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Pediatric nondysraphic intramedullary lipoma is very rare, and only limited cases have been reported. In the present case, we present two infant patients with these pathologies who were surgically treated. Previous literature on 20 patients with these diseases who had undergone surgical treatments was analyzed. Surgical treatment should be considered in most symptomatic patients, and laminoplastic laminotomy and internal debulking of the lipoma under intraoperative neurophysiological monitoring are mostly recommended. [ABSTRACT FROM AUTHOR]

Purpose: To determine the active principle responsible for the cytotoxic effect of Anthemis palestina (Reut. ex Kotschy) Reut. ex Boiss. (Asteraceae). Methods: A bioassay-guided fractionation was used to isolate the active principle, luteolin, which structure was elucidated using ¹H and 13C NMR. The cytotoxic effects of luteolin and doxorubicin (positive control) in the breast cancer cell lines MDA-MB-231 and MCF-7, and in normal fibroblasts, were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results: Luteolin was isolated from the ethyl acetate extract of the aerial parts of Anthemis palestina. With an IC50 value of 14.91 ± 5.77 µM for MDA-MB-231 cells, luteolin was less active than doxorubicin. However, with respect to MCF-7 cells, there was no significant difference in the cytotoxicity values of luteolin and doxorubicin, with IC50 value of 29.28 ± 11.85 µM for luteolin. However, with an IC50 value of 51.39 ± 18.51 µM against fibroblasts, luteolin was significantly safer than doxorubicin. Conclusion: Luteolin might be responsible for the cytotoxicity of Anthemis palestina. The high level of luteolin cytotoxicity indicates the potential benefits of Anthemis palestina, not only in terms of its taste, but also for its likely positive therapeutic impact on cancer, especially breast cancer. [ABSTRACT FROM AUTHOR]

Background: Mechanical stimuli play important roles in the proliferation and differentiation of adult stem cells. However, few studies on their effects on induced pluripotent stem cells (iPSCs) have been published. Methods: Human dermal fibroblasts were seeded onto flexible membrane-bottom plates and infected with retrovirus expressing the four reprogramming factors OCT4, SOX2, KLF and c-MYC (OSKM). The cells were subjected to equiaxial stretching (3% or 8% for 2, 4, or 7 days) and seeded on feeder cells (STO). The reprogramming into iPSCs was evaluated by the expression of pluripotent markers, in vitro differentiation into three germ layers and teratoma formation. Results: Equiaxial stretching enhanced reprogramming efficiency without affecting the viral transduction rate. iPSCs induced by transduction of four reprogramming factors and application of equiaxial stretching had characteristics typical of iPSCs in terms of pluripotency and differentiation potentials. Conclusions: This is the first study to show that mechanical stimuli can increase reprogramming efficiency. However, it did not enhance the infection rate, indicating that mechanical stimuli, defined as stretching in this study, have positive effects on reprogramming rather than on infection. Additional studies should evaluate the mechanism underlying the modulation of reprogramming of somatic cells into iPSCs. [ABSTRACT FROM AUTHOR]

This article discusses a case of Turner syndrome in a 33-month-old girl who was diagnosed with Xp22.33 deletion combined with 7p22.3 duplication. Turner syndrome is a chromosomal disorder that affects one out of 2,000 female births and is characterized by short stature, cardiovascular and renal abnormalities, gonadal dysgenesis, and ovarian failure. The degree of reproductive dysfunction can vary depending on the range of deletion of the X chromosome. The patient in this case had developmental delay, short stature, and Müllerian agenesis, and the diagnosis was confirmed through chromosomal microarray analysis. This is the first reported case of Turner syndrome due to Xp22.33 deletion combined with 7p22.3 duplication. [Extracted from the article]

Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to treat inflammatory responses little is known about anti-inflammatory effect of atractylodin in the human mast cell (HMC-1). Hence, we evaluated the effect of atractylodin on the release of IL-6, the involvement of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) and mitogen-activated protein kinases (MAPKs) in phorbol-12-myristate-13-acetate and A23187-induced HMC-1. In addition, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), phospholipase C (PLC) gamma 1, and AKT phosphorylation relevant to NPM-ALK signal pathway were assessed. IL-6 levels in the HMC-1 stimulated by phorbol-12-myristate-13-acetate and A23187 were apparently decreased by the treatment of atractylodin. Concurrently, atractylodin not only inhibited the phosphorylation of NPM-ALK, but also suppressed the phosphorylation of JAK2, STAT3, PLC gamma 1, and AKT. Furthermore, the activated mitogen-activated protein kinases (MAPKs) by phorbol-12-myristate-13-acetate and A23187 were inhibited by atractylodin. These results suggested that atractylodin might have a potential regulatory effect on inflammatory mediator expression through blockade of both the phosphorylation of MAPKs and the NPM-ALK signaling pathway. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid a-receptor (RARA) gene at 17q21. The current study presents the case of a 54-year-old female with APL carrying the atypical PML/RARA fusion signal due to a novel complex variant translocation t(15;16;17)(q22;q24;q21), as well as the classical PML/RARA fusion signal. Subsequent array comparative genomic hybridization revealed somatic, cryptic deletions on 3p25.3, 8q23.1 and 12p13.2-p13.1, and a duplication on 8q11.2; however, no genetic material loss or gain was observed in the breakpoint regions of chromosomes 15, 16 or 17. To the best of our knowledge, this is the first report of the coexistence of two abnormal clones, one classical and one variant, presenting simultaneously in addition to cryptic chromosome segmental imbalances in an adult APL patient. [ABSTRACT FROM AUTHOR]

