Publications by authors named "Hiroshi Suzuki"

932 Publications

Assisted reproductive techniques for canines: preservation of genetic material in domestic dogs.

J Reprod Dev 2021 Nov 29. Epub 2021 Nov 29.

Prefectural University of Hiroshima, Hiroshima 727-0023, Japan.

Assisted reproductive techniques (ARTs), such as artificial insemination, in vitro fertilization, and cryopreservation of gametes/zygotes, have been developed to improve breeding and reproduction of livestock and for the treatment of human infertility. Their widespread use has contributed to improvements in human health and welfare. However, in dogs, only artificial insemination using frozen semen is readily available as an ART to improve breeding and control genetic diversity. A recent priority in sperm cryopreservation is the development of alternatives to egg yolk, which is widely used as a component of the sperm extender. Egg yolk can vary in composition among batches and is prone to contamination by animal pathogens. The latter can be a problem for international exchange of cryopreserved semen. Low-density lipoprotein and skim milk are promising candidates for use as extenders, to ensure fertility after artificial insemination. Although not tested for its effects on fertility following artificial insemination, polyvinyl alcohol may also be a useful alternative to egg yolk as an extender. The development of cryopreservation techniques for canine embryos lags behind that for other mammals, including humans. However, given the success of non-surgical embryo transfer in 2011, studies have sought to refine this approach for practical use. Research on sperm cryopreservation has yielded satisfactory results. However, investigation of other approaches, such as cryopreservation of oocytes and gonadal tissues, remains insufficient. Techniques for the efficient induction of estrus may aid in the development of successful canine ARTs.
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http://dx.doi.org/10.1262/jrd.2021-111DOI Listing
November 2021

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J Pharmacol Exp Ther 2021 Nov 2. Epub 2021 Nov 2.

Drug Discovery Research, Astellas Pharma Inc., Japan.

Thymic stromal lymphopoietin (TSLP), positioned at the top of the inflammatory cascade, is a key regulator that enhances allergic inflammatory responses by activating T helper type 2 (Th2) cells, Group 2 innate lymphoid cells (ILC2), and myeloid dendritic cells (mDCs) via the TSLP receptor (TSLPR). We evaluated the inhibitory effects of ASP7266, a novel recombinant fully human IgG1 monoclonal antibody against TSLPR, on TSLP signaling and inflammation. The inhibitory effects of ASP7266 and the control antibody tezepelumab on TSLP and TSLPR interactions were investigated using a proliferation assay with TSLP stimulation and a chemokine production assay. The pharmacological effects of ASP7266 were investigated by examining differentiation of naive CD4+ T cells, ILC2 cytokine production, and ascaris extract-induced skin allergic reaction in cynomolgus monkeys. ASP7266 potently inhibited TSLP-induced cell proliferation and C-C motif chemokine ligand 17 (CCL17) production. Furthermore, ASP7266 inhibited TSLP-stimulated mDC-mediated naive CD4+ T cell differentiation, and IL-5 production by lineage-negative peripheral blood mononuclear cells (PBMCs), which can be considered ILC2, in vitro. In sensitized monkeys, ASP7266 completely suppressed ascaris extract-induced allergic skin reactions. Based on these results, ASP7266, a novel human therapeutic antibody against TSLPR, is a potential therapy for patients with allergic diseases. TSLP, positioned at the top of the inflammatory cascade, plays a key role in various allergic diseases, including asthma, chronic rhinosinusitis with nasal polyposis, and atopic dermatitis. Here we show that the anti-TSLPR antibody, ASP7266, exhibited excellent pharmacological activity in preclinical studies. Therefore, ASP7266 has the potential to be a promising treatment option for patients with allergic disorders.
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http://dx.doi.org/10.1124/jpet.121.000686DOI Listing
November 2021

Ultrasonographic observation in combination with progesterone monitoring for detection of ovulation in Labrador Retrievers.

Reprod Domest Anim 2021 Nov 1. Epub 2021 Nov 1.

Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.

Although it is well known that the ovulation occurs during a period of time after LH surge in dogs, there are few reports of observing the entire process of development, ovulation and luteinization of each follicle. This study aimed to detect the ovulation kinetics by ultrasonography in combination with progesterone monitoring and therefore identify the time-range of the ovulation process in a dog. Daily transabdominal ultrasonography and progesterone monitoring were conducted for 24 natural oestrus cycles of Labrador Retrievers. Ovarian follicles were observed as anechoic structure with contours before ovulation. Ovulation (follicular collapse) was defined as when follicles became cloudy and contours obscure by transabdominal ultrasonography. Ultrasound imaging was capable of identifying the day of ovulation for 94.7% (178/188) of the follicles through the appearance of collapsed follicle or corpus luteum. Ovulation was observed between LH 0 (the day of LH surge) and LH 5, with 48.0%, 33.5% and 15.0% for LH 2, LH 3 and LH 1, respectively. The total number of ovulations on LH 2 and LH 3 accounted for 81.5% (141/173) of the total ovulation in 24 cycles examined. Ovulation occurred in 12 cycles for 2 d and for 3 d in 12 cycles. Seventeen cycles (70.8%) with multiple days of ovulation showed the largest number of ovulations on LH 2. The average follicle diameter 3 d before the LH surge was less than 5 mm, then exceeded 5 mm 2 d before the LH surge. The average follicle diameter at the time of ovulation (follicular collapse) was 6.1 ± 1.0 mm (n = 118). On the day before ovulation, the average diameters of the follicles ovulated on LH 1, LH 2 and LH 3 were 5.0 ± 0.7 mm, 5.8 ± 1.2 mm and 6.2 ± 1.3 mm, respectively. There was a significant difference in the follicle diameter between LH1 and LH2 (p < .001), LH2 and LH3 (p < .05), and LH1 and LH3 (p < .001). Suggesting that it is difficult to estimate the ovulation day based on follicle size. This study showed that combination of ultrasonography with progesterone monitoring could follow follicular development, ovulation and luteinization of the ovary in Labrador Retrievers. The direct visualization of the ovulation was achieved in a non-invasive, labour-friendly way. Furthermore, the time-range of the ovulation process was clarified in a dog. These results may contribute to an accurate understanding of the optimum timing of mating and improved breeding efficiency, including artificial insemination and embryo transfer for Labrador Retrievers.
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http://dx.doi.org/10.1111/rda.14035DOI Listing
November 2021

Present and Future Status of Cardiovascular Emergency Care System in Urban Areas of Japan - Importance of Prehospital 12-Lead Electrocardiogram.

