Accumulation of MDM2 in pleomorphic xanthoastrocytomas

The molecular genetic basis and the tumorigenic mechanism of pleomorphic xanthoastrocytoma (PXA) still remain to be elucidated. The amplification of the mdm2 gene and accumulation of the MDM2 protein, which is considered to be one of the major cellular regulators of p53-mediated cell growth control, were studied in eight specimens of PXA obtained from five patients. All of the PXA samples showed at least focal immunopositivity for MDM2. However, none of the samples showed mdm2 gene amplification. These results suggest that accumulation of MDM2 without gene amplification may be one of the major molecular events occurring in the tumorigenesis of PXA.     

Molecular mechanism of DNA replication-coupled inactivation of the initiator protein in Escherichia coli: interaction of DnaA with the sliding clamp-loaded DNA and the sliding clamp-Hda complex

In Escherichia coli, the ATP-DnaA protein initiates chromosomal replication. After the DNA polymerase III holoenzyme is loaded on to DNA, DnaA-bound ATP is hydrolysed in a manner depending on Hda protein and the DNA-loaded form of the DNA polymerase III sliding clamp subunit, which yields ADP-DnaA, an inactivated form for initiation. This regulatory DnaA-inactivation represses extra initiation events. In this study, in vitro replication intermediates and structured DNA mimicking replicational intermediates were first used to identify structural prerequisites in the process of DnaA-ATP hydrolysis. Unlike duplex DNA loaded with sliding clamps, primer RNA-DNA heteroduplexes loaded with clamps were not associated with DnaA-ATP hydrolysis, and duplex DNA provided in trans did not rescue this defect. At least 40-bp duplex DNA is competent for the DnaA-ATP hydrolysis when a single clamp was loaded. The DnaA-ATP hydrolysis was inhibited when ATP-DnaA was tightly bound to a DnaA box-bearing oligonucleotide. These results imply that the DnaA-ATP hydrolysis involves the direct interaction of ATP-DnaA with duplex DNA flanking the sliding clamp. Furthermore, Hda protein formed a stable complex with the sliding clamp. Based on these, we suggest a mechanical basis in the DnaA-inactivation that ATP-DnaA interacts with the Hda-clamp complex with the aid of DNA binding.     

The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis

Rheumatoid arthritis (RA) is a polygenic autoimmune disease. The autoimmunity develops from synergistic actions of genetic and environmental factors. We generated a double-mutant mouse by crossing two murine models of RA, a gp130 mutant knock-in mouse (gp130F759/F759) and an HTLV-1 pX transgenic mouse (pX-Tg), in a C57BL/6 background, which is resistant to arthritis. The mice spontaneously developed severe arthritis with a much earlier onset than the gp130F759/F759 mice and with a much higher incidence than did the pX-Tg mice. The symptoms of gp130F759/F759 mice, including lymphoadenopathy, splenomegaly, hyper-gamma-globulinemia, autoantibody production, increases in memory/activated T cells and granulocytes in the peripheral lymphoid organs, and a decrease in the class II MHC(bright) CD11c+ population, were augmented in the double mutants. Marked reductions in incidence, severity and immunological abnormalities were seen in the triple mutant, IL-6-/-/gp130F759/F759/pX-Tg, indicating that the arthritis in the double mutant is IL-6 dependent. gp130F759/F759/pX-Tg is a unique mouse model for RA.     

Transient decrease in the CD45RA expression on T lymphocytes in neonates with fetal distress

To determine the expression of CD45 isoforms on T lymphocytes in neonates with fetal distress and to evaluate its diagnostic accuracy, peripheral blood samples were examined in 53 neonates who were classified into one of three groups: group I: 'control' group (n = 23), group II: 'mild distress' group (n = 15), and group III: 'moderate distress' group (n = 15). The expression of CD3 (mean +/- SD 24.2 +/- 10.1%), CD4 (23.0 +/- 5.7%), and CD45RA (27.3 +/- 9.6%) on total lymphocytes and the expression of CD45RA on CD4+ T lymphocytes (13.7 +/- 4.7%) in group III were significantly lower than in the other two groups 0-3 days after birth. Sensitivity and specificity of the CD45RA expression on CD4+ T lymphocytes for discrimination of group III were calculated as 0.79 and 1.0, respectively, when the cutoff value was 22.7%. The low CD3, CD4, and CD45RA expression returned to normal levels 10 days and more after birth. There were no differences in the CD8 and CD45RO expression between the groups. We conclude that CD4+ T lymphocytes from neonates with fetal distress show a transient decrease in the CD45RA expression without an increase in the CD45RO expression, and, therefore, analysis of the CD45 isoform expression is useful for laboratory evaluation of fetal distress.     

