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Introduction: 3-[ 18 F]fluoro-α-methyl-L-tyrosine ([ 18 F]FAMT) is a promising amino acid tracer targeting L-type amino acid transporter 1 (LAT1). One concern regarding the diagnosis using [ 18 F]FAMT is the possibility of false-negative findings because of its relatively low accumulation level even in malignant tumors. Moreover, preloading probenecid, an organic anion transporter inhibitor, markedly increased the tumor accumulation level of radioiodine-labeled α-methyltyrosine. In this study, we evaluated the usefulness of preloading probenecid in improving the tumor-imaging capability of [ 18 F]FAMT., Methods: Three biodistribution studies of [ 18 F]FAMT were conducted in normal mice to elucidate the usefulness of probenecid preloading. Later, a biodistribution study and positron emission tomography (PET) imaging of [ 18 F]FAMT were conducted with or without probenecid injection in tumor-bearing mice., Results: Probenecid preloading significantly delayed blood clearance and consequently enhanced the accumulation of [ 18 F]FAMT in the pancreas, a LAT1-positive organ. The effects of probenecid preloading were independent of the administration route. Tumor accumulation level in the biodistribution study and the maximum standardized uptake value in tumors on PET imaging of the probenecid preloading group were significantly higher than those of the control (without probenecid injection) group in tumor-bearing mice., Conclusions: Preloading probenecid significantly delayed blood clearance and consequently enhanced the accumulation of [ 18 F]FAMT in tumors. These results indicate that preloading probenecid could improve the diagnostic accuracy of [ 18 F]FAMT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to determine antibody responses in healthcare workers who receive the BNT162b2 mRNA COVID-19 vaccine and identify factors that predict the response., Methods: We recruited healthcare workers receiving the BNT162b2 mRNA COVID-19 vaccine at the Chiba University Hospital COVID-19 Vaccine Center. Blood samples were obtained before the 1st dose and after the 2nd dose vaccination, and serum antibody titers were determined using Elecsys® Anti-SARS-CoV-2S, an electrochemiluminescence immunoassay. We established a model to identify the baseline factors predicting post-vaccine antibody titers using univariate and multivariate linear regression analyses., Results: Two thousand fifteen individuals (median age 37-year-old, 64.3% female) were enrolled in this study, of which 10 had a history of COVID-19. Before vaccination, 21 participants (1.1%) had a detectable antibody titer (≥0.4 U/mL) with a median titer of 35.9 U/mL (interquartile range [IQR] 7.8 - 65.7). After vaccination, serum anti-SARS-CoV-2S antibodies (≥0.4 U/mL) were detected in all 1774 participants who received the 2nd dose with a median titer of 2060.0 U/mL (IQR 1250.0 - 2650.0). Immunosuppressive medication (p < 0.001), age (p < 0.001), time from 2nd dose to sample collection (p < 0.001), glucocorticoids (p = 0.020), and drinking alcohol (p = 0.037) were identified as factors predicting lower antibody titers after vaccination, whereas previous COVID-19 (p < 0.001), female (p < 0.001), time between 2 doses (p < 0.001), and medication for allergy (p = 0.024) were identified as factors predicting higher serum antibody titers., Conclusions: Our data demonstrate that healthcare workers universally have good antibody responses to the BNT162b2 mRNA COVID-19 vaccine. The predictive factors identified in our study may help optimize the vaccination strategy., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Targeted α-radionuclide therapy has attracted attention as a promising therapy for refractory cancers. However, the application is limited to certain types of cancer. Since L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers, we prepared an LAT1-selective α-radionuclide-labeled amino acid analog, 2-[ 211 At]astato-α-methyl-L-phenylalanine (2-[ 211 At]AAMP), and evaluated its potential as a therapeutic agent., Methods: 2-[ 211 At]AAMP was prepared from the stannyl precursor. Stability of 2-[ 211 At]AAMP was evaluated both in vitro and in vivo. In vitro studies using an LAT1-expressing human ovarian cancer cell line, SKOV3, were performed to evaluate cellular uptake and cytotoxicity of 2-[ 211 At]AAMP. Biodistribution and therapeutic studies in SKOV3-bearing mice were performed after intravenous injection of 2-[ 211 At]AAMP., Results: 2-[ 211 At]AAMP was stable in murine plasma in vitro and excreted intact into urine. Cellular uptake of 2-[ 211 At]AAMP was inhibited by treatment with an LAT1-selective inhibitor. After 24 h incubation, 2-[ 211 At]AAMP suppressed clonogenic growth at 10 kBq/ml, and induced cell death and DNA double-strand breaks at 25 kBq/ml. When injected into mice, 2-[ 211 At]AAMP exhibited peak accumulation in the tumor at 30 min postinjection, and radioactivity levels in the tumor were retained up to 60 min. The majority of the radioactivity was rapidly eliminated from the body into urine in an intact form immediately after injection. 2-[ 211 At]AAMP significantly improved the survival of mice (P < 0.05) without serious side effects., Conclusion: 2-[ 211 At]AAMP showed α-radiation-dependent cellular growth inhibition after it was taken up via LAT1. In addition, 2-[ 211 At]AAMP had a beneficial effect on survival in vivo. These findings suggest that 2-[ 211 At]AAMP would be useful for the treatment of LAT1-positive cancer., Advances in Knowledge and Implications for Patient Care: This is the first report of an LAT1-targeting radiopharmaceutical for α-radionuclide therapy; this agent would be applicable for the treatment of various types of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities., Methods: We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174., Findings: We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25-0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78)., Interpretation: Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG., Funding: Japan Agency for Medical Research and Development (grant CCT-B-2503)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The impact of chronic kidney disease (CKD) on the antiplatelet effect of clopidogrel and low-dose (3.75mg) prasugrel in Japanese patients is largely unknown., Methods: A total of 53 consecutive Japanese patients with stable coronary artery disease who received aspirin and clopidogrel were enrolled, and categorized by estimated glomerular filtration rate (eGFR): CKD group (n=15, eGFR<60ml/min/1.73m 2 ) and non-CKD group (n=38, eGFR≥60ml/min/1.73m 2 ). Clopidogrel was switched to 3.75mg prasugrel. Platelet reactivity measurement using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA) was performed at baseline (on clopidogrel) and day 14 (on prasugrel)., Results: The VerifyNow P2Y12 reaction units (PRU) during clopidogrel therapy was significantly higher in the CKD group than that in the non-CKD group (185.2±51.1 PRU vs. 224.3±57.0 PRU, p=0.02), whereas, the PRU with the prasugrel therapy in the CKD group and non-CKD group were not significantly different (149.9±51.1 PRU vs. 165.3±61.8 PRU, p=0.36). The PRU was significantly