Munekazu Naito

Aichi Medical University, Koromo, Aichi, Japan

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Publications (88)183.43 Total impact

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    ABSTRACT: Traditionally, surgical training meant on-the-job training with live patients in an operating room. However, due to advancing surgical techniques, such as minimally invasive surgery, and increasing safety demands during procedures, human cadavers have been used for surgical training. When considering the use of human cadavers for surgical training, one of the most important factors is their preservation. In this review, we summarize four preservation methods: fresh-frozen cadaver, formalin, Thiel’s, and saturated salt solution methods. Fresh-frozen cadaver is currently the model that is closest to reality, but it also presents myriad problems, including the requirement of freezers for storage, limited work time because of rapid putrefaction, and risk of infection. Formalin is still used ubiquitously due to its low cost and wide availability, but it is not ideal because formaldehyde has an adverse health effect and formalin-embalmed cadavers do not exhibit many of the qualities of living organs. Thiel’s method results in soft and flexible cadavers with almost natural colors, and Thiel-embalmed cadavers have been appraised widely in various medical disciplines. However, Thiel’s method is relatively expensive and technically complicated. In addition, Thiel-embalmed cadavers have a limited dissection time. The saturated salt solution method is simple, carries a low risk of infection, and is relatively low cost. Although more research is needed, this method seems to be sufficiently useful for surgical training and has noteworthy features that expand the capability of clinical training. The saturated salt solution method will contribute to a wider use of cadavers for surgical training.
    Full-text · Article · Jan 2016 · Anatomical Science International
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    ABSTRACT: Purpose: Postoperative sexual and urinary dysfunction may occur after rectal cancer surgery involving the pelvis, but this problem cannot be solved. The aim of this study was to examine the nerve morphology of the neurovascular bundle in cadavers to determine possible causes of nerve damage during surgery. Methods: Twenty-two formalin-fixed cadavers were used in the study. The cadavers were donated to the Tokyo Medical University. The study comprised histological evaluation of paraffin-embedded bilateral neurovascular bundle specimens from the cadavers. Four slides of 3-cm thick were made every 1 cm in a plane perpendicular to the rectum towards the pelvic floor from the peritoneal reflection in bilateral neurovascular bundles in 22 cadavers. The number of nerves, the mean nerve area, and the mean nerve diameter were measured in each slide. Results: The results were categorized into cases with high (group H) and low (group L) positions of the pelvis 1 cm above and 2 cm below the peritoneal reflection, respectively. There was no significant difference in the number of nerves between these groups. The nerve area and nerve diameter were significantly smaller in group L, and these characteristics were more marked in males. Conclusions: Our results show that the nerves of the neurovascular bundle became smaller in the deep pelvis. This may cause these nerves to be more susceptible to injury, resulting in nerve damage in the deep pelvis that leads to postoperative dysfunction. Particularly, this type of nerve damage may be a cause of postoperative sexual dysfunction in males.
    No preview · Article · Dec 2015 · International Journal of Colorectal Disease
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    ABSTRACT: Background The acupuncture point BL23 is located in the region of the posterior ramus of the second lumbar spinal nerve (L2) and has historically been used to treat conditions such as lower back pain, pollakiuria, erectile dysfunction, dysmenorrhoea, tinnitus, and vertigo. Some of these treatment effects have been hypothesised to be mediated by the sympathetic nervous system. It was recently discovered that the posterior ramus of the spinal nerve (PRSN) at L2 forms not two but three branches. Objective To examine the relationship between the acupuncture point BL23 and the L2 PRSN in order to consider the pathways possibly affected by BL23 acupuncture. Methods Acupuncture needles were inserted through the skin at BL23 to a depth of 3 cm a total of 13 times in eight donor cadavers (seven right-sided, six left-sided). Leaving the needle in place, ventral dissection was performed to determine the PRSN anatomy between the L1 and L3 spinal segments. In four cadavers, the relationship between the L2 spinal nerve and sympathetic branches was additionally evaluated. Following dissection, three-dimensional (3D) data were acquired using a photo scanner and 3D structural images were created using 3D computer graphics software. One additional (female) cadaver was studied without insertion of an acupuncture needle (due to significant scoliosis). Results The L2 PRSN was divided into medial, intermediate and lateral branches. The needle inserted at BL23 came to lie in the region of the intermediate or lateral branches in all cases. Rami communicantes were found between the L2 spinal nerve and sympathetic trunk with fibres going on to supply the superior hypogastric plexus. Conclusions Our findings suggest that acupuncture needles inserted at BL23 come into close proximity with the intermediate or lateral branch of the L2 PRSN, which could result in stimulation of both the somatic and sympathetic nervous systems.
