Optical pyrometer system for collisionless shock experiments in high-power laser-produced plasmas.

A temporally and spatially resolved optical pyrometer system has been fielded on Gekko XII experiments. The system is based on the self-emission measurements with a gated optical imager (GOI) and a streaked optical pyrometer (SOP). Both detectors measure the intensity of the self-emission from laser-produced plasmas at the wavelength of 450 nm with a bandpass filter with a width of ~10 nm in FWHM. The measurements were calibrated with different methods, and both results agreed with each other within 30% as previously reported [T. Morita et al., Astrophys. Space Sci. 336, 283 (2011)]. As a tool for measuring the properties of low-density plasmas, the system is applicable for the measurements of the electron temperature and density in collisionless shock experiments [Y. Kuramitsu et al., Phys. Rev. Lett. 106, 175002 (2011)].

Time evolution of collisionless shock in counterstreaming laser-produced plasmas.

We investigated the time evolution of a strong collisionless shock in counterstreaming plasmas produced using a high-power laser pulse. The counterstreaming plasmas were generated by irradiating a CH double-plane target with the laser. In self-emission streaked optical pyrometry data, steepening of the self-emission profile as the two-plasma interaction evolved indicated shock formation. The shock thickness was less than the mean free path of the counterstreaming ions. Two-dimensional snapshots of the self-emission and shadowgrams also showed very thin shock structures. The Mach numbers estimated from the flow velocity and the brightness temperatures are very high.

Microsomal prostaglandin E synthase-1 contributes to ischaemic excitotoxicity through prostaglandin E2 EP3 receptors.

BACKGROUND AND PURPOSE: Although microsomal prostaglandin E synthase (mPGES)-1 is known to contribute to stroke injury, the underlying mechanisms remain poorly understood. This study examines the hypothesis that EP(3) receptors contribute to stroke injury as downstream effectors of mPGES-1 neurotoxicity through Rho kinase activation. EXPERIMENTAL APPROACH: We used a glutamate-induced excitotoxicity model in cultured rat and mouse hippocampal slices and a mouse middle cerebral artery occlusion-reperfusion model. Effects of an EP(3) receptor antagonist on neuronal damage in mPGES-1 knockout (KO) mice was compared with that in wild-type (WT) mice. KEY RESULTS: In cultures of rat hippocampal slices, the mRNAs of EP(1-4) receptors were constitutively expressed and only the EP(3) receptor antagonist ONO-AE3-240 attenuated and only the EP(3) receptor agonist ONO-AE-248 augmented glutamate-induced excitotoxicity in CA1 neurons. Hippocampal slices from mPGES-1 KO mice showed less excitotoxicity than those from WT mice and the EP(3) receptor antagonist did not attenuate the excitotoxicity. In transient focal ischaemia models, injection (i.p.) of an EP(3) antagonist reduced infarction, oedema and neurological dysfunction in WT mice, but not in mPGES-1 KO mice, which showed less injury than WT mice. EP(3) receptor agonist-induced augmentation of excitotoxicity in vitro was ameliorated by the Rho kinase inhibitor Y-27632 and Pertussis toxin. The Rho kinase inhibitor HA-1077 also ameliorated stroke injury in vivo. CONCLUSION AND IMPLICATIONS: Activity of mPGES-1 exacerbated stroke injury through EP(3) receptors and activation of Rho kinase and/or G(i). Thus, mPGES-1 and EP(3) receptors may be valuable therapeutic targets for treatment of human stroke.

A groundbreaking new suturing device: the Excalibur.

BACKGROUND: Laparoscopic knot tying can be stressful. We reported two simple techniques, known as the Thumbs up! knot and the Tornado knot. We have further refined these procedures with the development of a new needle holder, called the Excalibur suturing needle holder. MATERIALS: This forceps differ from most conventional forceps in that the hinge is designed to stick out. The large hinge is stored out of the way when the forceps are closed, to prevent the thread accidentally catching. RESULTS: The thread is hooked on the projected hinge, which resembles the heel of a high-heel shoe. By using this forceps, the laparoscopic knot tying becomes easier for not only well experienced but also less experienced surgeons. CONCLUSIONS: The Excalibur, with its high heel, can complete knots with simple straight-line motion, making knot tying easier. This forceps will help reduce the stresses associated with intra-corporeal knot tying.

