Aiji Ohtsuka

Okayama University, Okayama, Okayama, Japan

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Publications (158)243.01 Total impact

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    ABSTRACT: Increased expression of collagen XV has been reported in hepatocellular carcinogenesis in mice. The aim of this study was to confirm the previous murine findings in human hepatocellular carcinoma (HCC) specimens, along with the histopathological distribution of collagen XV in tumoral tissues. Sixty-three primary HCC specimens were examined. Immunostaining of collagen XV and quantitative reverse transcriptional PCR of COL15A1, which encodes collagen XV, were performed. Positive staining of collagen XV was observed in all tumoral regions, regardless of differentiation level or pathological type of HCC, along the sinusoid-like endothelium, whereas collagen XV was not expressed in any non-tumoral region. The intensity score of collagen XV immunostaining and the mRNA value of COL15A1 were significantly correlated. COL15A1 expression in tumors was 3.24-fold higher than in non-tumoral regions. Multivariate analysis showed that COL15A1 expression was significantly higher in the absence of hepatitis virus and moderately differentiated HCC. COL15A1 mRNA was up-regulated in HCC and collagen XV was expressed along the sinusoid-like endothelium of HCC but not in non-tumoral regions, which implies that collagen XV contributes to the capillarization of HCC.
    International Journal of Clinical Oncology 08/2015; DOI:10.1007/s10147-015-0888-2 · 2.13 Impact Factor
  • Journal of Neurological Surgery, Part B: Skull Base 02/2015; 76(S 01). DOI:10.1055/s-0035-1546695 · 0.72 Impact Factor
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    ABSTRACT: The outcome measures in rheumatology clinical trials (OMERACT) scores are the most mature quantitation system for rheumatoid arthritis (RA) on magnetic resonance imaging (MRI). Direct measuring techniques of synovial volume have been reported with good reproducibility, although few reports have demonstrated the changes of these measures in response to treatment. To assess these clinical responses, we evaluated the correlation of the changes of clinical activity score 28-joints disease activity score (DAS28-CRP) with the changes of OMERACT scores and with synovial volume measurements. Eight RA patients who were treated by biologic agents were examined with MRI of the dominant affected wrist and finger joints before and one year after the treatment. The total OMERACT score was reduced from 48.0 to 41.3, and synovial volume was reduced from 15.4 to 8.8 milliliters. Positive correlations were seen between the changes of DAS28-CRP and the changes of OMERACT synovitis score (r=0.27), OMERACT total score (r=0.43) and synovial volume (r=0.30). Limited to synovium assessment, synovial volume showed a better correlation with DAS28-CRP than the OMERACT synovitis score. On the other hand, the OMERACT total score showed a higher correlation with DAS28-CRP than synovial volume, probably because the OMERACT total score includes scores for bone erosion and bone edema as well.
    Acta medica Okayama 02/2015; 69(1):29-35. · 0.70 Impact Factor
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    Critical Care 12/2014; 18(Suppl 2):P23-P23. DOI:10.1186/cc14026 · 4.48 Impact Factor
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    ABSTRACT: Background Trainee surgeons must have a good understanding of surgical anatomy. Especially in the hepatobiliary-pancreatic field, beginning surgeons often find it difficult to recognize the three-dimensional structure of the target organ and its complex anatomical correlation with surrounding organs. Conventional anatomy textbooks are not written with the aim of teaching these three-dimensional structures and complex correlations. We developed a novel teaching atlas of surgical anatomy using a multi-viewpoint and multi-layer three-dimensional camera system.Methods Layer-by-layer dissection of the upper abdominal organs of a cadaver was performed by expert surgeons. A stereoscopic camera system was used to capture a series of anatomical views. The images were remodeled in a multi-viewpoint and multi-layer manner.ResultsImages of each dissection layer could be viewed serially from the appropriate angle, which was tilted up to 90° along the anteroposterior axis. The clinical anatomy specific to the surgical procedure could thus be learned using this atlas system.Conclusions Rotatable three-dimensional panoramic views of local dissection of the upper abdominal organs of a cadaver were developed for educational purposes. Trainee surgeons could use these anatomical images instead of conventional anatomical atlases to learn how to perform surgical procedures such as pancreaticoduodenectomy and major hepatectomy.
