A third ascending hypothalamopetal pathway

Electrolytic lesions centered in the reticular formation or partial hemisections of the brain stem were induced stereotaxically at various levels from the medulla to the diencephalon. Nauta and Fink-Heimer methods were used to reveal degenerated fibers ascending through the upper brain stem. Degenerated fibers coursing rostrally through the subthalamus and ventrally to enter the lateral hypothalamus at tuberal levels were observed after lesions at all levels rostral to the medulla. The trajectory of this ascending pathway through the midbrain and diencephalon was distinct from that of the dorsal longitudinal fasciculus which is medial and that of the medial forebrain bundle which is ventral. Several lines of evidence suggest the hypothesis that this pathway is a component of the ascending reticular system which carries sensory information into the hypothalamus for correlation with hypothalamic visceral and behavioral functions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33552/1/0000053.pd

Universality of transport properties of ultra-thin oxide films

We report low-temperature measurements of current-voltage characteristics for highly conductive Nb/Al-AlOx-Nb junctions with thicknesses of the Al interlayer ranging from 40 to 150 nm and ultra-thin barriers formed by diffusive oxidation of the Al surface. In the superconducting state these devices have revealed a strong subgap current leakage. Analyzing Cooper-pair and quasiparticle currents across the devices, we conclude that the strong suppression of the subgap resistance comparing with conventional tunnel junctions originates from a universal bimodal distribution of transparencies across the Al-oxide barrier proposed earlier by Schep and Bauer. We suggest a simple physical explanation of its source in the nanometer-thick oxide films relating it to strong local barrier-height fluctuations which are generated by oxygen vacancies in thin aluminum oxide tunnel barriers formed by thermal oxidation.Comment: revised text and a new figur

Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma : endpoints of a spectrum of one disease?

In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis

Häufigkeit und Relevanz der Steatohepatitis bei Patienten mit kolorektalen Lebermetastasen

Meeting Abstract : Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008 Einleitung: Die Resektion von Lebermetastasen kolorektaler Karzinome stellt die einzige potentiell kurative Behandlungsoption dar. Wirksame Chemotherapeutika wie Oxaliplatin und Irinotecan sind in den Verdacht geraten durch histologische Veränderungen an der Leber das Resektionsausmass oder das Outcome von vorbehandelten Patienten zu gefährden.Die vorliegende Studie untersucht daher den Grad der Steatohepatitis bei Patienten mit kolorektalen Lebermetastasen in Abhängigkeit von der Chemotherapie. Material und Methoden: In einem Kollektiv von 100 konsekutiven Patienten (08/2002 bis 02/2006) (chemonaiv: n=32, 62,4 +/- 13,3 Jahre; neoadjuvante Chemotherapie: n=39, 62 +/- 10,2 Jahre und adjuvante Chemotherapie: n=29, 61,2 +/- 10,8 Jahre) wurde aus den intraoperativ gewonnenen Leberresektaten retrospektiv der NAFLD-Score nach Kleiner et al. (Hepatology 2005) erhoben. Zur morphologischen Beurteilung wurde die Hämatoxilin-Eosin-Färbung verwendet, während der Fibrosegrad anhand der Ladewig-Färbung und der Siderosegrad mittels der Berliner-Blau-Färbung bestimmt wurden.Anschließend erfolgte eine statische Analyse der Häufigkeit und Relevanz der Steatohepatitis in den einzelnen Gruppen im Hinblick auf Verlauf und Outcome der Leberresektion. Hierbei wurden multivariate Regression, Kruskal-Wallis-Test, chi2-Test oder Mann-Whitney-U-Test (p<0,05) verwendet. Ergebnisse: Im vorliegenden Patientengut zeigten 7 Patienten eine ausgeprägte NASH, während bei 69% der Patienten keinerlei Veränderungen im Sinne einer NASH vorlagen. Die subjektive Gesamtbeurteilung der Pathologen und der errechnete NASH-Score eine Übereinstimmung in 92%. (Cohen´s kappa 0,82; 95%-Konfidenzintervall [0,71-0,93]). Hinsichtlich des NASH-Score (p=0,462) oder seiner Komponenten konnten keine Unterschiede in Abhängigkeit vom Zeitpunkt der Chemotherapie (Chemonaiv/ neoadjuvant/ adjuvant) gefunden werden. Eine Analyse in Abhängigkeit der verwendeten Chemotherapeutika zeigte keine Unterschiede für den Gesamt-Score (p=0,897), jedoch signifikante Unterschiede für einzelne Komponenten: Portale Entzündung (p=0,045) und Vorliegen von Microgranulomen (p<0,001). Auch eine multivariate Analyse konnte weder den Einfluss von Substanz noch Zeitpunkt der Chemotherapie auf die Entwicklung einer NASH (p zwischen 0,35 und 0,92) nachweisen.Die Analyse des perioperativen Verlaufs (Transfusionsbedarf, Radikalität, Komplikationen, Liegedauer, postoperative Leberfunktion, Krankenhausmortalität) ergab keine signifikanten Unterschiede für Patienten mit oder ohne NASH. Schlussfolgerung: Das Vorliegen einer Steatohepatitis in unserem Patientengut war eine seltene Diagnose, die nicht in Zusammenhang mit Zeitpunkt der Chemotherapie oder verwendetem Chemotherapeutikum stand. Selbst das Vorliegen einer NASH scheint keinen relevanten Einfluss auf den perioperativen Verlauf oder das Outcome nach Leberresektion zu haben

