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M Takigawa

Publications and source records attributed to M Takigawa.

At least 55 records · Page 3Linked to original sources
PubMed2001

A device for stereotactic transection of fiber bundles in rats.

We have designed a device for stereotactic transection of fiber bundles in experiments using rats. Here, we present our assessment of its features relative to those of conventional methods. The instrument consists of a stainless steel cannula and a thin inner wire with a hook at one end and a hilt at the other. The hook can be extended or withdrawn freely by pushing or pulling the hilt. Lesions were evaluated in 12 male Wistar rats, after two targets, the anterior commissure (n=6) and the caudate-putamen (n=6), were transected. After the cannula was introduced into the target, the inner hook was extended in an anterior direction orthogonally to the transverse plane. Next, the entire device was pulled back along the insertion path to transect the neuronal fibers. Then the inner hook was withdrawn into the cannula and the entire device was removed. Seven days later, brains were removed for histologic processing. Microscopic examination demonstrated a slit like gap produced by transection at the target; the lesions were infiltrated by microglia and surrounded by gliosis. Adjacent regions were minimally damaged. The path of the cannula demonstrated only minimal gliosis. Unlike conventional methods, this device permits precise transection of deep fiber bundles with minimal damage to surrounding brain tissue.

Animals↗
PubMed2001

Effects of high frequency repetitive transcranial magnetic stimulation on P(300) event-related potentials.

OBJECTIVE: Auditory event-related potentials (P(300)-ERPs) were analyzed before and after repetitive transcranial magnetic stimulation (rTMS). METHODS: Two rTMS trains (10 Hz, 3 s, 100% motor threshold and 5 min interval) were delivered over the left frontal area in healthy subjects. P(300)-ERPs were recorded at 14 electrode sites on the scalp using a typical oddball paradigm before and after rTMS. The latencies and amplitudes of N(100), P(200), N(200) and P(300) were measured and compared. The directed coherence (DCOH) was estimated to demonstrate information flow between different cortical areas. RESULTS: rTMS significantly influenced P(300)-ERPs. The effects differed on the different components (P<0.001). The latency of P(300) significantly increased after stimulation, which was more obvious in the frontal and central areas. The changes in P(300) amplitude were not significant (P>0.05). The DCOH from the frontal, central, parietal and occipital areas to the temporal area was significantly higher than the DCOH from the temporal area to the former 4 areas (P<0.01). CONCLUSIONS: rTMS with the present parameters can affect P(300)-ERPs, leading to a delayed P(300) component and changes in information connections around the stimulated site. Our data suggest that rTMS may postpone neuronal activities related to cognitive processing.

Adult↗
PubMed2001

Novel mode of processing and secretion of connective tissue growth factor/ecogenin (CTGF/Hcs24) in chondrocytic HCS-2/8 cells.

The synthesis, processing, and secretion of human connective tissue growth factor (CTGF/Hcs24) in a human chondrocytic cell line, HCS-2/8, were analyzed immunochemically. By metabolic pulse-labeling, chasing, and subsequent immunoprecipitation analyses, active synthesis of CTGF was observed not only in growing HCS-2/8 cells, but also in confluent cells. However, secretion and processing of CTGF were found to be regulated differentially, depending upon the growth status. During phases of growth, HCS-2/8 cells released CTGF molecules immediately without sequestering them within the cell layer. In contrast, after the cells reached confluence, the secretion slowed, resulting in an accumulation of CTGF in the cells or extracellular matrices (ECMs). Also, in confluent cell layers, a 10 kDa protein that was reactive to an anti-CTGF serum was observed. This CTGF-related small protein was not detected immediately after labeling, but gradually appeared within 6 h after chase, which suggests its entity as a processed subfragment of CTGF. Surprisingly, the 10 kDa protein was stable even 48 h after synthesis, and was not released by ECM digestion, suggesting an intracellular maintenance and function. Taken together, the behavior of CTGF in HCS-2/8 cells is remarkably different from that reported in fibroblasts, which may represent unique roles for CTGF in the growth and differentiation of chondrocytes.

Amino Acid Sequence↗
PubMed2001

Aberrant brain activation following motor skill learning in schizophrenic patients as shown by functional magnetic resonance imaging.

