Useful manifestations to detect adenovirus in children with upper respiratory infections: A retrospective study.

OBJECTIVE: Approximately 1 million adenovirus immunochromatography (IC) kits are annually used in Japan. However, no practical strategies have been developed regarding their use for detecting adenovirus. The present study aims to verify the usefulness of clinical manifestations in making decisions regarding the use of adenovirus IC kits for children with upper respiratory infections (URI). METHODS: The medical records of 825 pediatric cases tested by IC kits for adenovirus were extracted from clinical laboratory department database over a 3-year period at our hospital. Among them, 585 patients were suspected adenovirus URI, and their clinical manifestations were reviewed. After data cleaning, 10 types of clinical manifestations were statistically analyzed between adenovirus IC kit-positive and -negative groups. Multivariate analysis was performed to select significant clinical manifestations using adenovirus IC kit positivity as the objective variable. RESULTS: Among 585 pediatric patients, the cases of 420 patients, with suitable data for whom no other pathogen was detected, were reviewed. Adenovirus was detected in 86 cases. Multivariate analysis identified a significant difference for three clinical manifestations: (1) fever ≥ 39.0°C, (2) rhinorrhea, and (3) tonsillar exudate. The negativity rate for the IC kit was 90% when none of the three manifestations was observed. CONCLUSIONS: The results suggested that IC kits for adenovirus tend to give negative results in cases that lack all the three above mentioned clinical manifestations.

Strong genetic structure over the American continents and transoceanic dispersal in the mangrove genus Rhizophora (Rhizophoraceae) revealed by broad-scale nuclear and chloroplast DNA analysis.

PREMISE OF THE STUDY: The global distribution of mangroves is attributed to interactions between long-distance propagule dispersal and geographical barriers, which are manifest in genetic structuring. Uncovering this genetic structure thus provides a window into the ecological, evolutionary, and phylogeographic history of mangroves. We used cpDNA and nuclear microsatellites to evaluate transbarrier (transoceanic and transisthmian) linkages in the genus Rhizophora in the Atlantic East Pacific (AEP) and South Pacific region. • METHODS: Leaf samples of 756 individuals of Rhizophora mangle, R. racemosa, R. ×harrisonii, and R. samoensis from 36 populations across the AEP supplied material from which we used the cpDNA haplotypes and nine microsatellite markers for population analyses. • KEY RESULTS: Clear genetic differentiation of cpDNA haplotypes was found between the Pacific and Atlantic populations in R. mangle and R. racemosa, supporting the hypothesis of the Central American Isthmus as a barrier to gene flow. Both cpDNA and microsatellite analyses support the hypothesis of recent and frequent transatlantic propagule dispersal for R. mangle. Finally, we provide strong evidence for genetic similarity of Pacific R. mangle and R. samoensis suggesting trans-Pacific dispersal of R. mangle. • CONCLUSION: The American continents are strong geographical barriers to dispersal of Rhizophora, to the point where the Pacific and Atlantic populations are distinct genealogical units, supporting the recommendation to treat the populations as separate conservation and management units. Trans-Pacific propagule dispersal of Rhizophora has occurred; R. mangle and R. samoensis might be the same species and this question should be resolved with further taxonomic study.

TFE3 transcriptionally activates hepatic IRS-2, participates in insulin signaling and ameliorates diabetes.

Using an expression cloning strategy, we have identified TFE3, a basic helix-loop-helix protein, as a transactivator of metabolic genes that are regulated through an E-box in their promoters. Adenovirus-mediated expression of TFE3 in hepatocytes in culture and in vivo strongly activated expression of IRS-2 and Akt and enhanced phosphorylation of insulin-signaling kinases such as Akt, glycogen synthase kinase 3beta and p70S6 kinase. TFE3 also induced hexokinase II (HK2) and insulin-induced gene 1 (INSIG1). These changes led to metabolic consequences, such as activation of glycogen and protein synthesis, but not lipogenesis, in liver. Collectively, plasma glucose levels were markedly reduced both in normal mice and in different mouse models of diabetes, including streptozotocin-treated, db/db and KK mice. Promoter analyses showed that IRS2, HK2 and INSIG1 are direct targets of TFE3. Activation of insulin signals in both insulin depletion and resistance suggests that TFE3 could be a therapeutic target for diabetes.

Genetic polymorphisms of the adenosine triphosphate-binding cassette transporters (ABCG2, ABCB1) and gefitinib toxicity.

The purpose of this study is to investigate associations between allelic variations of ABCG2 and ABCB1 with skin toxicity, diarrhea, liver injury and interstitial lung disease (ILD) in gefitinib-treated patients. A prospective clinical study of 83 Japanese patients with non-small-cell lung cancer was performed. Polymorphic loci in ABCG2 and ABCB1 were genotyped, and their effects on gefitinib toxicities were evaluated. ABCG2 34G>A was statistically associated with occurrence of skin rash; 13 (42%) of the 32 patients with at least one variant ABCG2 34G>A allele (G/A and A/A) developed grade 2 or worse skin rash, whereas only 10 (19%) of 51 patients homozygous for the reference allele (G/G) for the wild-type sequence for both alleles did so (P=0.046). There was no significant association between severe toxicities and polymorphisms of ABCG2 421C>A nor ABCB1 3435C>T. The results suggested that ABCG2 34G>A would be useful for predicting grade 2 or worse skin rash.