    No preview · Article · Oct 2015 · Acupuncture in Medicine
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    ABSTRACT: Exposure to di-(2-ethylhexyl) phthalate (DEHP) induces spermatogenic disturbance (SD) through oxidative stress, and affects the immune system by acting as an adjuvant. Recently, we reported that in mice, a low dose of DEHP, which did not affect spermatogenesis, was able to alter the testicular immune microenvironment. Experimental autoimmune orchitis (EAO) can be induced by repeated immunization with testicular antigens, and its pathology is characterized by production of autoantibodies and SD. In the present study, we investigated the effect of a low-dose DEHP on the susceptibility of mice to EAO. The exposure to DEHP-containing feed (0.01%) caused a modest functional damage to the blood-testis barrier (BTB) with an increase in testicular number of interferon gamma (IFN-γ)-positive cells and resulted in the production of autoantibodies targeting haploid cells, but did not affect spermatogenesis. While only single immunization with testicular antigens caused very mild EAO, the concurrent DEHP exposure induced severe EAO with significant increases in number of interferon gamma-positive cells and macrophages, as well as lymphocytic infiltration and serum autoantibody titer accompanied by severe SD. To summarize, the exposure of mice to the low-dose DEHP does not induce significant SD, but it may cause an increase in IFN-γ positive cells and modest functional damage to the BTB in the testis. These changes lead to an autoimmune response against haploid cell autoantigens, resulting in increased susceptibility to EAO.
    No preview · Article · Sep 2015 · Reproductive biology
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    ABSTRACT: The nerve to the abductor digiti minimi muscle (ADMM nerve) is the first branch of the lateral plantar nerve or originates directly from the posterior tibial nerve. Damage to the ADMM nerve is a cause of heel pain and eventually results in ADMM atrophy. It is known that ADMM atrophy occurs more often in females than in males, and the reason remains unclear. This study aimed to explore sex differences in the branching pattern, position, and angle of the ADMM nerve. Forty-two cadavers (20 males, 22 females) were dissected at Aichi Medical University between 2011 and 2015. Cases of foot deformity or atrophy were excluded and 67 ft (30 male, 37 female) were examined to assess the branching pattern, position, and angle of the ADMM nerve. The branching positions of the ADMM nerve were superior to the malleolar-calcaneal axis (MCA) in 37 ft (55 %), on the MCA in 10 ft (15 %), and inferior to the MCA in 20 ft (30 %). There was no case among male feet in which the ADMM nerve branched inferior to the MCA, whereas this pattern was observed in 19 of 37 female feet (51 %). The branching position of the ADMM nerve was significantly closer to the MCA in female feet than in male feet. There were no significant sex differences in the branching pattern and angle of the ADMM nerve. The ADMM nerve sometimes branches off inferior to the MCA in females, but not in males. This difference may be the reason for the more frequent occurrence of ADMM atrophy in females than in males.
    Full-text · Article · Jun 2015 · Journal of Foot and Ankle Research
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    ABSTRACT: Background: Because surgical training (ST) courses using cadavers have been performed to advance surgeons' techniques without any risk to patients, the new embalming methods to make cadavers the more soft and safe are desired. The aim of this study is to evaluate the suitability of cadavers embalmed by the saturated salt solution (SSS) method 1) for ST. Methods: Six cadavers were embalmed by three methods: formalin solution (FAS), Thiel solution (TS) 2) , and SSS methods. Fourteen surgeons evaluated the three embalming methods. Furthermore, seven trauma surgeons and two orthopedists operated these cadavers by 21 procedures. In addition, ultrasonography, central venous catheterization, and incision with cauterization followed by autosuture stapling were performed. Results: The SSS method produced cadavers with flexible joints (Table 1) and a high tissue quality suitable for ST (Figure 1).The surgeons evaluated the cadavers embalmed by the SSS method to be highly equal to those embalmed by the TS method (Figure 2). Ultrasound images were clear in the cadavers embalmed by both TS and SSS methods (Figure 3). Central venous catheterization could be performed in a cadaver embalmed by the SSS method and then be affirmed by X-ray (Figure 4). Lungs and intestines could be incised with cauterization and autosuture stapling in the cadavers embalmed by TS and SSS methods (Figure 1). Conclusion: Cadavers embalmed by the SSS method are sufficiently useful for ST not less than ones embalmed by TS method. The SSS method is considered to have a beneficial feature that it is simple and low-cost.