Safety and growth suppressive effect of intra-hepatic arterial injection of AdCMV-p53 combined with CDDP to rat liver metastatic tumors.

Surgical resection is thought to be the best treatment for liver carcinoma, including hepatocellular carcinoma and metastatic liver carcinoma if there are a small number of tumors. Liver carcinoma is one of the main causes of death from cancer worldwide. The prognosis of liver carcinoma is still poor. Mutation of p53, which is well known as a tumor suppressor gene, is observed in many cases of advanced liver carcinoma. Cancer gene therapy using p53, which transduces the wild-type p53 gene in the tumor, is a promising new strategy for treating liver carcinoma. Selective and less invasive gene delivery to the liver tumor is necessary for clinical liver tumor gene therapy. The first purpose of the current study was to determine the best way to deliver the gene of interest to the liver tumor selectively. The second purpose was to study the tumor suppressive effect of intrahepatic arterial injection of an adenovirus vector with the p53 gene (AdCMV-p53), followed by administration of CDDP and noting its side effects. We injected AdCMV-LacZ via hepatic arteries of rats bearing RCN-9 colon cancer metastasis in the liver. Injection via the hepatic artery resulted in more successful gene transduction to the liver tumor in a tumor-selective manner than did injection via the portal vein. At 48 hrs after arterial injection of AdCMV-p53, CDDP (3 mg/kg) was administered in the peritoneal cavity of each rat. The use of CDDP with arterial injection of AdCMV-p53 resulted in more extensive apoptosis in the rat liver tumors without any deterioration in liver function. In conclusion, hepatic arterial injection of an adenovirus vector is better than portal vein injection for gene transduction efficiency, and causes no liver function disorder even when the injection is combined with CDDP.

Cerebrospinal fluid amyloid beta(1-42) levels in the mild cognitive impairment stage of Alzheimer's disease.

Cerebrospinal fluid (CSF) levels of amyloid beta-protein ending at amino acid position 42 (CSF-A beta(1-42)) and CSF-tau levels were quantified by sandwich ELISAs in 19 patients with mild cognitive impairment (MCI) who eventually developed Alzheimer's disease (AD) on follow-up as well as in 15 age-matched normal controls and 54 AD patients at diverse stages of the disease. In the present study, the annual conversion rate was approximately 15%. The CSF-A beta(1-42) levels did not differ significantly between the normal control group and the MCI group, however, these values declined significantly once AD became clinically overt. In contrast to CSF-Abeta(1-42), CSF-tau levels were significantly increased in the MCI stage, and these values continued to be elevated thereafter, indicating that increased levels of CSF-tau may help in detecting MCI subjects who are predicted to develop AD. We propose that CSF-tau and CSF-A beta(1-42) must be used as two distinct biomarkers that should be applied appropriately in clinical settings.

Biochemical and immunohistological changes in the brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse.

