Proton Distribution Radii of

The root mean square radii of the proton density distribution in ^{16-24}O derived from measurements of charge changing cross sections with a carbon target at ∼900A MeV together with the matter radii portray thick neutron skin for ^{22-24}O despite ^{22,24}O being doubly magic. Imprints of the shell closures at N=14 and 16 are reflected in local minima of their proton radii that provide evidence for the tensor interaction causing them. The radii agree with ab initio calculations employing the chiral NNLO_{sat} interaction, though skin thickness predictions are challenged. Shell model predictions agree well with the data.

Dominance of Tensor Correlations in High-Momentum Nucleon Pairs Studied by (p,pd) Reaction.

The isospin character of p-n pairs at large relative momentum has been observed for the first time in the ^{16}O ground state. A strong population of the J,T=1,0 state and a very weak population of the J,T=0,1 state were observed in the neutron pickup domain of ^{16}O(p,pd) at 392 MeV. This strong isospin dependence at large momentum transfer is not reproduced by the distorted-wave impulse approximation calculations with known spectroscopic amplitudes. The results indicate the presence of high-momentum protons and neutrons induced by the tensor interactions in the ground state of ^{16}O.

Proton Distribution Radii of

Proton radii of ^{12-19}C densities derived from first accurate charge changing cross section measurements at 900A MeV with a carbon target are reported. A thick neutron surface evolves from ∼0.5 fm in ^{15}C to ∼1 fm in ^{19}C. The halo radius in ^{19}C is found to be 6.4±0.7 fm as large as ^{11}Li. Ab initio calculations based on chiral nucleon-nucleon and three-nucleon forces reproduce the radii well.

Measurement of Excitation Spectra in the

Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the η^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18 at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The momenta of deuterons emitted at 0° are precisely measured with the fragment separator (FRS) operated as a spectrometer. In contrast to theoretical predictions on the possible existence of deeply bound η^{'}-mesic states in carbon nuclei, no distinct structures are observed associated with the formation of bound states. The spectra are analyzed to set stringent constraints on the formation cross section and on the hitherto barely known η^{'}-nucleus interaction.

Proton radii of (12-17)B define a thick neutron surface in ¹7B.

The first determination of radii of point proton distribution (proton radii) of (12-17)B from charge-changing cross sections (σ(CC)) measurements at the FRS, GSI, Darmstadt is reported. The proton radii are deduced from a finite-range Glauber model analysis of the σ(CC). The radii show an increase from ¹³B to ¹7B and are consistent with predictions from the antisymmetrized molecular dynamics model for the neutron-rich nuclei. The measurements show the existence of a thick neutron surface with neutron-proton radius difference of 0.51(0.11) fm in ¹7B.

Prognostic role of immunosuppressive acidic protein in patients with esophageal cancer.

Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the host's immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 +/- 183 mg/mL vs. 739 +/- 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

Evidence for prevalent Z = 6 magic number in neutron-rich carbon isotopes.

The nuclear shell structure, which originates in the nearly independent motion of nucleons in an average potential, provides an important guide for our understanding of nuclear structure and the underlying nuclear forces. Its most remarkable fingerprint is the existence of the so-called magic numbers of protons and neutrons associated with extra stability. Although the introduction of a phenomenological spin-orbit (SO) coupling force in 1949 helped in explaining the magic numbers, its origins are still open questions. Here, we present experimental evidence for the smallest SO-originated magic number (subshell closure) at the proton number six in 13-20C obtained from systematic analysis of point-proton distribution radii, electromagnetic transition rates and atomic masses of light nuclei. Performing ab initio calculations on 14,15C, we show that the observed proton distribution radii and subshell closure can be explained by the state-of-the-art nuclear theory with chiral nucleon-nucleon and three-nucleon forces, which are rooted in the quantum chromodynamics.

Involvement of prostaglandin E receptor EP3 subtype and prostacyclin IP receptor in decreased acid response in damaged stomach.

