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The LBX1 gene is located near a single nucleotide polymorphism that is highly associated with susceptibility to adolescent idiopathic scoliosis and is considered one of the strongest candidate genes involved in the pathogenesis of this condition. We have previously found that loss of LBX1 from skeletal muscle results not only in spinal deformity but also in lean body mass, suggesting a potential role for LBX1 in energy metabolism. The purpose of the present study was to test this hypothesis by analyzing the phenotype of mice lacking LBX1 in skeletal muscle with a focus on energy metabolism. We found that loss of LBX1 rendered mice more resistant to high-fat diet-induced obesity, despite comparable food intake between mutant and control mice. Notably, the mutant mice exhibited improved glucose tolerance, increased maximal aerobic capacity, and higher core body temperature compared to control mice. In addition, we found that overexpression of LBX1 decreased glucose uptake in cultured cells. Taken together, our data show that LBX1 functions as a negative regulator of energy metabolism and that loss of LBX1 from skeletal muscle increases systemic energy expenditure resulting in lean body mass. The present study thus suggests a potential association between LBX1 dysfunction and lean body mass in patients with adolescent idiopathic scoliosis. [ABSTRACT FROM AUTHOR]

Sialic acid (Sia) is a group of acidic sugars with a 9-carbon backbone, and classified into 3 species based on the substituent group at C5 position: N -acetylneuraminic acid (Neu5Ac), N -glycolylneuraminic acid (Neu5Gc), and deaminoneuraminic acid (Kdn). In Escherichia coli , the sialate aldolase or N -acetylneuraminate aldolase (NanA) is known to catabolize these Sia species into pyruvate and the corresponding 6-carbon mannose derivatives. However, in bacteria, very little is known about the catabolism of Kdn, compared with Neu5Ac. In this study, we found a novel Kdn-specific aldolase (Kdn-aldolase), which can exclusively degrade Kdn, but not Neu5Ac or Neu5Gc, from Sphingobacterium sp. which was previously isolated from a Kdn-assimilating bacterium. Kdn-aldolase had the optimal pH and temperature at 7.0–8.0 and 50 °C, respectively. It also had the synthetic activity of Kdn from pyruvate and mannose. Site-specific mutagenesis revealed that N50 residue was important for the Kdn-specific reaction. Existence of the Kdn-aldolase suggests that Kdn-specific metabolism may play a specialized role in some bacteria. [ABSTRACT FROM AUTHOR]

Heterotopic ossification is abnormal bone formation in soft tissues that occurs primarily after injury and major surgery. This condition often causes local pain and limits joint motion in the affected limb. Currently, there is no effective treatment or prophylaxis for this condition other than surgical removal of the lesion. Recent studies suggest that retinoic acid receptor (RAR) agonists are effective in suppressing heterotopic ossification in patients with Fibrodysplasia Ossificans Progressiva, a congenital disorder characterized by progressive ossification of soft tissue, by suppressing the aberrant differentiation of mesenchymal stem cells in muscle. In this study, we aimed to elucidate the potential use of RAR agonists in suppressing injury‐induced ectopic tendon ossification using a mouse Achilles tenotomy model. Contrary to our initial hypothesis, administration of RAR agonists throughout the experimental period (5 weeks) accelerated ectopic tendon ossification in our model. Of note, in vitro differentiation experiments using tendon‐derived mesenchymal stem cells revealed that RAR agonists play opposing roles in osteogenic and chondrogenic differentiation, promoting the former and suppressing the latter. Indeed, we found that RAR agonists suppressed tendon ossification when administered before cartilage nodule formation, but promoted it when administered after. These results suggest that RAR agonists have a dual and opposing effect on tendon ectopic ossification, depending on the duration and timing of their administration. Our data may provide a basis for further investigation of the potential use of RAR agonists in the treatment of injury‐induced heterotopic ossification. [ABSTRACT FROM AUTHOR]

