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Biomedical subjects

Satoshi Tanaka

Publications and source records attributed to Satoshi Tanaka.

At least 55 records · Page 3Linked to original sources

Porphyrin-based organogels: control of the aggregation mode by a pyridine-carboxylic acid interaction.

To find a new strategy for designing porphyrin-based organogelators, hydrogen-bond-donating (carboxylic acid)/accepting (pyridine) substituents or electron-donating (dialkylamino)/withdrawing (pyridine) substituents were introduced into peripheral positions of a porphyrin (1cp or 1ep, respectively), and the gelation properties were compared with those of symmetrical reference compounds bearing two pyridyl substituents or two ester groups (1pp or 1ee, respectively). It was found that the symmetrical molecules show a solubility that is quite inferior to that of 1cp and 1ep having a dipole moment and precipitate from most organic solvents. 1cp, 1ep, and 1ee formed gels with cyclohexane, methylcyclohexane, and several alcoholic solvents, but scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations revealed that their superstructures constructed in the organogels are very different. In cyclohexane, 1cp resulted in a sheetlike structure, whereas 1ep and 1ee resulted in a fiberlike structure. The difference is attributed to the two-dimensional interactive forces in 1cp consisting of the porphyrin-porphyrin pi-pi stacking and the carboxylic acid-pyridine hydrogen bonding. In fact, when the hydrogen-bonding interaction was weakened by alcoholic solvents or by adding pyridine or N,N-(dimethylamino)pyridine, the sheetlike structure was transfigured to the fiberlike structure. Further detailed analyses of their aggregation modes were conducted by spectroscopic methods such as ultraviolet-visible (UV-vis) absorption, Fourier transform infrared (FT-IR), and X-ray diffraction (XRD). On the basis of these findings, the influence of these peripheral substituents on the gel formation and the aggregation mode was discussed.

Journal Article↗

Repetitive transcranial magnetic stimulation induces kf-1 expression in the rat brain.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive approach used for stimulating the brain, and has proven effective in the treatment of depression, however the mechanism of its antidepressant action is unknown. Recently, we have reported the induction of kf-1 in rat frontal cortex and hippocampus after chronic antidepressant treatment and repeated electroconvulsive treatment (ECT). In this study, we demonstrated the induction of kf-1 after rTMS in the rat frontal cortex and hippocampus, but not in hypothalamus. Our data suggest that kf-1 may be a common functional molecule that is increased after antidepressant treatment, ECT and rTMS. In conclusion, it is proposed that induction of kf-1 may be associated with the treatment induced adaptive neural plasticity in the brain, which is a long-term target for their antidepressant action.

Animals↗

Intracerebral pain processing in a Yoga Master who claims not to feel pain during meditation.

We recorded magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) following noxious laser stimulation in a Yoga Master who claims not to feel pain when meditating. As for background MEG activity, the power of alpha frequency bands peaking at around 10 Hz was much increased during meditation over occipital, parietal and temporal regions, when compared with the non-meditative state, which might mean the subject was very relaxed, though he did not fall asleep, during meditation. Primary pain-related cortical activities recorded from primary (SI) and secondary somatosensory cortices (SII) by MEG were very weak or absent during meditation. As for fMRI recording, there were remarkable changes in levels of activity in the thalamus, SII-insula (mainly the insula) and cingulate cortex between meditation and non-meditation. Activities in all three regions were increased during non-meditation, similar to results in normal subjects. In contrast, activities in all three regions were weaker during meditation, and the level was lower than the baseline in the thalamus. Recent neuroimaging and electrophysiological studies have clarified that the emotional aspect of pain perception mainly involves the insula and cingulate cortex. Though we cannot clearly explain this unusual condition in the Yoga Master, a change of multiple regions relating to pain perception could be responsible, since pain is a complex sensory and emotional experience.

Aged↗

Modality-specific cognitive function of medial and lateral human Brodmann area 6.