We investigated the roles of cyclooxygenase (COX) isozymes and prostaglandin E (PGE) receptor EP1 and EP3 subtypes or prostacyclin IP receptors in the decrease in acid secretion in the damaged mouse stomach. Male C57/BL6 mice, both wild type and animals lacking EP1, EP3, or IP receptors, were used after 18 h of fasting. Under urethane anesthesia, the stomach was mounted on an ex-vivo chamber and perfused with saline, and acid secretion as well as transmucosal potential difference (PD) was measured before and after exposure to 20 mM taurocholate Na (TC) for 20 min. Indomethacin, SC-560 or rofecoxib was given i.d. 30 min before TC. Mucosal exposure to TC in wild-type mice caused a reduction in PD, followed by decrease in acid secretion. Indomethacin attenuated the decrease in acid secretion after exposure to TC in wild-type mice, an effect mimicked by SC-560 but not rofecoxib, yet none of these drugs affected the decrease in PD. An altered acid response after exposure to TC was similarly observed in EP1 (-/-) mice but mitigated in mice lacking either EP3 or IP receptors, although a decrease in PD was observed in all groups. Furthermore, the decreased acid response was also attenuated by prior administration of the EP3- but not EP1- antagonist. Mucosal levels of PGE(2) and 6-keto PGF(1a) increased after exposure to TC in all groups of mice. In conclusion, the decrease in acid secretion in the damaged stomach is mediated by endogenous PGs derived from COX-1, through PGE(2)/EP3 receptors and prostacyclin/IP receptors.

Physiological properties and morphological characteristics of cutaneous and mucosal mechanical nociceptive neurons with A-delta peripheral axons in the trigeminal ganglia of crotaline snakes.

Primary A-delta nociceptive neurons in the trigeminal ganglia of immobilized crotaline snakes were examined by intrasomal recording and injection of horseradish peroxidase in vivo. Thirty-four neurons supplying the oral mucosa or facial skin were identified as A-delta nociceptive neurons which responded exclusively to noxious mechanical stimuli and had a peripheral conduction velocity ranging from 2.6 to 15.4 m/s. These neurons were subdivided into a fast-conducting type (FC-type) and a slowly conducting type (SC-type). Neurons of both types had a receptive field limited to a single spot which responded to pin prick stimulus with a threshold of more than 5 g. The FC-type neurons had a narrow spike followed by a shorter after-hyperpolarization. In contrast, SC-type neurons exhibited a broad spike with a hump on the falling phase and a longer after-hyperpolarization. The diameters of the stem, central and peripheral axons of the FC-type neurons were significantly thicker than those of the SC-type neurons, but there was no statistical difference in the soma size of the two types. Central axons of both types of neurons were thinner than their stem and peripheral axons. Dichotomizing fibers of peripheral axons were observed within the ganglion on 3 neurons. Central axons of the FC-type neurons terminated ipsilaterally in the nucleus principalis, the subnucleus oralis, interpolaris and caudalis and the interstitial nucleus, whereas those of the SC-type neurons generally projected only to the caudal half of the subnucleus interpolaris, subnucleus caudalis and interstitial nucleus ipsilaterally. The present data showed for the first time the physiological and morphological heterogeneity of the primary trigeminal A-delta nociceptive neurons and revealed that the trigeminal nucleus principalis and all the subdivisions of the trigeminal descending nucleus are involved in nociception as relay nuclei, but the subnucleus caudalis and the caudal half subnucleus interpolaris are the essential relay sites of the primary nociceptive afferents supplying the oral mucosa and facial skin. The interstitial nucleus also appears to play an important role in orofacial nociception.

Distinct morphological characteristics of touch, temperature, and mechanical nociceptive neurons in the crotaline trigeminal ganglia.

Intrasomal recording and horseradish peroxidase injection techniques were employed in vivo to determine the morphological characteristics of touch, temperature, and mechanical nociceptive neurons in the trigeminal ganglia of crotaline snakes. The touch neurons, with a peripheral axon conducting at the A-beta range, could be subdivided into tactile and vibrotactile neurons according to their response properties, but there were no morphological differences between them. These neurons exhibited a large and oval soma and possessed a set of large stem, peripheral, and central axons which were all myelinated and equal in diameter with a constriction at the bifurcation. The temperature neurons, which conducted peripherally at the A-delta range, were physiologically separated into thermosensitive and thermo-mechanosensitive neurons, which were also morphologically indistinguishable. The temperature neurons had a round soma of medium size and a set of medium axons with varied axonal bifurcation patterns. All axons of these neurons were myelinated, but the central axon was thinner than the stem and peripheral axons. The mechanical nociceptive neurons, which had a peripheral axon conducting at the A-delta range, were morphologically heterogeneous based on their conduction velocities. The neurons conducting at the fast A-delta range were morphologically similar to the temperature neurons in the ganglion excepting their thinner central axons, whereas those at the slow A-delta range had a thinner myelinated stem axon that gave rise to a thinner myelinated peripheral axon and an unmyelinated stem axon with a bifurcation of either a triangular expansion at the bifurcating point or a central axon arising straightforwardly from the constant stem and peripheral axons. This study revealed that distinct morphological characteristics do exist for the touch and temperature neurons and the subtypes of mechanical nociceptive neurons in the trigeminal ganglion, but not for the subfunctional types of touch neurons or temperature neurons.

