Acoustic characteristics of voluntary expiratory sounds after swallow for detecting dysphagia.

This research was designed to investigate the acoustic characteristics of voluntary expiratory sounds after swallow for detecting dysphagia. Forty-nine patients with complaints of swallow difficulty received a videofluorographic (VF) examination. They were divided into three groups: nine who did not have any apparent disease (Group N), 22 patients with head and neck cancer (Group H&N) and 18 patients with other diseases including cerebrovascular disease (Group OD). After liquid barium swallows, they exhaled voluntarily without voicing. Videofluorographic findings were classified into four groups: normal (Normal), acceptable swallow (Acceptable), swallow with residue (Resid) and swallows with penetration or aspiration (Pen/Asp). The duration of expiratory sounds was measured on the time waveform. Frequency characteristics of expiratory sounds were obtained using one-third octave band analysis ranging from 62·5 to 2000·0 Hz of central frequency. The averaged level of the 1000·0-Hz band was chosen as the reference band level (RB level). The revised averaged level of each band was obtained by subtracting the RB level from the averaged level of each band. Zero decibel of the revised magnitude of the 125·0-Hz band was set as the critical value to differentiate dysphagia (Resid or Pen/Asp) from no dysphagia (Normal or Acceptable). Comparison of this assessment with VF findings showed a significant percentage agreement (85·4%). These results suggest that frequency characteristics of post-swallow expiratory sounds can differentiate dysphagia from no dysphagia among multiple dysphagic patient groups.

Superconductivity induced by longitudinal ferromagnetic fluctuations in UCoGe.

From detailed angle-resolved NMR and Meissner measurements on a ferromagnetic (FM) superconductor UCoGe (T(Curie)∼2.5 K and T(SC)∼0.6 K), we show that superconductivity in UCoGe is tightly coupled with longitudinal FM spin fluctuations along the c axis. We found that magnetic fields along the c axis (H∥c) strongly suppress the FM fluctuations and that the superconductivity is observed in the limited magnetic-field region where the longitudinal FM spin fluctuations are active. These results, combined with model calculations, strongly suggest that the longitudinal FM spin fluctuations tuned by H∥c induce the unique spin-triplet superconductivity in UCoGe. This is the first clear example that FM fluctuations are intimately related with superconductivity.

Living donor liver transplantation from an asymptomatic mother who was a carrier for ornithine transcarbamylase deficiency.

Liver transplantation (LT) has been adopted as a radical treatment for ornithine transcarbamylase deficiency (OTCD), yielding favorable outcomes. Despite the fact that it is an inheritable disease, a blood relative who is heterozygous for the disorder must sometimes be used as a liver donor for living donor LT. There is ongoing discussion regarding the use of heterozygous donors, however, to our knowledge, no cases where donation was determined based on the Ornithine transcarbamylase (OTC) activity before LT have been reported. Between May 2001 and April 2011, 17 patients were indicated for living donor LT because of OTCD at our facility. There were three cases with heterozygous donor candidate (17.6%). All heterozygous candidates underwent a liver biopsy to measure their OTC activity before LT and made efforts to secure the safety of the both donor and recipient. Two of 3 candidates had headaches sometimes, and their activity was less than 40%, and thus they were not employed as the donor. One candidate with 104.4% activity was employed, yielding favorable outcomes. Our current experience supported the effectiveness of our donation criteria, however it is necessary to collect sufficient data on a large number of patients to confirm the safety of the procedure.

Enhanced NMR relaxation of Tomonaga-Luttinger liquids and the magnitude of the carbon hyperfine coupling in single-wall carbon nanotubes.

Recent transport measurements [Churchill et al. Nature Phys. 5, 321 (2009)] found a surprisingly large, 2-3 orders of magnitude larger than usual (13)C hyperfine coupling (HFC) in (13)C enriched single-wall carbon nanotubes. We formulate the theory of the nuclear relaxation time in the framework of the Tomonaga-Luttinger liquid theory to enable the determination of the HFC from recent data by Ihara et al. [Europhys. Lett. 90, 17,004 (2010)]. Though we find that 1/T(1) is orders of magnitude enhanced with respect to a Fermi-liquid behavior, the HFC has its usual, small value. Then, we reexamine the theoretical description used to extract the HFC from transport experiments and show that similar features could be obtained with HFC-independent system parameters.

GM1 ganglioside-bound amyloid beta-protein (A beta): a possible form of preamyloid in Alzheimer's disease.

