Interferon-gamma and interleukin-2 production by peripheral blood mononuclear cells from a patient with gold contact allergy.
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Biomedical subjects
Publications and source records attributed to T Koga.
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We experienced a 39-year-old male who developed neurological complication during a course of Mycoplasma pneumoniae pneumonia. The diagnosis of M. pneumoniae pneumonia was made on the basis of elevation of specific antibody (CF) titer in convalescent serum. Electroencephalogram showed diffuse damage in the brain, but no other abnormalities were not found on brain CT-scan and MRI. In the cerebrospinal fluid, the number of cells did not increase and the M. pneumoniae CF titer was not elevated. From these results, we concluded that encephalopathy in this patient was raised by an allergic reaction of the brain tissue to M. pneumoniae antigen. Until now, encephalitis or meningoencephalitis accompanied with M. pneumoniae infection has been reported by many investigators, but reports on encephalopathy due to M. pneumoniae are few. Therefore, we reported herein a case of encephalopathy following Mycoplasma pneumoniae pneumonia with several references.
Interactions between bacterial biofilms formed by Pseudomonas aeruginosa and clarithromycin, a macrolide having no anti-P. aeruginosa activity, were investigated. P. aeruginosa incubated for 10 days on membrane filters formed biofilms on the surfaces of the filters. The biofilms were characterized by dense colonizations of bacteria and thick membranous structures that covered the colonies. Treatment of the biofilms with a relatively low concentration of clarithromycin for 5 days resulted in an eradication of the membranous structures. Quantitative analysis of alginate and hexose was done to evaluate the quantity of polysaccharides in or on the biofilms. Treatment of the biofilms with clarithromycin decreased the quantity of alginate and hexose and therefore perhaps the quantity of polysaccharides as well. Eradication of the membranous structures of biofilms, or the decrease in the quantity of polysaccharides, resulted in an increase in the rate of penetration of antibiotics through bacterial biofilms. In vivo therapeutic effects of ofloxacin in the rat infection model, in which the biofilm mode of growth of P. aeruginosa is characteristic, were enhanced by oral coadministration of clarithromycin. It is suggested that clarithromycin eradicated glycocalyx produced by P. aeruginosa, or suppressed the production of glycocalyx, by unknown mechanisms and thereby enhanced the therapeutic efficacies of other antimicrobial agents against infections caused by P. aeruginosa.
A 190-kDa surface protein antigen (PAc) of Streptococcus mutans binds to human salivary components. For detection of specific binding of the PAc protein to human salivary components, a simple sandwich assay was used. Microtiter plates precoated with recombinant PAc (rPAc), PAc fragments, or S. mutans whole cells were allowed to react with human whole saliva and then were incubated with biotinylated rPAc. The biotinylated rPAc bound to salivary components was detected by use of alkaline phosphatase-conjugated streptavidin and p-nitrophenylphosphate. In this assay, the binding of whole cells of S. mutans and purified rPAc to salivary components was confirmed. For determination of a saliva-binding region of the PAc molecule, 14 truncated PAc fragments were constructed by use of the polymerase chain reaction and an expression vector, pAX4a+. The binding of these truncated PAc fragments to human salivary components was determined by the sandwich assay. Among the truncated PAc fragments, fragments corresponding to residues 39 to 864 and residues 39 to 1000 of PAc showed a high ability to bind to salivary components. Shorter recombinant fragments corresponding to residues 39 to 217, residues 200 to 481, residues 470 to 749, and residues 688 to 864 did not exhibit any binding ability. The fragment that corresponds to a proline-rich repeating region (residues 828 to 1000) bound directly to the PAc protein. These results suggest that residues 39 864 of the PAc molecule are important in the binding of the surface protein to human salivary components, and the proline-rich repeating region of the PAc protein may contribute to spontaneous self-aggregation of the PAc protein.