Abstract: We study the function for , and . We regard as a p-adic analytic function. We prove that satisfies a Frobenius equation and see that Jacobi sum appears in this equation. We consider the relation between the dimension of space of bounded solutions of and the dimension of the space of solutions of L in . We prove that for almost all primes and that for almost all primes if and only if for almost all primes. Moreover in this case is an algebraic function. [Copyright &y& Elsevier]

LBX1 is a gene located near a single‐nucleotide polymorphism, rs11190870, which is highly associated with susceptibility to adolescent idiopathic scoliosis. However, the potential involvement of LBX1 in the etiology of this spinal deformity has not been elucidated. In this study, we aimed to determine whether the lack of LBX1 in skeletal muscle results in spinal deformities in mice. We generated mutant mice in which the Lbx1 allele was conditionally excised under the control of a human muscle actin promoter. Mice lacking LBX1 from the skeletal muscle were fertile and available. The mutant mice had hypoplastic forelimbs and weighed less than control animals, but otherwise, there were no overt anomalies. The mice did not exhibit a scoliosis‐like spinal deformity; however, they developed moderate kyphosis as they grew old. These observations indicated that LBX1 is involved in limb development and potentially in the maintenance of spinal curvature/alignment in mice. [ABSTRACT FROM AUTHOR]

For improving the ozone consumption efficiency (OCE) of the ozone-electrolysis process, an ozone-electrolysis system with an independent electrolytic cell from an ozone contactor (indirect ozone injection system) and a three-dimensional electrode were introduced in this study. The reactor successfully enhanced the OCE and the ratio of 1,4-dioxane degradation rate to ozone injection rate (RDO) in comparison with the previous reactor. The three-dimensional electrode also contributed the improvement of the OCE and the RDO due to lowering the current density on the cathode. As the indirect ozone injection system allows higher degree of freedom for the reactor design, it is useful for application of ozone-electrolysis to practical water treatments. [ABSTRACT FROM AUTHOR]

We have developed a miniaturized 2 x 2 switch cell, a key component of single-flux-quantum switches. The cell was optimized using a full-custom design approach instead of our conventional cell-based design approach. The cell contains 74 Josephson junctions, and its power consumption is 16.8 μW. Its area is significantly reduced to 160 μm x 200 μm, which is 69% smaller than our conventional cell-based switch. We fabricated test chips using our 2.5-kA/cm² Nb standard process and confirmed a 40-GHz operation with a bias margin of ±8.5% by an on-chip test. We also designed 4 × 4 and 8 × 8 cross-bar switches using the 2 × 2 switch cells. The 40-GHz operation of the 4 × 4 switch was confirmed with a bias margin of ±4% by an on-chip test. The full function of the 8 × 8 switch was also confirmed with a bias margin of ±5% at a low frequency (10 kHz). The area of these switches was reduced to about half of that of our conventional switches. We discussed large-scale switches using our advanced high-Jc multilayer process. We estimated that area of a 32 x 32 switch designed for the advanced process are reduced by 83% compared to a switch designed for the standard process. [ABSTRACT FROM AUTHOR]

Conclusion. The results presented here provide evidence of the enhancing effect of oral fluoropyrimidine derivative S-1 in concomitant chemoradiotherapy for head and neck cancer and further insights into its biological mechanism. Objective. To investigate the additive effect of S-1 and radiation for human hypopharyngeal cancer. Materials and methods. Nude mice bearing hypopharyngeal cancer cells (H891) were used for an in vivo model. S-1 was administered at a volume of 0.01 mg/g body weight per mouse for 14 days, and tumors were irradiated with 2.0 Gy on days 1 and 8. Mice treated with either radiation or S-1 alone were used as controls. The growth of tumors in each group was measured and, after completion of the treatment, a focused DNA array was used to determine mRNA expression levels in the tumors of 132 genes related to 5-fluorouracil (5-FU), radiation or carcinogenesis. Results. The additive antitumor effect of S-1 and radiation was statistically confirmed on day 14 (p=0.01). DNA array assay showed significant changes in expression of several genes, including DNA repair gene POLD, angiogenesis-related genes bFGF and TP, DNA topoisomerase TOP2A, and nucleoside transporter gene ENT1. [ABSTRACT FROM AUTHOR]