Despite the fact that human Brodmann area 6 (BA6), a traditional "motor" area, is active during higher motor control involving various cognitive operations, the functional specialization within BA6 in the cognitive domain is essentially unknown. Furthermore, its functional relevance in cognition has been questioned because brain activity in BA6 during cognitive tasks has often been explained away as a concomitant, latent motor process. Therefore, we examined the structural-functional relationship of human BA6 in nonmotor cognitive functions and its functional relevance using both functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS). Subjects performed mental-operation (MO) tasks in which they serially updated verbal and spatial mental representations (MO-v and MO-s). In the fMRI experiments, activity in the medial BA6 was more increased in MO-v, whereas the activity in the lateral BA6 in both hemispheres was more in MO-s. Low-frequency rTMS to the medial BA6 disrupted only the performance of MO-v, whereas rTMS to the lateral BA6 in both hemispheres disrupted only MO-s. Hence the converging results demonstrate a functional double dissociation in which medial BA6 has a critical role in updating verbal information and lateral BA6 has a role in updating spatial information. The present study provides direct physiological evidence of modality-specific cognitive function within human BA6.

Adult↗

Stage-by-stage change in DNA methylation status of Dnmt1 locus during mouse early development.

Methylation of DNA is involved in tissue-specific gene control, and establishment of DNA methylation pattern in the genome is thought to be essential for embryonic development. Three isoforms of Dnmt1 (DNA methyltransferase 1) transcripts, Dnmt1s, Dnmt1o, and Dnmt1p, are produced by alternative usage of multiple first exons. Dnmt1s is expressed in somatic cells. Dnmt1p is found only in pachytene spermatocytes, whereas Dnmt1o is specific to oocytes and preimplantation embryos. Here we determined that there is a tissue-dependent differentially methylated region (T-DMR) in the 5' region of Dnmt1o but not in that of the Dnmt1s/1p. The methylation status of the Dnmt1o T-DMR was distinctively different in the oocyte from that in the sperm and adult somatic tissues and changed at each stage from fertilization to blastocyst stage, suggesting that active methylation and demethylation occur during preimplantation development. The T-DMR was highly methylated in somatic cells and embryonic stem cells. Analysis using Dnmt-deficient embryonic stem cell lines revealed that Dnmt1, Dnmt3a, and Dnmt3b are each partially responsible for maintenance of methylation of Dnmt1o T-DMR. In particular, there are compensatory and cooperative roles between Dnmt3a and Dnmt3b. Thus, the regulatory region of Dnmt1o, but not of Dnmt1s/1p, appeared to be a target of DNA methylation. The present study also suggested that the DNA methylation status of the gene region dynamically changes during embryogenesis independently of the change in the bulk DNA methylation status.

5' Untranslated Regions↗

Ca2+ influx-mediated histamine synthesis and IL-6 release in mast cells activated by monomeric IgE.

We previously demonstrated that histamine synthesis is drastically induced upon sensitization with an anti-DNP IgE clone, SPE-7, in IL-3-dependent mouse bone marrow derived mast cells (BMMC). We found that Ca2+ mobilization induced by SPE-7 exhibited a similar profile to the capacitative Ca2+ entry evoked by thapsigargin. Potentials for activation of mast cells were found to vary between different IgE clones, and a monovalent hapten, DNP-lysine, suppressed the activation induced by SPE-7. Ca2+ mobilization induced by SPE-7 was suppressed potently by the specific store-operated Ca2+ channel inhibitor, SK&F 96365, but not at all by Ca2+ channel inhibitors with more broad spectrum, La3+ and Gd3+, whereas the Ca2+ mobilization induced by Ag stimulation was suppressed by these inhibitors. Ca2+ mobilization was also induced by SPE-7 in in vitro differentiated mast cells, although the increases in histamine synthesis and IL-6 release were smaller than those in BMMC. These results suggest that Ca2+ influx operated by a distinct mechanism from that in Ag stimulation is essential for increased histamine synthesis and IL-6 release in mast cells.

Animals↗

Anesthetic management of a patient with beta-thalassemia intermedia undergoing splenectomy: a case report.

A 37-year-old man with beta-thalassemia intermedia (betaTI), a rare disease caused by partial or complete deficiency of beta-globin chain synthesis, fell into a hemolytic crisis. Severe anemia persisted despite frequent transfusions. Therefore, he was scheduled for splenectomy to alleviate the anemia. The preoperative laboratory data showed marked anemia and liver dysfunction. Echocardiography revealed hyperkinetic left ventricular motion and increased cardiac index (CI), indicating a compensatory hyperdynamic circulation induced by persistent, severe anemia. Our strategy during general anesthesia was to keep the hyperkinetic cardiovascular system steady. Hence, the hemodynamic parameters including the CI were measured using a Swan-Ganz catheter, and other physiological parameters were monitored perioperatively. Anesthesia was maintained with balanced anesthesia: isoflurane at low concentrations and fentanyl to avoid cardiovascular depression. Throughout the operation, vital signs were kept stable and the lactate/pyruvate ratio was unchanged, indicating that anaerobic metabolism did not increase. We report successful anesthetic management with attention to hemodynamic changes in a patient with betaTI.

