First Determination of the Level Structure of an sd-Shell Hypernucleus, _{Λ}

We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}→1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}→1/2^{+}), E1(1/2^{-}→1/2^{+}), and E1(1/2^{-}→3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN Interaction: Gamma-Ray Spectroscopy of _{Λ}

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

Search for the Θ+ pentaquark via the π(-)p→K(-)X reaction at 1.92 GeV/c.

The Θ(+) pentaquark baryon was searched for via the π(-)p→K(-)X reaction with a missing mass resolution of 1.4 MeV/c(2) (FWHM) at the Japan Proton Accelerator Research Complex (J-PARC). π(-) meson beams were incident on the liquid hydrogen target with a beam momentum of 1.92 GeV/c. No peak structure corresponding to the Θ(+) mass was observed. The upper limit of the production cross section averaged over the scattering angle of 2° to 15° in the laboratory frame is obtained to be 0.26 µb/sr in the mass region of 1.51-1.55 GeV/c(2). The upper limit of the Θ(+) decay width is obtained to be 0.72 and 3.1 MeV for J(Θ)(P)=1/2(+) and J(Θ)(P)=1/2(-), respectively, using the effective Lagrangian approach.

cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits.

The cardiac L-type Ca2+ channel is a textbook example of an ion channel regulated by protein phosphorylation; however, the molecular events that underlie its regulation remain unknown. Here, we report that in transiently transfected HEK293 cells expressing L-type channels, elevations in cAMP resulted in phosphorylation of the alpha1C and beta2a channel subunits and increases in channel activity. Channel phosphorylation and regulation were facilitated by submembrane targeting of protein kinase A (PKA), through association with an A-kinase anchoring protein called AKAP79. In transfected cells expressing a mutant AKAP79 that is unable to bind PKA, phosphorylation of the alpha1C subunit and regulation of channel activity were not observed. Furthermore, we have demonstrated that the association of an AKAP with PKA was required for beta-adrenergic receptor-mediated regulation of L-type channels in native cardiac myocytes, illustrating that the events observed in the heterologous expression system reflect those occurring in the native system. Mutation of Ser1928 to alanine in the C-terminus of the alpha1C subunit resulted in a complete loss of cAMP-mediated phosphorylation and a loss of channel regulation. Thus, the PKA-mediated regulation of L-type Ca2+ channels is critically dependent on a functional AKAP and phosphorylation of the alpha1C subunit at Ser1928.

Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine.

BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. RESULTS: One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. CONCLUSION: Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

Development of serotoninergic system in the brain and spinal cord of the chick.

(1) Development of serotonin positive cells and fibers was immunohistochemically studied by the use of an antibody against serotonin. (2) Serotoninergic neurons were first observed in the immature rohmbencephalon raphe nuclei on embryonic day (E)4, where two clusters of serotonin positive neurons were located: one observed at the rostral part of the rohmbencephalon corresponding to the dorsal raphe nuclei had many serotonin positive cells: the other located at the caudal part of the rohmbencephalon corresponding to the medullary raphe nuclei of the adult animals had only a small number of serotoninergic cells. (3) By E8 the number of serotonin positive cells in the brain stem increased, and virtually all the raphe nuclei found in an adult animal were located. (4) Serotonin positive fibers in the marginal layer reached up to the diencephalon and telencephalon on E6 and E8, respectively. (5) Serotonin positive cells were found beside the midline regions in the ventral part of the spinal cord of the embryonic as well as posthatching chick. (6) Because almost all the serotoninergic fibers in the spinal cord originated from the brain stem raphe nuclei, propriospinal serotonin positive cells were considered as phylogenetic vestiges. (7) Serotoninergic fibers were first found in the marginal layer of the cervical and lumbar spinal cord on E6 and E8, respectively. (8) There was a waiting period of a few days before they penetrated into the mantle layer. (9) Terminal arbolization of the serotoninergic fibers started from late embryonic periods (E16 less than), and was maximized within one week of hatching. (10) Thereafter the density of serotonin positive fibers decreased in all the regions of the spinal cord. (11) Developmental changes of the density of serotonin determined with a high performance liquid chromatography were the same as those determined through immunohistochemistry. Namely the density of serotonin increased linearly from E6 to hatching period, and reached the maximum value one week posthatching. (12( The density of the serotonin in the adult spinal cord was about half of the maximum value. (13) It is to say that the densities of serotonin and serotoninergic fibers transiently increased around one week posthatching. (14) Following the transient increase serotoninergic fibers were eliminated from the neuropil, the fibers were localized in the specific regions of the motor nucleus: motor neuron pools of extensor muscles of the hip joint in the lumbosacral spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Characteristics of ATPase activity and the subunit composition of myosin in the conduction system of bovine heart.