    Full-text · Poster · Mar 2015
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    ABSTRACT: A case of an additional right external iliac vein lacking a right common iliac vein was found in an 84-year-old female cadaver during a dissection course at Aichi Medical University in 2014. The findings are reported and discussed from the embryological and clinical viewpoints. The right and left iliac venous systems were macroscopically observed with attention to the homonymous arteries and the inferior vena cava. In this cadaver, a preaortic external iliac vein originated from a right external iliac vein and drained directly into the inferior vena cava. The preaortic and right external iliac veins surrounded the right external iliac artery. In addition, the right internal iliac vein drained into the left common iliac vein, and the right obturator vein drained into the right external iliac vein. Our findings suggested that normal external iliac veins developed from the ventral limb of the iliac venous system in this case. Our case has clinical importance for surgical complications such as hemorrhages in pelvic operations, phlebography, and especially central venous cauterization of the right femoral vein.
    No preview · Article · Feb 2015 · Anatomical Science International
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    ABSTRACT: The periareolar incision is the preferred method for mammaplasty because of the minimal scarring, and suturing of the superficial fascial system (SFS) is useful for avoiding hypertrophic scarring. In this report, we describe the anatomical location of the SFS around the nipple-areolar complex (NAC) and its histological structure. To define the location of the SFS, 20 healthy women were assessed by ultrasonography, and sections of the NAC of 10 female cadavers were examined under a light microscope. Ultrasonographic examination of sagittal sections of the breast revealed a hyperdense line immediately beneath the skin, which ran parallel with the skin and turned under the NAC. At the turning point, the line thickened to an average of 3.09 mm. The distance between the nipple and the thickest point of the hyperdense line was 10.14 mm on average. Histological structures of the line were collagen and elastic fibers containing smooth muscles that were connected to the dermis and adipose tissue. At the turning point, nerves, blood vessels, and mammary ducts were irregularly observed in the area of collagen and elastic fibers. These structures were intermingled, and the fiber bundle was very thick. The thickest area of the turning point is an area of the superficial layer of superficial fascia, which is a key structure around the NAC. The detailed anatomical data shown in our study provide good morphological landmarks for the closure of periareolar incisions. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.
    No preview · Article · Feb 2015 · Aesthetic Plastic Surgery
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    ABSTRACT: For managing major limb amputation, it is important to consider ischemic time and reperfusion injury by free radicals after the blood supply is reestablished. State of preservation during transplant surgery is crucial for the survival and function of the tissue, graft, or organ. In this study, we confirmed the effect of intermittent blood flow in rat ischemic hind limb and developed a new oxygenic preservation method using artificial oxygen carrying hemoglobin vesicles (HbVs). We first compared a continuous ischemic model and an intermittent reflow model on rat hind limb. At postoperative day 7, hind limbs were evaluated. Next, we performed total amputation, normothermic preservation by perfusion with extracellular-trehalose-Kyoto (ETK) solution or HbV, and microsurgical replantation of the left hind limb. Venous efflux was analyzed, the amputated limb evaluated after 6 hr perfusion, and the replantation outcome of each model was compared. In our early study, 24 hr continuous ischemic model necrotized, but intermittent reflow model almost survived except for partial necrosis at postoperative day 7. Scar tissue on the right limb showed myonecrosis and infiltration of inflammatory cells. Skeletal muscle on the right limb was structurally well maintained. Hemoglobin vesicle-treated limbs appeared to have much better oxygenation than ETK-treated limbs. Aerobic respiration remained in the amputated limb, gastrocnemius muscle was well maintained, and the overall replantation was successful in the limb preserved using HbV. These studies demonstrated that oxygenic preservation is effective for rat ischemic limb, suggesting that this method may be useful for other replantation and transplantation surgeries.
