Biomedical subjects

M Takigawa

Publications and source records attributed to M Takigawa.

At least 109 records · Page 6Linked to original sources

PubMed2000

Low sampling rate induces high correlation dimension on electroencephalograms from healthy subjects.

The aim of this paper was to elucidate the influence of sampling parameters in the non-linear analysis of a resting electroencephalogram (EEG) in healthy subjects. Electroencephalograms in 12 healthy volunteers were recorded and the signal digitized at 128, 256, 512 and 1024 Hz, respectively, with the resolution of 8 bits, 12 bits and 16 bits for each sampling rate. Correlation dimension was calculated on each data set. Results were demonstrated on brain maps and examined by analysis of variance (ANOVA). Correlation integral functions demonstrated four parts separated by critical points. The data showed that sampling rate significantly affected the estimation, while resolution did not influence the results. The correlation dimensions calculated with the sampling rate at or below 256 Hz were apparently higher than the results obtained at 1024 Hz. The values at 512 Hz and 1024 Hz did not differ. The data revealed that low sampling rate can severely distort the estimation of correlation dimension. The optimal sampling rate for analyzing resting EEG on normal subjects is 512 Hz. Limitation and aliasing phenomenon are discussed in the paper.

Adult↗

PubMed2000

Effect on electroencephalogram of chewing flavored gum.

The objective of the present study was to evaluate the effect on the electroencephalogram (EEG) of a chewing gum with and without our prepared new flavor. Electroencephalograms were obtained after the following three tests: chewing pure gumbase with sucrose (standard gumbase), chewing flavored standard gum and the inhalation of flavored aromatic oil. As the control, we used the pre-stimulus control EEG record without a stimulus. We examined the relationship between the pre-stimulus control record and the post-stimulus record using the changes of power in four bands. Chewing the standard gumbase led to an increase in the alpha wave and a decrease in the beta wave. Chewing the flavored standard gum and inhaling the flavored aromatic oil each increased the alpha and beta waves. In addition, chewing the flavored standard gum led to a change in the ratio of theta wave in the frontal area. The difference in the theta, alpha and beta bands in chewing gum with and without the added flavor suggested that the flavor as well as chewing could induce concentration with a harmonious high arousal state in brain function.

Adult↗

PubMed2000

Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice.

Quinolone antibacterial agents are well known to cause photoallergy as a side-effect. Murine photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy.

Animals↗

PubMed2000

Nonerythrodermic, leukemic variant of cutaneous T-cell lymphoma with indolent clinical course: Th2-type tumor cells lacking T-cell receptor/CD3 expression and coinfiltrating tumoricidal CD8 T cells.

As typically represented by Sézary syndrome, the leukemic form of cutaneous T-cell lymphoma (CTCL) mostly exhibits erythroderma. A patient with CTCL had slowly developing skin tumors as well as chronic leukemia. The tumor cell was CD4+ CD7- Th2 cells lacking T-cell receptor/CD3 complex and persistently occupied 27% to 48% of peripheral blood lymphocytes. In skin tumors, only 13% of tumor-infiltrating lymphocytes were malignant cells and substantial numbers of nonmalignant CD4+ or CD8+ T cells and B cells coinfiltrated. CD8+-infiltrating T cells had cytotoxic activity against the malignant T cell. Our case demonstrates the existence of the leukemic form of CTCL presenting with skin manifestation other than erythroderma and parapsoriatic patches. The nonerythrodermic feature and indolent course may be associated with the lack of T-cell receptor/CD3 expression and coinfiltration of a high percentage of nontumor lymphocytes, including tumoricidal CD8+ T cells.

Aged↗

PubMed2000

Acute infectious urticaria: clinical and laboratory analysis in nineteen patients.

We treated 19 Japanese patients with acute urticaria presumably caused by infection during the five years from 1994 to 1998. The patients' ages ranged from 2 to 66 years (8 males and 11 females). Most of them had urticaria, angioedema, high fever, neutrophilia, and high serum levels of C reactive protein (CRP). The skin rash lasted more than 24 hours. In four patients, a flow cytometric analysis revealed that the percentage of circulating T cells bearing T-cell receptor V beta 3 was decreased during the active stage and that this decrease was sustained for at least 2 to 3 weeks. This suggests that certain T-cell populations were numerically altered in association with the occurrence of the disease. A retrospective review indicated that the combination therapy with corticosteroid and antibiotics was more effective than the single use of either agent.

Acute Disease↗

PubMed2000

Directed coherence of EEG on ICSS rats with methamphetamine-induced hyperactivity and stereotyped behavior.