Comparison of DC and RF for lesioning white and grey matter

The morphology of brain lesions produced by anodal direct current and by radio frequency current was compared. The lesions were placed within or adjacent to number of myelinated fiber tracts of the forebrain and brain stem using a range of common current parameters. It was found that with the parameters used anodal current was relatively ineffective for destroying fiber tracts while radio frequency was equally effective for fiber tracts and cellular areas. Thus, differential applicabilities of these two lesion methods are indicated. Additional observations were made on the effect of cathode location upon the shape of anodal direct current lesions. There was a tendency for the anodal lesion to be drawn in the direction of the cathode but the effect was small and inconsistent and therefore its usefulness for controlling the shapes of anodal lesions seems minimal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22350/1/0000796.pd

The contact method: A simple technique for electrical self-stimulation without external leads

Electrical currents to reward areas of the brain were administered without the use of external leads by utilizing a method conceptually similar to that of the electronic drinkometer. A wire brush connected to the intracranial electrode protudes above the rat's head. By lifting its head the rat can make contact between the brush and a stimulation plate mounted horizontally overhead. The stimulation circuit is completed through the contact of the rat's feet with a grounded metal floor. Current thresholds and stimulation rates obtained by this method were identical to those obtained by the conventional method of stimulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33792/1/0000047.pd

Tidal Imprints of a Dark Sub-Halo on the Outskirts of the Milky Way II. Perturber Azimuth

We extend our analysis of the observed disturbances on the outskirts of the HI disk of the Milky Way. We employ the additional constraints of the phase of the modes of the observed HI image and asymmetry in the radial velocity field to derive the azimuth of the perturber inferred to be responsible for the disturbances in the HI disk. We carry out a modal analysis of the phase of the disturbances in the HI image and in SPH simulations of a Milky Way-like galaxy tidally interacting with dark perturbers, the relative offset of which we utilize to derive the perturber azimuth. To make a direct connection with observations, we express our results in sun-centered coordinates, predicting that the perturber responsible for the observed disturbances is between -50 \la l \la -10. We show explicitly that the phase of the disturbances in the outskirts of simulated galaxies at the time that best fits the Fourier amplitudes, our primary metric for the azimuth determination, is relatively insensitive to the equation of state. Our calculations here represent our continuing efforts to develop the "Tidal Analysis" method of Chakrabarti \& Blitz (2009; CB09). CB09 employed SPH simulations to examine tidal interactions between perturbing dark sub-halos and the Milky Way. They found that the amplitudes of the Fourier modes of the observed planar disturbances are best-fit by a perturbing dark sub-halo with mass one-hundredth that of the Milky Way, and a pericentric approach distance of $\sim 5-10~\rm kpc$. The overarching goal of this work is to attempt to outline an alternate procedure to optical studies for characterizing and potentially discovering dwarf galaxies -- whereby one can approximately infer the azimuthal location of a perturber, its mass and pericentric distance (CB09) from analysis of its tidal gravitational imprints on the HI disk of the primary galaxy.Comment: submitted to ApJ; 12 pages; higher resolution figures can be found at: http://astro.berkeley.edu/~sukanya/perturbersubmit.pd