Background As part of a National Emergency Obstetric and Newborn Care (EmONC) Needs Assessment, a special study was undertaken in July 2010 to examine the quality of cesarean deliveries in Afghanistan and examine the utility of direct clinical observation as an assessment method in low-resource settings. Methods This cross-sectional assessment of the quality of cesareans at 14 facilities in Afghanistan included a survey of surgeons regarding their routine cesarean practices, direct observation of 29 cesarean deliveries and comparison of observations with facility records for 34 additional cesareans conducted during the 3 days prior to the observation period at each facility. For both observed cases and record reviews, we assessed time intervals between specified points of care-arrival to the ward, first evaluation, detection of a complication, decision for cesarean, incision, and birth. Results All time intervals with the exception of "decision to skin incision" were longer in the record reviews than in observed cases. Prior cesarean was the most common primary indication for all cases. All mothers in both groups observed survived through one hour postpartum. Among newborns there were two stillbirths (7%) in observed births and seven (21%) record reviews. Although our sample is too small to show statistical significance, the difference is noteworthy. In six of the reviewed cesareans resulting in stillbirth, a fetal heart rate was recorded in the operating theater, although four were recorded as macerated. For the two fresh stillbirths, the cesarean surgeries were recorded as scheduled and not urgent. Conclusions Direct observation of cesarean deliveries enabled us to assess a number of preoperative, postoperative, and intraoperative procedures that are often not described in medical records in low resource settings. Comparison of observations with findings from provider interviews and facility records allowed us to infer whether observed practices were typical of providers and facilities and detect potential Hawthorne effects. [ABSTRACT FROM AUTHOR]

Background This study describes job satisfaction and intention to stay on the job among primary healthcare providers in countries with distinctly different human resource crises, Afghanistan and Malawi. Methods Using a cross-sectional design, we enrolled 87 health-care providers in 32 primary healthcare facilities in Afghanistan and 360 providers in 10 regional hospitals in Malawi. The study questionnaire was used to assess job satisfaction, intention to stay in the job and five features of the workplace environment: resources, performance recognition, financial compensation, training opportunities and safety. Descriptive analyses, exploratory factor analyses for scale development, bivariate correlation analyses and bivariate and multiple linear regression analyses were conducted. Results The multivariate model for Afghanistan, with demographic, background and work environment variables, explained 23.9% of variance in job satisfaction (F(9,73) = 5.08; P < 0.01). However, none of the work environment variables were significantly related to job satisfaction. The multivariate model for intention to stay for Afghanistan explained 23.6% of variance (F(8,74) = 4.10; P < 0.01). Those with high scores for recognition were more likely to have higher intention to stay (β = 0.328, P < 0.05). However, being paid an appropriate salary was negatively related to intent to stay (β = -0.326, P < 0.01). For Malawi, the overall model explained only 9.8% of variance in job satisfaction (F(8,332) = 4.19; P < 0.01) and 9.1% of variance in intention to stay (F(10, 330) = 3.57; P < 0.01). Conclusions The construction of concepts of health-care worker satisfaction and intention to stay on the job are highly dependent on the local context. Although health-care workers in both Afghanistan and Malawi reported satisfaction with their jobs, the predictors of satisfaction, and the extent to which those predictors explained variations in job satisfaction and intention to stay on the job, differed substantially. These findings demonstrate the need for more detailed comparative human resources for health-care research, particularly regarding the relative importance of different determinants of job satisfaction and intention to stay in different contexts and the effectiveness of interventions designed to improve health-care worker performance and retention. [ABSTRACT FROM AUTHOR]

Background: As part of a National Emergency Obstetric and Newborn Care (EmONC) Needs Assessment, a special study was undertaken in July 2010 to examine the quality of cesarean deliveries in Afghanistan and examine the utility of direct clinical observation as an assessment method in low-resource settings. Methods: This cross-sectional assessment of the quality of cesareans at 14 facilities in Afghanistan included a survey of surgeons regarding their routine cesarean practices, direct observation of 29 cesarean deliveries and comparison of observations with facility records for 34 additional cesareans conducted during the 3 days prior to the observation period at each facility. For both observed cases and record reviews, we assessed time intervals between specified points of care-arrival to the ward, first evaluation, detection of a complication, decision for cesarean, incision, and birth. Results: All time intervals with the exception of "decision to skin incision" were longer in the record reviews than in observed cases. Prior cesarean was the most common primary indication for all cases. All mothers in both groups observed survived through one hour postpartum. Among newborns there were two stillbirths (7%) in observed births and seven (21%) record reviews. Although our sample is too small to show statistical significance, the difference is noteworthy. In six of the reviewed cesareans resulting in stillbirth, a fetal heart rate was recorded in the operating theater, although four were recorded as macerated. For the two fresh stillbirths, the cesarean surgeries were recorded as scheduled and not urgent. Conclusions: Direct observation of cesarean deliveries enabled us to assess a number of preoperative, postoperative, and intraoperative procedures that are often not described in medical records in low resource settings. Comparison of observations with findings from provider interviews and facility records allowed us to infer whether observed practices were typical of providers and facilities and detect potential Hawthorne effects. [ABSTRACT FROM AUTHOR]

Background: An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases.Methods: A further analysis was conducted of the 2009-10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers.Results: The median number of severe PE/E cases in the past year was just 5 (range 0-42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0-130) at provincial hospitals and 108 (range 32-540) at regional and specialized hospitals (p < 0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There was a significant difference between doctors and midwives on only one item: continued use of anti-hypertensives after convulsions are controlled.Conclusions: Drugs and supplies needed to treat severe PE/E are widely available at EmONC facilities in Afghanistan, but providers lack knowledge in some areas, especially concerning the use of MgSO4 and diazepam. Providers who have specialized training or work at larger facilities are better at managing cases of severe PE/E. The findings suggest a need to clarify service delivery guidelines, offer refresher training, and reinforce best practices with supervision and reinforcement. [ABSTRACT FROM AUTHOR]