Adult↗

Combined neurolytic block of celiac, inferior mesenteric, and superior hypogastric plexuses for incapacitating abdominal and/or pelvic cancer pain.

Thirty-five patients with extensive abdominal or pelvic cancer who suffered uncontrolled, diffuse, extensive, and incapacitating pain were treated with a combination of neurolytic celiac plexus block (CPB), inferior mesenteric plexus block (IMPB), and superior hypogastric plexus block (SHGPB). The combination of neurolytic CPB, IMPB, and SHGPB was performed with alcohol, mainly using a transintervetebral disc approach. The combination neurolysis produced effective immediate pain relief in all the patients (visual analog scale (VAS), reduced from 8.8 +/- 0.2 to 0). This pain relief persisted during the first 3 months (VAS, 2.3 +/- 0.5) or until death. Morphine consumption was significantly decreased for the first 1 month (from 96 +/- 29 mg to 31 +/- 10 mg per day) after the neurolysis and thereafter continued to be lower than before the surgery, though not significantly so. No serious complications were observed to have been caused by the neurolytic procedure on the three sympathetic plexuses. Our preliminary clinical results suggest that the combination of neurolytic CPB, IMPB, and SHGPB improves the quality of life of patients who have incapacitating cancer pain, by reducing both the intensity of the pain and their opioid consumption, without serious complications. This combination procedure may provide a new therapeutic option for pain relief in patients with advanced cancer.

Abdominal Neoplasms↗

Quantitation of O6-methylguanine-DNA methyltransferase gene messenger RNA in gliomas by means of real-time RT-PCR and clinical response to nitrosoureas.

1. O6-methylguanine-DNA methyltransferase (MGMT) mRNA was measured in 50 malignant gliomas that had received 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) after the resection of the tumor by real-time reverse transcription-polymerase chain reaction (RT-PCR) using TaqMan probe. 2. The mean absolute value of MGMTmRNA normalized to the level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for 50 tumors was 1.29 x 10(4)+/- 1.28 x 10(4) copy/microg RNA (mean +/- SD). The amount of MGMTmRNA less than 6 x 10(3) copy/microg RNA was the most significant factor in predicting the initial effect of treatment with ACNU by multi-variant regression analysis (p = 0.0157). 3. These results suggest that quantitation of MGMTmRNA is the excellent method for predicting for the effect of ACNU in glioma therapy.

Adult↗

Compensation of intraoperative transcranial motor-evoked potential monitoring by compound muscle action potential after peripheral nerve stimulation.

It is often difficult to evaluate the results of transcranial motor-evoked potential (TCMEP) monitoring in patients under general anesthesia because these results are strongly affected by anesthetics and muscle relaxants. To exclude effects of muscle relaxants on TCMEP, compound muscle action potential (CMAP) by supramaximum stimulation of the median nerve immediately after transcranial stimulation (300 to 600 V) was recorded in 70 neurosurgical operations. A relative amplitude index (RAI) was defined as the amplitude of TCMEP after the operative procedure divided by the amplitude of TCMEP before the operative procedure. The RAI was calculated and was compensated by the amplitude of CMAP in 141 limbs. In 12 limbs of 7 patients with postoperatively progressed motor paresis, the compensated RAI was less than 0.2. The compensated RAI in all other 129 limbs of 63 patients without postoperative motor palsy was more than 0.2. These results suggest that compensation of TCMEP monitoring by CMAP is an easy and accurate method for removing the effects of muscle relaxants in TCMEP.

Action Potentials↗

Accessory molecules in the assembly of major histocompatibility complex class I/peptide complexes: how essential are they for CD8(+) T-cell immune responses?

Assembly of major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum is a highly coordinated process that results in abundant class I/peptide complexes at the cell surface for recognition by CD8(+) T cells and natural killer cells. During the assembly process, a number of chaperones and accessory molecules, such as transporter associated with antigen processing, tapasin, ER60, and calreticulin, assist newly synthesized class I molecules to facilitate loading of antigenic peptides and to optimize the repertoire of surface class I/peptide complexes. This review focuses on the relative importance of these accessory molecules for CD8(+) T-cell responses in vivo and discusses reasons that may help explain why some CD8(+) T-cell responses develop normally in mice deficient in components of class I assembly, despite impaired antigen presentation.

