Impaired CD4⁺ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination

高齢者のT細胞応答は立ち上がりが遅く収束は早い --新型コロナワクチン接種機会を活用した免疫応答の個人差・年齢差の解明--. 京都大学プレスリリース. 2023-01-13.T-Cell Responses in the Elderly Rise Slowly and Contract Quickly --Learning About Individual and Age Differences in Immune Response From COVID-19 Vaccinations--. 京都大学プレスリリース. 2023-01-13.Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥65 years) had fewer vaccine-induced spike-specific CD4⁺ T cells including CXCR3⁺ circulating follicular helper T cells and the TH1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after the second dose, compared with younger adults. Moreover, spike-specific TH1 cells in older adults expressed higher levels of programmed cell death protein 1, a negative regulator of T cell activation, which was associated with low spike-specific CD8⁺ T cell responses. Thus, an inefficient CD4⁺ T cell response after the first dose may reduce the production of helper T cytokines, even after the second dose, thereby lowering humoral and cellular immunity and reducing systemic reactogenicity. Therefore, enhancing CD4⁺ T cell response following the first dose is key to improving vaccine efficacy in older adults

A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting

During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the 125I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the modulation of energy homeostasis

Effects of clozapine and N-desmethylclozapine on synaptic transmission at hippocampal inhibitory and excitatory synapses

Clozapine is the first atypical antipsychotic, and improves positive and negative symptoms of many patients with schizophrenia resistant to treatment with other antipsychotic agents. Clozapine induces minimal extrapyramidal side effects, but is more often associated with seizures. A large number of studies have been conducted to elucidate pharmacological profiles of clozapine and its major active metabolite, N-desmethylclozapine (NDMC). However, there are only a limited number of electrophysiological studies examining their effects on synaptic transmission. In this study, we examined effects of clozapine and NDMC on synaptic transmission by measuring inhibitory and excitatory postsynaptic currents in rat cultured hippocampal neurons. We found that clozapine and NDMC have qualitatively similar actions. They depressed the inhibitory transmission at 1-30 μM, and the excitatory transmission at 30 μM, the former being much more sensitive. The depression of IPSCs by 30 μM of these drugs was associated with an increase in the paired-pulse ratio. The GABA-induced currents were suppressed by these drugs, but less sensitive than IPSCs. The AMPA-induced currents were slightly potentiated by these drugs at 30 μM. At 30 μM, clozapine and NDMC slightly suppressed Ca2+ and Na+ channels. These results strongly suggest that clozapine and NMDC depress the inhibitory synaptic transmission mainly by antagonizing postsynaptic GABAA receptors, but at higher concentrations additionally by acting on presynaptic site, possibly in part through inhibition of presynaptic Ca2+ and Na+ channels. Preferential depression of inhibitory synaptic transmission by clozapine and NDMC might contribute to therapeutic actions and/or side-effects of clozapine. © 2011 Elsevier B.V. All rights reserved

大量調理機器を用いた湿式加熱が野菜類の性状に与える影響

食品に適した大量調理機器を選択し、最適な調理条件を設定することで、嗜好・品質特性を高め、給食の調理における効率化および標準化に繋げる基礎資料を得ることを目的とした。大量調理機器は、鍋、スチコン、バリオを用い、湿式加熱による食品の調理特性を検討した。スチコンが最も加熱時間を要した。スチコン加熱は、湿式加熱のうち蒸気による凝縮熱伝導と熱風蒸し操作であるため、食材の表面から内部へ温度の上昇は緩慢となり、均一な加熱となることで野菜の糖度は高かった。バリオ加熱は、加熱初期の温度上昇が早く、デンプンの糊化が急速に進み、じゃがいもではビタミンＣが失われにくかったが、にんじんでは高温で加熱される時間が長くなりビタミンＣの分解が進んだ