    Journal of Hepato-Biliary-Pancreatic Sciences 08/2014; 21(8). DOI:10.1002/jhbp.108 · 2.99 Impact Factor
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    ABSTRACT: We have previously demonstrated the efficient and time-dependent transvascular localization of Sialyl Lewis X (SLX)-liposomes to inflammatory sites, but the final target of the SLX-liposomes remained uncertain. The aim of this study was to identify the target cells of the liposomes within the inflamed joints of collagen antibody-induced arthritis (CAIA) model mice. SLX-liposomes and unlabeled liposomes encapsulating high-density colloidal gold were administered intravenously into the caudal vein of CAIA mice on day 5 after induction of arthritis when the inflammatory score was maximal (n = 6 per group). Six hours or 24 h after liposome administration, animals were euthanized and hind limbs and ankles were excised without perfusion. After fixation, synovial tissues were examined by light microscopy after silver enhancement of colloidal gold or by transmission electron microscopy. Silver-enhanced signals were detected within the cells around E-selectin-positive blood vessels in the synovium of the SLX-liposome group. These cells were positive for the macrophage/monocyte marker F4/80 or neutrophil marker Ly-6G. Transmission electron microscopy detected the colloidal gold signals together with liposome-like structures within the phagosomes of synovial macrophages. Transmission electron microscopy and energy dispersive X-ray spectrometry could determine gold elements in the lysosomes of synovial macrophages. The results of the current study demonstrate that SLX-liposomes primarily targeting E-selectin in activated endothelial cells could potentially deliver their contents into inflammatory cells around synovial blood vessels in arthritic joints.
    Agents and Actions 11/2013; 63(2). DOI:10.1007/s00011-013-0682-4 · 2.35 Impact Factor
  • Toshihiko Matsuo · Yoshimasa Takeda · Aiji Ohtsuka
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    ABSTRACT: The purpose of this study was to develop a series of stereoscopic anatomical images of the eye and orbit for use in the curricula of medical schools and residency programs in ophthalmology and other specialties. Layer-by-layer dissection of the eyelid, eyeball, and orbit of a cadaver was performed by an ophthalmologist. A stereoscopic camera system was used to capture a series of anatomical views that were scanned in a panoramic three-dimensional manner around the center of the lid fissure. The images could be rotated 360 degrees in the frontal plane and the angle of views could be tilted up to 90 degrees along the anteroposterior axis perpendicular to the frontal plane around the 360 degrees. The skin, orbicularis oculi muscle, and upper and lower tarsus were sequentially observed. The upper and lower eyelids were removed to expose the bulbar conjunctiva and to insert three 25-gauge trocars for vitrectomy at the location of the pars plana. The cornea was cut at the limbus, and the lens with mature cataract was dislocated. The sclera was cut to observe the trocars from inside the eyeball. The sclera was further cut to visualize the superior oblique muscle with the trochlea and the inferior oblique muscle. The eyeball was dissected completely to observe the optic nerve and the ophthalmic artery. The thin bones of the medial and inferior orbital wall were cracked with a forceps to expose the ethmoid and maxillary sinus, respectively. In conclusion, the serial dissection images visualized aspects of the local anatomy specific to various procedures, including the levator muscle and tarsus for blepharoptosis surgery, 25-gauge trocars as viewed from inside the eye globe for vitrectomy, the oblique muscles for strabismus surgery, and the thin medial and inferior orbital bony walls for orbital bone fractures.
    Acta medica Okayama 04/2013; 67(2):87-91. · 0.70 Impact Factor
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    ABSTRACT: Most blood vessels contain elastin that provides the vessels with the resilience and flexibility necessary to control hemodynamics. Pathophysiological hemodynamic changes affect the remodeling of elastic components, but little is known about their structural properties. The present study was designed to elucidate, in detail, the three-dimensional (3D) architecture of delicate elastic fibers in small vessels, and to reveal their architectural pattern in a rat model. The fine vascular elastic components were observed by a newly developed scanning electron microscopy technique using a formic acid digestion with vascular casts. This method successfully visualized the 3D architecture of elastic fibers in small blood vessels, even arterioles and venules. The subendothelial elastic fibers in such small vessels assemble into a sheet of meshwork running longitudinally, while larger vessels have a higher density of mesh and thicker mesh fibers. The quantitative analysis revealed that arterioles had a wider range of mesh density than venules; the ratio of density to vessel size was higher than that in venules. The new method was useful for evaluating the subendothelial elastic fibers of small vessels and for demonstrating differences in the architecture of different types of vessels.