    Full-text · Article · Jan 2015 · Transplantation
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    ABSTRACT: Decabromodiphenyl ether (decaBDE) adversely affects reproduction and development. Our previous study showed that postnatal exposure to a low dose of decaBDE (0.025 mg/kg body weight/day) by subcutaneous injection on postnatal days (PNDs) 1 through 5 leads to reductions in testicular size and number of Sertoli cells and sperm, while higher dose of decaBDE (2.5 mg/kg body weight/day) had no significant differences about these. In the present study, we examined the molecular mechanism of these effects on mouse testes following postnatal exposure to a low decaBDE dose. We hypothesized that postnatal exposure to decaBDE may alter levels of serum thyroid hormones (THs) and testosterone, or the level of TH receptor alpha (Thra) transcripts and its splicing variants and androgen receptor (Ar) in Sertoli cells, adversely affecting spermatogenesis. To test this hypothesis, we examined serum TH and testosterone levels and the levels of transcripts of the Ar, Thra and its splicing variants, and Thra splicing factors (Hnrnpa1, Srsf1, and Hnrnph1) with qPCR in isolated mouse Sertoli cells exposed postnatally to decaBDE (0.025, 0.25, and 2.5 mg/kg). Levels of serum testosterone and transcripts encoding Ar, Thra, and its variant, Thra1, declined significantly in Sertoli cells of mice exposed to 0.025 mg decaBDE/kg. No significant differences in serum TH level or Thra2, Hnrnph1, or Srsf1 transcript levels were observed between control and decaBDE-exposed mice. However, the Thra1:Thra2 and Hnrnpa1:Srsf1 ratios were altered in Sertoli cells of mice exposed to 0.025 mg decaBDE/kg but not in cells exposed to 0.25 or 2.5 mg decaBDE/kg. These results indicate that postnatal exposure to a low dose of decaBDE on PNDs 1 through 5 lowers the testosterone level and the levels of Ar and Thra transcripts in Sertoli cells, accompanied by an imbalance in the ratios of Thra splicing variants, resulting in smaller testicular size and impaired spermatogenesis.
    Preview · Article · Dec 2014 · PLoS ONE
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    ABSTRACT: This article evaluates the suitability of cadavers embalmed by the saturated salt solution (SSS) method for surgical skills training (SST). SST courses using cadavers have been performed to advance a surgeon's techniques without any risk to patients. One important factor for improving SST is the suitability of specimens, which depends on the embalming method. In addition, the infectious risk and cost involved in using cadavers are problems that need to be solved. Six cadavers were embalmed by 3 methods: formalin solution, Thiel solution (TS), and SSS methods. Bacterial and fungal culture tests and measurement of ranges of motion were conducted for each cadaver. Fourteen surgeons evaluated the 3 embalming methods and 9 SST instructors (7 trauma surgeons and 2 orthopedists) operated the cadavers by 21 procedures. In addition, ultrasonography, central venous catheterization, and incision with cauterization followed by autosuture stapling were performed in some cadavers. The SSS method had a sufficient antibiotic effect and produced cadavers with flexible joints and a high tissue quality suitable for SST. The surgeons evaluated the cadavers embalmed by the SSS method to be highly equal to those embalmed by the TS method. Ultrasound images were clear in the cadavers embalmed by both the methods. Central venous catheterization could be performed in a cadaver embalmed by the SSS method and then be affirmed by x-ray. Lungs and intestines could be incised with cauterization and autosuture stapling in the cadavers embalmed by TS and SSS methods. Cadavers embalmed by the SSS method are sufficiently useful for SST. This method is simple, carries a low infectious risk, and is relatively of low cost, enabling a wider use of cadavers for SST.
    Full-text · Article · Dec 2014 · Medicine
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    ABSTRACT: Testicular cell transplantation has generally been performed by using immune-deficient recipient mice to investigate the biology of spermatogonial stem cells (SSCs), the production of transgenic animals, and restoration of fertility. Recently, we demonstrated that rat spermatogenesis can occur in the seminiferous tubules of immune-competent recipient mice via pretreatment with busulfan (Myleran, 1, 4-butanediol methanesulfonate, 40 mg/kg) after transplantation of rat SSCs. However, considering the immunosuppressive effect of busulfan, there is a possibility that busulfan itself causes immune suppression in immune-competent recipient mice. The aim of this study was to determine the effects of busulfan on the immune system and spermatogenesis in immune-competent recipient mice. The results showed that at 60 days after busulfan treatment, just the same time as the transplantation, the recovery could be seen in the immune system including cell counts and functions of T and B lymphocytes in the spleen, but the spermatogenesis was more compromised. This study demonstrated that after busulfan pretreatment the immune system in immune-competent recipient mice had recovered by the time that rat spermatogenesis could occur in the murine testis. It became clear that xenogenic spermatogenesis can be tolerated in seminiferous tubules in the testes of immune-competent mice.