Background: The Zambian Defence Force (ZDF) is working to improve the quality of services to prevent mother-to-child transmission of HIV (PMTCT) at its health facilities. This study evaluates the impact of an intervention that included provider training, supportive supervision, detailed performance standards, repeated assessments of service quality, and task shifting of group education to lay workers. Methods: Four ZDF facilities implementing the intervention were matched with four comparison sites. Assessors visited the sites before and after the intervention and completed checklists while observing 387 antenatal care (ANC) consultations and 41 group education sessions. A checklist was used to observe facilities’ infrastructure and support systems. Bivariate and multivariate analyses were conducted of findings on provider performance during consultations. Results: Among 137 women observed during their initial ANC visit, 52% came during the first 20 weeks of pregnancy, but 19% waited until the 28th week or later. Overall scores for providers’ PMTCT skills rose from 58% at baseline to 73% at endline (p=0.003) at intervention sites, but remained stable at 52% at comparison sites. Especially large gains were seen at intervention sites in family planning counseling (34% to 75%, p=0.026), HIV testing during return visits (13% to 48%, p=0.034), and HIV/AIDS management during visits that did not include an HIV test (1% to 34%, p=0.004). Overall scores for providers’ ANC skills rose from 67% to 74% at intervention sites, but declined from 65% to 59% at comparison sites; neither change was significant in the multivariate analysis. Overall scores for group education rose from 87% to 91% at intervention sites and declined from 78% to 57% at comparison sites. The overall facility readiness score rose from 73% to 88% at intervention sites and from 75% to 82% at comparison sites. Conclusions: These findings are relevant to civilian as well as military health systems in Zambia because the two are closely coordinated. Lessons learned include: the ability of detailed performance standards to draw attention to and strengthen areas of weakness; the benefits of training lay workers to take over non-clinical PMTCT tasks; and the need to encourage pregnant women to seek ANC early. [ABSTRACT FROM AUTHOR]

We report on an anesthetic experience with a 74-year-old female with Isaacs' syndrome, who underwent elective surgery for open rotator cuff repair. Isaacs' syndrome is a rare peripheral motor neuron disorder with clinical manifestations such as involuntary muscle twitching, cramps, mild weakness and increased sweating. To avoid prolonged neuromuscular blockade, the patient was observed with neuromuscular monitoring during total intravenous anesthesia with propofol, remifentanil, and atracurium. No adverse events were observed during the anesthetic management, and the patient recovered smoothly from the neuromuscular blockade. We describe the clinical characteristics of Isaacs' syndrome and its specific considerations in anesthesia. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor-β1 (TGF-β1) induces the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle cells. Lipid rafts are cholesterol-rich microdomains in cell membranes that reportedly play a key role in receptor-mediated signal transduction and cellular responses. In order to clarify whether lipid rafts are involved in TGF-β1-induced differentiation of hASCs into smooth muscle cells, we analyzed the lipid raft proteome of hASCs. Methods and Results: Pretreatment of hASCs with the lipid raft disruptor methyl-β-cyclodextrin abrogated TGF-β1-induced expression of a-smooth muscle actin, a smooth muscle cell marker, suggesting a pivotal role of lipid rafts in TGF-β1-induced differentiation of hASCs to smooth muscle cells. Sucrose density gradient centrifugation along with a shotgun proteomic strategy using liquid chromatography-tandem mass spectrometry identified 1002 individual proteins as the lipid raft proteome, and 242 of these were induced by TGF-β1 treatment. ADAM12, a disintegrin and metalloproteases family member, was identified as the most highly up-regulated protein in response to TGF-β1 treatment. TGF-β1 treatment of hASCs stimulated the production of both ADAM12 protein and mRNA. Silencing of endogenous ADAM12 expression using lentiviral small hairpin RNA or small interfering RNA abrogated the TGF-β1-induced differentiation of hASCs into smooth muscle cells. Conclusions: These results suggest a pivotal role for lipid raft-associated ADAM12 in the TGF-β1-induced differentiation of hASCs into smooth muscle cells. [ABSTRACT FROM AUTHOR]

Background: Epidrum® is a recently developed, air operated, loss of resistance (LOR) device for identifying the epidural space. We investigated the usefulness of Epidrum® by comparing it with the conventional LOR technique for identifying the epidural space. Methods: One hundred eight American Society of Anesthesiologists (ASA) physical status I or II patients between the ages of 17 and 68 years old and who were scheduled for elective surgery under combined spinal-epidural anesthesia were enrolled in this study. The patients were randomized into two groups: one group received epidural anesthesia by the conventional LOR technique (C group) and the second group received epidural anesthesia using Epidrum® (ED group). While performing epidural anesthesia, the values of variables were recorded, including the number of failures, more than 2 attempts, the incidence of dural puncture, the time needed to locate the epidural space, the distance from the skin to the epidural space and ease of performance, and the satisfaction scores. Results: The ED group showed a lower failure rate, fewer cases of more than 2 attempts, a lesser time to identify the epidural space, and better ease and satisfaction scores of procedure than the C group, with statistical significance. Conclusions: Using Epidrum® compared to the conventional LOR technique is an easy, rapid, and reliable method for identifying the epidural space. [ABSTRACT FROM AUTHOR]

Background: Bicarbonate, as an adjunct increasing the non-ionized form of local anesthetics, can reduce latency and prolong duration of regional nerve block. Warming of local anesthetics decreases pKa and also increases the non-ionized form of local anesthetics. We warmed ropivacaine to body temperature (37°C) and evaluated the sensory block onset time, motor block onset time and analgesic duration of axillary block. Methods: Patients were consecutively allocated to two groups of 22 patients each. Ropivacaine 150 mg (30 ml) at 20°C (room temperature) and 150 mg (30 ml) at 37°C (body temperature) was injected in group 1 and group 2, respectively. Sensory block and motor block was assessed every 5 minutes, for 30 minutes after injection. The duration of analgesia was recorded after operation. Results: In group 2, the onset times of both sensory and motor block of the radial, ulnar, median and musculocutaneous nerves were significantly reduced, compared to group 1. Also, the number of blocked nerves was increased in group 2, within 30 minutes after injection. Analgesia lasted for 2 hours longer in group 2, compared to group 1, but the difference was not statistically significant (P > 0.05). Conclusions: Warming of ropivacaine to 37°C can reduce the onset time of both sensory and motor block, during axillary block. [ABSTRACT FROM AUTHOR]

AbstractLiver X receptor-α (LXRα) functions as a major regulator of lipid homeostasis through activation of sterol regulatory element binding protein-1c (SREBP-1c), which promotes hepatic steatosis and steatohepatitis. NF-E2-related factor 2 (Nrf2) is the crucial transcription factor that is necessary for the induction of antioxidant enzymes. This study investigated the potential of liquiritigenin (LQ), a hepatoprotective flavonoid in licorice, to inhibit LXRα-induced hepatic steatosis, and the underlying mechanism of the action. LQ treatment attenuated fat accumulation and lipogenic gene induction in the liver of mice fed a high fat diet. Also, LQ had the ability to inhibit oxidative liver injury, as shown by decreases in thiobarbituric acid reactive substances formation and nitrotyrosinylation. Moreover, LQ treatment antagonized LXRα agonist (T0901317)-mediated SREBP-1c activation, and transactivation of the lipogenic target genes. LQ was found to activate Nrf2, and the ability of LQ to inhibit LXRα-mediated SREBP-1c activation was reversed by Nrf2 deficiency, which supports the inhibitory role of Nrf2 in LXRα-dependent lipogenesis. Consistently, treatment with other Nrf2 activators or forced expression of Nrf2 also inhibited LXRα-mediated SREBP-1c activation. Our results demonstrate that LQ has an efficacy to activate Nrf2, which contributes to inhibiting the activity of LXRα that leads to SREBP-1c induction and hepatic steatosis. Antioxid. Redox Signal.14, 733–745. [ABSTRACT FROM AUTHOR]

Idiopathic hypereosinophilic syndrome (IHES) is a heterogeneous spectrum of disorders characterized by hypereosinophilia and the presence of dysfunction in various end organs without an identifiable underlying cause. Neurological manifestations, including peripheral neuropathy, encephalopathy and cerebral thromboembolic or hemorrhagic disorders, can exist with IHES. We present a unique case of a 14-year-old girl with IHES and encephalitis involving the right temporo-parieto-occipital cortex. [ABSTRACT FROM AUTHOR]

The fast accumulation of mutant mouse strains in recent years has provided an invaluable resource for phenotype-based genetic screens. However, study of lymphoid phenotypes can be obscured or impractical if homozygous mutations cause early embryonic defects. To aid phenotype screening of germ line mutations in the lymphoid system, we developed a method to induce loss of heterozygosity (LOH) in developing lymphocytes through chromosome deletion. Chromosome deletion was triggered by Cre/loxP-mediated inverse sister chromatid recombination in the G2/M phase of the cell cycle, leading to the generation of daughter cells missing part of or the entire recombinant chromosome. We show that the resulting cells were viable and capable of additional rounds of cell division, thus providing raw materials for subsequent phenotypic assessment. We used the recombination system to induce LOH at the E2A locus in developing B cells. A significant loss of pro-B and pre-B cells was observed when the wild-type allele was removed by chromosome deletion from the E2A heterozygous mice, a result consistent with the required role for E2A in B cell development. We also demonstrated the effectiveness of Cre-mediated chromosome deletion in the LOH assay for HEB function in T cell development. Thus, the Cre-mediated chromosome deletion provides a new and effective method for genome-wide assessment of germ line mutations in the lymphoid system. [ABSTRACT FROM AUTHOR]

The etiology of human T-cell leukemia virus type 1 (HTLV-1)-induced adult T-cell leukemia is linked to the expression of the viral oncoprotein Tax. Although the mechanism of retroviral transformation is unknown, Tax interferes with fundamental cellular processes, including proliferation and apoptosis, and these events may directly link Tax to early steps in malignant progression. In this study, we examined the interplay between Tax and the potent proto-oncogene B-cell chronic leukemia protein 3 (Bcl3). Bcl3 is a critical regulator of cell survival and proliferation and is overexpressed in HTLV-1-infected cells. We found that Tax induced Bcl3 expression through stimulation of the NF-κB pathway. An intronic NF-κB binding site within the Bcl3 gene served as the primary target of Tax-induced NF-κB activation. We next considered the consequence of Bcl3 overexpression on Tax function. Interestingly, we found that Bcl3 formed a stable complex with Tax and that this complex potently inhibited Tax-dependent HTLV-1 transcription. Importantly, Bcl3 associated with the HTLV-1 promoter in a Tax-dependent manner and inhibited the binding of the critical cellular coactivator p300. The conserved ankyrin repeat domain of Bcl3 mediated both Tax binding and inhibition of p300 recruitment to the HTLV-1 promoter. Together, these data suggest that Tax-induced Bcl3 overexpression benefits the virus in two important ways. First, Bcl3 may promote cell division and thus clonal proliferation of the virus. Second, Bcl3 may attenuate virion production, facilitating immune evasion. One consequence of this regulatory loop may be Bcl3-induced malignant transformation of the host cell. [ABSTRACT FROM AUTHOR]

Transcriptional activation of human T-cell leukemia virus type 1 (HTLV-1) is mediated by the viral oncoprotein Tax, which utilizes cellular transcriptional machinery to perform this function. The viral promoter carries three cyclic AMP-response elements (CREs), which are recognized by the cellular transcription factor cAMP-response element-binding protein (CREB). Tax binds to GC-rich sequences that immediately flank the CREs. The coactivator CREB-binding protein (CBP)/p300 binds to this promoter-bound ternary complex, which promotes the initiation of HTLV-1 transcription. Protein kinase A phosphorylation of CREB at serine 133 facilitates transcription from cellular CREs by recruiting CBP/p300 via its KIX domain. However, it remains controversial whether CREB phosphorylation plays a role in Tax transactivation. In this study, we biochemically characterized the quaternary complex formed by Tax, CREB, KIX, and the viral CRE by examining the individual molecular interactions that contribute to Tax stabilization in the complex. Our data show KIX, Ser133-phosphorylated CREB, and vCRE DNA are all required for stable Tax incorporation into the complex in vitro. Consonant with a fundamental role for CREB phosphorylation in Tax recruitment to the complex, we found that CREB is highly phosphorylated in a panel of HTLV-1-infected human T-cell lines. Significantly, we show that Tax is directly responsible for promoting elevated levels of CREB phosphorylation. Together, these data support a model in which Tax promotes CREB phosphorylation in vivo to ensure availability for Tax transactivation. Because pCREB has been implicated in leukemogenesis, enhancement of CREB phosphorylation by the virus may play a role in the etiology of adult T-cell leukemia. [ABSTRACT FROM AUTHOR]