The ATPase activity, light chains and isoenzymes of myosin from specialized myocardial tissue (the A-V node, bundle of His, and right and left bundle branches) of bovine heart were compared with those of atrial and ventricular myosins. The order of Ca2+-activated ATPase activity was atrial greater than specialized myocardial tissue greater than ventricular myosin. SDS-polyacrylamide gel electrophoresis showed that myosin from the specialized myocardial tissue contained the light chains of both atrial and ventricular myosins. On the other hand, the specialized myocardial tissue contained one V3 isomyosin and showed no difference from ventricular myocardial tissue on pyrophosphate gel.

Immunohistochemical study on the development of serotoninergic neurons in the chick: I. Distribution of cell bodies and fibers in the brain.

The ontogenetic development of the serotoninergic system in the embryonic as well as in posthatching chick brain was studied with an indirect immunohistochemical technique with the aid of a specific antibody to serotonin (5-hydroxytryptamine). By embryonic day 4, rostral and caudal groups of serotonin-immunoreactive cell populations appeared in the mesencephalon and rostral and caudal rhombencephalon. At this stage, the rostral group had a considerable number of labelled cells that sent axons toward more rostral parts of brain, whereas the caudal group consisted of a small number of scattered serotonin-immunoreactive cells. The number of serotonin-positive cells increased with development, such that by embryonic day 8 almost all the serotoninergic cell groups found in the adult chick were already present. Serotoninergic-positive cells appeared in the paraventricular organ of the diencephalon as early as embryonic day 10. Judging from the cytoarchitectural organization of serotonin-immunoreactive cells, all of the serotoninergic cell groups in the chick brain seemed to be fully developed by embryonic day 16. On embryonic day 4, serotonin-immunoreactive fibers were found to enter into the marginal layer of the mesencephalon. Subsequently, serotonin-positive fibers ascended in the marginal layer of the brainstem up to the levels of the diencephalon and to the telencephalon on embryonic day 6 and 8, respectively. Serotonin-positive fibers, which first began to penetrate into the mantle layer on embryonic day 8, reached to the rostral pole of the telencephalon by embryonic day 10. In general, serotonin fibers were found in almost all brain regions by embryonic day 16. However, "terminal formation" in some nuclei did not seem to begin until the late embryonic or posthatching period. These observations indicate that the initial development of serotoninergic cell groups occurs during the first half of the 20th day of the incubation period of the chick. However, a longer time, ranging from early embryonic to posthatching stages, is necessary for the complete development of the serotoninergic projections.

Immunohistochemical study on the development of serotoninergic neurons in the chick: II. Distribution of cell bodies and fibers in the spinal cord.

Developmental changes of serotonin (5-hydroxytryptamine) neurons and fibers in the spinal cord of the embryo and posthatching chick were studied with immunohistochemical techniques with the aid of an antibody against serotonin. The first serotonin-immunoreactive fibers were found in the marginal layer of the cervical and lumbar spinal cord on embryonic days 6 and 8, respectively. There was a time lag of a few days between the first appearance of serotonin fibers in the marginal layer (embryonic days 6-8) and the time of penetration of serotonin fibers into the mantle layer (embryonic day 8 or older). The developments of serotonin innervation in the rostral parts of the spinal cord precedes that of caudal regions. Serotonin fibers penetrating into the mantle layer of the lumbar spinal cord were first found in lamina VII on embryonic day 8, whereas there were no serotonin-immunoreactive fibers in lamina IX by embryonic day 10. Large differences were found between embryonic day 16 and posthatching day 5 with regard to the density of serotonin varicosities and fibers in lamina IX, where profiles of soma and large-sized dendrites were heavily covered with varicosities. Laminae I and II first received serotonin fibers on embryonic day 16 and had a much denser innervation by posthatching day 5. There were no traces of serotonin fibers in lamina III in the stages examined up to posthatching day 5. Serotonin fibers were located in the lateral and ventral marginal layers in all specimens examined; only a few fibers were found in the dorsal marginal layer. Although few, serotonin-immunoreactive cell bodies were found in an area around the central canal of all animals from embryonic day 8 to adult. Some of these were located in the ependymal layer and sent processes toward the central canal; there were a small number of cells with long, fine processes. Serotonin-immunoreactive fibers in the spinal cord were not altered in regions rostral to the spinal transection, whereas all the serotoninergic fibers of the supraspinal origin were eliminated in the spinal cord caudal to the gap.