    No preview · Article · Nov 2014 · Anatomical Science International
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    ABSTRACT: Purpose: Surgical skills training (SST) courses using cadavers have been performed to advance a surgeon’s techniques without any risk to patients. One important factor for improving SST is the suitability of specimens, which depends on the embalming method. We analyzed the suitability for SST of the embalming method with the use of the saturated salt solution (SSS), which is composed mostly of high-level sodium chloride (NaCl). Methods: The SSS was prepared with reference to Coleman and Kogan (1998). Six cadavers were embalmed by three methods; formalin solution, Thiel’s solution (TS) and SSS methods. Infectious risk, range of motions, medical imaging and availabilities of the surgical devices were examined. 14 surgeons operated these cadavers by 21 procedures and evaluated the three embalming method. Results: The SSS method had a sufficient antibiotic effect and produced cadavers with flexible joints and a high tissue quality suitable for SST. The surgeons evaluated the cadavers embalmed by the SSS method to be highly equal those embalmed by the TS method. Ultrasound imaging, central venous catheterization, the electrosurgical device and the autosuture stapling device were available in the SSS-embalmed cadaver. Conclusions: Cadavers embalmed by the SSS method are sufficiently useful for SST. Because this method is so simple, carries a low infectious risk, and is relatively low cost, it seems to play a part in the world-wide dissemination of SST. Reference: Coleman R, Kogan I (1998) An improved low-formaldehyde embalming fluid to preserve cadavers for anatomy teaching. J Anat 192:443–446
    Full-text · Poster · Nov 2014
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    ABSTRACT: Experimental autoimmune orchitis is a useful model for studying testicular inflammation and germ/immune cell interactions. Th17 cells and their hallmark cytokine IL17A were reported to be involved in the development of autoimmune orchitis. The aim of the present work is to investigate the pathogenic role of IL17A in rat testis. In vitro experiments were performed in order to analyze effects of IL17A on Sertoli cell tight junctions. The addition of IL17A to normal rat Sertoli cell cultures induced a significant decline in transepithelial electrical resistance and a reduction of occludin expression and redistribution of occludin and claudin 11, altering the Sertoli cell tight junction barrier. Intratesticular injection of 1 μg of recombinant rat IL17A to Sprague-Dawley rats induced increased blood-testis barrier permeability, as shown by the presence of biotin tracer in the seminiferous tubule adluminal compartment, and delocalization of occludin and claudin 11. Results showed that IL17A induced focal inflammatory cell infiltration in the interstitium and germ cell sloughing in adjacent seminiferous tubules. Moreover, an increase in TUNEL+ apoptotic germ cells was also observed. Inflammatory ED1+ macrophages were the main population infiltrating the interstitium following IL17A injection. This correlated with an increase in mRNA expression of the monocyte chemoattractant protein Ccl2, its receptor Ccr2 and the vascular cell adhesion molecule Vcam1. Overall results suggest a relevant role of IL17A in the development of testicular inflammation, facilitating the recruitment of immune cells to the testicular interstitium and inducing impairment of blood-testis barrier function.
    No preview · Article · Sep 2014 · Cell and Tissue Research
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    ABSTRACT: Colostomy is conventional treatment for anal dysfunction. Recently, a few trials of anorectal transplantation in animals have been published as a potential alternative to colostomies; however, further development of this technique is required. In this study, we utilized a canine model of anorectal transplantation, evaluated the patency of our microsurgical anastomoses, and assessed the perfusion of the transplanted anus. We designed a canine anorectal transplantation model, wherein anorectal autotransplantation was performed in four healthy beagle dogs by anastomoses of the lower rectum, the bilateral pudendal arteries (PAs) and veins (PVs), and pudendal nerves (PNs). Postoperative graft perfusion was measured by indocyanine green (ICG) angiography and histological examination. The length of the anorectal graft including perianal skin, anal sphincter muscle, bilateral PAs, PVs, and PNs was 4.9 ± 0.3 cm. All diameters of the PAs, PVs, and PNs were large enough to be microscopically anastomosed. Both ICG angiography and histological examination demonstrated good graft perfusion, except for one case that lead to venous congestion. These results show that anastomosis of the bilateral PAs, PVs, and PNs is required for anorectal transplantation. This is the first successful report of canine anorectal autotransplantation.
