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Biomedical subjects

Hajime Tanaka

Publications and source records attributed to Hajime Tanaka.

At least 37 records · Page 2Linked to original sources

Origin of the excess wing and slow beta relaxation of glass formers: a unified picture of local orientational fluctuations.

Here we consider the relation between the excess wing and the slow beta relaxation, focusing on the degree of the coupling between cooperative rotational motion associated with creation and annihilation of metastable islands (alpha mode) and local rotational jump motion in a cage (slow beta mode). For a strongly coupled case the slow beta mode appears as the excess wing having the character of the alpha mode, while for a fully decoupled case as an independent local mode having the Arrhenius temperature dependence. We argue that the degree of the coupling between the two modes is controlled by the following two factors: (i) the relation between the characteristic size of metastable islands and the cage size and (ii) the disparity between the high-temperature Arrhenius behavior of the alpha mode and the Arrhenius behavior of the slow beta mode.

Journal Article↗

Enhancement of cytotoxic T-lymphocyte responses in patients with gastrointestinal malignancies following vaccination with CEA peptide-pulsed dendritic cells.

Carcinoembryonic antigen (CEA) is strongly expressed in a vast majority of gastrointestinal carcinomas. Recently, epitope peptides of CEA were identified. We have demonstrated HLA-A24-restricted peptide, CEA652[9] (TYACFVSNL), was capable of eliciting specific cytotoxic T lymphocytes (CTLs) which could lyse tumor cells expressing HLA-A24 and CEA. HLA-A24 is the most applicable MHC class I allele in the Japanese population. In this pilot study, we have used the peptide-pulsed dendritic cells (DCs) generated from peripheral blood mononuclear cells (PBMCs) supplemented with GM-CSF and IL-4 as the source of the vaccine. Eight patients with advanced CEA-expressing gastrointestinal malignancies received subcutaneous injections every 2 or 3 weeks. Immunomonitoring was performed by ELISpot (enzyme-linked immunosorbent spot) assay to measure the precursor frequency of CTLs and their capacity to elicit antitumor CTLs in vitro. Four of seven patients have developed their CTL response after vaccinations. DTH reaction was observed in one of eight patients at the DC-injected site. Skin biopsy at the injected site showed the infiltration of the lymphocytes. Furthermore, A24/CEA peptide tetramer assay revealed an increase in peptide-specific T-cell precursor frequency in vaccinated patients. No significant toxic adverse effects were observed, except for mild diarrhea in one case after three vaccinations. Three patients have shown stabilization of the disease after vaccinations. In conclusion, our results clearly demonstrated that our vaccination protocol was safe and might develop a CEA-specific CTL response in cancer patients.

Carcinoembryonic Antigen↗

Liquid-liquid transition in the molecular liquid triphenyl phosphite.

We found both nucleation-growth-type and spinodal-decomposition-type transformation from one liquid state to another in a "molecular liquid," triphenyl phosphite (TPP). Binodal and spinodal temperatures of this transition at ambient pressure were determined by the characteristics of morphological evolution, domain-growth kinetics, and rheological evolution. Furthermore, a distinct thermal signature of the glass transition of a second liquid was also detected in addition to that of an ordinary liquid. These findings strongly suggest the existence of a liquid-liquid transition; more precisely, a transformation of one supercooled liquid to a glassy state of another liquid, in TPP.

Journal Article↗

Radiation-induced rectal cancer originating from a rectocutaneous fistula: report of a case.

This report describes a patient with radiation-induced rectal cancer with an unusual history. A 51-year-old man was admitted in 2000 because of ichorrhea of the skin on the left loin. The patient had received irradiation for a suspicious diagnosis of a malignant tumor in the pelvic cavity in 1975. A subcutaneous abscess in the right loin appeared in 1989, and rectocutaneous fistula was noted in 1992. Moreover, radiation-induced rectal cancer developed in 2000. Plain computed tomography and magnetic resonance imaging of the pelvis demonstrated a presacral mass and tumor in the rectum. Finally, we diagnosed the presacral mass to be an abscess attached to the center of the rectal cancer. The rectum was resected by Miles' operation and a colostomy of the sigmoid colon was also performed. Many cases of radiation-induced rectal cancer have been reported. However, this is a rare case of radiation-induced rectal cancer originating from a presacral abscess and rectocutaneous fistula.