lower with the prasugrel therapy compared to that with the clopidogrel therapy both in the CKD group and in the non-CKD group., Conclusions: Antiplatelet effect of clopidogrel but not prasugrel is attenuated in patients with CKD. Prasugrel achieves a consistently lower platelet reactivity compared with clopidogrel regardless of the presence of mild to moderate CKD., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Metformin, widely used in the treatment of type 2 diabetes mellitus, reduces the risk of cancer and relapse after treatment. Fertility-sparing treatment for endometrial cancer (EC) with progestin is associated with a high chance of disease regression, and the high relapse rate continues to be a problem. We assessed the efficacy of metformin in preventing recurrence after medroxyprogesterone acetate (MPA) as fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and EC., Patients and Methods: This phase II study enrolled 17 patients with AEH and 19 patients with EC limited to the endometrium (age, 20-40 years). MPA (400 mg/day) and metformin (750-2250 mg/day) were administered for 24-36 weeks to achieve a complete response (CR). Metformin was administered until conception, even after MPA discontinuation. The primary end point was relapse-free survival (RFS) after remission. We analyzed all efficacy end points in the full analysis set., Results: The body mass index was ≥25 kg/m(2) in 27 patients (mean, 31 kg/m(2); range, 19-51 kg/m(2)), and the homeostasis model assessment for insulin resistance index was ≥2.5 in 24 patients (mean, 4.7; range, 0.7-21). Two patients showed progression at 12 weeks [6%; 95% confidence interval (CI) 2-18]. At 36 weeks, 29 (81%; 95% CI 65-90) patients achieved CR, and 5 (14%; 95% CI 6-29) patients achieved partial response. During a median follow-up of 38 months (range, 9-66 months) after remission, relapse was confirmed in three of the patients who had achieved CR (relapse rate, 10%). The 3-year estimated RFS rate was 89%. No patients experienced severe toxicity., Conclusions: Metformin inhibited disease relapse after MPA therapy. The combination of metformin and MPA in EC treatment should be studied further., Trial Registration Number: UMIN 000002210., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36(-/-) mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36(-/-) mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue (125)I-BMIPP and the glucose analogue (18)F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36(-/-) mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36(-/-) mice after cold exposure. These findings strongly suggest that CD36(-/-) mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The best therapeutic approach for patients with sub-clinical lymphoedema and symptomatic early-stage lymphoedema has not been determined yet., Methods: The prognosis of lymphatic function after lymphadenectomy for gynaecological cancer was observed in a cohort study of 192 lower limbs. Lymphatic function was evaluated by indocyanine green lymphography. Splash patterns were examined to determine if patients with this pattern tended to progress to symptomatic lymphoedema, and the efficacy of the compression therapy was also investigated. We also investigated the efficacy of lymphaticovenular anastomosis (LVA) in patients who exhibited a stardust pattern., Results: Patients with splash patterns on lymphography may progress to symptomatic lymphoedema with a significantly higher frequency compared with the others, with a relative ratio of 1.62. Compression therapy did not slow the progression of patients with splash patterns to stardust patterns. LVA for the patients who had recently shown stardust patterns eliminated the need for compression therapy in 44.8% of patients., Conclusion: Patients with splash patterns should be followed up carefully for sub-clinical lymphoedema. However, there is no method to completely prevent these patients from developing stardust patterns associated with symptomatic lymphoedema. When patients become symptomatic, their lymphatic function may be improved by LVA. However, the limited effectiveness of this procedure should be clearly explained to patients before surgery., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: 3-[(18)F]fluoro-α-methyl-l-tyrosine ([(18)F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. FAMT analogs labeled with (76)Br, a positron emitter with a long half-life (t(1/2)=16.1 h), could potentially be widely used as amino acid tracers for tumor imaging. In this study, 3-[(76)Br]bromo-α-methyl-l-tyrosine ([(76)Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors., Methods: In this study, both [(76)Br]BAMT and [(77)Br]BAMT were prepared. The in vitro and in vivo stability of [(77)Br]BAMT was evaluated by HPLC analysis. Cellular uptake and retention of [(77)Br]BAMT and [(18)F]FAMT were evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in normal mice and in LS180 tumor-bearing mice, and the tumors were imaged with a small-animal PET scanner., Results: [(77)Br]BAMT was stable in vitro but was catabolized after administration in mice. Cellular accumulation and retention of [(77)Br]BAMT were significantly higher than those of [(18)F]FAMT. In biodistribution studies, the tumor accumulation of [(77)Br]BAMT was higher than that of [(18)F]FAMT. However, some level of debromination was seen, which caused more retention of radioactivity in the blood and organs than was seen with [(18)F]FAMT. PET imaging with [(76)Br]BAMT enabled clear visualization of the tumor, and the whole-body image using [(76)Br]BAMT was similar to that using [(18)F]FAMT., Conclusions: [(77)Br]BAMT showed high levels of tumor accumulation, and [(76)Br]BAMT enabled clear visualization of the tumor by PET imaging. Although an improvement in stability is still needed, (76)Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: We have developed a method for producing no-carrier-added (64)Cu by using chelating resin bearing iminodiacetic acid groups., Methods: We optimized the conditions for the selective separation of radioactive Cu from Ni and Co using the chelating resin and produced no-carrier-added (64)Cu under the optimized conditions. We analyzed the amounts of the metal ions present in (64)Cu by inductively coupled-plasma mass spectroscopy (ICP-MS) and optical emission spectroscopy (ICP-OES), and performed radiolabeling of monoclonal antibodies in order to investigate the quality of the (64)Cu produced in this study., Results: Radioactive Cu was separated from Ni and Co with 0.1 and 2 M HCl solutions. The yield of (64)Cu isolated from the (64)NiO target was almost 87%. The radiochemical purity of (64)Cu obtained from different amounts of (64)NiO targets was >99% in all cases. We found that the (64)Cu solution presented extremely low amounts of the metal ions and showed high specific activity (average: 595 GBq/mumol). Moreover, the antibodies were labeled with (64)Cu with a high average efficiency (average: 88%)., Conclusions: We could efficiently separate (64)Cu by using short ion-exchange columns. The chelating ion-exchange method provides a high quality of (64)Cu that is sufficient for the synthesis of (64)Cu-labeled antibodies and medical applications.