    Microscopy and Microanalysis 03/2013; 19(2):1-9. DOI:10.1017/S1431927612014341 · 1.88 Impact Factor
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    ABSTRACT: Vertebrate collagen types XV and XVIII are broadly distributed basement membrane components, classified into a structurally distinct subgroup called "multiplexin collagens". Mutations in mammalian multiplexins are identified in some degenerative diseases such as Knobloch syndrome 1 (KNO1) or skeletal/cardiac myopathies, however, these progressive properties have not been elucidated. Here we investigated Drosophila mutants of Multiplexin (Mp), the only orthologue of vertebrate collagen types XV and XVIII, to understand the pathogenesis of multiplexin-related diseases. The mp mutants exhibited morphological changes in cardiomyocytes and progressive dysfunction of the skeletal muscles, reminiscent phenotypes observed in Col15a1-null mice. Ultrastructural analysis revealed morphologically altered mitochondria in mutants' indirect flight muscles (IFMs), resulting in severely attenuated ATP production and enhanced reactive oxygen species (ROS) production. In addition, mutants' IFMs exhibited diminished βPS integrin clustering and abolished focal adhesion kinase (FAK) phosphorylation. Furthermore, mutants' defective IFMs are improved by the administrations of cyclosporin A, an inhibitor against mitochondrial permeability transition pore (mPTP) opening or losartan, an angiotensin II type 1 receptor (AT1R) blocker. Thus, our results suggest that Mp modulates mPTP opening and AT1R activity through its binding to integrin and that lack of Mp causes unregulated mPTP opening and AT1R activity, leading to mitochondrial dysfunctions. Hence, our results provide new insights towards the roles of multiplexin collagens in mitochondrial homeostasis and may serve as pharmacological evidences for the potential use of cyclosporin A or losartan for the therapeutic strategies.
    The international journal of biochemistry & cell biology 02/2013; 45(5). DOI:10.1016/j.biocel.2013.02.001 · 4.05 Impact Factor
  • Article: In reply.
    Anesthesiology 02/2013; 118(2):469-70. DOI:10.1097/ALN.0b013e31827e3c53 · 5.88 Impact Factor
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    ABSTRACT: Background: Centrilobular ground-glass opacity (GGO) is one of the characteristic findings in chest high-resolution computed tomography (HRCT) of patients with pulmonary veno-occlusive disease (PVOD) and patients with pulmonary capillary hemangiomatosis (PCH). However, clinical differential diagnosis of these two diseases is difficult and has not been established. In order to clarify their differences, we compared the sizes of GGOs in chest HRCT and the sizes of capillary assemblies in pulmonary vascular casts between patients diagnosed pathologically with PVOD and PCH. Methods: We evaluated chest HRCT images for four patients with idiopathic pulmonary arterial hypertension (IPAH), three patients with PVOD and three patients with PCH, and we evaluated pulmonary vascular casts of lung tissues obtained from those patients at lung transplantation or autopsy. Results: Centrilobular GGOs in chest HRCT were observed in patients with PVOD and patients with PCH but not in patients with IPAH. We measured the longest diameter of the GGOs. The size of centrilobular GGOs was significantly larger in patients with PCH than in patients with PVOD (5.60±1.43 mm versus 2.51±0.79 mm, P<.01). We succeeded in visualization of the 3-dimensional structures of pulmonary capillary vessels obtained from the same patients with PVOD and PCH undergoing lung transplantation or autopsy and measured the diameters of capillary assemblies. The longest diameter of capillary assemblies was also significantly larger in patients with PCH than in patients with PVOD (5.44±1.71 mm versus 3.07±1.07 mm, P<.01). Conclusion: Measurement of the sizes of centrilobular GGOs in HRCT is a simple and useful method for clinical differential diagnosis of PVOD and PCH.
    Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 01/2013; 22(4). DOI:10.1016/j.carpath.2012.12.002 · 2.00 Impact Factor
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    ABSTRACT: Type 2 diabetes mellitus is linked to impaired skeletal muscle glucose uptake and storage. This study aimed to investigate the fiber type distributions and the three-dimensional (3D) architecture of the capillary network in the skeletal muscles of type 2 diabetic rats. Muscle fiber type transformation, succinate dehydrogenase (SDH) activity, capillary density, and 3D architecture of the capillary network in the soleus muscle were determined in 36-week-old Goto-Kakizaki (GK) rats as an animal model of nonobese type 2 diabetes and age-matched Wistar (Cont) rats. Although the soleus muscle of Cont rats comprised both type I and type IIA fibers, the soleus muscle of GK rats had only type I fibers. In addition, total SDH activity in the soleus muscle of GK rats was significantly lower than that in Cont rats because GK rats had no high-SDH activity type IIA fiber in the soleus muscle. Furthermore, the capillary diameter, capillary tortuosity, and microvessel volume in GK rats were significantly lower than those in Cont rats. These results indicate that non-obese diabetic GK rats have muscle fiber type transformation, low SDH activity, and reduced skeletal muscle capillary content, which may be related to the impaired glucose metabolism characteristic of type 2 diabetes.
    The Scientific World Journal 11/2012; 2012(6):680189. DOI:10.1100/2012/680189 · 1.73 Impact Factor
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    ABSTRACT: In contrast to the osseus part that develops from the tympanic ring of the squamous part of the temporal bone after birth, there is little information on fetal development of the cartilages surrounding the human external acoustic meatus. Using routine histology and immunohistochemistry, we examine sections of 22 fetuses (CRL 100-270mm) to study the development of these cartilages. Early external ear cartilages are composed of three groups: (1) a ring-like cartilage at the putative tragus on the anterior side of the meatus, (2) two or three bar-like cartilages along the inferior wall of the meatus, and (3) a plate-like cartilage in a skin fold for the putative helix on the posterior side. In contrast to the first and second pharyngeal arch cartilages, all the external ear cartilages express glial fibrillary acidic protein. Notably, the bar-like cartilages along the meatus are connected with a fascia-like structure to the second pharyngeal arch cartilage. Later, with considerable individual variation, new cartilage bars extend from the inferior cartilages to the superior side of the meatus. Thus, via an intermediate stage showing a chain of triangular elastic cartilages, a chain of bar-like cartilages on the inferior side appears to change into a complex of H-shaped cartilages. Numerous ceruminous glands are seen in the thick subcutaneous tissue overlying the cartilaginous part of the meatus. However, they do not insert into the cartilage. The external ear cartilages develop much earlier than, and independently of, the osseus part.
    Annals of anatomy = Anatomischer Anzeiger: official organ of the Anatomische Gesellschaft 09/2012; 195(2). DOI:10.1016/j.aanat.2012.07.009 · 1.48 Impact Factor
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    ABSTRACT: High mobility group box-1 (HMGB1) plays an important role in triggering inflammatory responses in many types of diseases. In this study, we examined the involvement of HMGB1 in traumatic brain injury (TBI) and evaluated the ability of intravenously administered neutralizing anti-HMGB1 monoclonal antibody (mAb) to attenuate brain injury. Traumatic brain injury was induced in rats or mice by fluid percussion. Anti-HMGB1 mAb or control mAb was administered intravenously after TBI. Anti-HMGB1 mAb remarkably inhibited fluid percussion-induced brain edema in rats, as detected by T2-weighted magnetic resonance imaging; this was associated with inhibition of HMGB1 translocation, protection of blood-brain barrier (BBB) integrity, suppression of inflammatory molecule expression, and improvement of motor function. In contrast, intravenous injection of recombinant HMGB1 dose-dependently produced the opposite effects. Experiments using receptor for advanced glycation end product (RAGE)(-/-) , toll-like receptor-4 (TLR4)(-/-) , and TLR2(-/-) mice suggested the involvement of RAGE as the predominant receptor for HMGB1. Anti-HMGB1 mAb may provide a novel and effective therapy for TBI by protecting against BBB disruption and reducing the inflammatory responses induced by HMGB1. ANN NEUROL 2012;72:373-384.
