Local outbreak of Streptococcus pneumoniae serotype 12F caused high morbidity and mortality among children and adults.

Pneumococcal serotype replacement is an important issue after the introduction of pneumococcal conjugate vaccine (PCV) in children. After the introduction of 13-valent PCV, the incidence of invasive pneumococcal diseases (IPD) caused by Streptococcus pneumoniae serotype 12F (Sp12F) have increased in some countries; however, an outbreak of Sp12F has not reported in the post-13-valent PCV era. We experienced a local outbreak of Sp12F during March through May 2016 in Tsuruoka city, Japan after the introduction of 13-valent PCV in 2013. The IPD patients were two children and seven adults, three of whom died with a rapid disease progress. Although the clear transmission route was not determined, eight of the nine patients (89%) had close contact with children, which suggests that transmitted colonisation of Sp12F among children and adults might be the source of transmission. Continuous monitoring of IPDs, along with the determination of pneumococcal serotypes, is warranted in the post-13-valent PCV era. New IPD control strategies may be needed if this fatal outbreak continues to occur.

Fabrication of SrGe2 thin films on Ge (100), (110), and (111) substrates.

Semiconductor strontium digermanide (SrGe2) has a large absorption coefficient in the near-infrared light region and is expected to be useful for multijunction solar cells. This study firstly demonstrates the formation of SrGe2 thin films via a reactive deposition epitaxy on Ge substrates. The growth morphology of SrGe2 dramatically changed depending on the growth temperature (300-700 °C) and the crystal orientation of the Ge substrate. We succeeded in obtaining single-oriented SrGe2 using a Ge (110) substrate at 500 °C. Development on Si or glass substrates will lead to the application of SrGe2 to high-efficiency thin-film solar cells.

Strategies for realizing photonic crystal fiber bandpass filters.

Numerical design strategies are presented to achieve efficient broad or narrow band-pass filters based on index-guiding, solid-core, and single-mode photonic crystal fibers (PCFs). The filtering characteristics have been verified through BPM solver. By scaling the pitch constant, the bandpass window can be shifted accordingly. The fiber design constitutes a fluorine-doped central core, enlarged air-holes surrounding the down-doped core, and small air-holes in the cladding. The proposed bandpass filter is based on controlling the leakage losses, so one can tune filter characteristics simply by changing its length. From numerical simulations we show that for large values of air-hole diameter in the first ring, the bandpass window is narrow, while for low doping concentration and small sized air-holes in the first ring, bandpass window is very broad. We also simulate how the hole-size and number of rings in the PCF cladding affects the device characteristics. We find that a 5-cm long PCF with down-doped core and eleven rings of air-holes can result in approximately 440 nm 3-dB bandwidth with more than 90% of transmission. The longer device has reduced transmission and smaller 3-dB bandwidth. Tolerance analysis has also been performed to check the impact of fiber tolerances on the performance of the PCF bandpass filter. It has been observed that the decrement in cladding hole-diameter by 1% reduces the transmission to 21% from its peak value of 93%, however +/-1% tolerance in the inner hole-diameter degrades the transmission to 75% from its peak.

Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal.

Activation of protein kinase C (PKC) by phorbol ester facilitates hormonal secretion and transmitter release, and phorbol ester-induced synaptic potentiation (PESP) is a model for presynaptic facilitation. A variety of PKC isoforms are expressed in the central nervous system, but the isoform involved in the PESP has not been identified. To address this question, we have applied immunocytochemical and electrophysiological techniques to the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) of rat auditory brainstem. Western blot analysis indicated that both the Ca(2+)-dependent "conventional" PKC and Ca(2+)-independent "novel" PKC isoforms are expressed in the MNTB. Denervation of afferent fibers followed by organotypic culture, however, selectively decreased "novel" epsilon PKC isoform expressed in this region. The afferent calyx terminal was clearly labeled with the epsilon PKC immunofluorescence. On stimulation with phorbol ester, presynaptic epsilon PKC underwent autophosphorylation and unidirectional translocation toward the synaptic side. Chelating presynaptic Ca(2+), by using membrane permeable EGTA analogue or high concentration of EGTA directly loaded into calyceal terminals, had only a minor attenuating effect on the PESP. We conclude that the Ca(2+)-independent epsilon PKC isoform mediates the PESP at this mammalian central nervous system synapse.