Developmental changes in density and distribution of serotoninergic fibers in the chick spinal cord.

Developmental changes of serotoninergic innervation in the chick spinal cord (third lumbosacral segment) were examined with an immunohistochemical technique using an antiserum to serotonin. In the 1-day-old hatched chick, serotoninergic fibers were located in laminae I, II, VII, IX, and X. A large number of serotonin-positive fibers and terminals were found around somal profiles of large neurons and in the neuropil of the medial and lateral parts of the lateral motor column (LMC). In the 1-week-old chick, the density of serotoninergic fibers was greatly increased in the posterior columns, and serotoninergic fibers were most densely aggregated in the dorsolateral part of the LMC. In the 2-week-old chick, a considerable decrease in the density of serotoninergic fibers was observed in the lateral funiculus and the gray matter (laminae I, II, VII, IX, and X). In the LMC, serotonin-positive fibers and terminals were largely absent from the neuropil, but were found preferentially around the somal profiles of large neurons. Between 1 and 2 weeks after hatching the density of varicosities and terminals in the neuropil of the dorsolateral and medial parts of the LMC decreased by 33% and 56%, respectively. In the 3-month-old chick, the density of serotoninergic fibers in laminae I, II, V, VII, and X had increased compared to younger ages. Serotonin-positive fibers were not evenly distributed in the LMC of the adult chicken; rather, they were densely aggregated around the soma and proximal dendrites of motoneurons in the dorsolateral LMC. Many neuronal soma in the medial and intermediate regions of the LMC lacked serotoninergic fibers.

Immunohistochemical study of the cells infiltrating human renal allografts by the ABC and the IGSS method using monoclonal antibodies.

Sixty renal allograft tissues obtained from 29 patients were stained with hematoxylin and eosin. These tissues were histologically classified into 4 patterns according to the distribution pattern of the infiltrating cells: normal, focal, focal-diffuse, and diffuse types. Clinical signs of acute rejection were observed in 88% of the patients with the diffuse type infiltration, and 83% of those with the focal-diffuse type infiltration but in only 13% of those with the focal type infiltration. Twenty-four renal allografts were analyzed by the ABC and the IGSS methods using monoclonal antibodies. The number of T cells (Leu 1) accounted for about 80% of the total number of infiltrating cells; 2-8% of the cells were B cells (Leu 12); about 10% were NK/K cells (Leu 7); and 4-6% were monocytes/macrophages (Leu M3). As to helper/inducer T cell (Leu3a) and killer/suppressor T cell (Leu2a), which are T lymphocyte subsets, there were more Leu3a- than Leu2a-positive cells in focal type tissue, but there were more Leu2a- than Leu3a-positive cells in focal-diffuse and diffuse type tissue. In most cases that developed clinical signs of acute rejection, there were more Leu2a- than Leu3a-positive cells. The Leu3a/Leu2a ratio in most of the AZA-administered cases dropped immediately after the transplantation and maintained a low value, but in the CSA-administered cases it decreased gradually post-transplant.

The prognostic value of serum immunosuppressive effect in patients with ovarian cancer.

Sixteen patients who underwent surgery and postoperative chemotherapy for carcinoma of the ovary were studied. Eleven survived more than 18 months without evidence of recurrence, and 5 died more than 5 months after surgery. Serial determinations were made preoperatively and postoperatively of the immunosuppressive effect of the serums of these patients on the response of normal lymphocytes to phytohemagglutinin stimulation. These determinations were plotted for each patient; the shapes of the curves for patients who survived are markedly different from those of patients who died. The prognostic value of these findings is discussed.