    Full-text · Article · Sep 2014 · Scientific Reports
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    ABSTRACT: The testis is an organ with immune privilege. The comprehensive blood-testis barrier formed by Sertoli cells protects autoimmunogenic spermatozoa and spermatids from attack by the body's immune system. The interleukin (IL)-6/IL-12 family cytokines IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Epstein-Barr virus-induced gene 3 [EBI3]), and IL-35 (p35/EBI3) play critical roles in the regulation of various immune responses, but their roles in testicular immune privilege are not well understood. In the present study, we investigated whether these cytokines are expressed in the testes and whether they function in the testicular immune privilege by using mice deficient in their subunits. Expression of EBI3 was markedly increased at both mRNA and protein levels in the testes of 10- or 12-week-old wild-type mice as compared with levels in 2-week-old mice, whereas the mRNA expression of p40 was markedly decreased and that of p35 was conserved between these two groups. Lack of EBI3, p35, and IL-12 receptor β2 caused enhanced infiltration of lymphocytes into the testicular interstitium, with increased interferon-γ expression in the testes and autoantibody production against mainly acrosomal regions of spermatids. Spermatogenic disturbance was more frequently observed in the seminiferous tubules, especially when surrounded by infiltrating lymphocytes, of these deficient mice than in those of wild-type mice. In particular, p35-deficient mice showed the most severe spermatogenic disturbance. Immunohistochemical analyses revealed that endothelial cells and peritubular cells in the interstitium were highly positive for p35 at both ages, and CD163+ resident macrophages positive for p35 and EBI3, possibly producing IL-35, were also detected in the interstitium of 12-week-old mice but not those of 2-week-old mice. These results suggest that p35 helps in maintaining the testicular immune privilege, in part in an IL-35-dependent manner.
    Full-text · Article · Apr 2014 · PLoS ONE
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    ABSTRACT: Scimitar syndrome is a rare anomaly involving a pulmonary vein flowing into the inferior vena cava (scimitar vein) and is commonly associated with lung hypoplasia wherein a scimitar vein drains the entire lung. We report a rare case of a scimitar vein draining only the right inferior lobe found in a 77-year-old male cadaver. In this case, no hypoplastic lung or abnormal lobulation were observed. The scimitar vein drained the inferior lobe of the right lung after piercing the diaphragm and draining into the inferior vena cava. The remaining two right pulmonary veins, draining the superior and middle lobes, terminated into the left atrium. To the best of our knowledge, this is the first report of a scimitar vein during gross anatomical dissection in an adult cadaver. In adults, scimitar veins are often benign, incidental findings, and little is known about them. The present case of a scimitar vein partially draining the lung without lung hypoplasia offers important insights into the formative processes of the pulmonary venous system.
    Full-text · Article · Mar 2014 · Anatomical Science International
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    ABSTRACT: Diethylstilbestrol (DES), an endocrine-disrupting chemical, is an infamous artificial estrogenic compound. Although neonatal exposure to DES has been shown to result in inflammation of the male reproductive system, it has not, to our knowledge, been reported to induce testicular inflammation. Here we report that neonatal exposure to DES caused granulomatous orchitis with spermatogenic disturbance in 4 of 17 ICR male mice at 12 weeks of age. In the animals with spermatogenic disturbance, we observed either seminiferous tubules containing only cells with Sertoli cell features (likely Sertoli cell syndrome), or tubule cells in maturation arrest that contained only spermatogonia and/or spermatocytes. Following neonatal DES exposure, 5-week-old mice exhibited inflammation in cauda epididymis; by 8 weeks, the inflammation had spread to all segments of epididymis but not the testis; by 12 weeks, inflammation of the epididymis was observed in all mice. These data indicated that cauda epididymis has increased sensitivity to neonatal DES exposure compared to other segments of epididymis and testis. The data also implied that neonatal DES exposure-induced inflammation in cauda epididymis extended gradually to the testis via corpus and caput during development.