    Annals of Neurology 09/2012; 72(3):373-84. DOI:10.1002/ana.23602 · 9.98 Impact Factor
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    ABSTRACT: Adaptation to constant vibration (acoustic oscillation) is likely to confer a specific morphology at the bone-tendon and bone-ligament interfaces at the ear ossicles, which therefore represent an exciting target of enthesis research. We histologically examined (i) the bone attachments of the tensor tympani and stapedius muscles and (ii) the annular ligament of the incudostapedial joint obtained from seven elderly donated cadavers. Notably, both aldehyde-fuchsin and elastic-Masson staining demonstrated that the major fibrous component of the entheses was not collagen fibers but mature elastic fibers. The positive controls for elastic fiber staining were the arterial wall elastic laminae included in the temporal bone materials. The elastic fibers were inserted deeply into the type II collagen-poor fibrocartilage covering the ear ossicles. The muscle tendons were composed of an outer thin layer of collagen fibers and an inner thick core of elastic fibers near the malleus or stapes. In the unique elastic fiber-mediated entheses, hyaluronan, versican and fibronectin were expressed strongly along the elastic fibers. The hyaluronan seemed to act as a friction-reducing lubricant for the elastic fibers. Aggrecan was labeled strongly in a disk- or plica-like fibrous mass on the inner side of the elastic fiber-rich ligament, possibly due to compression stress from the ligament. Tenascin-c was not evident in the entheses. The elastic fiber-mediated entheses appeared resistant to tissue destruction in an environment exposed to constant vibration. The morphology was unlikely to be the result of age-related degeneration.
    Journal of Anatomy 07/2012; 221(4):331-340. DOI:10.1111/j.1469-7580.2012.01542.x · 2.10 Impact Factor
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    ABSTRACT: Pharyngeal cooling decreases brain temperature by cooling carotid arteries. This study was designed to evaluate the principle of pharyngeal cooling in monkeys and humans. Monkeys (n = 10) were resuscitated following 12 min of cardiac arrest. Pharyngeal cooling (n = 5), in which cold saline (5°C) was perfused into the cuff at the rate of 500 ml/min, was initiated simultaneously with the onset of resuscitation for 30 min. Patients (n = 3) who were in an intensive care unit were subjected to 30 min of pharyngeal cooling under propofol anesthesia. In the animal study, core brain temperature was significantly decreased compared with that in the control group by 1.9°C (SD = 0.8, P < 0.001) and 3.1°C (SD = 1.0, P < 0.001) at 10 min and 30 min after the onset of cooling, respectively. The cooling effect was more evident in an animal with low postresuscitation blood pressure. Total dose of epinephrine, number of direct current shocks, and recovery of blood pressure were not different between the two groups. The pharyngeal epithelium was microscopically intact on day 5. In the clinical study, insertion of the cuff and start of perfusion did not affect heart rate or blood pressure. Tympanic temperature was decreased by 0.6 ± 0.1°C/30 min without affecting bladder temperature. The pharynx was macroscopically intact for 3 days. Pharyngeal cooling rapidly and selectively decreased brain temperature in primates and tympanic temperature in humans and did not have adverse effects on return of spontaneous circulation, even when initiated during cardiac arrest in primates.