Abscess↗

Relationship between Porphyromonas gingivalis, Epstein-Barr virus infection and reactivation in periodontitis.

The aim of this study was to assess the relationship-between Porphyromonas gingivalis, Epstein-Barr virus (EBV) infection and reactivation in periodontitis using real-time PCR. The mean proportion of P. gingivalis cells to total bacterial cells in the saliva from EBV-positive periodontitis patients was significantly higher than that in saliva from EBV-negative patients. An EBV-positive B-cell line was used to determine whether P. gingivalis sonicate induced reactivation of EBV, using real-time PCR to measure the virus genome in the culture medium. A significant increase in EBV numbers was observed after the stimulation with P. gingivalis sonicate. These findings suggest that the interaction between EBV and P. gingivalis is bi-directional, with EBV reactivation suppressing host defenses and permitting overgrowth of P. gingivalis, and P. gingivalis having the potential to induce EBV reactivation.

Adult↗

[Efficacy and safety of weekly taxol (TXL) for advanced recurrent breast cancer evaluated in a multi-center cooperative clinical trial].

A multi-center cooperative clinical trial was undertaken to evaluate the safety and efficacy of weekly taxol (TXL) therapy combined with short-premedication as a pretreatment in an effort to determine if TXL can be used in ambulatory treatment. TXL was administered at 60 mg/m2 to patients with advanced recurrent breast cancer once a week without a rest or with a rest for 1 week after treatment for 3 weeks. A total of 36 patients were finally enrolled. The site of recurrence was the local region in 8 patients, lung/pleura in 24, liver in 9, bone in 16, lymph nodes in 15, epicardium in 2, and brain metastasis in 2. The response was CR in 2, PR in 12, NC in 9, PD in 8, and NE in 5, with a response rate of 45.2%. Grade 4 anorexia was reported as non-hematotoxicity. All other adverse reactions, such as myalgia/arthralgia and peripheral neuropathy, were mild (grade 1 or 2). Hematotoxic effects observed in this study included only grade 3 leukopenia in 5 patients, neutropenia in 4, and decreases in hemoglobin in 1.

Adult↗

[Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia].

Tizanidine is a centrally acting alpha-2 adrenoreceptor agonist widely used in the treatment of spasticity in patients with cerebral or spinal injury, and it is causing drawsiness in some of them. Based on these drug actions, we administered tizanidine to 21 spastic quadriplegic children with severe sleep disturbance not improved by conventional therapies. All these patients were showing abnormalities of both the induction and maintenance of sleep. The dosage of tizanidine was 0.1 to 0.2 mg/kg/day, divided into two or three doses. If daytime drowsiness was severe, tizanidine admistration was restricted to just prior to bedtime. In 13 patients (61.9%), we found improvement in sleep induction and/or maintenance. Moreover, patients' families were satisfied with the treatment. There were no detectable side effects except facial pallor in two patients (9.5%) whose treatment was discontinued. Severe muscle hypertonia causes severe pain, which generates strong sympathetic nerve activity and subsequent sleep disturbance. We consider that tizanidine has direct effects on the induction of sleep, and promotes muscular relaxation bringing about good sleep. We conclude that tizanidine is useful for the treatment of refractory sleep disturbance in spastic quadriplegic patients.

Adolescent↗

Possible resolution of the Kauzmann paradox in supercooled liquids.

Generally, the entropy of the supercooled liquid decreases more rapidly than that of the crystal. Thus, the former, if we extrapolate it smoothly below the glass-transition temperature T(g), becomes equal to the latter at the so-called Kauzmann temperature T(K). Further extrapolation below T(K) leads to the unphysical situation that the entropy of disordered liquid is lower than the ordered crystal, which results in the violation of the third law of thermodynamics. This is known as the "Kauzmann paradox" which has been the key problem of liquid-glass transition for a long time. Here we propose a simple resolution of the Kauzmann paradox by answering a fundamental question of how deeply we can supercool a liquid. We argue that the lower metastable limit T(LML), below which a liquid should crystallize before its structural relaxation, is located above the Kauzmann temperature T(K). Thus, the entropy crisis at T(K) is naturally avoided by crystallization. We suggest that it is dynamic heterogeneity that destabilizes a deeply supercooled "equilibrium" liquid state as well as a glassy state against crystallization. This may have a significant implication on the stability of a glassy state, which is of industrial importance in relation to the storage of glassy material.

