Changes in presynaptic protein NACP/α-synuclein in an ischemic gerbil hippocampus

We observed temporal changes in NACP (precursor protein of non-Aβ component of Alzheimer's disease amyloid), a presynaptic protein a.k.a. α-synuclein, in the hippocampus after 5 min ischemia. Intense NACP immunoreactivity was seen transiently around cerebral blood vessels in the CA1 subfield on day 4, and NACP-positive unusual tubal and chain-like structures developed on month 6. We suggest that the changes in NACP may play an important role in the ischemic pathogenesis.     

Usefulness of oral wash specimens for detecting Chlamydia trachomatis from high-risk groups in Japan

Orogenital sex is recognized as a route for the transmission of Chlamydia trachomatis (CT) which thus causes male chlamydial urethritis. Patients with a pharyngeal CT infection have no gross lesions, but CT was tested by pharyngeal swabs. In this study, the usefulness of oral wash specimens for detecting CT was compared to that of swab specimens. In addition, oral wash specimens were also used to screen for CT pharyngeal infection. Eighteen female commercial sex workers in whom CT was detected from pharyngeal swabs were re-examined using both methods. The positive rate for CT was 44% by swabs and 61% by oral wash specimens. Forty-eight male students with CT-positive urine were also screened for pharyngeal CT infection. The positive rates were 6% by swabs and 10% by oral wash specimens. Our findings therefore indicate that oral wash specimens more effectively detected pharyngeal CT infection than pharyngeal swabs.     

Effects of MK-801 and Pentobarbital on Cholinergic Terminal Damage and Delayed Neuronal Death in the Ischemic Gerbil Hippocampus

The present study covers both the effects of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, and pentobarbital on cholinergic terminal damage and delayed neuronal death (DND) in ischemic gerbil. To study the above effects, in vivo microdialysis, immunohistochemical, and morphological techniques were used. MK-801 (3 mg/kg) or pentobarbital (50 mg/kg) were injected intraperitoneally 1 h or 30 min before 5 min ischemia, respectively. Each estimation was then carried out 4, 7, or 14 days after ischemia. Ischemia induced a significant decrease in acetylcholine (ACh) release and a disappearance of choline acetyltransferase (ChAT)-immunoreactivity in the hippocampus in addition to inducing DND. On day 4, MK-801 protected ischemia-induced DND in the hippocampal CA1 subfield. However, MK-801 had no effect against the decrease in ACh release in spite of protection of the decrease in ChAT-immunoreactivity. On day 7 and 14, no protective effect of MK-801 was observed in all estimations. It became clear that the mechanism of cholinergic terminal dysfunction is different from that involved in pyramidal cell death, i.e., excitative neurotoxicity induced by overabundant extracellular glutamate. Pentobarbital also provided protection against DND. However, protective effects of pentobarbital on the decrease in ACh release and the low ChAT-immunoreactivity were incomplete. Our present study indicated a limitation on the efficacy of NMDA receptor antagonist and barbiturate against cerebral ischemia.     

Cerebral oxygenation and hemodynamics during hyperventilation and sleep in patients with Rett syndrome

We continuously monitored changes in cerebral oxygenation and hemodynamics in the frontal lobes of six patients with Rett syndrome during the awake state, which is associated with hyperventilation (HV) and breath-holding (BH), and during sleep by near-infrared spectroscopy. We also monitored three adult volunteers during simulated episodes of HV and BH. In patients with Rett syndrome, the oxygenated hemoglobin (HbO₂) and total hemoglobin (HbT) decreased significantly during HV and BH in the awake state compared with the sleep state. The HbO₂ and HbT decreased gradually in adult volunteers in response to prolonged episodes of HV and BH. Further studies are required to investigate the relationship, if any, between the discovered continuous decreases in HbO₂ and HbT during the awake state and the brain damage seen in patients with Rett syndrome.     

Hev b 6.02 Is the Most Important Allergen in Health Care Workers Sensitized Occupationally by Natural Rubber Latex Gloves

BackgroundNatural rubber latex (NRL) allergy is a common occupational disease in health care workers (HCW). However, few reports have compared the major allergen of HCWs to those in gloves that are routinely used in the hospital. The aim of this study was to evaluate the major NRL allergens in gloves used by HCWs.MethodsWe studied 20 HCWs who were suspected to have latex allergy (LA). We performed a skin prick test (SPT) using NRL allergens. Serological testing was performed using the ImmunoCAP?. The total amount of protein and the antigenic protein concentrations extracted from NRL gloves were measured. Four different types of FITkit? were used to measure the concentrations of Hev b 1, 3, 5, and 6.02 in the gloves.ResultsA SPT using NRL extract identified 14 cases with positive reactions. The sensitivity and specificity of the SPT scores to the NRL glove extract were 100%. The sensitivity of latex specific IgE was 100% but the specificity was 14.2%. The sensitivity and specificity of rHev b 6.02 specific IgE were 100% in the LA group. The total amounts of protein from the medical gloves for surgery and examination were 265 μg/g and 95 μg/g, respectively. The antigenic protein concentrations in the gloves were 24.9 μg/g and 1.0 μg/g, respectively. The total amounts of the specific four allergens in the NRL gloves were 2.18 μg/g and 0.45 μg/g, respectively.ConclusionsWe concluded that the main allergen of HCWs who have been sensitized occupationally by NRL gloves was Hev b 6.02.     