Purpose. A decision matrix for identifying drugs for which pharmacogenetic drug monitoring (PDM) provides the greatest benefit in a Korean setting is described. Summary. We developed a decision matrix including the ethnic frequency of clinically relevant polymorphic cytochrome P-450 (CYP) enzymes, and the metabolic profiles and adverse drug reactions of drugs. Using the developed decision matrix based on the population allele frequencies of CYP enzymes, we identified potential candidates for PDM among the most commonly used drugs at Seoul National University Hospital (SNUH). Collectively, 17 of these drugs were largely metabolized by at least one polymorphic CYP enzyme. Pharmacogenetic information was used to identify CYP2C9, CYP2C19, and CYP2D6 as the major CYP enzymes of clinical importance for pharmacologic effect and safety in Koreans. The frequencies of poor and intermediate metabolizers among Koreans were 0% and 2.3–12% for CYP2C9, 12% and 42% for CYP2C19, and 0.44% and 28% for CYP2D6, respectively. The frequency of ultrarapid metabolizers of CYP2D6 was 2.28%. The decision matrix and pharmacogenetic information were used to identify seven drugs for PDM: warfarin, glimepiride, diazepam, amitriptyline, nortriptyline, codeine, and oxycodone. This approach can be applied to other institutional hospitals or other ethnic populations and would be helpful for advancing pharmacy practice. Further work is required to assess the practical and potential clinical relevance of pharmacogenetic variations on drugs of interest before the implementation of PDM. Conclusion. A decision matrix helped identify drugs for which PDM provides the greatest potential benefit at one Korean hospital. [ABSTRACT FROM AUTHOR]

The authors examine whether growth in earnings inequality has played out in ways that are class strengthening or class weakening. Using the Current Population Survey, they show that the absolute amount of inequality is increasing (a) between big classes, (b) between the occupations constituting big classes, and (c) within occupations. In relative terms, the share of total inequality occurring within occupations has declined, whereas the share of total inequality occurring between classes and between the occupations constituting big classes has tended to increase, most clearly for men. Although the majority of earnings inequality is still generated within occupations, especially rapid growth of the between-class and between-occupation components implies that the well-known takeoff in inequality has generated a "lumpier" earnings distribution with relatively stronger class and occupational distinctions. [ABSTRACT FROM AUTHOR]

A Claisen rearrangement/iodolactamization sequence starting from commercially available trifluoroacetaldehyde methyl hemiacetal, followed by a classical chemical resolution, provided enantiomerically pure 4,4-difluoro-3,3-dimethylproline (S)-1. No hazardous fluorination reagents were used, and the overall yield over 12 steps was greater than 28%. [ABSTRACT FROM AUTHOR]

Dichlorodihydrofluorescein (DCFH2) is a widely used probe for intracellular H2O2. However, H2O2 can oxidize DCFH2 only in the presence of a catalyst, whose identity in cells has not been clearly defined. We compared the peroxidase activity of Cu,Zn-superoxide dismutase (CuZnSOD), cytochrome c, horseradish peroxidase (HRP), Cu2+, and Fe3+ under various conditions to identify an intracellular catalyst. Enormous increase by bicarbonate in the rate of DCFH2 oxidation distinguished CuZnSOD from cytochrome c and HRP. Cyanide inhibited the reaction catalyzed by CuZnSOD but accelerated that by Cu2+ and Fe3+. Oxidation of DCFH2 by H2O2 in the presence of a cell lysate was also enhanced by bicarbonate and inhibited by cyanide. Confocal microscopy of H2O2-treated cells showed enhanced DCF fluorescence in the presence of bicarbonate and attenuated fluorescence for the cells pre-incubated with KCN. Moreover, DCF fluorescence was intensified in CuZnSOD-transfected HaCaT and RAW 264.7 cells. We propose that CuZnSOD is a potential intracellular catalyst for the H2O2-dependent oxidation of DCFH2. [ABSTRACT FROM AUTHOR]

Microbial modification of vegetable fatty acids can often lead to special changes in their structure and in biological function. A bacterial strain, Pseudomonas aeruginosa PR3, is known to carry out multiple hydroxylations on polyunsaturated fatty acids containing 1,4- cis, cis diene structural units, resulting in antibacterial activity. In this paper, in an effort to understand the overall mechanism involved in the varied biological functions of the complicated metabolites of bio-converted polyunsaturated fatty acids, we performed bioconversion of several polyunsaturated fatty acids using PR3, and determined their oxidative activities against fish oil. Bio-converted linoleic acid, eicosapentanoic acid, and docosahexanoic acid promoted effectively oxidation of fish oil. It is assumed that this oxidative effect could plausibly play an important role in the antimicrobial function of these bio-converted fatty acids. [ABSTRACT FROM AUTHOR]

CONTEXT: The World Health Organization (WHO) has developed a decision-making tool to be used by providers and clients during family planning visits to improve the quality of services. It is important to examine the tool's usability and its impact on counseling and decision-making processes during family planning consultations. METHODS: Thirteen providers in Mexico City were videotaped with family planning clients three months before and one month after attending a training session on the WHO decision-making tool. The videotapes were coded for client-provider communication and eye contact, and decision-making behaviors were rated. In-depth interviews and focus group discussions explored clients' and providers' opinions of the tool. RESULTS: After providers began using the decision-making tool, they gave clients more information on family planning, tailored that information more closely to clients' situations and more often discussed HIV/AIDS prevention, dual protection and condom use. Client involvement in the decision-making process and client active communication increased, contributing to a shift from provider-dominated to shared decision making. Clients reported that the tool helped them understand the provider's explanations and made them feel more comfortable talking and asking questions during consultations. After one month of practice with the decision-making tool, most providers felt comfortable with it and found it useful; however, they recommended some changes to the tool to help engage clients in the decision-making process. CONCLUSIONS: The decision-making tool was useful both as a job aid for providers and as a decision aid for clients. [ABSTRACT FROM AUTHOR]