Expression of Ca(2+)-activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract.

A role for small-conductance Ca(2+)-activated K(+) (SK) channels on spontaneous motility of the gastrointestinal tract has been suggested. Although four subtypes of SK channels were identified in mammalian tissues, the subtypes of SK channel expressed in the gastrointestinal tract are still unknown. In this study, we investigated the expression and localization of SK channels in the gastrointestinal tract. RT-PCR analysis shows expression of SK3 and SK4 mRNA, but not SK1 or SK2 mRNA, in the rat intestine. SK3 immunoreactivity was detected in the myenteric plexus and muscular layers of the stomach, ileum, and colon. SK3-immunoreactive cells were stained with antibody for c-kit, a marker for the interstitial cells of Cajal (ICC), but not with that for glial fibrillary acidic protein in the ileum and stomach. Immunoelectron microscopic analysis indicates that SK3 channels are localized on processes of ICC that are located close to the myenteric plexus between the longitudinal and circular muscle layers and within the muscular layers. Because ICC have been identified as pacemaker cells and are known to play a major role in generating the regular motility of the gastrointestinal tract, these results suggest that SK3 channels, which are expressed specifically in ICC, play an important role in generating a rhythmic pacemaker current in the gastrointestinal tract.

GTP-binding protein beta gamma subunits mediate presynaptic calcium current inhibition by GABA(B) receptor.

A variety of GTP-binding protein (G protein)-coupled receptors are expressed at the nerve terminals of central synapses and play modulatory roles in transmitter release. At the calyx of Held, a rat auditory brainstem synapse, activation of presynaptic gamma-aminobutyric acid type B receptors (GABA(B) receptors) or metabotropic glutamate receptors inhibits presynaptic P/Q-type Ca(2+) channel currents via activation of G proteins, thereby attenuating transmitter release. To identify the heterotrimeric G protein subunits involved in this presynaptic inhibition, we loaded G protein beta gamma subunits (G beta gamma) directly into the calyceal nerve terminal through whole-cell patch pipettes. G beta gamma slowed the activation of presynaptic Ca(2+) currents (I(pCa)) and attenuated its amplitude in a manner similar to the externally applied baclofen, a GABA(B) receptor agonist. The effects of both G beta gamma and baclofen were relieved after strong depolarization of the nerve terminal. In addition, G beta gamma partially occluded the inhibitory effect of baclofen on I(pCa). In contrast, guanosine 5'-O-(3-thiotriphosphate)-bound G(o)alpha loaded into the calyx had no effect. Immunocytochemical examination revealed that the subtype of G proteins G(o), but not the G(i), subtype, is expressed in the calyceal nerve terminal. These results suggest that presynaptic inhibition mediated by G protein-coupled receptors occurs primarily by means of the direct interaction of G(o) beta gamma subunits with presynaptic Ca(2+) channels.

Highly proliferative intratumoral fibroblasts and a high proliferative microvessel index are significant predictors of tumor metastasis in T3 ulcerative-type colorectal cancer.

Fibroblast and endothelial cell mitotic figures are seen in some areas of colorectal cancers, and the purpose of this study was to investigate whether the proliferative activity of fibroblasts and endothelial cells plays an important role in tumor progression of T3 ulcerative-type colorectal cancer. The tumor area of 157 colorectal cancers was divided into marginal elevated area and central depressed area (CDA), and at half the depth of the depression the CDA was in turn divided into CDA upper area (CDAU) and CDA lower area (CDAL). The proliferative activity of the tumor cells, fibroblasts, and endothelial cells was assessed immunohistochemically by double CD31/MIB-1 (anti--Ki-67 antigen) staining. The proliferative microvessel index was estimated as the percentage of microvessels lined by MIB-1-positive endothelial cells relative to the total microvessel count. Proliferative activities of tumor cells showed significant associations with those of fibroblasts and the proliferative microvessel indices in all of the corresponding areas. Proliferative activities of fibroblasts also showed significant associations with proliferative microvessel indices in all of the corresponding areas. Colorectal cancers with nodal metastasis showed significantly higher proliferative activities of fibroblasts in the CDAU than those without nodal metastasis (P <.001). The high proliferative activities of fibroblasts and proliferative microvessel indices in the CDAU showed significant associations with short distant organ metastasis-free periods in colorectal cancers without nodal metastasis (P <.001 and P =.010, respectively) and those with nodal metastasis (P =.024 and P =.036, respectively). Multivariate analysis showed that the highly proliferative fibroblasts in the CDAU significantly increased hazard rates of distant organ metastasis of colorectal cancer patients with nodal metastasis (P =.018). Proliferative activities of fibroblasts and endothelial cells in the CDAU are useful parameters for predicting tumor metastasis in patients with T3 ulcerative-type colorectal cancer. HUM PATHOL 32:401-409.