We investigated neurochemically and neuropathologically the utility of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice as a model of Parkinson's disease. The changes in dopamine D1 and D2 receptors and dopamine uptake sites were determined by quantitative autoradiography using [3H]SCH23390, [3H]raclopride and [3H]mazindol, respectively. Dopamine and 3,4-dihydroxyphenyl acetic acid (DOPAC) contents in the striatum were measured by high-performance liquid chromatography. The distribution of nigral neurons and reactive astrocytes was determined by immunohistochemical staining with antibody against tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). The mice received four intraperitoneal injections of MPTP (10 mg/kg) at 1-h intervals and then the brains were analyzed at 3 and 7 days after the treatments. No significant change in dopamine D1 receptors was observed in the striatum and substantia nigra after acute treatment with MPTP. Dopamine D2 receptors were reduced significantly in the substantia nigra only 7 days after the MPTP treatment, whereas striatum showed no significant change in the binding throughout the experiments. In contrast, dopamine uptake sites were reduced markedly in the striatum and substantia nigra 3 and 7 days after the MPTP treatment. Dopamine and DOPAC content were also reduced in the striatum 3 and 7 days after the MPTP treatment. An immunohistochemical study indicated a loss of the number of TH-positive neurons in the substantia nigra 7 days after the MPTP treatment. In contrast, numerous GFAP-positive astrocytes were evident in the striatum 7 days after the MPTP treatment. These results provide valuable information for the pathogenesis of acute stage of Parkinson's disease.

Sequential changes of cholinergic and dopaminergic receptors in brains after 6-hydroxydopamine lesions of the medial forebrain bundle in rats.

We studied sequential changes in muscarinic cholinergic receptors, high-affinity choline uptake sites and dopamine D2 receptors in the brain after 6-hydroxydopamine lesions of the medial forebrain bundle in rats. The animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks postlesion. [3H]Quinuclidinylbenzilate (QNB), [3H]hemicholinum-3 (HC-3) and [3H]raclopride were used to label muscarinic cholinergic receptors, high-affinity choline uptake sites and dopamine D2 receptors, respectively. The degeneration of nigrostriatal pathway produced a transient decrease in [3H]QNB binding in the parietal cortex of both ipsilateral and contralateral sides at 2 and 8 weeks postlesion. [3H]QNB binding also showed a mild but insignificant decrease in the ipsilateral striatum throughout the postlesion periods. No significant change was observed in the substantia nigra (SN) of both ipsilateral and contralateral sides throughout the postlesion periods. In contrast, [3H]HC-3 binding showed no significant change in the parietal cortex of both ipsilateral and contralateral sides during the postlesion. However, [3H]HC-3 binding was upregulated in the ipsilateral dorsolateral striatum throughout the postlesion periods. The ventromedial striatum also showed a significant increase in [3H]HC-3 binding at 1 week and 2 weeks postlesion. On the other hand, no significant change in [3H]raclopride binding was found in the parietal cortex of both ipsilateral and contralateral sides during the postlesion. [3H]Raclopride binding showed a conspicuous increase in the ipsilateral striatum (35-52% of the sham-operated values in the lateral part and 39-54% in the medial part) throughout the postlesion periods. In the contralateral side, a mild increase in [3H]raclopride binding was also found in the striatum (10-15% of the sham-operated values in the lateral part and 22% in the medial part) after lesioning. However, a significant decline in [3H]raclopride binding was observed in the ipsilateral SN and ventral tegmental area during the postlesion. The present study indicates that 6-hydroxydopamine injection of medial forebrain bundle in rats can cause functional changes in high-affinity choline uptake site in the striatum, as compared with muscarinic cholinergic receptors. Furthermore, our studies demonstrate an upregulation in dopamine D2 receptors in the striatum and a decrease in the receptors in the SN and ventral tegmental area after the 6-hydroxydopamine injection. Thus, these findings provide further support for neurodegeneration of the nigrostriatal pathway that occurs in Parkinson's disease.

Temporal changes of dopaminergic and glutamatergic receptors in 6-hydroxydopamine-treated rat brain.

Quantitative receptor autoradiography was used to examine the sequential patterns of changes in dopaminergic and glutamatergic receptors in the brain of rats lesioned with 6-hydroxydopamine. The animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks of postlesion. Degeneration of the nigrostriatal pathway caused a significant increase in dopamine D(2) receptors in the ipsilateral striatum from 1 to 8 weeks of postlesion. In the ipsilateral substantia nigra (SN), a significant decrease in dopamine D(2) receptors was also observed from 1 to 8 weeks of postlesion. On the other hand, dopamine D(1) receptors were increased in the ipsilateral ventromedial striatum from 2 to 4 weeks of postlesion. In the ipsilateral SN, a transient increase in dopamine D(1) receptors was observed only 1 week after lesioning. However, other regions in both ipsilateral and contralateral sides showed no significant change in dopamine D(1) and D(2) receptors during postlesion except for a transient change in a few regions. N-Methyl-D-aspartate (NMDA) receptors showed no significant changes in all brain regions studied during the postlesion. In contrast, a transient increase in excitatory amino acid transport sites was observed only in the frontal cortex and ventromedial striatum of the ipsilateral side at 2 weeks of postlesion. However, glycine receptors showed a significant change in any brain areas of both ipsilateral and contralateral sides after lesioning. The change in the brain areas of contralateral side was more pronounced than that of ipsilateral side for glycine receptors. In addition, dopamine uptake sites showed a severe damage in the ipsilateral striatum from 1 to 8 weeks after lesioning. In the contralateral side, in contrast, no significant change in dopamine uptake sites was found in the striatum during the postlesion. These results indicate that unilateral injection of 6-hydroxydopamine in the medial forebrain bundle can cause a significant increase in dopamine D(1) and D(2) receptors in the striatum. The increase in dopamine D(2) receptors was more pronounced than that in dopamine D(1) receptors in the striatum after 6-hydroxydopamine treatment. In contrast, dopamine uptake sites showed a severe damage in the striatum during the postlesion. Furthermore, our results support the existence of dopamine D(2) receptors on the neurons of SN, but not dopamine D(1) receptors. For glutamatergic receptor system, the present study suggests that the changes in glycine receptors may be more susceptible to degeneration of nigrostriatal pathway than NMDA receptors and excitatory amino acid transport sites. Thus, our findings are of interest in relation of degeneration of the nigrostriatal pathway that occurs in Parkinson's disease

Prolongation of liver allograft survival after interleukin-10 gene transduction 24-48 hours before donation.

BACKGROUND: Interleukin- (IL) 10 may be a potent regulator for controlling of allograft rejection. A single administration of IL-10 is not effective for controlling graft rejection. Gene transfer is an attractive vehicle for prolonging the expression of short-lived proteins. METHODS: Donor or recipient livers were transduced with 1 x 10(10) p.f.u. of replication-deficient adenovirus vectors harboring human IL-10 cDNA (AdCMVhIL-10) via the ileocecal vein before or after rat orthotopic liver transplantation. RESULTS: DA allografts given AdCMVhIL-10 24-48 hr before donation survived for more than 56 days in Lewis recipients, although DA allografts given the adenovirus vector 7 days or 6 hr before, and 3 days after transplantation were rejected within 30 days in recipients. Serum levels of human IL-10 in gene-transferred rats were maximum from day 2 to 7. The serum level of human IL-10 then decreased gradually, and human IL-10 was not detected by ELISA 30 days after gene-transduction. In gene-transduced long-term surviving liver allografts, IL-10 was expressed, and the expression of IL-4 was also up-regulated on posttransplant day 3, despite the expression of Th1 cytokines (IL-2 and interferon-gamma), although in rejected liver allografts, IL-2 and interferon-gamma were expressed without expression of IL-4 and IL-10. CONCLUSIONS: The prolongation of survival of IL-10 cDNA transferred liver allografts might be due to inhibition of the early phase of alloimmune-response by over expression of IL-10, despite the expression of IL-2 and interferon-gamma.

Sequential changes of [H]forskolin, [H]cyclohexyladenosine and [H]PN200-110 binding sites in the brain of 6-hydroxydopamine-lesioned rats.