A surface protein antigen (PAc) of Streptococcus mutans with a molecular mass of 190 kDa is considered to play an important role in the initial attachment of this streptococcus to the tooth surface. Two internal repeating amino acid sequences are present in the PAc molecule. One repeating region located in the N-terminal region is rich in alanine (A-region), and the other, located in the central region, is rich in proline (P-region). To identify antigenic epitopes on the A-region of the PAc protein, 82 sequential overlapping synthetic decapeptides covering one of the repetitive units of the A-region were synthesized. In the epitope scanning analyses using murine antisera raised against recombinant PAc (rPAc), multiple antigenic epitopes were found in the repetitive unit of the A-region, and some of them reacted with antisera to rPAc from BALB/c, B10, B10.D2, and B10.BR mice. In particular, a peptide YEAALKQY (residues 366 to 373) was recognized by anti-rPAc sera from all four strains of mice. The reactivities of anti-rPAc sera in the epitope scanning were confirmed by using a purified synthetic peptide, NAKATYEAALKQYEADLAA (corresponding to residues 361 to 379). Furthermore, antisera against a surface protein antigen PAg (SpaA) of Streptococcus sobrinus from BALB/c mice reacted strongly to residues 330 to 337, 362 to 369, and 366 to 373 of the PAc protein by the epitope scanning analysis. An AKATYEAALKQY (residues 362 to 373 of the PAc protein)-like sequence, AKANYEAKLAQY, was found within the A-region of S. sobrinus PAg, suggesting that the amino acid sequences AKA-YEA and YEA-L-QY may be major cross-reactive epitopes of the S. mutans PAc protein and the S. sobrinus PAg protein.
The genetic organization of the gene cluster containing pilA, the structural gene for type IV pilin of Pseudomonas aeruginosa, as well as the accessory genes pilB, pilC, and pilD, has been studied. DNA sequences capable of initiating transcription when fused to a promoterless lacZ gene have been identified in the pilA-pilB and pilB-pilC intergenic regions. Unlike pilA, which requires rpoN (encoding the sigma 54 subunit of RNA polymerase) and products of two regulatory genes, pilS and pilR, expression of pilB, pilC, or pilD did not depend on any of these transcriptional regulators. Moreover, transcription of pilA from the tac promoter in an rpoN mutant background resulted in piliated bacteria, suggesting that the RpoN-based regulatory network is specific for pilA and does not control expression of any other genes necessary for formation of pili. Insertion of the omega fragment containing strong transcriptional terminators into pilB, pilC, and pilD failed to have a polar effect on expression of downstream genes, as determined by the ability of each cloned gene to complement, in trans, the corresponding insertionally inactivated chromosomal copy. Insertions into pilC, however, resulted in decreased synthesis of PilD as determined by quantitation of PilD enzymatic activity in processing prepilin in vitro and by immunoassay. This finding suggests that PilD may require PilC for its optimal stability or correct membrane localization.
The effect of synthetic muramyl dipeptide on glycosaminoglycan synthesis in cultured rat costal chondrocytes was examined. Muramyl dipeptide alone had no effect on the glycosaminoglycan synthesis of rat chondrocytes, whereas Escherichia coli lipopolysaccharide and interleukin 1 alpha inhibited glycosaminoglycan synthesis in a dose dependent manner. Muramyl dipeptide, when added to chondrocyte cultures in the presence of lipopolysaccharide, enhanced the lipopolysaccharide induced inhibition of glycosaminoglycan synthesis in a dose dependent manner. Adjuvant active analogues of muramyl dipeptide, but not adjuvant inactive analogues, also enhanced the lipopolysaccharide induced inhibition of glycosaminoglycan synthesis. In combination with muramyl dipeptide, to inhibit glycosaminoglycan synthesis, lipopolysaccharide could be replaced with the synthetic lipid A, an active principle of lipopolysaccharide. These results show that the muramyl dipeptide portion of bacterial peptidoglycan enhances the susceptibility of rat chondrocytes to the lipid A portion of bacterial lipopolysaccharide, and therefore the interaction between chondrocytes and bacterial cell wall components might be involved in damaging the cartilage in inflammatory joint diseases.