BACKGROUND: Motor skill learning may be impaired in schizophrenia. While functional brain imaging studies have shown reduced activation during motor task performance in schizophrenic patients, brain activity changes with motor skill learning in these patients have not been studied by functional imaging. METHODS: A sequential complex motor task involving the right hand was performed by nine medicated schizophrenic patients and 10 age-matched healthy controls. Functional magnetic resonance images were obtained using a gradient echo, echoplanar imaging (EPI) pulse sequence before and after 1 week of training in performing the task. RESULTS: Bilaterally, patients showed significantly less blood oxygenation level-dependent (BOLD) signal response in the premotor area (PMA) before beginning motor training than controls. BOLD signal response increased in the left PMA of schizophrenic patients after 1 week of motor training; in contrast, the signal decreased in the left PMA of control subjects. Training effects concerning the number of finger movement sequences achieved did not differ between groups. Daily neuroleptic dose did not significantly affect changes with training in BOLD signal response in the PMA. CONCLUSIONS: These preliminary results suggest that schizophrenic patients have dysfunction of neural networks in areas including the PMA that are involved in executing a complex motor task. In terms of brain activity, motor learning may be less efficient or slower in the patients than in healthy subjects.

Adolescent↗
PubMed2001

Regional accumulation of 14C-zonisamide in rat brain during kainic acid-induced limbic seizures.

BACKGROUND: Zonisamide (ZNS) is an antiepileptic drug developed in Japan. Various experimental studies have investigated the effects of ZNS. However, the mechanism of action of ZNS against limbic seizures and secondary generalization is not well-known. We studied ictal regional accumulation of ZNS in the rat brain during kainic acid (KA)-induced limbic status epilepticus. METHODS: Fourteen male Wistar rats underwent a stereotactic operation. For recording the electroencephalogram (EEG), electrodes were placed in the left amygdala (LA), left dorsal hippocampus, and over the left sensorimotor cortex. For microinjection, a stainless steel cannula was also inserted into the LA. Seven days after surgery, rats were anesthetized and a catheter was inserted into the femoral vein. The animals were immobilized and allowed to recover from anesthesia for at least two hours. In eight rats, 1.0 microL (1.0 microg) of KA was injected into the LA, and 1.0 microL of phosphate buffer solution was injected into the LA in six control rats. Sixty minutes after injection, 14C-ZNS was administered intravenously, and an autoradiographic study was done. RESULTS: During limbic status epilepticus, only seizures in the sensorimotor cortex were markedly attenuated a few minutes after 14C-ZNS administration. Additionally, high uptake of 14C-ZNS was noted ipsilaterally in the sensorimotor cortex, parietal cortex and thalamus (lateral portion). In control rats, no EEG change was seen, and distribution of 14C-ZNS was rather homogeneous. CONCLUSIONS: These results suggested that ZNS suppresses secondary generalization of limbic seizures by a direct effect on the cerebral cortex.

Animals↗
PubMed2001

What are the most promising strategies for the therapeutic immunomodulation of allergic diseases?

Specific immunotherapy and other immunomodulatory strategies have long been a stronghold in the management of allergic diseases. In particular, "immunodeviation-therapy" or "vaccination for allergies", i.e. the redirection of Th2-type immune responses towards a Th1-response pattern, has become an ever more popular concept. The present feature of CONTROVERSIES complements our previous discussion of atopy (Röcken et al., Exp Dermatol 7: 97--104, 1998), and is dedicated to a critical analysis of the general problems and limitations one faces with the main immunomodulatory strategies traditionally considered in this context. We also explore alternative approaches that appear promising in order to achieve both a more effective and/or a more specific immunotherapy of allergic diseases. Given that the mast cell remains a key protagonist in the pathogenesis of allergic diseases finally, this feature examines how innovative, more selectively mast cell-targeted strategies may be developed for the management of allergic diseases.

Adult↗
PubMed2001

Analysis of photosensitivity in Japanese cancer-bearing patients receiving photodynamic therapy with porfimer sodium (Photofrin).