The earliest event so far known that occurs in the brain affected with Alzheimer's disease (AD) is the deposition and fibril formation of amyloid beta-protein (A beta). A beta is cleaved from a glycosylated membrane protein, called beta-amyloid protein precursor, and normally secreted into the extracellular space. Here we report on the presence of membrane-bound A beta that tightly binds GM1 ganglioside. This suggests that this novel A beta species, rather than secreted A beta, may act as a 'seed' for amyloid and further that intracellular abnormalities in the membrane recycling already exist at the stage of amyloidogenesis.

Nuclear magnetic resonance measurements in dynamically controlled field pulse.

We present the architecture of the versatile nuclear magnetic resonance (NMR) spectrometer with software-defined radio technology and its application to the dynamically controlled pulsed magnetic fields. The pulse-field technology is the only solution to access magnetic fields greater than 50 T, but the NMR experiment in the pulsed magnetic field was difficult because of the continuously changing field strength. The dynamically controlled field pulse allows us to perform NMR experiment in a quasi-steady field condition by creating a constant magnetic field for a short time around the peak of the field pulse. We confirmed the reproducibility of the field pulses using the NMR spectroscopy as a high precision magnetometer. With the highly reproducible field strength, we succeeded in measuring the nuclear spin-lattice relaxation rate 1/T1, which had never been measured by the pulse-field NMR experiment without dynamic field control. We also implement the NMR spectrum measurement with both the frequency-sweep and field-sweep modes and discuss the appropriate choices of these modes depending on the magnetic properties of the sample to be measured. This development, with further improvement at a long-duration field pulse, will innovate the microscopic measurement in extremely high magnetic fields.

NMR study of the Mott transitions to superconductivity in the two Cs3C60 phases.

We report a NMR and magnetometry study on the expanded intercalated fulleride Cs3C60 in both its A15 and face centered cubic structures. NMR allowed us to evidence that both exhibit a first-order Mott transition to a superconducting state, occurring at distinct critical pressures p{c} and temperatures T{c}. Though the ground state magnetism of the Mott phases differs, their high T paramagnetic and superconducting properties are found similar, and the phase diagrams versus unit volume per C60 are superimposed. Thus, as expected for a strongly correlated system, the interball distance is the relevant parameter driving the electronic behavior and quantum transitions of these systems.

Anisotropic magnetic fluctuations in the ferromagnetic superconductor UCoGe studied by direction-dependent 59Co NMR measurements.

We have carried out direction-dependent 59Co NMR experiments on a single crystal sample of the ferromagnetic superconductor UCoGe in order to study the magnetic properties in the normal state. The Knight-shift and nuclear spin-lattice relaxation rate measurements provide microscopic evidence that both static and dynamic susceptibilities are ferromagnetic with strong Ising anisotropy. We discuss that superconductivity induced by these magnetic fluctuations prefers spin-triplet pairing state.

Expression of multiple tau isoforms and microtubule bundle formation in fibroblasts transfected with a single tau cDNA.

Tau proteins are a class of low molecular mass microtubule-associated proteins that are specifically expressed in the nervous system. A cDNA clone of adult rat tau was isolated and sequenced. To analyze functions of tau proteins in vivo, we carried out transfection experiments. A fibroblast cell line, which was transfected with the cDNA, expressed three bands of tau, while six bands were expressed in rat brain. After dephosphorylation, one of the three bands disappeared, demonstrating directly that phosphorylation was involved in the multiplicity of tau. Morphologically, we observed a thick bundle formation of microtubules in the transiently and stably tau-gene-transfected cells. In addition, we found that the production of tubulin was prominently enhanced in the stably transfected cells. Thus, we suppose that tau proteins promote polymerization of tubulin, form bundles of microtubules in vivo, and play important roles in growing and maintaining nerve cell processes.

Ubiquitin is a component of paired helical filaments in Alzheimer's disease.

Paired helical filaments (PHF), which constitute a distinct type of pathological neuronal fiber, are the principal constituent of neurofibrillary tangles that occur in the brain of patients with Alzheimer's disease. Their insolubility in sodium dodecyl sulfate and urea has prevented the analysis of their subunit composition by gel electrophoresis. A monoclonal antibody (DF2) was isolated that specifically labeled PHF at both the light and electron microscopic levels. It labeled a small polypeptide (5 kilodaltons) that was shown to be ubiquitin in immunoblots of the soluble fraction of brain homogenates. To obtain direct evidence that ubiquitin is a component of PHF, PHF were treated with concentrated formic acid and digested with lysylendopeptidase; ubiquitin-derived peptides were then identified by reversed-phase high-performance liquid chromatography. Two fragments in the PHF digest were identified as derived from ubiquitin by protein sequencing. This procedure should make possible definitive identification of other PHF components.