Circ J 2021 Oct 22. Epub 2021 Oct 22.

Division of Cardiology, Yokohama City University Medical Center.

Acute cardiovascular disease, such as acute myocardial infarction and aortic disease, can lead to a serious life-threatening state within minutes to hours, so early accurate diagnosis, and appropriate treatment without delay are essential. To provide high-quality and timely treatment, 24-h availability of medical staff and cardiologists, as well as a cardiac catheterization laboratory are needed. In Japan, the number of patients with acute cardiovascular disease is increasing with the aging population and westernization of lifestyle; however, workstyle reforms for physicians, including a policy to limit overtime work, have been legislated. Under these conditions, it is necessary to centralize hospitals that treat cardiovascular emergency diseases as high-volume centers and build a patient triage system for allocating patients before hospital arrival. The prehospital 12-lead electrocardiogram (ECG) plays a central role in prehospital diagnosis and triage, and its importance will increase in future. We discuss the current and future state of the cardiovascular emergency medical care system utilizing prehospital 12-lead ECG in urban areas of Japan.
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http://dx.doi.org/10.1253/circj.CJ-21-0807DOI Listing
October 2021

Increase of serum uric acid levels associated with APOE ε2 haplotype: a clinico-genetic investigation and in vivo approach.

Hum Cell 2021 Nov 16;34(6):1727-1733. Epub 2021 Sep 16.

Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Elevated serum uric acid (SUA)-hyperuricemia-is caused by overproduction of urate or by its decreased renal and/or intestinal excretion. This disease, which is increasing in prevalence worldwide, is associated with both gout and metabolic diseases. Several studies have reported relationships between apolipoprotein E (APOE) haplotypes and SUA levels in humans; however, their results remain inconsistent. This prompted us to investigate the relationship between APOE polymorphisms and SUA levels. Our subjects were 5,272 Japanese men, premenopausal women, and postmenopausal women. Multiple linear regression analyses revealed the ε2 haplotype of APOE to be independently associated with higher SUA in men (N = 1,726) and postmenopausal women (N = 1,753), but not in premenopausal women (N = 1,793). In contrast, the ε4 haplotype was little related to SUA levels in each group. Moreover, to examine the effect of Apoe deficiency on SUA levels, we conducted animal experiments using Apoe knockout mice, which mimics ε2/ε2 carriers. We found that SUA levels in Apoe knockout mice were significantly higher than those in wild-type mice, which is consistent with the SUA-raising effect of the ε2 haplotype observed in our clinico-genetic analyses. Further analyses suggested that renal rather than intestinal underexcretion of urate could be involved in Apoe deficiency-related SUA increase. In conclusion, we successfully demonstrated that the ε2 haplotype, but not the ε4 haplotype, increases SUA levels. These findings will improve our understanding of genetic factors affecting SUA levels.
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http://dx.doi.org/10.1007/s13577-021-00609-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490264PMC
November 2021

Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease.

Circ J 2021 Sep 16. Epub 2021 Sep 16.

Department of Clinical-laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center.

Background: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results:106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity.

Conclusions: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.
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http://dx.doi.org/10.1253/circj.CJ-20-1271DOI Listing
September 2021

Induction of oestrus by administering Inhibin antiserum along with equine chorionic gonadotropin in anoestrous bitches.

Reprod Domest Anim 2021 Nov 17;56(11):1398-1405. Epub 2021 Aug 17.

Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.

As dogs experience oestrus only once or twice a year, it is necessary to establish an effective method of oestrous induction for efficient breeding. In the present study, we evaluated inhibin antiserum (IAS) on oestrous induction in anoestrous females. Bitches were administered 0.5 ml/kg IAS or a mixture of 50 IU/kg equine chorionic gonadotropin (eCG) and 0.5 ml/kg IAS and 500 IU human chorionic gonadotropin (hCG) administered 7 days after the mixture injection. As a control, bitches received 50 IU/kg eCG, with 500 IU hCG administered 7 days after eCG injection. Blood-tinged vaginal discharge, vulvar swelling, plasma progesterone concentrations and ovarian follicular development were assessed from day 0 to day 14. IAS alone injection did not induce oestrus in bitches at the anoestrous stage. Conversely, vulvar swelling, blood-tinged vaginal discharge and an estimated luteinizing hormone (LH) surge appeared on days 3-7, days 3-6 and days 7-9 after the IAS+eCG mixture injection, respectively, in all five bitches at the anoestrous stage. The average number of developing and ovulated follicles in bitches administered IAS+eCG was 8.8 and 9.6 respectively. A single eCG injection followed by hCG induced oestrous signs, with an average of 8.3 developing follicles and 4.5 ovulated follicles. This study revealed that IAS alone did not induce oestrus, but when IAS was used in combination with eCG, it induced oestrus and promoted a considerable number of ovulations in anoestrous dogs.
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http://dx.doi.org/10.1111/rda.14004DOI Listing
November 2021

Subacute Stent Thrombosis After Primary Percutaneous Coronary Intervention in a Middle-Aged Anabolic Steroid-Abusing Bodybuilder.

JACC Case Rep 2021 Apr 23;3(4):537-541. Epub 2020 Dec 23.

Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.

A 54-year-old male bodybuilder who was abusing anabolic steroids developed an acute ST-segment elevation myocardial infarction after strenuous strength training. Despite optimal use of dual antiplatelet therapy, on day 4 after primary coronary stenting, the patient suffered another acute coronary event due to subacute thrombosis, potentially pre-disposed by anabolic steroid use. ().
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http://dx.doi.org/10.1016/j.jaccas.2020.09.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302771PMC
April 2021

Cranial Nerve Palsy Secondary to Botulism After Black Tar Heroin Use.

J Am Board Fam Med 2021 Jul-Aug;34(4):808-810

From the University of California, Riverside, Department of Family Medicine, University of California, Riverside (HS); St. Bernardine Medical Center, Sound Critical Care, San Bernardino, CA (HR).

Introduction: Wound botulism (WB) is an uncommon but severe neuromuscular illness caused by the bacterium in an infected wound. There has been a dramatic increase in WB associated with black tar heroin injection in California.