A novel immunomodulating fraction, SP-MAF1, was isolated from soybeans as a polysaccharide-protein complex by hot water extraction followed by acid treatment, ethanol treatment, and chromatography on a DEAE-Sepharose CL-6B column, and was characterized in some biological activities. SP-MAF1 increased glycolysis and IL-1 production by macrophages, but did not affect TNF production. SP-MAF1 also increased splenocyte proliferation that was induced by LPS and ConA, and ConA-induced production of IL-2 by splenocytes. In an in vivo test, the mean survival times of SP-MAF1-treated mice bearing FM3A were significantly longer than those of non-treated group. Since SP-MAF1 affected macrophages and splenocytes but not tumor cell growth, this effect may be mediated by the host immune system. Furthermore SP-MAF1 had a capacity to suppress the TNBS-induced DTH reaction. These results suggested that SP-MAF1 could either enhance or suppress immune functions.
Behçet's disease (BD) affects the lung as well as the intestine, central nervous system, kidney, and other organs. Pulmonary vasculitis is one of the most severe complications in BD because it can cause fatal bleeding. Corticosteroids and other immunosuppressive drugs have been used to treat pulmonary vasculitis, but the efficacy of these agents has not yet been established. We administered FK506, a novel immunosuppressive agent, as a treatment for BD. A 21-year-old woman presented definitive symptoms of BD, ie, repeated oral and genital ulcers, folliculitis, and panuveitis. The patient showed localized pulmonary infiltrates on her chest x-ray film that were histologically proved to be venulitis consistent with BD. These pulmonary infiltrates evanesced after the oral administration of FK506 for 8 weeks; in addition, the skin lesions and uveitis improved. This clinical observation indicates that FK506 is an effective agent in the treatment of pulmonary vasculitis associated with BD.
Recent evidence suggests focal glomerulosclerosis may be analogous to atherosclerosis. To investigate the role of hypertension and hypercholesterolemia in the appearance of glomerular foam cells, 2, 6 or 9-month-old stroke-prone SHR (SHRSP) were fed the high fat cholesterol diet (2% cholesterol, 0.5% cholic acid, 7% lard, 0.2% methylthiouracil; HFC) for 4 weeks. Serum total cholesterol was significantly elevated in HFC. Form cells were observed in glomeruli of 6- and 9-month-old, but not 2-month-old SHRSP with dietary-induced hypercholesterolemia. The glomerular foam cells varied in quantity almost in parallel with the duration of severe hypertension. Glomeruli with foam cells prominently situated in juxtamedullary region. Foam cells were frequently seen in glomerular sclerotic area. These results suggest that hypertension rather than hyperlipidemia may be more important for glomerular deposition of lipid, especially in early lesions, and hyperlipidemia may play a role in the foam cells accumulation.
Diffuse panbronchiolitis (DPB) is a chronic airway disorder exclusively seen in Japan, characterized by chronic inflammation of the respiratory bronchioles leading to air flow obstruction. Although the pathogenesis of the disorder is unknown, current studies based on bronchoalveolar lavage (BAL) have implied an important role of neutrophil-mediated inflammation as a characteristic pathological feature of the disease. Interleukin 8 (IL-8), a cytokine with potent chemotactic activity for neutrophils, has been proven to have close association with many inflammatory disorders. In this study, neutrophil chemotactic activity (NCA) and IL-8 were measured in the BAL fluid in eight patients with DPB to examine the roles of IL-8 in the neutrophil recruitment to the lower respiratory tract in DPB. Significantly higher levels of NCA and IL-8 were demonstrated in the BAL fluid of DPB patients (71.6 +/- 3.6%, 491.9 +/- 48.0 pg/ml, respectively) compared with that of chronic bronchitis (CB) patients (24.8 +/- 2.8%, 54.1 +/- 13.9 pg/ml, p < 0.001) and of healthy control subjects (7.0 +/- 0.9%, 14.2 +/- 3.9 pg/ml, p < 0.001). The IL-8 values were positively correlated with the NCA in the BAL fluid of DPB patients. Treatment with anti-IL-8 could significantly inhibited the NCA. These results suggest that IL-8 plays an important role in the recruitment of neutrophils to the lower respiratory tract in DPB.