[A case of pulmonary inflammatory pseudotumor accompanied with increased serum immunoglobulin G levels and autoimmune pancreatitis].

A 77-year-old man with increased serum immunoglobulin G levels and autoimmune pancreatitis was found to have a chest X-ray abnormality. The chest X-ray and CT films showed a mass shadow in the right lower lobe and lymphadenopathy. Since transbronchial tumor biopsy did not obtain diagnostic material, CT-guided cutting needle biopsy was performed. The microscopic findings showed plasma cells and lymphocytes infiltrating the pleura and alveolar interstitium. A diagnosis of inflammatory pseudotumor was suspected, but it was difficult to exclude malignancy. Therefore, wedge resection of the right lower lobe including the mass and incisional biopsy of mediastinal lymph nodes were performed. Histopathologic examination of the resected specimen revealed inflammatory pseudotumor that was predominantly composed of mature plasma cells infiltrating in the bronchiolar wall, peribronchiolar interstitial tissue, alveolar wall, visceral pleura, the diaphragmatic area of the parietal pleura and mediastinal lymph nodes. Immunohistochemical staining revealed many IgG4-positive plasma cells diffusely infiltrated in the resected mass and lymph nodes. In this case, there is a possibility that patient developed autoimmune pancreatitis, pulmonary inflammatory pseudotumor and lymphadenopathy as part of systemic IgG4-related

A transcription factor of lipid synthesis, sterol regulatory element-binding protein (SREBP)-1a causes G(1) cell-cycle arrest after accumulation of cyclin-dependent kinase (cdk) inhibitors.

Sterol regulatory element-binding protein (SREBP)-1a is a unique membrane-bound transcription factor highly expressed in actively growing cells and involved in the biosynthesis of cholesterol, fatty acids, and phospholipids. Because mammalian cells need to synthesize membrane lipids for cell replication, the functional relevance of SREBP-1a in cell proliferation has been considered a biological adaptation. However, the effect of this potent lipid-synthesis activator on cell growth has never been explored. Here, we show that induction of nuclear SREBP-1a, but not SREBP-2, completely inhibited cell growth in inducible Chinese hamster ovary (CHO) cell lines. Growth inhibition occurred through G(1) cell-cycle arrest, which is observed in various cell types with transient expression of nuclear SREBP-1a. SREBP-1a caused the accumulation of cyclin-dependent kinase (cdk) inhibitors such as p27, p21, and p16, leading to reduced cdk2 and cdk4 activities and hypophosphorylation of Rb protein. In contrast to transactivation of p21, SREBP-1a activated p27 by enhancing stabilization of the protein through inhibition of SKP2 and KPC1. In vivo, SREBP-1a-expressing livers of transgenic mice exhibited impaired regeneration after partial hepatectomy. SREBP-1-null mouse embryonic fibroblasts had a higher cell proliferation rate than wild-type cells. The unexpected cell growth-inhibitory role of SREBP-1a provides a new paradigm to link lipid synthesis and cell growth.

[Three cases of transcatheter embolization for pulmonary arteriovenous fistula using detachable coils].

We report three cases of transcatheter embolization for pulmonary arteriovenous fistula (PAVF) using Interlocking detachable coils (IDC) and detachable fibered coils (DFC), and evaluate the outcome of transcatheter embolization with reference to previous reports. The three patients were women aged 56, 70 and 71 years. They had no symptoms, but chest radiographs were abnormal. None of them had Rendu-Osler-Weber disease. The three PAVFs were of the simple type, with a single feeding vessel and a single draining vein. In case 1, the feeding vessel arose from the left A4, while the feeding vessels in case 2 and 3 arose from the left A5. In case 1, we embolized the venous sac with detachable coils because the feeding vessel was short and kinked. In case 2 and 3, we embolized the feeding vessels closer as to the neck of the venous sac using detachable coils. The three PAVFs were all successfully embolized without severe complications, and transcatheter embolization seems to be an effective therapy.

Correlation of mitogen-activated protein kinase activities with cell survival and apoptosis in porcine granulosa cells.

