C-reactive protein levels in the serum of asthmatic patients.

BACKGROUND: Asthma is a chronic airway inflammatory disease caused by immune cells such as T lymphocytes and eosinophils. Recently, highly sensitive C-reactive protein (hs-CRP) assays have become available for detecting small changes in CRP levels within the reference range, allowing for the evaluation of clinical inflammation. OBJECTIVE: To investigate the relationship between hs-CRP levels and bronchial asthma. METHODS: We collected blood samples from 109 patients with bronchial asthma, with or without attacks, and measured serum eosinophil cationic protein levels, pulmonary function, and serum CRP levels using an hs-CRP assay. RESULTS: Mean serum hs-CRP levels were significantly higher in patients without attacks (0.473 mg/L) and with attacks (0.908 mg/L) (P < .001 for both) than in controls (0.262 mg/L). Serum hs-CRP levels were inversely correlated with forced expiratory volume in 1 second/forced vital capacity in asthmatic patients (r = -0.4915; P < .01). CONCLUSION: Serum hs-CRP levels may be related to the state of asthma exacerbation and allergic inflammation.     

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.     

Expression and function of X chromosome-linked inhibitor of apoptosis protein in Sjögren's syndrome

Apoptotic cell death in acinar and ductal epithelial cells is thought to play an important role in the development of salivary gland dysfunction in patients with Sjogren's syndrome (SS). We examined the expression of anti-apoptotic molecules in salivary glands from patients with SS. The labial salivary glands from six human T-cell leukemia virus (HTLV)-I-seronegative and eleven HTLV-I-seropositive SS patients were analyzed by immunohistochemistry. In vitro experiments were performed with a human salivary gland cell line (HSG cells). Immunohistologic analyses revealed that Bcl-2 and Bcl-x were preferentially expressed in salivary infiltrating mononuclear cells more than acinar and ductal epithelial cells. In contrast, strong X chromosome-linked inhibitor of apoptosis protein (XIAP) expression was evident in both acinar and ductal epithelial cells. The pattern of expression of these anti-apoptotic molecules was similar in both HTLV-I-seropositive and HTLV-I -seronegative SS patients. Western blot analysis confirmed expression of XIAP in cultured HSG cells. The expression of XIAP in HSG cells was increased by IL-1beta, TGF-beta1, or IL-10. However, XIAP expression was down-regulated by TNF-alpha, which induced apoptotic cell death of HSG cells with an increase in caspase-3 activity. These effects of TNF-alpha in HSG cells were antagonized by IL-1beta, TGF-beta1, or IL-10. Our results suggest that XIAP is important in regulating apoptotic cell death of acinar and ductal epithelial cells in patients with SS.     

A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy.

In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon.     

Inhibition of experimental metastasis and cell adhesion of murine melanoma cells by chondroitin sulfate-derivatized lipid, a neoproteoglycan with anti-cell adhesion activity

Chondroitin sulfate dipalmitoylphosphatidylethanolamine (CS-PE), when immobilized onto substratum, inhibited the adhesion of B16F10 mouse melanoma cells to fibronectin-coated dishes (anti-adhesion activity). CS-PE showed the most potent anti-adhesion activity for the melanoma cells among various GAG-PEs. CS-PE also inhibited the adhesion of B16F10 cells to Matrigel and the invasion of the cells into Matrigel. In the in vivo system of experimental metastasis, administration of B16F10 cells with CS-PE into C57BL/6 mice significantly inhibited lung metastasis. The inhibition degree of CS or hyaluronic acid-PE was lower than CS-PE. CS-PE administered intravenously into mice before the injection of B16F10 cells also inhibited metastasis. Pretreatment of B16F10 cells with CS-PE caused some but a lower degree of inhibition. When CS-PE was injected intravenously into mice, more binding in the lung was found than when CS was injected. CS-PE but not CS inhibited the retention in the lung of fluorochrome-labeled B16F10 cells when injected intravenously into mice. Since there was no significant effect of CS-PE on the viability and growth of B16F10 cells, the results suggest that CS-PE immobilized onto the subendothelial matrix may prevent melanoma cells from adhering to the subendothelial substrata of lung capillaries and inhibit subsequent invasion processes of metastasis.     

