Acute Effects of Whole-Body Proton Irradiation on the Immune System of the C57BL/6 Mouse

The acute effects of proton whole-body irradiation (WBI) on leukocytes, lymphocytes, and hematological parameters in the spleen and blood of C57BI/6 mice were examined and compared to the effects of photon (gamma) WBI derived from a 60cobalt (60Co) source. Adult, female C57BL/6 mice were exposed to a single dose (3 Gy, 0.4 Gy/min dose rate) of either proton WBI at the Bragg peak, proton WBI at the entry plateau, or Co WBI, and sacrifice intervals were at 1,4, 7, and 10 days post- WBI. Flow cytometry analysis of the spleen and peripheral blood showed depression in cell counts for all time points when compared to the non-irradiated control group. B (CD19+) and T-cytotoxic/suppressor (CD3+CD8+) lymphocytes were the most radiosensitive, while natural killer (NK1.1+) cells were the most radioresistant. Splenic T cells showed reduced responsiveness to mitogen stimulation for the first four days post- WBI, while splenic B cell responsiveness was reduced at all time periods. Analysis of hematological parameters showed depression of red blood cells, hemoglobin concentration, and hematocrit levels after 4 days post-WBI; platelet counts were low at days 4 and 10. Comparison of the proton and 60Co-irradiated groups showed few statistically significant differences among the radiation groups at any time point. These data indicate, for the very first time, that cells of the immune system are affected similarly by 3 Gy proton (Bragg peak and entry plateau) and gamma WBI. These findings could have a significant impact on future studies designed to maximize normal tissue protection during and after proton radiation exposure. Key words: Leukocytes, lymphocyte subsets, radiation, protons, whole-bod

Serotonin Augments Gut Pacemaker Activity via 5-HT3 Receptors

Serotonin (5-hydroxytryptamine: 5-HT) affects numerous functions in the gut, such as secretion, muscle contraction, and enteric nervous activity, and therefore to clarify details of 5-HT's actions leads to good therapeutic strategies for gut functional disorders. The role of interstitial cells of Cajal (ICC), as pacemaker cells, has been recognised relatively recently. We thus investigated 5-HT actions on ICC pacemaker activity. Muscle preparations with myenteric plexus were isolated from the murine ileum. Spatio-temporal measurements of intracellular Ca2+ and electric activities in ICC were performed by employing fluorescent Ca2+ imaging and microelectrode array (MEA) systems, respectively. Dihydropyridine (DHP) Ca2+ antagonists and tetrodotoxin (TTX) were applied to suppress smooth muscle and nerve activities, respectively. 5-HT significantly enhanced spontaneous Ca2+ oscillations that are considered to underlie electric pacemaker activity in ICC. LY-278584, a 5-HT3 receptor antagonist suppressed spontaneous Ca2+ activity in ICC, while 2-methylserotonin (2-Me-5-HT), a 5-HT3 receptor agonist, restored it. GR113808, a selective antagonist for 5-HT4, and O-methyl-5-HT (O-Me-5-HT), a non-selective 5-HT receptor agonist lacking affinity for 5-HT3 receptors, had little effect on ICC Ca2+ activity. In MEA measurements of ICC electric activity, 5-HT and 2-Me-5-HT caused excitatory effects. RT-PCR and immunostaining confirmed expression of 5-HT3 receptors in ICC. The results indicate that 5-HT augments ICC pacemaker activity via 5-HT3 receptors. ICC appear to be a promising target for treatment of functional motility disorders of the gut, for example, irritable bowel syndrome

Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and β-adrenoceptors

The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2 subtype providing a secondary backup role. Bladder relaxation, which is required for urine storage, is mediated by β-adrenoceptors, in most species involving a strong β3-component. An excessive stimulation of contraction or a reduced relaxation of the detrusor smooth muscle during the storage phase of the micturition cycle may contribute to bladder dysfunction known as the overactive bladder. Therefore, interference with the signal transduction of these receptors may be a viable approach to develop drugs for the treatment of overactive bladder. The prototypical signaling pathway of M3 receptors is activation of phospholipase C (PLC), and this pathway is also activated in the bladder. Nevertheless, PLC apparently contributes only in a very minor way to bladder contraction. Rather, muscarinic-receptor-mediated bladder contraction involves voltage-operated Ca2+ channels and Rho kinase. The prototypical signaling pathway of β-adrenoceptors is an activation of adenylyl cyclase with the subsequent formation of cAMP. Nevertheless, cAMP apparently contributes in a minor way only to β-adrenoceptor-mediated bladder relaxation. BKCa channels may play a greater role in β-adrenoceptor-mediated bladder relaxation. We conclude that apart from muscarinic receptor antagonists and β-adrenoceptor agonists, inhibitors of Rho kinase and activators of BKCa channels may have potential to treat an overactive bladder

Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses

Higher order structure of polymer spherulites

この論文は国立情報学研究所の電子図書館事業により電子化されました。研究会報告結晶性高分子の一般的な形態である球晶は、それを構成する微結晶(ラメラ晶)が分岐・衝突を繰り返してできた複雑な分岐網となっている。偏光顕微鏡下で特徴的な模様が見られることは古くから知られているが、この形態の定量化はされていない。今回我々は、偏光顕微鏡像の画像解析からこれを定量化しその性質を議論する

Ophthalmomyiasis in Hawaii.

Ophthalmomyiasis is the infestation of the eye by fly larvae. Commonly caused by Oestrus ovis, a female sheep botfly will accidentally deposit her larvae into a human eye, resulting in disease. Prompt recognition and treatment of this condition will improve patient care and reduce potential complications. We report a case of ophthalmomyiasis in a young man from Molokai who was infested while unloading a Christmas tree