[Induction chemotherapy (cisplatin + vinorelbine) is found to be markedly effective for squamous cell lung carcinoma with sarcoidosis--a case report].

A sixty-one-year-old man was admitted to our hospital because of a right lung tumor shadow. He had been diagnosed as having sarcoidosis at the age of fifty-seven. He was newly diagnosed as having squamous cell carcinoma by trans bronchial biopsy. He was treated with an induction chemotherapy (cisplatin 80 mg/m2 + vinorelbine 20 mg/m2) followed by right middle and lower lobectomy with a mediastinal nodal dissection, because the stage of his carcinoma was cT2N2M0. Resected lung tissue showed the disappearance of cancer cells. Dissected mediastinal and hilar lymph nodes showed many sarcoid granulomas. Cisplatin combined with vinorelbine might be an effective chemotherapy for non-small cell lung carcinoma.

[Experiences of minimally invasive great saphenous vein graft harvest using with endopath].

We have experienced 20 cases of minimally invasive great saphenous vein graft harvest using with endoscopy, Endopath, from March 1999. As we experienced cases, we can harvest great saphenous vein graft, about 30-40 cm in size, from only two 4-cm incisions for about 50 minutes. There are no wound infection, pain, and edema. Great saphenous vein graft harvesting with Endopath is less invasive, painless after surgery and makes patients satisfied about cosmetic problem.

Synthesis and properties of novel bifunctional nitrosamines with omega-chloroalkyl groups.

Novel N-nitroso-N-(acetoxymethyl)-omega-chloroalkylamines were synthesized and their chemical and biological properties were evaluated. The nitrosamines were expected to decompose through omega-chloroalkyldiazohydroxides in aqueous solution, and then to alkylate various cellular macromolecules. N-Nitroso-N-(acetoxymethyl)-2-chloroethylamine rapidly decomposed in aqueous solution, and the reaction rate was apparently independent of the pH of the solution. On the other hand, the rate of decomposition of chloropropyl and chlorobutyl homologs was pH-dependent, and increased in alkaline solution. When mutagenicity was assayed in Salmonella typhimurium TA1535 and TA92 for preliminary evaluation, all three compounds were directly mutagenic. The mutagenicity in Salmonella typhimurium TA1535, which can detect base-pair change mutation, clearly showed that these compounds induced DNA alkylation in vivo. The increase of alkyl chain length in chloroalkyl compounds increased the mutagenic activity, and the activities were stronger than those of the corresponding simple alpha-acetoxy nitrosamines lacking a chloro group, N-nitroso-N-(acetoxymethyl)alkylamines. Furthermore, the positive result in TA92 suggested that chlorinated nitrosamines cross-linked DNA like antitumor chloroethylnitrosoureas and that they are expected to be new lead compounds for antitumor agents.

Intracranial malignant meningioma with abdominal metastases associated with hypoglycemic shock: a case report.

A thirty-year-old male with an intracranial malignant meningioma, first diagnosed 9 years ago, with three recurrences was admitted with a hypoglycemic shock. The blood glucose level was 17 mg/dl, requiring treatment with high doses of intravenous and oral dextrose for improvement. A large metastatic tumor in the liver was noted. All hormones and peptides influencing blood glucose levels were in their normal levels. Chemo-embolization and injection of anti-cancer drugs was employed in the management of the metastatic tumor. Positron emission tomography was performed to measure the glucose metabolism of the abdominal tumor and it indicated that glucose consumption within the tumor was much elevated than the surrounding abdominal organs. Hypoglycemia secondary to primary hepatoma or islet-cell cancer has been frequently described, but a complication of metastatic meningioma is an exceedingly rare event. Elevated glucose consumption within the tumor might be addressed as one of the reasons for hypoglycemia, not due to the elevated serum levels of insulin or IGF, but due to the closely related blood glucose level.

