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Background At present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%‐20% of patients showing severe spermatogenesis disorders, including non‐obstructive azoospermia. Methods Literatures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized. Main findings (Results) Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty‐nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies. Conclusion Genetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing.

Purpose Mouse in vitro spermatogenesis is possible with classical organ culture methods, by placing the testis tissue at the interphase between culture medium and air. In this condition, however, a tissue piece tends to round up to be compact, whose central region suffers from shortage of nutrients and oxygen. In this study, the authors improved the culture condition by spreading each tissue thin and flat, by which they were able to get better access to the oxygen and nutrients. Methods Immature mouse testis tissues placed on agarose gel block were forced to spread flat by covering with a polydimethylsiloxane (PDMS) ceiling chip (PC chip). They were then cultured for weeks and evaluated by the transgene expression of Acr‐Gfp, which reflects the progression of spermatogenesis. Results Testis tissues covered with PC chip initiated and maintained spermatogenesis in its wider region than those without PC chip covering. Flow cytometric analysis demonstrated that the PC method yielded more numerous meiotic germ cells than those without PC. Immunohistochemical examination confirmed the authentic histological figure of spermatogenesis from spermatogonia up to round or elongating spermatids. Conclusions The PC chip method is simple and effective to improve the efficiency of in vitro spermatogenesis in the organ culture system.

Objective We evaluated avoidance behaviors of healthy partners of breast cancer patients and sought to (1) describe men's perception of their own avoidance behavior and (2) identify the background factors associated with such behavior. Methods An Internet-based survey was conducted, and analysis was performed on the responses of 368 male spouses of female breast cancer patients. Results Thirty to forty percent of spouses had some type of problem avoidance behavior toward their wives. There was a high correlation (r = 0.70, P

The management of acute scrotum can be challenging, especially in infants or patients with a neurological or neurodevelopmental disorder in whom presentation, diagnosis and definitive management tends to be delayed. This leads to poor outcomes, such as loss of the affected testis. Here we present two cases of testicular torsion in patients with neurodevelopmental disorders, and a further two cases of epidydimo-orchitis in whom measurement of CD64 expression on neutrophils was helpful for differential diagnosis. These data suggest that the levels of expression of CD64 by neutrophils, known as a marker of infection, could also be useful for differentiating between testicular torsion and infection in acute scrotum.

Background We examined factors associated with positive consequences for family members who served as caregivers of terminal cancer patients. Methods We conducted a nationwide cross-sectional survey of 501 bereaved family members who served as caregivers for terminal cancer patients. The main outcomes were measured by the previously developed Caregiving Consequences Inventory, which assesses perceived rewards and burdens of caregiving. Results Bereaved family caregivers reported high levels of perceived rewards and burden. Among the characteristics of bereaved family members, older age, female gender, and having a religion were associated with some domains of perceived rewards, but being a spouse of a patient was negatively associated with some domains of perceived rewards. Caregiver depression or perceived burden did not affect positive consequences of caregiving. However, receiving bereavement care was significantly associated with positive outcome in all four perceived reward domains (sense of mastery [adjusted odds ratio {aOR} = 1.69; 95% CI, 1.05–2.70]; appreciation for others [aOR = 2.19; 95% CI, 1.27−3.76]; meaning in life [aOR = 1.80; 95% CI, 1.13–2.89]; and reprioritization about his/her life [aOR = 2.02; 95% CI, 1.27–3.19]). Conclusions Family caregivers of terminal cancer patients experience burdens, but caregiving also has positive consequences. This study has important implications for the development of bereavement interventions that aim to encourage positive outcomes and reduce negative outcomes for caregivers. Copyright © 2012 John Wiley & Sons, Ltd.

Superficial siderosis is a progressive disorder of the central nervous system in which chronic intrathecal bleeding leads to hemosiderin deposition in the brain and spinal cord. Although it is hypothesized that oxidative stress caused by deposited iron contributes to the pathomechanism of superficial siderosis, there is a paucity of research supporting this hypothesis. We examined the cerebrospinal fluid of three patients with superficial siderosis for the oxidative stress marker 8-hydroxy-2′-deoxyguanosine. The origin of bleeding was identified in two of the three patients, who subsequently underwent surgical treatment. We detected elevated 8-hydroxy-2′-deoxyguanosine levels in the cerebrospinal fluid of all three patients that remained high in two patients, even after surgical treatment. Elevated 8-hydroxy-2′-deoxyguanosine levels suggest that oxidative stress is involved in the pathomechanism of superficial siderosis.