ATP-Binding Cassette Transporters↗

Reliability and validity of Japanese version of the Mini-International Neuropsychiatric Interview.

The Mini-International Neuropsychiatric Interview (MINI) is a short, structured diagnostic interview used as a tool to diagnose 16 axis I (Diagnostic and Statistical Manual) DSM-IV disorders and one personality disorder. Its original version was developed by Sheehan and Lecrubier. We translated the MINI into Japanese, and investigated the reliability and validity of the Japanese version of MINI. Eighty-two subjects participated in the validation of the MINI versus the Structured Clinical Interview for DSM-III-R (SCID-P). One hundred and sixty-nine subjects participated in the validation of the MINI versus an expert's professional opinion. Seventy-seven subjects were interviewed by two investigators and subsequently readministered by a third interviewer blind to the results of initial evaluation 1-2 days later. In general, kappa values indicated good or excellent agreement between MINI and SCID-P diagnoses. Kappa values indicated poor agreement between MINI and expert's diagnoses for most diagnoses. Interrater and test-retest reliabilities were good or excellent. The mean durations of the interview were 18.8 min for MINI and 45.4 min for corresponding sections of SCID-P. Overall, the results suggest that the MINI Japanese version succeeds in reliably and validly eliciting symptom criteria used in making DSM-III-R diagnoses, and can be performed in less than half the time required for the SCID-P.

Adolescent↗

Vastus lateralis oxygenation and blood volume measured by near-infrared spectroscopy during whole body vibration.

The purpose of this study was to investigate the effects of whole body vibration (WBV) on oxygenation of vastus lateralis muscle during squatting exercise. Eighteen male subjects [mean age, 27.3 +/- 6.0 (SD) years; mean height, 171.8 +/- 4.9 cm; mean weight, 64.4 +/- 6.1 kg] performed squatting exercise on a vibration platform for 3 min with and without vibration, and changes in oxygenation of the vastus lateralis muscle were determined by near-infrared spectroscopy. The muscle oxygenation levels and total haemoglobin and myoglobin levels (total Hb/Mb) decreased during squatting exercise with and without vibration. After exercise, the muscle oxygenation level and total Hb/Mb rapidly increased from the minimum value during exercise and remained constant for latter 10 min. The muscle oxygenation levels with vibration from 90 to 180 s after the start of squatting exercise were significantly lower than those without vibration. Total Hb/Mb with vibration from 90 s after the squatting exercise to 540 s were significantly higher than those without vibration. This study demonstrated that WBV exercise affects the oxygenation level of vastus lateralis muscle and reduces muscle oxygenation level compared to that with no WBV. Therefore, WBV exercise may be an efficient training stimulus for muscle deoxygenation.

Adult↗

Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos.

The hemangioblast in the mesoderm gives rise to both angioblasts and hematopoietic stem cells. The movement of hemangioblast precursor cells in the fetal trunk is a critical event in early embryogenesis. Vascular endothelial growth factor (VEGF) signaling is likely involved in this migration given the partial disturbance of VEGF receptor (VEGFR)-positive cell accumulation and migration in VEGFR2 null mice or mice with a truncated VEGFR1. However, it is not clear how the VEGF system regulates this migration or its direction. We show here that the expression of VEGF-A is dominant in the anterior portion of the embryo, whereas VEGFR1 and VEGFR2 are expressed in the posterior portion of the embryo. An inhibitor of VEGFR kinase blocked the migration of VEGFR-positive cells in a whole-embryo culture system. In addition, VEGFR-positive cells migrated toward a VEGFR1- or VEGFR2-specific ligand in vitro. Furthermore, VEGFR-positive cells derived from wild-type or VEGFR2(+/-) mice moved rapidly anteriorly, whereas cells derived from VEGFR2(+/-) mice carrying a truncated VEGFR1 [VEGFR1(TM-TK)(-/-)] migrated little when injected into wild-type mice. These results suggest that the VEGF-A protein concentrated in the anterior region plays an important role in the guidance of VEGFR-positive cells from the posterior portion to the head region by interacting with VEGFR in the mouse embryo.

Animals↗

Phospholipase C-delta1 and -delta3 are essential in the trophoblast for placental development.

