Heterosynaptic expression of depolarization-induced suppression of inhibition (DSI) in rat hippocampal cultures

金沢大学大学院医学系研究科保健学専攻Depolarization-induced suppression of inhibition (DSI) is a transient suppression of the inhibitory synaptic transmission, observed in the hippocampus and the cerebellum, upon postsynaptic depolarization. Using rat hippocampal cultures, we examined whether DSI is confined to the inhibitory synapses on the depolarized neuron or, if DSI can spread to those on neighboring non-depolarized neurons. Whole-cell recordings were performed in 108 neuronal pairs with the following synaptic responses. Stimulation of one neuron evoked the inhibitory autaptic currents (IACs) recurrently in that neuron and also elicited the inhibitory postsynaptic currents (IPSCs) orthodromically in the other neuron. In 38 of 108 pairs, the postsynaptic depolarization caused transient suppression of IPSCs (homosynaptic DSI). In 11 of the 38 pairs exhibiting the homosynaptic DSI, the depolarization also induced suppression of IACs (heterosynaptic DSI). The heterosynaptic DSI, like the homosynaptic DSI, depended on depolarizing pulse duration and was blocked by a phorbol ester. These results suggest that DSI can spread to the synapses on a neighboring non-depolarized neuron in rat hippocampal cultures

甲状腺癌リンパ節転移との鑑別が困難であった頸部神経鞘腫の１例

A female patient in her 60s visited her previous doctor because of a right cervical mass that exist for 7 years and gradually increased in size. As she was suspected of cervical lymph node metastasis of thyroid cancer, she was referred to our hospital. At the initial visit, a 5-cm right cervical mass and enlargement of the right lobe of the thyroid gland were observed. Fine needle aspiration cytology was performed on both, but no malignant findings were observed. To confirm the diagnosis and improve the patient’s appearance, a right lobectomy of the thyroid gland and resection of the right cervical mass were performed. A rapid intraoperative histological examination of the cervical mass revealed a schwannoma. The right thyroid tumor was diagnosed as follicular adenoma. Her postoperative course was good, and after several years of follow-up, patient consultation was terminated. Neurolemmoma is a benign tumor arising from Schwann cells in the nerve sheath, and it occurs frequently throughout the head and neck region, with 25%-45% of cases occurring in this region. Cervical schwannomas are characterized by irritation of the vagus nerve, brachial plexus, and sympathetic nerves. However, many patients present with only a painless neck mass, as in this case. Although the mass can be diagnosed by puncture aspiration cytology in some cases, sufficient specimens are often unavailable, and the diagnosis is made preoperatively in about half of all cases. Differential diagnoses of an anterior cervical mass include malignant lymphoma, cervical lymph node metastases of malignant tumors, submandibular gland tumors, and tuberculous lymph node metastases. In this patient, we also considered lymph node metastasis of thyroid cancer. However, a histological examination did not detect malignancy in either the thyroid gland or neck mass, and we considered that the thyroid follicular adenoma and the cervical schwannoma occurred independently. We report our experience of cervical schwannoma combined with thyroid tumor which was suspected of lymph node metastasis of thyroid cancer

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

AYA-generation lung cancer in a patient presenting with spontaneous pneumothorax : A case report

Background : Surgery for young patients（i.e., <２０ years of age）with early-stage lung cancer is extremely rare. To the best of our knowledge, only a few cases of lung cancer initially presented with spontaneous pneumothorax. Here, we report a case of AYA（adolescent and young adult）-generation lung cancer in a patient who presented with spontaneous pneumothorax. Case : An １８-year-old male was admitted to our hospital for new-onset left pneumothorax. Chest computed tomography incidentally revealed a pure ground-glass nodule（pGGN）in the left lower lobe（S８）with a bulla near the nodule. While chest tube drainage improved his condition, pneumothorax recurred two weeks later, prompting surgical for video-assisted partial resection of the left lung. Intraoperative findings showed that the bulla and nodule were distant. Histopathologic analysis was consistent with a diagnosis of adenocarcinoma in situ with a bleb. Conclusion : This study highlights the importance of considering the possibility of lung cancer in patients with irregular chest shadows, even those less than２０years of age. Computed tomography plays an important role in the diagnosis of lung cancer in patients with spontaneous pneumothorax

中毒性多結節性甲状腺腫

A woman in her 80s who was diagnosed with multiple thyroid tumors and subclinical hyperthyroidism 1 year previously was referred to our outpatient clinic due to deteriorated hyperthyroidism. She was diagnosed with dilated cardiomyopathy 4 years ago. Her cardiac function has been stabilized with medical conservative treatment. Blood autoantibody levels, including TSAb and TRAb, were within normal ranges. Ultrasonography and computed tomography revealed multiple tumor lesions in both thyroid lobes. Tc-99m scintigraphy showed multiple hot nodules in both thyroid lobes. Because the patient’s thyroid function had deteriorated, we selected surgical total thyroidectomy rather than radioisotope treatment as the most appropriate treatment. Histopathological examination of the resected specimen demonstrated multiple nodular lesions with a maximum size of 23 mm and a microlesion of papillary carcinoma 2 mm in diameter in the thyroid. A few days after surgery, thyroid function blood levels declined to the normal range

横隔膜縫縮術により著明な呼吸機能改善を得た横隔膜弛緩症の１例

A woman in her seventies visited the hospital two months after experiencing dyspnea on exertion. After chest radiographs and computed tomography of the chest showed elevation of the right diaphragm, she was referred to our department for further examination and management. Respiratory function tests revealed restricted ventilatory impairment with a vital capacity （VC） of 1.28 L and a %VC of 54.0%. Since there was no evidence of organic disease causing diaphragmatic paralysis and a slight movement of the diaphragm, we diagnosed the patient with right diaphragmatic eventration. Since she was symptomatic, we decided to treat her surgically. She was operated under general anesthesia, left lateral recumbency, single lung ventilation, and lateral open chest between the eighth ribs. The relaxed diaphragm was elevated, horizontal mattress sutures were placed. Considering the risk of diaphragm rupture, a 2-mm thick Gore-Tex sheet was fixed to the chest wall and diaphragm in a tent-like manner. The patient was discharged from the hospital on the fourth postoperative day. A chest radiograph postoperatively showed good diaphragmatic movement. Respiratory function tests also showed marked improvement, with a VC of 2.00 L and %VC of 86.3%. The patient’s subjective symptoms have disappeared, and she is currently outpatient observation

Clinical outcome of patients with recurrent or refractory localized Ewing's sarcoma family of tumors: A retrospective report from the Japan Ewing Sarcoma Study Group

[Background] Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. [Aim] This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. [Methods and results] Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed. The 5-year OS rate of the entire cohort was 48.3% (95% confidence interval, 29.9%-64.5%). Multivariate analysis of OS identified time to relapse or progression, but not stem cell transplantation (SCT), as the sole independent risk factor (hazard ratio, 35.8; P = .002). Among 31 patients who received salvage chemotherapy before local treatment, 21 received chemotherapy regimens that are not conventionally used for newly diagnosed ESFT. The objective response rate to first-line salvage chemotherapy was 55.2% in the 29 evaluable patients. Time to relapse or progression was significantly associated with response to first-line salvage chemotherapy (P = .006). [Conclusions] The present study fails to demonstrate significant clinical benefit of SCT for recurrent or refractory localized ESFT. Recently established chemotherapy regimens may increase the survival rate of patients with recurrent or refractory localized ESFT while attenuating the beneficial effect of SCT

Identification of a novel uterine leiomyoma GWAS locus in a Japanese population

Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10−25 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma