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Background: The co‐occurrence of myasthenia gravis and primary antiphospholipid syndrome (APS) is rare. Notably, both the diseases share common complement‐mediated mechanisms. Case Presentation: A 36‐year‐old woman, who was previously diagnosed with myasthenia gravis and APS, developed multiple embolisms, involving the brain, kidney and spleen, with severe anemia and platelet reduction. She was diagnosed as catastrophic APS, and intensive immunotherapies, including plasma exchange, high‐dose corticosteroid and rituximab, were introduced. After these therapies, symptoms of both APS and myasthenia gravis worsened, consistent with elevation of immunoglobulin G anti‐beta‐2‐glycoprotein‐I antibody and anti‐acetylcholine receptor antibody. We started eculizumab, which resulted in stabilizing the disease activity of both diseases without notable adverse events. Conclusions: Eculizumab can be effective for controlling multiple complement‐mediated pathophysiology. [ABSTRACT FROM AUTHOR]

In the southern Kalahari Desert, cooperatively breeding Southern Pied Babblers Turdoides bicolor frequently build their nests and forage in camelthorn trees Vachellia erioloba, a keystone species in the region, and blackthorn trees Senegalia mellifera, a widespread early successional shrub. Using Ivlev's electivity indices (Ei), we show that Southern Pied Babblers preferentially nest in camelthorn trees and preferentially forage in or under camelthorn and blackthorn trees. Southern Pied Babblers primarily forage on the ground; however, they will make use of arboreal resources when these are available. We observed the birds spending the highest proportion of foraging time off the ground during October, when breeding is also most common, compared with all other months within the austral summer breeding season. They are most likely to be observed foraging in camelthorn trees earlier in the breeding season and blackthorn trees later in the breeding season. We demonstrate that Southern Pied Babblers have a strong relationship with camelthorn trees, in which they prefer to both nest and forage. We highlight the importance of protecting camelthorn trees, a keystone species in the region, as part of the conservation and management of endemic Kalahari fauna such as the Southern Pied Babbler. In addition to contributing to the literature on keystone species, our observations raise questions about the ways in which avian reproduction in the arid zone could be decoupled from rainfall via the phenology of deep‐rooted tree species. [ABSTRACT FROM AUTHOR]

Introduction: To prospectively clarify whether endoscopic contact laser vaporization of the prostate (CVP) can be safely performed even in patients undergoing antithrombotic therapy. Methods: Fifty‐five patients treated with CVP were enrolled. Patients were assigned to: (i) the antithrombotic therapy group (n = 21, 38%); or (ii) control group without antithrombotic therapy (n = 34, 62%). All patients in the antithrombotic therapy group continued all antithrombotic agents during the perioperative period and thereafter. Results: No difference was noted in patient background between the two groups. In primary endpoints, decreases in the postoperative hemoglobin level were remarkable in the antithrombotic therapy group, while no serious effects were noted in either group. The control and antithrombotic therapy groups did not show a significant difference in the occurrence of catheter obstruction due to blood clots or serious hematuria following catheter removal. During follow‐up, transurethral coagulation for hemostasis was needed only in the antithrombotic therapy group, with a frequency of transurethral coagulation of up to 14%. In secondary endpoints, no difference in the occurrence of perioperative or late‐onset complications after surgery was noted between the two groups. Finally, no difference was noted in improvements in the International Prostate Symptom Score (IPSS), IPSS quality of life score, overactive bladder symptom score, maximum flow rate, or post‐voiding residual urine volume between the two groups throughout the follow‐up period. Conclusions: CVP can be performed safely and effectively in patients undergoing continuous antithrombotic therapy. However, the possibility of secondary bleeding after discharge in a subset of patients, such as those undergoing antithrombotic therapy, may be noted. [ABSTRACT FROM AUTHOR]