Ozonation combined with electrolysis (ozone–electrolysis) is a new advanced oxidation process for water treatment. The advantages of ozone–electrolysis are (1) that reagents such as hydrogen peroxide or ferrous salts are unnecessary, (2) there is less influence from chromaticity, and (3) electric power is only required for operation. However, electrolysis has a serious limitation, in that it requires electrical conductivity (EC). This research is aimed at developing an ozone–electrolysis reactor that is applicable to wastewater with low EC using a cation exchange membrane as solid electrolyte. Moreover, experimental evidence of hydroxyl radical (·OH) generation via the cathodic reduction of ozone was obtained. Competitive kinetics analysis, based on the experimental data from the ozone–electrolysis of a mixed solution of 1,4-dioxane and tert-butyl alcohol, revealed that ·OH contributed to 1,4-dioxane degradation. The ozone–electrolysis reactor was successfully applicable to degradation of 1,4-dioxane in both 1,4-dioxane solution (EC: less than 0.30μS/cm) and a landfill leachate treated by a low-pressure reverse osmosis membrane (EC: 0.06mS/cm). The use of a solid electrolyte was also very effective in reducing the electric power required for electrolysis. [Copyright &y& Elsevier]

Abstract: The pre-Holocene Cenozoic sequence outcrops in the terrestrial part of the eastern margin of the Mekong Basin. However, the stratigraphy of the sequence is still unclear. Its detailed stratigraphy and chronology were therefore studied along the Dong Nai River, southern Vietnam, and the lithofacies and the relations among the formations were investigated from the outcrops. The ages of the deposits were determined by using optically stimulated luminescence (OSL) dating. The Ba Mieu Formation was deposited about 176±52ka during marine isotope stage (MIS) 7–6. The Thu Duc Formation was deposited about 97±27ka during MIS 5. Both the Ba Mieu and Thu Duc formations are composed of fluvial and tidally influenced coastal deposits. The newly proposed Nhon Trach Formation was originally an eolian (blanket) deposit, but it has been partly reworked by fluvial processes. The Nhon Trach Formation was deposited about 10.9±4.7ka, in the last part of the Pleistocene to the beginning of the Holocene. The OSL ages for the Ba Mieu, Thu Duc, and Nhon Trach formations are younger than the ages previously assigned to these formations. [Copyright &y& Elsevier]

Traumatic heterotopic ossification is a condition in which extraskeletal bone formation occurs in soft tissues after injury. It most commonly occurs in patients who had major orthopedic surgery and in those with severe extremity injuries. The lesion causes local pain and can impair motor function of the affected limb, but there is currently no established prophylaxis or treatment for this condition. In this study, we show that immobilization at an early stage of the inflammatory response after injury can attenuate ossification formation in a murine Achilles tenotomy model. Gene expression analysis revealed a decrease in the expression of Tnf and an increase in the expression of Mkx, which encodes one of the master regulators of tendon differentiation, Mohawk. Notably, we found that TNF‐α suppressed the expression of Mkx transcripts and accelerated the osteogenic differentiation of tendon‐derived mesenchymal stem cells (MSCs), suggesting that TNF‐α acts as a negative regulator of Mkx transcription. Consistent with these findings, pharmaceutical inhibition of TNF‐α increased the expression of Mkx transcripts and suppressed bone formation in this mouse model. These findings reveal the previously unrecognized involvement of TNF‐α in regulating tendon MSC fate through suppression of Mkx expression and suggest that TNF‐α is a potential target for preventing traumatic heterotopic ossification. [ABSTRACT FROM AUTHOR]

