Counseling families and patients with prion disease

It is critical to provide sufficient information and psychosocial support to people who have concerns and questions related with prion disease, especially families and patients. The processes of information provision and psychological counseling require professional skills based on theories, and people' s needs should be considered. Grief counseling is also helpful for not only those who have lost their families but also people who are facing difficult diagnosis and rapid development of illness. With regard to familial prion disease, which is about 10 % of all cases, genetic counseling is useful to discuss genetics and genetic testing with people who are at risk. As a system of peer-support, there are prion disease family support groups available in Japan and other countries.     

Liposome‐Encapsulated Hemoglobin Accelerates Bronchial Healing After Pneumonectomy in the Rat With or Without Preoperative Radiotherapy

Liposome‐encapsulated hemoglobin (LEH) has been reported to accelerate wound healing in the stomach and skin in an experimental setting. LEH was tested in bronchial anastomotic healing after radiation and pneumonectomy in the rat. Sprague‐Dawley rats (n = 61) received preoperative radiation (20 Gy) to the chest and underwent left pneumonectomy with bronchial stump closure using the Sweet method 4 days later, when they were randomized to receive intravenous infusion of LEH with high O₂ affinity (P₅₀O₂ = 17 mm Hg, 10 mL/kg, n = 32) or saline (n = 29). Additional rats (n = 18) were treated in the same way without preoperative radiation. Bronchial anastomotic healing was evaluated 2 days after surgery by determining the bursting pressure and infiltration of neutrophils, monocytes, and macrophages. Bronchial bursting pressure was elevated in the rats receiving LEH both in the unirradiated group (LEH 212 ± 78 vs. saline 135 ± 63 mm Hg, P < 0.05) and in rats with preoperative radiation (LEH 162 ± 48 vs. saline 116 ± 56 mm Hg, P < 0.01). Moreover, the percentage of rats with bursting pressure <100 mm Hg tended to be smaller in the unirradiated group (LEH 1/9 [11.1%] vs. saline 4/9 [44.4%], NS) and was significantly reduced in irradiated animals (LEH 3/32 [9.4%] vs. saline 11/29 [38%], P < 0.05). There were no morphological differences except for macrophage infiltration to the anastomotic area, which was significantly prominent in the LEH‐treated rats (P < 0.05) regardless of the presence or absence of preoperative irradiation (IR). The results suggest that LEH with high O₂ affinity may improve mechanical strength and morphological findings in bronchial anastomosis in rats regardless of the presence or absence of preoperative IR. The irradiated rats later treated with LEH had equivalent or better bronchial healing than that of saline‐treated naïve animals undergoing pneumonectomy alone.     

Immunoglobulin switch circular DNA in the mouse infected with Nippostrongylus brasiliensis: evidence for successive class switching from mu to epsilon via gamma 1

We have characterized immunoglobulin switch circular DNA in mice infected with the nematode parasite Nippostrongylus brasiliensis. Two kinds of circular DNA were identified in the lymph nodes as excision products of switch recombination of immunoglobulin heavy-chain constant region (CH) genes. One is a recombinant between C mu and C gamma 1 (gamma 1 circle), and the other is a recombinant between C gamma 1 and C epsilon (epsilon circle). In the epsilon circle, a short piece of switch mu (S mu) sequence was inserted between S epsilon and S gamma 1 sequences. The inserted S mu sequence could be a trace of the preceding switch from C mu to C gamma 1. These findings indicate that parasitic infection can induce class switch recombinations in a successive manner, first from C mu to C gamma 1, and then from C gamma 1 to C epsilon.     

Storage and transport of isolated M. tuberculosis at public and private health institutions in Japan

PURPOSE: To obtain basic data about the present practices on storage and transport of isolated M. tuberculosis at public and private health institutions in Japan. METHOD: Survey forms regarding the practices on storage and transport of isolated M. tuberculosis were distributed and collected by post-mail in January 2007 to 76 local public health institutions, 145 public health centres, and 150 public or private hospitals. The questionnaire was adopted from the guidelines proposed by the Ministry of Health, Labour, and Welfare in 2006 on storage and transport of isolated M. tuberculosis. RESULTS: The respondents of the survey were as follows: 96.1% (73/76) from local public health institutions, 93.8% (136/145) from public health centres, and 73.3% (110/150) from hospitals. In general, local public health institutions conformed well to the proposed standards, however public health centres and hospitals were not compliant to some standards. SUMMARY: Based on the survey conducted on the practice of storage and transport of isolated M. tuberculosis, certain discrepancy was found among public health centres and hospitals.     

