Search PubMed⌕ Search

Biomedical subjects

Masanori Takahashi

Publications and source records attributed to Masanori Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

Microsatellite polymorphisms of the MICA gene among Japanese patients with Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a multisystemic inflammatory disease of unknown origin. Because some researchers have recently suggested a primary association of BD with the A6 allele of the human major histocompatibility complex class I chain-related A (MICA) gene, we investigated microsatellite polymorphisms of the MICA gene in subjects with and without BD. METHODS: This was a case-control study of 23 Japanese patients with BD and 23 Japanese volunteers without BD who were compared for MICA microsatellite polymorphisms using the polymerase chain reaction (PCR). We also analysed associations between 5 MICA alleles and the clinical features of patients. RESULTS: There was no significant difference between case patients and control subjects in phenotype frequencies. The MICA-A6 allele showed the strongest positive correlation with the human leukocyte antigen allele HLA-B51. Allele A5 showed a strong positive correlation with age at onset and a strong negative correlation with iridocyclitis and HLA-B51. A4 showed a strong negative correlation with ocular lesions and HLA-B51. Patients with the MICA-A6 allele had significantly higher HLA positivity than patients without the allele. INTERPRETATION: While the MICA-A6 allele had no significant association with BD, it showed a strong association with HLA-B51. This finding suggests that an association between MICA-A6 and BD may be a secondary phenomenon related to HLA-B51. As several associations with MICA alleles and clinical features have been found, further investigation is expected to elucidate the biological mechanism of action of the MICA protein relative to disease onset.

Adult↗
PubMed2005

Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues.

The use of stem cells has enabled the successful generation of simple organs. However, anatomically complicated organs such as the kidney have proven more refractory to stem-cell-based regenerative techniques. Given the limits of allogenic organ transplantation, an ultimate therapeutic solution is to establish self-organs from autologous stem cells and transplant them as syngrafts back into donor patients. To this end, we have striven to establish an in vitro organ factory to build up complex organ structures from autologous adult stem cells by using the kidney as a target organ. Cultivation of human mesenchymal stem cells in growing rodent embryos enables their differentiation within a spatially and temporally appropriate developmental milieu, facilitating the first step of nephrogenesis. We show that a combination of whole-embryo culture, followed by organ culture, encourages exogenous human mesenchymal stem cells to differentiate and contribute to functional complex structures of the new kidney.

Animals↗
PubMed2005

Identification of a novel type II classical cadherin: rat cadherin19 is expressed in the cranial ganglia and Schwann cell precursors during development.

To identify a novel type II classical cadherin, we searched the genome database and found rat cadherin19 (cad19) with high similarity to human cadherin19. We also found nucleotide sequences corresponding to rat cad19 in mouse and chicken genomes. In situ hybridization of rat cad19 revealed that rat cad19 mRNA was initially expressed in cephalic neural crest cells, and then in the cranial ganglia, migrating trunk neural crest cells, the nascent dorsal root ganglia, and the sympathetic ganglia. Expression of cad19 overlapped with that of neural crest markers, including Sox10 and AP-2, but cad19 expression was confined to subpopulations of the neural crest-derived cells, those typically observed in the satellite glia at the periphery of the ganglia and Schwann cell precursors along the peripheral nerves. cad19 mRNA was not detected in cells expressing Phox2b, an epibranchial placode-derived neurons, nor in those expressing neuronal markers such as Hu protein. These observations suggest that cad19 is expressed in neural crest-derived, non-neuronal cells. Although the expression of cad19 mRNA persisted in Schwann cell precursors at E14.5, it was no longer detected in maturing Schwann cells at later stages. These results suggest that cad19 is an evolutionarily conserved cadherin and may be involved in the early development of Schwann cells in the peripheral nervous system.

Amino Acid Sequence↗
PubMed2005

Gliogenic radial glial cells show heterogeneity in the developing mouse spinal cord.