A major disadvantage of a new cancer treatment, porfimer sodium (Photofrin)-mediated photodynamic therapy (PF-PDT), is photosensitivity for several weeks after cessation of the treatment. To characterize persistent sensitivity to visible light following PF-PDT, phototestings were performed in 59 Japanese cancer-bearing patients with a slide projector lamp 3 weeks or more after the treatment. The duration of photosensitivity was analyzed in relation to the patients' sex, skin phototype (SPT), site of tumor and liver function. There was no correlation of the photosensitivity persistency with the site of cancers and the function of liver. However, female subjects needed significantly longer recovery periods than male subjects from potential photosensitivity after PF-PDT. Patients with SPT2 were significantly more sensitive than patients with SPT3 and 4. These results suggest that the prolonged photosensitivity occurs after PF-PDT especially in female patients and in cases with a lighter SPT. Such patients should be carefully followed up for post-PDT photosensitivity.

Adult↗
PubMed2001

CTGF/Hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase (p38MAPK), and proliferation through a p44/42 MAPK/extracellular-signal regulated kinase (ERK).

Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/Hcs24. In the proliferation phase, CTGF/Hcs24 induced a approximately fivefold increase in the phosphorylation of p44/42 MAPK/ERK and a approximately twofold increase in that of p38 MAPK in an in vivo kinase assay. These inhibitors of MAPKK and MAPK suppressed phosphorylation of ets-like gene-1 (Elk-1) and nuclear activating transcription factor-2 (Atf-2) induced by CTGF/Hcs24 in a dose-dependent manner, respectively. Western blot analysis showed that phosphorylation of ERK was induced from 30 to 60 min and phosphorylation of p38 MAPK from 10 to 15 min after the addition of CTGF/Hcs24 in confluence HCS-2/8 cells. PD098059 suppressed the DNA synthesis of HCS-2/8 cells and RGC cells, while SB203580 did not. On the other hand, the p38 MAPK inhibitor, SB203580, completely inhibited the CTGF/Hcs24-induced synthesis of proteoglycans in HCS-2/8 cells and RGC cells but the MEK1/2 inhibitor, PD098059, did not. These results suggest that ERK mediates the CTGF/Hcs24-induced proliferation of chondrocytes, and that p38 MAPK mediates the CTGF/Hcs24-induced differentiation of chondrocytes.

Animals↗
PubMed2001

Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy.

Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone photoallergy.

Amino Acid Sequence↗
PubMed2001

Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4(+) T-regulatory cells and systemic collapse of antitumour immunity.

We investigated the relationship between transforming growth factor-beta (TGF-beta)-secreting T-regulatory (Tr) cells and anti-B16 melanoma immunity, and studied the association of early cytokines expressed at tumour sites with the generation of Tr cells. A large number of CD4(+) Tr cells producing interleukin (IL)-4, IL-10 and TGF-beta accumulated with functionally depressed CD8(+) cytotoxic T lymphocytes (CTLs) at tumour sites on day 20 after subcutaneous (s.c.) inoculation of B16 tumour cells. Tr cells consisted of two populations, which were termed T helper 3 (Th3) and Tr1 cells. B16-infiltrating Tr cells strongly inhibited the generation of B16-specific T helper 1 (Th1) cells in a TGF-beta-dependent manner and were assumed to suppress effective generation of CTLs. In addition, B16 cells markedly progressed in mice transferred adoptively by the cultured B16-infiltrating Tr cells compared with untreated mice. The capacity of these Tr cells to produce TGF-beta was hampered by neutralizing anti-IL-10 and partly anti-IL-4 monoclonal antibodies (mAbs) injected intralesionally during the early development of B16 tumours, and this treatment markedly attenuated B16 growth. Furthermore, a lesional injection of recombinant mouse IL-10 at an early tumour site resulted in the vigorous progression of B16 tumours. These results provide evidence that Tr cells, belonging to the T helper 3/T-regulatory 1 (Th3/Tr1) type, are activated in B16-bearing hosts under the influence of T helper 2 (Th2) cytokines, mainly IL-10 (produced at early tumour lesions), and that this regulatory T-cell population functions as a suppressor of anti-B16 immunity.

Animals↗
PubMed2001

Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide.