André proved the Dwork conjecture on the log-growth Newton polygon of p -adic differential equations. We consider conditions such that the left end points of generic log-growth Newton polygon and the left end point of special log-growth Newton polygon coincide. We give an upper bound of the highest slope of differential equations at generic point. This shows that these end points coincide if differential operator has rational function coefficients and the rank of differential operator is equal to 2. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is associated with a high plasma level of low-density lipoprotein (LDL) cholesterol, leading to an increased risk of cardiovascular diseases. To develop basic and translational research on FH, we here generated an FH model in a non-human primate (cynomolgus monkeys) by deleting the LDL receptor (LDLR) gene using the genome editing technique. Six LDLR knockout (KO) monkeys were produced, all of which were confirmed to have mutations in the LDLR gene by sequence analysis. The levels of plasma cholesterol and triglyceride were quite high in the monkeys, and were similar to those in FH patients with homozygous mutations in the LDLR gene. In addition, periocular xanthoma was observed only 1 year after birth. Lipoprotein profile analysis showed that the plasma very low-density lipoprotein and LDL were elevated, while the plasma high density lipoprotein was decreased in LDLR KO monkeys. The LDLR KO monkeys were also strongly resistant to medications for hypercholesterolemia. Taken together, we successfully generated a non-human primate model of hypercholesterolemia in which the phenotype is similar to that of homozygous FH patients. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is associated with a high plasma level of low-density lipoprotein (LDL) cholesterol, leading to an increased risk of cardiovascular diseases. To develop basic and translational research on FH, we here generated an FH model in a non-human primate (cynomolgus monkeys) by deleting the LDL receptor (LDLR) gene using the genome editing technique. Six LDLR knockout (KO) monkeys were produced, all of which were confirmed to have mutations in the LDLR gene by sequence analysis. The levels of plasma cholesterol and triglyceride were quite high in the monkeys, and were similar to those in FH patients with homozygous mutations in the LDLR gene. In addition, periocular xanthoma was observed only 1 year after birth. Lipoprotein profile analysis showed that the plasma very low-density lipoprotein and LDL were elevated, while the plasma high density lipoprotein was decreased in LDLR KO monkeys. The LDLR KO monkeys were also strongly resistant to medications for hypercholesterolemia. Taken together, we successfully generated a non-human primate model of hypercholesterolemia in which the phenotype is similar to that of homozygous FH patients. [ABSTRACT FROM AUTHOR]

This paper describes the syntheses, crystal structure analyses and physical properties of new D-A dyads containing tetrathiafulvalene (TTF) and 4,4-difluoro-4-bora-3a,4a-diaza- s-indacene (BODIPY) moieties linked by a p-phenylene or p-phenylenevinylene spacer for the development of photoresponsive organic conducting materials that can show photofunctionality in the visible region. The absorption spectra of the synthesized dyads recorded in CHCl3 show strong absorptions at 505 nm originating from the BODIPY moiety and weak charge-transfer absorptions at around 550 nm. The fluorescence corresponding to the BODIPY moiety was suppressed to less than half in all the dyads, which suggests the formation of photoinduced charge-transfer states. All the thin-film samples of the dyads spin-coated onto ITO-coated glass substrates exhibited electric current generation that are related to the absorption spectra of the thin films. In the crystalline samples of three dyads, the TTF moieties formed 1D conducting columns through the dimerization of the TTF moieties and relatively strong side-by-side interactions between neighbouring stacking columns. All the neutral crystals exhibited photoinduced conductivity along the stacking direction of the TTF moieties and the crystal with the weakest dimerization and the strongest side-by-side interaction showed the greatest photoconductivity of the three crystals. The PF6 salt of the dyad with a p-phenylene spacer and a 2:1 stoichiometry of the dyad and anion exhibited semi-conducting behaviour with a conductivity of 3.0 × 10-4 S cm-1 at room temperature and an activation energy of 0.18 eV, probably because this crystal has a half-filled Mott insulating band structure that originates from strongly dimerized intermolecular interactions. Upon photoirradiation, this salt showed a slight enhancement of conductivity. [ABSTRACT FROM AUTHOR]