We present a simple Bertrand competition model with a Hotelling (Economic Journal, Vol. 39 (1929), pp. 41–57) type spatial competition by incorporating the framework of partial privatization developed by Bos (Privatization: A Theoretical Treatment, Oxford, Clarendon Press, 1991). We investigate simultaneous price choice and sequential price choice with respect to fixed locations of firms and show how the degree of privatization of a public firm influences social welfare in a mixed duopoly market. We also analyse sequential price competition with respect to the location choice of firms.

Objective: The aims of this study were to validate an instrument for measuring bereaved family members' perceptions of caregiving consequences and to examine the association between caregiving consequences and psychological distress. Methods: Cross-sectional questionnaires were administered to family members of patients who had died in regional cancer centers. We measured the Caregiving Consequences Inventory (CCI), respondent's optimism, overall reward scale, and psychological distress and collected background data. A retest was conducted. Results: Bereaved families from two regional cancer centers were surveyed (N=189 and 109; effective response rate, 57 and 80%). By exploratory and confirmatory factor analyses, we identified four perceived reward domains: ‘mastery’, ‘appreciation for others’, ‘meaning in life’, and ‘reprioritization’, and one perceived burden domain. Although the four reward domains were highly correlated with each other (0.47

By incorporating a multinational private firm into the mixed duopoly model with Hotelling-type spatial competition, we show that the private firm's nationality is a matter of the public firm's location. As the share of foreign capital increases in the private (multinational) firm, the public firm moves to a central place. The effects of price regulation and sequential location choice are also discussed.

Future regulatory requirements in Japan will mandate that all high-pressure gas production companies impose a maintenance system based on predictive data rather than on equipment inspections. This paper describes a risk-based maintenance (RBM) system to achieve these new regulatory requirements. © 2005 American Institute of Chemical Engineers Process Saf Prog, 2005

Background: The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects. Methods: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese. Results and conclusion: There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P

TAK1 mitogen-activated protein kinase kinase kinase participates in the Interleukin-1 (IL-1) signaling pathway by mediating activation of JNK, p38, and NF-κB. TAK1-binding protein 2 (TAB2) was previously identified as an adaptor that links TAK1 to an upstream signaling intermediate, tumor necrosis factor receptor-associated factor 6 (TRAF6). Recently, ubiquitination of TRAF6 was shown to play an essential role in the activation of TAK1. However, the mechanism by which IL-1 induces TRAF6 ubiquitination remains to be elucidated. Here we report that TAB2 functions to facilitate TRAF6 ubiquitination and thereby mediates IL-1-induced cellular events. A conserved ubiquitin binding domain in TAB2, the CUE domain, is important for this function. We also found that TAB2 promotes the assembly of TRAF6 with a downstream kinase, IκB kinase (IKK). These results show that TAB2 acts as a multifunctional signaling molecule, facilitating both IL-1-dependent TRAF6 ubiquitination and assembly of the IL-1 signaling complex.