The regulation of granulosa cell survival and death is critical for determining the fate of ovarian follicles. Mitogen-activated protein kinases (MAPKs) play central roles in various cellular responses, but the relationship between MAPK activities and granulosa cell survival as well as death is poorly understood. The present study examines the roles of the extracellular signal-regulated kinase (ERK) and p38 MAPK activities in porcine granulosa cells in response to survival factors and oxidative stress. Cell survival and apoptosis were evaluated by Trypan blue staining, DNA fragmentation, and chromatin staining with Hoechst 33342. Cell survival induced by serum or by follicle-stimulating hormone (FSH) was inhibited when ERK activity was attenuated with PD98059, which led to the induction of apoptosis. The p38 inhibitor SB203580 significantly decreased the cell survival evoked by FSH, but not by serum. Even in the presence of 10% serum, H(2)O(2) caused apoptosis, indicating that H(2)O (2) may be an atretogenic factor or its mediator. Interestingly, this induction of apoptosis was also prevented by SB203580, suggesting that p38 is involved in an apoptotic pathway induced by H(2)O (2) as well as in a survival pathway evoked by FSH in granulosa cells. These results indicate that whereas ERK activity is critical to the survival of granulosa cells, p38 activity contributes to their survival or apoptosis depending on the stimulus.

[The effects of intrathecally administered baclofen on somato-sympathetic reflex potentials].

We investigated the antinociceptive effect of intrathecally administered S(-)-baclofen and R (+)-baclofen in cats using somato-sympathetic reflex potentials derived from lumbar sympathetic ganglion by stimulation of the femoral nerve. S(-)-baclofen 10 mg maximally reduced both A reflex potential and C reflex potential to 65.3% and 83.7% of control values, respectively, 1 minute after the administration, but these changes were not significant. The inhibition of A reflex potential at this dosage was greater than that of blood pressure and heart rate induced by the same dosage of S(-)-baclofen. While, R(+)-baclofen 1 mg maximally inhibited A reflex potential to 48.6% of control value 20 minutes after the administration, and this change was significant (P < 0.05). The inhibition of A reflex potential was greater than that of blood pressure and heart rate induced by the same dosage of R(+)-baclofen. This dosage of baclofen reduced C reflex potential to 66.4% of control value 10 minutes after the administration. The degree of reduction of A and C reflex potentials induced by 1 mg of R(+)-baclofen was higher in comparison with that induced by 10 mg of S(-)-baclofen. These reduction of A and C reflex potentials were reversed by 1 to 1.5 mg of intrathecally administered saclofen. These results indicate that R(+)-baclofen has higher potency than S(-)-baclofen and suggest that S(-)-baclofen and R(+)-baclofen show antinociceptive effect by intrathecal administration. On the other hand, it is possible that these two drugs exert antinociceptive effect via A delta fiber.

Cellular functions of mitogen-activated protein kinases and protein tyrosine phosphatases in ovarian granulosa cells.

A number of endocrine and paracrine factors regulate the follicular growth and atresia, which are closely associated with granulosa cell survival and apoptosis. However, the molecular mechanisms underlying the intracellular events induced by these factors are poorly understood. Here, we describe the correlation of mitogen-activated protein kinase (MAPK) activities with granulosa cell survival and apoptosis, and the cellular functions of protein tyrosine phosphatases (PTPs) in these cells based on our recent data. MAPKs play key roles in various cellular responses because numerous extracellular stimuli are integrated into MAPKs. The protein phospho-Tyr level regulated by protein tyrosine kinases (PTKs) and PTPs is a major control mechanism for processes as diverse as cell survival, proliferation, differentiation, and metabolism. Although PTKs are critically involved in granulosa cell survival and proliferation, there are no reports indicating the roles of PTPs in the ovary except for ours. Information about MAPKs and PTPs in these cells will provide a basis for the understanding of the molecular mechanisms controlling the fate of follicles.

Tyrosine phosphatase epsilonM stimulates migration and survival of porcine aortic endothelial cells by activating c-Src.

The cell growth, survival, and migration of vascular endothelial cells (ECs) are positively regulated by several protein tyrosine kinase receptors. Therefore, protein tyrosine phosphatases (PTPs) must also be important for these processes. The present study found that transmembranal PTPepsilonM, but not cytoplasmic PTPepsilonC, is expressed in porcine ECs and in rat smooth muscle cells, both of which were prepared from the aorta. The overexpression of wild-type PTPepsilonM promoted cell survival and migration in porcine aortic ECs even in medium without and with 1% serum, respectively. A catalytically inactive, substrate-trapping mutant of PTPepsilonM, respectively, did not affect and conversely suppressed cell survival and migration. Interestingly, the forced expression of wild-type PTPepsilonC reduced cell viability in contrast to PTPepsilonM in ECs lacking endogenous PTPepsilonC, indicating the biological significance of selective expression of PTPepsilon isoforms in the vasculature. PTPepsilonM activated c-Src kinase probably by directly dephosphorylating phospho-Tyr527, a negative regulatory site of c-Src. The increases in cell survival and migration induced by overexpressed PTPepsilonM were suppressed by the c-Src inhibitor SU6656. Considering the behaviors of vascular ECs in the pathogenesis of atherosclerosis, these data suggest that PTPepsilonM negatively regulates the development of this disease by activating c-Src.