Aims: To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia., Methods and Results: Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated., Conclusion: Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.

Since elevated levels of gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are associated with a poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging. In the present study, a cyclic decapeptide, cCTTHWGFTLC (CTT), was selected as a mother compound because of its selective inhibitory activity toward gelatinases. For imaging gelatinase activity in tumors, we designed a CTT-based radiopharmaceutical taking into consideration that (1) the HWGF motif of the peptide is important for the activity, (2) hydrophilic radiolabeled peptides show low-level accumulation in the liver and (3) an increase in the negative charge of radiolabeled peptides is effective in reducing renal accumulation. Thus, a highly hydrophilic and negatively charged radiolabel, indiun-111-diethylenetriaminepentaacetic acid ((111)In-DTPA), was attached to an N-terminal residue distant from the HWGF motif ((111)In-DTPA-CTT). In MMP-2 inhibition assays, In-DTPA-CTT significantly inhibited the proteolytic activity in a concentration-dependent fashion. When injected into normal mice, (111)In-DTPA-CTT showed low levels of radioactivity in the liver and kidney. A comparison of the pharmacokinetic characteristics of (111)In-DTPA-CTT with those of other CTT derivatives having different physicochemical properties revealed that the increase in hydrophilicity and negative charge caused by the conjugation of (111)In-DTPA reduced levels of radioactivity in the liver and kidney. In tumor-bearing mice, a significant correlation was observed between the accumulation in the tumor as well as tumor-to-blood ratio of (111)In-DTPA-CTT and gelatinase activity. These findings support the validity of the chemical design of (111)In-DTPA-CTT for reducing accumulation in nontarget tissues and maintaining the inhibitory activity of the mother compound. Furthermore, (111)In-DTPA-CTT derivatives would be potential radiopharmaceuticals for the imaging of gelatinase activity in metastatic tumors in vivo.