The effects of phenobarbital (PB; doses, 5, 10, and 25 mg/kg, intraperitoneally (i.p.)) and zonisamide (ZNS; doses, 30, 75, and 150 mg/kg, i.p.) on nitric oxide (NO) production, and those of coadministration of PB (5 mg/kg, i.p.) and ZNS (75 mg/kg, i.p.) on monoamines in the brain of the seizure-susceptible EL mouse were investigated. Nitric oxide production was obtained by measuring the combined level of nitrite plus nitrate (NOx). Zonisamide and PB dose-dependently suppressed the seizure of the EL mouse, and coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) induced a greater degree of seizure suppression than treatment with ZNS or PB alone. Although PB (5 mg/kg) had no effect on brain NOx levels, ZNS (150 mg/kg) and coadministration of ZNS (75 mg/kg) and PB (5 mg/kg) decreased NOx levels significantly. Phenobarbital (5 mg/kg) did not influence monoamines, while coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) decreased dihydroxyphenylacetic acid and increased 5-HT concentrations. The effect of the coadministration of two drugs on monoamines were similar to that of ZNS alone. These results suggest that one of the anticonvulsant effects of coadministration of PB and ZNS may be caused by changes in NOx levels.

Animals↗
PubMed2001

Influences of caffeine to nitric oxide production and zonisamide concentration in the brain of seizure-susceptible EL mice.

To investigate changes of nitric oxide (NO) productions and zonisamide (ZNS) concentrations in the brain of seizure-susceptible EL mice given caffeine orally, mice were given caffeine (600 microg/mL) solution ad libitum as a drinking fluid for 1-3 weeks. Nitric oxide production in the brain was determined by measuring levels of nitrite plus nitrate (NOx). The brain NOx levels of mice treated with caffeine for 3 weeks were significantly higher than the control. Seizures in mice treated with caffeine for 2 and 3 weeks were not suppressed by ZNS at a dose of 75 mg/kg. Serum ZNS concentrations of mice with caffeine intake for 1-3 weeks were higher than in untreated mice. Conversely, brain ZNS concentrations of mice with caffeine intake for the same periods were significantly lower than in untreated mice. These results suggested that caffeine influenced brain NO production and ZNS concentrations in the seizure susceptibility of EL mice.

Animals↗
PubMed2001

Hypersensitivity to mosquito bites as the primary clinical manifestation of a juvenile type of Epstein-Barr virus-associated natural killer cell leukemia/lymphoma.

Hypersensitivity to mosquito bites or mosquito allergy is a mysterious disorder that has been reported mainly in Japanese patients (at least 58 patients) in the first two decades of life. The skin lesion at bite sites is typically a bulla that develops into necrosis. Patients simultaneously exhibit a high temperature and general malaise and subsequently may experience lymphadenopathy and hepatosplenomegaly. Recent studies have revealed that this mosquito hypersensitivity is associated with chronic Epstein-Barr virus infection and natural killer cell leukemia/lymphoma. The natural killer cell, infected with monoclonal (or oligoclonal) Epstein-Barr virus, seems to be involved in the pathogenesis of the hypersensitivity. Half of the patients reported died of hemophagocytic syndrome (or malignant histiocytosis), granular lymphocyte proliferative disorder, or lymphomas. We propose that this disease, defined as the triad of hypersensitivity to mosquito bites, chronic Epstein-Barr virus infection, and natural killer cell leukemia/lymphoma, is a clinical entity mostly seen in Asians.

Adolescent↗
PubMed2001

Cell density-dependent proliferative effects of transforming growth factor (TGF)-beta 1, beta 2, and beta 3 in human chondrosarcoma cells HCS-2/8 are associated with changes in the expression of TGF-beta receptor type I.

In this study, the growth properties of the human chondrosarcoma cell line HCS-2/8, its response to transforming growth factor (TGF)-beta isoforms 1, 2, and 3, and its expression of TGF-beta receptors I and II were examined. We demonstrated that these tumor cells are not contact-inhibited and that they can proliferate in the absence of additional serum growth factors. In sparse cultures, all TGF-beta forms inhibited the growth of HCS-2/8 cells, whereas they induced a 2-fold increase of DNA synthesis in serum-fed confluent cultures. In serum-free confluent conditions only TGF-beta 1 stimulated the proliferation rate, whereas TGF-beta 2 was without effect and TGF-beta 3 was rather inhibitory. This bimodal effect of TGF-beta forms was associated with a greater level of TGF-beta receptor 1 mRNA in confluent HCS-2/8 than in sparse cultures, suggesting that the growth response to TGF-beta forms is dependent on the receptor profile expressed.