Books Reviewed Kim Samuel S. (ed.), KOREA's DEMOCRATIZATION, (YOUNG MI KIM), Hirata Keiko, CIVIL SOCIETY IN JAPAN: the growing role of NGOs in Tokyo's aid development policy, (DAVID M. POTTER), Preston Peter W. (ed.), POLITICAL CHANGE IN EAST ASIA, (FLAVIA MONCERI), Zhang Yumei, PACIFIC ASIA: the politics of development, (ALEXANDER C. TAN), Chan Adrian, CHINESE MARXISM, (C. S. GOTO-JONES), [ABSTRACT FROM AUTHOR]

The HFR1, a basic helix-loop-helix protein, is required for a subset of phytochrome A-mediated photoresponses in Arabidopsis. Here, we show that overexpression of the HFR1-ΔN105 mutant, which lacks the N-terminal 105 amino acids, confers exaggerated photoresponses even in darkness. Physiological analysis implied that overexpression of HFR1-ΔN105 activated constitutively a branch pathway of light signaling that mediates a subset of photomorphogenic responses, including germination, de-etiolation, gravitropic hypocotyl growth, blocking of greening, and expression of some lightregulated genes such as CAB, DRT112, PSAE, PSBL, PORA, and XTR7, without affecting the light-responsiveness of anthocyanin accumulation and expression of other light-regulated genes such as CHS and PSBS. Although the end-of-day far-red light response and petiole elongation were suppressed in the HFR1-ΔN105-overexpressing plants, flowering time was not affected by HFR1-ΔN105. In addition, the HFR1-ΔN105-overexpressing plants showed hypersensitive photoresponses in the inhibition of hypocotyl elongation, dependently on phytochrome A, FHY1, and FHY3 under FR light or phyB under R light, respectively. Moreover, our double mutant analysis suggested that the hypersensitive photoresponse is due to functional cooperation between HFR1-ΔN105 and other light-signaling components including HY5, a basic leucine zipper protein. Taken together, our results of gain-of-function approach with HFR1-ΔN105 suggest the existence of a complex and important basic helix-loop-helix protein-mediated transcriptional network controlling a branch pathway of light signaling and provide a useful framework for further genetic dissection of light-signaling network in Arabidopsis. [ABSTRACT FROM AUTHOR]

Examines the biochemical properties of Phosphatase 1 Nuclear Targeting Subunit (PNUTS), a protein that targets protein phosphatase (PP) 1 to the nucleus. Truncation and site-directed mutants of PNUTS; Results of in vitro RNA binding experiments; Regulation of PP1 activity by PNUTS.

Explores the advocacy on sexual responsibility among young individuals in Zimbabwe. Employment of logistic regression analysis; Use of multimedia approach in promoting sexual responsibility; Issues on reproductive health and safe sex.

The article presents a study focusing on tyrosinase inhibitors desmodianone H and uncinanone B obtained from Lespedeza maximowiczii shrub by using bioactivity-guided isolation. The findings of the study include the determination of structures of inhibitors by analysis of their nuclear magnetic resonance and mass spectrometry data, high antityrosinase activity shown by inhibitors, and the conclusion that it could be an effective skin-whitening agent.

Potassium trichloro(safrole)platinate(II), K[Pt(Saf)Cl 3] ( 1), reacts with piperidine to give cis-[Pt(Saf-1H)(Piperidine)Cl] ( 2). The interaction of 1with AgNO 3, SnCl 2, KOH, and ethanol−water solutions leads to formation of the dinuclear chelate ring complex [Pt 2(Saf-1H) 2Cl 2] ( 3). 1H and 13C NMR spectra and single-crystal X-ray diffraction show that in complexes 2and 3deprotonated safrole is bound up with platinum(II) both at a benzene carbon and at the ethylenic double bond of the side chain. [ABSTRACT FROM AUTHOR]

The article reflects on the threat felt by sex workers in Korea regarding the enforcement of the Special Law of the Ministry of Gender Equality. It is cited that those who made the law does not really know how tough the reality of life is for them. Act 10 of the Korean Constitution states that all people have the right to maintain the value and dignity as human beings and pursue their happiness. A petition to government officials made by the sex workers is presented.

Purpose: The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP). Methods: The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart. Results: PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups. Conclusion: Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years. [ABSTRACT FROM AUTHOR]

Studies the palladium-catalyzed amination, Stille coupling and Suzuki coupling of electron-deficient aryl fluorides. Amination in the presence of different catalysts; Capability of aryl fluorides to undergo palladium-catalyzed amination; Converging on the oxidative addition/reductive elimination pathway.

Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent studies have identified that Id3 plays a tumor-suppressor role in the development of Burkitt's lymphoma in humans and hepatosplenic T cell lymphomas in mice. In this article, we report rapid lymphoma development in Id2/Id3 double-knockout mice that is caused by unchecked expansion of invariant NKT (iNKT) cells or a unique subset of innate-like CDld-independent T cells. These populations began to expand in neonatal mice and, upon malignant transformation, resulted in mortality between 3 and 11 mo of age. The malignant cells also gave rise to lymphomas upon transfer to Rag-deficient and wild-type hosts, reaffirming their inherent tumorigenic potential. Microarray analysis revealed a significantly modified program in these neonatal iNKT cells that ultimately led to their malignant transformation. The lymphoma cells demonstrated chromosome instability along with upregulation of several signaling pathways, including the cytokine-cytokine receptor interaction pathway, which can promote their expansion and migration. Dysregulation of genes with reported driver mutations and the N F - κ B pathway were found to be shared between Id2/Id3 double-knockout lymphomas and human NKT tumors. Our work identifies a distinct premalignant state and multiple tumorigenic pathways caused by loss of function of Id2 and Id3. Thus, conditional deletion of Id2 and Id3 in developing T cells establishes a unique animal model for iNKT and relevant innate-like lymphomas. [ABSTRACT FROM AUTHOR]