Case Description: A 50-year-old male with heroin abuse presented to the emergency department with a 2-day history of dysphagia and dysarthria. Physical examination revealed slurred speech, inability to manipulate tongue, and slowed eye movements. The patient was also noted to have progressive weakness during hospitalization. Laboratory findings were unremarkable, and further workup, including a computerized tomography scan of the head and soft neck tissue, showed no abnormal findings. Given the history of heroin abuse in Southern California and findings on physical examination, a diagnosis of WB needed to be considered as the differential. The Department of Health was contacted, and treatment was initiated with botulism antitoxin and metronidazole. Despite the treatment, the patient's condition did not improve, and the patient died. The resulting diagnosis was confirmed by toxin A found in his serum a few days after the patient died.

Discussion: Progressive cranial nerve palsy with symmetric descending paralysis with heroin abuse should raise the suspicion of WB and require prompt diagnosis and treatment. This case highlights raising awareness of the disease could help lead to early diagnosis and treatment.
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http://dx.doi.org/10.3122/jabfm.2021.04.200644DOI Listing
October 2021

Model-based meta-analysis of changes in circulatory system physiology in patients with chronic heart failure.

CPT Pharmacometrics Syst Pharmacol 2021 09 16;10(9):1081-1091. Epub 2021 Jul 16.

Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.

To characterize and compare various medicines for chronic heart failure (CHF), changes in circulatory physiological parameter during pharmacotherapy were investigated by a model-based meta-analysis (MBMA) of circulatory physiology. The clinical data from 61 studies mostly in patients with heart failure with reduced ejection fraction (HFrEF), reporting changes in heart rate, blood pressure, or ventricular volumes after treatment with carvedilol, metoprolol, bisoprolol, bucindolol, enalapril, aliskiren, or felodipine, were analyzed. Seven cardiac and vasculature function indices were estimated without invasive measurements using models based on appropriate assumptions, and their correlations with the mortality were assessed. Estimated myocardial oxygen consumption, a cardiac load index, correlated excellently with the mortality at 3, 6, and 12 months after treatment initiation, and it explained differences in mortality across the different medications. The analysis based on the present models were reasonably consistent with the hypothesis that the treatment of HFrEF with various medications is due to effectively reducing the cardiac load. Assessment of circulatory physiological parameters by using MBMA would be insightful for quantitative understanding of CHF treatment.
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http://dx.doi.org/10.1002/psp4.12676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452295PMC
September 2021

Angle change of the A-domain in a single SERCA1a molecule detected by defocused orientation imaging.

Sci Rep 2021 07 1;11(1):13672. Epub 2021 Jul 1.

Department of Biochemistry, Asahikawa Medical University, Midorigaoka-higashi, Asahikawa, 078-8510, Japan.

The sarcoendoplasmic reticulum Ca-ATPase (SERCA) transports Ca ions across the membrane coupled with ATP hydrolysis. Crystal structures of ligand-stabilized molecules indicate that the movement of actuator (A) domain plays a crucial role in Ca translocation. However, the actual structural movements during the transitions between intermediates remain uncertain, in particular, the structure of E2PCa has not been solved. Here, the angle of the A-domain was measured by defocused orientation imaging using isotropic total internal reflection fluorescence microscopy. A single SERCA1a molecule, labeled with fluorophore ReAsH on the A-domain in fixed orientation, was embedded in a nanodisc, and stabilized on Ni-NTA glass. Activation with ATP and Ca caused angle changes of the fluorophore and therefore the A-domain, motions lost by inhibitor, thapsigargin. Our high-speed set-up captured the motion during EP isomerization, and suggests that the A-domain rapidly rotates back and forth from an E1PCa position to a position close to the E2P state. This is the first report of the detection in the movement of the A-domain as an angle change. Our method provides a powerful tool to investigate the conformational change of a membrane protein in real-time.
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http://dx.doi.org/10.1038/s41598-021-92986-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249593PMC
July 2021

Novel electrocardiographic criteria for short QT syndrome in children and adolescents.

Europace 2021 Jun 28. Epub 2021 Jun 28.

Aichi Children's Health and Medical Center, 7-426 Morioka-cho, Ohfu, Aichi 474-8710, Japan.

Aims: Although shortening of the corrected QT interval (QTc) is a key finding in the diagnosis of short QT syndrome (SQTS), there may be overlap of the QTc between SQTS patients and normal subjects in childhood and adolescence. We aimed to investigate electrocardiographic findings for differentiation of SQTS patients.

Methods And Results: The SQTS group comprised 34 SQTS patients <20 years old, including 9 from our institutions and 25 from previous reports. The control group comprised 61 apparently healthy subjects with an QTc of <360 ms who were selected from 13 314 participants in a school-based screening programme. We compared electrocardiographic findings, including QT and Jpoint-Tpeak intervals (QT and J-Tpeak, respectively), those corrected by using the Bazett's and Fridericia's formulae (cB and cF, respectively) and early repolarization (ER) between the groups. QT, QTc by using Bazett's formula (QTcB), QTc by using Fridericia's formula (QTcF), J-Tpeak, J-Tpeak cB, and J-Tpeak cF were significantly shorter in the SQTS group than in the control group. On receiver operating characteristic curve analysis, the area under the curve (AUC) was largest for QTcB (0.888) among QT, QTcB, and QTcF, with a cut-off value of 316 ms (sensitivity: 79.4% and specificity: 96.7%). The AUC was largest for J-Tpeak cB (0.848) among J-Tpeak, J-Tpeak cB, and J-Tpeak cF, with a cut-off value of 181 ms (sensitivity: 80.8% and specificity: 91.8%). Early repolarization was found more frequently in the SQTS group than in the control group (67% vs. 23%, P = 0.001).

Conclusion: A QTcB <316 ms, J-Tpeak cB < 181 ms, and the presence of ER may indicate SQTS patients in childhood and adolescence.
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http://dx.doi.org/10.1093/europace/euab097DOI Listing
June 2021

Effect of α-tocopheryloxy acetic acid, a vitamin E derivative mitocan, on the experimental infection of mice with Plasmodium yoelii.

Malar J 2021 Jun 24;20(1):280. Epub 2021 Jun 24.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.

Background: Malaria parasites are known to be vulnerable to oxidative stress. In this study, the effects of the administration of α-tocopheryloxy acetic acid (α-TEA), which is a vitamin E analogue mitocan, on Plasmodium yoelii infection in mice were examined.

