脳腫瘍におけるperivascular cellの免疫学的役割に関する研究

金沢大学医学部附属病院種々の実験動物において脳間質液や脳脊髄液が直接頚部リンパ節に流入していることが明らかにされ、頚部リンパ節は免疫学的に中枢神経系と密接な関係を持つことが示唆されている。一方、perivascular cellは免疫学的に独立した脳定住性マクロファージであり、脳脊髄液吸収経路におけるscavenging cellとして機能することが動物では見られている。本研究においてはラット移植脳腫瘍モデルを用いて、脳腫瘍移植後の脳、頚部リンパ節および体部リンパ組織における細胞性免疫反応を免疫組織化学およびフローサイトメトリーにより経時的に観察し脳腫瘍免疫における頚部リンパ節の役割について検討した。また、ヒト脳腫瘍組織においてperivascular cellは動物で見られるのと同様な役割を果たすのかどうか検討した。ラットC6神経膠腫細胞をラットの大脳基底核部に定位脳的に移植した。結果、ラットの頚部リンパ節において選択的に、脳腫瘍関連抗原の提示および認識、さらにはCD4およびCD8陽性Tリンパ球の増殖が行なわれ、これらの効果細胞が脳腫瘍内に浸潤すると考えられた。このことより、ラットにおいて頚部リンパ節は中枢神経系の局所リンパ節としての役割を果たし脳腫瘍免疫に深く関与していることが示唆された。ヒト脳腫瘍組織においてperivascular cellは免疫学的にmicrogliaやmacrophageとは独立した細胞群を形成した。さらに、MHC class II upregulationの様式より、ヒトの脳においてもperivascular cellはscavenging cellとして働くことが示唆された。Recent physiological and anatomical studies have demonstrated that a major fraction of brain interstitial and cerebrospinal fluid drains into cervical lymph nodes in a number of experimental animals. Perivascular cells form an immunophenotypically defined population that plays an important scavenging role in the perivascular fluid drainage pathways in the rat brain ; such cells may also act as antigen-presenting cells. To investigate the role of cervical lymph nodes in brain tumor immunity, temporal profiles of MHC class II molecules expression and T lymphocyte subsets in brain tumors, cervical lymph nodes and other lymphoid tissues were analyzed by immunocytochemistry and by flow cytometry. The present study also tests the hypotheses that (a) perivascular cells in human brain are distinct from microglia and haematogenous macrophages, and (b) perivascular cells within astrocytic tumors and peritumoral edematous brain tissue react in a similar way to perivascular cells in the rat brain. The results suggest that cervical lymph nodes act as regional lymph nodes in brain tumor immunity. In human brain, perivascular cells form a defined population of resident cells and are distinct from microglia, monocytes and macrophages. Upregulation of MHC class II and PGMI expression on perivascular cells in tumors and edematous brain, suggest that they play a similar scavenging role in the human brain to that seen in the rat brain.研究課題/領域番号:08671570, 研究期間(年度):1996 – 1997出典：研究課題「脳腫瘍におけるperivascular cellの免疫学的役割に関する研究」課題番号08671570（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-08671570/086715701997kenkyu_seika_hokoku_gaiyo/）を加工して作

正常圧水頭症モデルの確立

金沢大学医学部・附属病院本研究により、新しいラット水頭症モデルを開発することに成功した.Wistarラットを全身麻酔し、頚部リンパ節を手術顕微鏡下に摘出した.術後4、6、8、10、12週にラット(n=10)をパラホルムアルデヒドで灌流固定し、脳を視神経交叉のレベルで冠状にスライスし、切片を作製した。sham-operation後0、4、8、12週のラット(n=10)をコントロール群とした.冠状切片の表面積(A)と脳室腔の表面積(B)をNIH image analizing systemを用いて算出し、B/AをVentricular Index(VI)とし、脳室拡大、すなわち水頭症の指標とした.術後6週間以降、12週までのすべての群で、コントロール群と比較して統計学的に有意に(p<0.01)、VIの増加を認め、脳室拡大がみられた.組織学的には、脳室系の閉塞はなく、交通性水頭症であることが確認された.また、脳室上衣下にreactive astrocytosis、脳梁部白質にreactive microgliaの反応がみられた.以上より、このモデルは、頭蓋内に全く操作を加えずに交通性水頭症を発症させるものであり、病態を研究するのに極めて有用であると思われる.本研究の成果は、第12回国際神経病理学会(1994年10月、トロント、カナダ)のシンポジウムで発表した。研究課題/領域番号:06770148, 研究期間(年度):1994出典：研究課題「正常圧水頭症モデルの確立」課題番号06770148（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-06770148/）を加工して作