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the most common procedure in minimally invasive spine stabilization (MISt), details of the technique remain unclear. This technical report shows the mid-long-term clinical outcomes in patients who underwent posterior oblique square decompression (POSDe) with the three-step wanding technique of tubular MIS-TLIF for degenerative lumbar disease. Tubular MIS-TLIF (POSDe) was performed on 50 patients (males, 19; age, 69.2 ± 9.6 years), and traditional open surgery was performed (OS) on 27 (males, 4; age, 67.9 ± 6.6 years). We evaluated the clinical outcomes using the Visual Analog Scale for back pain, Japanese Orthopedic Association (JOA) scores, and JOA Back Pain Evaluation Questionnaire. We also assessed the fusion rate using the Bridwell grading system with computed tomography or plain radiography for at least 2 years postoperatively. Although there was no significant difference in the improvement rate of JOA scores between the two groups, the mean operation time and blood loss were significantly lower with MIS-TLIF than with OS. In the tubular MIS-TLIF group, there were no cases of deep wound infection; four cases had a pseudarthrosis, two had dural injury, and three had cage retropulsion. We revealed good clinical outcomes in patients who underwent POSDe. [ABSTRACT FROM AUTHOR]

Abstract: Surface pressure (π)–molecular area (A) and surface potential (ΔV)–A isotherms have been measured for two-component monolayers of four different perfluorocarboxylic acids [FCn; perfluorododecanoic acid (FC12), perfluorotetradecanoic acid (FC14), perfluorohexadecanoic acid (FC16), and perfluorooctadecanoic acid (FC18)] and dimyristoylphosphatidylethanolamine (DMPE) on 0.15M NaCl (pH 2) at 298.2K. The present study is focused on the miscibility and the interfacial behavior for the binary DMPE/FCn monolayers upon compression. From the isotherms, the miscibility has been elucidated in terms of the additivity rule, the interaction parameter, and the interaction energy. The interaction parameter (or energy) is compared with that for the previous dipalmitoylphosphatidylcholine (DPPC)/FCn systems [Colloids Surf. B 41 (2005) 285–298] to understand the effect of phospholipids’ polar headgroup on the binary miscibility. Furthermore, the phase behavior of the DMPE/FCn systems has been morphologically examined using fluorescence microscopy (FM) and atomic force microscopy (AFM). These images reveal the different interaction modes among the four systems; DMPE can be miscible with FC12 and FC14 and immiscible with FC16 and FC18 in the monolayer state. These systematic examinations indicate that the miscibility of perfluorocarboxylic acids and phospholipids depends on combination of hydrocarbon and fluorocarbon chain lengths and on phospholipids’ polar headgroups within a monolayer. [Copyright &y& Elsevier]