Journal Article↗

Relation between thermodynamics and kinetics of glass-forming liquids.

Vitrification of a supercooled liquid is often characterized by the hypothetical kinetic instability point, the Vogel-Fulcher temperature T0, and the thermodynamic one, the Kauzmann temperature T(K). The widely believed relation T0 congruent with T(K) is regarded as the supporting evidence of a direct connection between the thermodynamics and kinetics of glass-forming liquids. Here we demonstrate that T(K)/T(0) systematically increases from unity with a decrease in the fragility, contrary to the common belief. This systematic deviation may be explained by a synergistic effect between the weaker cooperativity and the stronger tendency of short-range ordering in stronger glass formers.

Journal Article↗

Optical manipulation of defects in a lyotropic lamellar phase.

Here we study the line defect in a hyperswollen lamellar phase of lyotropic liquid crystal by applying a laser trapping method. We have succeeded in directly measuring the tension of a single isolated line defect and the adhesion energy between two defects. We demonstrate a new possibility of intentional patterning of various defects by direct optical manipulation. Furthermore, local rheological measurements provide information on the membrane organization around a particle and also evidence suggesting that flow in a lamellar phase has a two-dimensional nature.

Journal Article↗

Detection of Streptococcus anginosus and 8-hydroxydeoxyguanosine in saliva.

Several studies have demonstrated a close association between Streptococcus (S.) anginosus infection and head and neck cancer. Accumulation of 8-hydroxy-deoxyguanosine (8-OHdG), which may result from the continuous generation of reactive oxygen species associated with chronic inflammation, has been reported in human preneoplastic lesions and in cancerous tissues. The purpose of the present investigation was to assess the salivary levels of S. anginosus and 8-OHdG in patients with periodontitis. Salivary levels of S. anginosus were measured by real-time PCR. S. anginosus was detected in 28 out of 38 (73.7%) of subjects. The 8-OHdG level was significantly higher in patients positive for S. anginosus than in patients negative for the bacterium. A significant decrease in S. anginosus and 8-OHdG levels was observed after initial periodontal treatment. Our findings indicate that, although the levels of S. anginosus are relatively low, there is a correlation between the salivary level of S. anginosus and 8-OHdG, and that periodontal treatment can decrease the levels of these hazard factors.

8-Hydroxy-2'-Deoxyguanosine↗

[Effective combination chemotherapy using weekly trastuzumab and paclitaxel in the treatment of a recurrent breast cancer patient with liver metastases].

A 48-year-old woman was diagnosed with multiple locoregional recurrence five months after receiving breast conserving surgery, and she underwent mastectomy. CEF therapy was combined following surgery; however, lung metastases developed 9 months after the initial surgery. A CR has been observed after monthly use of docetaxel alone for 14 months. Since multiple liver metastases were detected 17 months later, the patient was given monthly docetaxel infusions for 2 months followed by weekly trastuzumab infusions for 8 weeks, resulting in PD. Thereafter, combination of weekly trastuzumab with paclitaxel was used and a nearly CR remained for 10 months. Although multiple brain metastases were seen 36 months later, vertigo was mostly controlled with whole brain radiotherapy. Combination of weekly trastuzumab and paclitaxel therapy is effective for liver metastases from breast cancer and useful considering the slight side effects and possibility of long-term administration.

Antibodies, Monoclonal↗

Spontaneous partitioning of particles into cellar structures in a membrane system.