Methods: Alpha-TEA was mixed with diet and fed to C57BL/6J mice before and/or after infection. For parasite infection, 4 × 10 red blood cells infected with P. yoelii (strain 17XL) were inoculated by intraperitoneal injection. In another series of experiment, the effect of the oral administration of α-TEA on P. yoelii 17XL infection in mice was examined. Finally, the combined effect of α-TEA and dihydroartemisinin or chloroquine on P. yoelii 17XL infection was examined.

Results: When 0.25% α-TEA was mixed with the diet for 7 days before infection and 14 days after infection (in total for 21 days), for 14 days after infection, and for 11 days from the third day after infection, all P. yoelii 17XL-infected mice survived during the observation period. However, all control mice died within 12 days after infection. These results indicated that α-TEA functions effectively even when administered post-infection. The oral administration of α-TEA for P. yoelii 17XL infection was also significant. Although the infected mice in the solvent control died within 10 days after infection, 90% of the mice infected with P. yoelii 17XL survived during the observation period when treated with 10 mg/head/day of α-TEA for 3 days from day 3 after infection. Although the combined effect of α-TEA and dihydroartemisinin (DHA) or chloroquine on P. yoelii 17XL infection was significant, no synergistic or additive effects were observed from the survival curve.

Conclusions: This study showed the beneficial effects of α-TEA on the experimental infection of mice with P. yoelii 17XL. The stimulatory action of α-TEA on mitochondria and the accompanying reactions, such as reactive oxygen species production, and induction of apoptosis might have some effect on malarial infection.
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http://dx.doi.org/10.1186/s12936-021-03817-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223275PMC
June 2021

CT findings in a patient with Coronavirus Disease-19-associated acute pericarditis.

BJR Case Rep 2021 May 9;7(3):20210001. Epub 2021 Apr 9.

Department of Radiology, Showa University Fujigaoka Hospital, Yokohama, Japan.

Coronavirus Disease-19 (COVID-19)-associated acute pericarditis is a rare complication. Several cases have been reported, but those reports have not discussed any imaging findings. Here, we report a case of a 76-year-old female diagnosed with COVID-19-associated pericarditis without pneumonia, and present image findings of the patient's contrast-enhanced CT.
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http://dx.doi.org/10.1259/bjrcr.20210001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171139PMC
May 2021

Hydrophobic-hydrophilic crown-like structure enables aquatic insects to reside effectively beneath the water surface.

Commun Biol 2021 06 10;4(1):708. Epub 2021 Jun 10.

Preeminent Medical Photonics Education & Research Center, Institute for NanoSuit Research, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.

Various insects utilise hydrophobic biological surfaces to live on the surface of water, while other organisms possess hydrophilic properties that enable them to live within a water column. Dixidae larvae reside, without being submerged, just below the water surface. However, little is known about how these larvae live in such an ecological niche. Herein, we use larvae of Dixa longistyla (Diptera: Dixidae) as experimental specimens and reveal their characteristics. A complex crown-like structure on the abdomen consists of hydrophobic and hydrophilic elements. The combination of these contrasting features enables the larvae to maintain their position as well as to move unidirectionally. Their hydrophobic region leverages water surface tension to function as an adhesive disc. By using the resistance of water, the hydrophilic region serves as a rudder during locomotion.
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http://dx.doi.org/10.1038/s42003-021-02228-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192529PMC
June 2021

History of whole pelvis plus para-aortic radiation is a risk factor associated with febrile neutropenia during chemotherapy for recurrent cervical cancer.

Int J Clin Oncol 2021 Sep 4;26(9):1759-1766. Epub 2021 Jun 4.

Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan.

Background: Radiation-based therapy is widely used for advanced cervical cancer. Prior radiation-based therapy is a potential risk factor for febrile neutropenia (FN). However, the effect of irradiation field size on the incidence of FN during recurrent cervical cancer treatment is unclear. This study aimed to investigate the relationship between prior irradiation field size and FN development during recurrent chemotherapy.

Methods: This retrospective, observational study included cervical cancer patients who received recurrent chemotherapy between November 2006 and June 2020. The patients were classified into two groups based on the area of irradiation fields. The first group included patients with a history of whole pelvis (WP) irradiation (WP group). The second group had patients who underwent WP plus para-aortic lymph node (PAN) irradiation (WP + PAN group). The incidences of hematological toxicities and FN during the recurrent chemoradiotherapy were compared between the two groups.

Results: The FN incidence was significantly higher in the WP + PAN group than in the WP group (32.1% vs. 0%, P < 0.001). The incidence of Grade 4 neutropenia was not significantly different between the WP + PAN and WP groups. The nadir absolute neutrophil counts were significantly lower and the dose reduction or discontinuation rate of chemotherapy was significantly higher in the WP + PAN group than in the WP group.

Conclusion: History of WP plus PAN radiation is a risk factor for developing FN during recurrent cervical cancer chemotherapy.
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http://dx.doi.org/10.1007/s10147-021-01950-8DOI Listing
September 2021

Early Vascular Healing Following Bioresorbable-Polymer Sirolimus-Eluting Stent Placement Compared to That with Durable-Polymer Everolimus-Eluting Stent.

Int Heart J 2021 May 15;62(3):510-519. Epub 2021 May 15.

Division of Cardiology, Department of Medicine, Showa University School of Medicine.

A recent thinner strut drug-eluting stent might facilitate early strut coverage after its placement. We aimed to investigate early vascular healing responses after the placement of an ultrathin-strut bioresorbable-polymer sirolimus-eluting stent (BP-SES) compared to those with a durable-polymer everolimus-eluting stent (DP-EES) using optical coherence tomography (OCT) imaging.This study included 40 patients with chronic coronary syndrome (CCS) who underwent OCT-guided percutaneous coronary intervention (PCI). Twenty patients each received either BP-SES or DP-EES implantation. OCT was performed immediately after stent placement (baseline) and at 1-month follow-up.At one month, the percentage of uncovered struts reduced significantly in both the BP-SES (80.9 ± 10.3% to 2.9 ± 1.7%; P < 0.001) and DP-EES (81.9 ± 13.0% to 5.7 ± 1.8%; P < 0.001) groups, and the percentage was lower in the BP-SES group than in the DP-EES group (P < 0.001). In the BP-SES group, the percentage of malapposed struts also decreased significantly at 1 month (4.9 ± 3.7% to 2.6 ± 3.0%; P = 0.025), which was comparable to that of the DP-EES group (2.5 ± 2.2%; P = 0.860). The optimal cut-off value of the distance between the strut and vessel surface immediately after the placement to predict resolved malapposed struts was ≤ 160 μm for BP-SES and ≤ 190 μm for DP-EES.Compared to DP-EES, ultrathin-strut BP-SES demonstrated favorable vascular responses at one month, with a lower rate of uncovered struts and a comparable rate of malapposed struts.
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http://dx.doi.org/10.1536/ihj.20-627DOI Listing
May 2021

Specificity of tuberculin skin test improved by BCG immunization schedule change in Japan.