Components of diesel exhaust particles diversely enhance a variety of respiratory diseases related to infection or allergy: extracted organic chemicals and the residual particles after extraction differently affect respiratory diseases

Experimental and epidemiological studies have reported that diesel exhaust particles (DEP) can aggravate a variety of respiratory diseases including infection or allergy. However, the responsible components in DEP for the enhancement have not been identified. The present review demonstrates the different effects of the components of DEP on the respiratory diseases related to infection or allergy. We exposed mice to the organic chemicals (DEP-OC) and the residual carbonaceous nuclei (washed DEP) derived from DEP in the presence or absence of bacterial endotoxin (lipopolysaccharide: LPS) or allergen. In our first series of experiments, washed DEP combined with LPS synergistically exacerbated lung injury, which was concomitant with the enhanced lung expression of proinflammatory cytokines and chemokines, whereas DEP-OC combined with LPS did not. In contrast, our second series of experiments showed that DEP-OC, rather than washed DEP, enhanced allergen-related eosinophilic inflammation and proliferation of goblet cells in the airway epithelium, which was paralleled by the enhanced lung expression of eotaxin and interleukin-5. However, washed DEP with ovalbmin showed less change and increased the lung expression of interferon-gamma. It is suggested that DEP components diversely affect various types of respiratory diseases, while the combination of organic chemicals and carbonaceous nuclei (whole DEP) mostly aggravate respiratory diseases.     

Effects of components derived from diesel exhaust particles on lung physiology related to antigen

Our previous study has shown that diesel exhaust particles (DEP), main constituents in ambient particulate matters (PM), enhance airway hyperresponsivness in a murine model of allergic asthma (Takano et al., 1998). However, it remains unknown which components in DEP are responsible for the enhancement. The present study investigated the effects of repeated pulmonary exposure to DEP components (extracted organic chemicals in DEP; DEP-OC, carbonaceous nuclei of DEP after extraction; washed DEP) on lung physiology in the presence or absence of antigen. ICR mice were divided into six experimental groups. Vehicle, DEP components, ovalbumin (OVA), or DEP components plus OVA was administered intratrachally for 6 weeks. Twenty-four hr after the last instillation, cholinergic lung reactivity was examined. DEP components alone did not induce any facilitation of lung function as compared to vehicle alone. The values of total respiratory system resistance (R), elastance (E), Newtonian resistance (R(n)), tissue damping (G), and tissue elastance (H) were higher and the value of compliance (C) was lower in the OVA or the DEP component + OVA groups than in the vehicle group. In particular, the hyperreactivity was most prominent in the washed DEP + OVA group. The values in the DEP-OC + OVA group were not significantly different from those in the OVA group. These data suggest that carboneous component in DEP, rather than organic chemical one, can be attributable to the enhancement of lung hyperresponsiveness in allergic asthma.     

The NR4A nuclear receptor family in eosinophils

It is well-known that many members of the family of nuclear receptors have been implicated in human diseases, and metabolic disorders in particular. The NR4A nuclear receptor family consists of three members, Nur77, Nurr1, and NOR1. All of these are orphan receptors, and Nur77 and NOR1 exert possible pathological roles in immune diseases through the modulation of leukocyte functions. CD30 stimulation, which induces eosinophil-specific apoptosis, markedly enhances expression of Nur77 and NOR1 in eosinophils. This suggests the possibility of pharmacological modulation of Nur77- or NOR1-specific apoptotic pathways via receptor-dependent transactivation. In this review, we discuss treatment of allergic diseases by low molecular weight compounds acting through the NR4A receptor family to cause eosinophil apoptosis. NR4A nuclear receptor genes were selected following comprehensive analysis of differentially expressed genes in eosinophils of atopic dermatitis patients compared with healthy volunteers.     

Hyperexpression of FcgammaRI and Toll-like receptor 4 in the intestinal mast cells of Crohn's disease patients

We previously reported that human mast cells (MCs) express high affinity IgG receptor (FcgammaRI) and Toll-like receptor 4 (TLR4) in response to interferon (IFN)-gamma in vitro. The number of MCs is known to increase in Crohn's disease (CD) and ulcerative colitis (UC). We aimed to examine the expression and function of the receptors in these diseases by immunohistochemistry of the colonic mucosae and by in vitro experiments. The density of MCs expressing FcgammaRI, TLR4, or both proteins was significantly higher in CD than in UC or control samples. The density of TNF-alpha(+) MCs expressing FcgammaRI or TLR4 was significantly higher in CD than in control samples. LPS and IgG1 cross-linking synergistically induced a high level of TNF-alpha production in IFN-gamma-treated human MCs. Hyperexpression of FcgammaRI and TLR4 on MCs was related to the high frequency of TNF-alpha expression in CD, suggesting the activation of MCs via these receptors in vivo.