BACKGROUND AND AIM Thrombocytopenia typically worsens with the progression of liver disease and can become a major clinical complication. Several mechanisms that contribute to thrombocytopenia have been proposed, including hypersplenism accompanied by increased platelet sequestration, platelet destruction mediated by platelet-associated immunoglobulins (PAIgG), and diminished platelet production stimulated by thrombopoietin (TPO). The purpose of the present study was to evaluate the role of each of these mechanisms in patients with liver disease-associated thrombocytopenia. METHODS Twenty-nine patients with liver cirrhosis (LC), 20 of whom were hepatitis C virus (HCV)-seropositive, 29 chronic hepatitis (CH) patients, 24 of whom were HCV-seropositive, and 16 control patients without liver or hematopoetic disease were enrolled in this study. Serum TPO levels, PAIgG, and liver-spleen volumes were determined and correlation analyses were performed. RESULTS No differences in serum TPO levels were observed among the three groups. The PAIgG levels were significantly elevated in CH and LC patients (mean +/- SD: 56.5 +/- 42.3 and 144.6 +/- 113.6 ng/107 cells, respectively) compared with the controls (18.9 +/- 2.5 ng/107 cells, P < 0.001 for both). Spleen volume was significantly higher only in LC (428 +/- 239) compared with CH (141 +/- 55) and control (104 +/- 50 cm3) (P < 0.001), while liver volume was not significantly different between the three groups. Correlation analyses demonstrated a significant negative correlation between platelet count with PAIgG (r = - 0.517, P < 0.001) and spleen volume (r = - 0.531, P < 0.001), and no relationship between platelet count and serum TPO level (r = 0.076). CONCLUSIONS Serum TPO level may not be directly associated with thrombocytopenia in patients with chronic hepatitis and liver cirrhosis. In contrast, spleen volume and PAIgG are associated with thrombocytopenia in such patients, suggesting that hypersplenism and immune-mediated processes are predominant thrombocytopenic mechanisms.

MS-818 (2-piperadino-6-methyl-5-oxo-5, 6-dihydro (7H) pyrrolo [2,3-d]pyrimidine maleate), a newly synthesized heterocyclic pyrimidine derivative, promotes neurite outgrowth in neuronal cell lines. The survival-promoting effect of MS-818 on cultured neurons isolated from mouse cortices was examined. MS-818 promoted neuronal survival by inhibiting apoptosis in a dose-dependent manner. MS-818 treatment also activated mitogen-activated protein kinase (MAPK) of the extracellular signal regulation kinase 2, as demonstrated by Western blot analysis. The MAPK activation level in the cultures treated with MS-818 was almost equivalent to that in cultures treated with nerve growth factor but was less than that in cultures treated with epidermal growth factor and basic fibroblast growth factor (bFGF). MAPK was activated within 3 min after the addition of MS-818, and its activity level returned to baseline within 120 min. Its activation was protein kinase C independent. We further investigated the effect of concurrent treatment with MS-818 and bFGF on neuronal survival. MS-818 enhanced the neuronal survival-promoting effect of bFGF in shifting the half-maximally effective dose from 2.1 ng/ml to 0.036 ng/ml in the sigmoidal dose effect of bFGF and permitted nearly maximum MAPK activation. The enhancement by MS-818 of the neuronal survival-promoting effect of bFGF was accompanied by sustained activation of MAPK to a degree that far exceeded, in magnitude and duration, the cooperative effect of MS-818 and bFGF. These results indicate that MS-818 promotes neuronal survival and enhances the neurotrophic actions of bFGF through stimulation of synchronous signals that may elevate MAPK levels within neurons. J. Neurosci. Res. 54:604–612, 1998. © 1998 Wiley-Liss, Inc.

The purpose of this study was to determine whether use of transmitted laser light would enable a better assessment of human pulpal vitality than back-scattered light does (LDF: laser Doppler flowmetry). The experiments were carried out on ten upper central incisors in six subjects aged 23-28 years; five of the teeth were vital with no restoration, and five were non-vital. For use with transmitted laser light, the fibers within the probe of a conventional LDF apparatus were used, one for transmitting light onto the buccal surface, the other for receiving it at the palatal surface of the same tooth. For LDF, the probe was fixed at the buccal surface. Blood flow was measured at three different locations on each experimental tooth: the incisal third, the center and the cervical third of the tooth crown. In non-vital teeth, 1) output signals with transmitted laser light all registered zero, and no oscillation could be seen in recordings from any location on the tooth, but 2) LDF signals were above zero, there were regular oscillations related to heart rate, and passive increases in blood flow (corresponding to blood pressure increases) were recorded from both the center and the cervical third of the tooth, indicating that LDF registered blood flow of non-pulpal origin. In vital teeth, LDF signals were significantly higher than in non-vital teeth at each location on the tooth. At the central site on vital teeth, the output signals for transmitted laser light were about twice those seen with LDF, and passive blood flow changes corresponding to blood pressure increases were more clearly observed. These results indicated that transmitted laser light would be useful for the assessment of tooth pulp vitality both because the blood flow signals did not include flow of non-pulpal origin, and because its output signals and response to blood flow changes were clear and could easily be monitored.