アキレス腱付着部症に対しアキレス腱モーメントアーム長が及ぼす影響

Insertional Achilles tendinopathy (IAT) is caused by traction force of the tendon. The effectiveness of the suture bridge technique in correcting it is unknown. We examined the moment arm in patients with IAT before and after surgery using the suture bridge technique, in comparison to that of healthy individuals. We hypothesized that the suture bridge method influences the moment arm length. An IAT group comprising 10 feet belonging to 8 patients requiring surgical treatment for IAT were followed up postoperatively and compared with a control group comprising 15 feet of 15 healthy individuals with no ankle complaints or history of trauma or surgery. The ratio of the moment arm (MA) length/foot length was found to be statistically significant between the control group, the IAT group preoperatively and the IAT group postoperatively (p < 0.01). Despite no significant difference in the force between the control and preoperative IAT groups, a significantly higher force to the Achilles tendon was observed in the IAT group postoperatively compared to the other groups (p < 0.05). This study demonstrates that a long moment arm may be one of the causes of IAT, and the suture bridge technique may reduce the Achilles tendon moment arm.博士（医学）・甲第845号・令和4年9月28日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

足関節運動とアキレス腱の緊張がアキレス腱と踵骨間の接触圧に与える影響

Impingement between the Achilles tendon and the posterosuperior prominence of the calcaneus is considered to be a cause of insertional Achilles tendinopathy. The corresponding treatment intends to reduce tensile stress from calf muscles and avoid hyper-dorsiflexion of the ankle joint for decreasing the contact pressure; however, no study has reported on whether these treatments can decrease impingement. Thus, this study investigated the hypothesis that the tensile stress of the Achilles tendon and ankle motion affect the contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus. Six fresh-frozen cadaveric lower leg specimens were procured. Each specimen was set to a custom foot-loading frame and loaded with a ground reaction force of 40 N and a tensile load of 70 N along the Achilles tendon. The contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus was measured using a miniature pressure sensor under different tensile loadings of the Achilles tendon at the neutral ankle position. Similarly, the contact pressures during the ankle motion from a neutral position to maximum dorsiflexion were measured. The tensile load of the Achilles tendon and ankle motion affected the contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus. The contact pressure increased with tensile load or ankle dorsiflexion. Conditions with increasing the tensile load of the Achilles tendon or under ankle dorsiflexion increase the contact pressure between the Achilles tendon and the posterosuperior prominence of the calcaneus.博士（医学）・甲第806号・令和3年12月21日Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved

Bilateral male breast cancer with male potential hypogonadism

<p>Abstract</p> <p>Background</p> <p>Male breast cancer is a comparatively rare disease, and simultaneous bilateral male breast cancer is considered to be an extremely rare event. Risk factors are said to be genetic factors and hormonal abnormalities due to obesity or testicular diseases.</p> <p>Case presentation</p> <p>The patient was a 47-year-old Japanese male. His family had no history of female breast cancer. This patient also had hypospadias and hormonal examination indicated the presence of primary testicular potential hypogonadism, and these hormonal abnormalities seemed to be present since childhood or the fetal period. The bilateral breast cancer developed in this man at a comparatively young age, and histopathological studies of multiple sections showed that there was almost no normal epithelial cell in the ducts, while the ducts were almost completely filled with breast cancer cells.</p> <p>Conclusion</p> <p>It is thought that male breast cancer is caused by an imbalance between estrogen and testosterone. We cannot rule out the possibility that the breast cancer developed due to the effect of the slight elevation of estrogen over a long period of time, but the actual causative factors in this patient were unable to be definitively identified. In the future, we hope to further elucidate the causes of male breast cancer.</p

Dirac Operator Zero-modes on a Torus

We study Dirac operator zero-modes on a torus for gauge background with uniform field strengths. Under the basic translations of the torus coordinates the wave functions are subject to twisted periodic conditions. In a suitable torus coordinates the zero-mode wave functions can be related to holomorphic functions of the complex torus coordinates. We construct the zero-mode wave functions that satisfy the twisted periodic conditions. The chirality and the degeneracy of the zero-modes are uniquely determined by the gauge background and are consistent with the index theorem.Comment: 28 pages, 2 figure

Biologic markers in prostatic intraepithelial neoplasia: immunohistochemical and cytogenetic analyses

Objective:We evaluated the biological properties of High-grade prostatic intraepithelial neoplasia (PIN) by immunohistochemistry and fluorescence in situ hybridization (FISH) analysis in relation to normal tissue and carcinoma lesions. Materials and Methods:Immunohistochemical staining and FISH were performed on23formalin-fixed radical prostatectomy specimens taken from patients with PIN. Assays were performed using MIB-1, chromogranin A (CGA) and an anti-androgen receptor antibody (AR). A centromere probe for chromosome8was used to test for aneuploidy. Results:The MIB-1index of cancerous specimens (16.2±10.5%) was significantly higher than that of benign (1.9±1.6%, p<0.0001) or PIN (4.0±4.5%, p<0.0001) specimens. The percentage of CGA positive cells was significantly lower in normal tissue (1.2±1.8%) than in PIN (3.5±2.9%, p=0.012) or carcinoma (5.4±4.9%, p=0.005) lesions. Positive staining for AR was consistently observed in the nuclei of both benign and malignant epithelial cells, but positive cytoplasmic staining was also seen in PIN epithelial cells. No significant difference in FISH detected anomalies were found between PIN and carcinoma specimens. Conclusions:Our studies concerning proliferative activity, NE differentiation and chromosomal anomalies of prostatic specimens support the hypothesis that PIN is a biologically intermediate stage in the pathogenesis of prostatic carcinoma. The cellular distribution of AR was altered in PIN cells, but the role of AR in PIN is not yet clear