Psittacosis with increased gammadelta T cells in bronchoalveolar lavage fluid.

Experience with two cases of psittacosis is described here in which the number of gammadelta T cell receptor-positive T lymphocytes (gammadelta T cell) in the bronchoalveolar lavage fluid was markedly increased (25.1 and 66.9%) and CD8+ T cells were also increased with reversal of the CD4/CD8 ratio. These values improved to the normal range along with recovery of their radiographical findings. The present findings suggest that gammadelta T cells may play an important role in protection from lung injury caused by Chlamydia psittaci infection.

Functions of a rho-specific guanine nucleotide exchange factor in neurite retraction. Possible role of a proline-rich motif of KIAA0380 in localization.

The Rho/Rho kinase signaling pathway plays an essential role in neurite retraction and cell rounding in response to G(12/13)-coupled receptor activation in neuronal cells. The Rho guanine nucleotide exchange factor involved in these processes has not been identified. To monitor the activation state of Rho kinase, we developed a vimentin head/Rho kinase chimera, which is intramolecularly phosphorylated in a Rho-dependent manner at Ser(71) of the fused vimentin head. Using this system, we identified a clone termed KIAA0380, which contains the G alpha(12/13)-binding domain as well as a tandem of the Dbl homology/pleckstrin homology (DH/PH) domain, as an activator of Rho/Rho kinase signaling. Molecular dissection analyses revealed that a proline-rich motif C-terminally adjacent to DH/PH domain is essential for plasma membrane localization of KIAA0380 and cortical actin reorganization followed by cell rounding. In contrast, the DH/PH domain of KIAA0380 is localized in the cytoplasm, where it activates Rho/Rho kinase and induces stress fiber formation, consistent with results using p115 Rho guanine nucleotide exchange factor, which has a similar structure to KIAA0380 but lacks a proline-rich motif. These results suggest that upon stimulation, KIAA0380 translocates to the plasma membrane via the proline-rich motif and there activates Rho/Rho kinase signaling. In neuroblastoma Neuro2a cells, KIAA0380 was observed in the tips of neurites, a location where cortical actin reorganization is induced upon stimulation with lysophosphatidic acid. Ectopic expression of the N-terminal fragment inhibited lysophosphatidic acid-induced neurite retraction of Neuro2a cells. These results suggest that KIAA0380 plays an important role in neurite retraction through Rho-dependent signaling.

Serum markers of graft-versus-host disease after bone marrow transplantation.

BACKGROUND: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. OBJECTIVES: The purpose of this study was to determine clinically useful markers of acute graft-versus-host disease. METHODS: We measured the serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble c-kit, soluble Fas, soluble intercellular adhesion molecule-1, growth-related oncogene protein-alpha, thrombomodurin, and interleukin-16 in 13 patients at 1 to 7 weeks after allogenic bone marrow transplantation. RESULTS: The patients with acute graft-versus-host disease showed a significant increase of tumor necrosis factor, soluble tumor necrosis factor receptor 1, soluble Fas, soluble intercellular adhesion molecule-1, and growth-related oncogene protein-alpha, although there was a decrease of soluble c-kit. The increases of serum soluble tumor necrosis factor receptor 1, intercellular adhesion molecule-1, and growth-related oncogene protein-alpha were preceded by the elevation of soluble Fas. CONCLUSION: The patients with acute graft-versus-host disease had increased serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble Fas, and soluble intercellular adhesion molecule 1 and a decreased soluble c-kit level. Tumor necrosis factor-alpha and soluble c-kit were shown to be sensitive and specific parameters for graft-versus-host disease after bone marrow transplantation, and soluble Fas was shown to be a predictor of acute graft-versus-host disease after bone marrow transplantation.

Possible role of potassium channels in mu-receptor-mediated inhibition and muscarinic autoinhibition in acetylcholine release from myenteric plexus of guinea pig ileum.