The central nervous system of the mammalian embryo is organized according to the expression of region-specific transcription factors along the anteroposterior and/or the dorsoventral axis. For example, the dorsal ventricular zone (VZ) of the embryonic spinal cord expresses Pax3 and Pax7, the ventral VZ expresses Pax6, and the more ventral VZ expresses Nkx2.2. Properties of neuronal precursors located in the VZ are determined by the characteristic expression patterns of these transcription factors, leading to the generation of distinct classes of neurons. Recent studies demonstrated that radial glial cells produce neurons in addition to glia during central nervous system development. Thus, neuronal precursor diversity may be dependent upon the diversity of radial glial cells. To investigate this hypothesis, we analyzed the expression of radial glial cell markers and transcription factors in the mouse embryonic spinal cord. We show that radial glial cells indeed express domain-specific transcription factor. Moreover, they varied in expression of the astrocyte-specific glutamate transporter. The region where the astrocyte-specific glutamate transporter is strongly expressed in the ventral radial glial cells is closely related to the Pax6-expressing domain, and the weakly expressing region corresponding to the Nkx2.2-expressing domain. Furthermore, dorsal radial fibers expressed ephrin-B1. Thus, different types of radial glial cells exist in different domains defined by the transcription factor expression at E12.5. We also show that this diversity continues to the gliogenic stage of radial glial cells. This raises the idea that astrocytes generated from different domains along the dorsoventral axis in the mouse spinal cord have distinct characteristics.

Animals↗
PubMed2004

Survival of developing motor neurons mediated by Rho GTPase signaling pathway through Rho-kinase.

A variety of neurons generated during embryonic development survive or undergo programmed cell death (PCD) at later developmental stages. Survival or death of developing neurons is generally considered to depend on trophic support from various target tissues. The small GTPase Rho regulates diverse cellular processes such as cell morphology, cell adhesion, cell motility, and apoptosis. Rho-dependent serine-threonine protein kinase (Rho-kinase-ROK-ROCK), one of the effector proteins, transmits signals for some Rho-mediated processes. Here, we report the in vivo role of the Rho signaling pathway through Rho-kinase during development of motor neurons (MNs) in the spinal cord. We performed conditional expression of a dominant-negative form for RhoA (RhoA DN) or for Rho-kinase (Rho-K DN) in transgenic mice by using the Cre-loxP system to suppress the activity of these signaling molecules in developing MNs. Expression of RhoA DN reduced the number of MNs in the spinal cord because of increased apoptosis while preserving the gross patterning of motor axons. Expression of Rho-K DN produced developmental defects similar to those observed in RhoA DN expression. In addition, analysis of transgenic mice expressing Rho-K DN showed that the increased apoptosis of MNs was induced at the early embryonic stages before the initiation of PCD, and that MN death at the late embryonic stages corresponding to the period of PCD was moderately enhanced in the transgenic mice. These findings indicate that the Rho signaling pathway, primarily through Rho-kinase, plays a crucial role in survival of spinal MNs during embryogenesis, particularly at the early developmental stages.

Animals↗
PubMed2004

Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma.

OBJECTIVE: To evaluate the efficacy of a novel 2-stage treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for multiple hepatocellular carcinoma (HCC), which was previously unresectable. SUMMARY BACKGROUND DATA: Surgical resection is the treatment of choice for HCC, but the majority of patients with advanced HCC are not suitable candidates. PIHP is a minimally invasive surgery that allows high-dose regional chemotherapy of the liver, and our phase II studies have shown its profound efficacy for the local control of advanced HCC. METHODS: Twenty-five patients with multiple advanced HCC were enrolled in this prospective study. In the first stage, all patients underwent reductive hepatectomy: major hepatectomy in 13 patients and segmentectomy or less in 12. In 2 patients with subsegmentectomy, the retropancreatic and periportal metastatic lymph nodes were synchronously resected. Regardless of the type of hepatectomy, all patients routinely underwent cholecystectomy, and ligations of the right gastric artery and arterial collaterals of the remnant liver to increase the safety and efficacy of PIHP. In the second stage, PIHP with doxorubicin 60-120 mg/m2/treatment was planned for a period of 1 to 3 months after surgery. RESULTS: Of 25 enrolled patients, 22 successfully underwent PIHP an average of 1.8 times for the local control of residual liver tumors. In the remaining 3 patients, PIHP was abandoned because 2 had rapid disease progression and 1 had liver failure after surgery. In 22 patients with the 2-stage treatment, 19 (86%) had objective local tumor control (10 complete remissions and 9 partial responses with a median response duration of 16 months). The actuarial survival rate of all 25 patients was 42% at 5 years. CONCLUSIONS: Reductive surgery plus PIHP produced a strong antitumoral effect on multiple advanced HCC, when liver function allows this concentrated treatment approach, and offers long-term survival in a subset of patients who were previously deemed to have unresectable disease.