Joubert syndrome (JS) is characterized by the "molar tooth sign" (MTS) with cerebellar vermis agenesis, episodic hyperpnea, abnormal eye movements, and hypotonia. Ocular and oculomotor abnormalities have been observed; however, Horner syndrome (HS) has not been documented in children with JS. We present the case of a 2-month-old boy having ocular abnormalities with bilateral nystagmus, left-dominant bilateral ptosis, and unilateral miosis and enophthalmos of the left eye, which were compatible with HS. Brain magnetic resonance imaging (MRI) revealed the presence of the MTS. Neck MRI showed no definite lesion or mass around the cervical sympathetic chain. His global development was delayed. He underwent ophthalmologic surgery, and showed some improvement in his ptosis. To the best of our knowledge, the association of HS with JS has not yet been described. We suggest that early neuroimaging should be considered for neonates or young infants with diverse eye abnormalities to evaluate the underlying etiology. [ABSTRACT FROM AUTHOR]

The anti-inflammatory effects and molecular mechanism of 6,8-diprenyl-7,4'- dihydroxyflavanone (DDF), one of the flavanones found in Sophora tonkinensis, were assessed in vitro through macrophage-mediated inflammation in the present study. The anti-inflammatory effects of DDF were not previously reported. DDF inhibited the production of nitric oxide and the expression of tumor necrosis factor α, interleukin-1β, and interleukin-6. Furthermore, the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases (ERKs) in lipopolysaccharide-stimulated macrophages was suppressed by treatment with DDF. Therefore, DDF demonstrated potentially anti-inflammatory effects via the blockade of NF-κB and ERK activation in macrophages. [ABSTRACT FROM AUTHOR]

Background: Complications of abortion are one of the leading causes of maternal mortality worldwide, along with hemorrhage, sepsis, and hypertensive diseases of pregnancy. In Afghanistan little data exist on the capacity of the health system to provide post-abortion care (PAC). This paper presents findings from a national emergency obstetric and neonatal care needs assessment related to PAC, with the aim of providing insight into the current situation and recommendations for improvement of PAC services. Methods: A national Emergency Obstetric and Neonatal Care Needs Assessment was conducted from December 2009 through February 2010 at 78 of the 127 facilities designated to provide emergency obstetric and neonatal care services in Afghanistan. Research tools were adapted from the Averting Maternal Death and Disability Program Needs Assessment Toolkit and national midwifery education assessment tools. Descriptive statistics were used to summarize facility characteristics, and linear regression models were used to assess the factors associated with providers' PAC knowledge and skills. Results: The average number of women receiving PAC in the past year in each facility was 244, with no significant difference across facility types. All facilities had at least one staff member who provided PAC services. Overall, 70% of providers reported having been trained in PAC and 68% felt confident in their ability to perform these services. On average, providers were able to identify 66% of the most common complications of unsafe or incomplete abortion and 57% of the steps to take in examining and managing women with these complications. Providers correctly demonstrated an average of 31% of the tasks required for PAC during a simulated procedure. Training was significantly associated with PAC knowledge and skills in multivariate regression models, but other provider and facility characteristics were not. Conclusions: While designated emergency obstetric facilities in Afghanistan generally have most supplies and equipment for PAC, the capacity of healthcare providers to deliver PAC is limited. Therefore, we strongly recommend training all skilled birth attendants in PAC services. In addition, a PAC training package should be integrated into pre-service medical education. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is the most common and severe form of childhood muscular dystrophy. Females are affected in rare cases because of its' X-linked, recessive inheritance. A small number of female DMD carriers have muscle weakness to some extent. A healthy 8-month-old girl was brought to our tertiary center because of the elevated serum liver enzyme (aspartate aminotransferase (AST): 986 IU/mL, alanine aminotransferase (ALT): 1,126 IU/mL), that was first noted 1 month ago when she was hospitalized for an acute respiratory infection. Follow-up her serum liver enzyme, AST and ALT level remained increased to 613 and 1,049 IU/mL, respectively without serologic evidence of viral hepatitis. Serum creatinine kinase (CK) level was highly elevated to 5,245 U/L. She showed normal development. Pseudohyper-trophy of bilateral calf muscle was not observed, and Gowers' sign was not seen because of her young age. Electromyography and cardiac echocardiography showed no abnormal findings. A multiplex ligation-dependent probe amplification confirmed the heterozygote deletion mutation of DMD gene in exon 10-17. The result of karyotyping was normal 46,XX. She was diagnosed as an asymptomatic DMD carrier. Female carriers are usually asymptomatic but may have an elevated serum CK and/or mild calf hypertrophy. A girl with persistent elevated liver enzyme and CK level should be evaluated for the neuromuscular disease including DMD, despite her normal motor activity. [ABSTRACT FROM AUTHOR]

Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, and inhibition of this enzyme leads to profound hypoestrogenism. Here, we found that the basal expression and activity of aromatase were significantly increased in tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells compared to control MCF-7 cells. We further revealed that aromatase immunoreactivity in tumor tissues was increased in recurrence group after TAM therapy compared to non-recurrence group after TAM therapy. Phosphorylation of Akt, extracellular signal-regulated kinase (ERK), and p38 kinase were all increased in TAMR-MCF-7 cells. Inhibition of phosphoinositide 3-kinase (PI3K) suppressed the transactivation of the aromatase gene and its enzyme activity. Furthermore, we have also shown that PI3K/Akt-dependent cAMP-response element binding protein (CREB) activation was required for the enhanced expression of aromatase in TAMR-MCF-7 cells. Our findings suggest that aromatase expression is up-regulated in TAM-resistant breast cancer via PI3K/Akt-dependent CREB activation. [ABSTRACT FROM AUTHOR]

The heterodimeric Rag GTPases consisting of RagA (or RagB) and RagC (or RagD) are the key regulator activating the target of rapamycin complex 1 (TORC1) in response to the level of amino acids. The heterodimer between GTP-loaded RagA/B and GDPloaded RagC/D is the most active form that binds Raptor and leads to the activation of TORC1. Here, we present the crystal structure of Gtr1pGTP-Gtr2pGDP, the active yeast Rag GTPase heterodimer. The structure reveals that GTP-to-GDP conversion on Gtr2p results in a large conformational transition of this subunit, including a large scale rearrangement of a long segment whose corresponding region in RagA is involved in binding to Raptor. In addition, the two GTPase domains of the heterodimer are brought to contact with each other, but without causing any conformational change of the Gtr1p subunit. These features explain how the nucleotide-bound statuses of the two GTPases subunits switch the Raptor binding affinity on and off. [ABSTRACT FROM AUTHOR]