Alzheimer's disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea.

A method is described for the partial purification of the paired helical filaments that accumulate progressively in human neurons in Alzheimer's disease (senile dementia). Paired helical filaments have unusual solubility characteristics, including insolubility in sodium dodecyl sulfate, urea, reducing agent, and guanidine, which prevent analysis of their molecular composition by gel electrophoresis. The paired helical filaments appear to contain covalent bonds other than disulfide, which cross-link individual filaments into a rigid intracellular polymer. Thus, paired helical filaments appear to represent an example in neurons of an insoluble cross-linked protein. Covalently cross-linked protein polymers occur in lens senile cataracts and in terminally differentiated skin keratinocytes, suggesting that there may be a common mechanism for remodeling some structural proteins during cell aging.

Immunochemical evidence that fragments of phosphorylated MAP5 (MAP1B) are bound to neurofibrillary tangles in Alzheimer's disease.

To test the hypothesis that cortical neurons undergo massive sprouting in Alzheimer's disease brain, we investigated whether neurofibrillary tangles contain fetal antigens. Two monoclonal antibodies to tangles specifically labeled an approximately 300 kd protein in the neonatal brain homogenate, which was subsequently identified as MAP5 (MAP1B). Conversely, two monoclonal antibodies to MAP5 were found to stain tangles. All four reacted with only a phosphorylated species of MAP5. By careful immunochemical analysis, at least three independent phosphorylated epitopes that should have distinct conformations were shown to be shared by tangles and MAP5. However, several monoclonal antibodies to nonphosphorylated MAP5 did not stain tangles. From these observations, we conclude that fragments of phosphorylated MAP5 are bound to tangles. Since MAP5, in particular, a phosphorylated species, is known to be involved in neurite outgrowth, this result supports the sprouting hypothesis.

The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein.

We have purified and characterized the growth inhibitory factor (GIF) that is abundant in the normal human brain, but greatly reduced in the Alzheimer's disease (AD) brain. GIF inhibited survival and neurite formation of cortical neurons in vitro. Purified GIF is a 68 amino acid small protein, and its amino acid sequence is 70% identical to that of human metallothionein II with a 1 amino acid insert and a unique 6 amino acid insert in the NH2-terminal and the COOH-terminal portions, respectively. The antibodies to the unique sequence of GIF revealed a distinct subset of astrocytes in the gray matter that appears to be closely associated with neuronal perikarya and dendrites. In the AD cortex, the number of GIF-positive astrocytes was drastically reduced, suggesting that GIF is down-regulated in the subset of astrocytes during AD.

Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3(pE), in senile plaques.

We analyzed an amino-terminal modification of beta-amyloid (A beta) peptide in brain, using anti-A beta antibodies that distinguish distinct molecular species. Examination of cortical sections from 28 aged individuals with a wide range in senile plaque density revealed that a molecular species distinct from the standard A beta is deposited in the brain in a dominant and differential manner. This modified A beta peptide (A beta N3(pE)) starts at the 3rd aminoterminal residue of the standard A beta, glutamate, converted to pyroglutamate through intramolecular dehydration. Because plaques composed of A beta N3(pE) are present in equivalent or greater densities than those composed of standard A beta bearing the first amino-terminal residue (A beta N1) and because deposition of the former species appears to precede deposition of the latter, as confirmed with specimens from Down's syndrome patients, the processes involved in A beta N3(pE) production and retention may play an early and critical role in senile plaque formation.

Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43).

To learn about the carboxy-terminal extent of amyloid beta-protein (A beta) composition of senile plaques (SPs) in the brain affected with Alzheimer's disease (AD), we employed two end-specific monoclonal antibodies as immunocytochemical probes: one is specific for A beta 40, the carboxyl terminus of A beta 1-40, while the other is specific for A beta 42(43). In the AD cortex, all SPs that were labeled with an authentic antibody were A beta 42(43) positive, while only one-third of which, on the average, were A beta 40 positive. There was a strong correlation between A beta 40 positivity and mature plaques. Two familial AD cortices with the mutation of beta-amyloid protein precursor 717 (beta APP717) (Val to Ile) showed a remarkable predominance of A beta 42(43)-positive, A beta 40-negative plaques. Diffuse plaques, representing the earliest stage of A beta deposition, were exclusively positive for A beta 42(43), but completely negative for A beta 40.

Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments.