J Infect Chemother 2021 Sep 2;27(9):1306-1310. Epub 2021 May 2.

Division of Infectious Diseases and Pulmonary Medicine, Department of Internal Medicine, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, Japan.

Introduction: Tuberculin skin test (TST) has been used to diagnose tuberculosis (TB) and latent tuberculosis infection (LTBI). However, in Bacillus Calmette-Guérin (BCG) vaccinated patients, TST tends to produce false-positive results. According to the previous vaccination schedule, Japanese people were mandated to receive up to three doses of BCG-vaccine. The vaccination schedule was changed in 2003 and as per the new schedule, only infants are administered a dose of BCG vaccine. Our hypothesis is that this change can lead to a reduction in the cross-reaction to TST.

Methods: We evaluated the TST results obtained from 1097 recruits from six defense camps and 667 recruits from an air base. These TST data were divided into two groups according to the date of birth: a new group and an old group according to the BCG immunization schedule. We then analyzed positive and negative reaction of TST and erythema sizes.

Results: We confirmed that the change in BCG-vaccination schedule significantly decreased TST false-positive reaction (P = 1.4 × 10; risk ratio = 0.83; 95% confidence interval: 0.80-0.87) and erythema size (P = 1.1 × 10; mean difference = 6.6 mm; 95% confidence interval: 3.2 mm-9.9 mm).

Conclusions: We showed the reduction in BCG cross-reaction to TST, in the new BCG vaccination schedule group, compared to the old group, we also have extracted information on the improvement in the specificity of TST for LTBI and TB diagnosis, which resulted from BCG schedule change.
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http://dx.doi.org/10.1016/j.jiac.2021.04.016DOI Listing
September 2021

Designation Products: Boron Neutron Capture Therapy for Head and Neck Carcinoma.

Oncologist 2021 07 18;26(7):e1250-e1255. Epub 2021 May 18.

Center for Regulatory Science, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.

The Japanese Ministry of Health, Labour and Welfare approved a drug called borofalan ( B), a treatment system, and a dose calculation program for boron neutron capture therapy (BNCT) in March 2020. The application pertaining to the products submitted to the Pharmaceuticals and Medical Devices Agency was supported by a Japanese, open-label, uncontrolled trial (Study 002) in patients with unresectable, locally recurrent head and neck squamous cell carcinoma after chemoradiotherapy or radiotherapy, or in those with unresectable locally advanced or locally recurrent (LA/LR) head and neck nonsquamous cell carcinoma. The drug was administered as a single intravenous dose using infusion rates of 200 mg/kg per hour for the first 2 hours after the start of administration and 100 mg/kg per hour during irradiation. Neutron irradiation was performed using the devices at a single dose of 12 Gy-equivalent for oral, pharyngeal, or laryngeal mucosa for up to 60 minutes from 2 hours after the start of drug administration. The primary endpoint was the overall response rate (ORR). The results of Study 002 showed that the ORR based on an assessment of the Independent Central Review Committee per RECIST version 1.1 was 71.4% (90% confidence interval [CI], 51.3%-86.8%). The lower limit of the 90% CI exceeded the prespecified threshold for ORR. When BNCT is applied to patients with unresectable LA/LR head and neck cancer, precautions should be taken, and patients should be monitored for possible onset of dysphagia, brain abscess, skin disorder, crystal urine, cataract, and/or carotid hemorrhage. IMPLICATIONS FOR PRACTICE: Borofalan ( B), a treatment system and a dose calculation program for boron neutron capture therapy (BNCT), demonstrated significant efficacy in an open-label, uncontrolled trial in which overall response rate was the primary endpoint for patients with unresectable locally advanced or locally recurrent head and neck cancer. Although no information about survival benefits was obtained, BNCT will become an effective treatment option that is expected to manage local lesions that are intractable with any standard therapy. In addition, BNCT is expected to maintain quality of life of the intended patient population, on account of its high tumor selectivity and low invasiveness.
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http://dx.doi.org/10.1002/onco.13805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265361PMC
July 2021

The impact of pre-hospital 12-lead electrocardiogram and first contact by cardiologist in patients with ST-elevation myocardial infarction in Kanagawa, Japan.

J Cardiol 2021 09 27;78(3):183-192. Epub 2021 Apr 27.

Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa 227-8501, Japan.

Background pre-hospital 12-lead electrocardiogram (ECG) by emergency medical service (EMS) personnel at the site of first medical contact (FMC) and the physician of first contact both play important roles in managing patients with ST-elevation myocardial infarction (STEMI). However, in Japan, pre-hospital 12-lead ECG is not routinely performed by EMS personnel at the site of FMC and the physician of first contact is not always a cardiologist. Methods from October 2015 to October 2019, 2035 consecutive STEMI patients transported from the field by ambulance were analyzed from the K-ACTIVE registry. Based on the presence (+) or absence (-) of pre-hospital 12-lead ECG / first contact by cardiologist, patients were divided into 4 groups (+/+, +/-, -/+, -/-). Patient characteristics, FMC to door time, door to device time and in-hospital mortality were compared. Results the numbers of patients in each group were as follows (+/+, n = 987; +/-, n = 211; -/+, n = 610; -/-, n = 227). For patient characteristics, there were significant differences in the prevalence of dyslipidemia and the presence of chest pain. The FMC to door time was similar (median value, +/+, 24 min; +/-, 25 min; -/+, 24 min; -/-, 24 min; p = 0.23). The door to device time was the shortest in the +/+ group (median value, +/+, 65 min; +/-, 80 min; -/+, 69 min; -/-, 88 min; p < 0.0001). Crude in-hospital mortality was the highest in the -/- group (+/+, 3.9%; +/-, 2.4%; -/+, 5.8%; -/-, 11.9%; p < 0.0001). After adjustment for age and sex, the adjusted odds ratios for in-hospital mortality were as follows [odds ratio (with 95% confidence interval) +/+, 0.33 [0.19-0.57]; +/-, 0.19 [0.07-0.52]; -/+, 0.49 [0.29-0.86]; -/-, 1 [reference)]. Conclusion pre-hospital 12-lead ECG and the physician of first contact had a significant impact on the door to device time and in-hospital mortality. Continuous efforts should be made to improve acute management of STEMI.
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http://dx.doi.org/10.1016/j.jjcc.2021.04.001DOI Listing
September 2021

Impact of Exercise-Based Cardiac Rehabilitation on the Mid-Term Outcomes of Patients After Acute Myocardial Infarction Treated With Current Acute-Phase Management and Optimal Medical Therapy.