Background: An aggressive therapeutic strategy used in the early stages of generalized myasthenia gravis (MG), called early fast‐acting treatment (EFT), involves the use of plasmapheresis, intravenous immunoglobulin and/or intravenous high‐dose methylprednisolone (IVMP). The EFT strategy has been proven to have advantages in achieving a treatment goal of MG, minimal manifestations or better with oral prednisolone at a dose of ≤5 mg/day. Case presentation: A 72‐year‐old woman with anti‐acetylcholine receptor antibody‐positive MG underwent EFT. Even a modified IVMP regimen with a reduced dose of just 250 mg/day for 2 days, given after six cycles of plasmapheresis and 10 mg/day of oral prednisolone for 5 days, triggered a severe myasthenic exacerbation. Subsequent intravenous immunoglobulin therapy successfully averted a crisis. Conclusions: Such acute exacerbation after just 250 mg/day of IVMP for 2 days is rare. However, caution is required when using IVMP for EFT of MG, because the risk factors for exacerbation after IVMP use, and the best approach for treating the exacerbation, are not yet known. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle‐invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa‐4N0‐2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2‐4N0‐2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer‐specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non‐MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In vitro mouse spermatogenesis using a classical organ culture method became possible by supplementing basal culture medium with only the product of bovine serum albumin purified by chromatography (AlbuMAX), which indicated that AlbuMAX contained every chemical factor necessary for mouse spermatogenesis. However, since the identity of these factors was unclear, improvements in culture media and our understanding of the nutritional and signal substances required for spermatogenesis were hindered. In the present study, chemically defined media (CDM) without AlbuMAX was used to evaluate each supplementary factor and their combinations for the induction of spermatogenesis. Similar to in vivo conditions, retinoic acid, triiodothyronine (T3), and testosterone (T) were needed. Based on differences in spermatogenic competence between AlbuMAX, fetal bovine serum, and adult bovine serum, we identified α‐tocopherol, which strongly promoted spermatogenesis when combined with ascorbic acid and glutathione. Differences were also observed in the abilities of lipids extracted from AlbuMAX using two different methods to induce spermatogenesis. This led to the identification of lysophospholipids, particularly lysophosphatidylcholine, lysophosphatidic acid, and lysophosphatidylserine, as important molecules for spermatogenesis. New CDM formulated based on these results induced and promoted spermatogenesis as efficiently as AlbuMAX‐containing medium. In vitro spermatogenesis with CDM may provide a unique experimental system for research on spermatogenesis that cannot be performed in in vivo experiments. [ABSTRACT FROM AUTHOR]

IgG4-related disease is a systemic fibroinflammatory disorder that occasionally affects the prostate. It is usually considered that patients with IgG4-related disease are at high risk of developing malignancies. A 71-year-old man presented to our hospital with a chief complaint of urinary retention. Prostate biopsy revealed concomitant IgG4-related prostatitis and prostate cancer. IgG4-related prostatitis was a possible cause of urinary retention, and the aggressive nature of prostate cancer was the cause of the patient's death 2 years after diagnosis. This is the fourth case report of prostate cancer accompanied by IgG4-related prostatitis; however, there have been no reports of the two diseases coexisting with high clinical significance. Our case report indicates that patients diagnosed with IgG4-related prostatitis should be carefully followed up considering the risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: Tapering immunosuppressants is desirable in patients with well‐controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction‐associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction‐associated exacerbation when tacrolimus is tapered in stable patients with anti‐acetylcholine receptor antibody‐positive MG, and to determine the factors that predict exacerbations. Methods: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction‐associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. Results: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction‐associated exacerbation than in those without exacerbation. The cut‐off values determined in a receiver‐operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. Conclusion: Tapering of tacrolimus was possible in most patients with well‐controlled anti‐acetylcholine receptor antibody‐positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late‐onset disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We investigated the association of magnetic resonance imaging (MRI) findings and social activities with cognition in Japanese patients with multiple sclerosis (MS). Methods: Cognition was evaluated by the Brief International Cognitive Assessment for MS (BICAMS), using previously published data for 156 Japanese patients with MS. The BICAMS results were analyzed with available MRI data, focusing on hyperintense lesions on T2/fluid‐attenuated inversion recovery images. Logistic regression analysis was used to assess associations between the BICAMS scores and social activities (i.e. "student," "employed full time," "employed part time," "homemaker" and "unemployed because of MS"). The independent variables were the BICAMS scores, and the Expanded Disability Status Scale, sex, age at examination, education and disease duration. The dependent variable was the "social activity." Results: Analysis of variance showed that patients with MS and more cerebral lesions on MRI had lower scores in all three domains of the BICAMS (the Symbol Digit Modalities Test, the second edition of the California Verbal Learning Test and the revised Brief Visuospatial Memory Test). Scores of all three domains were also significantly lower in patients with cerebellar lesions. Regarding social activities, patients who were unemployed because of MS had lower BICAMS scores compared with employed patients. However, the BICAMS domain scores did not independently affect the other social activities. Conclusions: Higher numbers of cerebral lesions and the presence of cerebellar lesions evaluated by MRI affect cognitive function based on the BICAMS. Cognitive function might affect social activities in patients with MS. Higher numbers of cerebral lesions evaluated by MRI affect cognitive function based on the BICAMS. Cognitive function might affect social activities in patients with MS. [ABSTRACT FROM AUTHOR]