Conversation-oriented ASR with multi-look-ahead CBS architecture

During conversations, humans are capable of inferring the intention of the speaker at any point of the speech to prepare the following action promptly. Such ability is also the key for conversational systems to achieve rhythmic and natural conversation. To perform this, the automatic speech recognition (ASR) used for transcribing the speech in real-time must achieve high accuracy without delay. In streaming ASR, high accuracy is assured by attending to look-ahead frames, which leads to delay increments. To tackle this trade-off issue, we propose a multiple latency streaming ASR to achieve high accuracy with zero look-ahead. The proposed system contains two encoders that operate in parallel, where a primary encoder generates accurate outputs utilizing look-ahead frames, and the auxiliary encoder recognizes the look-ahead portion of the primary encoder without look-ahead. The proposed system is constructed based on contextual block streaming (CBS) architecture, which leverages block processing and has a high affinity for the multiple latency architecture. Various methods are also studied for architecting the system, including shifting the network to perform as different encoders; as well as generating both encoders' outputs in one encoding pass.Comment: Submitted to ICASSP202

Long-term predictive factors of the morphology based outcome in bare platinum coiled intracranial aneurysms: Evaluation by pre- and post-contrast 3D time-of-flight MR angiography

Purpose Our aim was to identify long-term predictive factors of the morphology-based outcome (MBO) of bare platinum coiled intracranial aneurysms. Materials and Methods A retrospective analysis of 96 bare platinum coiled intracranial aneurysms followed up from 1997 to 2016 using pre- and post-contrast 3D time-of-flight MR angiography (MRA) was performed. Logistic regression analysis was used to identify factors associated with a positive history of surrounding coil mass enhancement (SCME) and poor MBO. Spearman's rank correlation test was used to analyze the relationship between the initial angiographic result (IAR) class, sequential change of the SCME category, and MBO grade. Results Factors independently associated with poor MBO were incomplete IAR (OR=14.94, 95%CI: 2.46, 289.21, P=0.002) and a history of SCME (OR=4.13, 95% CI: 1.05, 18.65, P=0.043). The MBO grade strongly correlated with the IAR class (correlation coefficient [r]=0.84, P&lt;0.0001). MBO grade correlated with sequential change of the SCME category (r=0.56, P&lt;0.0001). The sequential change of the SCME category correlated with IAR class (r=0.53, P&lt;0.0001). Conclusion Although IAR and its class were strong long-term predictive factors of MBO, a history of SCME and upgrading of sequential change of SCME category were also long-term predictive factors of the MBO of bare platinum coiled intracranial aneurysms

Aneurysm clipping after partial endovascular embolization for ruptured cerebral aneurysms

The aim of this study was to investigate the advantages and disadvantages of a two-stage treatment for ruptured cerebral aneurysms; partial embolization in acute stage followed by clipping in chronic stage of subarachnoid hemorrhage. Between April 1997 and August 1999, twenty ruptured cerebral aneurysms were initially treated endovasculary using Guglielmi detachable coils in our institution. Among them, complete embolization could not be achieved in 6 lesions. For these lesions, subsequent clipping was added. The radiological and operative findings, and outcomes of these cases were retrospectively reviewed. In 1 case, rerupture occurred during the endovascular procedure. Rerupture was not observed in any cases in the postembolization period. In 2 cases, complications related to the clipping but not the endovascular procedure occurred. These complications included impaired visual acuity for unverified reasons, and memory disturbance due to sacrifice of a perforator arising from the anterior communicating artery. In 3 cases, coil extraction was needed during the clipping, because the loops of the coil extended into the residual neck. Complications related to coil extraction were not observed in these 3 cases. Acute partial embolization of ruptured aneurysm appears to be effective for the prevention of subsequent rerupture during the subacute period, in which treatment for vasospasm should be performed, and the clipping procedure. However, in the case of relatively large aneurysms, small arteries or other normal structures behind the aneurysm cannot be observed directly during surgery, because of the immovability of the embolized aneurysm. Further, complete clip closure is impossible when loops of coil herniate into the neck. In such situations, coil extraction with or without resection of the aneurysm might be necessary, and care must be taken not to damage parent artery and surrounding vessels