Adult↗
PubMed2004

The G12 family of heterotrimeric G proteins and Rho GTPase mediate Sonic hedgehog signalling.

Sonic hedgehog (Shh) is a secreted morphogen crucial for cell fate decision, cellular proliferation, and patterning during vertebrate development. The intracellular Shh signalling is transduced by Smoothened (Smo), a seven-transmembrane spanning protein that belongs to the G-protein coupled receptor family. Among four families of Galpha subunits, Galphai has been thought to be responsible for transducing Shh signalling, while several lines of evidence indicated that other signalling pathways may be involved. We found that the G12 family of heterotrimeric G proteins and the small GTPase RhoA are involved in Shh/Smo-mediated cellular responses, including stimulation of target gene promoter and inhibition of neurite outgrowth of neuroblastoma cells. We also found that the G12/RhoA pathway is responsible for Smo-induced nuclear import of GLI3 which is thought to transduce Shh signals to nucleus. Furthermore, misexpression of a G12-specific GTPase-activating protein in rat neural tubes leads to pertubation of motor neurone and interneurone development, mimicking the effects of decreased Shh signalling. These results show that Shh signalling is mediated in part by activating G12 family coupled signalling pathways. The participation of RhoA, a pivotal molecular switch in many signal transduction pathways, may help explain how Shh can trigger a variety of cellular responses.

Animals↗
PubMed2004

Unusual skin reactions after mosquito bites and Epstein-Barr virus reactivation in a patient with mantle cell lymphoma.

We detected Epstein-Barr virus (EBV) reactivation in a patient with mantle cell lymphoma (MCL). The patient, a 53-year-old Japanese man, had been referred to our hospital because of generalized lymphadenopathy, hepatosplenomegaly and lymphocytosis and gave a history of intense skin reactions to mosquito bites. The biopsied lymph node contained a monotonous proliferation of medium-sized lymphocytes with scant cytoplasm and slightly irregular nuclei that were CD5+, CD20+ and CD23-. Antibody titers of IgG against EBV viral capsid antigen and early antigen were increased, and EBV was detected in the lymphoma cells. This case may suggest a relationship between EBV and MCL.

Animals↗
PubMed2004

Neuromagnetic analysis of the late phase of the readiness field for precise hand movements using magnetoencephalography.

The aim of this study was to elucidate the cortical regulation of precise finger movements by using magnetoencephalography, with particular emphasis on the late phase of the readiness field. Magnetic brain signals were recorded non-invasively by 306 channel magnetoencephalography during the following two tasks. The first task, a simple task, was to bend the right thumb once as quickly as possible. The second task, a precise one, was to alternately oppose the thumb with the index finger and the middle finger of right hand. In this study, we confirmed that the differences between the two tasks were observed in the late phase of the readiness field, especially in the magnetic field 600 ms before the onset of movement. The activity of the magnetic field of the precise movement task was higher than the activity of the simple movement task. There were obvious differences in the spatial and temporal aspects of the left hemisphere. In the simple movement, the premotor area or motor area was activated in the late phase of the time window. The average latency from the EMG onset was -98.6+/-34.0 ms (n = 5). In the precise movement, the prefrontal area and the SMA were activated in the early and/or middle phases of the time window. The average latency from the EMG onset was -292.0+/-14.9 ms (n = 3) for the prefrontal cortex and -167.8+/-38.3 ms (n = 4) for the SMA. The premotor area or motor area was activated in the late stage of the RF. The average latency from the EMG onset was -111.6+/-61.4 ms (n = 5). Many studies have been performed on the movement-related readiness field. However, the activity of the prefrontal area and the SMA had not previously been studied in the late phase of the readiness field. Our study indicated that the prefrontal area and the SMA played important roles immediately before the onset of precise finger movement. The integration of the prefrontal area, the SMA, and the premotor area is important for the onset of precise finger movement.

Adult↗
PubMed2004

Research report: Frequencies of mica gene polymorphism: a comparison between Indonesians on Bacan Island and suburban Japanese.