Novel cyclopropapyrroloindole derivative (AT-3510) bearing methoxycarbonyl and trifluoromethyl groups.

The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moieties at the N6-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)-12m], the novel prodrug MCTFCPI derivative carrying a 5-(7-methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carb onyl group at the N6-position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.

Novel seco cyclopropa[c]pyrrolo[3,2-e]indole bisalkylators bearing a 3,3'-arylenebisacryloyl group as a linker.

We synthesized the novel seco cyclopropa[c]pyrrolo[3,2-e]indole (CPI) bisalkylators and evaluated their antitumor activity. Among these derivatives, 11a (AT-760), in which the two seco 3-methoxycarbonyl-2-trifluoromethyl CPI (MCTFCPI) moieties are connected with a 3,3'-(1,4-phenylene)bisacryloyl group, was found to exhibit more potent cytotoxicity and antitumor activity against HeLaS3 human uterine cervix carcinoma cells and Colon 26 adenocarcinoma cells, respectively, than 8 (bizelesin, U-77,779). It also appeared that compound 11a exhibits improved in vivo efficacy in the human colon CX-1 model when compared to either compound 8 or mitomycin C (MMC). Efficacious doses for 11a were found to be 2-fold lower than those for 8.

Substance P-like immunoreactive fibers in the trigeminal sensory nuclei of the pit viper, Trimeresurus flavoviridis.

Substance P-like immunoreactive nerve fibres were located in the trigeminal sensory system of the infrared-sensitive snake, Trimeresurus flavoviridis, using the immunohistochemical method. There are two trigeminal sensory systems in the medulla of this animal: the descending nucleus and the lateral descending nucleus. The descending nucleus is equivalent to the trigeminal spinal nucleus in other vertebrates, and the lateral descending nucleus is a special trigeminal sensory nucleus belonging to the infrared sensory system. In the present study we determined that the lateral descending nucleus is completely ensheathed by large numbers of substance P-like immunoreactive fibers. The distribution of these fibers seems to be similar to that of the thin vagal unmyelinated fibers, rather than to that of the thick trigeminal myelinated fibers. More substance P-like immunoreactive nerve fibers were observed in the lateral descending tract than in the descending tract. Almost no dense substance P-like immunoreactive fibers were found in these tracts rostral to the lateral descending nucleus or rostral to the subnucleus caudalis of the descending nucleus. The substance P-like immunoreactive fibers in the lateral descending tract extended to those of Lissauer's tract of the spinal cord, and the substance P-like immunoreactive fibers surrounding the Lissauer's tract were similar in appearance to those of the lateral descending nucleus. This nucleus seems to have developed from the elements existing in Lissauer's tract, and also to have a similar modulating function. The primary nucleus of the infrared sensory system is the most substance P-like immunoreactive nucleus in the trigeminal sensory system of this animal. Even in the trigeminal sensory system, substance P-like immunoreactive fibers seem not to be related solely to the nociceptive sensation.

Elastic properties and beta-sheet structure of connectin threads.

Connectin is a very long and flexible protein of striated muscle, linking myosin filaments to z discs in a sarcomere. Isolated native connectin in solution frequently forms elastic threads upon concentration of the solution, by side-by-side association of molecules. An X-ray diffraction study was performed to examine the presence of beta-sheet structure in artificially prepared threads. The elastic properties of such threads were measured at various temperatures. Negative temperature dependence of the elastic coefficient suggests that the elasticity of connectin threads is due to deformation of the three-dimensional structure and not to rubber-like behavior.

Studies toward the total synthesis of popolohuanone E: enantioselective synthesis of 8-O-methylpopolohuanone E.

[structure: see text]. 8-O-methylpopolohuanone E (2) was synthesized in a highly convergent manner starting from the cis-fused decalin derivative accessible from the (-)-Wieland-Miescher ketone analogue. The synthetic method features a biogenetic-type annulation of the phenolic and quinone segments to regioselectively construct the central tricyclic ring system as the key step.

Calcitonin gene-related peptide immunoreactivity in the trigeminal ganglion of Trimeresurus flavoviridis.

Crotaline snakes, which have infrared-sensitive pit organs, provide a good model for linking neuron morphology with sensory modality. In the trigeminal ganglion of the habu, Trimeresurus flavoviridis, cells positive for calcitonin gene-related peptide-like (CGRP) immunoreactivity were found to be of two types, darkly stained and lightly stained. They were pseudo-unipolar, having an axon divided into stem, peripheral branch, and central branch, all of which were 1 micron or less in diameter. Other, CGRP-negative cells in the ganglion were also pseudo-unipolar, but much larger. In configuration, some of the positive cells were similar to the neurons with A-delta fibers, and others to the neurons with C fibers that have been reported by other workers. On the basis of their distribution and density, and physiological studies by other workers, the CGRP-positive cells were judged to be not part of the infrared-receptive system, but to be involved in the transmission of nociception in small fibers.