We have investigated ubiquitinated paired helical filaments, which produce a proteinaceous smear in SDS-polyacrylamide gel electrophoresis and immunoblotting. The smear consisted largely of the carboxy-terminal portion of tau and ubiquitin. The ubiquitin-targeted protein was identified as tau in paired helical filaments, and the conjugation sites were localized to the microtubule-binding region. Most ubiquitin in paired helical filaments occurred as a monoubiquitinated form, and only a small proportion of ubiquitin formed multiubiquitin chains. There was a ubiquitin-negative smear, in which tau was much less processed in the amino-terminal portion. This strongly suggests that the amino-terminal processing of tau in paired helical filaments precedes its ubiquitination.

The carboxyl third of tau is tightly bound to paired helical filaments.

To obtain definitive evidence that tau is a component of paired helical filaments (PHF) in Alzheimer's disease, we fractionated and sequenced PHF-derived peptides according to a previously described procedure. In the PHF digest, we found four independent tau peptides that were located in the carboxyl third of tau. Subsequent extensive analysis of the PHF digest did not provide any other tau peptides. The conventional PHF antiserum and a new antiserum directed toward formic acid-denatured PHF reacted with the distinct CNBr fragments of tau localized on the carboxy-terminal portion of tau by protein sequencing. From these observations, we conclude that the carboxyl third of tau is tightly bound to PHF.

Transition of Spleen Volume Long After Pediatric Living Donor Liver Transplantation for Biliary Atresia.

PURPOSE: After undergoing the Kasai procedure for biliary atresia (BA), most patients develop severe splenomegaly that tends to be improved by liver transplantation. However, fluctuations in splenic volume long after transplantation remain to be elucidated. PATIENTS AND METHODS: Seventy-one consecutive patients who had undergone pediatric living donor liver transplantation (LDLT) for BA were followed up in our outpatient clinic for 5 years. They were classified into 3 groups according to their clinical outcomes: a good course group (GC, n = 41) who were maintained on only 1 or without an immunosuppressant, a liver dysfunction group (LD, n = 18) who were maintained on 2 or 3 types of immunosuppressants, and a vascular complication group (VC, n = 11). Splenic and hepatic volumes were calculated by computed tomography in 464 examinations and the values compared before and after the treatment, especially in the VC group. RESULTS: Splenic volume decreased exponentially in the GC group, with splenic volume to standard spleen volume ratio (SD) being 1.59 (0.33) 5 years after liver transplantation. Splenic volume to standard spleen volume ratios were greater in the VC and LD groups than in the GC group. Patients in the VC group with portal vein stenosis developed liver atrophy and splenomegaly, whereas those with hepatic vein stenosis developed hepatomegaly and splenomegaly. Interventional radiation therapy tended to improve the associated symptoms. CONCLUSIONS: Fluctuations in splenic volume long after pediatric LDLT for BA may reflect various clinical conditions. Evaluation of both splenic and hepatic volumes can facilitate understanding clinical conditions following pediatric LDLT.

Antibody Drug Treatment for Steroid-Resistant Rejection After Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

BACKGROUND: Antibody drugs have been used to treat steroid-resistant rejection (SRR) after liver transplantation. Although anti-thymocyte globulin has been used for SRR after liver transplantation in place of muromonab-CD3 since 2011 in Japan, the effectiveness of anti-thymocyte globulin after pediatric living-donor liver transplantation (LDLT) has not yet been reported. The aim of this study was to evaluate the effectiveness of antibody drug treatment for SRR after pediatric LDLT in our single center. METHODS: Between May 2001 and December 2013, 220 pediatric LDLTs were performed. Initial immunosuppression after LDLT included tacrolimus and methylprednisolone therapy. Acute rejection was diagnosed by use of a liver biopsy and the administration of steroid pulse treatment, and SRR was defined as acute rejection refractory to the steroid pulse treatment. RESULTS: Acute rejection and SRR occurred in 74 (33.6%) and 16 patients (7.3%), respectively. The graft survival rates of non-SRR and SRR were 92.4% and 87.5%, respectively (P = .464). The median concentration of alanine aminotransferase before and after the administration of antibody drug was 193.5 mU/mL (range, 8-508) and 78 mU/mL (range, 9-655), respectively (P = .012). The median rejection activity index before and after the administration of antibody drugs was 5 (range, 2-9) and 1 (range, 0-9), respectively (P = .004). After antibody drug treatment, 12 patients had cytomegalovirus infections, 2 patients had Epstein-Barr virus infections, 3 patients had respiratory infections, and 1 patient had encephalitis. The cause of death in 1 patient with SRR was recurrence of infant fulminant hepatic failure. CONCLUSIONS: Antibody drug treatment for SRR after pediatric LDLT is safe and effective.