Glucocorticoid anorexia in rats

The effects of two mineralocorticoids, two glucocorticoids and a compound possessing both activities on ad lib food intake, water intake and salt intake were investigated. Dose response curves for d-aldosterone, DOCA, 9 alpha fluorocortisone, corticosterone and dexamethasone were obtained following subcutaneous injections in different groups of rats. Results support the conclusion of a clear separation between the mineralocorticoids and glucocorticoids in terms of their effects on salt intake and food intake respectively. In general (but with some notable exceptions) glucocorticoid activity was associated with anorexia while mineralocorticoid activity was associated with enhanced salt appetite, and the two effects appeared entirely independent of each other. Single doses of dexamethasone and 9 alpha flurocortisone significantly reduced (pp&lt;0.001) increased salt intakes for 1 or more post injection days. The glucocorticoid data are discussed in terms of a possible modification of arterial-venous glucose utilization differences affecting hypothalamic sites or the possible activation of glucose sensitive hepatic cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22437/1/0000888.pd

Carbon Monoxide Abrogates Ischemic Insult to Neuronal Cells via the Soluble Guanylate Cyclase-cGMP Pathway

Purpose Carbon monoxide (CO) is an accepted cytoprotective molecule. The extent and mechanisms of protection in neuronal systems have not been well studied. We hypothesized that delivery of CO via a novel releasing molecule (CORM) would impart neuroprotection in vivo against ischemia-reperfusion injury (IRI)-induced apoptosis of retinal ganglion cells (RGC) and in vitro of neuronal SH-SY5Y-cells via activation of soluble guanylate-cyclase (sGC). Methods: To mimic ischemic respiratory arrest, SH-SY5Y-cells were incubated with rotenone (100 nmol/L, 4 h) ± CORM ALF186 (10–100 µmol/L) or inactivated ALF186 lacking the potential of releasing CO. Apoptosis and reactive oxygen species (ROS) production were analyzed using flow-cytometry (Annexin V, mitochondrial membrane potential, CM-H2DCFDA) and Western blot (Caspase-3). The impact of ALF186± respiratory arrest on cell signaling was assessed by measuring expression of nitric oxide synthase (NOS) and soluble guanylate-cyclase (sGC) and by analyzing cellular cGMP levels. The effect of ALF186 (10 mg/kg iv) on retinal IRI in Sprague-Dawley rats was assessed by measuring densities of fluorogold-labeled RGC after IRI and by analysis of apoptosis-related genes in retinal tissue. Results: ALF186 but not inactivated ALF186 inhibited rotenone-induced apoptosis (Annexin V positive cells: 25±2% rotenone vs. 14±1% ALF186+rotenone, p<0.001; relative mitochondrial membrane potential: 17±4% rotenone vs. 55±3% ALF186+rotenone, p<0.05). ALF186 increased cellular cGMP levels (33±5 nmol/L vs. 23±3 nmol/L; p<0.05) and sGC expression. sGC-inhibition attenuated ALF186-mediated protection (relative mitochondrial membrane potential: 55±3% ALF186+rotenone vs. 20±1% ODQ+ALF186+rotenone, p<0.05). ALF186 protected RGC in vivo (IRI 1255±327 RGC/mm2 vs. ALF186+IRI 2036±83; p<0.05) while sGC inhibition abolished the protective effects of ALF186 (ALF186+IRI 2036±83 RGC/mm2 vs. NS-2028+ALF186+IRI 1263±170, p<0.05). Conclusions: The CORM ALF186 inhibits IRI-induced neuronal cell death via activation of sGC and may be a useful treatment option for acute ischemic insults to the retina and the brain

DFT Calculations of Isotropic Coupling Constants of Phenoxyl and Aroxyl Radicals

Hybrid density-functional calculations were carried out to corroborate the identity of phenoxyl radicals observed by EPR spectroscopy after oxidation of selected mono- and polyphenols with horseradish peroxidase/hydrogen peroxide or after alkaline autoxidation. Whereas quantitative correlations of experimental and theoretical coupling constants were less satisfactory, we could confirm formation of a bi-radical after initial oxidation of 2,4,6-trimethylphenol, the mesomeric structures of gallate ester aroxyl radicals and identify the radical site of a model gallotannin, hamamelitannin