MHC class I chain related gene A (MICA) is located near the HLA-B gene on the short arm of human chromosome 6. In the transmembrane (TM) of region of MICA, there is a trinucleotide repeat (GCT/AGC) microsatellite polymorphism in exon 5. Five alleles with 4, 5, 6 and 9 repetitions or 5 repetitions with 1 additional nucleotide insertion (GGCT) are identified and they were named A4, A5, A5.1, A6, and A9 respectively. We report the allele frequencies of 127 Indonesians on Bacan Island and 250 Japanese in the Kanto area. From the genotyping result, the frequency among Indonesians was as follows: A4 15.4%, A5 26.0%, A5.1 16.5%, A6 5.5%, and A9 36.6%. The frequency among Japanese was as follows: A4 20.6%, A5 28.1%, A5.1 10.8%, A6 27.2%, and A9 13.2%. Allele 9 is significantly increased and allele 6 significantly decreased in Indonesians compared with Japanese subjects. The results suggested that MICA microsatellite polymorphism are quite different in each race. Among Indonesians, the frequency of MICA-A9 allele, which was reported to be negatively associated with Behçet's disease, was significantly higher, whereas the MICA-A6 allele frequency, which was reported to be positively associated with Behçet's disease, was significantly lower among Japanese.

Asian People↗
PubMed2004

[Erythrocyte from Duchenne muscular dystrophy is fragile].

Intermittent indirect hyperbilirubinemia was occasionally observed in Duchenne muscular dystrophy (DMD) patients. We suspected that hyperbilirubinemia might be caused by hemolysis of fragile erythrocytes due to damaged endothelium, which was reported in DMD. To examine the fragility of erythrocytes, we performed osmotic resistance test in 25 DMD, 12 myotonic dystrophy (DM), 12 amyotrophic lateral sclerosis (ALS) and 24 healthy volunteers (male 15, female 9). Minimum resistance (beginning point of hemolysis) of DMD (0.447 +/- 0.016%) was higher than that of age matched male controls (0.425 +/- 0.018%: p = 0.0008) and that of DM (0.440 +/- 0.015%) was also higher than that of total controls (0.423 +/- 0.016%, p = 0.0077). The number of poikilocytes was increased in DMD (35.45 +/- 41.17 per a high magnitude field), however no obvious correlation was detected between the ratio of poikilocytes and resistances. Total bilirubin showed correlation (p = 0.029) to minimum resistance. These findings suggested that erythrocyte membrane is fragile in DMD. Involvement of endothelial damage could not be proven, because all investigated patients showed normal tissue plasminogen activator inhibitor-1. Although the mechanism of fragile erythrocytes in DMD is still unknown, we should pay attention to interpret bilirubin in DMD, because hemolysis due to erythrocyte fragility may influence the value.

Aged↗
PubMed2003

Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells.

BACKGROUND: The coordinated activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) is critical for the induction of vascular and visceral smooth muscle cell (SMC) dedifferentiation. We previously reported that on the forced activation of both MAPKs, visceral SMCs secrete a non-heparin-binding protein factor(s) that is involved in the dedifferentiation of neighboring SMCs. In this study, we sought to identify the dedifferentiation factor(s) derived from vascular SMCs (VSMCs). METHODS AND RESULTS: We fractionated the VSMC dedifferentiation factor(s) in the conditioned medium obtained from differentiated VSMCs in which both ERK and p38MAPK were forcedly activated and identified epiregulin as a major autocrine/paracrine factor for VSMC dedifferentiation. The epiregulin-induced VSMC dedifferentiation was mediated through the coordinated activation of ERK and p38MAPK. Unsaturated lysophosphatidic acid and platelet-derived growth factor-BB, which are potent VSMC dedifferentiation factors, rapidly upregulated epiregulin mRNA expression in an ERK- and p38MAPK-dependent manner. Reverse transcriptase-polymerase chain reaction and/or immunohistological analyses revealed the restricted expression of epiregulin in human atherosclerotic and balloon-injured rat arteries, in which the phenotypic modulation of medial VSMCs occurred in vivo. CONCLUSIONS: Epiregulin is released from VSMCs primed by atherogenic factors and acts as a major autocrine/paracrine factor for VSMC dedifferentiation. It may be involved in the progression of vascular remodeling such as atherosclerosis.

Animals↗
PubMed2003

Significant role of middle hepatic vein in remnant liver regeneration of right-lobe living donors.