Heart Lung Circ 2021 Sep 16;30(9):1320-1328. Epub 2021 Apr 16.

Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.

Background: Early reported beneficial effects of cardiac rehabilitation (CR) have recently been disputed. The present study aimed to investigate the clinical impact of CR on the mid-term outcomes of patients following ST-segment elevation myocardial infarction (STEMI) treated with currently available management.

Methods: This study reviewed 145 consecutive patients who underwent primary coronary intervention and were discharged without any disability after STEMI during 2013-2015.

Results: Among the patients, 66 (45.5%) completed an outpatient CR program (CR group) and 79 were their non-CR counterparts or patients who dropped out of the program (N-D group). There were no between-group differences in patient demographics and clinical profiles, including door-to-balloon times and prescriptions. A total of 27 patients developed major adverse cardiac and cerebrovascular events (MACCE) during follow-up. The MACCE-free survival rates were 88% and 76% in the CR and N-D groups, respectively (log-rank, p=0.04). Cox proportional analysis demonstrated that inclusion in the N-D group was a significant predictor of MACCEs (HR, 2.36; 95% CI, 1.07-5.74; p=0.03). In the CR group, peak oxygen consumption and ventilatory efficiency determined by cardiopulmonary exercise testing significantly improved after the program (p<0.01).

Conclusions: The impact of CR on the mid-term prognosis of patients with STEMI, even in the current myocardial infarction management era, was beneficial.
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http://dx.doi.org/10.1016/j.hlc.2021.03.268DOI Listing
September 2021

Substantial anti-gout effect conferred by common and rare dysfunctional variants of URAT1/SLC22A12.

Rheumatology (Oxford) 2021 Nov;60(11):5224-5232

Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama.

Objectives: Gout, caused by chronic elevation of serum uric acid levels, is the commonest form of inflammatory arthritis. The causative effect of common and rare variants of ATP-binding cassette transporter G2 (ABCG2/BCRP) on gout risk has been studied, but little attention has been paid to the effect of common (rs121907892, p.W258X) and rare variants of urate transporter 1 (URAT1/SLC22A12) on gout, despite dysfunctional variants of URAT1 having been identified as pathophysiological causes of renal hypouricaemia.

Methods: To address this important but overlooked issue, we investigated the effects of these URAT1 variants on gout susceptibility, using targeted exon sequencing on 480 clinically defined gout cases and 480 controls of Japanese males in combination with a series of functional analyses of newly identified URAT1 variants.

Results: Our results show that both common and rare dysfunctional variants of URAT1 markedly decrease the risk of gout (OR 0.0338, reciprocal OR 29.6, P = 7.66 × 10-8). Interestingly, we also found that the URAT1-related protective effect on gout eclipsed the ABCG2-related causative effect (OR 2.30-3.32). Our findings reveal only one dysfunctional variant of URAT1 to have a substantial anti-gout effect, even in the presence of causative variants of ABCG2, a 'gout gene'.

Conclusion: Our findings provide a better understanding of gout/hyperuricaemia and its aetiology that is highly relevant to personalized health care. The substantial anti-gout effect of common and rare variants of URAT1 identified in the present study support the genetic concept of a 'Common Disease, Multiple Common and Rare Variant' model.
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http://dx.doi.org/10.1093/rheumatology/keab327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566256PMC
November 2021

Potential Association of Circulating MicroRNA-181c and MicroRNA-484 Levels with Cardiorespiratory Fitness after Myocardial Infarction: A Pilot Study.

Prog Rehabil Med 2021 18;6:20210017. Epub 2021 Mar 18.

Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.

Objectives: In the field of exercise physiology, there has been great interest in exploring circulating microRNAs (miRs) as potential biomarkers. However, it remains to be determined whether circulating miRs reflect cardiorespiratory fitness. The aim of this study was to investigate the association between circulating levels of specific miRs and cardiorespiratory fitness evaluated by cardiopulmonary exercise testing (CPET) after acute myocardial infarction (MI).

Methods: Twenty patients who had had an acute MI were included. All patients underwent CPET in the convalescent phase. Quantitative real-time polymerase chain reaction analyses for miR-181 members (a/b/c) and miR-484 were performed to determine the expression levels in the peripheral blood of the included patients and healthy control subjects (n=5).

Results: Post-MI patients showed impaired exercise tolerance and ventilatory efficiency in CPET analysis. Compared with controls, circulating levels of miR-181a and 181c were gradually and significantly elevated through the 1st to 7th days after acute MI, whereas miR-181b and miR-484 were not. Circulating miR levels did not correlate with clinical or echocardiographic parameters. However, circulating levels of miR-181c and miR-484 on the 7th day showed significant positive correlations with the anaerobic threshold and peak oxygen consumption from CPET analysis. Moreover, miR-181c levels were inversely associated with the ventilatory inefficiency index. Patients with high exercise capacity after MI showed significantly higher expressions of circulating miR-181c and miR-484 than those with low exercise capacity.

Conclusions: The results of this pilot study suggest that circulating levels of miR-181c and miR-484 after acute MI may be predictive biomarkers of post-MI cardiorespiratory fitness.
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http://dx.doi.org/10.2490/prm.20210017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972949PMC
March 2021

Clinical predictors for bradycardia and supraventricular tachycardia necessitating therapy in patients with unexplained syncope monitored by insertable cardiac monitor.

Clin Cardiol 2021 May 16;44(5):683-691. Epub 2021 Mar 16.