Purpose To determine whether reactive oxygen species ( ROS) in semen samples could be measured with the Monolight™ 3010 Luminometer. Methods Using the Monolight™ 3010 Luminometer, the ROS was measured in the unprocessed semen samples of infertile male patients, as well as the luminescence of 190 semen samples. The samples were classified as 'luminescence-detectable' (n = 89) and 'luminescence-undetectable' (n = 101). Thereafter, the luminescence of the semen samples that had been obtained from the 715 infertile patients was measured and compared by using Sperm Motility Analyzing System measurements. Moreover, in order to investigate the ROS measurement consistency, the chemiluminescence values of 84 samples were measured concurrently by using the Monolight™ 3010 Luminometer and the 1251 Luminometer™. Results The semen volume, sperm motility, and progressive motility of the samples were significantly higher in the luminescence-undetectable samples. The sperm motility, straight-line velocity, curvilinear velocity, mean amplitude head displacement, beat cross frequency, and progressive motility showed an inverse correlation with the logarithmic-transformed luminescence level in the luminescence-detected samples. The integrated chemiluminescence levels in the 84 samples were correlated. Conclusion The substance that was measured in the unprocessed semen with the Monolight™ 3010 Luminometer and stimulated chemiluminescence is ROS. [ABSTRACT FROM AUTHOR]

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 < .001) between problem avoidance behavior at the time of diagnosis and subsequent problem behavior (mean follow-up period after diagnosis: 1.3 + 1.1 years). The characteristics of spouses with avoidant behaviors included having wives with recurrence, having wives treated with anticancer drug therapy or total resection, and having their own experience of cancer. Covariance structure analysis revealed 2 factors related to the background of spouses with problem avoidance behavior: (1) having a sense of difficulty in coping (beta = 0.68, P < .001) and (2) having a poor marital relationship (beta = -0.27, P < .001).Conclusions: Our findings suggest that problem avoidance behavior among healthy male partners of breast cancer patients is common and correlates with difficulty coping and a poor marital relationship. It is important to address both the problem avoidance behavior itself and to support couples early, before this behavior surfaces. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups ( P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy. J. Med. Virol. 82:1364-1370, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Radiologic diagnosis of colorectal foreign bodies is usually not very difficult, because inserted materials are often clearly visible on plain abdominal radiographs. However, when they are radiolucent, a plain abdominal radiograph has been reported to be useless. As radiolucent colorectal foreign bodies appear as radiolucent artificial contours or air-trapped materials in the pelvis, almost always the diagnosis itself can be made by careful evaluation of plain abdominal radiographs. We encountered a case of casting type of radiolucent colorectal foreign body formed from polyurethane foam. It presented us with unexpected radiologic findings and led to diagnostic difficulties. [ABSTRACT FROM AUTHOR]

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

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 Bös ( 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. [ABSTRACT FROM AUTHOR]

Background: Epidural anaesthesia is an efficient method of providing both regional anaesthesia and post-operative pain relief. Detection of the epidural space is critical, but it is difficult to predict the depth of the epidural space. Published results are inconsistent. We retrospectively investigated the differences in the depth of the epidural space depending on the puncture site, approach type and physical findings of patients. Methods: All surgical patients from 1994 to 2005 were included in the study and 4964 cases were analysed. The recorded distance from the needle tip to the skin surface was defined as the depth of the epidural. The differences in the depth were compared according to the puncture site, level and approach. We then searched for the factors determining the depth using multivariate regression analysis. Results: The depth in upper thoracic sites (T1/2–T9/10) was 5.0 (1.0) cm [mean (SD), n= 465] via the midline approach and 5.2 (1.0) cm ( n= 1226) via the paramedian approach. For lumbar sites, the depth was 4.1 (0.9) cm ( n= 1835) via the midline approach and 4.6 (1.0) cm ( n= 298) via the paramedian approach. In the multivariate regression analysis, patient age, body weight and more cephalad puncture were significantly and positively correlated with the depth at thoracic sites. Conclusions: The epidural space was deeper at upper thoracic sites than lower thoracic or lumbar sites. The depth with the paramedian approach was greater than with the midline approach at both sites. Patient age and weight were positive factors for depth. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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 < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required. © 2005 Blackwell Publishing Asia Pty Ltd [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To elucidate how hepatitis C virus (HCV) with multiple variants (quasispecies) is transmitted and adapts to the host during infection, we compared nucleotide and deduced amino acid sequences from hypervariable region1 (HVR1) of the E2 gene of HCV between a donor and a recipient who developed hepatitis after a needlestick accident. Thirty clones from each subject were sequenced after PCR amplification, cloning, and purification of plasmid DNA from single colonies of transformed bacteria. Genetic analysis revealed that the recipient''s viral sequences were much less diverse than the donor''s. We found a single predominant HCV HVR1 clone of the recipient in 22/30 isolates with the same amino acid sequence, and mimic clones in 8/30 isolates with only one amino acid substitution. These were all absent in the donor, who had 21 highly diverse sequences. Phylogenetic analysis of virus E1/E2 gene sequences showed that the recipient''s unique sequences were related to the population of variants from the donor, in whom one isolate had 96% similarity to the recipient''s predominant amino acid sequence. These results suggest that a minor subset of the donor''s HCV variants is selectively transmitted to the recipient, and that the selection determines the predominant variant in the new host. [Copyright &y& Elsevier]