CONTEXT: Family planning services are frequently used and important services for American women, yet little is known about their quality. Service quality has important implications for women’s reproductive health. If women do not receive adequate information and tools, and learn appropriate skills, from their providers, they may be hampered in their efforts to control their fertility. METHODS: A variety of strategies, including database, journal and Internet searches, were used to identify published and unpublished U.S. studies on family planning service quality that came out between 1985 and 2005. Studies were categorized by their focus, and key points of their methodologies and findings were assessed. RESULTS: Twenty-nine studies were identified, most of which were based on client surveys. Most conceptualized quality as a multidimensional construct, but a uniform definition of quality is lacking, and the domains studied have not been consistent. The available studies focus on four areas: assessments of quality, its correlates, its consequences for client behavior and attitudes, and clients’ values and preferences regarding services. Relations between clients and service facility staff have typically been rated favorably, but communication, patient-centeredness and efficiency have been rated more poorly. Service quality varies by characteristics of the facility, provider, client and visit. Research on the consequences of service quality for clients’ contraceptive behavior or risk of unintended pregnancy has been very limited and yielded mixed results. CONCLUSIONS: Studies that assess service quality need stronger designs and greater consistency in measures used so that results are comparable. [ABSTRACT FROM AUTHOR]

Fractalkine (FKN) has been implicated in modulation of angiogenesis and vascular inflammation, but the underlying mechanism has not been elucidated. We have investigated the molecular mechanism by which FKN regulates angiogenesis. We found that recombinant FKN increases in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells and stimulates in vivo angiogenesis. FKN-induced angiogenesis was accompanied by phosphorylation of ERK, Akt, and endothelial nitric oxide (NO) synthase (eNOS), as well as an increase in NO production. These biochemical events and angiogenesis were completely inhibited by the G protein-coupled receptor inhibitor pertussis toxin. Inhibitors of Raf-1, MEK, phosphatidylinositol 3-kinase (PI3K), and eNOS or transfection with dominant-negative forms of ERK and Akt significantly suppressed the angiogenic activity of FKN. However, inhibitors of Raf-1 and MEK or a dominant-negative ERK mutant blocked FKN-induced ERK, but not Akt and eNOS, phosphorylation. The PI3K inhibitor and a dominant-negative mutant of Akt suppressed Akt and eNOS phosphorylation and NO production. Our results demonstrated that FKN stimulated angiogenesis by activating the Raf-1/MEK/ERK and PI3K/Akt/eNOS/NO signal pathways via the G protein-coupled receptor CX3CR1, indicating that two pathways are required for full angiogenic activity of FKN. This study suggests that FKN may play an important role in the pathophysiological process of inflammatory angiogenesis. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is known as a key regulator of angiogenesis during endochondral bone formation. Recently, we demonstrated that TNF-related activation-induced cytokine (TRANCE or RANKL), which is essential for bone remodeling, also had an angiogenic activity. Here we report that VEGF up-regulates expression of receptor activator of NF-κ B (RANK) and increases angiogenic responses of endothelial cells to TRANCE. Treatment of human umbilical vein endothelial cells (HUVECs) with VEGF increased both RANK mRNA and surface protein expression. Although placenta growth factor specific to VEGF receptor-1 had no significant effect on RANK expression, inhibition of downstream signaling molecules of the VEGF receptor-2 (Flk-1/KDR) such as Src, phospholipase C, protein kinase C, and phosphatidylinositol 3'-kinase suppressed VEGF-stimulated RANK expression in HUVECs. Moreover, the MEK inhibitor PD98059 or expression of dominant negative MEK1 inhibited induction of RANK by VEGF but not the Ca[sup 2+] chelator 1,2-bis(2aminophenoxy)ethane-N,N,N',N'-tetraacetic acidacetoxymethyl ester (BAPTA-AM). VEGF potentiated TRANCE-induced ERK activation and tube formation via RANK up-regulation in HUVECs. Together, these results show that VEGF enhances RANK expression in endothelial cells through Flk-1/KDR-protein kinase CERK signaling pathway, suggesting that VEGF plays an important role in modulating the angiogenic action of TRANCE under physiological or pathological conditions. [ABSTRACT FROM AUTHOR]

Reports that mastoparan selectively activates phospholipase (PL) D2 in cell membranes. Mastoparan stimulation in PLD in cell membrane fractions; Location of mastoparan-sensitive PLD2 in the plasma membranes; Enzymatic characteristics of PLD2 activation by mastoparan and the interactions with PI 4,5-bisphosphate.

Three genes encoding 3-hydroxy-3-methylglutaryl- CoA reductase (HMGR, EC1.1.34), which converts HMG-CoA into mevalonate in the early key step of the plant isoprenoid pathway, were isolated by RT-PCR and rice cDNA and genomic library screening. A genomic Southern blot analysis confirmed that HMGR genes are present in three copies in rice. Of the three, the HMGR 2 gene (Hmg2) obtained as a cDNA clone and its genomic clone had 4 exons and 3 introns, and encoded a 576 amino acid peptide containing an open reading frame of 1,728 bp with a calculated Mw. of 61,150. The structure of rice Hmg2 had common features, based on its nucleotide and deduced amino acid sequence homologies, with other plant HMGR genes published to date. Rice Hmg2 transcripts were constitutively detected in all parts of the rice plant, except in lamina and their levels were high particularly in the leaf part of the dark-grown seedlings and mature flowers. Our result showed that mRNA levels of rice Hmg2 were strongly induced in seedlings and influorescence in the early development stage. Rice Hmg2 possibly has a housekeeping role involved in the sterol biosynthesis, among the possible roles of plant HMGR genes that have been suggested in other plants [Weissenborn et al. (1995)]. [ABSTRACT FROM AUTHOR]

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroidstimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves' disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and antithyroidstimulating hormone (TSH) receptor antibody were all negative. During followup, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Wholeexome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant. [ABSTRACT FROM AUTHOR]