Significance of volume embolization ratio as a predictor of recanalization on endovascular treatment of cerebral aneurysms with Guglielmi detachable coils

The purposes of this study are, firstly, to define the relationship between volume embolization ratio (VER) and degree of angiographical occlusion in endovascular treatment with Guglielmi detachable coils, and secondly, to examine influences of neck and dome sizes of aneurysms on the VER and the angiographical treatment result, and thirdly, to determine the relationship between the VER and the recanalization of coiled aneurysms. Fifty-two aneurysms in 46 patients were examined. VER ranged 8.1-31.9% (mean 18.5%). The mean VERs of each categories based on angiographical treatment results were 23.1% in complete occlusion, 16.1% in neck remnant and 12.2% in incomplete occlusion, respectively. The VER correlated significantly with both neck and dome size, while the angiographical treatment result was only affected by neck size. Five aneurysms showed aneurysmal recanalization among followed-up 41 aneurysms. All recanalized aneurysms were large, and their VERs were in range of 10.4-17.6%. Measurement of VER is useful to estimate the degree of occlusion objectively and to predict the aneurysmal recanalization. A small aneurysms with a small neck is relatively easy to achieve high VER and angiographical complete occlusion, with the consequence of less recanalization. On the other hand, a large aneurysm is liable to recanalize due to low VER, even if there was little filling of contrast medium in the aneurysmal cavity

Prognostic value of metastin expression in human pancreatic cancer

<p>Abstract</p> <p>Background</p> <p><it>KiSS-1 </it>was identified as a metastasis-suppressing gene in melanoma cells. The <it>KiSS-1 </it>gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood.</p> <p>Methods</p> <p>We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay.</p> <p>Results</p> <p>Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%), while strong expression of GPR54 was detected in 30 tumors (56.6%). Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047). Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04). Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02). Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1–4.7; p = 0.03), and the patients with a high plasma metastin level (n = 6) did not die after surgical resection.</p> <p>Conclusion</p> <p>Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.</p

Influenza A (H5N1) Viruses from Pigs, Indonesia

TOC summary: Pigs may serve as intermediate hosts in which this avian virus can adapt to mammals

Molecular epidemiology of avian influenza viruses circulating among healthy poultry flocks in farms in northern Vietnam.

Repeated epizootics of highly pathogenic avian influenza (HPAI) virus subtype H5N1 were reported from 2003 to 2005 among poultry in Vietnam. More than 200 million birds were killed to control the spread of the disease. Human cases of H5N1 infection have been sporadically reported in an area where repeated H5N1 outbreaks among birds had occurred. Subtype H5N1 strains are established as endemic among poultry in Vietnam, however, insights into how avian influenza viruses including the H5N1 subtype are maintained in endemic areas is not clear. In order to determine the prevalence of different avian influenza viruses (AIVs), including H5N1 circulating among poultry in northern Vietnam, surveillance was conducted during the years 2006-2009. A subtype H5N1 strain was isolated from an apparently healthy duck reared on a farm in northern Vietnam in 2008 and was identified as an HPAI. Although only one H5N1 virus was isolated, it supports the view that healthy domestic ducks play a pivotal role in maintaining and transmitting H5N1 viruses which cause disease outbreaks in northern Vietnam. In addition, a total of 26 AIVs with low pathogenicity were isolated from poultry and phylogenetic analysis of all the eight gene segments revealed their diverse genetical backgrounds, implying that reassortments have occurred frequently among strains in northern Vietnam. It is, therefore, important to monitor the prevalence of influenza viruses among healthy poultry between epidemics in an area where AIVs are endemic

Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022