Receptor autoradiographic technique was studied to investigate sequential changes in adenylyl cyclase, adenosine A1 receptors and L-type calcium channels in the striatum and substantia nigra 1-8 weeks after unilateral 6-hydroxydopamine injection of the medial forebrain bundle in rats. [3H]Forskolin, [3H]cyclohexyladenosine (CHA) and [3H]PN200-110 were used to label adenylyl cyclase, adenosine A1 receptors and L-type calcium channels, respectively. The degeneration of the nigrostriatal pathway caused a significant increase in [3H]forskolin binding in the striatum of both the ipsilateral and contralateral sides from 2 to 4 weeks post-lesion. The ipsilateral substantia nigra showed a transient increase in [3H]forskolin binding 4 weeks post-lesion. In contrast, [3H]CHA binding showed no significant change in most brain areas after lesioning. On the other hand, a conspicuous decrease in [3H]PN200-110 binding was observed in the dorsolateral striatum of ipsilateral side 4 weeks post-lesion. Thereafter, the striatum of both the ipsilateral and contralateral sides showed a significant decrease in [3H]PN200-110 binding 8 weeks post-lesion. These results demonstrate that unilateral 6-hydroxydopamine into the medial forebrain bundle of rats can experimentally cause a significant increase in adenylyl cyclase binding sites in the striatum and substantia nigra, whereas no conspicuous change in adenosine A1 receptors is observed in these areas during post-lesion. In contrast, L-type calcium channels were progressively damaged in the striatum after unilateral 6-hydroxydopamine treatment. These findings suggest that adenylyl cyclase and calcium system may contribute to the degeneration processes of the dopaminergic neurones.

Silent cerebral infarction: a potential risk for pneumonia in the elderly.

OBJECTIVE: To determine whether patients who have silent cerebral infarction are more likely to develop pneumonia than are controls without silent cerebral infarction. DESIGN: We examined 269 community-residing participants of the senior day-care centre without history of previous stroke, and then followed them over a two-year period to assess pneumonia. On the basis of computerized tomography scans, they were divided into two groups: no infarction (n = 102) and cerebral hemispheric infarction (n = 167). Cerebral infarcts were further divided into deep and superficial infarcts. RESULTS: The incidence of pneumonia was significantly higher in subjects with silent cerebral infarction (19.8%) than in controls (4. 9%) (odds ratio, 4.67 [95% CI, 1.87-11.67]; P < 0.01). Deep infarcts were more closely associated with the incidence of pneumonia (29.1%) than superficial infarcts (7.6%) (odds ratio, 5.00 [CI, 1.91-13.08]; P < 0.01). CONCLUSIONS: Elderly subjects with silent cerebral infarction were more likely to develop pneumonia than were controls without silent cerebral infarction. Amongst hemispheric silent cerebral infarcts, those located in the deep brain structures may be an important predictor of the development of pneumonia.

Allograft transduction of IL-10 prolongs survival following orthotopic liver transplantation.

Interleukin-10 (IL-10) is an ideal candidate cytokine for suppressing the alloimmune response in transplantation. To determine whether genetic modulation of the hepatic graft with IL-10 could prolong survival following orthotopic liver transplantation, we constructed a replication-deficient adenovirus vector expressing human IL-10 (AdCMVhIL-10). Intraportal injection of this vector into a donor rat 24-48 h before grafting resulted in efficient release of IL-10 into the circulation of a recipient rat after transplantation. Moreover, levels of hIL-10 from the suprahepatic vena cava were significantly (1.48-fold) higher than those from the infrahepatic vena cava (P = 0.013), indicating local IL-10 production within the transduced hepatic graft. AdCMVhIL-10 induced a prolongation of median survival to more than 87 days, with two of five transduced grafts showing more than 100 days of ongoing survival, when compared with 11 days for grafts transduced with a control adenovirus vector carrying the E. coli beta-galactosidase gene (P = 0.0021) and 11 days for untreated grafts (P = 0.0021). Pathological findings occurring in the AdCMVhIL-10-transduced hepatic grafts revealed no evidence of progressive rejection reaction resulting in graft failure. These results demonstrate that hepatic grafts modulated by IL-10 gene transfer make local and effective immunosuppression feasible in the transplantation setting.