Abstract 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Midkine (MK) is a new member of the heparin binding neurotrophic factor family. MK plays important roles in development and carcinogenesis and has several important biological effects, including promotion of neurite extension and neuronal survival. However, the mechanism by which MK exerts its neurotrophic actions on neurons has not been elucidated to date. We have established an apoptosis induction system by serum deprivation in primary neuronal cultures isolated from mouse cerebral cortices. Neuronal apoptosis induced by serum deprivation was accompanied by the activation of caspase-3. MK, when added into the culture medium, inhibited the induction of apoptosis and activation of caspase-3 in a dose-dependent manner. Extracellular signal-regulated kinase (ERK) and Akt were not activated by serum deprivation, whereas ERK and Akt were rapidly activated by addition of MK. In addition, the trophic actions of MK of suppressing apoptosis and suppressing the activation of caspase-3 were abolished by concomitant treatment with PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, and with wortmannin or LY294002, specific inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase). These PI 3-kinase inhibitors also inhibited the activation of ERK in response to MK, demonstrating a link between ERK and the caspase-3 pathway that is modulated by the PI 3-kinase activation. These... [ABSTRACT FROM AUTHOR]

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 expenments were carned 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 arid 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 be- cause 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 he monitored. [ABSTRACT FROM AUTHOR]

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Sympathetic regulation of periodontal ligament blood flow (PLBF) is well-attested; however, vasodilator responses mediated by parasympathetic nerve fibers have yet to be conclusively demonstrated in the periodontal ligament (PL). The present study was designed to determine whether parasympathetic vasodilator mechanisms do or do not exist in the cat PL. In our cats, the cervical sympathetic trunks were sectioned bilaterally prior to any stimulation in order to eliminate sympathetic effects on the vascular beds under study. Dynamic changes in PLBF, with mandibular lip blood flow (LBF) recorded for comparison, were investigated in cat mandibular canine teeth using laser Doppler flowmetry. The peripheral cut ends of the facial and glossopharyngeal nerve roots, which have been reported to contain parasympathetic nerve fibers to the oral tissues, were electrically stimulated intracranially. Such stimulation caused blood flow to increase in the ipsilateral PL and lip, without an increase in systemic blood pressure. These vasodilator responses in the PL and lip were sensitive to ganglion blockade (with hexamethonium), indicating vasodilatation via activation of parasympathetic vasodilator fibers. In contrast, although intracranial stimulation of the trigeminal nerve root also induced increases in both PLBF and LBF, these were unaffected hexamethonium, but reduced by tripelennamine, indicating antidromic vasodilatation via the trigeminal sensory nerve. These results suggest that parasympathetic vasodilator mechanisms do exist in feline PL. [ABSTRACT FROM AUTHOR]

The purpose of the study was to calibrate the laser Doppler signals with simultaneous measurements made by the H2 gas clearance method in the cat gingiva. Four young adult cats were used, weighing from 2.5 to 4.8 kg for the study. The GBF values measured and those measured by the H2 gas clearance were plotted. The results suggest that stimulation of the ipsilateral cervical sympathetic trunk for 5 mm induced a stable and long-lasting decrease in gingival blood flow (GBF) during stimulation.

This article focuses on a study on the acute response of periodontal ligament blood flow to external force application. For this study ten adult cats were used, each weighing from 2.4 to 4.5 kg. They were anesthetized with an i.m. injection of ketamine hydrochloride, 35 mg/kg initially, and then with an i.v. injection of Nembutal 35 mg/kg, supplemented when necessary with additional doses of 5 mg/kg. The trachea was cannulated, and the blood pressure in the femoral artery was monitored continuously by means of a pressure transducer, and recorded on a polygraph. The animal's head and jaws were fixed by a steel rod secured to the jaws by dental acrylic.