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in phosphoinositide turnover and is involved in a variety of physiological functions. We analyzed PLCdelta1 knockout mice and found that PLCdelta1 is required for the maintenance of skin homeostasis. However, there were no remarkable abnormalities except hair loss and runting in PLCdelta1 knockout mice, even though PLCdelta1 is broadly distributed. Here, we report that mice lacking both PLCdelta1 and PLCdelta3 died at embryonic day 11.5 (E11.5) to E13.5. PLCdelta1/PLCdelta3 double-knockout mice exhibited severe disruption of the normal labyrinth architecture in the placenta and decreased placental vascularization, as well as abnormal proliferation and apoptosis of trophoblasts in the labyrinth area. Furthermore, PLCdelta1/PLCdelta3 double-knockout embryos supplied with a normal placenta by the tetraploid aggregation method survived beyond E14.5, clearly indicating that the embryonic lethality is caused by a defect in trophoblasts. On the basis of these results, we conclude that PLCdelta1 and PLCdelta3 are essential in trophoblasts for placental development.

Animals↗

Effects of the endothelin receptor antagonist bosentan on hemodynamics, symptoms and functional capacity in Japanese patients with severe pulmonary hypertension.

BACKGROUND: Endothelin (ET)-1 has a pathogenic role in pulmonary arterial hypertension (PAH). Recent clinical studies carried out in Western populations showed that blockade of the ET receptors by bosentan improves pulmonary hemodynamics and exercise capacity. In the present study, the efficacy of bosentan was assessed in Japanese patients with PAH. METHOD AND RESULTS: Because the pharmacokinetics of bosentan and its metabolites are similar in Japanese and Caucasian subjects, the same dose of bosentan, 125 mg twice daily, was administered in the Japanese open-label clinical trial. In 18 patients, mean pulmonary arterial pressure decreased from 52.4+/-13.8 to 46.8+/-13.8 mmHg (p=0.003) and cardiac index increased from 2.20+/-0.74 to 2.61 +/-0.72 L.min(-1).m(-2) (p=0.002). The 6-min walking distance increased from 410+/-89.5 to 494+/-86.0 m (p<0.0001). The dyspnea index (Borg scale) decreased from 3.2+/-2.4 to 2.2+/-1.7 (p=0.02). The specific activity scale (SAS) gradually increased throughout the study period from 2.9+/-0.8 to 4.6+/-1.9 METs (p=0.0005). WHO Class improved in 10 patients. CONCLUSION: Bosentan was well tolerated and improved the hemodynamics, symptoms, exercise capacity, and quality of life of Japanese patients with PAH. Thus, bosentan can be a valuable therapeutic option in Japanese patients.

Adult↗

Blurred vision caused by inflammation of the optic nerves due to a pituitary abscess.

A 48-year-old woman was admitted to our institution complaining of headache and a 2-month history of blurred vision and increased urinary volume. T(1)-weighted magnetic resonance (MR) imaging with gadolinium showed a ring-enhanced mass lesion in the pituitary. Fluid-attenuated inversion recovery MR imaging showed high-intensity lesions in the optic nerves, hypothalamus, and thalamus. The histological diagnosis was pituitary abscess. The blurred vision was caused by inflammation, but not compression, of the optic nerves due to the pituitary abscess outside the hypophysis.

Abscess↗

Biopsy of brain stem glioma using motor-evoked potential mapping by direct peduncular stimulation and individual adjuvant therapy. Case report.

A 23-year-old man presented with a brain stem glioma manifesting as a 6-month history of right hemiparesis and diplopia. Serial magnetic resonance imaging showed an intrinsic diffuse brain stem glioma that gradually localized to the left cerebral peduncle after initial adjuvant therapy. Surgery was performed through a left subtemporal transtentorial approach under motor-evoked potential (MEP) mapping by direct peduncular stimulation. The lateral aspect of the midbrain was exposed, a train of five bipolar 25 mA pulses was applied, and MEPs recorded from the extremities. MEPs were only recorded from the left extremities even with left cerebral peduncular stimulation. Partial resection of the tumor was safely performed, with slight temporary neurological worsening. The histological diagnosis was anaplastic astrocytoma. Individual adjuvant therapy based on the results of real-time reverse transcription-polymerase chain reaction of O6-methylguanine-deoxyribonucleic acid methyltransferase achieved an almost complete tumor response. Surgery under pyramidal tract mapping and intensive postoperative adjuvant therapy resulted in a good outcome despite the presence of a generally intractable intrinsic brain stem glioma.

Adult↗