The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For 111In-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of d-Lys(8) which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, stromal cell-derived factor-1alpha, to CXCR4 in a concentration-dependent manner with an IC50 of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more 111In-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that 111In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.

Skeletal lesions are not uncommon in von Recklinghausen neurofibromatosis. Most of them are considered to be dysplastic in nature. Association of osteomalacia or rickets with neurofibromatosis has been documented only rarely. Reported herein is a 40-year-old woman with known von Recklinghausen neurofibromatosis who presented with bone pain, multiple pseudofractures, marked increase in osteoid by bone biopsy, and hypophosphatemia with renal phosphate wasting. Treatment with oral phosphate and vitamin D was effective. A survey of the literature revealed that 34 similar cases have been reported in the past. Although the exact pathogenetic mechanism remains to be determined, osteomalacia in neurofibromatosis appears to be distinct from more common dysplastic skeletal affections of this disease, being characterized by later onset in adulthood as a rule, renal phosphate loss with hypophosphatemia, multiple pseudofractures in typical cases, and response to treatment with pharmacological dose of vitamin D with or without phosphate supplement.

For the purpose of clarifying cellular differentiation of epithelioid sarcoma, studies based on various methods were performed. Enzyme histochemical studies showed that epithelioid sarcoma tumor cells have characteristics intermediate between epithelial cells and the large plump cells of synovial sarcoma-incomplete epithelial differentiation. For alkaline phosphatase and adenosine triphosphatase particularly, positive cells and negative cells coexisted, as in the large plump cells of synovial sarcoma. Immunohistochemical studies for alpha 1-antitrypsin, alpha 1-antichymotrypsin, vimentin, and keratin also showed that epithelioid sarcoma tumor cells are very similar to the large plump cells of synovial sarcoma and have incomplete epithelial differentiation. For example, the examinations of serial sections and double staining methods revealed that keratin-positive cells are always vimentin-positive in epithelioid sarcoma and in the monophasic area of synovial sarcoma. Electron-microscopically, bundles of intermediate filaments and filopodia toward the intercellular lumen were observed, as in the monophasic area of synovial sarcoma. The results of enzyme-histochemical and immunohistochemical studies of non-neoplastic synovial lining cells, performed here for the first time, are also discussed.

For the purpose of clarifying the histogenesis of clear cell sarcoma of tendons and aponeuroses (CCS) as well as the problem of whether or not CCS is a heterogeneous group of neoplasms, studies based on various methods were performed. Analysis of glycosaminoglycans gave the same results for amelanotic CCS and synovial sarcoma, and the DOPA reaction gave the same negative results for amelanotic CCS and synovial sarcoma. However, the DOPA reaction was also negative in an amelanotic recurrent tumor of a melanotic CCS, and electron-microscopic studies revealed a close resemblance between amelanotic CCS and melanotic CCS. Further, enzyme histochemical studies showed definite differences between synovial sarcoma and amelanotic CCS but gave identical results for amelanotic and melanotic CCS. Immunohistochemical studies revealed the presence of S-100 protein in all CCS cases, both amelanotic and melanotic. These results indicate that CCS is not a heterogeneous group of neoplasms, and that both amelanotic and melanotic CCS are of neural crest origin.

As an initial step to elucidate the nature of the unique characteristics of the crystalloids of alveolar soft part sarcoma, a three-dimensional model of the crystalloids was prepared by digital image analysis of electron micrographs by computer. It was revealed that occult periodicities are present at two intervals, 60 A and 380 A, in the filamentous structure of the crystalloid; and it was also revealed by the observation of each cross-section that two globular substances with a diameter of 60 A are arranged in a dumbbell pattern in each filamentous structure. The model prepared based on these data showed the double strands crossing each other at intervals of 380 A, each of which consists of successive arrangement of the globular substances with a diameter of 60 A. This structure is clearly similar to that of actin. The similarities and differences between these results and the well-known studies of the organization of naturally occurring actin bundles are discussed.