    Anesthesiology 05/2012; 117(1):117-25. DOI:10.1097/ALN.0b013e3182580536 · 5.88 Impact Factor
  • Neuroscience Research 09/2011; 71. DOI:10.1016/j.neures.2011.07.1779 · 1.94 Impact Factor
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    ABSTRACT: High mobility group box-1 (HMGB1) exhibits inflammatory cytokine-like activity in the extracellular space. We previously demonstrated that intravenous injection of anti-HMGB1 monoclonal antibody (mAb) remarkably ameliorated brain infarction induced by middle cerebral artery occlusion in rats. In the present study, we focused on the protective effects of the mAb on the marked translocation of HMGB1 in the brain, the disruption of the blood-brain barrier (BBB), and the resultant brain edema. Middle cerebral artery occlusion in the rat was used as the ischemia model. Rats were treated with anti-HMGB1 mAb or control IgG intravenously. BBB permeability was measured by MRI. Ultrastructure of the BBB unit was observed by transmission electron microscope. The in vitro BBB system was used to study the direct effects of HMGB1 in BBB components. HMGB1 was time-dependently translocated and released from neurons in the ischemic rat brain. The mAb reduced the edematous area on T2-weighted MRI. Transmission electron microscope observation revealed that the mAb strongly inhibited astrocyte end feet swelling, the end feet detachment from the basement membrane, and the opening of the tight junction between endothelial cells. In the in vitro reconstituted BBB system, recombinant HMGB1 increased the permeability of the BBB with morphological changes in endothelial cells and pericytes, which were inhibited by the mAb. Moreover, the anti-HMGB1 mAb facilitated the clearance of serum HMGB1. These results indicated that the anti-HMGB1 mAb could be an effective therapy for brain ischemia by inhibiting the development of brain edema through the protection of the BBB and the efficient clearance of circulating HMGB1.
    Stroke 05/2011; 42(5):1420-8. DOI:10.1161/STROKEAHA.110.598334 · 5.72 Impact Factor
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    ABSTRACT: Multiplexin (Mp) is the Drosophila orthologue of vertebrate collagens XV and XVIII. Like them, Mp is widely distributed in the basement membranes of the developing embryos, including those of neuroblasts in the central and peripheral nervous systems, visceral muscles of the gut, and contractile cardioblasts. Here we report the identification of mutant larvae bearing piggyBac transposon insertions that exhibit decrease Mp production associated with abdominal cuticular and wing margin defects, malformation of sensory organs and impaired sensitivity to physical stimuli. Additional findings include the abnormal ultrastructure of fatbody associated with abnormal collagen IV deposition, and reduced Wingless deposition. Collectively, these findings are consistent with the notion that Mp is required for the proper formation and/or maintenance of basement membrane, and that Mp may be involved in establishing the Wingless signaling gradients in the Drosophila embryo.
    Matrix biology: journal of the International Society for Matrix Biology 05/2011; 30(4):258-66. DOI:10.1016/j.matbio.2011.03.008 · 5.07 Impact Factor
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    ABSTRACT: The fascia pelvis parietalis (FPP) or endopelvic fascia is a well-known structure, but few studies described the detailed histological architecture, including the composite fiber directions. We hypothesized a gender-specific fiber architecture corresponding to the functional demand. For the first step to examine this hypothesis, we investigated specimens from 27 adult cadavers (10 males and 17 females) and 11 midterm fetuses (five males and six females) using immunohistochemistry and aldehyde-fuchsin staining. The adult female FPP was a solid, thick monolayered structure that was reinforced by abundant elastic fibers running across the striated muscle fibers, but it contained little or no smooth muscles (SM). In contrast, the male FPP was multilayered with abundant SM. In midterm fetuses, SM originated from the inferior part of the bladder and extended inferiorly along the gender-specific courses. Thus, we found a clear intergender difference in FPP architecture. However, the functional significance remained unknown because the basic architecture was common between nulliparous and multiparous women. Rather than for meeting the likely mechanical demands of pregnancy and vaginal delivery, the intergender difference of the FPP seemed to result from differences in the amount and migration course of bladder-derived SM as well as in hormonal background.
    Clinical Anatomy 05/2011; 24(4):469-77. DOI:10.1002/ca.21042 · 1.33 Impact Factor

Publication Stats

2k Citations
243.01 Total Impact Points


  • 1983–2015
    • Okayama University
      • • Department of Human Morphology
      • • Department of Neurology
      • • Faculty of Medicine
      • • Department of Bacteriology
      • • Department of Pharmacology
      Okayama, Okayama, Japan
  • 2008
    • Annamalai University
      Anamalainagar, Tamil Nādu, India
  • 2005
    • Assiut University
      • Department of Anatomy
      Asyūţ, Muhafazat Asyut, Egypt