Cross education of muscular strength during unilateral resistance training and detraining

Abstract. The purpose of the present study was to examine the changes in maximum voluntary isometric contraction (MVC) in the contralateral untrained limb during unilateral resistance training and detraining, and to examine the factors inducing these changes by means of electrophysiological techniques. Nine healthy males trained their plantar flexor muscles unilaterally 4 days·week^–1 for 6 weeks using 3 sets of 10–12 repetitions at 70–75% of one-repetition maximum a day, and detrained for 6 weeks. Progressive unilateral resistance training significantly (P<0.05) increased MVC, integrated electromyogram (iEMG), and voluntary activation in the trained and contralateral untrained limbs. The changes in MVC after training were significantly correlated with the changes in iEMG in both limbs. No significant changes occurred in MVC, voluntary activation, and iEMG in the contralateral limb after detraining. The changes in MVC after detraining did not correlate with the changes in voluntary activation or iEMG in either limb. Training and detraining did not alter twitch and tetanic peak torques in either limb. These results suggest that the mechanisms underlying cross education of muscular strength may be explained by central neural factors during training, but not solely so during detraining. Electronic Publication     

Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice

Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-gamma), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha), resulting in macrophage activation and recruitment of circulating monocytes to initiate chronic granuloma formation. The cytokine that mediates macrophage activation is IFN-gamma, and, like IL-12, IL-18 was shown to activate Th1 cells and induce IFN-gamma production by these cells. In order to investigate the role of IL-18 in mycobacterial infection, IL-18-deficient mice were infected with Mycobacterium tuberculosis and Mycobacterium bovis BCG Pasteur, and their capacities to control bacterial growth, granuloma formation, cytokine secretion, and NO production were examined. These mice developed marked granulomatous, but not necrotic, lesions in their lungs and spleens. Compared with the levels in wild-type mice, the splenic IFN-gamma levels were low but the IL-12 levels were normal in IL-18-deficient mice. The reduced IFN-gamma production was not secondary to reduced induction of IL-12 production. The levels of NO production by peritoneal macrophages of IL-18-deficient and wild-type mice did not differ significantly. Granulomatous lesion development by IL-18-deficient mice was inhibited significantly by treatment with exogenous recombinant IL-18. Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-gamma expression.     

Cleavage of integrin by mu-calpain during hypoxia in human endometrial cells

PROBLEM: The distribution and activation of mu-calpain and possible cleavage of integrin in human endometrial cells under hypoxic condition were investigated. METHOD OF STUDY: Human endometrial epithelial and stromal cells were subjected to hypoxia, and subsequently used for immunostaining and western blot analysis. RESULTS: The proform of mu-calpain was detected in the cytoplasm of normal cells, and displayed a substantial decrease after hypoxia. Conversely, the active form of mu-calpain was not detected in normal cells, but was abundant after hypoxia. The cytoplasmic domain of integrin beta3 was also detected in the cytoplasm of endometrial cells. Western blot analysis confirmed that both the proform of mu-calpain and the integrin beta3 cytoplasmic domain decreased during hypoxia. CONCLUSIONS: Mu-calpain is activated in human endometrial cells during hypoxia and that subsequent cleavage of the integrin beta3 cytoplasmic domain may give some adverse effects to the function of human endometrium.     

Interleukin (IL)-5 but not immunoglobulin E reconstitutes airway inflammation and airway hyperresponsiveness in IL-4-deficient mice

We studied the role of interleukin (IL)-4, IL-5, and allergen-specific immunoglobulin (Ig) E in the development of allergen-induced sensitization, airway inflammation, and airway hy-perresponsiveness (AHR). Normal, IL-4-, and IL-5-deficient C57BL/6 mice were sensitized intraperitoneally to ovalbumin (OVA) and repeatedly challenged with OVA via the airways. After allergen sensitization and airway challenge, normal and IL-5-deficient, but not IL-4-deficient, mice developed increased serum levels of total and antigen-specific IgE levels and increased IL-4 production in the lung tissue compared with nonsensitized control mice. Only normal mice showed significantly increased IL-5 production in the lung tissue and an eosinophilic infiltration of the peribronchial regions of the airways, whereas both IL-4- and IL-5-deficient mice had little or no IL-5 production and no significant eosinophilic airway inflammation. Associated with the inflammatory responses in the lung, only normal mice developed increased airway responsiveness to methacholine after sensitization and airway challenge; in both IL-4- and IL-5-deficient mice, airway responsiveness was similar to that in nonsensitized control mice. Reconstitution of sensitized, IL-4-deficient mice before allergen airway challenge with IL-5, but not with allergen-specific IgE, restored eosinophilic airway inflammation and the development of AHR. These data demonstrate the importance of IL-4 for allergen-driven airway sensitization and that IL-5, but not allergen-specific IgE, is required for development of eosinophilic airway inflammation and AHR after this mode of sensitization and challenge.     

Evaluation of DNA probes for specific detection of Vibrio cholerae O139 Bengal.

Two DNA probes, 2R1 and 2R3, prepared from a region in the chromosome specific for the lipopolysaccharide O side chains of Vibrio cholerae O139 (M.K. Waldor and J.J. Mekalanos, Lancet 343:1366, 1994) were examined for their specificity and sensitivity. Both probes did not hybridize with any strain of V. cholerae belonging to serogroups other than O139 and to any of the other species examined belonging to the family Vibrionaceae. Among the 126 strains of V. cholerae O139 examined, probe 2R1 hybridized with 125 strains while probe 2R3 hybridized with all 126 strains. Both probes were found to be highly specific and sensitive and can be used for the specific identification of V. cholerae O139.