A study of the effects of active listening on listening attitudes of middle managers

The present study was conducted to clarify the direct effects of active listening (AL) training given to middle managers in a local government. Altogether, 345 middle managers participated in 13 AL training sessions over two years. We developed the Inventive Experiential Learning (IEL) method, and used it as the central training method in this study. To investigate how well the participants learned AL, we asked the middle managers to answer a shorter version of the Active Listening Attitude Scale (ALAS) consisting of two subscales-i.e. "Listening Attitude" and "Listening Skill"-before training, one month after and three months after training. Altogether, 284 middle managers answered the questionnaire three times. The scores of each subscale were analyzed by repeated measurement analysis of variance. The participants were divided into three groups using the percentile values of the original sample of ALAS, i.e. low-score group (-24%), medium-score group (25-75%) and high-score group (76%-), and the proportionate changes were examined. The results showed both the "Listening Attitude" and "Listening Skill" subscales increased significantly after training. Analysis of the percentiles showed that the proportion of the low-score group decreased and that of the high-score group increased in both subscales, from one to three months after training. These changes are considered to indicate that the participants have learned AL although they attended AL training for only one day.     

Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma

Chloasma (melasma), an acquired hypermelanosis, is often recalcitrant to various treatments and an amenable, as well as safe, pigment-reducing modality is needed. We investigated that the reducing effect of proanthocyanidin, a powerful antioxidant, on chloasma in a one-year open design study. Proanthocyanidin-rich grape seed extract (GSE) was orally administered to 12 Japanese woman candidates with chloasma for 6 months between August 2001 and January 2002 and to 11 of these 12 for 5 months between March and July 2002. Clinical observation, L* value (lightening) and melanin index, and size (length and width) measurements of chloasma were performed throughout the study period. The first 6 months of GSE intake improved or slightly improved chloasma in 10 of the 12 women (83%, p < 0.01) and following 5 months of intake improved or slightly improved chloasma in 6 of the 11 candidates (54%, p < 0.01). L* values also increased after GSE intake (57.8 +/- 2.5 at the start vs 59.3 +/- 2.3 at 6 months and 58.7 +/- 2.5 at the end of study). Melanin-index significantly decreased after 6 months of the intake (0.025 +/- 0.005 at the start vs 0.019 +/- 0.004 at 6 months) (p < 0.01), and also decreased at the end of study (0.021 +/- 0.005) (p < 0.05). GSE is effective in reducing the hyperpigmentation of women with chloasma. The beneficial effects of GSE was maximally achieved after 6 months and these was no further improvement after this period. The latter GSE intake for 5 months may prevent chloasma from becoming worse prior to the summer season. GSE is safe and useful for improving chloasma.     

Successful Removal After Radiotherapy and Vascular Embolization in a Huge Tentorial Epithelioid Hemangioendothelioma: A Case Report

Intracranial epithelioid hemangioendothelioma (E-HE) is an extremely rare, vasoformative tumor with variable biological behavior. A huge E-HE confined to the upper side of the tentorium has not been documented previously. Recognizing E-HE as a specific vascular tumor is important, and complete tumor removal guarantees long-term survival. Here, we report an intracranial E-HE of a 24-year-old woman with the initial symptoms of progressive headache over several years. Magnetic resonance imaging revealed a huge tumor attached to the upper side of the right tentorium, with tentorial and tonsillar herniation, and secondary syringomyelia in the upper cervical spinal cord. The initial surgical attempt to remove the lesion was abandoned due to profuse bleeding from the tumor. One year after irradiation and 5 days after vascular embolization, the tumor could be removed totally. The final definitive diagnosis as E-HE was made by special immunohistochemical and electron microscopic study. The patient is free from the tumor 9 years after the second operation. Thus, E-HE is a highly vascular-rich tumor to excise, and we stress need for preoperative embolization and/or irradiation to remove huge tumor completely.     

High body mass index correlates with increased risk of venous irritation by vinorelbine infusion

BACKGROUND: Vinorelbine is currently one of the most active chemotherapeutic agents. However, it is also a moderate vesicant that is well known to cause venous irritation and phlebitis. We conducted this study to identify clinical risk factors related to the incidence of venous irritation caused by peripheral vinorelbine infusion. METHODS: Medical records were used to investigate retrospectively a total of 201 cases of non-small cell lung cancer treated with a chemotherapeutic regimen containing vinorelbine. Venous irritation was evaluated in every course and graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Gender, age, body mass index (BMI), chemotherapeutic regimen, dose of vinorelbine and prior chemotherapy were used as clinical variables. RESULTS: A total of 928 vinorelbine infusions were administered to the 201 patients, among whom venous irritation occurred in 63 (31%). The incidence of venous irritation was 28% in the normal BMI (<25) group and 45% in the high BMI (25 or more) group and the difference between the two groups was statistically significant (P = 0.037). There were no significant correlations between the incidence of venous irritation and the clinical variables except BMI. In the multivariate analysis BMI was also a significant independent variable that correlated with increased risk of venous irritation (P = 0.017). CONCLUSIONS: Care is required when using vinorelbine to treat patients with a high BMI, especially with regard to the development of venous irritation.