Periodic flows downstream from a centrifugal pump impeller in vaneless and vaned diffusers were measured by using a single hole yawmeter and a phase-locked sampling method. The flows were also calculated by an inviscid flow analysis using the blade-surface singularity method. The periodic variations in calculated static pressure with the impeller rotating quantitatively agree well with the measured ones. The flow behaviors in the vaned diffuser are discussed, citing measured and calculated results. The potential interaction between the impeller and the diffuser blades appears more strongly than the impeller-wake interaction. The appearance of static pressure fluctuations due to the impeller's rotating in the fully vaned zone is different from that in the semivaned zone of the diffuser. The existence of the peripheral blade surface of the impeller outlet with an outlet edge of the pressure surface causes violent pressure fluctuations in the vaned diffuser. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is now a treatment for women with uterine factor infertility to have a child. However, UTx is still largely at the experimental stage, and many medical issues remain unsolved. Therefore, adequate studies in large animals including non‐human primates are required for validation of these issues. UTx research, especially in non‐human primates, can provide important information for its full establishment in humans due to the anatomical and physiological similarities between the two. We accumulated data from UTx studies using cynomolgus macaques since 2009 and established autologous and allogeneic UTx models which led to deliveries after performing the procedure. In this paper, we summarized key points to develop UTx models in cynomolgus macaques based on our experience. UTx models in non‐human primates can surely contribute new and beneficial knowledge in this field and can be useful for the further development of UTx in humans. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to examine the allowable warm ischemic time and pathological changes due to ischemia and reperfusion injury in the uterus of the cynomolgus monkey as a model for uterus transplantation.Material and Methods: Six female cynomolgus monkeys were used in the study. The uterus was resected from the vaginal canal and connected through the bilateral ovarian and uterine arteries and veins only. One animal was used as a control. In the other five animals, the bilateral uterine and ovarian vessels were clamped for 0.5, 1, 2, 4 and 8 h, respectively. Biopsy of the smooth muscle tissue of corpus uteri was performed after each ischemic time and after subsequent reperfusion for 3 h. Biopsy samples were observed by light and electron microscopy. Menstruation recovery was monitored.Results: There were no particular findings in both light and electron microscopy after ischemia for up to 2 h and after subsequent reperfusion. There were no marked changes after ischemia for 4 h, but dilated nuclear pores and rough endoplasmic reticulum swelling were found after reperfusion. These changes also occurred, along with mitochondrial swelling and cristae loss after ischemia for 8 h, and plasma membrane loss, nuclear fragmentation and chromatin condensation were found after reperfusion. Periodical menstruation restarted in all animals with ischemia up to 4 h, but the animal with ischemia for 8 h had amenorrhea and uterine atrophy.Conclusions: The uterus of the cynomolgus monkey tolerates warm ischemia for up to 4 h. [ABSTRACT FROM AUTHOR]

Presents information pertaining to the allylsilylation of carbon--carbon and carbon--oxygen unsaturated bonds through the use of the radical process. Description of the carbometalation of alkenes and alkynes; Information on the radical-based allylation with allylstannanes; Potential of the reactions of terminal alkynes.

In the long-lasting decommissioning of the Fukushima Daiichi Nuclear Power Station (1F), the dismantling of nuclear fuel debris (NFD) remaining in the damaged reactors is an unavoidable but significant issue with many technical difficulties. The dismantling is presumed to involve mechanical and/or thermal processing of NFD, generating significant concentrations of particulates containing α -radionuclides (α -aerosols) that pose significant health risk upon inhalation. In order to minimize the radiation exposure of workers with α -aerosols during the dismantling/decommissioning process at 1F, it is essential to monitor the concentration of α -aerosols at the point of initial generation, i.e. inside the primary containment vessels (PCV) of the damaged reactors. Toward this end, an in-situ monitoring system for α -aerosols (in-situ alpha air monitor: IAAM) was developed and its technical performance was investigated under the conditions expected for the actual environments at 1F. IAAM was confirmed to fulfill four technical requirements: (1) steady operation under high humidity, (2) operation without using filters, (3) capability of measuring high counting rates of α -radiation, and (4) selective measurement of α -radiation even under high radiation background with β / γ -rays. IAAM is capable of selectively measuring α -aerosols with a concentration of 3.2 × 102 Bq/cm 3 or higher without saturation under high humid environment (100%-relative humidity) and under high background with β / γ -radiation (up to 100 mSv/h of γ -radiation). These results demonstrate promising potential of IAAM to be utilized as a reliable monitoring system for α -aerosols during the dismantling of NFD, as well as the whole long-lasting decommissioning of 1F. • An in-situ α -aerosol monitoring system (IAAM) that operated in high humidity and high radiation background was developed. • IAAM was developed as a combined assembly of FFP, heater, thin ZnS scintillator, and MA-PMT. • IAAM is capable of selectively measuring α -radiation without using filters in high humidity and high β / γ -rays background. • The maximum counting rate achieved by IAAM was 2.1 × 107 cpm, which is equivalent to 3.2 × 102 Bq/cm 3 of α -aerosols. • IAAM demonstrates promising potential to be utilized during the dismantling of fuel debris at FDNPS(1F). [ABSTRACT FROM AUTHOR]

Studies the acid-catalyzed intramolecular addition of a hydroxy group to alpha-alkylated vinylsilanes. Cyclization efficiency and rate; Geometry of the C-C double bond and the silyl group; Stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans.