Division of Cardiology, Department of Medicine, Showa University, Tokyo, Japan.

Background: Insertable cardiac monitors (ICMs) improve diagnostic yield in patients with unexplained syncope. The most of cardiac syncope is arrhythmic causes include paroxysmal bradycardia and supraventricular tachycardia (SVT) in patients with unexplained syncope receiving ICM. Predictors for bradycardia and SVT that necessitate therapy in patients with unexplained syncope are not well known.

Hypothesis: This study aimed to investigate predictors of bradycardia and SVT necessitating therapy in patients with unexplained syncope receiving ICMs.

Methods: We retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope. We performed Cox's stepwise logistic regression analysis to identify significant independent predictors for bradycardia and SVT.

Results: One hundred thirty-two patients received ICMs to monitor unexplained syncope. During the 17-month follow-up period, 19 patients (14%) needed pacemaker therapy for bradycardia; 8 patients (6%) received catheter ablation for SVT. The total estimated diagnostic rates were 34% and 48% at 1 and 2 years, respectively. Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p = .02) was an independent predictor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p = .008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p = .006) were identified as significant independent predictors for SVT.

Conclusion: Syncope during effort, and palpitations or history of atrial fibrillation were independent predictors for bradycardia and for SVT. ICMs are useful devices for diagnosing unexplained syncope.
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http://dx.doi.org/10.1002/clc.23594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119800PMC
May 2021

Clinical significance of prehospital 12-lead electrocardiography in patients with ST-segment elevation myocardial infarction presenting with syncope: from a multicenter observational registry (K-ACTIVE study).

Heart Vessels 2021 Oct 12;36(10):1466-1473. Epub 2021 Mar 12.

Showa University Fujigaoka Hospital, Yokohama, Japan.

Patients with acute myocardial infarction (AMI) presenting with syncope have poor clinical outcomes partly due to a delay in the diagnosis. Although the impact of prehospital 12-lead electrocardiography (PHECG) on the reduction of first medical contact (FMC)-to-device time and subsequent adverse clinical events in patients with AMI has been demonstrated, the impact of PHECG for the patients presenting with syncope remains to be elucidated. This study aimed to explore the impact of PHECG on 30-day mortality in patients with ST-segment elevation myocardial infarction (STEMI) presenting with syncope. From a cohort of multi-center registry [Kanagawa-ACuTe cardIoVascular rEgistry (K-ACTIVE)], a total of 90 consecutive patients with STEMI presenting with syncope were included. The 30-day mortality were compared between patients with PHECG (PHECG group, n = 25) and those without PHECG (non-PHECG group, n = 65). There was no significant difference in the baseline clinical characteristics between the 2 groups. FMC-to-device time was significantly shorter in the PHECG group than in the non-PHECG group (122 [86, 128] vs. 131 [102, 153] min, p = 0.03) due to the shorter door-to-device time. Thirty-day mortality was significantly lower in the PHECG group than in the non-PHECG group (16.0 vs. 44.6%, p = 0.03). In conclusion, PHECG was associated with shorter FMC-to-device time and lower 30-day mortality in patients with STEMI presenting with syncope.
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http://dx.doi.org/10.1007/s00380-021-01832-zDOI Listing
October 2021

Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout.

Int J Mol Sci 2021 Feb 16;22(4). Epub 2021 Feb 16.

Institute of Rheumatology, 128 00 Prague, Czech Republic.

The gene is a well-established hyperuricemia/gout risk locus encoding a urate transporter that plays a crucial role in renal and intestinal urate excretion. Hitherto, p.Q141K-a common variant of ABCG2 exhibiting approximately one half the cellular function compared to the wild-type-has been reportedly associated with early-onset gout in some populations. However, compared with adult-onset gout, little clinical information is available regarding the association of other uricemia-associated genetic variations with early-onset gout; the latent involvement of ABCG2 in the development of this disease requires further evidence. We describe a representative case of familial pediatric-onset hyperuricemia and early-onset gout associated with a dysfunctional ABCG2, i.e., a clinical history of three generations of one Czech family with biochemical and molecular genetic findings. Hyperuricemia was defined as serum uric acid (SUA) concentrations 420 μmol/L for men or 360 μmol/L for women and children under 15 years on two measurements, performed at least four weeks apart. The proband was a 12-year-old girl of Roma ethnicity, whose SUA concentrations were 397-405 µmol/L. Sequencing analyses focusing on the coding region of identified two rare mutations-c.393G>T (p.M131I) and c.706C>T (p.R236X). Segregation analysis revealed a plausible link between these mutations and hyperuricemia and the gout phenotype in family relatives. Functional studies revealed that p.M131I and p.R236X were functionally deficient and null, respectively. Our findings illustrate why genetic factors affecting ABCG2 function should be routinely considered in clinical practice as part of a hyperuricemia/gout diagnosis, especially in pediatric-onset patients with a strong family history.
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http://dx.doi.org/10.3390/ijms22041935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920026PMC
February 2021

C-terminal peptide (hCTP) of human chorionic gonadotropin enhances in vivo biological activity of recombinant Japanese eel follicle-stimulating hormone and luteinizing hormone produced in FreeStyle 293-F cell lines.

Gen Comp Endocrinol 2021 05 2;306:113731. Epub 2021 Feb 2.

Tuna Aquaculture Division, Aquaculture Research Department, Fisheries Technology Institute, Japan Fisheries Research and Education Agency, 1551-8 Taira-machi, Nagasaki 851-2213, Japan. Electronic address:

Gonadotropins (Gths), follicle-stimulating hormone (Fsh), and luteinizing hormone (Lh) play central roles in the reproductive biology of vertebrates. In this study, recombinant single-chain Japanese eel Gths (rGth: rFsh and rLh), and recombinant chimeric Gths (rGth-hCTPs: rFsh-hCTP and rLh-hCTP; rGth-eCTPs: rFsh-eCTP and rLh-eCTP) with an extra O-glycosylation site (either a C-terminal peptide of human (hCTP) or equine (eCTP) chorionic gonadotropin), which are known to prolong the half-life of glycoprotein were produced in HEK293 cells and highly purified. Lectin blot analyses demonstrated that all these recombinant Gths contained N-glycans of the high mannose and complex types. In contrast, only rGth-hCTPs and rGth-eCTPs possessed highly sialylated O-linked oligosaccharides. Further analyses of glycans by liquid chromatography-mass spectrometry suggested that the species, amount, and degree of sialylation of N-glycans were comparable among recombinant Fshs and recombinant Lhs, while the amount of O-glycans with sialic acids in rGth-hCTPs was higher than that in the corresponding rGth-eCTPs. The serum levels of recombinant Gths in male eels significantly increased 12-24 h after a single injection of the Gths. The levels of rGth-hCTPs tended to be higher than those of the corresponding rGths and rGth-eCTPs throughout the experimental period, coinciding with the serum fluctuations of 11-ketotestosterone (11KT). The long-term treatment of male eels with these recombinant Gths also revealed the superiority of rGth-hCTPs in assisted reproduction; thus, the serum levels of 11KT and gonadosomatic indices in eels treated with rGth-hCTPs were higher than those in eels treated with the corresponding rGths and rGth-eCTPs. The induction of the entire process of spermatogenesis was only histologically observed in rGth-hCTPs-treated eels. These findings strongly suggest that hCTP enhances the in vivo biological activity of recombinant Japanese eel Gths due to the high abundance of O-linked glycans with sialylated antennae.
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http://dx.doi.org/10.1016/j.ygcen.2021.113731DOI Listing
May 2021

Early Vascular Response to Ultrathin Biodegradable Polymer Sirolimus-Eluting Stents for the Treatment of ST-Elevation Myocardial Infarction After Plaque Rupture.

Int Heart J 2021 ;62(1):42-49

Division of Cardiology, Department of Medicine, Showa University School of Medicine.

Recent clinical studies suggest that newer-generation drug-eluting stents that combine ultrathin struts and nanocoating (biodegradable polymer sirolimus-eluting stents, BP-SES) could improve long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, the early vascular response to BP-SES in these patients has not been investigated so far.We examined this response in 20 patients with STEMI caused by plaque rupture using frequency-domain optical coherence tomography (OCT) to understand the underlying mechanisms. Plaque rupture was diagnosed by OCT before PCI with BP-SES implantation was performed. OCT was again performed before the final angiography (post-PCI) and after 2 weeks (2W-OCT).BP-SES placement caused protrusion of atherothrombotic material into the stent lumen and incomplete stent apposition in all patients. After 2 weeks, incomplete stent apposition was significantly reduced (% malapposed struts: post-PCI 4.7 ± 3.3%; 2W-OCT 0.9 ± 1.2%; P < 0.0001), and the percentage of uncovered struts also significantly decreased (% uncovered struts: post-PCI; 69.8 ± 18.3%: 2W-OCT; 29.6 ± 11.0%, P < 0.0001). The maximum protrusion area of the atherothrombotic burden was significantly reduced (post-PCI 1.36 ± 0.70 mm; 2W-OCT 0.98 ± 0.55 mm; P = 0.004).This study on the early vascular responses following BP-SES implantation showed rapid resolution of atherothrombotic material and progression of strut apposition and coverage. (UMIN000041324).
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http://dx.doi.org/10.1536/ihj.20-458DOI Listing
February 2021

ATG5 is instrumental in the transition from autophagy to apoptosis during the degeneration of tick salivary glands.

PLoS Negl Trop Dis 2021 01 29;15(1):e0009074. Epub 2021 Jan 29.

Key Laboratory of Animal Parasitology of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

Female tick salivary glands undergo rapid degeneration several days post engorgement. This degeneration may be caused by the increased concentration of ecdysone in the hemolymph during the fast feeding period and both autophagy and apoptosis occur. In this work, we first proved autophagy-related gene (ATG) and caspase gene expression peaks during degeneration of the tick salivary glands. We explored the regulatory role of Rhipicephalus haemaphysaloides autophagy-related 5 (RhATG5) in the degeneration of tick salivary glands. During the fast feeding phase, RhATG5 was cleaved and both calcium concentration and the transcription of Rhcalpains increased in the salivary glands. Recombinant RhATG5 was cleaved by μ-calpain only in the presence of calcium; the mutant RhATG5191-199Δ was not cleaved. Treatment with 20-hydroxyecdysone (20E) led to programmed cell death in the salivary glands of unfed ticks in vitro, RhATG8-phosphatidylethanolamine (PE) was upregulated in ticks treated with low concentration of 20E. Conversely, RhATG8-PE decreased and Rhcaspase-7 increased in ticks treated with a high concentration of 20E and transformed autophagy to apoptosis. High concentrations of 20E led to the cleavage of RhATG5. Calcium concentration and expression of Rhcalpains were also upregulated in the tick salivary glands. RNA interference (RNAi) of RhATG5 in vitro inhibited both autophagy and apoptosis of the tick salivary glands. RNAi of RhATG5 in vivo significantly inhibited the normal feeding process. These results demonstrated that high concentrations of 20E led to the cleavage of RhATG5 by increasing the concentration of calcium and stimulated the transition from autophagy to apoptosis.
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http://dx.doi.org/10.1371/journal.pntd.0009074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875341PMC
January 2021

Male advantage observed for in vitro fertilization mouse embryos exhibiting early cleavage.

Reprod Med Biol 2021 Jan 30;20(1):83-87. Epub 2020 Oct 30.

Obihiro University of Agriculture and Veterinary Medicine Obihiro Japan.

Purpose: Mouse embryos forming blastocoele early vs those forming late are predominantly male. We examined whether the male advantage could be recognized at an earlier stage of development.

Methods: The IVF embryos were classified into early, intermediate, and late development groups based on the time of the third cleavage, and the and genes were detected to identify their sex in the classified embryos. Furthermore, embryos that were classified based on the time of the third cleavage were transferred to recipient animals and the sex ratio of the fetuses was determined at birth.

Results: Approximately 90% of the early-developing embryos that exhibited third cleavage as early as 47 hours after insemination were male when analyzed using PCR at the blastocyst stage. PCR analysis showed that 61% of the intermediate-developing embryos (third cleavage occurring 48-50 hours after insemination) and 45% of late-developing embryos (third cleavage occurring at 51 hours or later postinsemination) were male. After embryo transfer, the early-developing embryos produced 80% males, while intermediate- and late-developing embryos produced 56% and 45% males, respectively.

Conclusions: Male embryos tend to develop faster than female embryos during early stage of preimplantation in mice.
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http://dx.doi.org/10.1002/rmb2.12355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812486PMC
January 2021
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