For adult patients with end-stage liver disease, living-donor liver transplantation (LDLT) of right-lobe grafts with or without the middle hepatic vein (MHV) has been increasingly used in recent years. We investigated the role of the MHV in donor remnant liver regeneration after right-lobe LDLT, which has not been described in previous studies. A total of eight living donors were included in this study of right-lobe LDLT. Four donors underwent right lobectomy (without MHV), and the remaining four underwent extended right lobectomy (with MHV). Regeneration of the donor remnant liver was assessed by volumetric computed tomography studies before and 90 days after LDLT. Comparison between the right-lobe and extended right-lobe donors did not show a clear-cut difference in the net increase of remnant liver volume at 3 months. However, the mean volume increase of the medial segment at the 90th postoperative day was 7% in the extended right-lobe donors and 61% in the right-lobe donors, showing a lower value in the remnant livers without MHV. The MHV plays a specific role in remnant liver regeneration of right-lobe living donors. We expect that this knowledge will contribute to securing a margin of safety in right-lobe LDLT.

Adult↗
PubMed2003

Spindle epithelial tumor with thymus-like differentiation of the thyroid: a case report with pathological and molecular genetics study.

We report an unusual case of spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid present in a 6-year-old boy. The tumor, located at both the left lobe and isthmus, was a circumscribed mass with slightly gritty whorled appearance. Microscopically, the lobulated, highly cellular, spindle cell neoplasm was arranged in intersecting bundles and fascicles separated by fibrous bands. Benign-appearing glands entrapped within fibrous bands and foci of squamous differentiation within spindle cells were observed. Immunohistochemically, the spindle cells were diffusely positive for cytokeratins, vimentin, and alpha-smooth muscle actin and patchily reactive for muscle-specific actin and epithelial membrane antigen, exhibiting myoepithelial differentiation. The spindle cells were also patchily immunopositive for p53 protein. Molecular genetic analysis revealed Ki-ras gene mutations at codons 13 (GGC(gly) to AGC(ser)) and 15 (GGC(gly) to AGC(ser)) on the same allele. Mutation of the p53 gene was not detected. This is the first report on Ki-ras oncogene mutations in a case of SETTLE.

Actins↗
PubMed2003

Influences of probiotic bacteria on organic acid production by pig caecal bacteria in vitro.

The mechanism of action of probiotics is largely unknown. A potential mechanism should be to increase the production of short-chain fatty acids (SCFA), known modulators of gut functions, by the bacterial ecosystem in the large intestine. The present paper reviews our recent studies in which the capacity of probiotic bacteria to increase the production of SCFA by pig caecal bacteria was investigated using batch-culture and continuous-culture techniques. All four commercial probiotic preparations and three strains of probiotic bacteria dose-dependently accelerated the net production of SCFA, succinic acid and lactic acid without changing the acid profile, and slowed the net production of NH4. Effects on organic acid production did not vary among different probiotic species. Neither probiotic preparations nor probiotic bacteria affected the organic acid production from glucose, gastric mucin, starch or lactose, or organic acids produced:added saccharide. Glucose abolished these effects of probiotic preparations. However, the capacity of probiotics to increase SCFA production was not modified by gastric mucin, starch or lactose. These results indicate that probiotic bacteria increase SCFA production by accelerating the breakdown of carbohydrates that are resistant to indigenous bacteria, and suggest that the concept of prebiotics in terms of SCFA production as a measure of probiotic function is arguable.

Ammonia↗
PubMed2003

Magnetoencephalographic study of the starting point of voluntary swallowing.

Clear findings relative to where in the brain the starting point of voluntary swallowing is controlled were obtained in the present magnetoencephalographic study. Namely, the cerebral activity was observed in the cingulate gyrus and supplementary motor area for about 80 ms between 1,000 and 1,500 ms before swallowing in all test subjects. Thus, it is clear that this type of central control mechanism also plays an important role in complicated swallowing movements.

Adult↗
PubMed2003

[Simultaneous determination of N-methylcarbamate and urea pesticides in agricultural products by LC/MS].

A simultaneous determination method of 7 N-methylcarbamate and 7 urea pesticides in agricultural products by liquid chromatography/mass spectrometry (LC/MS) has been developed. Under reversed-phase liquid chromatographic conditions, 14 pesticides were analyzed using electrospray ionization (ESI) with simultaneous acquisition of positive ions and negative ions. Fourteen pesticides were extracted with acetone, 10% NaCl solution was added, and the pesticides were re-extracted with dichloromethane. The extract was concentrated under reduced pressure, and dissolved in methanol. The detection limits of 14 pesticides ranged from 0.0012 to 0.0056 microgram/g. The recoveries of pesticides were from 36.5 to 112.5% [RSD (n = 3) ranged from 0.5 to 48.1%] for 4 agricultural products.

Carbamates↗