Ameloblastoma cell lines derived from different subtypes demonstrate distinct developmental patterns in a novel animal experimental model

Objective: Ameloblastoma is a representative odontogenic tumor comprising several characteristic invasive forms, and its pathophysiology has not been sufficiently elucidated. A stable animal experimental model using immortalized cell lines is crucial to explain the factors causing differences among the subtypes of ameloblastoma, but this model has not yet been disclosed. In this study, a novel animal experimental model has been established, using immortalized human ameloblastoma-derived cell lines. Methodology: Ameloblastoma cells suspended in Matrigel were subcutaneously transplanted into the heads of immunodeficient mice. Two immortalized human ameloblastoma cell lines were used: AM-1 cells derived from the plexiform type and AM-3 cells derived from the follicular type. The tissues were evaluated histologically 30, 60, and 90 days after transplantation. Results: Tumor masses formed in all transplanted mice. In addition, the tumors formed in each group transplanted with different ameloblastoma cells were histologically distinct: the tumors in the group transplanted with AM-1 cells were similar to the plexiform type, and those in the group transplanted with AM-3-cells were similar to the follicular type. Conclusions: A novel, stable animal experimental model of ameloblastoma was established using two cell lines derived from different subtypes of the tumor. This model can help clarify its pathophysiology and hasten the development of new ameloblastoma treatment strategies

Acute Polyradiculoneuropathy Associated With Salmonella Gastroenteritis

We reported a case of acute polyradiculoneuropathy associated with Salmonella gastroenteritis. A68-year-oldman developed progressive motor weakness and areflexia following the febrile illness and diarrhea caused by a strain of Salmonella species O8 group. He showed a rapid and complete recovery from the illness. This is the first report in which Salmonella gastroenteritis might be etiologically related to an acute polyradiculoneuropathy

Immobilization-induced hypersensitivity associated with spinal cord sensitization during cast immobilization and after cast removal in rats

This study examined mechanical and thermal hypersensitivity in the rat hind paw during cast immobilization of the hind limbs for 4 or 8 weeks and following cast removal. Blood flow, skin temperature, and volume of the rat hind paw were assessed in order to determine peripheral circulation of the hind limbs. Sensitization was analyzed by measuring the expression of the calcitonin gene-related peptide (CGRP) in the spinal dorsal horn following cast immobilization. Two weeks post immobilization, mechanical and thermal sensitivities increased significantly in all rats; however, peripheral circulation was not affected by immobilization. Cast immobilization for 8 weeks induced more serious hypersensitivity compared to cast immobilization for 4 weeks. Moreover, CGRP expression in the deeper lamina layer of the spinal dorsal horn increased in the rats immobilized for 8 weeks but not in those immobilized for 4 weeks. These findings suggest that immobilization-induced hypersensitivity develops during the immobilization period without affecting peripheral circulation. Our results also highlight the possibility that prolonged immobilization induces central sensitization in the spinal cord.The final publication is available at link.springer.co

Effects of continuous passive motion on the expression of membrane type 1-matrix metalloproteinase in rat immobilized muscles

We examined the effects of continuous passive motion（ CPM） on membrane type 1-matrix metalloproteinase（ MT1-MMP） expression in rat immobilized muscles. Eight-week-old male Wister rats were used for each of two trials, one with 2 weeks, and another one with 4 weeks of immobilization with/without CPM. In each trial, rats were immobilized（ immobilization group）, and immobilized and simultaneously given CPM （CPM group）. The soleus muscle of each rat was evaluated by gelatin zymography, western blotting and reverse transcription-polymerase chain reaction（ RT-PCR）. Gelatin zymography revealed a greater level of gelatinase activity in the extract of the muscles of the immobilization group than in those of the control and CPM group. The expressions of matrix metalloproteinase 2 （MMP-2） and MT1-MMP mRNA in the muscle extract of the immobilization group were also greater than those in the control and CPM group. Our results suggested that joint immobilization induces expression of MT1-MMP, a cleavage enzyme of MMP-2 in muscles, resulting in muscular degeneration, and that CPM can prevent these changes

Antiphospholipid Antibodies in Patients with Myasthenia Gravis

We measured antiphospholipid antibodies in sera from 94 patients with myasthenia gravis (MG). We found lgG aCL in 14/94 (14.9 % )lgM aCL in 6/94 (6.4 %) and LA in 4/56 (7.1 %) patients with MG. As a whole 21 of 94 (22.3 % ) patients with MG had some aPL. There was no correlation between the presence of aPL and the severity of MGthe presence of hyperplasia of thymustiter of the antiacetylcholine receptor antibodies or anti-single stranded DNA antibodies. Though the percentage of malignant thymoma with aPL were higher than that of malignant thymoma without aPLwe thought that aPL were not the specific antibody in malignant thymoma. In MGaPL did not play as the aCL syndrome and seemed to be non-specific antibodies

Low-level laser irradiation promotes the recovery of atrophied gastrocnemius skeletal muscle in rats.

Low-level laser (LLL) irradiation promotes proliferation of muscle satellite cells, angiogenesis and expression of growth factors. Satellite cells, angiogenesis and growth factors play important roles in the regeneration of muscle. The objective of this study was to examine the effect of LLL irradiation on rat gastrocnemius muscle recovering from disuse muscle atrophy. Eight-week-old rats were subjected to hindlimb suspension for 2 weeks, after which they were released and recovered. During the recovery period, rats underwent daily LLL irradiation (Ga-Al-As laser; 830 nm; 60 mW; total, 180 s) to the right gastrocnemius muscle through the skin. The untreated left gastrocnemius muscle served as the control. In conjunction with LLL irradiation, 5-bromo-2-deoxyuridine (BrdU) was injected subcutaneously to label the nuclei of proliferating cells. After 2 weeks, myofibre diameters of irradiated muscle increased in comparison with those of untreated muscle, but did not recover back to normal levels. Additionally, in the superficial region of the irradiated muscle, the number of capillaries and fibroblast growth factor levels exhibited significant elevation relative to those of untreated muscle. In the deep region of irradiated muscle, BrdU-positive nuclei of satellite cells and/or myofibres increased significantly relative to those of the untreated muscle. The results of this study suggest that LLL irradiation can promote recovery from disuse muscle atrophy in association with proliferation of satellite cells and angiogenesis.The definitive version is available at www.blackwell-synergy.com and www.expphysiol.org

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target