Clinical evaluation of patients with inflammatory connective tissue diseases complicated by cytomegalovirus antigenemia.

We evaluated the occurrence of cytomegalovirus (CMV) infection and the background characteristics in twenty-three hospitalized patients with inflammatory connective tissue diseases including systemic lupus erythematosus, polymyositis/dermatomyositis, rheumatoid vasculitis, microscopic polyangitis, and Takayasu's arteritis. Cytomegalovirus antigenemia was demonstrated in 10 of 23 evaluable patients. Five of ten patients with CMV antigenemia developed symptomatic CMV disease (all cases of fever, two cases of liver involvement, two cases of interstitial pneumonia, and one case of unknown organ involvement), whereas the remaining five patients were asymptomatic. Most of CMV antigenemia-positive patients had been administered intravenous steroid pulse, or in combination with immunosuppressive agents intravenously or orally because of refractory disease activity. Particularly, in patients who received intravenous methylprednisolone pulse in combination with additional intravenous cyclophosphamide pulse, the incidence of CMV antigenemia was markedly higher (four out of four). Four of ten CMV antigenemia-positive patients simultaneously showed detection of Pneumocystis jiroveci in induced sputum by PCR, increase in level of serum beta-D-glucan and the finding of geographical ground-glass opacities on chest computed tomography. These findings suggested that patients with connective tissue diseases under intensive immunosuppressive therapies (intravenous steroid pulse in combination with additional intravenous cyclophosphamide pulse in particular) are highly susceptible to CMV infection and disease, and that patients complicated by CMV antigenemia are susceptible to combined opportunistic infection such as Pneumocystis pneumonia.

Different susceptibilities of Staphylococcus and Gram-negative rods to epigallocatechin gallate.

We examined the antibacterial effects of epigallocatechin gallate (EGCg, the main constituent of tea catechins) against various strains of Staphylococcus and Gram-negative rods. Compared to the minimum inhibitory concentrations (MICs) of EGCg against S. aureus, S. epidermidis, S. hominis, and S. haemolyticus (50-100 micro g/ml), higher MICs (>or=800 micro g/ml) were observed against Gram-negative rods, including Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens. And difference was observed between the binding abilities of EGCg with viable S. aureus and with E. coli. The bactericidal activity of EGCg for S. aureus was blocked dose-dependently by purified peptidoglycan but not by lipopolysaccharide or dextran. It was also found that peptone and protein, but not amino acids, in the culture medium greatly affected the antibacterial activity of EGCg. These results indicate that the structure of the bacterial cell wall and the different affinities of EGCg with the various cell wall components are responsible for the different susceptibilities of Staphylococcus and Gram-negative rods to EGCg.

Enhanced expression of interferon-inducible protein 10 associated with Th1 profiles of chemokine receptor in autoimmune pulmonary inflammation of MRL/lpr mice.

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic lupus erythematosus (SLE)-like disease. The natural history of the pulmonary involvement and the underlying mechanism of leukocyte infiltration into the lungs of MRL/lpr mice and SLE patients remains elusive. We aimed to investigate the expression profiles of chemokines and chemokine receptors in the lung of the SLE-prone mouse. We examined the correlation between lung inflammation and expression of IP-10 (interferon-gamma-inducible protein 10), a CXC chemokine, and TARC (thymus- and activation-regulated chemokine), a CC chemokine, in MRL/lpr mice, MRL/Mp-+/+ (MRL/+) mice, and C57BL/6 (B6) control mice. The extent of cell infiltration in the lung was assessed histopathologically. Reverse transcriptase PCR showed up-regulation of IP-10 mRNA expression in the lungs (P < 0.05) of MRL/lpr mice, in comparison with MRL/+ or B6 mice. The increase paralleled increased expression of a specific IP-10 receptor, CXCR3, and correlated with the degree of infiltration of mononuclear lymphocytes. In contrast, lung expression of TARC and its specific receptor, CCR4, were suppressed in MRL/lpr mice. Immunohistology showed that macrophage-like cells were the likely source of IP-10. Flow cytometric analyses revealed that the CXCR3-expressing cells were mainly infiltrating CD4 T cells and macrophages, which correlated with the degree of mononuclear lymphocyte infiltration. Recent data suggest that Th1 cells and Th1-derived cytokines play an important role in the development of SLE-like disease in MRL/lpr mice. Our results suggest that IP-10 expression in the lung is involved, through CXCR3, in the pathogenesis of pulmonary inflammation associated with migration of Th1 cells.

[A case with systemic lupus erythematosus presenting with reversible edematous lesion in cerebellum].

We report the case of a 24-year-old woman with systemic lupus erythematosus (SLE). The patient presented with cervical erythema and multiple arthralgia in December, 1996. Based on the high level of antinuclear antibody and the positivity for anti-double-stranded-DNA antibody, we diagnosed the patient as having SLE. Her symptoms improved and her condition was maintained following steroid treatment. In August 2000, the patient suddenly had headache, nausea, vertigo, cerebellar ataxia, fixation nystagmus, and intention tremor. She was negative for the anti-phospholipid antibody. The cerebrospinal fluid IgG index and the IL-6 level were high. MRI of the right cerebellar hemisphere showed an equal-signal-intensity region in the T 1-enhanced image, and a high-signal-intensity region with a diffuse undefined border in the T 2-enhanced image. The increased cerebral blood flow at the site corresponding to a cerebellar lesion detected by magnetic resonance imaging (MRI) was observed by brain single photon emission computed tomography (SPECT). The central nervous system (CNS) lupus was confirmed by the presence of a lesion in the cerebellum. The abnormalities detected in MRI and SPECT images of the brain disappeared immediately after the steroid pulse therapy, and symptoms such as ataxic gait were improved. This patient was diagnosed as having acute neuropsychiatric SLE with cerebellar symptoms that are rarely observed as a localized neural sign of SLE. The MRI and SPECT images suggested the presence of an inflammatory edematous lesion that was confined in the cerebellar hemisphere. This is considered to be due to the increase of vasopermeability.

Additive, indifferent and antagonistic effects in combinations of epigallocatechin gallate with 12 non-beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus.

Additive, indifferent and antagonistic effects were observed in combinations of epigallocatechin gallate (EGCg, a main constituent of tea catechins) with12 non-beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). The combinations of EGCg with the inhibitors of either protein or nucleic acid synthesis showed additive or indifferent effects. These antibiotics included tetracycline, minocycline, chloramphenicol, streptomycin, gentamicin, kanamycin, erythromycin, rifampicin and ofloxacin. In contrast, EGCg showed an antagonistic tendency against glycopeptide antibiotics (vancomycin, teicoplanin and polymyxin B). The common property of these antibiotics is the peptide backbone structure, suggesting a direct binding of EGCg with the antibiotics. The above results indicate that tea catechins may affect the activities of antibiotics both positively and negatively.

Epigallocatechin gallate synergistically enhances the activity of carbapenems against methicillin-resistant Staphylococcus aureus.

Combinations of carbapenems and epigallocatechin gallate (EGCg; a main constituent of tea catechins) showed potent synergy against 24 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). MICs of imipenem in the presence of EGCg at 3.125, 6.25, 12.5, and 25 microg/ml, were restored to the susceptible breakpoint (< or =4 microg/ml) for 8, 38, 46, and 75% of the MRSA isolates, respectively. Similar results were also observed for combinations of panipenem or meropenem and EGCg. Therefore, the combinations may be worthy of further evaluation in vivo against MRSA infection.