    No preview · Article · Jan 2014
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    ABSTRACT: Background: Testis is known as one of the immunologically privileged organs. In particular, blood-testis barrier formed by Sertoli cells protects autoimmunogeneic spermatozoa and spermatid from attack by the self-immune system. Moreover, it was demonstrated that Sertoli cells, Leydig cells and a few population of testicular macrophages exhibit immunosuppressive activity. Recent studies also suggest a possibility that some cytokines in the testis contribute to maintaining the immune privilege. Interleukin (IL)-35 is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12. Although it is IL-35 has an important role in immunosuppression, its role in the testis remains unknown. Methods and Findings: In the present study, we investigated the role of intra-testicular IL-35 by histochemistry, immunohistochemistry and real-time RT-PCR using wild-type C57BL/6 mice and EBI3- and p35-deficient mice. EBI3 expression was detected in a part of CD163-positive macrophages and acrosomal regions of spermatids in testis of wild-type mice. Intriguingly, p35 expression was coincidently detected in a part of EBI3- and F4/80-positive macrophages, and also in basal lamina of seminiferous tubules, endothelial cells and acrosomal region of spermatids. A significant increase in the number of seminiferous tubules with spermatogenic disturbance was observed in both EBI3- and p35-deficient mice, compared with that in wild-type mice. Especially, p35-deficient mice showed severe spermatogenic disturbance. Moreover, CD4-, CD8- and B220-positive infiltrating cells were detected in the testicular interstitium of EBI3- and p35-deficient mice, but not of wild-type mice. Intra-testicular mRNA expression of interferon-gamma was significantly increased in EBI3- and p35-deficient mice. A similar increase in the expression of IL-10 was observed only in p35-deficient mice. Finally, autoantibodies to spermatids were detected in sera obtained from EBI3- and p35-deficient mice, but not from wild-type mice. Conclusions: In testis, there are EBI3- and p35-double positive macrophages, possibly producing immunosuppressive IL-35. And, lack of either EBI3 or p35 causes infiltration of lymphocytes into testis and spermtatogenic disturbance. These results indicate that IL-35 plays an important role in maintaining the testicular immune privilege.
    No preview · Article · Jan 2014 · Reproductive Immunology and Biology
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    ABSTRACT: Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been reported to induce spermatogenic disturbance through oxidant stress and affect the immune system as an adjuvant. However, the effect of DEHP on the testicular immune microenvironment has not yet been investigated. In the present study, we examined the testicular immune microenvironment after exposure to doses of DEHP, previously identified as no-observed-adverse-effect levels. Adult male mice were administered food containing 0%, 0.01% or 0.1% DEHP and then testes were analyzed. The results showed that a slight but significant spermatogenic disturbance appeared in the 0.1% DEHP group but not in the 0.01% DEHP group at 8 weeks. It was also demonstrated that lymphocytes and F4/80- and MHC class II- positive cells were significantly increased with the elevation of IL-10 and IFN-γ mRNA expressions in the testes of not only the 0.1% DEHP group but also the 0.01% DEHP group at 8 weeks. Histochemical analyses involving horseradish peroxidase (HRP) as a tracer showed that a little blood-borne HRP had infiltrated into the lumen of a few seminiferous tubules beyond the blood-testis-barrier in both the 0.1% and 0.01% DEHP groups at 8 weeks. This indicates that a dose of DEHP that has little effects on spermatogenesis can change the testicular immune microenvironment with functional damage of the blood-testis barrier.
    Full-text · Article · Jul 2013 · Journal of Reproduction and Development

Publication Stats

562 Citations
183.43 Total Impact Points

Institutions

  • 2014-2016
    • Aichi Medical University
      • Department of Anatomy
      Koromo, Aichi, Japan
    • University of Buenos Aires
      • Faculty of Medicine
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2004-2015
    • Tokyo Medical University
      • Department of Anatomy
      Edo, Tokyo, Japan
  • 2012
    • National Research Institute for Child Health and Development, Tokyo
      Edo, Tōkyō, Japan
  • 2008-2012
    • Tokyo Medical and Dental University
      Edo, Tokyo, Japan