Hayato Terayama

Absence of the celiac trunk: case report and review of the literature.

The authors report a rare variation of the absence of the celiac trunk in a Japanese cadaver, with the left gastric, splenic, common hepatic, and superior mesenteric arteries arising independently from the abdominal aorta in the routine dissection of a 95‐year‐old Japanese male cadaver. The incidence and developmental and clinical significance of this variation is discussed with a detailed review of the literature. Knowledge of such case has important clinical significance in an abdominal operation or invasive arterial procedure, that is, Appleby procedure and liver transplantation, laparoscopic surgery, and radiological procedures in the upper abdomen. Clin. Anat. 21:283–286, 2008.

Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder

Panic disorder (PD) is the repeated sudden occurrence of panic attacks, episodes characterized by psychological symptoms. Peripheral benzodiazepine receptor (PBR) is closely associated with personality traits for anxiety tolerance, and that it holds promise as a biological marker of stressful conditions. We have performed association analyses using the polymorphism to determine the PBR in PD. We screened the subjects for sequence variations within the 5′ region, the coding region (exons 2–4), and the 3′ noncoding region. One novel missense variant in exon 4, derived from the nucleotide transition in codon 162 (CGT → CAT:485G > A) resulting in an arginine‐to‐histidine (Arg → His) change, was detected in these subjects. The 485G > polymorphism of the PBR gene was analyzed in 91 PD patients and 178 controls. The genotypic and allelic analyses of the 485G > A revealed significant differences between the panic patients and the comparison subjects (P = 0.021 and 0.014, respectively). The present study provides new and important evidence that variation in the PBR gene influences susceptibility to PD.

Experimental autoimmune orchitis as a model of immunological male infertility

Clinically, 60–75% of male infertility cases are categorized as idiopathic spermatogenic disturbance. In previous studies of this condition, lymphocytic infiltration and immune deposits were present in several testis biopsy specimens, indicating that inflammatory or immunological factors contribute to the occurrence of the lesions. However, there is currently little evidence regarding immunological infertility in men. Previously, we established an immunological infertility model, experimental autoimmune orchitis (EAO), that can be induced in mice by two subcutaneous injections of viable syngeneic testicular germ cells without the use of any adjuvant. In this EAO model, lymphocytes surround the tubuli recti and then induce spermatogenic disturbance. In addition, after the active inflammation stage of this model, the seminiferous epithelium is damaged irreversibly, resembling the histopathology of human male idiopathic spermatogenic disturbance. In the majority of patients with testicular autoimmunity, there is a chronic and asymptomatic development of the inflammatory reaction. Therefore, this disease is very difficult to diagnose at the ongoing stage, and it is possible that the histopathology of idiopathic spermatogenic disturbance in the clinic is reported at the post-active inflammation stage of autoimmune orchitis. In this review, the histopathology of EAO before and after inflammation is discussed, comparing it with human orchitis.

A rare case of inferior mesenteric artery arising from the superior mesenteric artery, with a review of the review of the literature

Anatomical variations of the inferior mesenteric artery (IMA) are uncommon. Generally, the IMA is very stable, arises directly from the abdominal aorta at the level of the third lumbar vertebra. We describe here an extremely rare case in which the IMA arose from the superior mesenteric artery. The findings were made during routine dissection of the cadaver of a 79-year-old Japanese man. This present case is the ninth report of this variation and was associated with gastrophrenic trunk, hepatosplenic trunk, hypoplastic spleen and accessory spleen. Clinically, cases like this highlight the importance of knowing the IMA anatomy and the possibility of its numerous variations in surgical procedures such as right hemicolectomy, resection of the transverse colon, left hemicolectomy, sigmoidectomy, and en bloc resection of the head of the pancreas and the superior mesenteric vessels. The developmental significance of this variation is also discussed with a detailed review of the literature.

Anatomical study of superior cluneal nerve entrapment.

OBJECT Entrapment of the superior cluneal nerve (SCN) in an osteofibrous tunnel in the space surrounded by the iliac crest and the thoracolumbar fascia is a cause of low-back pain (LBP). Several anatomical and surgical reports describe SCN entrapment as a cause of LBP, and a recent clinical study reported that patients with suspected SCN disorder constitute approximately 10% of the patients suffering from LBP and/or leg symptoms. However, a detailed anatomical study of SCN entrapment is rare. The purpose of this study was to investigate the courses of SCN branches and to ascertain the frequency of SCN entrapment. METHODS Branches of the SCN were dissected in 109 usable specimens (54 on the right side and 55 on the left side) obtained in 59 formalin-preserved cadavers (average age at death 84.8 years old). All branches were exposed at the points where they perforated the thoracolumbar fascia. The presence or absence of an osteofibrous tunnel was ascertained and, if present, the entrapment of the branches in the tunnel was determined. RESULTS Of 109 specimens, 61 (56%) had at least 1 branch running through an osteofibrous tunnel. Forty-two medial (39%), 30 intermediate (28%), and 14 lateral (13%) SCN branches passed through such a tunnel. Of these, only 2 medial branches had obvious entrapment in an osteofibrous tunnel. There were several patterns for the SCN course through the tunnel: medial branch only (n = 25), intermediate branch only (n = 11), lateral branch only (n = 4), medial and intermediate branches (n = 11), medial and lateral branches (n = 2), intermediate and lateral branches (n = 4), and all branches (n = 4). CONCLUSIONS Several anatomical variations of the running patterns of SCN branches were detected. Entrapment was seen only in the medial branches. Although obvious entrapment of the SCN is rare, it may cause LBP.