Usefulness of measuring electrically evoked auditory brainstem responses in children with inner ear malformations during cochlear implantation

Conclusions: EABR is a reliable and effective way of objectively confirming device function and implant-responsiveness of the peripheral auditory neurons up to the level of the brainstem in cases of inner ear malformation. Objective: To investigate the usefulness of measuring the intra-operative electrically evoked compound action potential (ECAP) and electrically evoked auditory brainstem response (EABR) in patients with and without congenital inner ear anomalies during cochlear implantation. Method: Thirty-eight consecutive children (40 ears) aged 5 or younger with congenital profound hearing loss. Twenty-four (25 ears) lacked congenital inner ear anomalies. The 14 patients (15 ears) with a malformation had common cavities (four ears), incomplete partition type I (three ears), cochlea hypoplasia type III (three ears), enlarged vestibular aqueduct (four ears), and cochlear nerve canal stenosis (one ear). Main outcome measures are ECAP and EABR responses. Results: Of the 25 ears lacking any malformation, 21, three, and one showed ‘Good’, ‘Variable’, and ‘No’ ECAP responses, respectively, and 24 and one showed ‘Good’ and ‘Variable’ intra-cochlear responses, respectively. Of the 15 ears with a malformation, two showed ‘Good’ ECAP responses, nine had ‘Variable’ ECAP responses, and four showed ‘No’ ECAP responses. Moreover, five showed ‘Good’ EABR responses and 10 showed ‘Variable’ EABR responses.     

Genetic variants of ApoE and ApoER2 differentially modulate endothelial function

It is poorly understood why there is greater cardiovascular disease risk associated with the apolipoprotein E4 (apoE) allele vs. apoE3, and also greater risk with the LRP8/apolipoprotein E receptor 2 (ApoER2) variant ApoER2-R952Q. Little is known about the function of the apoE–ApoER2 tandem outside of the central nervous system. We now report that in endothelial cells apoE3 binding to ApoER2 stimulates endothelial NO synthase (eNOS) and endothelial cell migration, and it also attenuates monocyte–endothelial cell adhesion. However, apoE4 does not stimulate eNOS or endothelial cell migration or dampen cell adhesion, and alternatively it selectively antagonizes apoE3/ApoER2 actions. The contrasting endothelial actions of apoE4 vs. apoE3 require the N-terminal to C-terminal interaction in apoE4 that distinguishes it structurally from apoE3. Reconstitution experiments further reveal that ApoER2-R952Q is a loss-of-function variant of the receptor in endothelium. Carotid artery reendothelialization is decreased in ApoER2^−/− mice, and whereas adenoviral-driven apoE3 expression in wild-type mice has no effect, apoE4 impairs reendothelialization. Moreover, in a model of neointima formation invoked by carotid artery endothelial denudation, ApoER2^−/− mice display exaggerated neointima development. Thus, the apoE3/ApoER2 tandem promotes endothelial NO production, endothelial repair, and endothelial anti-inflammatory properties, and it prevents neointima formation. In contrast, apoE4 and ApoER2-R952Q display dominant-negative action and loss of function, respectively. Thus, genetic variants of apoE and ApoER2 impact cardiovascular health by differentially modulating endothelial function.Cardiovascular disease risk is modified by common genetic variants of apolipoprotein E (apoE) and its receptor apolipoprotein E receptor 2 (ApoER2), which is a member of the LDL receptor family. Compared with the most common allele apoE3, individuals with the apoE4 allele have an increased risk of atherosclerosis and coronary heart disease (1, 2). The LRP8 gene, which encodes ApoER2, is a major gene locus for premature atherosclerosis and acute myocardial infarction identified in four independent human populations. In particular, homozygous carriers of the ApoER2-R952Q variant have a twofold increased risk of these conditions (3–5). ApoER2-R952Q also has an additive effect with apoE4, with the combined genotype QQ/E4 showing a 3.9-fold greater susceptibility to cardiovascular disease (5). ApoER2 polymorphism-associated risk is independent of cholesterol levels (3–5), and although apoE4 may impact LDL abundance (2), there is also evidence that apoE4-associated risk goes well beyond changes in lipoprotein status (6–9). Whereas there is considerable understanding of the biology of the apoE–ApoER2 tandem in the central nervous system and in Alzheimer’s disease (10), the basis for the cardiovascular impact of the receptor and apoE variants remains unclear.Our prior work demonstrated that ApoER2 is expressed in endothelial cells, where it plays a critical role in the pathogenesis of the antiphospholipid syndrome (APS) (11). The receptor is enriched in caveolae/lipid rafts in which signaling molecules regulating endothelial NOS (eNOS) are compartmentalized (12, 13). We now know that in APS, antiphospholipid antibody recognition of the cell surface protein β2-GPI on endothelial cells promotes β2-GPI dimerization and interaction with the extracellular domain of ApoER2, causing the activation of PP2A and eNOS antagonism. The resulting decrease in bioavailable NO underlies APS-related thrombosis (11). However, the normal function of the receptor in endothelium, and whether and how it modulates apoE actions on endothelium, are unknown.In addition to regulating thrombogenesis, eNOS-derived NO plays a major role in cardiovascular protection via promotion of the integrity of the endothelial cell monolayer and attenuation of endothelial cell–leukocyte adhesion (13). Recognizing that eNOS enzymatic activity is both positively and negatively modulated by signaling molecules in endothelial caveolae/lipid rafts (14), to better understand the biology of ApoER2 in endothelium we hypothesized that apoE3 binding to the receptor activates eNOS. Experiments were performed in cell culture and in mice to test this hypothesis and to determine whether genetic variants in apoE or ApoER2 disrupt this process and thereby adversely impact endothelial function.