Cell Division↗
PubMed2001

Cell-type-specific trans-activation of herpes simplex virus thymidine kinase promoter by the human T-cell leukemia virus type I Tax protein.

The human T-cell leukemia virus type I Tax protein (HTLV-I Tax) is known as a trans-activating factor for a variety of genes, including those of cytokines. Here, we show that Tax is capable of activating the herpes simplex virus thymidine kinase (HSV-TK) promoter in certain mammalian cell lines. In murine NIH 3T3 fibroblasts and human HeLa cells, trans-activation by Tax was remarkably strong, whereas in human chondrocytic HCS-2/8 and monkey kidney Cos-7 cells, the responsiveness of the TK promoter to Tax was poor. Deletion analysis revealed that one of the two previously described Sp1 sites is required for the Tax responsiveness, whereas the CTF binding site is not. The results suggest possible interactions between the oncogenic Tax protein and the viral TK in coinfected cells in vivo. Care should be taken in the context of HTLV-I research, as the HSV-TK promoter has been widely used in molecular biology and gene therapeutics.

3T3 Cells↗
PubMed2001

Regulatory mechanism of human connective tissue growth factor (CTGF/Hcs24) gene expression in a human chondrocytic cell line, HCS-2/8.

CTGF/Hcs24 is a multi-functional growth factor that potentiates either the growth or differentiation of mesenchymal cells, according to the biological conditions. Among various functional aspects of CTGF/Hcs24, it is especially notable that CTGF/Hcs24 may promote endochondral ossification in growth cartilage through all stages, and it is highly expressed in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8). In this study, to clarify the regulatory mechanism of CTGF/Hcs24 gene expression in chondrocytes, we analyzed the transcriptional activity of the CTGF/Hcs24 promoter and the effect of the CTGF/Hcs24 3'-untranslated region (3'-UTR) on gene expression in HCS-2/8 by means of an established DNA transfection and luciferase reporter gene assay system. As a result, the luciferase activity of the CTGF/Hcs24 promoter was found to be remarkably high in HCS-2/8. The 3'-UTR of the CTGF/Hcs24 gene strongly repressed the luciferase activity in HCS-2/8, when it was linked to the downstream of the luciferase reporter gene, suggesting its functionality also in chondrocytic cells. Deletion analysis of the CTGF/Hcs24 promoter clarified a major segment responsible for the enhanced CTGF/Hcs24 promoter activity in HCS-2/8. The TGF-beta response element in the DNA segment was active in HCS-2/8, and point mutations in the element moderately decreased the highly maintained promoter activity with total loss of TGF-beta responsiveness. These results indicate that the strong expression of the CTGF/Hcs24 gene in HCS-2/8 was mainly caused by high transcriptional activity of the CTGF/Hcs24 promoter, and that the TGF-beta response element is one of the critical elements that support the high transcription activity.

3' Untranslated Regions↗
PubMed2001

EEG modification induced by repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is a powerful, noninvasive tool for investigating cortical physiologic functions in the brain. However, EEG spectral analysis has not been investigated extensively in rTMS study. The authors investigated the influence of rTMS on the EEG power spectrum by stimulating the left frontal cortex in 32 healthy subjects. Stimulation parameters were a 10-Hz frequency, a 3-second duration, and a 100% motor threshold. The data showed that rTMS increased the peak frequency of EEG across the scalp within 2 minutes after stimulation, whereas the value decreased at 3 to 4 minutes. The mean absolute powers within 3 minutes after rTMS did not differ from those estimated before rTMS, but increased uniformly at 4 to 5 minutes. The spectra did not change after sham stimulation. These results indicate that rTMS can influence cortical activities significantly by increasing the frequency and amplitude of EEG, and is a useful tool for helping us understand brain functions.

Adult↗