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We examined the activity of defensins from human neutrophils against Mycobacterium avium complex (MAC). MAC were cultured in the presence of defensins at 37 degrees C for 4-48 hours. After incubation, colony counts were enumerated by colony-forming units (CFU). Human neutrophil peptide-1 (HNP-1) at 5 micrograms/ml had the ability to kill MAC. We tested 8 strains of MAC. HNP-1 was successful in killing every strain, although the degree of killing varied from strain to strain. We also found that HNP-2 and HNP-3 were as effective in killing MAC as HNP-1. We suggest that defensins play an important role in the host defenses against MAC.
The effects of Dilazep on immunologically induced glomerular injuries were examined. Accelerated Masugi nephritis in rats produced glomerulosclerosis with proteinuria following administration of a single dose of nephrotoxic serum (NTS). When 5 mg/kg/day of Dilazep had been administered prior to the NTS injection, the proteinuria was resolved rapidly after reaching a maximum level. The glomeruli 3 months later showed significant suppression of glomerulosclerosis and lesser adhesive lesions as compared to those in control rats with Masugi nephritis. On the other hand, when Dilazep was administered from 2 weeks after the injection of NTS, the rats displayed persistent proteinuria and glomerulosclerosis at similar levels to those in the Masugi group. Dilazep appears to exert some protective effects in the early stages of glomerular injuries induced by immunological mechanisms.
Flomoxef (FMOX), an oxacephem antibiotic of beta-lactam antibiotic family, was administered to 16 infants including 6 neonates and 10 premature infants at a dose of 20 or 40 mg/kg via intravenous injection, and plasma and urinary concentrations and the urinary recovery were determined. In addition, FMOX was administered via intravenous injection at daily doses averaging 85.5 mg/kg divided into 2 to 4 times for durations averaging 9 days to 96 infants from 0- to 90-day old (mainly neonates and premature infants). In 44 of the 96 infants with bacterial infections, clinical and bacteriological efficacies were evaluated, and prophylactic effects of FMOX were determined in the remaining 52 infants. Adverse reaction and laboratory tests abnormalities were evaluated also. The obtained results are summarized as follows. 1. Upon administration of FMOX at 20 or 40 mg/kg to neonates and premature infants via intravenous injection, plasma concentrations, half-lives and AUC were determined. In 3 neonates of 5, 7 and 16 days of ages administered with 20 mg/kg of FMOX, peak plasma concentrations of 62.5 to 99.7 micrograms/ml were achieved in 5 or 15 minutes after injection. Half-lives of FMOX in these neonates were 1.48 to 1.78 hours and AUC's were 112 to 161 micrograms.hr/ml. The same dose (20 mg/kg) of FMOX was administered to 3 premature infants of 5- 16- and 19-day of ages and initial blood samples were obtained at 5 minutes after injection from the 5-day old subject and at 15 minutes after injection from the 16-and 19-day old subjects. Peak plasma concentrations of 63.6 to 79.9 micrograms/ml were observed in the samples. Half-lives were 1.69 to 2.20 hours and AUC's were 174 to 201 micrograms.hr/ml. When 3 neonates (one 17-day old and two 24-day old subjects) were administered with 40 mg/kg of FMOX, peak plasma concentrations obtained at 5 minutes after injection were 99.7 to 122.0 micrograms/ml. Half-lives were 1.28 to 1.92 hours and AUC's were 170 to 357 micrograms.hr/ml.(ABSTRACT TRUNCATED AT 400 WORDS)