Immunosuppressive effect of serum in patients with ovarian carcinoma.

Cell-mediated immune response was measured in 23 patients with ovarian cystadenocarcinoma, 38 patients with benign ovarian tumor, and 44 healthy volunteers. The method used two indexes: the lymphocyte response per unit volume of peripheral blood to phytohemagglutinin (PHA) and the immunosuppressive effect of serum on the response of normal lymphocytes to PHA stimulation. The lymphocyte response per 50 microliter peripheral blood did not differ significantly between patients with ovarian cancer and healthy volunteers. The serum effect, in contrast, differed significantly between malignant and benign ovarian tumors, and was found to increase significantly even when the cancer masses were as small as about 5 x 5 x 5 cm in size, ie, in FIGO Stage I. It is our belief that the measurement of the serum effect in patients with any ovarian tumor enables the early detection of ovarian cancer.

Ipsilateral connections of the anterior cingulate cortex with the frontal and medial temporal cortices in the macaque monkey.

The present study was attempted to study ipsilateral corticocortical connections of the anterior part (area 24) of the cingulate cortex of the macaque monkey by means of wheat germ agglutinin-conjugated peroxidase (WGA-HRP) method. In 2 out of 4 Japanese monkeys (Macaca fuscata) that were injected with WGA-HRP into the anterior part of the cingulate cortex, the sites of injection were successfully localized within the cortical regions corresponding to areas 24a and 24b. The results obtained from these monkeys indicate that areas 24a and 24b in the anterior part of the cingulate cortex are reciprocally connected with the prefrontal, premotor, and motor cortical regions, and also with the medial temporal cortical regions. Areas 24a and 24b were strongly connected with the lateral and medial prefrontal cortices and area 6a beta of the premotor cortex, moderately with the remaining premotor cortex, and weakly with the motor cortex. In the medial temporal cortex, areas 24a and 24b were strongly connected with the prosubiculum, entorhinal cortex (area 28), and perirhinal cortex (areas 35 and 36), and weakly with areas TF and TH of the parahippocampal gyrus, throughout their rostrocaudal extent. In addition, areas 24a and 24b projected to the molecular layer of the CAI subfield of Ammon's horn and the external pyramidal layer of the presubiculum. Our findings suggest that areas 24a and 24b of the anterior cingulate cortex may constitute relays in the reciprocal pathways between the prefrontal cortex and the hippocampal, entorhinal and/or perirhinal cortical regions.

Comparative evaluation of a 5-day Hershberger assay utilizing mature male rats and a pubertal male assay for detection of flutamide's antiandrogenic activity.

A 5-day Hershberger assay utilizing mature male rats and a pubertal male assay were evaluated for the ability to detect antiandrogenic compounds such as flutamide, an androgen receptor antagonist. Six days after the operation, implantation with two silicon capsules containing testosterone (T) (30 mg/capsule) in castrated rats provided the ventral prostate and seminal vesicle weights as well as serum T and luteinizing hormone (LH) levels equivalent to those of the controls (non-castrated, non-implanted rats). Castrated rats implanted with two T-capsules (6 rats/dose) were treated by gavage for 5 days with vehicle (0.5% carboxymethylcellulose) or flutamide (0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles and the levator ani plus bulbocavernosus muscles (> or =0.6 mg/kg/day) and ventral prostate (> or =2.5 mg/kg/day), and an increase in serum LH levels (> or =2.5 mg/kg/day), but no changes in serum T levels. When age-matched intact male rats were treated with 10-mg/kg/day flutamide, a significant increase in serum T levels was observed concomitant with a tendency of increased LH. The organ weights were also decreased; however, the changes were less than those in the castrated, T-implanted rats. Immature intact male rats (10 rats/dose) were treated for 20 days with flutamide (0, 0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles, ventral prostate, and levator ani plus bulbocavernosus muscles at 2.5 and 10 mg/kg/day. Serum LH levels, but not T levels, were increased at 10 mg/kg/day. Statistical significance of some of these changes was not observed in the 6 animals/dose examined. Our findings support that the Hershberger assay, in the current conditions, is the most sensitive among the assays examined and a useful short-term screening method for the detection of antiandrogenic compounds.