Describes the scope and mechanistic aspects of the silicon-directed cyclization. Application to the stereoselective synthesis of distributed tetrahydrofurans; Acid-catalyzed cyclization of vinylsilanes bearing a hydroxy group.

Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globulin and rituximab were administered to induce immunosuppression and a triple maintenance regimen was used. Menstruation resumed in all animals with long-term survival, except one, which was euthanized due to infusion associated adverse reaction to antithymocyte globulin. Donor-specific antibodies (DSA) were detected in cases 2, 4, and 5, while humoral rejection occurred in cases 4 and 5. Post-transplant lymphoproliferative disorder (PTLD) developed in cases 2 and 3. Pregnancy was attempted in cases 1, 2, and 3 but was achieved only in case 2, which had haploidentical donor and recipient MHCs. Pregnancy was achieved in case 2 after recovery from graft rejection coincident with DSA and PTLD. A cesarean section was performed at full-term. This is the first report of a successful livebirth following allogeneic UTx in nonhuman primates, although the delivery was achieved via UTx between a pair carrying haploidentical MHCs. Experimental data from nonhuman primates may provide important scientific knowledge needed to resolve unsolved clinical issues in UTx. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is a potential option for women with uterine factor infertility to have a child. The clinical features indicating irreversible rejection of the uterus are unknown. In our experimental series of allogeneic UTx in cynomolgus macaques, six female macaques were retrospectively examined, which were unresponsive to treatment with immunosuppressants (i.e. irreversible rejection). Clinical features including general condition, hematology, uterine size, indocyanine green (ICG) fluorescence imaging by laparotomy, and histopathological findings of the removed uterus were evaluated. In all cases, general condition was good at the time of diagnosis of irreversible rejection and thereafter. Laboratory evaluation showed temporary increases in white blood cells, lactate dehydrogenase and C-reactive protein, then these levels tended to decrease gradually. In transabdominal ultrasonography, the uterus showed time-dependent shrinkage after transient swelling at the time of diagnosis of irreversible rejection. In laparotomy, a whitish transplanted uterus was observed and enhancement of the transplanted uterus was absent in ICG fluorescence imaging. Histopathological findings in each removed uterus showed hyalinized fibrosis, endometrial deficit, lymphocytic infiltration and vasculitis. These findings suggest that uterine transplantation rejection is not fatal, in contrast to rejection of life-supporting organs. Since the transplanted uterus with irreversible rejection atrophies naturally, hysterectomy may be unnecessary. [ABSTRACT FROM AUTHOR]

Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated in four recipients (cases 1–4) after allogeneic UTx in cynomolgus macaques. Immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. Postoperative ultrasonography and biopsy of the transplanted uterus and immunoserological examinations were performed. All four recipients survived for >3 months after surgery, but continuous menstruation did not resume, although temporary menstruation occurred (cases 1 and 2). All animals were euthanized due to irreversible rejection and no uterine blood flow (cases 1, 2 and 4) and post-transplant lymphoproliferative disorder (case 3). Donor-specific antibodies against MHC class I and II were detected in cases 1, 2 and 4, but not in case 3. Peripheral lymphocyte counts tended to elevate for CD3+, CD20+ and NK cells in conjunction with uterine rejection, and all animals had elevated stimulation indexes of mixed lymphocyte reaction after surgery. Establishment of allogeneic UTx in cynomolgus macaque requires further exploration of immunosuppression, but the clinicopathological features of uterine rejection are useful for development of human UTx. [ABSTRACT FROM AUTHOR]