Histopathology of the tubuli recti at the start of experimental autoimmune orchitis in mice.

We previously established an experimental model of autoimmune orchitis (EAO) by means of immunization with testicular germ cells (TGC) alone in mice and confirmed that the disease can be transferred to mice that had received CD4+ but not CD8+ or B lymphocytes obtained from TGC-immunized donor mice. The tubuli recti (TR) are special in that lymphocytes first accumulate around them before spreading to the peripheral seminiferous tubules in EAO. However, the minute changes in the TR remain unknown. Therefore, we investigated the histopathology of the TR before the induction of spermatogenic disturbance. The results revealed that the first infiltrating lymphocytes around the TR were not only of T-cell but also of B-cell lineage. Moreover, it was also shown that some of these infiltrating lymphocytes migrated into the TR, with resultant degeneration of the TR epithelium before damage to the seminiferous epithelium. These findings indicate that TR epithelial cells are the first targets of autoreactive T and B lymphocytes in EAO.

Contribution of IL-12/IL-35 common subunit p35 to maintaining the testicular immune privilege.

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.

Postinflammation stage of autoimmune orchitis induced by immunization with syngeneic testicular germ cells alone in mice

We previously established an immunological infertility model, experimental autoimmune orchitis (EAO), which can be induced by two subcutaneous injections of viable syngeneic testicular germ cells on days 0 and 14 in mice without using any adjuvant. In this EAO model, CD4+ T-cell-dependent lymphocytic infiltration and immune deposits were found with spermatogenic disturbance on day 120. However, the late stage of EAO (= postactive inflammation stage on day 365) has not yet been investigated. Therefore, we investigated the histopathological characteristics of the late stage. The results revealed that the lymphocytic infiltration finally resolved; however, the seminiferous epithelium persistently showed maturation arrest and the Sertoli cell-only feature. In the seminiferous tubules showing maturation arrest, both proliferation and apoptosis of germ cells had occurred simultaneously. It was also noted that there were deposits of immunoglobulin G and the third component of complement on the thickened basement membrane of seminiferous tubules in the late stage of EAO. These results indicate that histopathology after active inflammation in EAO comprises persistent damage to the seminiferous epithelium and may resemble the histopathology of “idiopathic disturbance of spermatogenesis” in man.

The serotonin-2A receptor polymorphism and smoking behavior in Japan.

Epidemiological and genetic studies on smoking behavior have been performed, and in this study the human serotonin 2A receptor (HTR2A) polymorphism was examined in 82 smoking behaviorists and 125 healthy controls. HTR2A consists of at least 14 subtypes, depression and anxiety occur due to agonists, and hallucination, fever heat, psychomotor excitement and other symptoms also occur. The polymorphism in HTR2A (102T/C, –1438A/G) was identified by means of the polymerase chain reaction followed by restriction fragment length polymorphism, and the Fagerstrom Test for Nicotine Dependence was used to determine the extent of smoking behavior. The results suggest that the HTR2A (102T/C, –1438G/A) polymorphism might not be associated with susceptibility to a risk factor for developing smoking behavior. Further studies are required to determine whether or not the novel serotonin receptor (5-HTR) polymorphism reflects the pathogenesis of smoking behavior.

GRP78 Suppresses Lipid Peroxidation and Promotes Cellular Antioxidant Levels in Glial Cells following Hydrogen Peroxide Exposure

Oxidative stress, caused by the over production of reactive oxygen species (ROS), has been shown to contribute to cell damage associated with neurotrauma and neurodegenerative diseases. ROS mediates cell damage either through direct oxidation of lipids, proteins and DNA or by acting as signaling molecules to trigger cellular apoptotic pathways. The 78 kDa glucose-regulated protein (GRP78) is an ER chaperone that has been suggested to protect cells against ROS-induced damage. However, the protective mechanism of GRP78 remains unclear. In this study, we used C6 glioma cells transiently overexpressing GRP78 to investigate the protective effect of GRP78 against oxidative stress (hydrogen peroxide)-induced injury. Our results showed that the overexpression of GRP78 significantly protected cells from ROS-induced cell damage when compared to non-GRP78 overexpressing cells, which was most likely due to GRP78-overexpressing cells having higher levels of glutathione (GSH) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two antioxidants that protect cells against oxidative stress. Although hydrogen peroxide treatment increased lipid peroxidation in non-GRP78 overexpressing cells, this increase was significantly reduced in GRP78-overexpressing cells. Overall, these results indicate that GRP78 plays an important role in protecting glial cells against oxidative stress via regulating the expression of GSH and NQO1.