Membranes are often used for material partitioning in biological systems and industry. Here we report a novel physical mechanism of particle partitioning using topological transformation of bilayer membranes. Upon phase separation of a homogeneous sponge phase of a membrane system into a dense sponge and a water phase, we found quite unusual partitioning behavior of particles into the cellar structure of a water phase. The compartments next to one having particles always have no particles, and those next to a compartment having no particles always have particles. We confirm that this partitioning is purely geometrically induced, and thus it may be universal.

Lipid Bilayers↗

Laponite: aging and shear rejuvenation of a colloidal glass.

We study the nonlinear rheological behavior and the microscopic particle dynamics for a colloidal glass, to see whether recently developed models for driven glassy systems can be applied to predict the rheology. Qualitatively, all the findings predicted by the models can be retrieved in our system. Notably, the viscosity decreases strongly with the shear rate. Since it is difficult to predict non-Newtonian viscosities of colloidal systems due to long-ranged hydrodynamic interactions, this shows the promise of this approach for predicting flow behavior. In addition, the measurements allow us to relate the microscopic diffusion dynamics to the macroscopic viscosity of the system.

Journal Article↗

Nonuniversal nature of dynamic critical anomaly in polymer solutions.

Critical anomaly of viscosity has been studied for ideal polymer solutions, focusing on its dependence on the molecular weight of polymer M(w). According to the conventional understanding that polymer solutions should belong to the same dynamic universal class as classical fluids, the critical exponent of viscosity y(c) should be a universal constant (approximately 0.04). Contrary to this, we find that y(c) significantly decreases with increasing M(w). This unusual behavior can be explained by the dynamic coupling of critical concentration fluctuations with an additional slow viscoelastic mode intrinsic to polymer solutions. Our dynamic light scattering measurements support this picture.

Journal Article↗

A novel mutation in the GNE gene and a linkage disequilibrium in Japanese pedigrees.

Distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive muscular disorder characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood and sparing of the quadricep muscles. The UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene was recently identified as the causative gene for hereditary inclusion body myopathy (HIBM). To investigate whether DMRV and HIBM are allelic diseases, we conducted mutational analysis of the GNE gene of six Japanese DMRV pedigrees and found that all the pedigrees share a homozygous mutation (V572L) associated with a strong linkage disequilibrium, suggesting a strong founder effect in Japanese DMRV pedigrees.

Carbohydrate Epimerases↗

A case of neurilemmoma of the breast.

Neurilemmoma of the breast is rarely seen, although it is common at intracranial or peripheral sites. There have been only 14 cases described in the literature. We present the fifteenth case of a 64-year-old woman with neurilemmoma of the breast, the first to be diagnosed by fine needle aspiration cytology. Fibroadenoma must be distinguished from this tumor. Complete removal is the treatment of choice, considering the possibility of local recurrence and malignant change.

Biopsy, Needle↗

[Combined use of melatonin and low-dose flunitrazepam for treatment of sleep disturbance in a child with spastic quadriplegia: evaluation using polysomnography].

A 14-year-old boy born at 39 gestational weeks with the birth weight of 3,250 g, had severe mental retardation and spastic quadriplegia of unknown etiology from early childhood. At 7 years of age, disturbance of night sleep appeared with several awakenings. Combined treatment with melatonin (MLT; 0.04 mg/kg) and flunitrazepam (FNZ; 0.025 mg/kg) was more effective than monotherapy with FNZ for the sleep disturbance. Difference of the effects of the combined therapy and the monotherapy for the sleep disturbance were assessed by polysomnographies (PSGs), consisted of EEG (C3, C4), bipolar EOG and surface EMG on the mentalis muscle. The PSGs were performed twice at 13 years 6 months old, and at 14 years 1 month old. In both trials, the number of awakening was fewer, total sleep time was longer, percent (%) stage I and II were lower and %REM sleep was larger in combined MLT and FNZ therapy than in FNZ monotherapy. The present study suggests that the combined MLT and FNZ therapy not only reduces awakening during sleep but also normalizes sleep architecture. This therapy is valuable because normalization of sleep is important for the developing brain as it reflects the normal functioning of the aminergic neurons of the midbrain and the brainstem which have important roles for morphological and functional development of the brain in immature brain.

Adolescent↗