Stented elephant trunk method for multiple thoracic aneurysms.

Stent-grafting and open graft replacement was introduced to reduce the complications of suture anastomosis in the descending aorta. We applied this technique in the treatment of a patient with multiple thoracic aneurysms. The elephant trunk procedure was used for thromboexclusion. A single branched graft was placed easily without twisting. In patients with aneurysms at both the proximal and distal thoracic aorta, combined stent-grafting and open graft replacement is an excellent approach.

Developmental changes in serotonin levels in the chick spinal cord and brain.

Developmental changes in 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the developing chick spinal cord and brain were examined using high-performance liquid chromatography with electrochemical detection and immunohistochemistry. On embryonic day (E)6 only small amounts of 5-HT (0.086 ng) and 5-HIAA (0.0144 ng) were found in the spinal cord. By contrast, large amounts of 5-HT (x30) and 5-HIAA (x60) were detected in non-neuronal tissue outside the spinal cord; a similar distribution of 5-HT was also detected by immunohistochemistry. Up to E10, the highest concentrations of 5-HT in the spinal cord were found in the cervical region, followed by the thoracic and lumbar regions. In embryos older than E16, as well as in posthatched chicks, however, the highest and lowest concentrations of 5-HT were found in the lumbar and thoracic spinal cord, respectively. The concentration of spinal cord 5-HT reached maximal values on posthatching day (P)7, after which there was a marked decrease. By P120, 5-HT levels in the spinal cord decreased to the same level as on E10-E16. Concentrations in the brain, however, gradually increased with development. The basic pattern of development of 5-HIAA was similar to that of 5-HT.

Differential innervation of specific motor neuron pools by serotoninergic fibers in the chick spinal cord.

A new technique in which cholera toxin subunit B conjugated to horseradish peroxidase is injected in chick muscles followed by perfusion with Zamboni's fixative for serotonin immunocytochemistry allows one to visualize immunoreactive fibers and retrogradely labelled motoneurons in alternate sections. Using these procedures, we have found that there is a differential innervation by serotoninergic fibers of motoneuron pools that project to specific muscles or muscle groups. Dense clusters of serotonin-positive fibers were located in the motoneuron pools of extensors of the hip joint consisting of the lateral iliotibialis, ischioflexorius, iliofibularis, accessorius and caudilioflexorius muscles.

The pattern of distribution of serotoninergic fibers in the anterior horn of the chick spinal cord.

The pattern of distribution of serotonin positive fibers in the motor nuclei of the chick spinal cord was examined immunohistochemically by using an antiserum against serotonin. A dense aggregation of serotoninergic fibers was located around anterior horn cells in the cervical spinal cord. In the brachial spinal cord, serotoninergic fibers were densely aggregated in the medial motor column and in the parts of the lateral motor column. There were two regions of serotonin immunoreactivity in the lateral motor column of the brachial spinal cord; one located in the ventromedial regions where a dense aggregation of serotoninergic fibers was found, and the reminder of the lateral motor column where only a few serotoninergic fibers were observed. The region containing a dense cluster of serotoninergic fibres around profiles of motoneuron somata and proximal dendrites appears to correspond to motor neuron pools of flexor muscles. In the thoracic spinal cord a high density of serotoninergic fibers was found in the motor nucleus. In the lumbosacral spinal cord (segments LS1-LS8) serotoninergic fibers were not observed in the medial motor column. However, there were five regions in the lateral motor column, where a high density of serotoninergic fibers was found. These very likely correspond to motor neuron pools of muscles which extend the hip joint.

The effect of body position on a free-floating ball thrombus as observed by transesophageal echocardiography.

Two cases of free-floating left atrial ball thrombi (FLABT) in association with mitral stenosis were observed by transesophageal echocardiography (TEE). Our report describes the relation between body position and thrombi kinetics. Both cases demonstrated similar kinetics. In the supine and right lateral decubitus positions, the thrombi recoiled from and sometimes became entrapped within the mitral valve. In the sitting and left lateral decubitus positions, the thrombi appeared to be nearly fixed and did not contact with the mitral valve. Our results indicate that the latter two positions prevent thrombi disintegration and incarceration into the mitral valve. Finally, TEE is an extremely useful tool for assessing the safest position for individuals with FLABT.