Methamphetamine (MAP) can reinforce intracranial self-stimulation (ICSS) in rats, that is, reward-seeking behavior. However, the ICSS can be inhibited by the stereotyped behavior induced by MAP. This study was designed to observe the mutual information flow between prefrontal cortex (PFC) and ventral tegmental area (VTA) using directed coherence (DC) analysis during the hyperactivity and stereotyped behavior induced by administration of MAP (a derivative of amphetamine). The DC from PFC to VTA increased at 5-7 Hz in the hyperactivity as compared to the stereotypy. In contrast, enhanced information flow from VTA to PFC was observed in the stereotypy as compared to the hyperactivity. We found a reciprocal information flow between PFC and VTA corresponding to the hyperactivity and stereotyped behavior that was induced by administration of MAP.

Animals↗

PubMed2000

Ca2+ oscillations in response to methamphetamine in dopamine neurons of the ventral tegmental area in rats subchronically treated with this drug.

Mesolimbic dopamine neurons in the ventral tegmental area (VTA), which project to the nucleus accumbens and prefrontal cortex, play an important role in the regulation of emotion, rewarding, and cognition. The dopamine neurons in the VTA have also been implicated in schizophrenia and drug abuse. Methamphetamine (METH) can induce a schizophrenia-like psychosis. Thus, the VTA is a likely effector site for the action of METH. However, effects of METH on the mesolimbic dopamine neurons are largely unknown. We treated adult SD rats with METH (5 mg/kg/day) or saline for 7 days, isolated single VTA neurons from these treated rats, and monitored the neuronal activities by measuring cytosolic Ca2+ concentration ([Ca2+]i), which was followed by immunocytochemical identification of dopamine neurons. Acute administration of METH under superfusion conditions concentration-dependently increased [Ca2+]i in VTA dopamine neurons isolated from METH- and saline-treated rats. Furthermore, acutely administered METH induced oscillations of [Ca2+]i only in the dopamine neurons of the METH-treated group. The METH-induced [Ca2+]i oscillations were inhibited by Ca2+-free conditions and by Ca2+ channel blockers. In conclusion, subchronic METH treatment sensitizes VTA dopamine neurons to this drug, resulting in induction of [Ca2+]i oscillations. This sensitization of VTA dopamine neurons may account, at least in part, for the psycho-stimulant effects of METH, such as the dependence on and sensitization to METH.

Animals↗

PubMed2000

Effects of CTGF/Hcs24, a product of a hypertrophic chondrocyte-specific gene, on the proliferation and differentiation of chondrocytes in culture.

Recently, we cloned a messenger RNA (mRNA) predominantly expressed in chondrocytes from a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8, by differential display PCR and found that its gene, named hcs24, was identical with that of connective tissue growth factor (CTGF). Here we investigated CTGF/Hcs24 function in the chondrocytic cell line HCS-2/8 and rabbit growth cartilage (RGC) cells. HCS-2/8 cells transfected with recombinant adenoviruses that generate CTGF/Hcs24 sense RNA (mRNA) proliferated more rapidly than HCS-2/8 cells transfected with control adenoviruses. HCS-2/8 cells transfected with recombinant adenoviruses that generate CTGF/Hcs24 sense RNA expressed more mRNA of aggrecan and type X collagen than the control cells. To elucidate the direct action of CTGF/Hcs24 on the cells, we transfected HeLa cells with CTGF/Hcs24 expression vectors, obtained stable transfectants, and purified recombinant CTGF/Hcs24 protein from conditioned medium of the transfectants. The recombinant CTGF/Hcs24 effectively promoted the proliferation of HCS-2/8 cells and RGC cells in a dose-dependent manner and also dose dependently increased proteoglycan synthesis in these cells. In addition, these stimulatory effects of CTGF/Hcs24 were neutralized by the addition of anti-CTGF antibodies. Furthermore, the recombinant CTGF/Hcs24 effectively increased alkaline phosphatase activity in RGC cells in culture. Moreover, RT-PCR analysis revealed that the recombinant CTGF/Hcs24 stimulated gene expression of aggrecan and collagen types II and X in RGC cells in culture. These results indicate that CTGF/Hcs24 directly promotes the proliferation and differentiation of chondrocytes.

Adenoviridae↗

PubMed2000

Low-energy diet in atopic dermatitis patients: clinical findings and DNA damage.

Undernutrition without malnutrition (low-energy diet) increases maximum longevity, reduces the incidence of several cancers and delays their onset, in animal studies. It has also been demonstrated by experimental study that caloric restriction provides a beneficial effect on various inflammatory diseases. In this study, we offered a low-energy diet to patients with atopic dermatitis (AD). Nineteen adult patients (5 males and 14 females aged 15 to 36 years) were enrolled in the study which lasted 8 weeks. The energy intake was 55% of nutritional requirements; protein was 75%, calcium 180%, iron 130%, vitamin A 105%, vitamin C 250% and vitamin E 110% of the daily requirement. No patient experienced adverse reaction, and none dropped out of the trial. Body weight, body mass index (BMI), and systolic blood pressure had decreased significantly by the end of study. The SCORAD (scoring atopic dermatitis) index, which combines objective (extent and intensity of lesions) and subjective (daytime pruritus and sleep loss) criteria, was reduced significantly. In 11 patients with severe AD, there was a significant reduction in oxidative DNA damage. The change in the inflammatory intensity score and the change in BMI caused by energy restriction showed a significant positive correlation. The change in oxidative DNA damage levels and the change in BMI showed a positive correlation. These results clarify the relationship between weight loss and the improvement of AD. It may be hypothesized that this low-energy diet which included several additional nutrients has a possibility to reduce inflammatory symptoms of patients with AD.

Adolescent↗

PubMed2000

Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis.

OBJECTIVE: To determine the serum levels and clinical correlation of connective tissue growth factors (CTGF) in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc, n = 32), diffuse cutaneous SSc (dSSc, n = 28), systemic lupus erythematosus (SLE, n = 30), polymyositis/dermatomyositis (PM/DM, n = 20), and healthy control subjects (n = 30) were examined by ELISA for detection of CTGF. RESULTS: Serum CTGF levels in patients with SSc were significantly higher than those in patients with SLE or PM/DM, and in controls. CTGF levels in patients with dSSc were significantly higher than those in patients with lSSc. As for clinical correlation of CTGF, SSc patients with elevated CTGF had pulmonary fibrosis, decreased DLCO, and decreased vital capacity more frequently than those with normal CTGF levels. Further, DLCO and vital capacity were inversely and directly correlated with serum CTGF levels in patients with SSc. The dSSc patients with disease duration of 1-3 years had significantly elevated levels of CTGF compared with dSSc patients with duration < 1 year or more than 3 years. CONCLUSION: Serum CTGF levels were increased in patients with SSc, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. In addition, it appears that production of CTGF is involved in the development or maintenance of fibrosis rather than in initiation of fibrosis in SSc. These data suggest that CTGF plays a critical role in the development of fibrosis in SSc.

Adolescent↗

PubMed2000

Ex vivo gene delivery using an adenovirus vector in treatment for cartilage defects.

OBJECTIVE: To realize local selective gene expression in grafted chondrocytes for cartilage defect, we investigated the usefulness of an ex vivo gene delivery method using an adenovirus vector. METHODS: Beta-galactosidase gene (LacZ) was transfected using an adenovirus vector to chondrocytes isolated from rat joints. The cells were then embedded into collagen gel, and LacZ expression in the gel was examined using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining; beta-galactosidase activity was also measured. The collagen gel containing transfected chondrocytes was grafted to the experimental cartilage defects, and the expression of delivered gene was histologically examined after X-gal staining of the tissue containing the grafted area. RESULTS: X-gal positive chondrocytes in the gel accounted for 82% at one week and 55% at 8 weeks after gene delivery. Beta-galactosidase activity decreased with time, but its expression was maintained even at 8 weeks after gene delivery. Chondrocytes used in the allograft maintained their morphology, and the expression of delivered gene continued during the 8 week period. CONCLUSION: In this ex vivo method, delivered gene can be expressed efficiently for a long time; this method would be useful in allografts for cartilage defects.

Adenoviridae↗

PubMed2000

[Mechanism of drug dependency: answers to the questions of KATO].

The complicated mechanisms of drug dependency were discussed from the perspective of a reward, especially the perspective of psychic dependency of the brain. In Kato's article, the following questions were raised. (1) Improper usage of terminology in describing the objective pharmacological behavior and describing the subjective psychic experience, e.g. the term "obsessional comfort". (2) The enhanced effects of morphine and d-amphetamine in ICSS (intracranial self-stimulation) were not suitably regarded, as these might be the results of stimulus current running in the brain. The conclusion that "morphine and d-amphetamine are 2 kinds of addictive drugs due to the reinforcement effects on ICSS" appears to be putting the incidental before the fundamental because these are addictive drugs in clinical use. (3) It was unknown why the basic problem of drug dependency was limited to psychic stimulant (antihypnotic, etc.), and why only opiates were represented as an addictive drug. (4) The conclusion that the reinforcement effects of barbital and benzodiazepine were not observed in ICSS contradicted Kato's conclusion, in which the reinforcement effects were detected in an experiment involving self-administration. (5) He reiterated that the usage of terminology was confused in describing the psychic experience and pharmacological behavioral. In response to the comments of the editors, I would answer the questions as follows: It is well-known that the terminologies used in psychiatry are strict and prudent. This should also be the case in the description of pharmacological behaviors in animal models. The author admitted Kato's profound relevant experiences in drug dependency, and did not disapprove of his criticisms about the terminology used in the article to describe objective behaviors and observe subjective experience. That article was excerpted from one of my lectures, which to some extent allowed freedom in phrases and sentences. The following are my answers to Kato's questions.

Animals↗

PubMed2000

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids of patients with temporomandibular joint osteoarthritis.

AIMS: Imbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may be involved in the breakdown of articular cartilage matrix of the temporomandibular joint (TMJ). In this study, MMPs, TIMPs, and MMP-1/TIMP-1 complex levels were examined in TMJ synovial fluid samples aspirated from TMJ osteoarthritis (OA) patients (2 males, 8 females; mean age, 29.7 years) and asymptomatic control subjects (2 males, 8 females; mean age, 23.6 years) to determine the likelihood of increased proteolytic activity in the OA joints. METHODS: The various types of MMPs and TIMPs were detected by Western blotting with monoclonal antibodies and gelatin zymography. The MMP-1/TIMP-1 complex level was measured by an enzyme-linked immunosorbent assay kit. All aspirates were first analyzed for total protein content and then individually diluted to make the total protein levels equivalent. RESULTS: The mean MMP-1/TIMP-1 complex concentration in the synovial fluids of the OA patients was 3.92 +/- 1.39 ng/mL; this value was significantly lower (P < 0.05) than the value from control subjects (5.46 +/- 1.32 ng/mL). Matrix metalloproteinase-1 (52 kDa), MMP-3 (57 kDa), TIMP-1 (28 kDa), and TIMP-2 (26 kDa) were detected in all of the normal and the OA samples. However, MMP-1 (28 kDa), MMP-2 (72 kDa), MMP-3 (45 kDa), and MMP-9 (83 kDa) were detected in higher concentration in the OA samples. CONCLUSION: These findings suggest a strong association between the OA-active joints and the presence of biologically active forms of known tissue degradation enzymes (MMP-1, MMP-3, and MMP-9).

Adolescent↗

PubMed1999

Activation of epidermal growth factor receptor promotes late terminal differentiation of cell-matrix interaction-disrupted keratinocytes.

The biological effects of epidermal growth factor receptor (EGFR) activation may differ between epidermal suprabasal and basal keratinocytes, since growth factors are mitogenic in adherent cells only in the presence of cell-extracellular matrix (ECM) interaction. To investigate biological effects of EGFR activation on keratinocytes without cell-ECM interaction, we cultured normal human keratinocytes on polyhydroxyethylmethacrylate-coated plates, which disrupt cell-ECM but not cell-cell interaction. The cells initially expressed keratin 10 (K10) and then profilaggrin, mimicking sequential differentiation of epidermal suprabasal keratinocytes. The addition of EGF or transforming growth factor-alpha promoted late terminal differentiation (profilaggrin expression, type 1 transglutaminase expression and activity, and cornified envelope formation) of the suspended keratinocytes, while suppressing K10 expression, an early differentiation marker. These effects were attenuated by EGFR tyrosine kinase inhibitor PD153035 or an anti-EGFR monoclonal antibody, whereas protein kinase C inhibitors H7 and bisindolylmaleimide I or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059 abolished profilaggrin up-regulation but not K10 suppression. Since the antidifferentiative role of EGFR on cell-ECM interaction-conserved keratinocytes has been well documented, our results indicate that the biological effects of EGFR on keratinocytes are influenced by cell-ECM interaction and suggest that EGFR activation promotes rather than inhibits the terminal differentiation of suprabasal epidermal keratinocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1999

Subtype-associated metabolite differences in the temporal lobe in schizophrenia detected by proton magnetic resonance spectroscopy.

Brain imaging studies have indicated that the medial temporal lobe functions aberrantly in schizophrenic patients. Both diagnostic subtype and gender may affect functional and morphologic abnormalities in this region. We investigated subtype- and gender-associated differences in metabolites in the left medial temporal lobe in 40 medicated schizophrenic patients by proton magnetic resonance spectroscopy and compared findings with those in 40 healthy control subjects. Peaks corresponding to N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine-phosphocreatine (Cr), and inositol were measured. Schizophrenic patients showed a decrease in the NAA/Cr ratio in the left medial temporal lobe, and patients with the disorganized subtype of illness showed significantly lower NAA/Cr and Cho/Cr ratios than those with paranoid schizophrenia. The NAA/Cr ratio in patients with the undifferentiated subtype also was significantly lower than in the paranoid subtype. No significant associations were observed between metabolite ratios and clinical symptom scores, age at onset of illness, or gender. These findings suggest that patients with the disorganized and undifferentiated subtypes have greater impairments in neuronal integrity or function in the left medial temporal lobe than patients with other subtypes of schizophrenia.

Aspartic Acid↗

PubMed1999

Nitric oxide production is decreased in the brain of the seizure susceptible EL mouse.

To investigate nitric oxide production in the brain of the EL mouse, an inbred mutant strain of the ddY mouse that is susceptible to convulsive seizures, we measured whole brain nitric oxide metabolites, and counted the number of nitric oxide-producing cells in the parietal cortex and striatum. Nitric oxide metabolites in the brain and serum were determined by measuring levels of nitrite plus nitrate. Nitric oxide-producing cells were demonstrated histochemically by staining for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. Levels of nitrite plus nitrate in the whole brain were significantly lower than those of the control mice, although levels of nitrite plus nitrate in the serum did not differ between groups. There were significantly fewer NADPH-diaphorase-positive cells in the parietal cortex and striatum of the EL mouse compared to the ddY controls. These results suggest that lower nitric oxide production in the brain may be related to the susceptibility of the EL mouse to convulsive seizures.

Animals↗

PubMed1999

Immunohistochemical localization of connective tissue growth factor in the rat central nervous system.

Connective tissue growth factor (CTGF) is an immediate early growth-responsive gene but its distribution and significance in the central nervous system (CNS) are unknown. We investigated the distribution of CTGF-like immunoreactivity (CTGF-IR) in the rat CNS using a specific antiserum against CTGF oligopeptide. The majority of CTGF-IR was observed in astrocytes. Ependymal cells lining the wall of the cerebral ventricle and tanycytes lining the central canal of the spinal cord showed the strongest CTGF-IR, while there was a diffuse but weak signal in the gray matter of the spinal cord. CTGF-IR was also detected in the cytoplasm of a subpopulation of pyramidal neurons in the cerebral cortex. Our results showed that CTGF-IR is widely distributed in the CNS at both regional and cellular levels, suggesting a complex functional role in the CNS.

Animals↗

PubMed1999

Depletion of IL-10- and TGF-beta-producing regulatory gamma delta T cells by administering a daunomycin-conjugated specific monoclonal antibody in early tumor lesions augments the activity of CTLs and NK cells.

It has been demonstrated that gamma delta T cells accumulating in early tumor lesions and those purified from spleen cells of tumor-bearing mice attenuate the activity of CTLs and NK cells. We, therefore, investigated whether depletion of gamma delta T cells from early lesions of tumors results in restoration of CTL and NK cell activities and subsequent regression of tumors. A daunomycin-conjugated anti-gamma delta TCR mAb UC7-13D5 (Dau-UC7) was prepared to efficiently deplete gamma delta T cells. An in vitro study revealed that Dau-UC7 specifically lysed gamma delta TCR+ cells and effectively inhibited splenic gamma delta T cells from tumor-bearing mice to produce cytotoxic cell-suppressive factors. Furthermore, intralesional injections of Dau-UC7 at an early stage of tumor development led to augmentation of tumor-specific CTL as well as NK cell activities and to the resultant regression or growth inhibition of the tumors. On analysis of cytokine profile, gamma delta T cells transcribed mRNAs for IL-10 and TGF-beta, but not IL-4 or IFN-gamma, suggesting the T regulatory 1-like phenotype. Finally, a blocking study with mAbs showed that the inhibitory action of gamma delta T cells on CTLs and NK cells was at least partly mediated by IL-10 and TGF-beta. These results clearly demonstrated the novel mechanism by which T regulatory 1-like gamma delta T cells suppress anti-tumor CTL and NK activities by their regulatory cytokines in early tumor formation.

Adjuvants, Immunologic↗