Effect of anakinra on arthropathy in CINCA/NOMID syndrome

CINCA/NOMID is an autoinflammatory disorder characterized by the triad of neonatal onset of cutaneous symptoms, chronic meningitis, and recurrent fever and it presents with distinctive osteoarthropathy, synovitis mainly of the large joints and overgrowth of epimetaphyseal cartilage, particularly of the long bones. The cartilage overgrowth eventually causes osseous overgrowth and deformity that persists beyond skeletal maturity and leads to limb length discrepancy, joint contracture, and early degenerative arthropathy. Autoinflammation in CAPS/NOMID has been proven to derive from excessive release of interleukin-1 (IL-1). It has been well documented that the IL-1 receptor antagonist anakinra (Kineret(R)) helps mitigate systemic inflammation in the disorder. However, a general consensus has not been reached on its beneficial effect on osteoarthropathy. The case of a girl with CINCA/NOMID syndrome who showed dramatic improvement of osteoarthropathy after anakinra treatment is reported. A 4-year-old girl suffered at the age of 10 months from a generalized urticarial skin lesion with recurrent episodes of fever and growth disorder. Blood examination revealed persistent massive neutrophilia, anemia and intense acute phase response. She manifested knee joint swelling with limited ROM when she was 20 months old and was diagnosed as being CINCA/NOMID based on characteristic findings of radiograph despite negative CIAS1 mutation. Radiological examination demonstrated metaphyseal fraying and cupping and widening of the growth plate in the distal femur. MR imaging showed mottled gadolinium enhancement at the chondrosseous junction. Neither significant joint effusion nor synovitis was identified. At 2 years and 7 months of age, anakinra, 2 mg/kg/day given by regular daily subcutaneous injections, was started. A few days after the initiation of the treatment, her clinical symptoms and laboratory findings of active inflammation were promptly alleviated. She was not able to walk unaided prior to the treatment, but she walked independently 1 month after the treatment. Follow-up radiographs and MR imaging showed that growth plate widening and gadolinium enhancement at the chondrosseous junction were less conspicuous. Furthermore, longitudinal growth of the femur and tibia was identified during 20 months of observation

ダイジョ DIOSCOREA ALATA L. ノ セイチョウ カテイ ニ オケル ケイヨウ コンケイ ノ ガンスイリツ ノ ヘンカ

関東地域で収穫可能なダイジョの1品種を用いて,地下部の塊茎のみならず塊茎デンプンのソースである地上部の茎葉における生長過程の含水率の変化を調べた。その結果,生長時期の推移に伴う茎葉含水率と塊茎の含水率の変化には顕著な差異が認められた。すなわち,茎葉の含水率は生長期間の大半を通して緩やかに減少するが,塊茎の含水率は肥大初期に急速に減少し,その後横這いから緩やかな減少傾向を示した。塊茎では,肥大初期にはその組織が主に若い柔組織細胞で構成されているため水分含量が高いが,肥大が旺盛になるにつれてデンプンの蓄積が進み,それに伴って含水率が低下したものと推測された。このことから,ダイジョの塊茎の含水率の推移は,品種の塊茎成熟度の特性を評価する有効な方法となる可能性が考えられた。Greater yam (Dioscorea alata L.) is one of the yams and still a staple food tuber crop in parts of developing and self-sustaining agriculture in tropical Asia. Yam tuber contains high moisture content, which changes during growth stages. The present research investigated changes of moisture content in tubers and tops of an early cultivar, which is able to riper in the Kanto Metropolitan area. According to the results, remarkable differences were observed in changes of moisture content of tubers and tops of growing plants. Moisture content of tops gradually decreased throughout whole growth stages, while that of tubers rapidly decreased at the early stage of growth and thereafter tended to reduce gradually. In the earlier stage of growth, tubers consisting of young parenchyma seems to maintain higher moisture content. But as the growth of tuber progresses, starch is accumulated and moisture content of the tuber is thought to be reduced. From these results, the changes of moisture content in tubers will be an useful indicator for tuber maturity

ダイジョ DIOSCOREA ALATA L. ノ セイチョウ カテイ ニ オケル ケイヨウ コンケイ ノ ガンスイリツ ノ ヘンカ

関東地域で収穫可能なダイジョの1品種を用いて,地下部の塊茎のみならず塊茎デンプンのソースである地上部の茎葉における生長過程の含水率の変化を調べた。その結果,生長時期の推移に伴う茎葉含水率と塊茎の含水率の変化には顕著な差異が認められた。すなわち,茎葉の含水率は生長期間の大半を通して緩やかに減少するが,塊茎の含水率は肥大初期に急速に減少し,その後横這いから緩やかな減少傾向を示した。塊茎では,肥大初期にはその組織が主に若い柔組織細胞で構成されているため水分含量が高いが,肥大が旺盛になるにつれてデンプンの蓄積が進み,それに伴って含水率が低下したものと推測された。このことから,ダイジョの塊茎の含水率の推移は,品種の塊茎成熟度の特性を評価する有効な方法となる可能性が考えられた。Greater yam (Dioscorea alata L.) is one of the yams and still a staple food tuber crop in parts of developing and self-sustaining agriculture in tropical Asia. Yam tuber contains high moisture content, which changes during growth stages. The present research investigated changes of moisture content in tubers and tops of an early cultivar, which is able to riper in the Kanto Metropolitan area. According to the results, remarkable differences were observed in changes of moisture content of tubers and tops of growing plants. Moisture content of tops gradually decreased throughout whole growth stages, while that of tubers rapidly decreased at the early stage of growth and thereafter tended to reduce gradually. In the earlier stage of growth, tubers consisting of young parenchyma seems to maintain higher moisture content. But as the growth of tuber progresses, starch is accumulated and moisture content of the tuber is thought to be reduced. From these results, the changes of moisture content in tubers will be an useful indicator for tuber maturity