It is known that mu-agonists inhibit electrical field stimulation (EFS)-evoked ACh release from longitudinal muscle myenteric plexus (LMMP) preparation of guinea pig ileum when muscarinic autoinhibition does not fully work. In the present study, the possible role of K+ channels in the mechanisms of mu-agonists-induced inhibition and autoinhibition of ACh release was studied. In the presence of atropine, which blocks the autoinhibition, non-selective K+ channel blockers, tetraethylammonium (TEA) and 4-aminopyridine (4-AP), reversed the inhibitory effect of mu-agonists, morphine and [D-Ala2, N-Me-Phe4, Gly5-ol] enkephalin, on EFS-evoked ACh release, but not that of kappa-agonist U-50,488. Apamin, iberiotoxin or glibenclamide did not affect the inhibition of ACh release by morphine. On the other hand, in the absence of atropine (under the autoinhibition working condition), 4-AP increased EFS-evoked ACh release, but atropine did not further increase ACh release in the presence of 4-AP. In contrast, although TEA did not affect EFS-evoked ACh release, atropine increased ACh release in the presence of TEA. These results suggest that the inhibitory effects of mu-agonists and muscarinic autoinhibition on the ACh release are associated with activation of different types of K+ channels in the guinea pig LMMP preparations: the former is associated with 4-AP- and TEA-sensitive K+ channels and the latter is associated with 4-AP- but not TEA-sensitive K+ channels.

Structural and functional conservation at the boundaries of the chicken beta-globin domain.

We show that the 3' boundary of the chicken beta-globin locus bears striking structural similarities to the 5' boundary. In erythroid cells a clear transition in DNase I sensitivity of chromatin at the 3' end of the locus is observed, the location of this transition is marked by a constitutive DNase I hypersensitive site (HS), and DNA spanning this site has the enhancer-blocking capacity of an insulator. This HS contains a binding site for the transcription factor CTCF. As in the case of the 5' insulator, the CTCF site is both necessary and sufficient for the enhancer-blocking activity of the 3' boundary. The position of this insulator is consistent with our proposal that it may function to maintain the distinct regulatory programs of the globin genes and their closely appended 3' neighbor, an odorant receptor gene. We conclude that both boundaries of the chicken beta-globin domain are capable of playing functionally similar roles and that the same protein is a necessary component of the molecular mechanism through which these boundaries are defined.

[Recent advances in echocardiographic diagnosis of ischemic heart disease].

Before the early 1990s, the diagnostic usefulness of echocardiography for ischemic heart disease had been relatively limited compared with that for other cardiac diseases such as valvular disease, congenital anomalies and cardiomyopathies. The principal role of echocardiography was to assess persistent regional wall motion abnormality as well as to detect complications of myocardial infarction. However, recent technological advances have created many newer applications of echocardiography in this field. One of the most important advances was seen in the field of stress echocardiography. Dobutamine stress echocardiography has become an established method of diagnosing transient myocardial ischemia due to coronary stenosis and assessing the myocardial viability of a persistently akinetic segment. More recently, several new contrast agents have been developed or will be available in the near future to visualize the blood stream within the left heart cavity and myocardial blood flow. Simultaneously, new ultrasound technologies including harmonic imaging and gated intermittent imaging have enhanced the selective visualization of contrast agents and will contribute to noninvasive imaging of coronary microcirculation. Harmonic imaging has also been shown to improve quality of B-mode image without a contrast agent and will play an important role in the clinical recognition of wall motion abnormality in patients with ischemic heart disease. Recent advances in three-dimensional technology have enabled accurate measurements of left ventricular volume and ejection fraction without any geometrical assumption, which may be especially important for the evaluation of ischemic patients who often have a deformed left ventricular cavity due to remodeling.

Evidence that 3'-phosphorylated polyphosphoinositides are generated at the nuclear surface: use of immunostaining technique with monoclonal antibodies specific for PI 3,4-P(2).

Phosphatidylinositol (PI) 3,4-P(2) is a phosphoinositide that has been shown to be important for signal transduction in growth factor stimulation. We have produced monoclonal antibodies specific for PI 3,4-P(2), which were able to detect PI 3,4-P(2) generated in 293T cells treated with H(2)O(2), or in MKN45/BD110 cells expressing activated PI 3-kinase in immunostaining. Prolonged treatment with 0.05% Tween 20 resulted in detection of staining not only at the plasma membrane, but also at the nuclear surface, indicating that 3'-phosphorylated phosphoinositides can be generated and function in the nucleus.