Distribution of NADPH-diaphorase in the central nervous system of an infrared-sensitive snake, Trimeresurus flavoviridis.

The distribution of NADPH-diaphorase (NADPH-d) activity was studied in the central nervous system of an infrared sensitive snake. An inhibitor of nitric oxide synthase, dichloroindophenol (DPIP), was used to distinguish the characteristics of NADPH-d activity. Intensely and weakly NADPH-d-stained neurons and fibers were found in discrete regions throughout the snake brain and cervical spinal cord, such as the olfactory bulb, subcommissural organ, stratum griseum periventriculare, locus coeruleus, dorsal root, dorsal horn, and area X. It was particularly noticed that the trigeminal descending nuclei and reticular formation of the medulla oblongata contained many positive neurons and fibers, but the lateral descending nucleus and nucleus reticularis caloris (infrared sensory nuclei) certainly did not. The positive neurons and fibers were also observed in supraspinal sensory ganglia. DPIP inhibited NADPH-d activity in all regions except for the olfactory/vomeronasal nerve and glomeruli. The results prove for the first time the presence of NADPH-d activity in the ophidian brain and suggest that nitric oxide may be involved in many neural functions, but not in infrared sensory processing.

A new tectal afferent nucleus of the infrared sensory system in the medulla oblongata of Crotaline snakes.

The existence of an infrared sensory neuron group with ascending fibers which directly reach the optic tectum in Crotaline snakes was confirmed with three methods. (1) With the retrograde horseradish peroxidase (HRP) method, labeled neurons were not found within the nucleus descendens lateralis nervi trigemini (DLV), but in an unnamed cell group located immediately ventral to the DLV of the contralateral side at the transitional portion between the nucleus oralis (DVo) and the nucleus interpolaris (DVi). This unnamed cell group, which was seen only in the Crotalinae, was provisionally called the 'new nucleus'. (2) Normal brain series of 15 species were stained by the methods of Bodian-Otsuka, Klüver-Barrera and Nissl staining to compare the cytoarchitecture of the medulla oblongata. The 'new nucleus' was found only in species belonging to the Crotalinae. This nucleus was situated in fiber tracts which appeared to correspond to the lemniscus spinalis and tractus spino-cerebellaris of the reptilian medulla oblongata, and contained medium-sized multipolar or fusiform neurons. (3) In an electrophysiological study 16 single units responding unimodally to an infrared stimulus were recorded. Three of these recording sites were determined with Pontamine sky blue marking to be near or within the 'new nucleus'.

Infrared sensory neurons in the trigeminal ganglia of crotaline snakes: transganglionic HRP transport.

Trigeminal neurons were labeled by inserting HRP into holes cut in the pit receptor membranes of a crotaline snake, Agkistrodon blomhoffi brevicaudus. Neurons were labeled in the ophthalmic ganglion and the maxillary division of the maxillo-mandibular ganglion, and the HRP was further transported across the ganglia and through the lateral descending trigeminal tract (dlv) to label axon terminals exclusively in the dlv nucleus (DLV). In 6 successful preparations, 7.1-19.3% of totals of 5568-5986 cells in the maxillary division of the ganglion were labeled, but none at all were labeled in the mandibular division. Only a few or none at all were labeled in the ophthalmic ganglion. Cells in the two ganglia ranged in size from 10 to 55 micrometers, but large cells (greater than or equal to 40 micrometers) were scarce (4.9% of the total population). All HRP-labeled neurons fell in the median range of 20-39 micrometers. We concluded that these ganglion cells were infrared neurons, and were therefore the origin of the A delta fibers in the pit membrane. There were no HRP-labeled neurons above or below this range, in spite of the fact that smaller cells (less than or equal to 19 micrometers) made up 35.8% of the total population. In normal Nissl preparations we found both light- and dark-staining cells, but the size range of neither corresponded to the size range of infrared neurons.

A suspected infrared-recipient nucleus in the brainstem of the vampire bat, Desmodus rotundus.

We discovered in the brainstem of infrared-sensitive vampire bats, Desmodus rotundus, a specific nucleus not known in other species of bats. Because it corresponded in location and histological features to the infrared nucleus of infrared-sensitive snakes, we suggest the probability of its being part of the infrared processing system of vampire bats.