and a fourfold or greater rise in HI antibody titer after vaccination were regarded as a positive antibody response. Thirty-seven (50.3%) and 36 (49.3%) of the 73 vaccinees, respectively, given the nasal LTB*-combined vaccine showed positive IgA and HI antibody responses to one or more of the three vaccine strains. In comparison, positive antibody responses in the group given vaccine alone were 32.7% for IgA and 30.6% for HI antibody. There was a significant difference between these two groups. These results suggest that the nasal LTB*-combined vaccine could enhance the production of higher levels not only of serum HI antibody but IgA antibodies in the respiratory tract than do the nasal vaccine alone.

[Association of Chlamydia pneumoniae infection with otitis media with effusion].

Chlamydia pneumoniae has recently been recognized to cause various human respiratory tract diseases, including pharyngitis, bronchitis and pneumonia. The most common pathogens of respiratory tract infections such as Streptococcus pneumoniae and Haemophilus influenzae are frequently present in middle ear effusions. Therefore, it is possible that C. pneumoniae play a role in otitis media with effusion (OME). Isolation of C. pneumoniae from middle ear aspirates of OME was performed by the culture method using the HeLa 229 or HL cell line. Identification as C. pneumoniae was based on positive staining for inclusions by a species-specific fluorescein-conjugated monoclonal antibody. C. pneumoniae was recovered from 17.8% (13 of 73) of the patients with acute OME, and 7.1% (3 of 42) of those with chronic OME, Moreover, antibodies to C. pneumoniae were measured by the microimmunofluorescence method in 14 patients who yielded the agent, and all of them had detectable antibodies to C. pneumoniae. Evidence of recent or current infection by the organism was found in nine patients on the basis of either on IgM antibody titer of 1:16 or higher, or a four-fold rise in the titer of IgG antibody. The study findings indicate that C. pneumoniae can cause OME and that the organism is a new candidate as an etiological agent of middle ear diseases.

[The pathogenic role of Chlamydia trachomatis in otitis media with effusion].

There are conflicting views concerning middle ear infections due to Chlamydia trachomatis. To ascertain the etiological role of this agent in otitis media with effusion, middle ear effusions were cultured for C. trachomatis and other bacterial flora. A total of 102 patients with otitis media with effusion (OME) were recruited for this study. The study population included 66 patients with acute OME (AOME) and 36 patients with chronic OME (COME). As Chlamydia pneumoniae, the third species of Chlamydia, is also known to be isolated from middle ear effusion of OME, the fluorescent-antibody technique using anti-C. pneumoniae or anti-C. trachomatis antibodies was employed in order to identify the inclusion bodies isolated on HeLa 229 cells as C. trachomatis. C. trachomatis was recovered from 7 patients (10.6%) with AOME and from 8 (22.2%) patients with COME. Bacteria were cultured from 20 of 63 patients with AOME and from 13 of 28 patients with COME. Pathological bacteria were cultured from only 2 patients with C. trachomatis infection in the middle ear. Only normal skin flora, no bacterial pathogens, were isolated from the remainder. Antibodies to C. trachomatis in serum were measured by a microimmunofluorescent method in 13 patients with C. trachomatis infection in the middle ear. Antichlamydial antibody of the IgG type was detected in 84.6% (11/13) of these patients. These results suggest that C. trachomatis causes middle ear infections and plays an etiological role in the pathogenesis of otitis media with effusion.