Efficacy of Brazilian Propolis against Herpes Simplex Virus Type 1 Infection in Mice and Their Modes of Antiherpetic Efficacies

Ethanol extracts (AF-06, 07, and 08, 10 mg/kg) of Brazilian propolis were administered orally to cutaneously herpes simplex virus type 1 (HSV-1)-infected mice three times daily on days 0 to 6 after infection to evaluate their efficacies against HSV-1 infection and significantly limited development of herpetic skin lesions. AF-07 and 08 significantly reduced virus titers in brain and/or skin on day 4 without toxicity, but AF-08 had no anti-HSV-1 activity in vitro. AF-06 and 08 significantly enhanced delayed-type hypersensitivity (DTH) to inactivated HSV-1 antigen in infected mice. Oral AF-08-administration significantly augmented interferon (IFN)-γ production by HSV-1 antigen from splenocytes of HSV-1-infected mice, while direct exposure of splenocytes of infected mice to AF-06 significantly elevated IFN-γ production in vitro. Thus, AF-08 might have components that are active in vivo even after oral administration and those of AF-06 might be active only in vitro. Because DTH is a major host defense for intradermal HSV-1 infection, augmentation of DTH response by AF-06 or 08, directly or indirectly, respectively, may contribute to their efficacies against HSV-1 infection. In addition, AF-06 and 07 possibly contain anti-HSV-1 components contributing to their efficacies. Such biological activities of Brazilian propolis may be useful to analyze its pharmacological actions

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

The 18F-labeled fibroblast activation protein inhibitor (FAPI) [18F]FAPI- 74 has the benefit of a higher synthetic yield and better image resolution than 68Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [18F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [18F]FAPI-74 PET scanning was performed 60min after the intravenous injection of [18F]FAPI-74 (240631 MBq). The [18F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n 5 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [18F]FAPI-74 PET were also compared with those on [18F]FDG PET for available patients (n = 19). Results: [18F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUVmax, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [18F]FAPI-74 PET also showed significantly higher uptake than [18F]FDG PET (median SUVmax, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P 5 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P 5 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P 5 0.046], respectively). In 6 patients, [18F]FAPI-74 PET detected more metastatic lesions than [18F]FDG PET. Conclusion: [18F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [18F]FDG PET. [18F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18F-labeled FAPI ligand might serve a higher demand in clinical care in the future.This research was originally published in JNM. Tadashi Watabe, Sadahiro Naka, Mitsuaki Tatsumi et.al. Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions. J Nucl Med. 2023, 64(8), 1225-1231. © SNMMI

KCNQ1 subdomains involved in KCNE modulation revealed by an invertebrate KCNQ1 orthologue

KCNQ1 channels are voltage-gated potassium channels that are widely expressed in various non-neuronal tissues, such as the heart, pancreas, and intestine. KCNE proteins are known as the auxiliary subunits for KCNQ1 channels. The effects and functions of the different KCNE proteins on KCNQ1 modulation are various; the KCNQ1–KCNE1 ion channel complex produces a slowly activating potassium channel that is crucial for heartbeat regulation, while the KCNE3 protein makes KCNQ1 channels constitutively active, which is important for K+ and Cl− transport in the intestine. The mechanisms by which KCNE proteins modulate KCNQ1 channels have long been studied and discussed; however, it is not well understood how different KCNE proteins exert considerably different effects on KCNQ1 channels. Here, we approached this point by taking advantage of the recently isolated Ci-KCNQ1, a KCNQ1 homologue from marine invertebrate Ciona intestinalis. We found that Ci-KCNQ1 alone could be expressed in Xenopus laevis oocytes and produced a voltage-dependent potassium current, but that Ci-KCNQ1 was not properly modulated by KCNE1 and totally unaffected by coexpression of KCNE3. By making chimeras of Ci-KCNQ1 and human KCNQ1, we determined several amino acid residues located in the pore region of human KCNQ1 involved in KCNE1 modulation. Interestingly, though, these amino acid residues of the pore region are not important for KCNE3 modulation, and we subsequently found that the S1 segment plays an important role in making KCNQ1 channels constitutively active by KCNE3. Our findings indicate that different KCNE proteins use different domains of KCNQ1 channels, and that may explain why different KCNE proteins give quite different outcomes by forming a complex with KCNQ1 channels

Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation

Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis